Discussion on the Mechanism of Gandoufumu Decoction Attenuates Liver Damage of Wilson's Disease by Inhibiting Autophagy through the PI3K/Akt/mTOR Pathway Based on Network Pharmacology and Experimental Verification.
Discussion on the Mechanism of Gandoufumu Decoction Attenuates Liver Damage of Wilson's Disease by Inhibiting Autophagy through the PI3K/Akt/mTOR Pathway Based on Network Pharmacology and Experimental Verification.
复制标题
肝豆复母汤通过PI 3 K/Akt/mTOR通路抑制自噬减轻肝豆状核变性肝损害机制的网络药理学探讨及实验验证。
DOI：
10.1155/2023/3236911
复制
发表时间：
2023
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
肝豆复母汤是一种常用的治疗肝豆状核变性肝损害的中药。然而，其具体的分子机制目前仍不清楚。自噬作为WD肝损伤的一个重要因素，近年来受到了广泛的研究。因此，本研究旨在探讨GDFMD对WD肝损伤中自噬的影响，为GDFMD治疗WD肝损伤提供科学依据。 利用网络药理学方法预测GDFMD治疗WD肝损伤的分子机制和自噬相关通路。血清铜测定试剂盒测定血清铜含量。酶联免疫吸附试验（ELISA）用于定量肝酶和氧化应激相关指标的血清水平。苏木精-伊红（HE）、Masson和天狼星红染色用于表征肝脏病理变化。透射电子显微镜、免疫荧光和Western印迹分析用于评估自噬活性。还通过Western印迹分析评估了GDFMD对典型自噬相关途径（PI 3 K/Akt/mTOR途径）分子的影响。 GDFMD有效地减弱血清肝酶、氧化应激、自噬和肝组织病理学损伤程度，并降低血清铜含量。通过网络药理学方法，确定PI 3 K/Akt/mTOR通路是GDFMD治疗WD肝损伤的典型自噬相关通路。用GDFMD处理激活了PI 3 K/Akt/mTOR通路，这种作用能够被PI 3 K拮抗剂LY 294002或自噬诱导剂Rapa（雷帕霉素）抵消。 GDFMD通过PI 3 K/Akt/mTOR途径作用，通过自噬抑制对WD产生治疗作用。
Gandoufumu decoction (GDFMD) is a traditional Chinese medicine that has been widely used to treat Wilson's disease (WD) liver damage patients. However, its specific molecular mechanism currently remains unclear. Autophagy as a key contributor to WD liver damage has been intensely researched in the recent years. Therefore, the aim of this present study is to explore the effect of GDFMD on autophagy in WD liver damage, and the final purpose is to provide scientific evidence for GDFMD treatment in WD liver damage. The molecular mechanisms and autophagy-related pathways of GDFMD in the treatment of WD liver damage were predicted using network pharmacology. Copper assay kit was used to determine copper content in serum. Enzyme-linked immunosorbent assay (ELISA) was utilized to quantify serum levels of liver enzymes and oxidative stress-related indicators. Hematoxylin-eosin (HE), Masson, and Sirius red staining were used for the characterization of liver pathological changes. Transmission electron microscopy, immunofluorescence, and Western blot analyses were used to evaluate autophagy activity. The impact of the GDFMD on typical autophagy-related pathway (PI3K/Akt/mTOR pathway) molecules was also assessed via Western blot analysis. GDFMD effectively attenuated serum liver enzymes, oxidative stress, autophagy, and degree of hepatic histopathological impairment and reduced serum copper content. Through network pharmacological approaches, PI3K/Akt/mTOR pathway was identified as the typical autophagy-related pathway of GDFMD in the treatment of WD liver damage. Treatment with GDFMD activated the PI3K/Akt/mTOR pathway, an effect that was able to be counteracted by LY294002, a PI3K antagonist or Rapa (rapamycin), an autophagy inducer. GDFMD imparted therapeutic effects on WD through autophagy suppression by acting through the PI3K/Akt/mTOR pathway.
登录
查看更多内容
影响因子：
4.6
作者：
Novikov FN;Panova MV;Titov IY;Stroylov VS;Stroganov OV;Chilov GG
通讯作者：
Chilov GG
影响因子：
6
作者：
Moulis M;Vindis C
通讯作者：
Vindis C
影响因子：
5.6
作者：
Guo Q;Zheng K;Fan D;Zhao Y;Li L;Bian Y;Qiu X;Liu X;Zhang G;Ma C;He X;Lu A
通讯作者：
Lu A
影响因子：
4
作者：
Chen, Yonghua;Zhang, Bo;Yang, Wenming
通讯作者：
Yang, Wenming
影响因子：
20.1
作者：
Orogo AM;Gustafsson ÅB
通讯作者：
Gustafsson ÅB