Campomanesia lineatifolia Ruiz & Pav.: caracterização fitoquímica, estudos mecanísticos da atividade gastroprotetora e avaliação da atividade anti-Helicobacter pylori

• Ano de defesa: 2021
• Autor(a) principal: Nívea Cristina Vieira Neves
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; Brasil; FARMACIA - FACULDADE DE FARMACIA; Programa de Pós-Graduação em Ciências Farmacêuticas; UFMG
• Palavras-chave em Português: Campomanesia lineatifolia; Úlcera gástrica; Atividade anti-inflamatória; Helicobacter pylori
• Link de acesso: http://hdl.handle.net/1843/41895; https://orcid.org/0000-0001-6565-7925

Campomanesia lineatifolia Ruiz and Pav. (Myrtaceae) is an edible native species found in the Amazon Rainforest, popularly known as gabiroba. In Brazil, Campomanesia species are traditionally used for medicinal purposes such as gastrointestinal disorders. Previous studies conducted by our research group demonstrated high phenolic content and high antioxidant activity for C. lineatifolia ethanolic extract, suggesting a relation with its ethnopharmacological use as antidiarrheal, gastric ulcer and healing. The objective of this study was to evaluate the phytochemistry, gastroprotective, anti-inflamatory, and anti-Helicobacter pylori activities of C. lineatifolia, and to contribute to its chemical-biological standardization. For this, an optimized extractive method was developed to obtain a phenolic-enriched extract, and an analytical method by ultra-performance liquid chromatography for qualitative and quantitative evaluation. Next, high-speed countercurrent chromatography and spectroscopic methods were respectively used to isolate and characterize chemical compounds in optimized extract. Gas chromatography-mass spectrometry analysis was used to identify the chemicals present in the essential oil. To evaluate the gastroprotective, anti-inflammatory and anti-H. pylori activities, in vivo assays were performed in experimental gastric ulcer models, and in vitro assays. Results of the extractive planning allowed selecting the ethanolic extract obtained by reflux system as the one enriched in phenolics. Analyzes obtained by liquid chromatography-mass spectrum and nuclear magnetic resonance in 13C and 1H allowed the identification of 15 chemical compounds in the optimized ethanolic extract, of which 12 were new for the species, with the flavonoids quercitrin and myricitrin being the major substances, thus being quercitrin selected as a marker for the development of the analytical method. In the essential oil analysis, 8 chemicals were identified, representing a total of 98.09%, with 3-hexen-1-ol (46.15%) and α-cadinol (20.35%) being the major constituents. In vivo assay in ethanol-induced ulcer model demonstrated that the extract protected the stomach of mice, at doses of 100 and 250 mg/Kg, and promoted an increase in gastric mucus. In indomethacin-induced ulcer model, mice treated with the extract showed a reduction of the inflammatory cytokines CXCL-1 and IL-6, and inhibition of the NF-κB pathway in gastric tissue. In vitro assays in LPS-stimulated THP-1 cells showed that the extract and isolated compounds, quercitrin and myricitrin, were able to reduce TNF-α and NF-κB. In vitro anti-H. pylori activity assays showed that the ethanolic extract was able to inhibit bacterial growth of commercial (0.49 μg/mL) and clinical (125-250 μg/mL) strains. Furthermore, the essential oil also showed anti-H. pylori activity at the lowest concentration tested (0.6%) in commercial and clinical isolated strains. In conclusion, the C. lineatifolia extract was chemically optimized and standardized, and the in vitro and in vivo assays suggest a mechanistic relationship between gastroprotection and anti-inflammatory activity, and mucosal protective mucus stimulator, in addition to anti-H. pylori activity. This opens perspectives for an herbal medicine as new therapeutic option for patients with gastric ulcers, considering that current clinical management protocols do not include drugs that have these pharmacological activities in association.