Integrating network pharmacology and animal experimental validation to investigate the mechanism of lotus leaf in obesity

IF 4.8 2区医学 Q2 IMMUNOLOGY

International immunopharmacology Pub Date : 2025-01-03 DOI:10.1016/j.intimp.2024.113719

Haojing Li , Wenli Li , Yuanyuan Wu , Huimin Wu , Xiaojun Cai

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引用次数: 0

Abstract

Background

Lotus leaf and its extracts have been reported to exert various beneficial effects; however, their anti-obesity mechanisms remain relatively unclear. Therefore, we investigated the mechanism by which lotus leaf regulates obesity using network pharmacology, molecular docking, and animal experimentation.

Methods

Network pharmacology was used to identify potential targets and pathways through which lotus leaf regulates obesity. Molecular docking technology was used to verify the interaction between lotus leaves and core targets of obesity. Additionally, a rat model of obesity induced using a high-fat diet was established to examine the anti-obesity effects of lotus leaf. Moreover, western blotting was performed to examine the expression levels of the target proteins and elucidate the molecular mechanisms of lotus leaf.

Results

Quercetin, nuciferin, catechin, kaempferol, and isorhamnetin were identified as the main active compounds in the lotus leaves involved in obesity treatment. Network pharmacology analysis identified fibroblast growth factor (FGF) 15 and farnesoid X receptor (FXR) as core targets of lotus leaf, and the AGE-RAGE signaling pathway in diabetic complications, neuroactive ligand-receptor interactions, insulin resistance, and cancer pathways, as biomechanistic pathways by which lotus leaf ameliorates obesity. Additionally, molecular docking analysis indicated a strong binding affinity between the main active ingredients of lotus leaf and the core targets. Moreover, western blotting showed that lotus leaf significantly downregulated FGF15 and FXR protein expression in intestinal tissues.

Conclusions

Lotus leaf ameliorates obesity through several pathways, including by downregulating FGF15 and FXR, providing a novel basis for the development of natural drug therapy for obesity.

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结合网络药理学和动物实验验证，探讨荷叶对肥胖的作用机制。

背景：据报道，荷叶及其提取物具有多种有益作用；然而，它们的抗肥胖机制仍然相对不清楚。为此，我们采用网络药理学、分子对接、动物实验等方法研究荷叶调控肥胖的机制。方法：利用网络药理学方法，鉴定荷叶调节肥胖的潜在靶点和通路。利用分子对接技术验证荷叶与肥胖核心靶点之间的相互作用。此外，我们还建立了高脂饮食诱导的肥胖大鼠模型，以研究荷叶的抗肥胖作用。利用western blotting检测靶蛋白的表达水平，阐明荷叶的分子机制。结果：鉴定出槲皮素、nucifin、儿茶素、山奈酚和异鼠李素是荷叶中参与肥胖治疗的主要活性成分。网络药理学分析发现，成纤维细胞生长因子（FGF） 15和法内甾体X受体（FXR）是荷叶的核心靶点，而糖尿病并发症、神经活性配体受体相互作用、胰岛素抵抗和癌症途径中的AGE-RAGE信号通路是荷叶改善肥胖的生物机制途径。分子对接分析表明，荷叶主要活性成分与核心靶点具有较强的结合亲和力。western blotting结果显示，荷叶显著下调肠道组织中FGF15和FXR蛋白的表达。结论：荷叶通过下调FGF15和FXR等多种途径改善肥胖，为开发天然药物治疗肥胖提供了新的基础。

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

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.