Berberine Prevents Disease Progression of Nonalcoholic Steatohepatitis through Modulating Multiple Pathways
<b>Background and Aims</b>: The disease progression of nonalcoholic fatty liver disease (NAFLD) from simple steatosis (NAFL) to nonalcoholic steatohepatitis (NASH) is driven by multiple factors. Berberine (BBR) is an ancient Chinese medicine and has various beneficial effects on metaboli...
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MDPI AG
2021-01-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/2/210 |
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| author | Yanyan Wang Yun-Ling Tai Derrick Zhao Yuan Zhang Junkai Yan Genta Kakiyama Xuan Wang Emily C. Gurley Jinze Liu Jinpeng Liu Jimin Liu Guanhua Lai Phillip B. Hylemon William M. Pandak Weidong Chen Huiping Zhou |
| author_facet | Yanyan Wang Yun-Ling Tai Derrick Zhao Yuan Zhang Junkai Yan Genta Kakiyama Xuan Wang Emily C. Gurley Jinze Liu Jinpeng Liu Jimin Liu Guanhua Lai Phillip B. Hylemon William M. Pandak Weidong Chen Huiping Zhou |
| author_sort | Yanyan Wang |
| collection | DOAJ |
| description | <b>Background and Aims</b>: The disease progression of nonalcoholic fatty liver disease (NAFLD) from simple steatosis (NAFL) to nonalcoholic steatohepatitis (NASH) is driven by multiple factors. Berberine (BBR) is an ancient Chinese medicine and has various beneficial effects on metabolic diseases, including NAFLD/NASH. However, the underlying mechanisms remain incompletely understood due to the limitation of the NASH animal models used. <b>Methods</b>: A high-fat and high-fructose diet-induced mouse model of NAFLD, the best available preclinical NASH mouse model, was used. RNAseq, histological, and metabolic pathway analyses were used to identify the potential signaling pathways modulated by BBR. LC–MS was used to measure bile acid levels in the serum and liver. The real-time RT-PCR and Western blot analysis were used to validate the RNAseq data. <b>Results</b>: BBR not only significantly reduced hepatic lipid accumulation by modulating fatty acid synthesis and metabolism but also restored the bile acid homeostasis by targeting multiple pathways. In addition, BBR markedly inhibited inflammation by reducing immune cell infiltration and inhibition of neutrophil activation and inflammatory gene expression. Furthermore, BBR was able to inhibit hepatic fibrosis by modulating the expression of multiple genes involved in hepatic stellate cell activation and cholangiocyte proliferation. Consistent with our previous findings, BBR’s beneficial effects are linked with the downregulation of microRNA34a and long noncoding RNA H19, which are two important players in promoting NASH progression and liver fibrosis. <b>Conclusion</b>: BBR is a promising therapeutic agent for NASH by targeting multiple pathways. These results provide a strong foundation for a future clinical investigation. |
| first_indexed | 2024-03-09T04:06:16Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T04:06:16Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-196a8eaf79bc4c698900c2d12f6a79c82023-12-03T14:06:01ZengMDPI AGCells2073-44092021-01-0110221010.3390/cells10020210Berberine Prevents Disease Progression of Nonalcoholic Steatohepatitis through Modulating Multiple PathwaysYanyan Wang0Yun-Ling Tai1Derrick Zhao2Yuan Zhang3Junkai Yan4Genta Kakiyama5Xuan Wang6Emily C. Gurley7Jinze Liu8Jinpeng Liu9Jimin Liu10Guanhua Lai11Phillip B. Hylemon12William M. Pandak13Weidong Chen14Huiping Zhou15Department of Microbiology and Immunology, Medical College of Virginia and McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, 1220 East Broad Street, MMRB-5044, Richmond, VA 23298, USADepartment of Microbiology and Immunology, Medical College of Virginia and McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, 1220 East Broad Street, MMRB-5044, Richmond, VA 23298, USADepartment of Microbiology and Immunology, Medical College of Virginia and McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, 1220 East Broad Street, MMRB-5044, Richmond, VA 23298, USADepartment of Microbiology and Immunology, Medical College of Virginia and McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, 1220 East Broad Street, MMRB-5044, Richmond, VA 23298, USADepartment of Microbiology and Immunology, Medical College of Virginia and McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, 1220 East Broad Street, MMRB-5044, Richmond, VA 23298, USADepartment of Internal Medicine, Medical College of Virginia and McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, Richmond, VA 23298, USADepartment of Microbiology and Immunology, Medical College of Virginia and McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, 1220 East Broad Street, MMRB-5044, Richmond, VA 23298, USADepartment of Microbiology and Immunology, Medical College of Virginia and McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, 1220 East Broad Street, MMRB-5044, Richmond, VA 23298, USADepartment of Biostatistics, Virginia Commonwealth University, Richmond, VA 23298, USADepartment of Computer Science, University of Kentucky, Lexington, KY 40506, USADepartment of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L6M0L8, CanadaDepartment of Pathology, Medical College of Virginia, 23298 Virginia Commonwealth University, Richmond, VA 23298, USADepartment of Microbiology and Immunology, Medical College of Virginia and McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, 1220 East Broad Street, MMRB-5044, Richmond, VA 23298, USADepartment of Internal Medicine, Medical College of Virginia and McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, Richmond, VA 23298, USASchool of Pharmaceutical Science, Anhui University of Chinese Medicine, Qianjiang, Hefei 230012, ChinaDepartment of Microbiology and Immunology, Medical College of Virginia and McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, 1220 East Broad Street, MMRB-5044, Richmond, VA 23298, USA<b>Background and Aims</b>: The disease progression of nonalcoholic fatty liver disease (NAFLD) from simple steatosis (NAFL) to nonalcoholic steatohepatitis (NASH) is driven by multiple factors. Berberine (BBR) is an ancient Chinese medicine and has various beneficial effects on metabolic diseases, including NAFLD/NASH. However, the underlying mechanisms remain incompletely understood due to the limitation of the NASH animal models used. <b>Methods</b>: A high-fat and high-fructose diet-induced mouse model of NAFLD, the best available preclinical NASH mouse model, was used. RNAseq, histological, and metabolic pathway analyses were used to identify the potential signaling pathways modulated by BBR. LC–MS was used to measure bile acid levels in the serum and liver. The real-time RT-PCR and Western blot analysis were used to validate the RNAseq data. <b>Results</b>: BBR not only significantly reduced hepatic lipid accumulation by modulating fatty acid synthesis and metabolism but also restored the bile acid homeostasis by targeting multiple pathways. In addition, BBR markedly inhibited inflammation by reducing immune cell infiltration and inhibition of neutrophil activation and inflammatory gene expression. Furthermore, BBR was able to inhibit hepatic fibrosis by modulating the expression of multiple genes involved in hepatic stellate cell activation and cholangiocyte proliferation. Consistent with our previous findings, BBR’s beneficial effects are linked with the downregulation of microRNA34a and long noncoding RNA H19, which are two important players in promoting NASH progression and liver fibrosis. <b>Conclusion</b>: BBR is a promising therapeutic agent for NASH by targeting multiple pathways. These results provide a strong foundation for a future clinical investigation.https://www.mdpi.com/2073-4409/10/2/210NAFLDbile acidsinflammationfibrosis |
| spellingShingle | Yanyan Wang Yun-Ling Tai Derrick Zhao Yuan Zhang Junkai Yan Genta Kakiyama Xuan Wang Emily C. Gurley Jinze Liu Jinpeng Liu Jimin Liu Guanhua Lai Phillip B. Hylemon William M. Pandak Weidong Chen Huiping Zhou Berberine Prevents Disease Progression of Nonalcoholic Steatohepatitis through Modulating Multiple Pathways Cells NAFLD bile acids inflammation fibrosis |
| title | Berberine Prevents Disease Progression of Nonalcoholic Steatohepatitis through Modulating Multiple Pathways |
| title_full | Berberine Prevents Disease Progression of Nonalcoholic Steatohepatitis through Modulating Multiple Pathways |
| title_fullStr | Berberine Prevents Disease Progression of Nonalcoholic Steatohepatitis through Modulating Multiple Pathways |
| title_full_unstemmed | Berberine Prevents Disease Progression of Nonalcoholic Steatohepatitis through Modulating Multiple Pathways |
| title_short | Berberine Prevents Disease Progression of Nonalcoholic Steatohepatitis through Modulating Multiple Pathways |
| title_sort | berberine prevents disease progression of nonalcoholic steatohepatitis through modulating multiple pathways |
| topic | NAFLD bile acids inflammation fibrosis |
| url | https://www.mdpi.com/2073-4409/10/2/210 |
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