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水黄皮乙酸乙酯提取物的胃保护作用及其作用机制。

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

机构信息

Department of Antibiotics, Federal University of Pernambuco, Cidade Universitária, Av. Arthur de Sá, S/N, 50670-901, Recife, PE, Brazil.

Department of Antibiotics, Federal University of Pernambuco, Cidade Universitária, Av. Arthur de Sá, S/N, 50670-901, Recife, PE, Brazil; Department of Chemistry, Federal Institute of Education, Science and Technology of Pernambuco, Fazenda Sapé, S/N, Zona Rural Barreiros, 55560-000, PE, Brazil.

出版信息

Biomed Pharmacother. 2019 Apr;112:108582. doi: 10.1016/j.biopha.2019.01.043. Epub 2019 Feb 16.

DOI:10.1016/j.biopha.2019.01.043
PMID:30780106
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 EC 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.

摘要

目的

木榄(Avicennia schaueriana Stapf)是一种地方性红树林物种,被巴西传统社区广泛用作民间疗法,用于治疗风湿病、溃疡和皮肤伤口。本研究旨在评估木榄叶乙酸乙酯提取物(As-AcOEt)的胃保护潜力。

方法

采用超高效液相色谱-二极管阵列检测-四级杆飞行时间质谱联用技术(UPLC-DAD-QTOF-MS/MS)对木榄叶乙酸乙酯提取物中的化学成分进行鉴定。测定总酚、类黄酮和单宁的含量,并采用 DPPH 和 ABTS 法评价抗氧化活性。评估 As-AcOEt 的急性毒性和对盐酸/乙醇诱导的胃溃疡的胃保护活性,并研究涉及一氧化氮、巯基化合物和前列腺素作用机制的机制。

结果

提取物中检测到萜类化合物、类黄酮和单宁。As-AcOEt 表现出抗氧化活性,DPPH 的 EC 为 42.2 ± 4.4 μg/mL,ABTS 自由基抑制率为 73.2%。UPLC-DAD-QTOF-MS/MS 分析鉴定出没食子酸、没食子酸衍生物、鞣花酸、杨梅素五糖苷、杨梅素脱氧己糖苷、槲皮素五糖苷、槲皮素脱氧己糖苷和其他化合物。在该物种中首次分离出没食子酸。在急性毒性试验中,未观察到死亡或评估变量发生变化。在乙醇诱导的溃疡模型中,As-AcOEt 降低溃疡指数,50、100 和 200mg/kg 分别达到 83.8%、88.5%和 86.9%的抑制率。MPO 水平降低,并用提取物处理的动物的胃黏膜得到保存。预先给予 Nω-硝基-L-精氨酸甲酯(L-NAME;NO 阻断剂)或 carbenoxolone(CBXN;NP-SH 阻断剂)可逆转 As-AcOEt 的胃保护作用,但先前给予吲哚美辛不能逆转这种作用。

结论

本研究结果表明,木榄叶提取物具有胃保护作用,提示一氧化氮和非蛋白巯基化合物参与,但不涉及前列腺素。因此,巴西民间医学中使用木榄来治疗胃部疾病具有科学依据。

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