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An Overview of Genus Malachra L.—Ethnobotany, Phytochemistry, and Pharmacological Activity

The genus Malachra L. belongs to the family Malvaceae. It includes herbs or subshrubs of nine accepted species with approximately thirty synonyms, and it has been widely used in community folk medicine to treat health problems including inflammation, nasal obstruction, leishmaniasis, malaria, childbirth, kidney disorders, fever, respiratory tract diseases, among others. From the genus Malachra L., flavonoids, steroids, triterpenes, anthocyanins, leucoanthocyanins, saponins, carbohydrates, phenols, glycosides, and alkaloids have been isolated and identified. Some pharmacological reports have indicated that the genus has antidiarrheal, antiepileptic, antiulcerogenic, antioxidant, anticonvulsant, antiviral, anticancer, antibacterial, anthelmintic, and hepatoprotective properties. However, there have been limited studies of bioactive molecules with pharmacological and biological activities associated with Malachra alceifolia Jacq., Malachra capitata (L.) L., Malachra fasciata Jacq., Malachra radiata (L.) L., Malachra ruderalis Gürke., Malachra rudis Benth., Malachra helodes Mart., Malachra urens Poit. ex Ledeb. & Alderstam., and Malachra officinalis Klotzsch. In this review, we consider the conservation of these species to save the ancestral knowledge of their traditional use in populations, and their pharmacological potential for future studies in search of alternatives for solutions to diseases in humans and animals and tools for the design and search of potential bioactive compounds against infectious and non-infectious agents.


Introduction
Various populations of some regions of the world use medicinal plants to cure and prevent their health problems [1]. However, the World Health Organization (WHO) has defined ancestral and traditional knowledge resources obtained from plants, extracts, fractions, or compounds as a primary source for the identification of molecules, substances, or active principles to be used in the development of drugs and phytomedicines for disease prevention [2][3][4]. Secondary metabolites derived from plant species such as Taxus brevifolia (Paclitaxel) [5], Catharanthus roseus (Vincristine) [6], Digitalis lanata (Digoxin) [7], Ephedra distachya (Ephedrine) [8], Artemisia annua (Artemisinin) [9], Salix alba (acetylsalicylic acid) [10], and Papaver somniferum (morphine) [11] have been used as drugs with anticancer, cytotoxic, antimicrobial, analgesic, inflammatory, antiestrogenic, antiallergic, antioxidant, and other activities [12,13]. Note that ancestral and traditional community activities have used medicinal plants for phytotherapy in primary health care and for validation of their ethnopharmacological use [14,15].
There are about 382,000 accepted plant species names in the world [16,17]. The criteria for considering the acceptance, name, and synonyms of a plant species are defined method of the PRISMA guidelines for data selection, a scientific question was posed with the following heading: P: genus Malachra L. in the family Malvaceae, I: Included species, C: accepted, ambiguous, and unchecked species, O: taxonomy, botanical descriptions, geographical distribution, phytochemistry, ethnobotany, pharmacological, and biological activities of species. Articles, abstracts, and university repositories with descriptions of phytoconstituents using clear methodology for obtaining extracts, fractions, compounds, and plant part used.

3.
Articles, abstracts, and university repositories with pharmacological and biological descriptions using clear methodology in the evaluation of doses, concentrations, biological models used, and controls.
The exclusion criteria were those studies that did not meet criteria one, two, and three. There were fifteen bibliographic registers identified in the database; records deleted eight (congress abstract six, taxonomic website version not updated one (http://www. theplantlist.org/, accessed on 1 March 2022), article without pharmacological description one); articles evaluated for eligibility eight; articles accepted for the study seventy-nine; flora microsites accepted nine; graduate work four.

Taxonomy the Genus Malachra
According to World Flora Online, the genus Malachra L. belongs to the family Malvaceae, the group of angiosperms with the largest accepted name reports, including 14,539 scientific species names, 4465 accepted species names, and 245 genera [39]. The botanical characteristics of this family describe its growth as shrub, tree, herb, liana/vine, subshrub, aquatic, terrestrial, hemiepiphytic, and rupicolous [17,40]. The genus Malachra L. has nine species with accepted names and prolific taxonomic synonyms with adjusted morphological descriptions [17]. However, in the Flora World website Malachra officinalis Klotzsch., is accepted, whereas in other flora websites such as https://powo.science. kew.org/, https://wcvp.science.kew.org/, and https://www.tramil.net/es, (accessed on 1 March 2022), this species is not accepted (Tables 1 and 2). There is no information on this species provided in this review due to its limited studies.

Botanical Description of the Species of the Genus Malachra L.
The genus Malachra L. is represented by herbs or suffrutes, sometimes puberulent, generally hispid, or with stinging trichomes. Leaves are simple or palmately lobed; acute, acuminate, or obtuse at the apex; truncated or subcordate at the base; serrated or crenated; and generally pubescent. They also present: bracteate inflorescences; axillary or terminal heads; broadly cordate-ovate bracts at the base, with prominent nerves often alternating with whitish areas, although it can be in other parts green and sessile. Absent calliculus (except in M. radiata); small calyx, five-lobed; white, yellow, or lilac corolla; and fivelobed leaves can also be observed. Additionally, schizocarpal fruits have the shape of a wheel similar to a cheese that can be split into five ripe wing types; flowers are in heads, surrounded by bracts larger than them [17, [41][42][43].
Malachra alceifolia Jacq. is a herb or shrub, 1. 6 m tall. The aerial parts and petioles are hispid, simple or split, flavescent, tuberculate base, scattered hairs, short, star-shaped, and long forming knots, with stem pubescence and a green to reddish color. The leaves are simple, opposite, and lobed, with up to five lobes, with pubescence, and their margins are serrated or toothed. There are inflorescences in axillary heads with the presence of acuminate bracts and flowers with five petals, 2 to 3 cm in diameter, with a yellow coloration. The fruits have bracts and persistent calyx, with numerous seeds, up to 2 mm in diameter, dark colored, and flattened ( Figure 1) [44].  Malachra capitata Linn. is a herb or subshrub, up to 2 m tall, with stem pubescence and green to orange coloration. The leaves are simple, opposite, palmate or lobed, with up to five lobes; the texture of the leaves is velvety and their margins are crenulate or serrated. Inflorescences are peduncular and axillary, with the presence of lanceolate bracts; flowers have five petals, 1 cm in diameter, with a white coloration. Schizocarpic fruits have single seeds up to 3 mm in diameter, and are dark colored ( Figure 2) [45].
Malachra radiata (L.) L. is a herb or suffrutex, 1.5 m tall, with stem pubescence and green and purple coloration. The leaves are simple, opposite, palmate or lobed, with up to seven lobes; the texture of the leaves is velvety, and their margins are crenulate or serrated, and most apical leaves may have a triangular shape. Inflorescences are pedicular and terminal, with the presence of ovate or acute bracts; flowers have five petals, 2.5 cm in  Malachra capitata Linn. is a herb or subshrub, up to 2 m tall, with stem pubescence and green to orange coloration. The leaves are simple, opposite, palmate or lobed, with up to five lobes; the texture of the leaves is velvety and their margins are crenulate or serrated. Inflorescences are peduncular and axillary, with the presence of lanceolate bracts; flowers have five petals, 1 cm in diameter, with a white coloration. Schizocarpic fruits have single seeds up to 3 mm in diameter, and are dark colored ( Figure 2) [45].

Figure 2. Malachra capitata Linn.
Malachra fasciata Jacq. is a herb or subshrub, up to 2 m tall, with stem pubescence, simple or stellate trichomes up to 7 mm, and green to orange coloration. The leaves are simple, opposite, ovate, truncated at the base, acute at the apex, lobed or deeply parted, otherwise crenate-serrate, pubescent above with appressed trichomes. The heads are short-stalked bracts, 2-6 per head, lance/ovate, subcordate at the base, acute at the apex, often ciliate, prominently hispid. Calyx 4 to 5 mm, hispid; petals white 6-8 mm, mericarps light brown to grayish green, reticulate veined ( Figure 3) [46]. Malachra radiata (L.) L. is a herb or suffrutex, 1.5 m tall, with stem pubescence and green and purple coloration. The leaves are simple, opposite, palmate or lobed, with up to seven lobes; the texture of the leaves is velvety, and their margins are crenulate or serrated, and most apical leaves may have a triangular shape. Inflorescences are pedicular and terminal, with the presence of ovate or acute bracts; flowers have five petals, 2.5 cm in diameter, with a lilac coloration and purple at the base. Schizocarpic fruits have numerous seeds, up to 2 mm in diameter, and are dark colored ( Figure 4) [47].  Malachra ruderalis Gürke. is an annual herb, up to 3 m high, with stem pubescence and green coloration. The leaves are simple, opposite, palmate or lobed, with up to five lobes; the texture of the leaves is velvety, and their margins are crenulate; the most apical leaves have a triangular shape. It shows pedicular inflorescence with terminal or acute Malachra ruderalis Gürke. is an annual herb, up to 3 m high, with stem pubescence and green coloration. The leaves are simple, opposite, palmate or lobed, with up to five lobes; the texture of the leaves is velvety, and their margins are crenulate; the most apical leaves have a triangular shape. It shows pedicular inflorescence with terminal or acute axillary bracts, five petals, 3 cm long, with yellow schizocarpic fruit with numerous dark-colored seeds up to 2 mm in diameter ( Figure 5) [48,49]. Malachra rudis Benth. is a perennial herb, up to 0.7 m high, with a stem that has very short pubescence, and its coloration is light green. The leaves are simple, opposite, lobed, with up to three lobes; velvety texture; crenulated margins with pedicular, axillary, or terminal inflorescence; ovate bracts with five petals; 1.5 cm in long. Schizocarpic fruits are yellow to white with numerous seeds up to 1 mm in diameter, one per carpel ( Figure 6) [48][49].  Malachra rudis Benth. is a perennial herb, up to 0.7 m high, with a stem that has very short pubescence, and its coloration is light green. The leaves are simple, opposite, lobed, with up to three lobes; velvety texture; crenulated margins with pedicular, axillary, or terminal inflorescence; ovate bracts with five petals; 1.5 cm in long. Schizocarpic fruits are yellow to white with numerous seeds up to 1 mm in diameter, one per carpel ( Figure 6) [48,49]. Malachra rudis Benth. is a perennial herb, up to 0.7 m high, with a stem that has very short pubescence, and its coloration is light green. The leaves are simple, opposite, lobed, with up to three lobes; velvety texture; crenulated margins with pedicular, axillary, or terminal inflorescence; ovate bracts with five petals; 1.5 cm in long. Schizocarpic fruits are yellow to white with numerous seeds up to 1 mm in diameter, one per carpel ( Figure 6) [48][49]. Malachra urens Poit. ex Ledeb. & Alderstam is an annual herb, up to 1 m high, with pubescent stems of different sizes and green to orange coloration. The leaves are simple, opposite and lobed, with up to three lobes relatively marked, with pubescence; the margins of the leaves are toothed, about 3-12 cm long. Inflorescences are peduncular racemes with acuminate, boat-shaped, pubescent bracts. Flowers have five petals, 2 to 3 cm in long, with a yellow color. Schizocarpic fruits have mericarps and pubescent bracts, with numerous seeds, up to 2 mm in long, dark colored, and flat ( Figure 7) [48,49].

Geographical Distribution of the Genus Malachra L.
The genus Malachra L. is geographically distributed in tropical and subtropical America, west tropical Africa, and Southwest Asia [49].
The species of the genus Malachra L. are native to: South America countries (northeast Argentina, Bolivia, north Brazil, northeast Brazil, southeast Brazil, Colombia, Ecuador, with a yellow color. Schizocarpic fruits have mericarps and pubescent bracts, with nu ous seeds, up to 2 mm in long, dark colored, and flat (Figure 7) [48][49].  The genus Malachra L. is geographically distributed in tropical and subtropical A ica, west tropical Africa, and Southwest Asia [49]. The genus Malachra L. is geographically distributed in tropical and subtropical America, west tropical Africa, and Southwest Asia [49].

Species
The distribution of the species in Brazil and Colombia covers most of the regions [43,50]. The species with the highest abundance are found in Colombian Caribbean, denoting their preference for warmer climates. In terms of their ecology, they prefer open habitats such as the savannah and scrublands; however, they can occur less frequently in dry and humid forests. There have been a few reports on the conservation status of the species in the genus Malchara L. In this study, in Table 4, only the conservation status of Malachra alceifolia Jacq., in Colombia, is included.

Species of the Genus Malachra L. with Ethnobotanical Use
Medicinal plants of traditional use have been included in the Traditional and Complementary Medicine (TCM) report by the World Health Organization (WHO). Many of them are used in developing countries such as Chile and Colombia, with usages of 71% and 40% of the population, respectively [51,52]. Table 5 lists and describes the species of the genus Malachra L. with reported medicinal use, including vernacular name, part of the plant used, condition treated, preparation and administration, and the country where its use has been reported. The species in the genus Malachra L. with the highest reported ethnobotanical use are M. alceifolia Jacq., (for treatment of inflammation, clogged nose, during malaria, childbirth, drunk headache, kidney disorder, fever, and headache), M. capitata (L.) L., (for pain, diarrhea, convulsion, hepatic cirrhosis, inflammation, pyrexia, ulcer, dementia, treatment of wounds, gastric disorders, jaundice, childbirth, malaria headache, and fever), M. fasciata Jacq., (for emollients, hemorrhoids, fever, impotence, gonorrhea, rheumatism, demulcent, and diuretic), M. ruderalis Gürke., (for pulmonary diseases, fever, cough, sore throat, flu, colds, whooping cough, pulmonary diseases, COVID-19, stomach problems, diarrhea, fever, skin spots, skin infections, gastritis, stress inflammation, and vaginal infection). 7. Phytochemistry Species of the Genus Malachra L.
Phytoconstituents are chemical compounds that plants synthesize as a defense mechanism against biotic and abiotic environmental conditions; they play key roles in biological processes [58,59]. Many phytoconstituents isolated from the genus Malachra L., such as flavonoids, coumarins, carbohydrates, glycosides, triterpenes, alkaloids, tannins, and saponins, exhibit pharmacologic activity. Table 6 lists the phytoconstituents reported only in Malachra species: M. alceifolia Jacq., M. capitata (L.) L., and M. fasciata Jacq, see Figure 10 molecular structure of some compounds isolated from species of the genus Malachra L. Table 6. Major phytoconstituents identified in species of the genus Malachra L.

Stem
Tetradecanoic acid, ethyl ester; [27,28] pentadecanoic acid, 2,6,10,14tetramethyl methyl ester (     Generally, organic compounds obtained from extracts, fractions, and isolated compounds of plant species possess unique structural characteristics among which the geometrical and energetic interactions of the atoms stand out; chirality and stereoisomers of molecular structures, intermolecular interactions, hydrogen bond acceptors and donors, molecular mass, diversity of ring systems, among others, become tools of interest for medicinal chemistry in drug development, to improve the potency, for pharmacokinetic properties, and to reduce the toxicity of new drugs [60]. However, the secondary metabolites isolated from plant species constitute a group of chemical molecules with a great diversity of biological activities applied to the pharmaceutical, cosmetic, and food sectors [61]. Gallic acid (GA) is a phenolic compound with anti-inflammatory, antimicrobial, hepatoprotective, neuroprotective, and carcinogenic properties that prevent gastrointestinal, cardiovascular, metabolic, and neuropsychological diseases [62]. The livers of Wistar rats exposed to carbon tetrachloride in doses of 50 mg/kg and 100 mg/kg GA, were evaluated by decreasing serum liver enzymes, regulating the expression of proinflammatory genes, and regulating the expression of antioxidant genes [63]; mercuric chloride induced at 200 mg/kg, increased glutathione peroxidase, superoxide dismutase, and catalase activity, and decreased the level of glutathione in liver tissue [64]. Caffeic acid has antimicrobial potential against Staphylococcus aureus strains with MICs from 256 µg/mL to 1024 µg/mL [65]. The compound quercetin isolated from extracts and organic fractions of Allium cepa L., Morus alba, Camellia sinensis, Moringa oleifera, and Centella asiatica, at doses between 50 and 100 mg/kg, and evaluated in in vivo models, showed antiulcer activity [66]. Beta-sitosterol isolated chloroform extract of Corchorus capsularis L. leaves has been shown to exhibit a significant effect against trypanothione reductase Leishmania donovani promastigotes at IC50 = 17.7 ± 0.43 µg/mL [67], and the dipeptide aurantiamide acetate patent has an effect of resisting influenza virus and an inhibition effect on a cytopathic Generally, organic compounds obtained from extracts, fractions, and isolated compounds of plant species possess unique structural characteristics among which the geometrical and energetic interactions of the atoms stand out; chirality and stereoisomers of molecular structures, intermolecular interactions, hydrogen bond acceptors and donors, molecular mass, diversity of ring systems, among others, become tools of interest for medicinal chemistry in drug development, to improve the potency, for pharmacokinetic properties, and to reduce the toxicity of new drugs [60]. However, the secondary metabolites isolated from plant species constitute a group of chemical molecules with a great diversity of biological activities applied to the pharmaceutical, cosmetic, and food sectors [61].
Gallic acid (GA) is a phenolic compound with anti-inflammatory, antimicrobial, hepatoprotective, neuroprotective, and carcinogenic properties that prevent gastrointestinal, cardiovascular, metabolic, and neuropsychological diseases [62]. The livers of Wistar rats exposed to carbon tetrachloride in doses of 50 mg/kg and 100 mg/kg GA, were evaluated by decreasing serum liver enzymes, regulating the expression of proinflammatory genes, and regulating the expression of antioxidant genes [63]; mercuric chloride induced at 200 mg/kg, increased glutathione peroxidase, superoxide dismutase, and catalase activity, and decreased the level of glutathione in liver tissue [64]. Caffeic acid has antimicrobial potential against Staphylococcus aureus strains with MICs from 256 µg/mL to 1024 µg/mL [65]. The compound quercetin isolated from extracts and organic fractions of Allium cepa L., Morus alba, Camellia sinensis, Moringa oleifera, and Centella asiatica, at doses between 50 and 100 mg/kg, and evaluated in in vivo models, showed antiulcer activity [66]. Beta-sitosterol isolated chloroform extract of Corchorus capsularis L. leaves has been shown to exhibit a significant effect against trypanothione reductase Leishmania donovani promastigotes at IC 50 = 17.7 ± 0.43 µg/mL [67], and the dipeptide aurantiamide acetate patent has an effect of resisting influenza virus and an inhibition effect on a cytopathic effect mediated by the influenza A virus CN106431960B, filing date: 11 November 2018, legal status: active [68].

Species of the Genus Malachra L. with Pharmacological Activity
Applications of plant remedies in traditional medicine are still central in the health systems in some countries of world [69]. The biogenesis and biosynthesis of phytoconstituents in plant species provide an opportunity for medicinal chemistry to advance pharmacological studies for treating pathologies that have been little studied [70]. Table 7 summarizes the most important pharmacological activities reported for the genus Malachra L., such as antidiarrheal, anti-epileptic, antiulcerogenic, antioxidant, anticonvulsant, hepatoprotective, antiviral, anticancer, antibacterial, and anthelmintic properties. The bibliographic search describes only the pharmacological activities of M. alceifolia Jacq., M. capitata (L.) L., and M. fasciata Jacq.

Conclusions
This review provides information and analysis of published scientific data on eight species of the genus Malachra L. of the family Malvaceae: Malachra alceifolia Jacq., Malachra capitata (L.) L., Malachra fasciata Jacq., Malachra radiata (L.) L., Malachra ruderalis Gürke., Malachra rudis Benth., Malachra helodes Mart., Malachra urens Poit., and Malachra urens Poit. ex Ledeb. & Alderstam. The plants are widely distributed in America, Africa, and Asia, with a greater distribution of species in the tropical and subtropical regions of Colombia and Brazil. These plant species have shown important applications in traditional medicine since their aqueous extracts are used for treating infectious, inflammatory, respiratory, digestive, and neurological problems. The active phytoconstituents isolated from the genus may be useful for the evaluation and identification of molecular targets against infectious pathogens or inflammatory processes. The presence of groups of metabolites such as flavonoids, sterol-terpenoids, and phenolics, including gallic acid, caffeic acid, quercetin, and β-sitosterol compounds may be associated with biological processes with activities such as antidiarrheal, antiepileptic, antiulcerogenic, antioxidant, anticonvulsant, hepatoprotective, antiviral, anticancer, antibacterial, and anthelmintic, with inflammatory activity being the most widespread. In turn, the presence of peptides with pharmacological potential, contribute to the search for drugs against oncological, metabolic, cardiovascular, and neglected tropical diseases. Therefore, this review contributes to the baseline knowledge for the search of information on the validation of the therapeutic use and conservation of traditional and ancestral knowledge of plant biodiversity in America, Africa, and Asia countries, as well as contributes to basic concepts for future research aimed at the discovery of new drugs.