Abstract
Helicteres genus, Malvaceae, has pantropical distribution, encompasses about 60 species, 31 of them found in Brazil. Species belonging to this genus are used for treatment of various diseases and aroused scientific interest in search for bioactive compounds present in these plants. In this context, this review aims to provide a complete and concise overview of scientific advances in phytochemical and pharmacological studies of these species and their use by folk medicine. The presented data were collected from scientific databases, ‘Web of Science’, ‘Scifinder’, ‘Pubmed’, ‘Sciencedirect’, and ‘Google Scholar’, using the keyword ‘Helicteres’. The species H. isora and H. angustifolia, found in Asia, are the most explored scientifically, whereas studies of species of this genus found in Americas are still rare, being possible to highlight studies carried out in Brazil with H. velutina and H. eichleri. About 149 compounds were isolated and characterized in the genus, being emphasized terpenoids, flavonoids and lignoids. These species have demonstrated various pharmacological properties in vitro and in vivo, incluinding insecticide, antidiabetic, antitumor and hepatoprotective activities. The presented data show the importance of studies carried out isolating bioactive compounds from this genus that may be used in several diseases’ treatment or/as prototypes to development of new drugs.
Keywords:
Helicteres L.; secondary metabolite; ethnopharmacological relevance; scientific studies
INTRODUCTION
The use of natural products by mankind with the purpose of supplying physical and biological needs is an ancient practice, being the knowledge acquired transmitted throughout the generations.11 Eloy, C. C.; Vieira, D. M.; Lucena, C. M.; Andrade, M. O.; Gaia Scientia
2014, Volume Especial Populações Tradicionais, 189.
2 Machado, V. R.; Lang, K. L.; Durán, F. J.; Cabrera, G. M.; Palermo, J. A.; Schenkel, E. P.; Bernardes, L. S. C.; Quim. Nova
2015, 38, 37.-33 Barreiro, E. J.; Bolzani, V. S.; Quim. Nova
2009, 32, 679. Previous studies have allowed the association of chemical constituents present in the medicinal species and their respective pharmacological activities, based on experimental researches including knowledges of botany, chemistry, biochemistry and pharmacology, greatly contributing to the discovery of bioactive natural products.44 Oliveira, L. F. G.; Gilbert, B.; Villas-Bôas, G. K.; Rev. Fitos
2013, 8, 33.,55 Bonomi, T. J.; Góes, J. A.; Machado, M. S.; Silva, R. M. L.; Malheiros, A.; Quim. Nova
2018, 41, 36.
In this context, species of Sterculiaceae clade, Malvaceae sensu lato, have aroused great interest in the scientific environment and stand out for their importance in industrial, economic, medicinal, food and ornamental production, as well their chemical and biological properties.66 Deshpande, H. A.; Bhalsing, S. R.; Res. Biotechnol. 2015, 6, 31.,77 Teles, Y. C. F.; Gomes, R. A.; Oliveira, M. S.; Lucena, K. L.; Nascimento, J. S.; Agra, M. F.; Igoli, J. O.; Gray, A. I.; Souza, M. F. V.; Quim. Nova 2014, 37, 1491.
Among the genus belonging to this group, we highlight Helicteres L., whose biological and pharmacological effects of some species used in folk medicine were scientifically confirmed through the isolation, structural characterization and pharmacological activities developed by its secondary metabolites.88 Balogun, S. O.; Damazo, A. S.; Martins, D. T. O.; J. Ethnopharmacol. 2015, 166, 176.
Helicteres L. genus has pantropical distribuition, comprising approximately 60 species in America and Asia, with no species common to both continents. In Asia, the most studied species chemically and pharmacologically are H. isora, H. angustifolia and H. hirsute. China has about ten species, of which only one is endemic.99 Ya, T.; Gilbert, M. G.; Dorr, L. J.; Flora of China 2007, 12, 240.
In America, there are 38 species distributed from Mexico to Argentina, with no reports of occurence for Ecuador and Chile. Among the most scientifically studied species in the continent, we can highlight H. sacarolha, H. eichleri and H. velutina, the last two endemic in Brazil, which is considered the center of diversity of this genus in Americas, having a registered occurrence of 31 species, 23 of which are exclusive from cerrado, caatinga and dry forests.1010 Cruz, F. R.; Master's thesis, Universidade de São Paulo, Brasil, 2007.
11 Goldberg, L.; Rev. Biol. Trop.
2009, 57, 161.-1212 Fernandes, D. A.; Souza, M. S. R.; Teles, Y. C. F.; Oliveira, L. H. G.; Lima, J. B.; Conceição, A. S.; Nunes, F. C.; Silva, T. M. S.; Souza, M. F. V.; Molecules
2018, 23, 2784.
Based on the presented data, the objective of this review is to make a survey about the traditional use of Helicteres genus species, as well as evaluating their chemical and pharmacological potential to show the importance of this genus and provide a basis for future research.
METHODOLOGY
Available information on traditional uses, phytochemical study, botanical characteristics and biological activities of Helicteres genus were collected from scientific databases: ‘Web of Science’, ‘Scifinder’, ‘Pubmed’, ‘Sciencedirect’, and ‘Google Scholar’, using articles, books, dissertations and theses published until July 2019, using the keyword ‘Helicteres’. This way, we came across 173 scientific papers. The interest in scientific studies focusing on species of this genus for the development of new drugs has increased over the years due to the promising results of the scientific studies conducted with Helicteres.
The study selection and data extraction were performed by one author (DAF) and confirmed by others (EBA, MSRS, MFVS). The extracted data were summarized in tabular form and a narrative description was used to provide a summary of updated information.
RESULTS AND DISCUSSION
Botanical profile and pollinatio
The Helicteres L. species are characterized morphologically as erect shrubs or sub-bushes, with showy, zygomorph, pedicellate flowers usually pendulous and odorless (Figure 1), with a long androgynophore and ten transverse stamens grafted in to a yellow to red corolla; fruits are distinct, spiral capsules.1313 Cristóbal, C. L.; Bonplandia
2001, 11, 1.
14 Silva, C. A.; Ferreira, D. S.; Koch, A. K.; Araújo-Silva, L. E.; Acta. Bot. Bras.
2010, 24, 462.-1515 https://www.flickr.com/photos/tags/helicteres, accessed in September 2019.
https://www.flickr.com/photos/tags/helic...
Helicteres plants. A) H. isora, B) H. angustifolia, C) H. sacarolha, D) H. brevispera, E) H. grazumifolia1515 https://www.flickr.com/photos/tags/helicteres, accessed in September 2019.
https://www.flickr.com/photos/tags/helic...
Its showy flowers are strongly attracted to bats and hummingbirds, as described in studies with H. ovata,1616 Sazima, M.; Plant Biol.
1988, 101, 269.H. brevispira, H. sacarolha,1717 Franceschinelli, E. V.; Kesseli, R.; Heredity
1999, 82, 355.
18 Franceschinelli, E. V.; Bawa, K. S.; Heredity
2000, 84, 116.-1919 Franceschinelli, E. V.; Bawa, K. S.; Braz. J. Bot.
2005, 28, 163. and H. lhotzkyana.1414 Silva, C. A.; Ferreira, D. S.; Koch, A. K.; Araújo-Silva, L. E.; Acta. Bot. Bras.
2010, 24, 462.,2020 González, A. M.; Cristóbal, C. L.; Bonplandia
1997, 287.H. isora flowers, present at Asia, are large and open daily, being visited by birds and insects that assist in pollination during the day.2121 Atluri, J. B.; Rao, S. P.; Reddi, C. S.; Curr. Sci.
2000, 78, 713.
Ethnopharmacological relevance
Almost all parts of Helicteres L. plants, including roots, bark and aerial parts, are reported to be traditionally used in several countries and tribes for therapeutic purposes (Table 1).
The juice of H. isora root is used in Tradicional Chinese Medicine for diabetes treatment, while fruit extract is used in various intestinal disorders to relieve colic and as an anthelmintic medicine against tapeworm.2222 Venkatesh, S.; Reddy, G. D.; Reddy, Y. S. R.; Sathyavathy, D.; Reddy, B. M.; Fitoterapia
2004, 75, 364.
23 Purnomo, L.; Darsono, L.; Santosa, S.; Journal Kedokteran Maranatha
2010, 3, 39.-2424 Dayal, R.; Singh, A.; Ojha, R. P.; Mishra, K. P.; Journal of Medicinal Plants Studies
2015, 3, 95.
The root tea of H. angustifolia is used to treat influenza symptoms and to inhibit tumor growth.2525 Li, K.; Lei, Z.; Hu, X.; Sun, S.; Li, S.; Zhang, Z.; J. Ethnopharmacol. 2015, 172, 61.H. sacarolha preparations with roots and leaves, in form of decoction, infusion or maceration, are used for liver complications, ovarian inflammation, amenorrhea and blood purification,88 Balogun, S. O.; Damazo, A. S.; Martins, D. T. O.; J. Ethnopharmacol. 2015, 166, 176. while the aerial parts of H. velutina are used by indigenous tribe Pankarare/Brazil as insect repellent.2626 Santos, E. A.; Carvalho, C. M.; Costa, A. L. S.; Conceição, A. S.; Moura, F. B. P.; Santana, A. E. G.; Evidence-Based Complementary Altern. Med. 2012, ID 846583.
Ethnopharmacological research with species of this genus acts as a subsidy to the pharmaceutical interest and registration of the empirical uses of medicinal plants in traditional communities associated with chemical-pharmacological tests generates useful knowledges to lead to the development of new drugs.
Phytochemistry profile
In literature, 46 references on the phytochemistry field with species of Helicteres genus were found, 39 of which referring to the studies with H. isora and H. angustifolia. Furthemore, papers reporting research in this area with the species H. hirsute,3838 Satake, T.; Kamiya, K.; Saiki, Y.; Hama, T.; Fujimoto, Y.; Kitanaka, S.; Kimura, Y.; Uzawa, J.; Endang, H.; Umar, M.; Chem. Pharm. Bull. 1999, 47, 1444.,4646 Chin, Y. W.; Jones, W. P.; Rachman, I.; Riswan, S.; Kardono, L. B. S.; Chai, H. B.; Farnsworth, N. R.; Cordell, G. A.; Swanson, S. M.; Cassady, J. M.; Kinghorn, A. D.; Phytother. Res. 2006, 20, 62.H. vegae,4747 Olivas-Quintero, S.; López-Ângulo, G.; Montes-Avila, J.; Díaz-Camacho, S. P.; Vega-Aviña, R.; López-Valenzuela, J. Á.; Salazar-Salas, N. Y.; Delgado-Vargas, F.; Pharm. Biol. 2017, 55, 1473.H. velutina1212 Fernandes, D. A.; Souza, M. S. R.; Teles, Y. C. F.; Oliveira, L. H. G.; Lima, J. B.; Conceição, A. S.; Nunes, F. C.; Silva, T. M. S.; Souza, M. F. V.; Molecules 2018, 23, 2784. and H. eichleri4848 Assis, E. B.; Master's thesis, Universidade Federal da Paraíba, Brasil, 2019. were found, 149 compounds were isolated and identified from Helicteres (Table 2) among the most reported classes. All substances are compiled in the Table 2 (compounds) and Figure 2 (structures).
Terpenoids and steroids
Terpenoids and its oxygenated, acetylated and dehydrogenated derivatives are hydrocarbons of plant origin.8484 Yadav, N.; Yadav, R.; Goyal, A.; Int. J. Pharm. Sci. Rev. Res. 2014, 27, 272. Many of these molecules have biological activities that are used for the treatment of human diseases. These molecules have led to six major classes of drugs in the last century: steroids, tocopherols, texanes, artemisinins, ingenans and cannabinoids.8585 Wang, G.; Tang, W.; Bidigare, R. R. In Natural products: Drug discovery and therapeutic medicine; Zhang, L.; Demain, A., eds.; Humana Press: Totowa, NJ, USA, 2005, p. 197.,8686 Jansen, D. J.; Shenvi, R. A.; Future Med. Chem. 2014, 6, 1127.
Fifty terpenoids were isolated and identified from H. isora, H. angustifolia, H. hirsuta, H. eichleri and H. velutina, evidencing this class as the predominant compounds in Helicteres genus (Table 2). In a preliminary bioassay, cucurbitacins D (4) and J (8) exhibited significant inhibitory activities against hepatocellular carcinoma and malignant melanoma cells in vitro.5151 Chen, W.; Tang, W.; Lou, L.; Zhao, W.; Phytochemistry 2006, 67, 1041.
Compounds 3β-O (trans-coumaroyl) betulinic acid (15), pyracrenic acid (16), 3β-acetoxy-27-[(4-hydroxybenzoyl)oxy]lup-20(29)-en-28-oic acid (32) and 3β-acetoxy-27-[(4-hydroxybenzoyl)oxy]olean-12-en-28-oic acid methyl (39), showed significant cytotoxic activities against human colorectal cancer and human gastric cancer cell lines in vitro.4444 Pan, M. H.; Chen, C. M.; Lee, S. W.; Chen, Z. T.; Chem. Biodiversity 2008, 5, 565. The compound 10-methyl, 4-isopropenyl, dodecahydro-ethanophenanthrene (48) exhibited considerable antimicrobial and antispasmodic activities.6464 Sandhya, P.; Grampurohit, N. D.; Pharmacogn. Mag. 2008, 4, 107.
Steroids are one of the less widespread classes in isolated from species of Helicteres genus, with only seven representatives (50-56).
Phytosteroids are steroidal substances extracted from plant species, the most common being β-sitosterol (51) and Stigmasterol (52). This class of substances has carbonic skeleton formed by the cyclopentanoperhydrophenanthrenic ring,8787 Santos, R. A. F.; Master's thesis, Universidade Federal da Bahia, Brazil, 2010. highlightin the β-sitosterol, which presented antimicrobial and larvicidal activities.8888 Kumar, D.; Singh, R. K.; Farooq, S.; World J. Pharm. Res. 2017, 6, 1102.,8989 Fernandes, D. A.; Barros, R. P. C.; Teles, Y. C. F.; Oliveira, L. H.; Lima, J. B.; Scotti, M. T.; Nunes, F. C.; Conceição, A. S.; Souza, M. F. V.; Molecules 2019, 24, 2315.
Flavonoids and phenolic compounds
Flavonoids represent one of the most important and diverse groups of phenolic compounds among natural products.9090 Santos, D. S.; Rodrigues, M. M. F.; Estação Científica 2017, 7, 29.,9191 Sobrinho, T. J. S. P.; Gomes, T. L. B.; Cardoso, K. C. M.; Amorim, E. L. C.; Quim. Nova 2010, 33, 288. Among the phytotherapics currently studied, flavonoids have been highlighted due to their wide range of biological and/or pharmacological actions demonstrated under both experimental and human conditions.9292 Flambó, D. F. A. L. P.; Master's thesis, Universidade Fernando Pessoa, Porto, Portugal, 2013.
Twenty-nine flavonoids were isolated from Helicteres genus, with emphasis on heterosides (69),3636 Kamiya, K.; Saiki, Y.; Hama, T.; Fujimoto, Y.; Endang, H.; Umar, M.; Satake, T.; Phytochemistry 2001, 57, 297.,7171 Buckingham, J.; Munasinghe, V. R. N.; Dictionary of Flavonoids with CD-ROM; CRC Press: Boca Raton, FL, USA, 2015, T-334, 857. sulphated (78-80) and heterosides glycosulphated (65-67).1212 Fernandes, D. A.; Souza, M. S. R.; Teles, Y. C. F.; Oliveira, L. H. G.; Lima, J. B.; Conceição, A. S.; Nunes, F. C.; Silva, T. M. S.; Souza, M. F. V.; Molecules 2018, 23, 2784.,3636 Kamiya, K.; Saiki, Y.; Hama, T.; Fujimoto, Y.; Endang, H.; Umar, M.; Satake, T.; Phytochemistry 2001, 57, 297. Among those compounds, tiliroside (70) and 7,4′-di-O-methyl-8-O-sulphate flavone (78) have larvicidal activity against Aedes aegypti,8888 Kumar, D.; Singh, R. K.; Farooq, S.; World J. Pharm. Res. 2017, 6, 1102. while 7,4’-O-methylisoscutellarein (60) have shown anti-inflammatory activity by inhibiting neutrophil recruitment and decreasing IL-1β and TNF-α production in vitro.9393 Teles, Y. C.; Ribeiro-Filho, J.; Agra, M. F.; Siheri, W.; Igoli, J. O.; Gray, A. I.; Souza, M. F.; Nat. Prod. Res. 2015, 30, 1880.
Besides the flavonoids, it was possible to identify 18 phenolic compounds (85-102) with different nuclei, among them rosmarinic acid (85) isolated from H. isora fruits, H. angustifolia and H. vegae roots and H. eichleri aerial parts. Scientific studies of this substance have proven its antioxidant, anti-inflammatory, antifibrosis, hepatoprotective and antineoplasic activities.9494 Cao, W.; Hu, C.; Wu, L.; Xu, L.; Jiang, W.; J. Pharm. Sci. 2016, 132, 131.
Some studies also report the compounds quantification in species of Helicteres genus, among which are total phenolic content, flavonoids and condensed tannins of H. vegae.4747 Olivas-Quintero, S.; López-Ângulo, G.; Montes-Avila, J.; Díaz-Camacho, S. P.; Vega-Aviña, R.; López-Valenzuela, J. Á.; Salazar-Salas, N. Y.; Delgado-Vargas, F.; Pharm. Biol.
2017, 55, 1473. It was also accomplished the phenolics, flavonoids and saponins quantification of H. hirsuta4545 Pham, H. N. T.; Nguyen, V. T.; Vuong, Q. V.; Bowyer, M. C.; Scarlett, C. J.; J. Food Process. Preserv.
2017, 41, 1745.,9595 Pham, H. N. T.; Vuong, Q. V.; Bowyer, M. C.; Scarlett, C. J.; Chem. Pap.
2017, 71, 2233.,9696 Pham, H. N. T.; Vuong, Q. V.; Bowyer, M. C.; Scarlett, C. J.; Asia-Pac. J. Chem. Eng.
2017, 12, 332. and H. isora, to evaluate their antioxidant potential.9797 Jain, A.; Sinha, P.; Desai, N. S.; Int. J. Pharm. Sci. Res. 2014, 5, 1320.
98 Sharma, S.; Bhargava, S.; Mehta, A.; World J. Pharm. Pharm. Sci.
2017, 6, 1471.-9999 Bhat, B. A.; Int. J. Bioassays
2012, 1, 177.
Lignoids
Twenty-one lignoids were isolated and identified from H. isora, H. angustifolia, H. hirsuta and H. velutina species, most of them found in the roots and fruits. Yin et al. (2016)5757 Yin, X.; Lu, Y.; Cheng, Z. H.; Chen, D. F.; Molecules 2016, 21, 1506. isolated two benzofuran lignans of H. angustifolia that were evaluated for anti-complementary activity in vitro and showed potent activity when compared to heparin (positive control). Tezuka et al. (2000)7474 Tezuka, Y.; Terazono, M.; Kusumoto, T. I.; Hatanaka, Y.; Kadota, S.; Hattori, M.; Namba, T.; Kikuchi, T.; Tanaka, K.; Supriyatna, S.; Helv. Chim. Acta 2000, 83, 2908. isolated and identified six dimeric neolignans from fruits of H. isora: Helicterins B (120), C (115), D (117), E (116) and F (118), which showed mild inhibitory activity against avian myeloblastosis virus reverse transcriptase (AMV-RT), having an emphasis on the inhibitory activity of Helicterins A (119), which was identical to the antineoplasic drug doxirubicin, with an IC50 of 66 µM. This can be of interest for the development of new therapeutic alternatives.
Quinones
Quinones are structurally characterized as cyclic α, β-dienics, and have considerable toxicological and pharmacological interests due to their biooxidation-reduction properties and ability to catalyze biological electrical transfer.100100 Sousa, E. T. S.; Lopes, W. A.; Andrade, J. B.; Quim. Nova 2016, 39, 486. However, biological studies involving isolated quinones of Helicteres species are scarce, as it is necessary to investigate possible biological actions not yet explored. So far, ten quinones have been isolated and identified in the studied genus (123-132), and the compounds that best represent this class were sesquiterpene quinones and O-benzoquinones, isolated from H. angustifolia roots.4040 Chen, C. M.; Chen, Z. T.; Hong, Y. L.; Phytochemistry 1990, 29, 980.,4242 Wang, M.; Liu, W.; Phytochemistry 1987, 26, 578.,5151 Chen, W.; Tang, W.; Lou, L.; Zhao, W.; Phytochemistry 2006, 67, 1041.
Other compounds
Beyond to previously detailed compounds, other classes of metabolites, such as amines, saponins, lactones, coumarins, alcohols, fatty acids, alkaloids, pheophytins and tannins (133-149) (Table 2, Figure 1), were less frequently detected in this genus.
Aleykutty & Akhila (2012),8080 Aleykutty, N. A.; Akhila, S.; Int. J. Comput. Appl. Technol. 2012, 45, 8. by means of a computational approach, predicted the antidiabetic potential of the chemical constituents identified in H. isora, especially the indolalkylamine, Yohimbine (142), which presented the best binding energy with the enzyme aldose reductase and the insulin receptor protein, pharmacological targets for glycemic control.
Pharmacology study
Pharmacological potential of Helicteres species has gained prominence, especially with H. isora and H. angustifolia, that have a long history of use in traditional Chinese medicine. Researches have been developed about antidiabetic, antiulcerogenic and antitumor activities within Helicteres species in order to confirm the activities reported by folk medicine (Table 3).
Anti-inflammatory and analgesic activity
Natural products are widely used in folk medicine to treat inflammatory conditions, including fever, pain, migraine and arthritis, being targets for the development of new anti-inflammatory drugs.172172 Lalrinzuali, K.; Vabeiryureilai, M.; Jagetia, G. C.; Int. J. Inflammation 2016, ID 8247014. Studies with plant extracts have shown promissory activity.173173 Ior, L. D.; Otimenyin, S. O.; Umar, M.; J. Pharm. 2012, 2, 33.
H. isora root extract showed antinociceptive activity in mice.101101 Venkatesh, S.; Laxmi, K. S.; Reddy, B. M.; Ramesh, M.; Fitoterapia 2007, 78, 146.H. angustifolia n-butanol fraction has anti-inflammatory and analgesic activity.104104 Jiang, C.; Wu, M.; Qin, Q.; Meng, X.; Liu, B.; China J. Tradit. Chin. Med. Pharm. 2010, 25, 1672. Non-clinical mice studies have showed through photoacoustic spectroscopy that H. gardneriana extract induces a significant reduction in the inflamed area.106106 Melo, J. O.; Pedrochi, F.; Baesso, M. L.; Hernandes, L.; Truiti, M. C. T.; Baroni, S.; Bersani-Amado, C. A.; Pharm. Res. 2011, 28, 331. Studies with extracts from the aerial parts of H. hirsute has been conducted in order to discover their mechanisms of action against inhibition of COX1 and COX2 in vitro7070 Nguyen, T. T.; Gao, X.; Nikles, S.; Pferschy-Wenzing, E. M.; Kunert, O.; Bauer, R.; Reviews of Clinical Pharmacology and Drug Therapy 2017, 15, 48. (Table 3).
Antitumor and cytotoxic activity
Cancer is one of the leading causes of mortality in the world. About 60% of current anticancer drugs are from natural origin, with emphasis on plant species that are rich in anticancer agents and can be used as an alternative to chemotherapeutic drugs as they are less toxic.174174 Jeena, K.; Liju, V. B.; Kuttan, R.; Int. J. Pharm. Pharm. Sci. 2015, 7, 341. The effects of plant-derived natural products have been investigated to a large extent on cancer cell proliferation, survival, invasion and metastasis due to bioactivity and the diversity of their chemical constituents.6060 Su, D.; Gao, Y.-Q.; Dai, W.-B.; Hu, Y.; Wu, Y.-F.; Mei, Q.-X.; Evidence-Based Complementary Altern. Med. 2017, ID 5180707.,175175 Cardoso, M. F. C.; da Silva, I. M. C. B.; dos Santos Júnior, H. M.; Rocha, D. R.; Araújo, A. J.; Pessoa, C.; de Moraes, M. O.; Lotufo, L. V. C.; da Silva, F. C.; Santos, W. C.; Ferreira, V. F.; J. Braz. Chem. Soc. 2013, 24, 12.
Helicteres are used to decrease tumor progression by folk medicine. In order to evaluate this activity, extracts, fractions and isolated substances have been studied through the evaluation of cytotoxic activity mainly in liver, lung, colon and breast cancers (Table 3).
The acetone extract of H. isora fruits exhibited better cytotoxic activity in vitro against lung cancer cells.107107 Raaman, N.; Balasubramanian, K.; J. Acad. Ind. Res. 2012, 1, 148. Studies with the terpenes Helicteric acid (38), oleanolic acid (45) and betulinic acid (12) isolated from H. angustifolia have shown important anticancer activity and showed that compounds could decrease proliferation and induce apoptosis in HT-29 colorectal cancer cells in vitro.6060 Su, D.; Gao, Y.-Q.; Dai, W.-B.; Hu, Y.; Wu, Y.-F.; Mei, Q.-X.; Evidence-Based Complementary Altern. Med. 2017, ID 5180707. A similar activity was developed by the compounds 2, 3, 3 β-O-[(E)-coumaroyl] betulinic acid (15) and pyracrenic acid (16).4444 Pan, M. H.; Chen, C. M.; Lee, S. W.; Chen, Z. T.; Chem. Biodiversity 2008, 5, 565.
In vivo studies revealed that hydroethanolic extract flavonoid-rich of H. sacarolha and phenolic compounds have good activity in ovarian cancer cell lineages, being non-toxic when ingested orally,88 Balogun, S. O.; Damazo, A. S.; Martins, D. T. O.; J. Ethnopharmacol. 2015, 166, 176. while hidroethanolic stem bark extract of H. isora shows activity against hepatocellular carcinoma in mice.167167 Shah, D. V.; Shyale, S. S.; Soloman, S. S.; World J. Pharm. Pharm. Sci. 2015, 4, 788.
Hepatoprotective activity
Extracts of several plant species have shown hepatoprotective activity176176 Lin, E.-Y.; Chagnaadorj, A.; Huang, S.-J.; Wang, C.-C.; Chiang, Y.-H.; Cheng, C.-W.; Evidence-Based Complementary Altern. Med.
2018, ID 4130307.
177 Yahya, F.; Mamat, S. S.; Kamarolzaman, M. F. F.; Seyedan, A. A.; Jakius, K. F.; Mahmood, N. D.; Shahril, M. S.; Suhaili, Z.; Mohtarrudin, N.; Susanti, D.; Somchit, M. N.; Teh, L. K.; Salleh, M. Z.; Zakaria, Z. A.; Evidence-Based Complementary Altern. Med.
2013, ID 636580.-178178 Akther, N.; Shawl, A. S.; Sultana, S.; Chadan, B. K.; Akther, M.; J. Pharm. Res.
2013, 7, 565. and approximately 100 of these species have been used in the preparation of over 700 herbal formulations that are available for use in prevention and treatment of liver disease.179179 Das, K. L. S.; Pharmacogn. Res.
2011, 3, 13.,180180 Bhaargavi, V.; Jyotsna, G. S. L.; Tripurana, R.; Int. J. Pharm. Sci. Res.
2014, 5, 690.
The hepatic protection exerted by the H. isora and H. angustifolia species was also investigated in vivo, where the main parameters of alterations in liver enzymes production and serum markers are evaluated. H. isora bark ethanolic extract and H. angustifolia water extract demonstrated hepatoprotective activity against carbon tetrachloride induced liver damage in rats and mice, respectively.116116 Kumar, N.; Singh, A. K.; Asian-Pac. J. Trop. Biomed. 2014, 4, S22. The methyl helicterate (30) isolated from H. angustifolia acts on carbon tetrachloride in induced hepatic fibrosis of rats, which may be associated with its free radical scavenging action and antioxidant activity. Another proposed mechanism of action of this substance would be the inhibits activation of hepatic stellate cells, modulating apoptosis and autophagy.120120 Huang, Q.; Li, Y.; Zhang, S.; Huang, R.; Zheng, L.; Wei, L.; He, L.; Liao, M.; Li, L.; Zhuo, L.; Lin, X.; J. Ethnopharmacol. 2012, 143, 889.,121121 Zhang, X. L.; Chen, Z. N.; Huang, Q. F.; Bai, F. C.; Nie, J. L.; Lu, S. J.; Wei, J. B.; Lin, X.; Cell. Physiol. Biochem. 2018, 51, 897.
Antidiabetic and hypolipidemic activity
Available literature shows that various chemical compounds with antidiabetic properties have been identified in some plant species,181181 Emordi, J. E.; Agbaje, E. O.; Oreagba, I. A.; Iribhogbe, O. I.; BMC Complementary Altern. Med. 2016, 15, 468.,182182 Severino, V. G. P.; Monteiro, A. F.; Silva, M. F. G. F.; Lucarini, R.; Martins, C. H. G.; Quim. Nova 2015, 38, 42. among which we can highlight some belonging to the Helicteres genus.
The ethanolic extract of H. isora roots causes significant reduction in glucose, triglyceride and insulin levels in mouse plasma, suggesting that it has insulin sensitizing and hypolipidemic activity with potential use in the treatment of type 2 diabetes.2828 Chakrabarti, R.; Vikramadithyan, R. K.; Mullangi, R.; Sharma, V. M.; Jagadheshan, H.; Rao, Y. N.; Sairam, P.; Rajagopalan, R.; J. Ethnopharmacol. 2002, 81, 343. Researches over this species have also proven the antidiabetic activity of the aqueous extracts of its peels, stem and fruits.3030 Kumar, G.; Banu, G. S.; Murugesan, A. G.; Pandian, M. R.; J. Ethnopharmacol. 2006, 107, 304.,127127 Kumar, G.; Banu, G. S.; Murugesan, A. G.; Hum. Exp. Toxicol. 2009, 28, 689.,129129 Vijay, K. P.; Laxman, B. C.; Ashok, R. S.; Bansilal, S. S.; Janardhan, P. M.; J. Biol. Sci. Opin. 2013, 1, 5.
The extract and n-butanolic fractions of H. isora have shown good in vivo activity with antihyperglycemic activity, reducing glucose and total cholesterol levels.123123 Venkatesh, S.; Reddy, G. D.; Reddy, B. M.; Pharm. Biol. 2003, 41, 347.,124124 Tiwari, V.; Singh, A.; Tiwari, A.; Nat. Prod. J. 2012, 2, 9. Saponin-rich fractions also exhibit this activity in vitro and in vivo.126126 Bhavsar, S. K.; Singh, S.; Giri, S.; Jain, M. R.; Santani, D. D.; J. Ethnopharmacol. 2009, 124, 426.,130130 Bhavsar, S. K.; Foller, M.; Gu, S. C.; Vir, S.; Shah, M. B.; Bhutani, K. K.; Santani, D. D.; Lang, F.; J. Ethnopharmacol. 2009, 126, 386. Molecular docking with insulin receptors was analyzed with compounds isolated from H. isora fruits,183183 Vennila, S.; Bupesh, G.; Saravanamurali, K.; SenthilKumar, V.; SenthilRaja, R.; Saran, N.; Magesh, S.; Bioinformation 2014, 10, 263. and the results suggested that they may be useful for treating diabetes.
H. angustifolia roots aqueous and ethanolic extracts have also shown significant antidiabetic activity in vivo, significant alpha-glucosidase inhibitory and moderate enhanced glucose consumption activity, while having low cytotoxicity and acute toxicity.138138 Hu, X.; Cheng, D.; Zhang, Z.; Pharm. Biol. 2016, 54, 938.,139139 Hu, X. S.; Cheng, D. L.; Li, K. J.; Wang, L. B.; Yang, X.; Sun, S.; Wang, Y. P.; Li, S. H.; Lei, Z. F.; Zhang, Z. Y.; Riv. Eur. Sci. Med. Farmacol. 2016, 20, 1423.
Antioxidant activity
Antioxidants are important for preventing human diseases. Naturally occurring antioxidants such as ascorbic acid, vitamin E and phenolic compounds can reduce the oxidative damage associated with various diseases including cancer, cardiovascular disease, cataract, atherosclerosis, diabetes, arthritis, immune deficiency diseases and aging.2727 Basniwal, P. K.; Suthar, M.; Rathore, G. S.; Gupta, R.; Kumar, V.; Pareek, A.; Jain, D.; Indian J. Nat. Prod. Resour. 2009, 8, 483.
Evaluation of antioxidant activity of the species H. isora, H. angustifolia, H. hirsuta and H. vegae, mainly with respect to fruit extract,141141 Kumar, V.; Sharma, M.; Lemos, M.; Shriram, V.; J. Pharm. Res. 2013, 6, 620. rich fractions of saponins2424 Dayal, R.; Singh, A.; Ojha, R. P.; Mishra, K. P.; Journal of Medicinal Plants Studies 2015, 3, 95. and polissacarids,147147 Jain, A.; Ranade, R.; Pritam, P.; Joshi, N.; Vavilala, S. L.; Jain, A.; Am. J. Life Sci. 2014, 2, 292. showed that they are capable of inhibiting in vitro peroxidation radicals such as DPPH (1,1-diphenyl-2-picryl-hydrazyl), H2O2 (Hydrogen peroxide), NO (Nitric Oxide), ABTS (2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)), TBARS (thiobarbituric acid-reactive substances), FRAP (ferric reducing antioxidant power) and CUPRAC (cupric reducing antioxidant capacity).
Antimicrobial and antiviral activity
In the current scenario, due to the various pathogenic microorganisms, infectious diseases are still one of the leading reasons behind the worldwide death rates.184184 Sharma, V.; Chaudhary, U.; Asian J. Pharm. Clin. Res. 2016, 9, 96. The emergence of multiple commonly used antibiotic drug resistant bacteria is a severe health problem and major challenge for global drug discovery programs,154154 Anburaja, V.; Nandagopalan, V.; Prabha, A. L.; J. Ecobiol. 2010, 26, 211. and the use of plant extracts and isolated compounds with known antimicrobial properties becomes an important alternative in therapeutic treatments.185185 Nascimento, G. G. F.; Locatelli, J.; Freitas, P. C.; Silva, G. L.; Braz. J. Microbiol. 2000, 31, 247.
H. isora and H. angustifolia organic extracts have been extensively studied for their potential to act as antimicrobial agents.150150 Akshatha, S.; Chaithra, K. J.; Priyanka, A.; Priyanka, L.; Prashith, K. T. R.; Raghavendra, H. L.; World J. Pharm. Pharm. Sci. 2015, 4, 1793. Among the isolated compounds, oleanolic acid (45)8888 Kumar, D.; Singh, R. K.; Farooq, S.; World J. Pharm. Res. 2017, 6, 1102. and β-sitosterol (51)8888 Kumar, D.; Singh, R. K.; Farooq, S.; World J. Pharm. Res. 2017, 6, 1102. showed good antibacterial activity, while methyl helicterilate compound (49) showed potential antiviral activity162162 Huang, Q. F.; Yang, H.; Wei, G.; Lin, X.; Zhang, S. J.; Huang, R. B.; Chin. J. Exp. Tradit. Med. Formulae 2011, 179. (Table 3).
Other activities
Other activities have been reported from Helicteres species. H. isora stems aqueous extract showed no toxicity when administered orally at concentrations of 100 and 200 mg/kg in rats.3939 Kumar, G.; Banu, G. S.; Murugesan, A. G.; Pandian, M. R.; Iran. J. Pharm. Res. 2007, 6, 123. Researchers also evaluate antispasmodic,3737 Pohocha, N.; Grampurohit, N. D.; Phytother. Res. 2001, 15, 49. gastroprotective,88 Balogun, S. O.; Damazo, A. S.; Martins, D. T. O.; J. Ethnopharmacol. 2015, 166, 176. anthelmintic167167 Shah, D. V.; Shyale, S. S.; Soloman, S. S.; World J. Pharm. Pharm. Sci. 2015, 4, 788. and larvicide against Aedes aegypti larvae1212 Fernandes, D. A.; Souza, M. S. R.; Teles, Y. C. F.; Oliveira, L. H. G.; Lima, J. B.; Conceição, A. S.; Nunes, F. C.; Silva, T. M. S.; Souza, M. F. V.; Molecules 2018, 23, 2784.,4848 Assis, E. B.; Master's thesis, Universidade Federal da Paraíba, Brasil, 2019. activities, among others. In addition, studies were also carried out to evaluate the nutritional value of H. isora fruits and stems.186186 Gayathri, P.; Gayathri, D. S.; Srinivasan, S.; Saroja, S.; Hygeia: J. Drugs Med. 2010, 2, 57.
CONCLUSIONS
Helicteres L. is one of the genera belonging to Sterculiaceae clade in Malvaceae family with several notable activities. Previous studies have revealed that terpenoids, flavonoids and lignoids are the dominant constituents of Helicteres species. However, information about this genus is scarce and not systematic. The in vitro and in vivo studies carried out to date prove traditional medicine reports regarding the activities of those species. However, pharmacological tests with isolated substances are still rare from this genus and its compounds, especially those unpublished in the literature, resulting in unexplored potentials.
Given the presented data, it is extremely important to continue exploring the chemical and biological potentials of these and other species present in the American and Asian flora, considering the need to find substances with biological activities that may be used for mankind benefit.
ACKNOWLEDGMENTS
The authors thank the Coordenação de Aperfeiçoamento do Ensino Superior (CAPES) and the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).
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Publication Dates
-
Publication in this collection
22 July 2020 -
Date of issue
June 2020
History
-
Received
11 Nov 2019 -
Accepted
12 Feb 2020 -
Published
20 Apr 2020