Avaliação do potencial farmacoquímico da Dimorphandra mollis Benth. (fava- d’anta): do extrativismo sustentável ao desenvolvimento de fitoterápico

Abstract

Introduction: Dimorphandra mollis Benth. is a native Brazilian plant, widely valued due to its high content of rutin, a flavonoid with antioxidant, anti-inflammatory, cardioprotective, and antidiabetic properties. Objective: To develop a herbal medicine from the hydroalcoholic extract of D. mollis pods for the treatment of atopic dermatitis (AD). Materials and methods: The bibliometric analysis included 122 publications collected from the Scopus and Web of Science databases, using the Bibliometrix, VOSviewer, Biblioshiny, Excel, and OriginPro software packages. Patent prospecting was performed in the USPTO, WIPO, EPO, and INPI databases, using terms related to the species and filtering by language and CPC classification. The botanical material was collected in Jardim (CE). The pods were dried, pulverized, and analyzed for particle size, moisture, and total ash. Preliminary phytochemical screening identified secondary metabolites, and extracts were obtained by fractional percolation with hydroalcoholic solvents under different conditions. Rutin and quercetin were quantified by High Performance Liquid Chromatography (HPLC). Analyses were performed using an Ultra Performance Liquid Chromatography (UPLC) system. n silico studies were performed with the isolated molecules to predict biological activity, cytotoxicity, antibacterial potential, pharmacokinetic and toxicological parameters, and skin permeation. In vivo tests were conducted with zebrafish (Danio rerio). The procedures were approved by CEUA-UECE, protocol no. 04009489/2023. Based on the fluid extract of D. mollis, a phytotherapeutic formulation was developed. The parameters evaluated included pH, spreadability, viscosity, density, optical microscopy, and centrifugation. Finally, the quantification of the active ingredients in the formulation was performed by CLAE, using methanol extraction, sonication, and centrifugation, with comparison to analytical standards. Results: Bibliometric analysis identified 122 publications on Dimorphandra between 1969 and 2023, with an annual growth of 2.6%, 3,592 citations, and international collaboration in 10.66% of the studies. The Journal of Ethnopharmacology was the most cited, and the article with the greatest impact had 157 citations. The patentometric analysis revealed 109 records, with 26 eligible patents (classes A23 and A61), mostly in WIPO (45%), highlighting Brazil's low participation in the international scenario. In the pharmacognostic study of D. mollis, the plant powder was classified as coarse (0.774 mm), with moisture content (9,67 ± 0,86) and ash content (1,0447 ± 0,0140%) within standards. Phytochemistry revealed a high concentration of flavonoids in the fruits, in addition to saponins, resins, tannins, triterpenes, alkaloids, and steroids. Extraction with 50% ethanol resulted in a better chromatographic profile and higher flavonoid content, with hot 50% ethanol extraction showing a better chromatographic profile (Rf = 0.37 for rutin and Rf = 0.67 for quercetin) and higher total flavonoid content. In addition, among the compounds detected by UPLC, hispidulin, syringetin, and protocatechuic acid stand out as the first report for the genus Dimorphandra. In silico analyses indicated anti-inflammatory, antioxidant, and vasoprotective potential for rutin and quercetin, with low cytotoxicity. In the in vivo model with zebrafish, the extract was non-toxic (LC50 > 950 mg/mL), increased locomotion, and reduced edema, confirming antinociceptive and anti-inflammatory effects. The emulgel formulation showed stability for 60 days, maintaining pH, viscosity, spreadability, and concentration of markers under refrigeration and room temperature. In the oven, there was thermal degradation of flavonoids, highlighting the importance of temperature control to ensure the effectiveness of the formulation. Conclusion: The results validate the feasibility of using fava-d'anta as an active ingredient of bioactive plant origin in pharmaceutical and cosmetic formulations.