Abstract | ETHNOPHARMACOLOGICAL RELEVANCE:
Nonalcoholic fatty liver disease ( NAFLD) is a manifestation of metabolic syndrome in the liver and the leading cause of chronic liver disease worldwide. Digeda-4 decoction (DGD-4) is a commonly prescribed Mongolian herbal drug for treating acute and chronic liver injury and fatty liver. However, the mechanisms underlying the improvement of dislipidemia and liver injury via treatment with DGD-4 remain unclear. Disassembling a prescription is an effective approach to studying the effects and mechanisms underlying Mongolian medicine prescriptions. By disassembling a prescription, it is feasible to discover effective combinations of individual herbs to optimize a given prescription. Accordingly, we disassembled DGD-4 into two groups: the single Lomatogonium rotatum (L.) Fries ex Nym (LR) (DGD-1) and non-LR (DGD-3). AIM OF THIS STUDY: To study whether DGD-4 and its disassembled prescriptions have protective effects against tyloxapol (TY)-induced NAFLD and to explore the underlying mechanisms of action and compatibility of prescriptions. MATERIAL AND METHODS:
NAFLD mice were developed by TY induction. Biochemical horizontal analyses, enzyme-linked immunosorbent assay, and liver histological staining were performed to explore the protective effects of DGD-4 and its disassembled prescriptions DGD-3 and DGD-1. Furthermore, we performed immunohistochemical analyses and Western blotting to further explore the expression of target proteins. RESULTS: DGD-4 and its disassembled prescriptions could inhibit TY-induced dislipidemia and liver injury. In addition, DGD-4 and its disassembled prescriptions increased the levels of p-AMPKα and p-ACC, but decreased the levels of SREBP1c, SCD-1, SREBP-2, and HMGCS1 proteins. The activation of lipid metabolic pathways SIRT1, PGC-1α, and PPARα improved lipid accumulation in the liver. Moreover, DGD-4 could inhibit hepatocyte apoptosis and treat TY-induced liver injury by upregulating the Bcl-2 expression, downregulating the expression of Bax, caspase-3, caspase-8, and the ratio of Bax/Bcl-2, and positively regulating the imbalance of oxidative stress (OxS) markers (such as superoxide dismutase [SOD], catalase [CAT], malondialdehyde [MDA], and myeloperoxidase [MPO]). DGD-1 was superior to DGD-3 in regulating lipid synthesis-related proteins such as SREBP1c, SCD-1, SREBP-2, and HMGCS1. DGD-3 significantly affected the expression of lipid metabolic proteins SIRT1, PGC-1α, PPARα, apoptotic proteins Bcl-2, Bax, caspase-3, caspase-8, and the regulation of Bax/Bcl-2 ratio. However, DGD-1 showed no regulatory effects on Bax and Bcl-2 proteins. CONCLUSION: This study demonstrates the protective effects of DGD-4 in the TY-induced NAFLD mice through a mechanism involving improvement of dyslipidemia and apoptosis by regulating the AMPK/ SIRT1 pathway. Although the Monarch drug DGD-1 reduces lipid accumulation and DGD-3 inhibits apoptosis and protects the liver from injury, DGD-4 can be more effective overall as a therapy when compared to DGD-1 and DGD-3.
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Authors | Xiaoping Ji, Qianqian Ma, Xuan Wang, Hui Ming, Guihua Bao, Minghai Fu, Chengxi Wei |
Journal | Journal of ethnopharmacology
(J Ethnopharmacol)
Vol. 317
Pg. 116827
(Dec 05 2023)
ISSN: 1872-7573 [Electronic] Ireland |
PMID | 37348794
(Publication Type: Journal Article)
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Copyright | Copyright © 2023. Published by Elsevier B.V. |
Chemical References |
- AMP-Activated Protein Kinases
- Caspase 3
- tyloxapol
- Caspase 8
- bcl-2-Associated X Protein
- Sirtuin 1
- PPAR alpha
- Sterol Regulatory Element Binding Protein 1
- Proto-Oncogene Proteins c-bcl-2
- Lipids
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Topics |
- Mice
- Animals
- Non-alcoholic Fatty Liver Disease
(chemically induced, drug therapy, metabolism)
- AMP-Activated Protein Kinases
(metabolism)
- Caspase 3
(metabolism)
- Caspase 8
(metabolism)
- bcl-2-Associated X Protein
(metabolism)
- Sirtuin 1
(metabolism)
- PPAR alpha
(metabolism)
- Sterol Regulatory Element Binding Protein 1
(metabolism)
- Liver
(metabolism)
- Apoptosis
- Proto-Oncogene Proteins c-bcl-2
(metabolism)
- Dyslipidemias
(chemically induced, drug therapy, complications)
- Prescriptions
- Lipids
(pharmacology)
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