Pharmacognosy Reviews, 2023; 17(34):338-381. www.phcogrev.com Review Article Pharmacognosy Reviews, Vol 17, Issue 34, Jul-Dec, 2023338 DOI: 10.5530/phrev.2023.17.13 Copyright Information : Copyright Author (s) 2023 Distributed under Creative Commons CC-BY 4.0 Publishing Partner : EManuscript Tech. [www.emanuscript.in] Ethnobotany, Pharmacology and Major Bioactive Metabolites from Impatiens Genus Plants and their Related Applications Fabián Vinicio Delgado-Rodríguez*, Nien Tzu Weng-Huang, Arlene Loría Gutiérrez, David Arias-Núñez, Christopher Rosales-Leiva Instituto de Investigaciones Farmacéuticas (INIFAR), College of Pharmacy, University of Costa Rica, San Pedro de Montes de Oca, San José, COSTA RICA. ABSTRACT Impatiens genus comprises several species important for agriculture and food industries, ethnobotany, and research in pharmacology, phytochemistry, biotechnology and pharmaceutical sciences. In this paper, a systematic review of ethnobotanical uses, bioactivities discovered, and research applications reported for Impatiens plants and their major bioactive constituents are presented aiming to provide an integrative comprehension of relevance of the genus in the mentioned fields and to give guidance for the further research of unexplored or poorly investigated species of this genus. Through this review, an update on this expanding area of research is also provided. According to revisited information, most of bioactive compounds are phenolics, phytosterols, triterpenoids, and peptides. There is a wide spectrum of applications investigated for Impatiens plants extracts and their bioactive metabolites, however, in most cases, they are related to their antimicrobial, cytotoxic, anti-inflammatory, anti-anaphylactic, and antioxidant properties. Further efforts are needed to evaluate the efficacy and safety of Impatiens plants extracts and bioactive compounds to get a complete perspective of their potential applications. Most plants from Impatiens genus with ethnobotanical interests have been poorly studied, therefore, more research of them will be useful to validate their use, to verify their safety and to isolate their main bioactive compounds. Keywords: Impatiens, Ethnobotany, Bioactivities, Metabolites, Toxicity, Applications. INTRODUCTION Balsaminacea family is integrated by two genera, Hydrocera and Impatiens. Hydrocera only has one member corresponding to Hydrocera triflora endemic from Southeastern Asia while Impatiens has around 1000 species of plants and new species are constantly discovered. Most of Impatiens species have a palaeotropical origin,[1,2] however, there are few species endemic from Eurasia, North America, and Central America.[1-5] Several plants of Impatiens genus have relevance for agriculture, ethnomedicine and pharmacology. For instance, I. walleriana and I. hawkeri are ornamental plants with annual wholesales of $65 and $54 million in the United States, respectively.[6,7] Figure 1 contains images of the most relevant species of Impatiens genus for the horticulture industry. Furthermore, I. balsamina exemplifies a plant of the genus Impatiens relevant due its ethnobotanical use and pharmacological properties. This plant is included in Ayurveda and is used in the traditional medicine of China, Taiwan, and Korea as a remedy for inflammatory diseases and infections.[8] Naphthoquinones, flavonoids and triterpenoids are the principal active compounds responsible of the anti-inflammatory and antimicrobial effects demonstrated by the extracts of I. balsamina.[9,10] Literature indicates a growing interest for the development of products with therapeutic applications using extracts or metabolites from Impatiens plants. Soaps prepared using I. capensis plant extracts have been investigated for the prevention of dermatitis due to poison ivy/oak contact.[11] A mouthwash with the active principle 2-methoxy-1,4-naphthoquinone (1), a naphthoquinone present in I. balsamina, has shown promissory results for its application in oral candidiasis prophylaxis in Human Immunodeficiency Virus (HIV)-infected subjects and denture wearers.[12] Edible species I. balsamina and I. walleriana have gained attention in food industry due their potential application as functional foods.[13-16] Received: 03-03-2023; Revised: 28-04-2023; Accepted: 05-06-2023. Correspondence: Fabián Vinicio Delgado-Rodríguez Instituto de Investigaciones Farmacéuticas (INIFAR), College of Pharmacy, University of Costa Rica (11501-2060), San Pedro de Montes de Oca, San José, COSTA RICA. Email: fabian.delgadorodriguez@ucr.ac.cr Pharmacognosy Reviews, Vol 17, Issue 34, Jul-Dec, 2023 339 Delgado-Rodríguez, et al.: Impatiens genus: Ethnobotany, Pharmacology and Bioactive Metabolites Despite the available information related to the chemical constitution and pharmacological activities about Balsaminaceae plants,[9,10,17] we identified the necessity of a deep and integrative review of reported ethnobotanical applications of these plants to guide their further research. Additionally, it is relevant to review the corresponding biological activities in the same way to get an update about this expanding field of research and to define investigation approaches that could be covered to define applications for Impatiens plants, including the development of safe and effective products for healthcare from their bioactive extracts and metabolites. SEARCH METHODOLOGY The review comprises full-text research articles and book chapters available in the following databases: ACS publications, EBSCOhost, Google Scholar, PubMed, ScienceDirect, SpringerLink, Taylor and Francis Online and Wiley Online Library. For the search in these data bases, the keyword “Impatiens” was combined with the terms “Biological activity”, “Pharmacology”, “Pharmacological activity”, “in vitro activity”, “in vivo activity”, “Toxicity”, “Compounds”, “Chemical constituents”, “Ethnobotanical use”, “Ethnopharmacology” and “Traditional medicine”. Boolean operator “AND” was used to combine the search words, this allowed to do an exhaustive search of information available about ethnobotany, pharmacology, and toxicology of plants from Impatiens genus considering their major active compounds. References related with sole chemical characterization of extracts and isolation of natural products without biological activity evaluation were excluded. The information from 398 full-text references was selected to prepare the review. Additional information about ethnobotanical uses of Impatiens was obtained from the following electronic databases: Moerman´s online Native American Ethnobotany Database (University of Michigan-Dearborn),[18] Plant Resources of South East Asia (PROSEA foundation),[19] Plant Resources of Tropical Africa (PROTA foundation),[20] Prelude Medicinal Plants Database (Royal Museum for Central Africa),[21] and Subject Database of China Plant (Institute of Botany, Chinese Academy of Science).[22] The botanical recognition of the scientific name of each species reported in the review was corroborated through International Plant Names Index database.[23] Additional 25 references known by authors were used to discuss information and as a complement in the development of the review. ETHNOBOTANICAL USES Impatiens alboflava In Indonesia, flowers are used to treat cancer and fever.[24] Impatiens apalophylla In China, decoction from whole plant is used to treat menstruation disorders and blood stasis, including those present after partum. It is also employed to treat rib and abdominal pain. The mashes from whole herb are externally applied to cure pain, injuries, and traumatisms.[22,25,26] Figure 1: Examples of Impatiens species relevant for agriculture, ethnobotany and pharmacology research. (A) I. balsamina (cultivated specimen); (B) I. hawkeri (cultivated specimen); (C) I. hawkeri (naturalized specimen, Coto Brus Region, Costa Rica); (D) I. walleriana (naturalized specimen, Coto Brus Region, Costa Rica). Pharmacognosy Reviews, Vol 17, Issue 34, Jul-Dec, 2023340 Delgado-Rodríguez, et al.: Impatiens genus: Ethnobotany, Pharmacology and Bioactive Metabolites Impatiens arguta In China, crushed leaves are used as hemostatic.[27] Flowers are used to dissolve clots, to treat amenorrhea pain and to relieve abdominal pain. They are employed to treat postpartum blood stasis, stillbirth, difficult urination, carbuncles, and furunculosis.[22,25] In Bhutan, leaves from I. arguta are used to treat old wounds.[28] Impatiens auricoma In Mayotte archipelago, leaves decoction is used to treat hemorrhoids.[21] Impatiens balsamina In China, aerial parts are used as edible vegetable and as a remedy for articular rheumatism, bruises, and beriberi. Flowers are used to prepare beverages employed to prevent illness, in the form of tea and wine.[9,29-33] Their juice has been used as a natural purple dye for staining cloths and fingernails.[19,25,34,35] Flowers are used externally or orally as treatment for several illnesses, including rheumatic pain, limb numbness, intercostal pain, fractures, pain associated with menorrhagia, amenorrhea, leucorrhea, carbuncle, wounds, furunculosis, swelling, blood stasis, gooseflesh, intoxications, insect and snake bites, and fungal (ringworm, dandruff and nail fungal infections) and parasitic infections.[9,19,22,26,30,31,36,37] There are other uses reported in China for I. balsamina. Decoctions from whole herb are externally used to treat rheumatoid arthritis, cervical osteophytes, and musculoskeletal contractures. They are also used to treat swelling, tinea sore, snake bites, athlete’s food, pruritus, bleeding and external infections.[26,34,36,38-40] Tea from whole herb is internally used to treat bacterial and fungal infections.[9,30,31,40,41] Mashes from the same material are applied over affected areas to treat furuncles and carbuncles.[26,42] It is reported that decoction from aerial parts is drunken to ease parturition.[43] It is also used to treat rheumatism, wounds, and foot diseases.[36] Other specific organs from I. balsamina are used in China. Decoction from stems is employed to promote blood circulation and to treat rheumatic paralysis, musculoskeletal contractures, pain, arthritis, intoxications, carbuncles, wounds, swelling, amenorrhea and dysmenorrhea, sores, and pyogenic infections.[22,25,36,44,45] Decoction from older stems with large nodes is used to treat swelling and edema, and to wash abscesses, while dried stems are employed as remedy for difficult labor, pain, leg cramps, and rheumatism. They are also utilized to improve blood circulation. Juice from stems is combined with rice liquor and the mixture is externally used to treat contusions.[37] The decoction or mashes from stems are externally applied to treat bruises, swelling, snake bites, erysipelas, ringworm, and carbuncles.[22] Decoction from leaves is used as anti-inflammatory. Poultices from leaves are applied to wounds, pustules, torn nails, and felons.[19] Seeds are used to promote blood flow, to treat difficult parturition and to relieve post-childbirth pain.[22,25,46] Additionally, seeds have been used as an expectorant and as a bactericide.[15,47] Their decoction is used to treat esophagus and gastric cancer associated abdominal masses, hiccups, amenorrhea, difficult childbirth, bone hyperplasia, dirty teeth, bone choking throat and sores.[15,22,25,26,35-37,48-52] The powder from seeds is externally applicated to treat sores and swelling. Seeds are also utilized to remove teeth with caries.[37] Roots are used to promote blood circulation and to treat edema, rheumatism, tendon pain, bruises, torn nail swelling, and leucorrhea.[19,22,36] The use of I. balsamina is not recommended in pregnant women.[26] In Nepal, the plant extract is used to promote hair growth.[53] In India, I. balsamina plant is used as a cathartic, diuretic, and emetic and to treat dysentery and jaundice. Pulverized seeds are used to treat liver disorders.[15,30,32,41,54-56] Leaves from I. balsamina are crushed, mixed with water, and given orally to treat malaria.[56] Leaf paste is used to treat cuts, wounds, burns, fractures, and to relieve fever and inflammation.[57-60] It is also used to relieve itching between fingers during monsoons.[61,62] The paste is applied on abdomen to treat urinary disorders. Stems juice is externally applied to threat calluses.[63] Flower tea is used to treat jaundice.[64] Flowers are used as an antiseptic and neuroprotective, and their paste is applied on forehead to treat fever.[65] In Pakistan, I balsamina is used to treat join pain and juice from leaves is used against gastrointestinal disorders.[66,67] In Bangladesh, flowers are used to treat lumbago, neuralgia, burns and scalds.[15] In Sri Lanka, the plant is used to treat boils and burns.[60] In Thailand, the aerial parts are used as tonic and to treat puncture wounds, abscesses in nails, swelling and ulcers associated with allergic reactions to detergents.[36,68-70] Decoction from aerial parts, leaves and roots is drunken to ease parturition and to treat dysmenorrhea and amenorrhea.[43,71,72] I. balsamina leaves are used externally to treat abscesses, nail infections, and skin fungal diseases.[73] In Taiwan, whole plant is used to treat rheumatism, swelling, and fingernail inflammation.[41,46,74] In Japan, petals juice or sochu petal macerate are applied on the skin to alleviate dermatitis, urticaria, burns, and insect bites.[9,32,46,75,76] In Korea, I. balsamina is used to treat carbuncles, tuberculosis, scurvy, and dysentery. The stems are used to treat constipation and acute gastritis.[15,36,77,78] The infusion from whole herb is drunk to treat indigestion and sterility, while infusion from flowers and leaves is drunk to treat pollakiuria.[79,80] Beauty-salt™ is a product made of solar salt and I. balsamina extract that has been used to treat inflammatory disorders in Korea.[81] In Hawaii, the herb is used as emetic, cathartic, and diuretic. It is utilized to treat ulcers and cancer.[41,82,83] Flowers are used as cooling, tonic, and antiseptic.[82,83] Pharmacognosy Reviews, Vol 17, Issue 34, Jul-Dec, 2023 341 Delgado-Rodríguez, et al.: Impatiens genus: Ethnobotany, Pharmacology and Bioactive Metabolites In Philippines, leaves are heated and applied with oil on forehead to treat headache.[84] Leaves are pounded and externally used to dissolve felons.[15,37] Ground leaves and flowers are externally applied to treat burns, insect bites and swollen muscles.[85] In Malaysia, whole plant decoction is used to treat hypertension and leaves paste is used to treat split nails, felons and to soothe skin irritation.[15,86-89] Leaves are utilized to treat snake bites.[41] In Indonesia, the whole herb has ritual uses[90] and is utilized as an antimalarial and as remedy for felons and wounds.[37,91] Leaves are considered edible material, they are ground with black pepper and ginger and the mixture is taken to treat beriberi.[19,92] Leaves and stems are used as an anti-infective for wounds.[36,93] Flowers are used as a component of concoctions used to prepare traditional beauty masks.[94] Boiled seeds and flowers are used to treat cancer and fever.[24,95] In Brunei, root decoction is taken to treat irregular menstruation.[15,19,32] In Indochina, the decoction made from leaves is used to wash the hair and to help it to grow.[37] In Mauritius, decoction from stems and roots of I. balsamina is drunk to ease childbirth. Juice from the stem is used as emetic, cathartic, and diuretic. Flowers are used for lumbago, intercostal neuralgia and to remove blood stasis.[21,96] Leaf poultices are applied for wound healing and to treat paronychia.[21,96-98] Leaves are used to relieve surgery pain and to facilitate parturition.[21,97,98] In Türkiye, the herb is pounded with garlic and applied in the head after shaving the hair to treat sunstroke.[99] The plant is also used to treat heart stroke and hair loss.[36] In Canary Islands, leaves are used to treat wounds, hemorrhoids, and diabetes.[100] In Ecuador, the infusion from fresh leaves and flowers is drunk to cure internal infections.[101] In Colombia, flower decoction is drunk and its ointment is externally applied to treat snake bites.[102] In Guyana, leaves are mashed and mixed with salt and castor oil to treat whitlow and ingrown toenails.[103] Impatiens baronii In Madagascar, decoction from aerial parts is used as a febrifuge.[104] Impatiens bicolor In Pakistan, juice and powder from stems and seeds are used as diuretic and to treat kidney stones and joints pain.[105] The paste made from leaves is externally applied to treat joint pains.[89,106] Seeds are eaten as a brain tonic.[107] Extracts from whole plant are used as laxative and cooling agents.[106] Fruits and seeds are used as antihypertensives, diuretics, cooling agents and tonics.[86,108,109] In India, fruits are used as edible material.[110] Leaves are given to buffalos to promote milk production.[109] Impatiens bicornuta In Nepal, whole plant decoction is used to treat inflammation. Leave paste is used to treat joints pain.[111] Impatiens blepharosepala In China, whole herb is used to treat rheumatic pain in joints, fractures, and amenorrhea. Roots are used as a treatment for anemia, trauma, and bleeding.[22] Impatiens brachycentra In Pakistan, seeds are chewed as tonic, and they are used to treat anxiety and joints pain. The oil from seeds has the same uses.[112] Flowers, leaves and roots are used as cathartics, emetics, and diuretics.[113] Poultices made of seeds are used topically to treat burns.[114] Impatiens burtonii In Cameroon, infusion from leaves is drunken to treat female infertility.[21,115] Leaves and stems are macerated and drunk by pregnant women to treat swelling of inferior limbs. Macerate from leaves is used to clean babies.[116] Impatiens capensis This plant is mainly used by American Natives of United States and Canada. The plant is an ingredient of green corn medicine used in Cherokee tribe as an emetic and to prevent colic and parasitosis. Decoctions and infusions from whole herb are taken to promote appetite and diuresis. They are used to treat chest cold, stomach cramps, and burns. Their external application is used to treat soreness, sprains, and bruises and to wash liver spots. Decoctions and infusion from leaves are used as a remedy for jaundice and measles. Decoction from stems is drunk to ease childbirth. Infusions from roots are used to bath babies with hives and are drunk to promote diuresis. Herbal decoctions and infusions that includes I. capensis as an ingredient are employed to treat fever, difficult urination, kidney diseases, and edema. Plant juice is rubbed on head to treat headache and is externally applied on skin to cure nettle sting and poison ivy/oak rash. Poultices from crushed whole plants, leaves, flowers, or stems are externally applied to heal burns, bruises, wounds, rash, and eczema, especially those related to poison ivy/oak contact. Crushed leaves are rubbed on children to treat stomachache. Baths made from spicebush berries and I. capensis are used to treat heart failure. The plant is used as a sources of dyes.[11,18,117-121] Decoction from I. capensis is used as an abortive in Croatia.[122] Impatiens chinensis In China, decoction from whole plant is used as a remedy for fever, pain, intoxication, low blood flow, dysentery, diarrhea, urinary infections, pulmonary tuberculosis, child pneumonia, swelling, abscesses, and carbuncles.[22,25,26] The plant mashes are used externally to treat carbuncles, furuncles, and malignant boils. The use of this plant is not recommended to pregnant women.[26] In India, plant juice is used to treat burns and internally to treat gonorrhea.[123] The plant is used to relieve pain, to promote blood circulation and to treat urinary infections.[124] Pharmacognosy Reviews, Vol 17, Issue 34, Jul-Dec, 2023342 Delgado-Rodríguez, et al.: Impatiens genus: Ethnobotany, Pharmacology and Bioactive Metabolites Impatiens clavigera In China, whole plant is used to treat skin injuries and burns. It is used to treat carbuncles swelling and poison.[22,25] Impatiens cyanantha In China, whole plant is used to relax and activate tendons and to treat injuries, traumatisms, and snake bites.[25] It is used for abdominal pain, children malnutrition, swelling and pain.[22] Impatiens davidii In China, plant decoction is used to treat abdominal pain, indigestion, infantile malnutrition, swelling and pain.[22,26] Impatiens dichroa In Central African Republic, macerate from stem and leaves is drunk to treat headache.[21] Impatiens dycentra In China, seeds and whole herb decoctions are used to promote blood circulation and to remove blood stasis. They are used as diuretic and detoxification agent. Smashed whole herb is externally applied to treat bruises.[22] Impatiens edgeworthii In Pakistan, seeds are chewed as a tonic and to treat anxiety and joints pain. The oil from seeds has the same uses.[112] Extracts from whole plant and flowers are used as antimicrobials to treat urinary infections, gonorrhea, and fever.[109,125-127] Powder or extracts from whole herb are used to treat kidney stones, hyperacidity, and pain.[109,128] Paste from whole plant and poultices from seeds are used topically to treat burns.[60,114,125-127,129] Flowers are used externally to treat burns.[109] Fruits with seeds are taken to treat sexual disfunction.[130] Impatiens ethiopica In Ethiopia, I. ethiopica roots powder is warmed and applied on wounds.[131] Impatiens glandulifera In Pakistan, I. glandulifera is used to treat joints pain.[66,67] Seeds are chewed as tonic and as treatment to anxiety and joints pain. The oil from seeds has the same applications.[112] The paste made from roots or extracts from roots are applied to cool hands and feet. Roots, leaves and flowers powders and decoctions are used as antidepressant, anxiolytic, hypnotic and to treat snake bites.[128,132-134] Leaves are applied externally to treat burns.[109] The infusion from flowers are used for eye washes.[125] Juice from flowers is used as a cooling and tonic agent.[67,109] Flowers are also utiized to treat joints pain and as cathartic, diuretic, and emetic.[109] In India, flowers are used to treat snake bites.[133] Paste from leaves is used as a cooling agent for hands and feet.[135] Fruits, seeds, leaves, and stems are used as edible material.[136,137] Paste and powder from the leaves of I. glandulifera are externally used to treat sun burns and joints pain.[138] Impatiens griffithii In Malaysia, flowers are used for dyeing fingernails.[19] Impatiens hawkeri In Papua New Guinea, I. hawkeri is considered as a magical and ceremonial plant.[139,140] Leaves are used to treat scabies[141] and are eaten by women to promote pregnancy.[142] They are mixed with leaves from Coleus scutellarioides and then rubbed on the abdomen of pregnant women to relieve labor pains. Leaves are chewed by women to promote labor. Juice from leaves is rubbed in the legs of small children with walking retardation. The cooked whole plant is given to children with stomachache.[19,142,143] In Brazil, it is reported that in close environments, the plant can induce tearing, headache, and allergy.[144] Impatiens henryi In China, whole herb is used to treat rheumatic pain.[22] Impatiens holocentra In China, whole plant is used as fodder.[145] Impatiens irvingii In Guinea, flowers macerate is used as an antidiabetic.[146] In Liberia, leaves are used as edible material. In Democratic Republic of Congo, Gabon and Sudan, the plant is used to produce vegetable salt. In Democratic Republic of Congo, stem juice is instilled in nostrils to treat headaches and stems oil is rubbed to treat bone tuberculosis. Herbal decoctions including I. irvingii roots are used to treat female infertility. In Ivory Coast, the plant is used as a treatment for schistosomiasis.[20,21] Impatiens latifolia In India, the plant is considered as edible material.[147] Leaves are used to relieve headache and gastrointestinal disorders.[148] Impatiens lecomtei In China, whole herb is used to treat livestock sores and is given to them after birth.[149] Impatiens lemannii In Pakistan, whole plant infusion is drunk to relieve pain.[128] Impatiens leptocaulon In China, the decoctions or wine macerates from roots of I. leptocaulon are taken to promote blood circulation and are used as analgesic. They are also employed to treat rheumatoid arthritis and limb numbness. The mashes from roots are applied externally to treat bruises, swelling, and pain.[22] Pharmacognosy Reviews, Vol 17, Issue 34, Jul-Dec, 2023 343 Delgado-Rodríguez, et al.: Impatiens genus: Ethnobotany, Pharmacology and Bioactive Metabolites Impatiens longialata In China, whole herb is used to promote blood circulation, muscle relaxation, and regulation of menstruation.[22] Impatiens loulanensis In China, whole plant is used to relax and to activate tendons, and to treat injuries, traumatisms, and snake bites.[25] Impatiens masisiensis In Democratic Republic of Congo, plant juice is taken or externally applied to treat snake bites. Leaves decoction is used to treat hematuria. Crushed leaves and stems are applied to treat skin injuries, mosquito bites and livestock theileriosis.[21] Impatiens meruensis I. meruensis is utilized as edible plant in Uganda.[150] Impatiens microcentra In China, roots are used as antipyretic and analgesic. Plant is used for muscle pain and sore throat relief.[22] Impatiens mooreana In New Guinea, petals and young leaves from I. mooreana are rubbed on skin to treat burns.[37,151] Impatiens niamniamensis In Congo Democratic Republic, the juice from leaves is instilled in each nostril to treat pneumonia. The decoction from leaves is used as treatment for gonorrhea and epilepsy. Mashes from whole plants are applied externally to promote wound healing.[152] Leaves are considered edible material and are used to produce vegetable salt. In Congo, leaves are eaten to cure heart illnesses. In both countries mentioned, leaves poultices and dressings are used to treat wounds, sores, and painful conditions.[20] Impatiens noli-tangere In Romania, the plant is used as anti-inflammatory, astringent, hemostatic and to promote wound healing.[153] Herbal baths with I. noli-tangere have been reported as treatments for general weakness and musculoskeletal weakness or disability in extremities.[154] Tincture from leaves is used as an astringent and diuretic remedy. Dry leaf powder is used as a purgative, laxative, and emetic agent.[155] In China, decoctions from roots, flowers and whole plants are used to reduce blood stasis and to treat irregular menstruation, dysmenorrhea, bruises, rheumatism, and scrotal eczema.[22] Decoction from of I. noli-tangere whole plants is employed to clear “heat” (a set of symptoms that include fever, unconsciousness, delirium, dysphoria, thirst, constipation, oral ulcers, mouth sore, and dry eye).[156] The mashes of the plant are externally used to treat bruises, rheumatic pain, and scrotal eczema.[26] Impatiens notolopha In China, aerial parts are used as edible material.[157] Impatiens nzoana Leaves have been used in Liberia to treat involuntary urination on bed.[158] Impatiens omeina In China, roots are used as an analgesic.[22] Impatiens parviflora In Czechia, seeds are edible and are recognized by their nutty pleasant flavor.[159] In Uzbekistan and Kyrgyzstan, whole herb is used as antimicrobial, hemostatic and as treatment for uterine diseases.[160-162] Impatiens pallida This plant is mainly used by American Natives of United States and Canada. The plant is also used as an ingredient of green corn medicine used by Cherokee tribe. Crushed herb and juice are rubbed on skin to treat wounds, bruises, mosquito bites and poison ivy/oak related rash and eczema. Herb and leaves infusions or decoctions are drunk to treat fever, measles, and pain during parturition. Infusion from roots is used to bath babies with hives. Crushed leaves are rubbed on children abdomen to treat stomachache.[18] Impatiens platypetala Leaves are used in Indonesia to treat skin eruptions and as a diuretic for children.[19,37] Impatiens pritzelii In China, the rhizomes of I. pritzelii var. hupehensis are used to promote blood circulation and to treat rheumatism, limb numbness, bleeding, joints swelling and pain, wounds, burns, traumatisms, abdominal pain and distention, enteritis, dysentery, diarrhea, acute stomachache, amenorrhea, and dysmenorrhea.[25,163-167] Fresh leaves are mashed to treat bruises, traumatic bleeding, boils and snake bites.[22] Impatiens puberula In Nepal, whole plant is used to treat indigestion.[111] Impatiens pterosepala In China, whole plant is applied for wounds treatment.[22] Impatiens pulchra In China, stems and leaves are boiled and eaten.[168] Impatiens racemosa In India, the paste from leaves and roots is mixed with mustard oil and applied externally to treat rheumatic pains.[169] Leaves are Pharmacognosy Reviews, Vol 17, Issue 34, Jul-Dec, 2023344 Delgado-Rodríguez, et al.: Impatiens genus: Ethnobotany, Pharmacology and Bioactive Metabolites used for gastrointestinal disorders.[148] Fruits are used in Bhutan to treat cold and cough.[28] Impatiens rothi In Ethiopia, root powder is warmed and applied on wounds.[131] Impatiens scabrida In Pakistan, whole herb is used as a laxative and diuretic on farm animals.[170,171] In India, I. scabrida is used as fodder plant and stems are used as an abortifacient.[172,173] In Nepal, the plant is used to feed farm animals suffering fever, fruits are use as edible material and oil from seeds is used to relieve muscle pain and fever.[174-176] Impatiens siculifera In China, roots, whole plants and seeds are used as circulatory tonics and as remedies to treat rheumatoid pain and numbness, edema, swelling, inflammation, burns, scalds, bruises, carbuncles, and fractures.[22,26,177,178] Stems are used to treat fever, intoxications, phlegm, pain, injuries, and burns.[25] Decoction from whole plants is used to treat “heat”. Mashes of the plant are used to treat burns and wounds.[26] Impatiens stuhlmannii In Congo Democratic Republic, juice from whole herb is topically used to promote wound healing.[152] It is taken to improve virility and is used as a tonic and a remedy for anemia and cachexia.[21] In Uganda, leaves, stems and flowers are crushed and applied externally to treat lupus, skin rash, wounds, swelling, ulcers and infections.[21,179] In Rwanda, herbal decoctions including I. stuhlmannii leaves are used to treat paralytic diseases (hemiplegia, paraplegia, and polio). Fruits and leaves are used to treat external parasitosis. In Burundi, leaves are given to livestock to treat theileriosis.[21] Impatiens sulcata In China, seeds are used as edible material, the plant paste is applied to prevent urticaria and its mucilage is used as a abortifacient.[25,180] In Nepal, fruits are used as edible material and seed oil is used externally to relieve body pain and fever.[176] Impatiens textorii I. textorii is used in Japan, Korea, and Northeast China to treat allergic disorders, inflammation, ulcers, and infections in skin. The whole plant extract has been used as a detoxifying agent and as treatment for carbuncles, contusions, and superficial infections, including fingernail inflammations.[22,181-183] In China, decoctions from roots are used to promote circulation and to treat abdominal pain and swelling. Mashes from roots are externally used to treat pain, carbuncle sores, bruises, and snake bites.[22] In Korea, I. textorii is considered as a poisonous plant.[184] Impatiens tienchuanensis In China, stems and seeds are used for pain relief.[22] Impatiens tinctoria In Ethiopia, I. tinctoria subsp. abyssinica powdered roots are given to cattle to treat blackleg.[21,185] Leaves, stems and fruits are used to treat external parasitosis.[21] Red dye from tubers of I. tinctoria is used as cloth dye and as a beauty treatment, it is applied on skin to toughen it and to prevent fungal infections.[20,186-188] Root decoction is used to treat abdominal pain and as a purgative.[20] Root powder from I. tinctoria is warmed and applied on palm wounds.[131] Stems are chewed to treat mouth and throat problems.[20,187] In Kenya, decoction from roots is used to promote fertility.[21,189] Impatiens trilobata In Bangladesh, the plant is used to treat boils.[60] Impatiens tripetala In India, the plant is used to promote appetite.[190] Impatiens uliginosa In China, poultices from whole herb are used to treat snake bites, wounds, abscesses, ulcers, burns, scabies, herpes, psoriasis on hands and feet and scrotal eczema. Whole herb and roots are used internally or externally to relax muscles and to treat mouth sores, leprosy, plague, tuberculosis, migraine, apoplexy, colds, cough, epistaxis, hemoptysis, hematemesis, irregular menstruation, dysmenorrhea, postpartum bleeding, edema, rheumatism, arthritis, vomiting, diarrhea, difficult urination, bladder and kidney stones, acute nephritis, urinary tract infection, hematuria, hypertension, esophageal cancer, polydipsia, abdominal pain (pain in liver, spleen and stomach), jaundice, brain and tendon disorders, impotence and tonsillitis. Flowers are used to promote hair growth, to moist skin, and to dispel “cold” (a term used in Traditional Chinese Medicine as a reference for symptoms that include hypothermia, cold limbs, lost appetite, diarrhea, nausea, and vomiting).[156] The fruit is used for irregular menstruation.[22] The plant is used as a source of dyes for nails.[191] Impatiens urticifolia In Nepal, root paste is used to treat skin burns. Juice form leaves are used to treat urinary infections.[60,111] Impatiens walleriana In Ethiopia, roots are used by women to strength hair and are given to pigs as fodder.[21,192] In Tanzania, I. walleriana stems are used to treat liver pain while roots are used as abortifacient.[15,143,193] In Malawi, boiled roots and stems are also used as an abortifacient.[21] In Indonesia, flowers are used to treat cancer and fever.[24] In Brazil, the plant is used to treat uterus infections.[194] In Costa Rica, leaves, and young shoots from I. Pharmacognosy Reviews, Vol 17, Issue 34, Jul-Dec, 2023 345 Delgado-Rodríguez, et al.: Impatiens genus: Ethnobotany, Pharmacology and Bioactive Metabolites walleriana are rubbed on the skin to relieve insect bites pruritus and to heal hand wounds.[103,195] BIOLOGICAL ACTIVITIES Antimicrobial activity There is wide variability among reported results for the evaluation of the antimicrobial activity of different extracts from Impatiens plants. Phatthalung et al. reports that ethanol extract from I. balsamina stems has weak activity against Acinetobacter baumannii, reducing its growth to 9.77% at concentration of 250 µg/mL under broth dilution assay.[196] According to Grosvenor et al., the ethanol extract from I. balsamina stems and leaves has antibacterial activity against Staphylococcus aureus based on agar diffusion assay results.[93] Naitullah et al. reports that ethanol extract from I. balsamina leaves shows antifungal activity against Candida albicans with Inhibition Zone Diameters (IZD) from 6.00 to 13.66 mm according to agar diffusion assays.[197] The ethanol extract from I. balsamina leaves has antibacterial activity against Propionibacterium acnes with IZD in the range of 11.4-17.9 mm based on the same assay.[198] The ethanol (70%) extract from I. balsamina leaves has antibacterial activity against Escherichia coli and Shigella sonnei when 2.5 mg are applied in agar diffusion assay obtaining IZD values ranging from 13.7 to 14.7 mm. This extract can act synergically with chloramphenicol against both microorganisms.[199] Voravuthikunchai et al. indicates that aqueous extract from I. balsamina leaves is inactive against E. coli O157:H7 strains.[200] However, Hartanti et al. reported that aqueous extract from I. balsamina stems has antibacterial activity against S. aureus according to agar diffusion assay with IZD value of 16.43 mm when 20 µL of the extract are applied on test bacterial culture.[201] Comparison of the antibacterial activity of the ethanol and aqueous extracts from I. balsamina against S. aureus demonstrated that the ethanol extract is more potent with Minimal Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) of 6.3 and 25 mg/mL, respectively.[202] Kamble et al. reported the comparison of the antibacterial activity of the aqueous and ethanol extracts from I. balsamina leaves against E. coli, Bacillus subtilis, and Pseudomonas aeruginosa, using agar diffusion assay, results showed that ethanol extract has the best antibacterial profile with IZD values ranging from 10 mm to 19 mm.[203] Methanol and chloroform extracts from I. balsamina leaves have antimicrobial activity against Pseudomonas putida, Vibrio cholerae, Shigella flexneri and Streptococcus pyogenes with IZD values in the range of 6-22 mm.[204] The hexane extract from the leaves of I. balsamina has antibacterial activity against S. aureus, Klebsiella pneumonia, Proteus vulgaris, E. coli, Serratia marcescens, and P. aeruginosa with MIC and MBC ranging from 25 to 100 mg/mL.[205] Determination of the antimicrobial activity of the hexane, petroleum ether, acetone, methanol, and aqueous extracts from I. balsamina whole plants against Shigella boydii, Salmonella Paratyphi, P. vulgaris, S. aureus, C. albicans, and Cryptococcus neoformans, using agar diffusion assay, showed IZD values ranging from 1 mm to 36 mm.[206] The comparative evaluation of the antimicrobial activity of the ethanol, benzene, chloroform, methanol, petroleum ether, and aqueous extracts from leaves and roots of I. balsamina on B. cereus, K. pneumoniae, S. aureus, E. coli, S. typhimurium, P. aeruginosa, C. albicans, Aspergillus niger, Aspergillus flavus, Penicillium sp., and Trichoderma reesei showed that ethanol extract is the most active with MIC values in the range of 1-4 mg/mL.[207] Ethanol, petroleum ether, and ethyl acetate extracts from seeds of I. balsamina have shown antimicrobial activity against Bacillus anthracis, E. coli, and A. niger with IZD values ranging from 7.03 to 23 mm according to agar diffusion assay.[208] Ethanol extracts from flowers and seeds of I. balsamina have demonstrated activity under the same assay against S. aureus, P. aeruginosa and E. coli with IZD values in the range of 3.50-23.00 mm. Flower extract is the most active with IZD ranging from 7.83 to 23.00 mm.[209] The hexane, ethyl acetate, and ethanol extracts from I. balsamina flowers showed IZD ranging from 6.6 to 20.8 mm against S. aureus, E. coli, and C. albicans.[210] The comparative analysis of the antimicrobial activity of the petroleum ether (60-90°C), diethyl ether, chloroform, methanol, and water extracts from I. balsamina stems against B. subtilis, S. aureus, E. coli, S. boydii, Saccharomyces cerevisiae, Candida utilis, A. niger, Aspergillus oryzae, Penicillium italicum, and Penicillium digitatum demonstrated that petroleum ether and diethyl ether extracts are the most potent against test microorganisms (MIC ranges of 125-1000 µg/mL and 500-1000 µg/mL, respectively). Diethyl ether extract is active against all test strains while petroleum ether is not active against E. coli.[29] The evaluation of the antimicrobial activity of the ethanol (70% v/v) extracts from stems or leaves of I. balsamina recollected at different harvest times showed that extracts from leaves have the best results in agar diffusion assay with IZD values ranging from 8 to 15 mm after their application at concentration of 4 mg/mL in agar plates inoculated with Vibrio parahaemolyticus, Listeria monocytogenes, S. aureus, B. cereus, S. typhimurium, E. coli, C. albicans, or Clostridium perfringens. All test strains were susceptible to leaves extracts.[211] The ethanol (80:20 v/v, acidified with trifluoro acetic acid 0.5% v/v) extracts from orange and pink flowers of I. balsamina have shown antimicrobial activity on B. cereus, S. aureus, L. monocytogenes, E. coli, P. aeruginosa, S. typhimurium, Aspergillus fumigatus, Aspergillus versicolor, A. niger, Penicillium funiculosum, Penicillium ochrochloron, and Penicillium verrucosum var. cyclopium with MIC and MBC/Minimal Fungicidal Concentration Pharmacognosy Reviews, Vol 17, Issue 34, Jul-Dec, 2023346 Delgado-Rodríguez, et al.: Impatiens genus: Ethnobotany, Pharmacology and Bioactive Metabolites (MFC) values in the ranges of 0.006-0.20 and 0.012-0.40 mg/mL, respectively.[212] The evaluation of the antibacterial activity of the ethanol extracts from I. balsamina fruits, whole plants, seeds and the mixture of roots, leaves and stems demonstrated that the extract from fruits is the most active against Helicobacter pylori (including antibiotic-resistant strains) with MIC and MBC values in the ranges of 1.25-5 and 1.25-2.5 µg/mL, respectively. Comparative analysis of the antibacterial activity of extracts made from fruits using water, acetone, ethyl acetate or n-hexane against the same strains shows that acetone and ethyl acetate are the most active extracts with MIC and MBC values ranging from 0.625 to 2.5 µg/ mL.[46,213-215] Ethanol extract from I. balsamina aerial parts has anti-quorum sensing activity on Chromobacterium violaceum.[216] The acetone extract from I. balsamina leaves can inhibit the quorum sensing system on C. violaceum at concentration of 0.5 and 1 mg/mL. This extract has antibacterial activity against P. aeruginosa with a MIC of 3.125 mg/mL. At concentration of 1.56 mg/mL, the extract can inhibit Las A protease and chitinase activities of P.aeruginosa by 100% and 78.42%, respectively. It also can reduce the production of pyocyanin and biofilm formation on P. aeruginosa cultures by 93.33% and 30.75%, respectively. This extract is positive for the presence of 5,3’-dihydroxy flavone, 3-O-glucoside-6”- O-p-coumaroyl, luteolin 4’-O-glucoside, isorhamnetin 3-O-galactoside-6”-rhamnoside, quercetin 3-O-rutinoside (rutin) (2), kaempferol (3), and quercetin (4) according to High Performance Liquid Chromatography Coupled to Mass Spectrometry (HPLC-MS) analysis.[217] Aritonang et al., indicates that aqueous extract obtained from I. balsamina fresh leaves shows antibacterial activity against S. aureus and E. coli under agar diffusion assay. The antibacterial activity of the extract is enhanced by its formulation with AgNO3 nanoparticles. Formulations of the extract with 5 mM of AgNO3 have activity against S. aureus without difference in comparison with the activity of ciprofloxacin used as a positive control.[218] Carbon dots made with I. balsamina stems powder have antibacterial activity against Gram-positive bacteria with MIC values in the range of 0.08-0.02 mg/mL against S. aureus, Enterococcus faecium and B. subtilis, this preparate was inactive on Gram-negative bacteria (Salmonella sp, E. coli, and P. aeruginosa). The carbon dots act by promoting oxidative stress in bacterial cells.[219] The essential oil from I. balsamina aerial parts has antibacterial activity against S. aureus, E. coli, Citrobacter sp., Acinetobacter sp., and Klebsiella sp., when tested with a dilution factor of 1/250 on agar dilution assay. According to Gas Chromatography Coupled to Mass Spectrometry (GC-MS) analysis, β-thujone is the most abundant compound in the essential oil.[220] The comparative determination of the antimicrobial activity of the ethanol extracts from I. glandulifera roots, leaves, flowers and seeds and their low molecular weight peptide fractions (LMWPF, < 30 kDa) showed that LMWPF derived from leaves extract has the highest antimicrobial activity against S. aureus (MIC: 4200 µg/mL), Staphylococcus epidermidis (MIC: 1050 µg/ mL) and E. coli (MIC: 525 µg/mL). LMWPF from root extract is the most potent preparate against Streptococcus sanguinis and Streptococcus mutans with MIC of 62.5 µg/mL in both cases. The comparative evaluation of the cytotoxic activity of LMWPFs on human fibroblasts (BJ) indicates that evaluated LMWPFs, despite their antimicrobial activity, have low cytotoxicity against normal cells (half-maximal Inhibitory Concentration (IC50) values higher than 1000 µg/mL).[221] The study of the antibacterial activity of the methanol and chloroform extracts from I. walleriana leaves on Enterococcus faecalis, Enterococcus sp., B. subtilis, S. aureus, P. aeruginosa, E. coli, Salmonella sp., and K. pneumoniae indicates that methanol extract is the most active with IZD values in the range of 10-16 mm when applying 20 µL at concentration of 125 mg/mL on agar diffusion assay.[222] The evaluation of the antimicrobial activity of the ethanol (80% v/v, acidified with trifluoro acetic acid 0.5% v/v) extracts from I. walleriana orange and pink flowers against B. cereus, S. aureus, L. monocytogenes, E. coli, P. aeruginosa, S. typhimurium, A. fumigatus, A. versicolor, A. niger, P. funiculosum, P. ochrachloron, and P. verrucosum var. cyclopium demonstrated MIC and MBC/MFC values in the ranges of 0.025-0.20 and 0.05-0.4 mg/mL, respectively.[223] The comparative determination of the antimicrobial properties of ethanol (35 and 50%) and aqueous extracts from I. noli-tangere whole plants showed that aqueous extract is the most active against E. coli, S. aureus, B. subtilis, Proteus sp., and C. albicans.[224] The ethanol (50%) extracts from I. noli-tangere, obtained by microfiltration and ultrafiltration, have values of Total Phenolic Content (TPC) and Total Flavonoid Content (TFC) in the ranges of 590.2-983.7 mg of Gallic Acid Equivalents (GAE)/L and 184.8-449.5mg of Quercetin Equivalents (QE)/L, respectively. The combination of this extracts with the ethanol extract (70%) from Symphytum officinale gave an antibacterial mixture with IZD values from 4 to 21 mm in agar diffusion assays using S. aureus, S. epidermis, B. cereus, Proteus mirabilis, and E. coli as test bacteria.[225] The analysis of the antibacterial activity of the aqueous, ethanol and ethyl acetate extracts from I. tinctoria roots against S. aureus, S. epidermidis, S. pyogenes, Streptococcus agalactiae, E. faecalis, E. coli, S. typhimurium, S. flexneri, S. sonnei, P. aeruginosa, K. pneumoniae and P. mirabilis indicates that ethyl acetate extract is the most active with MIC and MBC values in the ranges of 0.7-16 and 8-32 mg/mL, respectively.[187] The evaluation of the antifungal activity of the aqueous, ethanol and ethyl acetate extracts from I. tinctoria roots against C. albicans, Trichophyton Pharmacognosy Reviews, Vol 17, Issue 34, Jul-Dec, 2023 347 Delgado-Rodríguez, et al.: Impatiens genus: Ethnobotany, Pharmacology and Bioactive Metabolites rubrum, Trichophyton mentagrophytes, A. niger, and A. flavus showed that the ethyl acetate extract is the most active with MIC and MFC values within the ranges of 0.7-32 and 1-64 mg/mL, respectively.[188] The study of the antibacterial activity of n-hexane, chloroform, ethyl acetate, and methanol extracts from aerial parts of I. bicolor showed that methanol extract has the best activity profile with IZD values ranging from 7 to 11 mm.[226] In other study, the n-butanol fraction rich in saponins obtained from the methanol (50%) extract of the leaves of I. capensis was inactive against S. epidermidis, S, aureus, B. subtilis, P. aeruginosa, E. coli and C. albicans.[120] The comparative study of the antimicrobial activity of the petroleum ether, ethyl acetate and methanol extracts obtained from the aerial parts of I. sulcata against E. coli, S. aureus, S. typhimurium, K. pneumoniae, Trichoderma viride, A. niger, and A. fumigatus demonstrated that ethyl acetate extract has the widest antimicrobial spectrum with IDZ values ranging from 10 mm to 22 mm.[180] Szewczyk et al. reported results for the comparative study of the antimicrobial activity of the methanol/acetone/water (3/1/1 v/v/v) extracts obtained from the aerial parts of six Impatiens species corresponding to I. balfourii, I. balsamina, I. glandulifera, I. noli-tangere, I. parviflora and I. walleriana. All extracts are active with MIC values ranging from to 125 µg/mL to 1000 µg/mL. However, I. noli-tangere extract is active against a higher number of test pathogens including S. aureus, S. epidermidis, M. luteus, B. subtilis, B. cereus, S. pneumoniae and C. albicans. The Ultra-High Performance Liquid Chromatography Coupled to Diode Array and Mass Spectrometry Detectors (UHPLC-DAD-MS) analysis identified quercetin 3-O-galactoside, quercetin 3-O-glucoside (isoquercetin) (5), and kaempferol 3-O-glucoside (astragalin) (6) as specific components present in I. noli-tangere extract, other compounds, including phenolic acids and glycosides derived from kaempferol, eriodictyol and quercetin were also detected without specific or absolute designation of their sugar moiety.[227] The comparative evaluation of the antimicrobial activity of the ethanol (80%) extracts from I. balsamina, I. walleriana and I. hawkeri whole plants against S. aureus, S. epidermidis, S. pyogenes, Streptococcus pneumoniae, P. aeruginosa, E. coli, C. albicans, and A. niger indicates that I. balsamina extract, has the best antimicrobial activity profile. It is active against all Gram-positive bacteria and C. albicans with MIC values ranging from 2.5 to 10 mg/mL. This extract has bactericidal effect against S. aureus, S. pyogenes, S. pneumoniae with an MBC value of 10 mg/mL.[8] The ethanol extract from I. balsamina flowers has shown antimicrobial activity against Monilinia fructicola, Colletotrichum lindemuthianum, A. niger, Penicillium notatum, Pythium debaryanum, Rhodotorula glutinis and S. aureus with IZD values ranging from 16 to 37.7 mm in agar diffusion assay. Compound 1 was isolated as the active antifungal principle. This compound has antifungal activity against Rhodotorula glutinis with IZD value of 24.7 mm when tested at concentration of 960 µg/mL in agar diffusion assay. The same substance has shown IC50 of 3.65 µg/mL on M. fructicola without phytotoxicity actions on tomato and beans shootings.[228] Similarly, Yang et al. has reported the isolation of 1 from the dichloromethane fraction of I. balsamina aerial parts ethanol extract by its bioguided fractionation using Artemia salina toxicity assay. This compound shows antibacterial activity against S. aureus, B. cereus, Bacillus megaterium, B. subtilis, Aeromonas salmonicida and Aquaspirillum serpens with MIC values ranging from 2 to 64 µg/mL. The isolated compound also has antifungal activity against C. albicans, Fusarium oxysporum, A. fumigatus, Microsporum gypsum and T. mentagrophytes with MIC values from 0.31 to 2.5 µg/mL. I. balsamina aerial parts tea contains 16.5 µg/mL of 1 according to High Performance Liquid Chromatography Coupled to Diode Array Detector (HPLC-DAD) analysis.[10,40] The fractionation of methanol extract from I. balsamina whole plants guided by broth dilution assay also allowed the isolation of 1. This compound is active on A. niger (MIC: 10 µg/mL), C. neoformans (MIC: 10 µg/mL), Epidermophyton floccosum (MIC: 5 µg/mL), B. subtilis (MIC: 5 µg/mL) and S. typhimuriun (MIC: 20 µg/mL).[229] Compound 1 showed antibacterial activity against Methicillin-Resistant S. aureus (MRSA) strains (MIC range of 61.5-125 µg/mL). It also shows synergic antibacterial activity against MRSA strains in combination with α-mangostin rich extract (95% w/w) obtained from Garcinia mangostana pericarp according to checkerboard dilution assay. Crystal violet absorption assay indicates that 1 induces cell wall disruption at concentration of 31.25 µg/mL in MRSA. Compound 1 has MRSA antibiofilm formation activity at concentration range from 1/16 to 1/2 of MIC.[230] Compound 1 and spinasterol (7) have been isolated from the acetone extract of I. balsamina fruits and the ethanol extract of a mixture made of I. balsamina roots, leaves, and stems. Both compounds have antibacterial activity against antibiotic resistant H. pylori strains, 1 has MIC and MBC values in the ranges of 0.156-0.625 and 0.313-0.625 µg/mL, respectively, while 7 demonstrates MIC and MBC values within the interval of 20-80 µg/mL. The activity of 1 is not influenced by pH values within 4-8. Measuring of the quantity of 1 among different anatomical sections of I. balsamina by HPLC-DAD analysis indicates that fruit is the organ with the highest level of this active substance (43.92 mg/g). It is proposed that 1 can act by promoting Reactive Oxygen Species (ROS) production that compromises bacterial cell viability.[10,74,213-215,231] Docking experiments suggest that 7 can potentially binds to cytotoxin-associated gene A (CagA), an oncogenic protein factor expressed by H. pylori. In this way, 7 may inhibit the interaction between CagA and phosphatidylserine of gastric epithelial cells, a process implicated in the activation of prooncogenic proteins Pharmacognosy Reviews, Vol 17, Issue 34, Jul-Dec, 2023348 Delgado-Rodríguez, et al.: Impatiens genus: Ethnobotany, Pharmacology and Bioactive Metabolites and the inactivation of tumor suppressors proteins in gastric cells. This in silico evidence shows that 7 can potentially be a starting point for the development of molecules useful to prevent gastric cancer related with H. pylori infections.[232] In other studies, compound 1 has demonstrated antibacterial activity against MRSA with a MIC of 15.6 µg/mL. It has antifungal activity on C. albicans and T. rubrum with MIC values of 7.8 and 3.9 µg/mL, respectively. According to checkerboard assay, this metabolite exerts additive activity with ampicillin against MRSA. Likewise, 1 has synergic antifungal effect with clotrimazole against C. albicans and T. rubrum.[233] A mouthwash containing 1 at concentration 0.025% has demonstrated protective activity against Candida growth in oral cavity of HIV-infected patients or denture wearers.[234,235] The use of mouthwash with 1 at 0.025% can reduce the count of Candida sp. colonies in the oral cavity of HIV-infected subjects and denture wearers with minimum changes in the genotype of isolated Candida species. This result suggests that mouthwash with 1 as active principle can be effective as a prophylactic agent against oral candidiasis in HIV-infected patients and denture wearers with low risk of antifungal resistance induction.[12] Oral sprays containing α-mangostin (5 mg/mL), 1 (250 µg/mL) or a combination of both (at concentration of 5 mg/mL and 250 µg/mL, respectively) were effective to inhibit the growth of S. mutants, Porphyromonas gingivalis and C. albicans. Among the assayed formulations, the one that only has 1 (250 µg/mL) as active principle was the most effective against C. albicans with MIC and MFC of 6,25% v/v, however, against S. mutans, the formulation that combines α-mangostin (5 mg/mL) and 1 (250 µg/mL) was the most effective with MIC and MBC of 6.25% (v/v) and 25% (v/v), respectively. All spray formulations shown MIC and MFC values of 25% (v/v) against P. gingivalis. The spray formulation that combines both components have the highest inhibitory activity against biofilm formation by all microorganisms tested.[236] There is interest in the application of 1 as a low toxicity antifungal agent for crops protection. This compound has shown inhibitory effects against P. digitatum growth, a fungi pathogen of citrus, with a MIC of 5.0 μg/mL in broth dilution assay. Changes in mycelia morphology have been observed after treatment of P. digitatum with 1, twisting and swelling are the main reported changes. Based on transcriptomic, proteomic and metabolomic analyses of the effects of 1, it has been observed that this molecule exerts its inhibitory action against P. digitatum by affecting the synthesis of amino acids and cell wall components.[237] Compound 1 reduce P. italicum mycelial growth by 97.54% at concentration of 6.0 µg/mL. The proteomic profile of treated cultures indicates a remarkable disruption in the expression of fundamental proteins for energy metabolism and stimulus response.[238] Compound 2-hydroxy-1,4-naphthoquinone (lawsone) (8), another naphthoquinone isolated from Impatiens balsamina,[239] is recognized by its antiparasitic activity against Plasmodium falciparum (IC50 = 1.9x10-4 M) and nematodes. This compound acts by inhibition of dihydroorotate dehydrogenase enzyme. The ethanol extract from I. balsamina stems has decreased the motility of Caenorhabditis elegans by about 30% at concentration of 10 mg/mL.[54] The determination of the antimicrobial activity of the main naphthoquinones presents in I. balsamina leaves corresponding to 1, 8 and 2,2´-methylenebis(3-hydroxy-1,4-naphthoquinone) (9), against S. aureus, S. epidermidis, B. subtilis, E. coli, P. acnes, H. pylori, and S. mutans, showed that 1 is the most active substance with MIC and MBC values in the range of 3.5-125 µg/mL and 7.8-125 µg/mL, respectively. This compound demonstrated bactericidal effect on all assayed bacteria except P. acnes.[239] Compounds 3 and 4 have shown activity against P. acnes, including clindamycin-resistant strains, with MIC and MBC in the ranges of 32-64 µg/mL and 64-256 µg/mL, respectively. Both compounds can show synergism in combination with clindamycin with fractional inhibitory concentration indexes ranging from 0.187 to 0.562.[77,240] I. balsamina is recognized as an important source of antimicrobial peptides. Four antimicrobial peptides (Ib-AMP1 (10), Ib-AMP2 (11), Ib-AMP3 (12), and Ib-AMP4 (13)) have been isolated from I. balsamina seeds. They showed activity against several fungi and bacterial strains with low in vitro toxicity on human cells.[241-245] Ib-AMP peptides are constituted by 20 amino acids in length and they are encoded as part of the same transcript. It is known that 10 associates with cell membranes and induces death of fungus by unknown process different than pore formation and cell lysis induction.[242] Results from circular dichroism spectroscopy and proton nuclear magnetic resonance spectroscopy show that 10 has two hydrophilic zones at opposite ends that are separated by a large hydrophobic zone. Data indicates the existence of three β-turns located at residues 9-12, 10-13, and 12-15.[246] Ib-AMP peptides activity is 2-20 times higher on filamentous fungi than yeast. It is proposed that this difference is a consequence of the higher content of chitin in cellular wall of filamentous fungi that enhance Ib-AMP peptides binding.[247] Compound 10 has antifungal activity with MIC values against C. albicans and A. flavus ranging from 2.5 to 5 µM, for oxidized peptide, or between 10 and 20 µM for the reduced form. The study of mechanism of antifungal activity of 10 showed that the oxidized peptide disrupts liposomal membranes composed of phosphatidylcholine and phosphatidylserine. Moreover, it is known that 10 can enter C. albicans cytoplasm, few is known about this internalization process and fungi death mechanism triggered by 10 inside the cell, but it has been observed that 10 associates with cell membrane and intracellular organelles of C. albicans.[247,248] Pharmacognosy Reviews, Vol 17, Issue 34, Jul-Dec, 2023 349 Delgado-Rodríguez, et al.: Impatiens genus: Ethnobotany, Pharmacology and Bioactive Metabolites Compound 10 shows activity against pathogenic bacteria that includes E. coli O157:H7, P. aeruginosa, S. aureus and B. cereus with MIC values ranging from 50 to  200 µg/mL according to broth microdilution assay. This peptide exerts bactericidal activity on E. coli O157:H7, P. aeruginosa and S. aureus with MBC values within the range of 50 to 400 µg/mL. Compound 10 does not have antibacterial residual activity.[249] This compound promotes an increase in the number of E. coli O157:H7 permeable cells (56.18%) compared to control (untreated cells), additionally, peptide 10 promotes potassium and Adenosine Triphosphate (ATP) efflux from cells. Other effects include dissipation of membrane potential and reduction of Deoxyribonucleic Acid (DNA), Ribonucleic Acid (RNA) and protein synthesis in E. coli O157:H7 cells.[250] Compound 12 reduces A. flavus germinated conidia growth by 41.2% at concentration of 25 µM according to broth dilution assay. This peptide does not show activity against non-germinated conidia of A. flavus. In contrast, 12 has strong activity against non-germinated and germinated conidia of Fosarium moniliforme, it reduces their viability by 95,3% and 99,5% at concentration of 25 µM, respectively. According to binding affinity assays, 12 has high affinity for chitin. This binding is viewed as a critical process for 12 antifungal activity.[251] The comparison of the antifungal activity of Ib-AMP peptides indicates that 13 is the most active peptide. This compound exerts inhibitory activity on plant pathogenic fungi strains corresponding to Alternaria longipes, Botrytis cinerea, Cladosporium sphaerospermum, Fusarium culmorum, P. digitatum, Trichoderma viride, Verticillium alboatrum, Gloeosporium solani, Nectria galligena, Phialophora malorum and Sclerotinia sclerotiorum. The IC50 of 13 varies between 1 to 150 µg/mL in broth dilution assay and is significantly increased when culture media is supplemented with calcium. Compound 13 is also the most active Ib-AMP against human pathogenic Gram-positive bacteria (B. subtilis, Micrococcus luteus, S. aureus, and E. faecalis) and plant pathogenic Gram-negative bacteria (Xanthomonas campestris pathovar pelargonii and Xanthomonas oryzae). This peptide shows IC50 values ranging from 5 to 20 µg/ mL against these microorganisms.[251-254] In other study, Fan et al. reports that 13 has shown antibacterial activity in broth microdilution assay against B. megaterium (MIC: 0.49 µM), B. subtilis (MIC: 0.98 µM), M. luteus (MIC: 1.97 µM), Enterococcus casseliflavus (MIC: 1.57 µM), E. faecalis (MIC: 15.74 µM), Vancomycin-resistant Enterococci (MIC: 31.48 µM), S. aureus (MIC: 3.15 µM), MRSA (MIC: 9.84 µM), S. epidermidis (MIC: 31.48 µM), Streptococcus oralis (MIC: 31.48 µM), Staphylococcus saprophyticus (MIC: 0.98 µM), S. agalactiae (MIC: 62.97 µM), S. pneumoniae (MIC: 7.87 µM), S. pyogenes (MIC: 3.15 µM), Klebsiella oxytoca (MIC: 15.74 µM), K. pneumoniae (MIC: 47.23 µM), E. coli (MIC: 3.15 µM), P. aeruginosa (MIC: 62.97 µM). Compound 13 has demonstrated synergic effect when is combined with thymol against K. pneumonia and E. faecalis. Furthermore, it has synergic activity against E. faecalis when combined with silver nitrate.[255] The antibacterial activity of 13 also varies according to growth media conditions used in inhibition assays. This peptide exerts antibacterial activity against the following Gram-positive bacteria: B. megaterium, B. subtilis, M. luteus, S. agalactiae, E. faecalis, S. oralis, S. epidermidis, S. aureus, S. pneumoniae, S. pyogenes and Enterococcus casseliflavus. It also shows activity against Gram-negative bacteria, including K. oxytoca, K. pneumoniae, E. coli and P. aeruginosa. The MIC obtained for this peptide in broth microdilution assay on mentioned bacteria range from 1.25 to 160 μg/mL in calcium-free media, however, in culture media containing calcium, the MIC varies between 10 and 160 μg/mL on all bacteria excepting S. oralis, S. epidermidis, K. oxytoca and P. aeruginosa whose growth is not completely inhibited within that concentration range.[256] According to Quartz Crystal Microbalance with Dissipation (QCM–D) experiments, 13 at test concentration of 200 µg/mL, can penetrate unilamellar liposomes made of 1,2-dioleoyl-sn -glycero-3-phosphocholine (DOPC) used as a model of cellular membranes. Studies with QCM-D also showed the existence of resealing phase after 13 insertions on liposomes surface. Experiments on DOPC liposomes with encapsulated calcein, a fluorescent probe, have demonstrated that 13 induces calcein release with maximal response at concentration of 100 μg/mL. Bactericidal kinetics evaluation of 13 showed that it can kill 98% of S. aureus cells in 10 min at concentration of 40 μg/mL. Observation of E. coli cells after treatment with 500 μg/mL of 13 for 20 min revealed leaking of part of their cytoplasm without loss of their characteristic rod shape. This result indicates that 13 does not produce lyses of cell wall. Instead, integration of the evidence obtained from these studies suggests that 13 exerts its bactericidal action in an insertion–poration–resealing pattern that occurs repeatedly on bacterial cell surface.[257] Compound 13 can be produced successfully by biotechnology strategies. It was expressed in E. coli BL21 and its bactericidal activity evaluated against Acinetobacter calcoaceticus, P. vulgaris, P. mirabilis, Enterobacter cloacae, S. marcescens, Pseudomonas stutzeri, P. aeruginosa, K. oxytoca, Klebsiella aerogenes, Citrobacter freundii, E. coli, E. faecium, S. pneumoniae, Staphylococcus haemolyticus, S. epidermidis, and S. aureus (including MRSA strains) resulted in MIC values in the range of 1.5-128 µg/mL on susceptible strains. Only A. calcoaceticus, P. aeruginosa, C. freundii are not susceptible at maximum test concentration of 128 µg/mL.[245,258] According to data obtained from models of MRSA induced wound infection and septicemia on Syrian mice, 13 expressed in E. coli BL21 are effective to promote wound healing and to span survival time on treated animals.[245] Pharmacognosy Reviews, Vol 17, Issue 34, Jul-Dec, 2023350 Delgado-Rodríguez, et al.: Impatiens genus: Ethnobotany, Pharmacology and Bioactive Metabolites Several research works have been done to improve the antimicrobial activity of Ib-AMP peptides through structure modifications. One of them has allowed to discover that 10 with oxidized cysteine residues in the form of disulfide bridges is 4-fold more potent than the reduced form of the peptide against in vitro cultures of C. albicans and A. flavus.[242] Wang et al. reported the optimization of 10 antibacterial activity by modifying its amino acid sequence. Four analog peptides were synthetized without disulfide bonds of 10. In analogue 1, one amino acid from both, N-terminal and C-terminal extremes, was removed in comparison to 10. Analogues 2, 3 and 4 have the same modifications than analogue 1 but they include a substitution of L-proline at eighth position. In analogue 2, 3 and 4, L-proline was substituted by D-proline, alanine peptoid residue, and lysine peptoid residue, respectively. The analogues are more active against E. coli, P. aeruginosa, S. typhimurium, B. subtilis, S. epidermidis, S. aureus than 10. Analogue 4 has the lower MIC values (2-16 µM) according to broth microdilution assays. All analogues and 10 have minimal hemolytic concentration higher than 400 µM. These analogue peptides promote a higher increase in S. aureus membrane permeability and depolarization than 10. According to circular dichroism spectroscopy, peptides acquire a β-sheet conformation in negative charged micelles that function as a bacterial membrane-mimetic environment. It is suggested that this conformation is important to compromise the bacterial membrane integrity.[259] The antibacterial and hemolytic profile of 13 have been optimized according to experimental results obtained for synthetic analogues of this peptide. It is possible to get a peptide with more than 100-fold potency of 13 (reducing the IC50 against E. coli from > 100 to 1 µM) without hemolytic activity at concentration equivalent to its antibacterial IC50 value. This peptide can be obtained by the elimination of disulfide bonds and the replacement of amino acid residues: cysteine at sixth, seventh and sixteenth positions by methionine, proline at position eleventh by arginine, tyrosine at position fifteenth by methionine, and cysteine at twentieth position by tryptophane.[260] Peptides Ib-M1, Ib-M2, and Ib-M6 are analogues of 13 that have shown antibacterial activity against E. coli. From them, Ib-M2 is the most active with MIC and MBC values of 3.1 and 7.6 µM, respectively.[261] Other synthetic peptides derived from 10 and 13 have improved antifungal activity against B. cinerea, F. culmorum, S. cerevisiae, and Pichia pastoris.[262] It has been proposed that Impatiens species can host endophyte microorganisms that produce antimicrobial products. Co-culture experiments have demonstrated that actinomycetes isolated from I. chinensis can inhibit the growth of plant pathogenic fungi that includes Verticillium dahlia, F. oxysporum, Colletotrichum orbiculare, Fusarium graminearum, Exserohilum turcicum, Curvularia lunata and B. cinerea. This actinomycetes also show activity against S aureus.[263] Antineoplastic activity Comparison of the cytotoxic activity of petroleum ether, ethyl acetate, and butanol extracts from I. balsamina seeds indicates that ethyl acetate extract has the strongest inhibitory effect on proliferation of human prostate adenocarcinoma (PC-3), human prostate epithelial carcinoma (RV1), and human androgen-sensitive prostate adenocarcinoma (LNCaP) cell lines with IC50 values of 32, 69 and 85 μg/mL, respectively. This extract, at concentrations of 40 and 80 µg/mL, can inhibit Matrix Metalloproteinase 2 (MMP-2) expression and reduce the cell migration of PC-3 and RV1 cells according to transwell matrigel migration assay. At the same concentrations, the extract induces cell cycle arrest at the G0/G1 phase and apoptosis in PC-3 and LNCaP cells. Apoptosis is triggered by the activation of caspase 3 and the increase of B-cell lymphoma 2 associated X protein (Bax) activation and decrease in the activity of B-cell lymphoma 2 (Bcl-2) protein. The extract can reduce the phosphorylation of protein kinase B (Akt) and Extracellular Signal-Regulated Kinases (ERK) proteins, this promotes a reduction in cell growth and proliferation.[52] The methanol extract from I. balsamina herb can promote cytotoxic effects against Human Oral Squamous Cell Carcinoma (HSC-4) cell line in a dose-depending pattern at concentrations in the range of 10-40 µg/mL. This extract promotes activation of caspase 3, cleavage of poly-adenosine diphosphate-ribose polymerase, DNA fragmentation, nuclei condensation and apoptosis. The extract reduces the phosphorylation of Akt and promotes its degradation. It also reduces survivin protein and messenger RNA (mRNA) expression and promotes Bax activation and its translocation to mitochondria. Similar effects are observed against Human Oral Squamous Cell Carcinoma (OSC-20) cell line when the extract is tested at concentration of 100 µg/mL.[264] The methanol extract from I. balsamina can reduce the cell viability of Human Oral Squamous Carcinoma (HSC-2) cell line by 30% approximately. This extract induces the activation of 5'-Adenosine Monophosphate-Activated Protein Kinase (AMPK) pathway and attenuates mammalian Target of Rapamycin (mTOR) signaling. The extract promotes the expression of BH3-interacting domain death agonist (Bid), Bcl-2 homologous antagonist/killer (Bak) and Bcl-2-associated agonist of cell death (Bad) proteins, as consequence, it induces cell apoptosis in HSC-2 cells.[265] The evaluation of the cytotoxicity of the ethanol (80:20 v/v, acidified with trifluoro acetic acid 0.5% v/v) extracts from the orange and the pink flowers of I. balsamina against human breast adenocarcinoma (MCF-7), human non-small cell lung cancer (NCI-H460), human cervical carcinoma (HeLa), human hepatocellular carcinoma (HepG2), and normal porcine liver (PLP2) cell lines demonstrated that all cancer cells are susceptible to extracts. The extract from pink flowers is the most potent with Pharmacognosy Reviews, Vol 17, Issue 34, Jul-Dec, 2023 351 Delgado-Rodríguez, et al.: Impatiens genus: Ethnobotany, Pharmacology and Bioactive Metabolites IC50 values ranging from 90 to 167 µg/mL. None of the extracts are active at a concentration of 400 µg/mL against PLP2 used as normal cells.[212] The ethanol extract (80%) from whole plants of I. balsamina is cytotoxic against normal mouse embryonic fibroblast (NIH 3T3) and HeLa cells (IC50 of 49.6 and 33.7 µg/mL, respectively). Results from xenograft model in Swiss albino mice using Dalton's Lymphoma ascites (DLA) cell line indicates that extract prolongs life span, reduces blood count of tumor cells, attenuates weight gain, and partially counteracts changes in hematological parameters (counts of white blood cells count, red blood cells, and platelets; packed cell volume; hemoglobin) when is given at daily oral dose of 200 mg/kg or 400 mg/kg.[10,82] Ding et al. reported the isolation 1 from the chloroform extract of I. balsamina leaves through chromatographic fractionation guided by the results of 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT) cell viability assay on HepG2 cells. The crude extract and the isolated compound showed IC50 values of 41.5 and 6.08 µg/mL, respectively.[10,266] Compounds 1, balsamitril (14), balsamitril-3-O-β-D-glucoside (15), (3S,4R)-3,4-dihydroxy-3,4-dihydronaphthalen-1(2H)-one (16), trans-(3S,4S)-3,4-dihydroxy-1-tetralone (17), hydroquinone (18), p-hydroxybenzoic acid (19), p-hydroxybenzoic acid methyl ester (20), protocatechuic acid (21), vanillic acid (22), tyrosol (23), trans-p-coumaric acid (24), and trans-ferulic acid (25) were isolated from I. balsamina white flowers methanol (80%) extract. The evaluation of their cytotoxicity against human lung adenocarcinoma (A-549), human ovarian adenocarcinoma (SK-OV-3), human malignant melanoma (SK-MEL-2), and human colorectal cancer (HCT-15) cell lines showed that 1 has the best antineoplastic profile with IC50 values of 25.51 and 1.03 µM against A-549 and SK-MEL-2 cells. The IC50 values against SK-OV-3 and HCT-15 cells are > 30 µM.[267] The bioassay-guided fractionation of methanol extract from aerial parts of I. balsamina using luciferase test on Human Embryonic Kidney cell line (HEK293) allowed the isolation of 1 as a compound that downregulates T Cell Factor protein (TCF)/β-catenin complex transcriptional activity (IC50 of 2.9 µM). This cellular process is necessary for protein expression when Wnt signaling pathway is active. The activation of Wnt pathway can induce carcinogenesis, therefore, compounds that inhibits these signaling events are considered as potential agents to suppress cell growth.[268] Compound 1 exerts cytotoxicity against A-549 cell line according to cell viability assays (IC50 of 7.5 µM). The compound induces apoptosis in A-549 cells at concentration of 10 µM without distinction of cell cycle phase. In vitro assay using fluorogenic probe 2′,7′-dichlorodihydrofluorescein diacetate (DCFDA) reveals that 1 promotes ROS generation in A-549 cell cultures. This ROS generation triggers damage in DNA and activation of c-Jun N-terminal Kinase (JNK) and p38 Mitogen-Activated Protein Kinase (MAPK) proteins, these processes are responsible of apoptosis induction in A-549 cells exposed to 1.[269,270] Moreover, 1 induces cytotoxicity on human stomach adenocarcinoma (MKN45) cells with IC50 of 24.01 μM. This substance promotes S and G2/M phases cell cycle arrest, disrupts cell membrane potential, increases the production of ROS, and triggers apoptosis via Bax expression and cytochrome c release from mitochondria.[271] Daud et al. reported that 1 and apigenin (26), a flavonoid present in several Impatiens species,[182,212,225,272-275] can reduce the viability of human breast triple-negative adenocarcinoma (MDA-MB-231) cells (IC50 of 29 µM). Compounds 1 and 26 reduce the glucose up-take (approximated reduction of 40%) at concentrations of 29 and 100 µM, respectively. On the other hand, 1 reduces lactate production and the expression of Akt and glucose transporter 1 (GLUT-1) mRNAs.[276] According to Liew et al., 1 reduces the cell viability of MDA-MB-231 cells by approximately 60% at concentration of 20 µM. This compound can decrease the cell migration and invasion according to results of wound-healing migration and Matrigel invasion assays when evaluated at concentration range of 2.5-7.5 µM. Compound 1 reduces the activity of Matrix Metallopeptidase 9 (MMP-9) in cell secreted protein fraction by 75% at concentration of 7.5 µM.[277] The exposition of MDA-MB-231 cells to 1, at concentration of 7.5 μM, promotes changes in the proteome including a reduction in the expression of nineteen proteins implicated in cytoskeleton organization, protein synthesis and folding, protein covalent modification, ribosome processing, cell adhesion, epithelial-mesenchymal transition, Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation, cell cycle DNA transcription, DNA repair, DNA methylation, nucleotide synthesis, immune response, mRNA processing and membrane trafficking. Furthermore, the expression of seven proteins implicated in oxidative stress response and protein tyrosine phosphatase activity is increased. Among those proteins which expression is reduced, S100-A4 and laminin-binding protein (RPSA) are highlighted due their roll in metastasis promotion while the increase in E-cadherin expression is also remarkable considering its role in preventing epithelial-mesenchymal transition. Another change observed in treated cells is the reduction in NF-κB and ERK1/2 phosphorylation.[278] The treatment of human Burkitt lymphoma (Raji) cells with 1 at concentration of 40 µM induces changes in the expression of genes implicated in MAPK, Phosphoinositide 3-kinase (PI3K), and NF-кB signaling pathways. Up-regulated genes participate in cell cycle, apoptosis, and tumor suppressor while down-regulated genes are involved in apoptosis inhibition, angiogenesis, and cell cycle, they mainly correspond to transcription factors and proto-oncogenes.[279] Pharmacognosy Reviews, Vol 17, Issue 34, Jul-Dec, 2023352 Delgado-Rodríguez, et al.: Impatiens genus: Ethnobotany, Pharmacology and Bioactive Metabolites Balsaminone A (27), B (28) and C (29) have been isolated from I. balsamina seed ethanol extract. Cytotoxic activity of these compounds has been evaluated on human liver cancer (Bel-7402), A-549, and HeLa cell lines. According to results, 27 is the most active compound with IC50 of 9.36, 11.25 and 9.73 µM on A-549, Bel-7402 and HeLa cells, respectively. The other two compounds have IC50 values ranging from 19.05 to 64.69 µM against the same cell lines.[10,50] Compounds 1, 28, balsaminone D (30), and balsaminone E (31), were isolated from the ethanol (75%) of I. balsamina flowers. The cell viability assay against tumor necrosis factor α (TNF-α) stimulated rat hepatic stellate (t-HSC/Cl-6) cells showed that 30 is the most potent compound (IC50 of 30.54 µM).[280] Compounds 2, 3, 4, 6, kaempferol 3-O-rutinoside (nicotiflorin) (32), kaempferol 3-O-α-rhamnoside-7,4-di-O-β-galactoside (33), 6-methoxykaempferol 3-O-β-D-glucosyl(1′′′→2′′)-β-D- glucopyranosyl-(6′′′-(E)-caffeoyl)-7-O-β-D-glucopyranoside (34), dihydromyricetin (35), myricetin (36), 1,2-O-(4-dihydroxy- benzoyl)-2,4,6-trihydroxyphenylacetic acid (37), methyl 2-O-(4-hydroxybenzoyl)-2,4,6-trihydroxyphenylacetate (38), 2-O-(4-hydroxybenzoyl)-4-O-β-D-glucopyranosyl-6- hydroxyphenylacetic (39), methyl 2-O-(4-hydroxybenzoyl)- 4-O-β-D-glucopyranosyl-6-hydroxyphenylacetate (40), ethyl 2-O-(4-hydroxybenzoyl)-4-O-β-D-glucopyranosyl-6- hydroxyphenylacetate (41), butoxy 2-O-(4-hydroxybenzoyl)-4 -O-β-D-glucopyranosyl-6-hydroxyphenylacetate (42), butoxy 2-O-(4-hydroxybenzoyl)-4,6-dihydroxyphenylacetate (43), (6-O-p-coumaroyl)-β-D-glucopyranosyl-2-O-(4-hydroxy benzoyl)-4-O-β-D-glucopyranosyl-6-hydroxyphenylacetate acid (44), and 4-O-β-D-glucopyranosyl-2,6-dihydroxyphenylacetic acid (45) were isolated from the ethanol (75%) extract of I. balsamina flowers. The evaluation of their cytotoxicity against t-HSC/Cl-6 cells indicates that 36 is the most active compound with a IC50 value of 15.91µg/mL.[281] Aromatase enzyme is considered as a molecular target in metastatic estrogen-dependent breast cancer. Aromatase inhibition in vitro assay indicates a IC50 value of 10 µM for 36. FlexX docking studies, have shown that binding complexes between 36 and human aromatase have energies ranging from - 23 to kJ/mol to -13 kJ/mol for the best 20 poses.[282] Imbalosides A (46), B (47) and C (48) are oleanane-type triterpenoidal glycosides isolated from the white flowers of I. balsamina. The cytotoxicity of the compounds was tested in vitro on A-549, SK-MEL-2, SK-OV-3, and human invasive breast carcinoma (BT549) cell lines. No compound is cytotoxic against SK-OV-3 and SK-MEL-2 cell lines at concentration of 30 µM. Only 48 exhibited low cytotoxic on A-549 cell line (IC50 = 29.8 µM) while 47 and 48 are cytotoxic on BT549 cell line (IC50 of 26.4 µM and 29.2 µM, respectively).[283,284] Compounds balsaminsides A (49), B (50), C (51) and D (52) were isolated from the ethyl acetate fraction obtained from the ethanol (75%) extract of I. balsamina flowers. These compounds demonstrated anti-hepatic fibrosis activity on t-HSC/Cl-6 cells with IC50 range of 13.9-98.91 μM. Compound 49 is the most potent compound.[13,33] Honsenkol A-3-O-β-D-glucopyranosyl-26-O-β-D-glu copyranosyl-28-O-β-D-glucopyranosyl-O-β-D-glucopyranose (53) and (3S,4R,17R,20S)-17-hydroxy-3-O-β-D- xylopyranose(12)-β-D-glucopyranosyl-26-O-β-D-glucopyran osyl-28-O-β-D-glucopyranosyl-21,24-epoxybaccharane (54) were isolated from ethanol extract (80%) of I. balsamina seeds. Compound 54 has demonstrated cytotoxic activity on human melanoma (A375) cells with IC50 of 114.96 μM.[51] Model of tumorigenesis induction in Swiss Webster albino mice by topic exposition to dimethylbenzanthracene and croton oil demonstrated that the external application of the ethanol extract from leaves of I. balsamina and 1, in the area where the skin tumorigenesis has been promoted, can protect internal organs (stomach, pancreas, duodenum, and spleen) against the development of histological alterations observed in non-treated animals.[285] The comparative study of the cytotoxicity of the n-hexane, ethyl acetate and methanol extracts from stems, leaves and roots of I. glandulifera against A-549, human glioma (U373) and human melanoma (SMEL-28) cell lines indicates that ethyl acetate extract from stems is the most active with a median IC50 of 33 μg/mL. The compounds 1 and 7 were isolated from the ethyl acetate extract from the stems, leaves and roots, while glanduliferin A (55) and glanduliferin B (56) were obtained from the ethyl acetate extract from stems. The evaluation of the cytotoxicity of these isolated compounds against the after mentioned cell lines showed that 1 is the most active compound with IC50 values in the range of 2-3 µg/mL.[286] Seeds from several Impatiens species, including I. balsamina, I. bracteata, I. campanulata, I. chinensis, I. cuspidata, I. gardneriana, I. jurpia, I. latiflora, I. latifolia, I.pulchra, I. oppositifolia, I. pulcherrima, I. racemosa, I. racemulosa, I. stenantha, I. talbotii, I. tomentosa, and I. viscida have α-parinaric acid (57) in quantities in the range of 3.18-34.15%. Seeds from I. racemulosa have the highest content of this unsaturated fatty acid.[287] Compound 57 is also the mayor fatty acid present in the oil of I. edgeworthii seeds.[288] Cytotoxicity of 57 was evaluated using in vitro cell viability assays with fetal rat astrocytes (36B10), rat glioma (C6), human glioma (A172), and human monocytic leukemia (U-937) cell lines. The test compound induces a cell death percentage of 20% in fetal rat astrocytes at concentration of 40 μM. At 4 μM, 57 promotes a cell death percentage of 70% in 36B10 line. In C6 and A172 glioma lines, cell mortality is 70% and 82% when they are exposed to 57 at concentration of 12 μM, respectively. In U-937 cell line, the cell mortality induced by 57 is 90% at concentration Pharmacognosy Reviews, Vol 17, Issue 34, Jul-Dec, 2023 353 Delgado-Rodríguez, et al.: Impatiens genus: Ethnobotany, Pharmacology and Bioactive Metabolites of 4 μM. Isoprostane is increased in cell cultures treated with 57 and cytotoxicity of this compound is attenuated when culture media is supplemented with α-tocopherol, this observation suggest that 57 acts via oxidative stress induction.[289] Moreover, it has been demonstrated that 57 induces cell death in 36B10 line via JNK upregulation and p38 MAPK downregulation according to western blotting and Reverse Transcription-Polymerase Chain Reaction (RT-PCR) analyses of cell cultures treated with 57.[290] IPS-1 (58) and IPS-2 (59) were isolated from the n-butanol fraction of methanol extract form the leaves of I. parviflora. According to the Vibrio harveyi mutagenicity assay, both compounds are no mutagenic at concentration of 40 ng/mL. Compound 58 is cytotoxic on A375 and human melanoma (HTB140) cell lines inducing a reduction in cell viability of 69.51% and 39.81% at concentration of 50 µg/mL, respectively. Compound 58 also reduces the viability in prostate cancer Du145 and PC-3 cell lines by 49.61% and 17.32%, at the same test concentration, respectively. However, 58 is inactive against human melanoma (WM793), BJ and normal human prostate epithelium (PNT2) cells at concentration of 50 µg/mL.[161] Compounds monogalactosyl diacylglycerol 1 (MGDG-1) (60) and digalactosyl diacylglicerol 1 (DGDG-1) (61) have been isolated from the methanol extract of I. parviflora. The cytotoxicity of these compounds has been tested against WM793, HTB140, A-375, and human keratinocyte (HaCaT) cell lines. Compound 60 is more active than 61 with IC50 of 15.14 µg/mL against A375. However, this value is > 50 µg/mL on the remaining cell lines. Compound 60 shows synergic cytotoxicity in combination with doxorubicin on A-375 cell line. It also inhibits around 40% of tyrosinase enzyme activity at concentration of 500 µg/mL while 61 is inactive. Lactate dehydrogenase viability assay performed on HepG2 cell indicates that 60 and 61 have not hepatotoxicity activity at concentration of 100 µg/mL.[291] Impatienoside G (62) was isolated from the n-butanol fraction of the ethanol-water (7:3) extract obtained from I. siculifera whole herb. This compound showed cytotoxic activity against human acute myeloid leukemia (HL-60), human stomach adenocarcinoma (KATO-III), and A-549 cells with IC50 values of 21.8, 36.7, and 24.8 µM, respectively.[177] Impatiprins A (63), B (64), and C (65) were isolated from n-butanol fraction from the methanol extract of I. pritzelii Hook. f. var. hupehensis rhyzomes. According to cytotoxicity assays, 63 has IC50 values of 106.5, 134.57, and 157.83 µM against Balb/c mice sarcoma tumor (S-180), HeLa and HepG2 cell lines, respectively. Compound 64 has IC50 values of 37.40, 44.93, and 55.78 µM against S-180, HeLa and HepG2, respectively. Compound 65 is inactive on the same cell lines.[163] Compounds 62, scaberoside A2 (66), 3-O-β -D-glucuronopyranosyl-echinocystic acid-28- O -β-D-apiofuranosy l - (1→3)[O -β-D-xy lopyranos e y l ) (1→4)]-O-α-L-rhamnopyranosyl-(1→2)-β-L-arabinopyaranoside (67), and 3-O-β-D-glucuronopyranosyl-echinocystic acid 28-O-β-D-apiofuranosyl-(1→3)[O-β-D-xylopyranosyl-(1→4)]- O-α-L-rhamnopyranosyl-(1→2)-β-D-xylopyranoside (68), were isolated from I. pritzelii var. hupehensis rhizome ethanol (50%) extract. Compound 62 is the most potent in reducing the cell viability of Balb/c mice lymphocytes. It reduced the cell viability by 38.9% at concentration of 80 µg/mL.[167] The evaluation of the cytotoxicity of the esterified triterpenoid and fatty acid fractions derived from the petroleum ether (45-60°C) extracts of I. glandulifera and I. noli-tangere seeds, leaves and roots revealed that triterpenoid fractions from the seeds of I. noli-tangere and I. glandulifera are the most active against human myeloblastic leukemia cell lines (HL-60 and HL-60/MX2) with IC50 values in the interval of 11.69-88.07 µg/mL. According to GC-MS and Gas Chromatography Coupled to Flame Ionization Detector (GC-FID) analyses, α-spinasterol acetate is the most abundant compound in the I. glandulifera triterpenoid fraction (21.63%) while 5α-lup-20(29)-en-3β-ol acetate is the mayor component of I. noli-tangere triterpenoid fraction (13.08%).[292] The cytotoxicity of the methanol extract from I. textorii aerial parts was evaluated on the following cell lines: HeLa, human gastric adenocarcinoma (MK-1), murine melanoma (B16F10), and human T-cell lymphotropic virus type1-infected T cells (MT-1 and MT-2 cell lines). In the case of MT-1 and MT-2, it is remarkable that lymphotropic virus type 1 can induce adult T-cell leukemia/lymphoma. The extract is active against B16F10 cells with IC50 in the range of 50–100 µg/mL. It is also active on MT-1 and MT-2 with IC50 in the range of 10–100 µg/mL.[293,294] The study of the cytotoxicity of the methanol extract from I. textorii whole plants and its n-hexane, ethyl acetate, n-butanol, and water fractions against human gastric adenocarcinoma (AGS), human colorectal adenocarcinoma (HT-29), HeLa, and A-549 cell lines shows that the ethyl acetate is the most active, promoting a reduction on cell viability higher than 90% at concentration of 500 µg/mL against all tested cell lines.[295] The ethanol fraction from I. textorii flower n-hexane extract reduces the cell viability (approximately 40% reduction) of mouse melanoma (B16BL6) cells at concentration of 400 µg/ mL. In comparison to non-treated control cultures, the extract, at test concentration of 200 µg/mL, counteracts cell proliferation (17%), melanin production (57.48%), tyrosinase enzymatic activity (36.90%), and protein expression of melanocyte inducing transcription factor (MITF) (50.7%) and tyrosinase (59.54%) on B16BL6 cells stimulated with α-melanocyte-stimulating hormone (α-MSH).[183] The n-butanol fraction, rich in saponins, obtained from the methanol (50%) extract of the leaves of I. capensis has cytotoxic effects against MCF-7 cell line completely suppressing its proliferation at concentration of 100 µg/mL. The fraction has Pharmacognosy Reviews, Vol 17, Issue 34, Jul-Dec, 2023354 Delgado-Rodríguez, et al.: Impatiens genus: Ethnobotany, Pharmacology and Bioactive Metabolites only cytostatic activity against HT-29 cell line inhibiting its proliferation by 35% approximately. The fraction is inactive on A375 cell line.[120] The leaves from I. walleriana have anthocyanins and carotenoids with reported approximated amounts of 8.577 µmol of cyaniding 3-O-glucoside equivalents (C3GE)/g and 1 mg/g, respectively. The aqueous extract from I. walleriana leaves shows cytotoxicity against AGS and SK-OV-3 with IC50 of 2.5 and 1.6 mg/mL, respectively. This extract can induce apoptosis on test cells according to flow cytometry analysis.[296] Similarly, it is reported that aqueous extract from the aerial parts of I. walleriana has IC50 of 2.87 mg/mL against AGS cell line.[297] The ethanol (80% v/v, acidified with trifluoro acetic acid 0.5% v/v) extract from I. walleriana orange flowers its more cytotoxic against HeLa, HepG2, MCF-7, and NCI-H460 cell lines (IC50 in the range of 177.3-333.4 µg/mL) than extract from I. walleriana pink flowers. None of these extracts are cytotoxic at concentration 400 µg/mL against PLP2 cells.[223] Anti-inflammatory and analgesic activities The evaluation of the anti-inflammatory activity of the water and ethanol extracts from the stems and roots of I. balsamina using the carrageenan induced paw edema model in Wistar rats demonstrated that ethanol extracts from stems and roots, at oral dose of 50 mg/kg, have the best anti-inflammatory profile.[298] The aqueous extract from the leaves of I. balsamina has shown anti-inflammatory activity in cotton pellet implantation, granuloma pouch sub-acute inflammation, and formaldehyde arthritis chronic inflammation model using Wistar rats. The oral dose of 2000 mg/g shows the highest anti-inflammatory properties on the experimental models. According to toxicity assays, the extract does not induce toxicity signs at oral dose of 3000 mg/kg.[299] Furthermore, the aqueous extract from leaves of I. balsamina has shown anti-inflammatory activity in albino rat model of carrageenan induced paw edema and analgesic effects on tail flick model when given at oral dose in the range of 500-1000 mg/kg.[300] Other extracts from leaves can be active too, the oral administration of the ethanol extract from leaves and stems of I. balsamina at dose of 500 mg/kg significantly reduces paw edema and joints inflammation on Wistar rats model of arthritis induced by intraplantar injection of complete Freund's adjuvant. A reduction in TNF-α in plasma of treated animals is also reported.[301] Aqueous and ethanol extracts from I. balsamina seeds have analgesic and anti-inflammatory effects in models of xylene ear edema in mice and egg-white induced foot swelling and granuloma.[302] The methanol extract from I. balsamina petals has TPC and TFC values of 103.26 mg GAE/g and 64.69 mg QE /g, respectively. The antinociceptive activity of the extract has been studied through animal models using Swiss albino mice. The extract reduces acetic acid-induced writhing response when given at oral dose of 50 mg/ kg. Similar results are observed in formalin-induced paw licking test, the extract reduces the licking response in mice at oral dose of 50 mg/kg. The extract increases the latency time in hot plate test, specially at oral dose of 400 mg/kg, this effect is antagonized by naloxone. According to tail immersion test, the extract increases the latency time at oral dose of 100 mg/kg, response that is also antagonized by naloxone. Results from hole cross and open field tests have shown that extract promotes depression of central nervous system 30 min after the treatment of mice with oral doses of 400 mg/kg and 100 mg/kg, respectively.[303] The ethanol (80% v/v, acidified with trifluoro acetic acid 0.5% v/v) extract from pink flowers of I. balsamina can reduce the production of Nitric Oxide (NO) on Lipopolysaccharide (LPS) stimulated murine macrophage (RAW 264.7) cell line with IC50 of 164 µg/mL. This extract is more potent than extract obtained from orange flowers (IC50 of 281 µg/mL).[212] Several studies on anti-inflammatory mechanism of Impatiens plants extracts and metabolites have been carried out. Protein denaturation is a common process in inflammatory events, the ethanol extract from I. balsamina seeds shows inhibitory activity against bovine serum thermal denaturation with IC50 of 210 µg/mL.[304] According to the in vitro evaluation of chemiotaxis inhibitory activity through Boydan chamber assay, using human Polymorphonuclear leukocytes (PMN) and monocytes as test cells and formyl-Methionyl-Leucyl-Phenylalanine (fMLP) as a chemoattractant, compound 1 can reduce chemiotaxis with IC50 of 7.63 µg/mL. Compound 1 can also inhibit myeloperoxidase enzyme from PMN stimulated with phorbol 12-myristate 13-acetate (PMA) (IC50 of 24.6 µg/mL). Luminol assay indicates that 1 reduces the production of ROS in human whole blood cells, PMN and monocytes with IC50 values of 8.51, 9.43 and 6.49 µg/mL, respectively.[305] Oral sprays containing α-mangostin (5 mg/mL), 1 (250 µg/mL) or a combination of both (at concentration of 5 mg/mL and 250 µg/mL, respectively) are effective to reduce NO production on RAW 264.7 cells stimulated with LPS with low cytotoxicity. The formulation that combines α-mangostin (5 mg/mL) and 1 (250 µg/mL) does not show cytotoxicity at concentrations equal or lower than 6.25 µg/mL but shows the best NO production inhibitory activity (reduction of 200% on NO production) on RAW 264.7 cell cultures at concentration of 0.78 µg/mL.[236] Beauty-saltTM is a food additive used in Korea as remedy for inflammatory illnesses. The ingredients of this product include solar salt and I. balsamina extracts. Beauty-saltTM treatment of Human Mast (HMC-1) cells stimulated with a mixture of PMA and the Calcium Inophore A23187 (PMACI) significantly reduces the production of Thymic Stromal Lymphopoietin (TSLP), Interleukin (IL) 1β and IL-8 mRNAs and their expression at concentration of 1 mg/mL without a significant reduction of cell viability in comparison to control cells. This product inhibits Pharmacognosy Reviews, Vol 17, Issue 34, Jul-Dec, 2023 355 Delgado-Rodríguez, et al.: Impatiens genus: Ethnobotany, Pharmacology and Bioactive Metabolites caspase 1 enzymatic activity and its expression. Moreover, Beauty-saltTM can reduce the activation of receptor-interacting- serine/threonine-protein kinase 2 (RIP2) and NF-κB. It also inhibits the phosphorylation of ERK and JNK, thus, it is proposed that Beauty-saltTM attenuates the expression of pro-inflammatory cytokines through the inhibition of caspase 1/NF‐κB/RIP2/MAP kinase pathway.[16] Compound 3, a flavonoid present in Beauty-salt™, at concentrations of 0.2 µg/mL and 2 µg/mL, inhibits in a dose-response manner the expression of clusters of differentiation 11, 14 and 44 induced in human leukemia monocytic (THP-1) cell cultures by their stimulation with IL-32. Compound 3, at concentrations of 0.02, 0.2, and 2 µg/mL, reduces the enzymatic activity of caspase 1 and the production of TSLP, IL-1β, IL-18 and TNF-α on THP-1 cells exposed to IL-32. Results from western-blotting analysis suggest that 3 reduces the production of proinflammatory cytokines by inhibiting the p38-MAPK/NF-κB/caspase 1 pathway. Compound 3, at doses of 0.02, 0.2, and 2 µg/mL, reduces the production of NO, IL-6, IL-8, TSLP and TNF-α in THP-1 cells stimulated with LPS. Compound 3 is not cytotoxic on THP-1 cells at assayed concentrations.[81] Compounds 46, 47 and 48 were isolated from white flowers of I. balsamina. They showed inhibitory action on NO production on cultures of murine microglia (BV-2) cell line stimulated with LPS with (IC50 values of 41.0, 33.8, and 34.8 µM, respectively). These results suggest that tested compounds could serve as anti-neuroinflammatory agents.[283] Similar results are reported by Kim et al., the ethyl acetate fraction from the methanol extract of I. balsamina white petals reduces NO production in BV-2 cells stimulated with LPS (IC50 of 5.3 μg/mL). Compounds 2, 3, 4, 5, 6, 32, 35, kaempferol 3-O-α-L-rhamnopyranosyl-(1→2)-β-D- glucopyranoside (69), and kaempferol 3-O-β-D-allopyranoside (70), were isolated from the active ethyl acetate fraction. These compounds reduce the NO production on BV-2 microglial cells treate