Evaluation of anti-nociceptive and anti-inflammatory activities of the methanol extract of Holigarna caustica (Dennst.) Oken leaves.

ETHNOPHARMACOLOGICAL RELEVANCE: Holigarna caustica (Dennst.) is commonly used in traditional medicine to treat a variety of painful conditions such as eye irritation, inflammation, arthritis, skin diseases, cuts and wounds. AIM OF THE STUDY: The present study was undertaken to investigate the anti-nociceptive and anti-inflammatory activities of the methanol extract of H. caustica leaves and to elucidate its possible mechanism(s) of action. MATERIALS AND METHODS: Fresh leaves of H. caustica were collected, dried, and extracted with methanol (MEHC). MEHC was subjected to activity testing, using chemical-induced (acetic acid and formalin test) and heat-induced (hot plate and tail immersion test) pain models. To determine the possible mechanism behind the anti-nociceptive activity of MEHC, the opioid antagonist naltrexone was used to evaluate the involvement of opioid receptors in the case of formalin, hot plate and tail immersion tests, while the involvement of the cGMP and ATP-sensitive K+ channel pathways were assessed using methylene blue and glibenclamide respectively, in the acetic acid-induced writhing test. In parallel, the carrageenan-induced paw oedema model was used to determine the anti-inflammatory potential of the extract. Exploratory and motor behaviours were evaluated by the open-field test. Various bioactive compounds potentially responsible for the anti-nociceptive and anti-inflammatory activities were ascertained using GC-MS analysis. RESULTS: MEHC showed strong, significant and dose-dependent anti-nociceptive activity in all chemical-induced and heat-induced pain models at all experimental doses. The association of opioid receptors with the observed anti-nociceptive effects was confirmed by using naltrexone. The cGMP and ATP-sensitive K+ channel pathway was also shown to be involved in the anti-nociceptive activity of MEHC. In addition, MEHC exhibited a dose-dependent inhibition of inflammatory oedema induced by carrageenan. MEHC was not connected with changes in either the locomotor activity or motor responses of mice. In a GC-MS analysis, 40 compounds were identified, among which twelve are documented bioactive compounds with potent analgesic and anti-inflammatory properties. CONCLUSIONS: Our current study revealed that MEHC possesses strong central and peripheral anti-nociceptive as well as anti-inflammatory activity. It may also be concluded that both opioid receptors as well as the cGMP and ATP-sensitive K+ channel pathway are involved in the anti-nociceptive mechanism of MEHC. This study rationalizes the ethnomedicinal use of H. caustica leaves in various painful conditions.

Current state of knowledge on the traditional uses, phytochemistry, and pharmacology of the genus Hymenaea.

ETHNOPHARMACOLOGICAL RELEVANCE: Plants of the genus Hymenaea (Fabaceae) are used in South American and Asian traditional medicines to treat a multitude of disorders, like cough, diarrhea, dysentery, intestinal colic, pulmonary weakness, asthma, anemia, sore throat, and for the treatment of kidney problems, viral related disorders, chronic cystitis, bronchitis, and bladder infections. Some Hymenaea species are also used as vermifuge, and for the treatment of arthritis, and inflammation conditions. This review deals with updated information on the traditional uses, phytochemistry and pharmacology of ethnomedicinally important Hymenaea species in order to provide an input for the future research prospects. METHODS: Literature available in various recognized databases including Google Scholar, PubMed, SciFinder, Scopus, Springer, Wiley, ACS, Scielo and Web of Science, as well as from theses, dissertations, books, reports, and other relevant websites (www.theplantlist.org), are surveyed, analysed, and included in this review. Herein, the literature related to chemical constituents and pharmacological activities were searched in November 2016. RESULTS: The literature provided information on ethnopharmacological uses of the South American and African species of the genus Hymenaea (e.g., H. courbaril, H. stigonocarpa, H. onblogifolia, H. martiana, H. parvifolia (South America) and H. verrucosa (African species)) for the treatment of multi-factorial diseases. From these plant species, more than 130 compounds, including fatty acids, flavonoids, terpenoids and steroids, phthalides, phenolic acids, procyanidins and coumarins were identified. Experimental evidences confirmed that the Hymenaea spp. could be used in treating inflammatory disorders, asthma, diarrhea, and some microbial infections. However, reports on the toxicity of Hymenaea species remain scarce. CONCLUSION: Plants of this genus have offered bioactive samples, both from crude extracts and pure compounds, thus substantiating their effectiveness in traditional medicine. However, intensive investigations of all the species of Hymenaea spp. relating to phytochemical and pharmacological properties, especially their mechanism of action, safety and efficacy could be the future introspection.