Total glucosides of Picrorhizae Rhizome alleviate non-alcoholic steatohepatitis (NASH) by specifically targeting acyl-CoA oxidase 1
Nonalcoholic steatohepatitis (NASH), a chronic liver disease characterized by the accumulation of fat in the liver, is highly prevalent on a global scale. In this study, we investigated the effects of total glucosides of Picrorhizae Rhizome (TGPR), the primary active ingredients in traditional Chine...
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Elsevier
2024-11-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024159051 |
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| author | Fang-Fang Zhuo Xiao-Qing Li Jun Zhang Fu-Ming Zhang Zhao-Hui Song Yi He Li Ding Dan Liu Peng-Fei Tu Xiao-Hui Ma Ke-Wu Zeng |
| author_facet | Fang-Fang Zhuo Xiao-Qing Li Jun Zhang Fu-Ming Zhang Zhao-Hui Song Yi He Li Ding Dan Liu Peng-Fei Tu Xiao-Hui Ma Ke-Wu Zeng |
| author_sort | Fang-Fang Zhuo |
| collection | DOAJ |
| description | Nonalcoholic steatohepatitis (NASH), a chronic liver disease characterized by the accumulation of fat in the liver, is highly prevalent on a global scale. In this study, we investigated the effects of total glucosides of Picrorhizae Rhizome (TGPR), the primary active ingredients in traditional Chinese herbal medicine derived from Picrorhiza scrophulariiflora Pennell. TGPR is known for its efficiency in attenuating NASH, in mouse models induced by methionine-choline deficient (MCD) diet or high-fat diet (HFD). Our findings indicated that TGPR exhibited efficacy in reducing hepatic steatosis and lowering serum lipid levels, specifically triglyceride and total cholesterol in the NASH model. Meanwhile, TGPR exhibited a suppressive effect on the production of pro-inflammatory cytokines. Mechanistically, we identified acyl-CoA oxidase 1 (Acox1) as a crucial cellular target of TGPR, influencing lipid metabolism and ATP production to treat NASH. Additionally, we found that the major components of TGPR, including Picroside I, Picroside II, and Picroside IV, exhibit significant binding abilities to the target Acox1 at its catalytic C-terminal α-domain, stabilizing its protein expression. TGPR binding to Acox1 facilitated the degradation of fatty acids via the Acox1-mediated MAPK signaling pathways, and consequently plays a role in regulating energy metabolism and reducing liver inflammation. In summary, our study demonstrates that TGPR effectively counteracts NASH by specifically targeting Acox1, thereby providing a significant clinical solution for the treatment of NASH. |
| format | Article |
| id | doaj-art-8ff0c5c1ebb8465ea282dc3d720154f9 |
| institution | Kabale University |
| issn | 2405-8440 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj-art-8ff0c5c1ebb8465ea282dc3d720154f92024-11-15T06:13:50ZengElsevierHeliyon2405-84402024-11-011021e39874Total glucosides of Picrorhizae Rhizome alleviate non-alcoholic steatohepatitis (NASH) by specifically targeting acyl-CoA oxidase 1Fang-Fang Zhuo0Xiao-Qing Li1Jun Zhang2Fu-Ming Zhang3Zhao-Hui Song4Yi He5Li Ding6Dan Liu7Peng-Fei Tu8Xiao-Hui Ma9Ke-Wu Zeng10State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, ChinaNational Key Laboratory of Chinese Medicine Modernization, Tasly Academy, Tasly Pharmaceutical Group Co., Ltd., Tianjin, 300410, ChinaNational Key Laboratory of Chinese Medicine Modernization, Tasly Academy, Tasly Pharmaceutical Group Co., Ltd., Tianjin, 300410, ChinaNational Key Laboratory of Chinese Medicine Modernization, Tasly Academy, Tasly Pharmaceutical Group Co., Ltd., Tianjin, 300410, ChinaNational Key Laboratory of Chinese Medicine Modernization, Tasly Academy, Tasly Pharmaceutical Group Co., Ltd., Tianjin, 300410, ChinaNational Key Laboratory of Chinese Medicine Modernization, Tasly Academy, Tasly Pharmaceutical Group Co., Ltd., Tianjin, 300410, ChinaSchool of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, ChinaProteomics Laboratory, Medical and Healthy Analytical Center, Peking University Health Science Center, Beijing, 100191, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China; Corresponding author.National Key Laboratory of Chinese Medicine Modernization, Tasly Academy, Tasly Pharmaceutical Group Co., Ltd., Tianjin, 300410, China; Corresponding author.State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China; Corresponding author.Nonalcoholic steatohepatitis (NASH), a chronic liver disease characterized by the accumulation of fat in the liver, is highly prevalent on a global scale. In this study, we investigated the effects of total glucosides of Picrorhizae Rhizome (TGPR), the primary active ingredients in traditional Chinese herbal medicine derived from Picrorhiza scrophulariiflora Pennell. TGPR is known for its efficiency in attenuating NASH, in mouse models induced by methionine-choline deficient (MCD) diet or high-fat diet (HFD). Our findings indicated that TGPR exhibited efficacy in reducing hepatic steatosis and lowering serum lipid levels, specifically triglyceride and total cholesterol in the NASH model. Meanwhile, TGPR exhibited a suppressive effect on the production of pro-inflammatory cytokines. Mechanistically, we identified acyl-CoA oxidase 1 (Acox1) as a crucial cellular target of TGPR, influencing lipid metabolism and ATP production to treat NASH. Additionally, we found that the major components of TGPR, including Picroside I, Picroside II, and Picroside IV, exhibit significant binding abilities to the target Acox1 at its catalytic C-terminal α-domain, stabilizing its protein expression. TGPR binding to Acox1 facilitated the degradation of fatty acids via the Acox1-mediated MAPK signaling pathways, and consequently plays a role in regulating energy metabolism and reducing liver inflammation. In summary, our study demonstrates that TGPR effectively counteracts NASH by specifically targeting Acox1, thereby providing a significant clinical solution for the treatment of NASH.http://www.sciencedirect.com/science/article/pii/S2405844024159051Nonalcoholic steatohepatitis (NASH)Total glucosides of Picrorhizae RhizomeTarget identificationAcyl-CoA oxidase 1 (Acox1)Fatty acids |
| spellingShingle | Fang-Fang Zhuo Xiao-Qing Li Jun Zhang Fu-Ming Zhang Zhao-Hui Song Yi He Li Ding Dan Liu Peng-Fei Tu Xiao-Hui Ma Ke-Wu Zeng Total glucosides of Picrorhizae Rhizome alleviate non-alcoholic steatohepatitis (NASH) by specifically targeting acyl-CoA oxidase 1 Heliyon Nonalcoholic steatohepatitis (NASH) Total glucosides of Picrorhizae Rhizome Target identification Acyl-CoA oxidase 1 (Acox1) Fatty acids |
| title | Total glucosides of Picrorhizae Rhizome alleviate non-alcoholic steatohepatitis (NASH) by specifically targeting acyl-CoA oxidase 1 |
| title_full | Total glucosides of Picrorhizae Rhizome alleviate non-alcoholic steatohepatitis (NASH) by specifically targeting acyl-CoA oxidase 1 |
| title_fullStr | Total glucosides of Picrorhizae Rhizome alleviate non-alcoholic steatohepatitis (NASH) by specifically targeting acyl-CoA oxidase 1 |
| title_full_unstemmed | Total glucosides of Picrorhizae Rhizome alleviate non-alcoholic steatohepatitis (NASH) by specifically targeting acyl-CoA oxidase 1 |
| title_short | Total glucosides of Picrorhizae Rhizome alleviate non-alcoholic steatohepatitis (NASH) by specifically targeting acyl-CoA oxidase 1 |
| title_sort | total glucosides of picrorhizae rhizome alleviate non alcoholic steatohepatitis nash by specifically targeting acyl coa oxidase 1 |
| topic | Nonalcoholic steatohepatitis (NASH) Total glucosides of Picrorhizae Rhizome Target identification Acyl-CoA oxidase 1 (Acox1) Fatty acids |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024159051 |
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