Network Pharmacology-Based Approaches of Rheum undulatum Linne and Glycyrriza uralensis Fischer Imply Their Regulation of Liver Failure with Hepatic Encephalopathy in Mice

Biomolecules

Kwang-Il Park¹  SuYoun Baek²  Kwang-Youn Kim³  TaeWoo Oh³  HyunJu Do³  YoungWoo Kim⁴  EunHye Lee⁵ 

[1] College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Korea;Institute for Phylogenomics and Evolution, Kyungpook National University, Daegu 41566, Korea;Korea Institute of Oriental Medicine, Daegu 41062, Korea;School of Korean Medicine, Dongguk University, Gyeongju 38066, Korea;School of Medical Science, Kyungpook National University, Daegu 41566, Korea;

关键词: rheum undulatum;    glycyrriza uralensis;    hepatic encephalopathy;    mmp-9;    neuroinflammation;   

DOI  :  10.3390/biom10030437

来源: DOAJ

【 摘 要 】

Rheum undulatum and Glycyrrhiza uralensis have been used as supplementary ingredients in various herbal medicines. They have been reported to have anti-inflammatory and antioxidant effects and, therefore, have potential in the treatment and prevention of various liver diseases. Considering that hepatic encephalopathy (HE) is often associated with chronic liver failure, we investigated whether an R. undulatum and G. uralensis extract mixture (RG) could reduce HE. We applied systems-based pharmacological tools to identify the active ingredients in RG and the pharmacological targets of RG by examining mechanism-of-action profiles. A CCl₄-induced HE mouse model was used to investigate the therapeutic mechanisms of RG on HE. We successfully identified seven bioactive ingredients in RG with 40 potential targets. Based on an integrated target−disease network, RG was predicted to be effective in treating neurological diseases. In animal models, RG consistently relieved HE symptoms by protecting blood−brain barrier permeability via downregulation of matrix metalloproteinase-9 (MMP-9) and upregulation of claudin-5. In addition, RG inhibited mRNA expression levels of both interleukin (IL)-1β and transforming growth factor (TGF)-β1. Based on our results, RG is expected to function various biochemical processes involving neuroinflammation, suggesting that RG may be considered a therapeutic agent for treating not only chronic liver disease but also HE.

【 授权许可】

Unknown