Journal
PHYTOMEDICINE
Volume 98, Issue -, Pages -Publisher
ELSEVIER GMBH
DOI: 10.1016/j.phymed.2022.153960
Keywords
Schisandrin B; CB2 receptor; Kupffer cell polarization; Liver fibrosis; NF-kappa B; p-p38
Categories
Funding
- National Natural Science Foundation of China [81773797]
- Traditional Chinese Medicine Inheritance and Scientific and Technological Innovation Project of Shanghai Municipal Health Commission [ZYCC2019025]
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This study identified schisandrin B as the most effective component for attenuating liver fibrosis and proved that CB2 is a potential target for anti-liver fibrosis. The findings showed that schisandrin B improves CCl4-induced liver fibrosis by suppressing the NF-kappa B and p38 MAPK pathways.
Background: Lignans, the major bioactive components of Schisandra chinensis, displays an anti-liver fibrosis effect. However, which one is the most effective lignan and what is its molecular mechanisms are still unclear. Purpose: This research aimed to screen the most effective components of lignans, identify and verify its pharmacological target, and investigate its molecular mechanism against liver fibrosis. Methods: First, the most effective lignans were screened by a comprehensive RAW264.7/CMC system and LPSinduced RAW264.7. Second, the potential targets were predicted by a liver fibrosis domain-specific chemo-genomics knowledgebase and further verified by competition binding assay. Third, the effect of anti-liver fibrosis was evaluated by employing RAW264.7, co-cultured hepatic stellate cells (HSC) and CCl4-induced liver fibrosis CB2(-/-) mice. The qPCR, ELISAs, western blot analyses, and immunofluorescence were used to evaluate the expression of main inflammatory factors and key proteins in NF-kappa B and p38 MAPK pathway. Results: Schisandrin B was identified as the most effective component for attenuating liver fibrosis, and CB2 was proven to be a potential target for anti-liver fibrosis. The in vitro and in vivo assays indicated that schisandrin B ameliorated CCl4-induced liver fibrosis through suppressing NF-kappa B and p38 MAPK pathway in Kupffer cells by targeting CB2 receptor Conclusion: Schisandrin B targets CB2 receptor to inhibit Kupffer cell polarization by downregulating the NF-kappa B and p38 MAPK signaling pathways for ameliorating liver fibrosis.
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