Betulin alleviated ethanol-induced alcoholic liver injury via SIRT1/AMPK signaling pathway

Bai, Ting; Yang, Yong; Yao, You-Li; Sun, Peng; Lian, Li-Hua; Wu, Yan-Ling; Nan, Ji‐Xing

doi:10.1016/j.phrs.2015.12.022

Cited by 88 publications

(59 citation statements)

References 40 publications

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“…Recent studies suggested that defective SIRT1 in hepatocytes has a critical role of the development of NAFLD, as liver-specific Sirt1 −/− mice exhibit excessive accumulation of lipid droplets91011. In addition, multiple reports demonstrated that there is a synergistic interaction between SIRT1 and AMPK in regulating lipid metabolism89121314. As we reported previously, hepatic SIRT1 improves lipid homeostasis by positively regulating AMPK to modulate lipid metabolic imbalance in response to long-term nutrient intake.…”

supporting

confidence: 68%

Lycium barbarum polysaccharide attenuates high-fat diet-induced hepatic steatosis by up-regulating SIRT1 expression and deacetylase activity

et al. 2016

Sci Rep

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In this study, we aimed to investigate the protective effects and underlying mechanism of Lycium barbarum polysaccharide (LBP) on high-fat-induced nonalcoholic fatty liver disease (NAFLD). Recently, sirtuin 1 (SIRT1) has been shown to play an important role in the regulation of hepatocellular lipid metabolism. Here, we demonstrated that LBP up-regulates SIRT1 deacetylase activity and protein expression by enhancing the NAD+/NADH ratio. Subsequently, LBP promoted LKB1 deacetylation and AMPK phosphorylation via SIRT1-dependent signalling. We also found that LBP increases acetyl-CoA carboxylase (ACC) phosphorylation and adipose triglyceride lipase (ATGL) protein expression and decreases fatty acid synthase (FAS) by activating the SIRT1/LKB1/AMPK pathway in vitro and in vivo. However, SIRT1 small interfering RNA (siRNA)-mediated knockdown reversed the LBP-mediated effects on ACC, FAS and ATGL. Moreover, LBP elevated carnitine palmitoyltransferase-1 alpha (CPT-1α) expression by suppressing malonyl-CoA accumulation. Taken together, our data indicate that LBP plays a vital role in the regulation of hepatic lipid metabolism and that pharmacological activation of SIRT1 by LBP may be a strategy for the prevention of NAFLD.

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confidence: 68%

Lycium barbarum polysaccharide attenuates high-fat diet-induced hepatic steatosis by up-regulating SIRT1 expression and deacetylase activity

et al. 2016

Sci Rep

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“…Inhibition of hsp90 by 17-dimethylamino-ethylamino-17-demethoxygeldanamycin ameliorated the steatosis and liver inflammation induced by chronic-plus-binge ethanol feeding, which suggests that hsp90 is a promising therapeutic target for the treatment of ALD 96 . More recently, the chronic-plus-binge ethanol feeding model has also been used to test the therapeutic potential of many drugs/compounds, including a CB2 agonist 62 , betulin (a triterpene from the bark of Betula platyphylla Suk) 97 , luteolin (a flavonoid) 98 , Lactobacillus rhamnosus GG 99 , Korean Red Ginseng 100 , glycycoumarin (a representative coumarin from traditional Chinese Medicine licorice) 101 , flaxseed oil enriched in α-linolenic acid (a plant-derived n-3 polyunsaturated fatty acid) 102 , thymoquinone (a biologically active compound isolated from the seeds of Nigella sativa L.) 103 , and β-caryophyllene (BCP: a plant-derived FDA-approved food additive with anti-inflammatory properties) 104 . The data from these studies revealed that treatment with all of these components ameliorated the chronic-plus-binge alcohol-induced liver inflammation and steatosis in mice.…”

Section: Application Of Chronic-plus-binge Ethanol Model In Testing Tmentioning

confidence: 99%

Animal Models of Alcoholic Liver Disease: Pathogenesis and Clinical Relevance

et al. 2017

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Alcoholic liver disease (ALD), a leading cause of chronic liver injury worldwide, comprises a range of disorders including simple steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma. Over the last five decades, many animal models that have been useful for the study of ALD pathogenesis have been developed. Recently, a chronic-plus-binge ethanol feeding model was reported. This model induces significant steatosis, hepatic neutrophil infiltration, and liver injury. A clinically relevant model of high-fat diet feeding plus binge ethanol was also developed, which highlights the risk of excessive binge drinking in obese/overweight individuals. All of these models recapitulate some features of the different stages of ALD and have been widely used by many investigators to study the pathogenesis of ALD and test therapeutic drugs/components. However, these models are somewhat variable, depending on mouse genetic background, ethanol dose, and animal facility environment. This review focuses on these models and discusses these variations and some methods to improve the feeding protocol. The pathogenesis, clinical relevance, and translational studies of these models are also discussed.

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“…This was accompanied by reversion of Parkin transcriptional inhibition, enhanced lysosome biogenesis, and fusion with mitophagosomes [28]. Another polyphenol, betulin, was also reported to alleviate ethanol-induced alcoholic liver injury via the SIRT1-AMPK signalling pathway to enhance lipophagy [118]. Whether betulin can concomitantly upregulate mitophagy to attenuate mitochondrial oxidative stress under alcohol-induced hepatotoxicity remains to be elucidated.…”

Section: Polyphenols and Mitophagymentioning

confidence: 99%

Mitophagy Transcriptome: Mechanistic Insights into Polyphenol‐Mediated Mitophagy

Tan

Wong

2017

Oxidative Medicine and Cellular Longevity

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Mitochondria are important bioenergetic and signalling hubs critical for myriad cellular functions and homeostasis. Dysfunction in mitochondria is a central theme in aging and diseases. Mitophagy, a process whereby damaged mitochondria are selectively removed by autophagy, plays a key homeostatic role in mitochondrial quality control. Upregulation of mitophagy has shown to mitigate superfluous mitochondrial accumulation and toxicity to safeguard mitochondrial fitness. Hence, mitophagy is a viable target to promote longevity and prevent age-related pathologies. Current challenge in modulating mitophagy for cellular protection involves identification of physiological ways to activate the pathway. Till date, mitochondrial stress and toxins remain the most potent inducers of mitophagy. Polyphenols have recently been demonstrated to protect mitochondrial health by facilitating mitophagy, thus suggesting the exciting prospect of augmenting mitophagy through dietary intake. In this review, we will first discuss the different surveillance mechanisms responsible for the removal of damaged mitochondrial components, followed by highlighting the transcriptional regulatory mechanisms of mitophagy. Finally, we will review the functional connection between polyphenols and mitophagy and provide insight into the underlying mechanisms that potentially govern polyphenol-induced mitophagy.

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Betulin alleviated ethanol-induced alcoholic liver injury via SIRT1/AMPK signaling pathway

Cited by 88 publications

References 40 publications

Lycium barbarum polysaccharide attenuates high-fat diet-induced hepatic steatosis by up-regulating SIRT1 expression and deacetylase activity

Lycium barbarum polysaccharide attenuates high-fat diet-induced hepatic steatosis by up-regulating SIRT1 expression and deacetylase activity

Animal Models of Alcoholic Liver Disease: Pathogenesis and Clinical Relevance

Mitophagy Transcriptome: Mechanistic Insights into Polyphenol‐Mediated Mitophagy

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