Gastroprotective effect of ethyl acetate extract from Avicennia schaueriana Stapf & Leechman and underlying mechanisms

Abstract

Objective: Avicennia schaueriana Stapf is an endemic mangrove species widely used by traditional Brazilian communities as a folk remedy for the treatment of rheumatism, ulcers, and skin wounds. The aim of the present study was to evaluate the gastroprotective potential of the ethyl acetate extract from the leaves of A. schaueriana (As-AcOEt).

Methods: Ultra-performance liquid chromatography coupled with diode-array detection and quadrupole time-of-flight mass spectrometry (UPLC-DAD-QTOF-MS/MS) was performed to identify chemical constituents of the ethyl acetate extract from the leaves ofA. schaueriana. Total phenols, flavonoids and tannins were determined and antioxidant activity was evaluated using the DPPH and ABTS methods. The acute toxicity of As-AcOEt and gastroprotective activity on HCl/ethanol-induced gastric ulcers were assessed and mechanisms of action involving the role of nitric oxide, sulfhydryl compounds, and prostaglandins were investigated.

Results: Terpenes, flavonoids and tannins were detected in the extract. As-AcOEt exhibited antioxidant activity, with an EC₅₀ of 42.2 ± 4.4 μg/mL (DPPH) and 73.2% inhibition of ABTS radicals. UPLC-DAD-QTOF-MS/MS analysis identified gallic acid, gallic acid derivative, ellagic acid, myricetin pentoside, myricetin deoxyhexose, quercetin pentoside, quercetin deoxyhexose, and other compounds. Gallic acid was isolated in this species for the first time. During the acute toxicity test, no deaths or changes occurred in the variables evaluated. In the ethanol-induced ulcer model, As-AcOEt reduced the ulcerative lesion index, with 50, 100 and 200 mg/kg achieving 83.8, 88.5 and 86.9% inhibition, respectively. MPO levels decreased and the gastric mucosa of the animals treated with the extract was preserved. Pre-treatment with N-omega-nitro-l-arginine methyl ester (L-NAME; NO blocker) or carbenoxolone (CBXN; NP-SH blocker) reversed the gastroprotective effect of As-AcOEt, but this effect was not reversed with the previous administration of indomethacin.

Conclusion: The present findings reveal that the extract from the leaves ofA. schaueriana has gastroprotective effects, suggesting the involvement of nitric oxide and nonprotein sulfhydryl compounds, but not prostaglandin. Therefore, the use of A. schaueriana in Brazilian folk medicine for the treatment of gastric disorders has a scientific basis.

Keywords: Antioxidant; Liquid chromatography; Nitric oxide; Prostaglandin; Ulcer.