1. Patchouli alcohol alleviates metabolic dysfunction-associated steatohepatitis via inhibiting mitochondria-associated endoplasmic reticulum membrane disruption-induced hepatic steatosis and inflammation in rats.
- Author
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Xie X, Liao Y, Lin Z, Luo H, Wei G, Huang N, Li Y, Chen J, Su Z, Yu X, Chen L, and Liu Y
- Subjects
- Animals, Male, Rats, Liver pathology, Liver drug effects, Liver metabolism, Mitochondria drug effects, Mitochondria metabolism, Fatty Liver drug therapy, Fatty Liver metabolism, Fatty Liver pathology, Sterol Regulatory Element Binding Protein 1 metabolism, Sterol Regulatory Element Binding Protein 1 genetics, Lipid Metabolism drug effects, Anti-Inflammatory Agents therapeutic use, Anti-Inflammatory Agents pharmacology, Inflammation drug therapy, Pogostemon, Signal Transduction drug effects, Endoplasmic Reticulum metabolism, Endoplasmic Reticulum drug effects, Diet, High-Fat adverse effects, Sesquiterpenes therapeutic use, Sesquiterpenes pharmacology, PPAR alpha metabolism, Endoplasmic Reticulum Stress drug effects, Rats, Sprague-Dawley
- Abstract
Metabolic dysfunction-associated steatohepatitis (MASH) is a severe metabolic dysfunction-associated steatotic liver disease (MASLD) characterized by abnormal hepatic steatosis and inflammation. Previous studies have shown that Patchouli alcohol (PA), the primary component of Pogostemonis Herba, can alleviate digestive system diseases. However, its protection against MASH remains unclear. This study explored the protective effects and underlying mechanism of PA against high-fat diet-induced MASH in rats. Results showed that PA considerably reduced body weight, epididymal fat, and liver index and attenuated liver histological injury in MASH rats. PA alleviated hepatic injury by inhibiting steatosis and inflammation. These effects are associated with the improvement of SREBP-1c- and PPARα-mediated lipid metabolism and inhibition of the STING-signaling pathway-mediated inflammatory response. Moreover, PA-inhibited hepatic endoplasmic reticulum (ER) stress and mitochondrial dysfunction, reducing SREBP-1c and STING expressions and enhance PPARα expression. PA treatment had the strongest effect on the regulation of mitogen fusion protein 2 (Mfn2) in inhibiting mitochondrial dysfunction. Mfn2 is an important structural protein for binding ERs and mitochondria to form mitochondria-associated ER membranes (MAMs). MASH-mediated disruption of MAMs was inhibited after PA treatment-induced Mfn2 activation. Therefore, the pharmacological effect of PA on MASH is mainly attributed to the inhibition of MAM disruption-induced hepatic steatosis and inflammation. The findings of this study may have implications for MASH treatment that do not neglect the role of Mfn2-mediated MAMs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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