Network Pharmacology-Based Approaches of <i>Rheum undulatum</i> Linne and <i>Glycyrriza uralensis</i> Fischer Imply Their Regulation of Liver Failure with Hepatic Encephalopathy in Mice
<i>Rheum undulatum</i> and <i>Glycyrrhiza uralensis</i> 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...
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MDPI AG
2020-03-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/3/437 |
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| author | Su Youn Baek Eun Hye Lee Tae Woo Oh Hyun Ju Do Kwang-Youn Kim Kwang-Il Park Young Woo Kim |
| author_facet | Su Youn Baek Eun Hye Lee Tae Woo Oh Hyun Ju Do Kwang-Youn Kim Kwang-Il Park Young Woo Kim |
| author_sort | Su Youn Baek |
| collection | DOAJ |
| description | <i>Rheum undulatum</i> and <i>Glycyrrhiza uralensis</i> 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 <i>R. undulatum</i> and <i>G. uralensis</i> 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 CCl<sub>4</sub>-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. |
| first_indexed | 2024-12-11T06:31:41Z |
| format | Article |
| id | doaj.art-c2d5b119b2624dd1ac268ecba3bbd65f |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-12-11T06:31:41Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-c2d5b119b2624dd1ac268ecba3bbd65f2022-12-22T01:17:30ZengMDPI AGBiomolecules2218-273X2020-03-0110343710.3390/biom10030437biom10030437Network Pharmacology-Based Approaches of <i>Rheum undulatum</i> Linne and <i>Glycyrriza uralensis</i> Fischer Imply Their Regulation of Liver Failure with Hepatic Encephalopathy in MiceSu Youn Baek0Eun Hye Lee1Tae Woo Oh2Hyun Ju Do3Kwang-Youn Kim4Kwang-Il Park5Young Woo Kim6Institute for Phylogenomics and Evolution, Kyungpook National University, Daegu 41566, KoreaSchool of Medical Science, Kyungpook National University, Daegu 41566, KoreaKorea Institute of Oriental Medicine, Daegu 41062, KoreaKorea Institute of Oriental Medicine, Daegu 41062, KoreaKorea Institute of Oriental Medicine, Daegu 41062, KoreaCollege of Veterinary Medicine, Gyeongsang National University, Jinju 52828, KoreaSchool of Korean Medicine, Dongguk University, Gyeongju 38066, Korea<i>Rheum undulatum</i> and <i>Glycyrrhiza uralensis</i> 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 <i>R. undulatum</i> and <i>G. uralensis</i> 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 CCl<sub>4</sub>-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.https://www.mdpi.com/2218-273X/10/3/437<i>rheum undulatum</i><i>glycyrriza uralensis</i>hepatic encephalopathymmp-9neuroinflammation |
| spellingShingle | Su Youn Baek Eun Hye Lee Tae Woo Oh Hyun Ju Do Kwang-Youn Kim Kwang-Il Park Young Woo Kim Network Pharmacology-Based Approaches of <i>Rheum undulatum</i> Linne and <i>Glycyrriza uralensis</i> Fischer Imply Their Regulation of Liver Failure with Hepatic Encephalopathy in Mice Biomolecules <i>rheum undulatum</i> <i>glycyrriza uralensis</i> hepatic encephalopathy mmp-9 neuroinflammation |
| title | Network Pharmacology-Based Approaches of <i>Rheum undulatum</i> Linne and <i>Glycyrriza uralensis</i> Fischer Imply Their Regulation of Liver Failure with Hepatic Encephalopathy in Mice |
| title_full | Network Pharmacology-Based Approaches of <i>Rheum undulatum</i> Linne and <i>Glycyrriza uralensis</i> Fischer Imply Their Regulation of Liver Failure with Hepatic Encephalopathy in Mice |
| title_fullStr | Network Pharmacology-Based Approaches of <i>Rheum undulatum</i> Linne and <i>Glycyrriza uralensis</i> Fischer Imply Their Regulation of Liver Failure with Hepatic Encephalopathy in Mice |
| title_full_unstemmed | Network Pharmacology-Based Approaches of <i>Rheum undulatum</i> Linne and <i>Glycyrriza uralensis</i> Fischer Imply Their Regulation of Liver Failure with Hepatic Encephalopathy in Mice |
| title_short | Network Pharmacology-Based Approaches of <i>Rheum undulatum</i> Linne and <i>Glycyrriza uralensis</i> Fischer Imply Their Regulation of Liver Failure with Hepatic Encephalopathy in Mice |
| title_sort | network pharmacology based approaches of i rheum undulatum i linne and i glycyrriza uralensis i fischer imply their regulation of liver failure with hepatic encephalopathy in mice |
| topic | <i>rheum undulatum</i> <i>glycyrriza uralensis</i> hepatic encephalopathy mmp-9 neuroinflammation |
| url | https://www.mdpi.com/2218-273X/10/3/437 |
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