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基于网络药理学和实验验证探讨冬凌草甲素治疗代谢相关脂肪性肝病的作用机制。

Exploring the mechanism of dendrobine in treating metabolic associated fatty liver disease based on network pharmacology and experimental validation.

机构信息

Traditional Chinese Medicine Department, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 Wanping South Road, Fenglin Street, Xuhui District, Shanghai, 200030, China.

Nanmatou Community Health Service Center, 696 Pusan Road, Pudong New District, Shanghai, 200125, China.

出版信息

Hereditas. 2024 May 16;161(1):17. doi: 10.1186/s41065-024-00322-2.

Abstract

BACKGROUND

This study investigates the therapeutic mechanisms of dendrobine, a primary bioactive compound in Dendrobium nobile, for Metabolic Associated Fatty Liver Disease (MASLD) management. Utilizing network pharmacology combined with experimental validation, the clinical effectiveness of dendrobine in MASLD treatment was assessed and analyzed.

RESULTS

The study demonstrates significant improvement in liver function among MASLD patients treated with Dendrobium nobile. Network pharmacology identified key targets such as Peroxisome Proliferator-Activated Receptor Gamma (PPARG), Interleukin 6 (IL6), Tumor Necrosis Factor (TNF), Interleukin 1 Beta (IL1B), and AKT Serine/Threonine Kinase 1 (AKT1), with molecular docking confirming their interactions. Additionally, dendrobine significantly reduced ALT and AST levels in palmitic acid-treated HepG2 cells, indicating hepatoprotective properties and amelioration of oxidative stress through decreased Malondialdehyde (MDA) levels and increased Superoxide Dismutase (SOD) levels.

CONCLUSION

Dendrobine mitigates liver damage in MASLD through modulating inflammatory and immune responses and affecting lipid metabolism, potentially by downregulating inflammatory mediators like TNF, IL6, IL1B, and inhibiting AKT1 and Signal Transducer and Activator of Transcription 3 (STAT3). This study provides a theoretical basis for the application of dendrobine in MASLD treatment, highlighting its potential as a therapeutic agent.

摘要

背景

本研究探讨了铁皮石斛中的主要生物活性化合物石斛碱治疗代谢相关脂肪性肝病(MASLD)的作用机制。采用网络药理学结合实验验证的方法,评估和分析了石斛碱治疗 MASLD 的临床疗效。

结果

研究表明,铁皮石斛治疗 MASLD 患者的肝功能显著改善。网络药理学鉴定了关键靶点,如过氧化物酶体增殖物激活受体γ(PPARG)、白细胞介素 6(IL6)、肿瘤坏死因子(TNF)、白细胞介素 1β(IL1B)和 AKT 丝氨酸/苏氨酸激酶 1(AKT1),分子对接证实了它们的相互作用。此外,石斛碱显著降低了棕榈酸处理的 HepG2 细胞中 ALT 和 AST 的水平,表明其具有保肝作用,并通过降低丙二醛(MDA)水平和增加超氧化物歧化酶(SOD)水平来改善氧化应激。

结论

石斛碱通过调节炎症和免疫反应以及影响脂质代谢来减轻 MASLD 中的肝损伤,其可能通过下调 TNF、IL6、IL1B 等炎症介质,并抑制 AKT1 和信号转导及转录激活因子 3(STAT3)来发挥作用。本研究为石斛碱在 MASLD 治疗中的应用提供了理论依据,凸显了其作为治疗药物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4724/11097442/80eb861291e4/41065_2024_322_Fig1_HTML.jpg

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