Mechanism elucidation and biochemometric-based screening of substances in Schisandra chinensis leaves for alcoholic liver injury

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-04-11 DOI:10.1016/j.phymed.2025.156757

Yifan Bing , Xiang Zou , Xiaolong Yang , Xuejing Yang , Jiejing Sheng , Zhongyuan Qu

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引用次数: 0

Abstract

Background

Alcoholic liver injury (ALI) represents a major international public health concern with no targeted pharmacological intervention and a dearth of clinical trial-approved medications for its management. The dried leaves of Schisandra chinensis (SCL) are rich in flavonoids, lignans, polysaccharides, and other active ingredients with anti-inflammatory, antioxidant, and antitumour activities and are commonly applied in the treatment of osteoarthritis, diabetes, and neurodegenerative diseases. The crude lignans of SCL have been reported to treat CCl₄-induced acute liver injury, and SCL tea has also been reported to have hepatoprotective effects. The components of SCL are currently the focus of investigation; however, conclusive pharmacological studies on SCL in the treatment of ethanol-induced ALI are rare.

Purpose

This study aimed to identify the bioactive components and elucidate the mechanism of action of SCL against ALI.

Methods

The optimal month for harvesting SCL was first determined using a cellular ALI model. Immediately afterwards, the efficacy of SCL was evaluated based on cellular ALI model and ALI mice model. The expression levels of NLRP3 inflammasome-associated proteins were examined via Western blotting. To identify the bioactive components of SCL, the common components in 10 batches of SCL were identified by UPLC‒Q-TOF‒MS/MS. Subsequent analysis via correlation identified common elements' pharmacological impacts, filtering for substances with notable contributions to effectiveness. Finally, potential bioactive components were further identified through molecular docking and verified in ALIcell models.

Results

SCL has the best efficacy in early August, and by improving hepatic aminotransferase activity, regulating lipid metabolism, alleviating oxidative stress, reducing the release of inflammatory mediators, and inhibiting the expression of NLRP3-related pyroptosis proteins, it plays a role in alleviating ALI. A total of 32 common components were identified in 10 batches of SCL. Through correlation analysis, 10 functional components, including Schisandrin B, Angeloylgomisin Q, Chlorogenic acid, Rutin, Schisandrin C, p-Hydroxycinnamic acid, Schisandrin A, Schisandrol A, Gomisin J, and Schisantherin B, were screened. Further screening using molecular docking identified 4 key functional components, Rutin, Chlorogenic acid, Schisandrin C, and Schisantherin B, which were verified to mitigate ethanol-induced liver damage.

Conclusion

The present study demonstrated that SCL prevented ALI, with the main contributing components being rutin, chlorogenic acid, pentosidine C and pentosidine B. Hence, our latest study offers significant experimental proof indicating SCL as a promising prospect for ALI prevention.

Abstract Image

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五味子叶中酒精性肝损伤物质的生物化学筛选及机制研究

背景：酒精性肝损伤（ALI）是一个主要的国际公共卫生问题，没有针对性的药物干预，也缺乏临床试验批准的治疗药物。五味子干叶含有丰富的黄酮类化合物、木脂素、多糖和其他具有抗炎、抗氧化和抗肿瘤活性的活性成分，通常用于治疗骨关节炎、糖尿病和神经退行性疾病。据报道，SCL粗木脂素可治疗ccl4诱导的急性肝损伤，而SCL茶也有保护肝脏的作用。SCL的组成部分是目前研究的重点；然而，关于SCL治疗酒精性ALI的结论性药理学研究很少。目的鉴定SCL抗ALI的活性成分，阐明其作用机制。方法首先采用细胞ALI模型确定SCL的最佳采收月份。随后，采用细胞ALI模型和小鼠ALI模型评价SCL的疗效。Western blotting检测NLRP3炎性小体相关蛋白的表达水平。采用UPLC-Q-TOF-MS /MS对10批SCL中常见的活性成分进行鉴定。随后通过相关性分析确定了常见元素的药理学影响，过滤了对有效性有显著贡献的物质。最后，通过分子对接进一步鉴定潜在的生物活性成分，并在ALIcell模型中进行验证。结果scl在8月初疗效最佳，可通过提高肝脏转氨酶活性、调节脂质代谢、减轻氧化应激、减少炎症介质的释放、抑制nlrp3相关焦亡蛋白的表达，起到缓解ALI的作用。在10批SCL中共鉴定出32种常见成分。通过相关分析，筛选出五味子素B、angelylgomisin Q、绿原酸、芦丁、五味子素C、对羟基肉桂酸、五味子素A、五味子素A、五味子素J、五味子素B等10种功能成分。进一步通过分子对接筛选，鉴定出芦丁、绿原酸、五味子甲素C、五味子甲素B等4种关键功能成分，证实其具有减轻乙醇性肝损伤的作用。结论SCL具有预防ALI的作用，其主要作用成分为芦丁、绿原酸、戊苷C和戊苷b。本研究为SCL预防ALI提供了重要的实验证据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.