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基于网络药理学的方法探索灵芝和安络小皮伞素 K 治疗 2 型糖尿病的药理机制。

A network pharmacology-based strategy to explore the pharmacological mechanisms of Antrodia camphorata and antcin K for treating type II diabetes mellitus.

机构信息

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.

Honest and Humble Biotechnology Co., Ltd., 72 Dazhong Street, New Taipei City 251, Taiwan.

出版信息

Phytomedicine. 2022 Feb;96:153851. doi: 10.1016/j.phymed.2021.153851. Epub 2021 Nov 15.

Abstract

BACKGROUND

Diabetes mellitus is a chronic carbohydrate metabolism disorder, which could develop a series of complications and thus lead to poor quality of life or even mortality. Antrodia camphorata is a rare parasitic fungus and has been proven to be effective for treating type II diabetes.

PURPOSE

This study aims to evaluate the anti-diabetic activities of A. camphorata and its main compound antcin K, as well as to demonstrate the mechanisms.

STUDY DESIGN AND METHODS

Network pharmacology was used to explore the potential targets of 12 major compounds of A. camphorata on diabetes. The core targets were analyzed by protein-protein interactions and the key pathways were enriched by Kyoto Encyclopedia of Genes and Genomes (KEGG). The anti-diabetic effects of A. camphorata and antcin K were evaluated using a high-fat diet (HFD)-induced diabetic mice model and oral glucose tolerance test (OGTT). The mRNA expressions were assessed using qPCR.

RESULTS

Network pharmacology revealed 17 core targets between the 12 compounds and diabetes. The insulin resistance and NF-κB signaling pathways were enriched using KEGG. Five insulin resistance-related targets were focused on and antcin K (1/2) was discovered in the compound-target-pathway network. In vivo studies exhibited that A. camphorata and antcin K could dose-dependently reduce blood levels of glucose and lipids, decrease serum levels of insulin and leptin, and increase serum levels of adiponectin in HFD mice (p < 0.05). The mechanism could be through modulating the expressions of Tnfα, Il6, and Pparγ. The OGTT test also showed the down-regulatory effects of A. camphorata and antcin K on blood glucose.

CONCLUSION

This study demonstrates that A. camphorata and its major compound antcin K possess potent anti-diabetic effects. The mechanism may be through the insulin resistance pathway.

摘要

背景

糖尿病是一种慢性碳水化合物代谢紊乱,可导致一系列并发症,从而导致生活质量下降甚至死亡。樟芝是一种罕见的寄生真菌,已被证明对治疗 2 型糖尿病有效。

目的

本研究旨在评估樟芝及其主要化合物安特京 K 的抗糖尿病活性,并阐明其机制。

研究设计与方法

采用网络药理学方法探讨樟芝 12 种主要化合物对糖尿病的潜在靶点。通过蛋白质-蛋白质相互作用分析核心靶点,并通过京都基因与基因组百科全书(KEGG)富集关键途径。采用高脂饮食(HFD)诱导的糖尿病小鼠模型和口服葡萄糖耐量试验(OGTT)评估樟芝和安特京 K 的抗糖尿病作用。采用 qPCR 评估 mRNA 表达。

结果

网络药理学揭示了 12 种化合物与糖尿病之间的 17 个核心靶点。KEGG 富集到胰岛素抵抗和 NF-κB 信号通路。聚焦于 5 个与胰岛素抵抗相关的靶点,并在化合物-靶标-途径网络中发现了安特京 K(1/2)。体内研究表明,樟芝和安特京 K 可剂量依赖性降低 HFD 小鼠的血糖和血脂水平,降低血清胰岛素和瘦素水平,增加血清脂联素水平(p<0.05)。其机制可能是通过调节 Tnfα、Il6 和 Pparγ 的表达。OGTT 试验也表明樟芝和安特京 K 对血糖有下调作用。

结论

本研究表明樟芝及其主要化合物安特京 K 具有显著的抗糖尿病作用。其机制可能是通过胰岛素抵抗途径。

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