JBCS

INTRODUCTION

Medicinal plants constitute the main therapeutic source of folk medicine. Traditional knowledges are passed through generations due to the stark believes that come since primitive folks and healers. Previous ethno-pharmaceutical-botanical studies form the foundation to the development of new drugs from medicinal herbs.¹

Plants provide an essential economic role as they are used as a drug source.² This fact rises in developing countries due to lesser side effects and easy access that low-income populations have to those plants, making them an almost inexhaustible source of remedies for those people.³

Several chemical compounds that act as potential therapeutic agents have been isolated from plant species.⁴ Studies about those compounds are based on ethnobotanical, chemical and pharmacological knowledges, aiming to find out new bioactive molecules. On this context, species from Malvaceae sensu lato family arouse major interests of the scientific community due to the fact that those species are important economic sources in agriculture, decorations, manufacturing, food and medicine.⁵

Among several genus belonging to Malvaceae sensu lato, we highlight Pavonia Cav., which has several biological and pharmacological activities described in literature about folk medicine. Those activities have been confirmed through the isolation, identification and characterization of secondary metabolites, as well as several pharmacological activities described for those compounds.⁶

The genus Pavonia Cav. includes approximately 271 species distributed worldwide, being more diverse in America and Africa, with only two species being recorded for Asia. A lot of chemical and pharmacological studies with species P. odorata and P. zeylanica are described in literature, mostly for India, due to the traditional medicine system Ayuverda.⁷

Approximately 224 species can be found in America, ranging from USA to Uruguay, including the Antilles and excluding Chile. In Africa, approximately 46 species can be found.⁸ In Brazil, 136 species of Pavonia can be found, ranging from Amazon rainforest, Caatinga, Cerrado, Atlantic Forest, Pampas and Pantanal wetlands.⁹

Based on presented data, this review aims to accomplish a bibliographical survey about traditional uses of Pavonia species and evaluate the chemical and pharmacological potential of this genus in order to drive future researches based on natural products as a source of new drugs.

 

METHODOLOGY

Information about the use of plants by folk medicine, phytochemical studies, botanic characteristics and pharmacological activities of genus Pavonia have been based and collected from scientific data banks such as: 'Web of Science', 'Scifinder', 'Pubmed' and 'Scholar Google', using papers, books, dissertation and thesis from the year 1918 until April 2021 and searching for the keyword 'Pavonia'. Following this methodology, we consulted 156 scientific articles, having, as inclusion criteria, the presence of information regarding the use of Pavonia genus in traditional medicine, phytochemical studies, pharmacological and/or biological activities. The exclusion criteria of the articles involved repetition of those in different databases, review articles that contained references used in the manuscript, information with the keyword 'Pavonia' that do not concerns the genus, articles with only botanical data or articles not available for access on the platforms used. A single patent referring to the species P. schiedeana (JP 2001181172A (2001)) was found as part of a cosmetic composition.

The development of this revision paper aimed the study of this genus in order to expand the scientific interest through knowledge of isolated compounds with several biological activities, as those are the candidates to new drugs isolated from Pavonia species.

The present study and data have been extracted by the author (JBLA) and confirmed by other (DAF, CMS, PIVS, MFVS). All data are resumed in tables and their descriptions have been resumed as updated information.

 

RESULTS AND DISCUSSION

Botanical description

Pavonia comprises species of herbs, shrubs and bushes. Its flowers are, generally, solitary, composed by four epicalyxes, several free bracteoles, a tubulous and cupuliform calyx composed by five petals, carpels uniovulate and stigma capitate (Figure 1). The fruits are schizocarp, formed by five mericarps with a nervous-reticulate dorsal face, smooth lateral faces and smooth or striated obovoid or reniform seeds.¹⁰

 

 

Some species of Pavonia possess floral nectaries formed by multicellular glandular trichomes, providing a thick area located near the internal base of calyx. This characteristic attracts hummingbirds, which are pollinators of tubulous flowers, such as P. glazioviana¹¹ and P. multiflora. Species that possesses flowers with twisted corolla and short staminal tube formed by free stamens, such as P. malacophylla, P. varians, P. zeylanica and P. distinguenda, are pollinated by bees.¹²

Ethnopharmacological relevance

Different species of Pavonia Cav. are related in folk medicine as a treatment for several diseases. Among the most used parts of those plants used by some tribes in therapeutics are flowers, bark, roots, rhizomes and flowers (Table 1).

 

 

Juice of P. odorata leaves is used by traditional medicine Ayuverda as a treatment for dysentery, gonorrhea and halitosis, whereas leaves macerate as a paste are used as a treatment for rheumatism, foot infections and antipyretic.^13-18

Powder from seeds of P. senegalensis is used as a contraceptive.¹⁹ Decoct of P. urens roots is largely used as a treatment for toothache.^20,21 Brewing of roots and leaves of P. zeylanica, as well as decocts, powder and pastes are largely used by eastern communities as a treatment for osteoarthritis, joint pain, bone fractures, cough with discharge and healing of wounds.^22-26 Leaves' juice and the entire plant prepared as infusion are also used for its vermifuge and purgative properties.^27-30

Several ethnopharmacological studies regarding Pavonia species have been described in literature, which give us basis for deepening the chemical and pharmacological knowledge of those herbs, since many of the pharmacological activities are related to traditional use of medicinal plants, therefore providing essential information to the development of new drugs.

Chemical composition

Based on literature data, 29 references in the area of phytochemistry have been find to species of the genus Pavonia: 10 papers referred to species P. odorata (06) and P. zeylanica (04); 9 papers referred to species P. malacophyla (03), P. glazioviana (03) and P. sepium (03), and; 2 papers referred to P. cancelatta. Besides, several other papers have been related in this field with the species P. varians, P. xanthogloea, P. sepioides, P. distinguenda, P. multiflora, P. hastata, P. lasiopetala, P. schiedeana and P. alnifolia. 169 compounds have been isolated and/or identified in the genus Pavonia (Table 2), comprehending the most diverse classes of secondary metabolites ever related.

 

 

Fat acids, terpenoids, steroids, flavonoids, phenolics and other compounds such as pheophytins, hydrocarbons and volatile oils are some of the substances that can be found in the genus Pavonia. A broad profile of such compounds within has been detected in a study of the chemical composition of oils in the aerial parts of the species Pavonia odorata through hyphenated gas chromatography techniques coupled with mass spectrometry.¹⁰⁵ All compounds and their chemical structures are related in Table 2 and Figure 2, respectively.

 

 

Fatty acids

Fatty acids are molecule that consists of the most diverse lipids and, by enzymatic action, become free fatty acids, presenting powerful biological activities.¹²²

Studies described in literature review that activities of those compounds depend on the level of unsaturation and the size of hydrocarbons chain, resulting antibacterial, antifungal and antimycobacterial activities.^123,124 A recent study has shown that P. malacophylla and P. cancellata have palmitic, oleic and linoleic acids as majoritarian fatty acids.¹²⁵

Eighteen fatty acids have been isolated and identified in species P. sepium, P. odorata and P. zeylanica (Table 2). Palmitic (3) and caproic (10) fatty acids showed significant activities in preparatory in silico studies as having inhibitory properties for the activities of glycerol-kinase enzyme from the fungus Epidermophyton floccosum¹⁰⁴ and inhibitory properties for the alcohol-dehydrogenase enzyme from the protozoan Entamoeba histolytica.⁵³

Terpenoids and steroids

Terpenoids can be find in several groups of organisms. In plants, they are present under distinct aspects such as volatile molecules or adhered to resins. Their oxygenated, hydrogenated and dehydrogenated derivates have hydrocarbons as a base-structure, being widely distributed among plant species.¹²⁶

Forty-six terpenoids have been isolated and identified in P. odorata, P. multiflora, P. malacophylla, P. glazioviana and P. distinguenda, being the last one of the most common of Pavonia species. Terpenoids α-amirine (19) and β-amirine (20) showed in vitro antibacterial activities against Escherichia coli.¹⁰⁷ The terpenoid cicloart-23Z-en-3β-25-diol (28) also presented in vitro antimicrobial activities against Escherichia coli, Pseudomonas aeruginosa, Candida tropicalis, Candida parapsilopsis e Aspergillus fumigatus.¹¹⁰

Compounds loliolide (26) and the taraxerol p-metoxybenzoate (27) have demonstrated significant in vitro activities on the inhibition of electrons flux in photosystem II of plants, therefore allowing those molecules to become future candidates to herbicides as they prevent photosynthesis.¹²⁷

Steroids are a minority class in Pavonia genus, with only five isolated compounds (65-69). Phytosteroids share as common structure ciclopentanoperidrofenaterne as carbonic skeleton, being β-sitosterol and stigmasterol the most common steroids of this genus and commonly encountered attached to sugar monomers.¹²⁸

Flavonoids and phenolic compounds

Flavonoids are the most important and diversified class of phenolic compounds among natural products, being relatively abundant secondary metabolites and responsible for several functions in plants' organisms.¹²⁹

Seventeen flavonoids have been isolated from Pavonia species, being sixteen of those members of subclass flavone (70-84) and one, to flavanonol subclass (85). Many isolated flavonoids have glycosids attached to their structures.

Among the isolated compounds, flavonoid 5,7-dihydroxy-3,8,4'-trimethoxyflavone (79) has demonstrated in vitro antimicrobial, in silico anticancer, in vitro antineoplasic, in vitro antiprotozoal and in vito photoprotective activities.^130,131

The compound tiliroside (70) has demonstrated in vitro and in vivo antihypertensive activities, leading to reduction of peripheric vascular and vasorelaxant resistances by blocking the Calcium channels dependent of voltage (Ca_V) in cells of vascular smooth muscle (VSMCs);¹³² in vitro antimicrobial activity;^31,107 in silico antidiabetic activity through interaction with human pancreatic α-amylase enzyme;¹¹⁴ in vitro anticancer and anticolinesterasic activities.³¹

Nineteen phenolic compounds (87-105) have been identified and isolated from the species P. xanthogloea, P. sepioides, P. multiflora and P. schiedeana. Studies demonstrated that those compounds presented different activities. Gross ethanolic extract and fractions of ethyl acetated from extractive process of P. sepioides leaves have shown a large quantity of phenolic compounds present on the samples, which explains the antioxidant activity of those substances against free radicals inhibitions tests through the methods of DPPH and ABTS.¹¹⁹

Besides that species, other studies have shown a large potential of antioxidant activity as a primordial activity of those phenolic compounds such as described for P. xanthogloea, P. zeylanica, P. odorata, P. distinguenda, P. varians, P. glazioviana and P. procumbens.^{31,44,82,83,90,105,117,133-135}

Other compounds

Differently from previously mentioned compounds, other classes of secondary metabolites have been isolated and identified in a lesser frequency on Pavonia species. Among those compounds, we can list alcohols, aldehydes, ketones, pheophytins and hydrocarbons (106 171) (Table 2, Figure 2).

Chaves¹⁰⁷ has conducted a phytochemical study of P. malacophylla, isolating and identifying the compound 17³-ethoxy-phaeophorbide A (104), which has presented in vitro antibacterial activity against Staphylococcus aureus and Escherichia coli.

Pharmacological study

Several pharmacological activities involving Pavonia species have been arousing interest of scientific community hence there is a large collection of reports of their use in folk medicine. Researches have been developed to confirm the anti-inflammatory, analgesic, antioxidant, cytotoxic, antitumoral, antidiabetic, antimicrobial and antiviral potential of Pavonia species through scientific analysis (Table 3).

 

 

Anti-inflammatory and analgesic activities

Plants constitute a vast and precious source of natural products, which are essential to human health as they play several biological roles such as anti-inflammatory and analgesic activities, as it has been demonstrated by some studies over extracts and isolated compounds.¹⁰⁶

Alcoholic extract of P. zeylanica leaves has shown in vivo anti-inflammatory activity in rat foot edema induced by carrageenan and in vivo antinociceptive activity by inhibition of arachidonic acid formation.⁸⁸ Methanolic, chloroformic and ethyl acetate extracts of P. odorata roots have also demonstrated in vivo anti-inflammatory activity in albino rat foot edema induced by carrageenan.¹⁰⁶ (Table 3).

Antioxidant activity

Antioxidants are substances that control the action of free radicals, minimizing the risk of diseases, specially those related to oxidative damage on nervous system. Naturally, some enzymes are responsible for the protection of harmful effects of free radicals, such as catalasis and dismutasis superoxide, as well as natural products with antioxidant action such as ascorbic acid, tocopherol, phenolics and flavonoids.¹³³

The evaluation of antioxidant activity of extracts from the aerial parts of Pavonia species has shown the presence of phenolics and flavonoids as its constituents, having those compounds demonstrated a huge antioxidant potential in tests through the methods DPPH (1,1-diphenil-2-picril-hidrazil), H₂O₂ (hydrogen peroxide), NO (nitric oxide), ABTS (2,2'-azino-bis(3-etilbenzotiazoline-6-sulphonic) acid), FRAP (Ferric Reduction Antioxidant Power), SNP (Sodium Nitroprussiate radicals), phosphomolybdenium reduction, ORAC (Oxygen Radical Absorbance Capacity) and TBARS (Thiobarbituric Acid Reactive Substances) (Table 3).

Cytotoxic and anticancer activities

Cancer is one of the most lethal diseases that affects humankind. Some phytochemical studies have demonstrated anticancer potentials in several plants due to their chemoprotective and antioxidant properties, which make plants an option to minimize the adverse effects of conventional cancer treatments.¹⁵⁶

Extracts and isolated compounds from P. glazioviana, P. distinguenda and P. odorata have demonstrated anticancer activities. The tiliroside flavonoid isolated from P. distinguenda has shown in vitro anticancer activity against leukemic, ovarian, colon, prostate, kidney, breast, resistant breast and melanoma cells, besides being cytotoxic to Artemia salina larvae.³¹

Other flavonoid isolated from P. glazioviana (5,7-dihydroxy-3,8,4'-trimethoxyflavone) (79) has shown in silico anticancer activity against carcinogen uterine and ovarian cells, while having in vitro antineoplastic activity against sarcoma, carcinoma, melanoma and squamous cell carcinoma.^130,131

Extracts from the whole plant of P. odorata has shown in vitro anticancer activity against Ehrlich Ascites Carcinoma (EAC), lung and breast cancer.^44,138

Antidiabetics activity

Several plants are used by folk medicine worldwide against diabetes.⁸⁶ Some of the species quoted in literature are P. zeylanica and P. odorata. Extracts from their leaves, stems and roots have been evaluated regarding their in vitro antidiabetic activity, being constated a significant reduction of glycose levels in bloodstream.^86,136,139

In silico hypoglycemic activity of the tiliroside flavonoid isolated from P. varians through the interaction of this compound with human pancreatic α-amylase enzyme presented a lesser linking energy of -9.4 kcal/mol, being more stable in its active site when compared to the standard drug acarbose, that presented an energy of -7.6 kcal/mol.¹¹⁴

Antimicrobial activity

Bacterial resistance has been increasing significatively in the last years, which leads to high mortalities caused by generalized infections. This fact is a consequence of ungovernable use of antibiotics. For those reasons, the search for new natural compounds with antimicrobial activity and new action mechanisms if necessary for the control of such micro-organisms.¹⁴⁰

Extracts, fractions and compounds isolated from Pavonia species have shown a great antimicrobial potential that has already been described in literature. Among the compounds that were tested against several fungal and bacterial lineages, we have α-amirine (19), β-amirine (20), 17³-ethoxy-phaeophorbide A (104)¹⁰⁷ isolated from P. malacophylla, cycloart-23Z-en-3β,25-diol (28), 5,7-dihydroxy-3,8,4'-trimethoxyflavone (79)¹¹⁰ isolated from P. glazioviana, tiliroside (70)^31,107 isolated from P. malacophylla e P. distinguenda and caproic (10) and palmitic (3)¹⁰⁴ acids identified in P. odorata (Table 3).

Other activities

Other activities have been related for Pavonia species. Methanolic extract from P. odorata leaves has shown in vitro larvicide and repellent activities against Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus.¹⁵³ Researches have shown anti-hypertensive,^36,116,132 anti-helminthic,^{35,141-143,152} anti-urolithic,³⁴ gastroprotective,¹⁴⁹ laxative,¹³⁶ photoprotective,¹³¹ antiretroviral^146,147 and several other kinds of activities.

Furthermore, a study on P. senegalensis has showed that fresh liquid ethanolic extract of leaves has not a very strong toxicity, becoming nephrotoxic and slightly hepatotoxic after 28 days.⁶⁸

 

CONCLUSIONS

Pavonia Cav. is one of the largest genus on Malvaceae sensu lato family and has showed different biologic activities amongst its species, which have already been mentioned in literature and scientific proved. Studies have shown that fatty acids, terpenoids, flavonoids and phenolics are the most common classes of secondary metabolites on this genus. Pharmacological in vivo, in vitro and in silico tests have given the researches promissory results due to the presence of those compounds, both isolated and present on the extracts, corroborating the reports of use of those herbs in folk medicine.

Nonetheless, there is a major need of keep exploring chemical and biological potentials of Pavonia species, both already and never studied, since medicinal plants are almost inexhaustible sources of bioactive molecules that can help the treatment and cure of several diseases that affect human populations worldwide.

This paper is a database with very relevant information from both phytochemical and biological studies of Pavonia species that can be further explored, aiming to understand the use of Pavonia by traditional medicine in various diseases, becoming alternatives for therapies by the use of these natural products with emphasis on the benefit of the world population.

 

ACKNOWLEDGMENTS

We thank Coordenação de Aperfeiçoamento do Ensino Superior (CAPES) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for all the support to our researches.

 

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