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杜仲叶活性成分对大鼠胃溃疡的保护作用:涉及 PI3K/Akt/NF-κB 通路。

Protective effect of active components of Eucommia ulmoides leaves on gastric ulcers in rats: Involvement of the PI3K/Akt/NF-κB pathway.

机构信息

Henan University of Chinese Medicine, Zhengzhou, China.

Engineering Technology Research Center for Comprehensive Development and Utilization of Authentic Medicinal Materials from Henan, Zhengzhou, China.

出版信息

J Food Sci. 2022 Jul;87(7):3207-3222. doi: 10.1111/1750-3841.16214. Epub 2022 Jun 22.

DOI:10.1111/1750-3841.16214
PMID:35733355
Abstract

Eucommia ulmoides leaves are widely developed as food and medicines in China and Japan. Its main components have anti-inflammatory properties against gastric ulcers. The purpose of this study was to assess the protective role of an extract derived from the active components of Eucommia ulmoides leaves (EUL 50) against a gastric ulcer and analyze the underlying antiulcer mechanism. The main components of EUL 50 were identified using an ultra-performance liquid chromatography (UPLC) method. Network pharmacology and molecular docking were performed to predict the possible mechanism of action of EUL 50 in the treatment of gastric ulcers. The rats received EUL 50 intragastric administration twice a day for 3 days. Hydrochloric acid/ethanol (HCl/EtOH) was utilized to induce gastric ulcers, followed by histopathological and histochemical evaluation of the ulcer tissues and determination of the main oxidative stress parameters and inflammatory cytokines. The expression of PI3K/Akt/NF-κB pathway-related proteins was measured. Neochlorogenic acid, chlorogenic acid, rutin, and so on were identified as the major components of EUL 50 by UPLC. The prediction results identified the PI3K/Akt/NF-κB signaling pathway as the main possible protective mechanism against gastric ulcers. Furthermore, in a dose-dependent manner, EUL 50 reduced gastric tissue damage. In addition, the high dose of EUL 50 administration resulted in remarkable reductions in the levels of malondialdehyde (MDA), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and interleukin-1β (IL-1β) by 22.64%, 42.61%, 57.78%, and 56.51%, respectively, and suppression of the phosphorylation of Akt, p65, IKKα, and IκBα by 60.87%, 67.65, 74.58%, and 59.57%, respectively, and increased the antioxidant enzyme activity. EUL 50 is rich in flavonoids and organic acids that can act on the PI3K/Akt/NF-κB signaling pathway; as a result, oxidative stress and inflammation are considerably reduced, and gastric ulcers caused by HCl/EtOH are reduced. PRACTICAL APPLICATION: As a medicinal and food substance, Eucommia ulmoides leaves are widely used in the development of health products. EUL 50, a moderately polar part of E. ulmoides leaves, was obtained by extraction and enrichment and was found to have a better protective effect against HCl/EtOH-induced gastric ulcers. This finding can enrich the traditional application of E. ulmoides leaves and provide a basis for their health product development.

摘要

杜仲叶在中国和日本被广泛用作食品和药品。其主要成分具有抗炎特性,可对抗胃溃疡。本研究旨在评估从杜仲叶活性成分中提取的提取物(EUL 50)对胃溃疡的保护作用,并分析其潜在的抗溃疡机制。使用超高效液相色谱(UPLC)方法鉴定 EUL 50 的主要成分。通过网络药理学和分子对接预测 EUL 50 治疗胃溃疡的可能作用机制。大鼠每天两次胃内给予 EUL 50 连续 3 天。使用盐酸/乙醇(HCl/EtOH)诱导胃溃疡,然后对溃疡组织进行组织病理学和组织化学评价,并测定主要氧化应激参数和炎性细胞因子。测量 PI3K/Akt/NF-κB 通路相关蛋白的表达。通过 UPLC 鉴定出 EUL 50 的主要成分有新绿原酸、绿原酸、芦丁等。预测结果表明,PI3K/Akt/NF-κB 信号通路是对抗胃溃疡的主要可能保护机制。此外,EUL 50 呈剂量依赖性地减轻胃组织损伤。此外,高剂量的 EUL 50 可使丙二醛(MDA)、肿瘤坏死因子 α(TNF-α)、白细胞介素 6(IL-6)和白细胞介素 1β(IL-1β)的水平分别降低 22.64%、42.61%、57.78%和 56.51%,同时使 Akt、p65、IKKα 和 IκBα 的磷酸化分别降低 60.87%、67.65%、74.58%和 59.57%,并提高抗氧化酶活性。EUL 50 富含黄酮类和有机酸,可作用于 PI3K/Akt/NF-κB 信号通路;因此,氧化应激和炎症得到了显著减轻,HCl/EtOH 引起的胃溃疡也得到了减轻。实际应用:作为一种药用和食用物质,杜仲叶广泛应用于保健品的开发。EUL 50 是杜仲叶的中等极性部分,通过提取和富集得到,对 HCl/EtOH 诱导的胃溃疡具有更好的保护作用。这一发现丰富了杜仲叶的传统应用,为其保健品的开发提供了依据。

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