Combined Use of Bicyclol and Berberine Alleviates Mouse Nonalcoholic Fatty Liver Disease
Nonalcoholic fatty liver disease (NAFLD), ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), is a liver disease worldwide without approved therapeutic drugs. Anti-inflammatory and hepatoprotective drug bicyclol and multi-pharmacological active drug berberine, respectively, have sh...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-02-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.843872/full |
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| author | Hu Li Nan-Nan Liu Jian-Rui Li Biao Dong Mei-Xi Wang Jia-Li Tan Xue-Kai Wang Jing Jiang Lei Lei Hong-Ying Li Han Sun Jian-Dong Jiang Zong-Gen Peng Zong-Gen Peng |
| author_facet | Hu Li Nan-Nan Liu Jian-Rui Li Biao Dong Mei-Xi Wang Jia-Li Tan Xue-Kai Wang Jing Jiang Lei Lei Hong-Ying Li Han Sun Jian-Dong Jiang Zong-Gen Peng Zong-Gen Peng |
| author_sort | Hu Li |
| collection | DOAJ |
| description | Nonalcoholic fatty liver disease (NAFLD), ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), is a liver disease worldwide without approved therapeutic drugs. Anti-inflammatory and hepatoprotective drug bicyclol and multi-pharmacological active drug berberine, respectively, have shown beneficial effects on NAFLD in murine nutritional models and patients, though the therapeutic mechanisms remain to be illustrated. Here, we investigated the combined effects of bicyclol and berberine on mouse steatosis induced by Western diet (WD), and NASH induced by WD/CCl4. The combined use of these was rather safe and better reduced the levels of transaminase in serum and triglycerides and cholesterol in the liver than their respective monotherapy, accompanied with more significantly attenuating hepatic inflammation, steatosis, and ballooning in mice with steatosis and NASH. The combined therapy also significantly inhibited fibrogenesis, characterized by the decreased hepatic collagen deposition and fibrotic surface. As per mechanism, bicyclol enhanced lipolysis and β-oxidation through restoring the p62-Nrf2-CES2 signaling axis and p62-Nrf2-PPARα signaling axis, respectively, while berberine suppressed de novo lipogenesis through downregulating the expression of acetyl-CoA carboxylase and fatty acid synthetase, along with enrichment of lipid metabolism-related Bacteroidaceae (family) and Bacteroides (genus). Of note, the combined use of bicyclol and berberine did not influence each other but enhanced the overall therapeutic role in the amelioration of NAFLD. Conclusion: Combined use of bicyclol and berberine might be a new available strategy to treat NAFLD. |
| first_indexed | 2024-12-23T00:19:00Z |
| format | Article |
| id | doaj.art-e6cbf5bb267341f4972f2dfeb692ca96 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-23T00:19:00Z |
| publishDate | 2022-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-e6cbf5bb267341f4972f2dfeb692ca962022-12-21T18:07:19ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-02-011310.3389/fphar.2022.843872843872Combined Use of Bicyclol and Berberine Alleviates Mouse Nonalcoholic Fatty Liver DiseaseHu Li0Nan-Nan Liu1Jian-Rui Li2Biao Dong3Mei-Xi Wang4Jia-Li Tan5Xue-Kai Wang6Jing Jiang7Lei Lei8Hong-Ying Li9Han Sun10Jian-Dong Jiang11Zong-Gen Peng12Zong-Gen Peng13Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaKey Laboratory of Biotechnology of Antibiotics, The National Health and Family Planning Commission (NHFPC), Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaNonalcoholic fatty liver disease (NAFLD), ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), is a liver disease worldwide without approved therapeutic drugs. Anti-inflammatory and hepatoprotective drug bicyclol and multi-pharmacological active drug berberine, respectively, have shown beneficial effects on NAFLD in murine nutritional models and patients, though the therapeutic mechanisms remain to be illustrated. Here, we investigated the combined effects of bicyclol and berberine on mouse steatosis induced by Western diet (WD), and NASH induced by WD/CCl4. The combined use of these was rather safe and better reduced the levels of transaminase in serum and triglycerides and cholesterol in the liver than their respective monotherapy, accompanied with more significantly attenuating hepatic inflammation, steatosis, and ballooning in mice with steatosis and NASH. The combined therapy also significantly inhibited fibrogenesis, characterized by the decreased hepatic collagen deposition and fibrotic surface. As per mechanism, bicyclol enhanced lipolysis and β-oxidation through restoring the p62-Nrf2-CES2 signaling axis and p62-Nrf2-PPARα signaling axis, respectively, while berberine suppressed de novo lipogenesis through downregulating the expression of acetyl-CoA carboxylase and fatty acid synthetase, along with enrichment of lipid metabolism-related Bacteroidaceae (family) and Bacteroides (genus). Of note, the combined use of bicyclol and berberine did not influence each other but enhanced the overall therapeutic role in the amelioration of NAFLD. Conclusion: Combined use of bicyclol and berberine might be a new available strategy to treat NAFLD.https://www.frontiersin.org/articles/10.3389/fphar.2022.843872/fullnonalcoholic fatty liver diseasebicyclolberberinecombinationlipid metabolismgut microbiota |
| spellingShingle | Hu Li Nan-Nan Liu Jian-Rui Li Biao Dong Mei-Xi Wang Jia-Li Tan Xue-Kai Wang Jing Jiang Lei Lei Hong-Ying Li Han Sun Jian-Dong Jiang Zong-Gen Peng Zong-Gen Peng Combined Use of Bicyclol and Berberine Alleviates Mouse Nonalcoholic Fatty Liver Disease Frontiers in Pharmacology nonalcoholic fatty liver disease bicyclol berberine combination lipid metabolism gut microbiota |
| title | Combined Use of Bicyclol and Berberine Alleviates Mouse Nonalcoholic Fatty Liver Disease |
| title_full | Combined Use of Bicyclol and Berberine Alleviates Mouse Nonalcoholic Fatty Liver Disease |
| title_fullStr | Combined Use of Bicyclol and Berberine Alleviates Mouse Nonalcoholic Fatty Liver Disease |
| title_full_unstemmed | Combined Use of Bicyclol and Berberine Alleviates Mouse Nonalcoholic Fatty Liver Disease |
| title_short | Combined Use of Bicyclol and Berberine Alleviates Mouse Nonalcoholic Fatty Liver Disease |
| title_sort | combined use of bicyclol and berberine alleviates mouse nonalcoholic fatty liver disease |
| topic | nonalcoholic fatty liver disease bicyclol berberine combination lipid metabolism gut microbiota |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.843872/full |
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