Schisandrin B mitigates hepatic steatosis and promotes fatty acid oxidation by inducing autophagy through AMPK/mTOR signaling pathway

Yan, Li-Shan; Zhang, Shuofeng; Luo, Guoan; Cheng, Brian Chi‐Yan; Zhang, Chao; Wang, Yiwei; Qiu, Xinyu; Zhou, Xiaohong; Wang, Qing-Gao; Song, Xue-Lan; Pan, Si-Yuan; Zhang, Yi

doi:10.1016/j.metabol.2022.155200

Cited by 69 publications

(21 citation statements)

References 54 publications

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“…HepG2 cells are widely used in in vitro NAFLD models because they have the characteristics of hepatocytes that accumulates intracellular lipids by FFA treatments such as oleic acid and/or palmitic acid [ 9 , 34 , 35 ]. Many studies have reported that the exposure of HepG2 cells to 0.5–1 mM of FFA for 24 h results in significant lipid accumulation [ 16 , 36 , 37 ]. To evaluate the involvement of isoquercitrin in regulating lipid metabolism, HepG2 cells were pretreated with isoquercitrin for 6 h with doses from 1 to 50 μM and co-treated with FFA (0.5 mM) composed of oleic acid and palmitic acid (2:1) for 24 h. As shown in Figure 2 A, treatment with increasing doses of isoquercitrin consistently decreased Oil-Red-O staining when compared with that in FFA-only treated samples.…”

Section: Resultsmentioning

confidence: 99%

Effect of Isoquercitrin on Free Fatty Acid-Induced Lipid Accumulation in HepG2 Cells

et al. 2023

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Liver metabolic disorders and oxidative stress are crucial factors in the development of nonalcoholic fatty liver disease (NAFLD); however, treatment strategies to combat NAFLD remain poorly established, presenting an important challenge that needs to be addressed. Herein, we aimed to examine the effect of isoquercitrin on lipid accumulation induced by exogenous free fatty acids (FFA) using HepG2 cells and elucidate the underlying molecular mechanism. The cells were exposed to 0.5 mM FFA to induce intracellular lipid accumulation, followed by co-treatment with isoquercitrin to confirm the potential inhibitory effect on FFA-induced lipid production. HepG2 cells exposed to FFA alone exhibited intracellular lipid accumulation, compromised endoplasmic reticulum (ER) stress, and enhanced expression of proteins and genes involved in lipid synthesis; however, co-treatment with isoquercitrin decreased the expression of these molecules in a dose-dependent manner. Furthermore, isoquercitrin could activate AMP-activated protein kinase (AMPK), a key regulatory protein of hepatic fatty acid oxidation, suppressing new lipid production by phosphorylating acetyl-CoA carboxylase (ACC) and inhibiting sterol regulatory element-binding transcription factor 1 (SREBP-1)/fatty acid synthase (FAS) signals. Overall, these findings suggest that isoquercitrin can be employed as a therapeutic agent to improve NAFLD via the regulation of lipid metabolism by targeting the AMPK/ACC and SREBP1/FAS pathways.

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Section: Resultsmentioning

confidence: 99%

Effect of Isoquercitrin on Free Fatty Acid-Induced Lipid Accumulation in HepG2 Cells

et al. 2023

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“…Recently, Mei et al [ 42 ] reported that isosteviol sodium, a sweetener isolated from Stevia rebaudiana, inhibited lipid deposition by enhancing autophagy via Sirt1/AMPK signaling. In addition, accumulating evidence suggests that the AMPK/mTOR pathway plays a central role in the regulation of autophagy initiation in NAFLD [ 43 , 44 , 45 , 46 , 47 ]. These findings indicate that enhancing autophagy via AMPK/mTOR signaling may play a pivotal role in attenuating the development of NAFLD.…”

Section: Discussionmentioning

confidence: 99%

Red Pepper Seeds Inhibit Hepatic Lipid Accumulation by Inducing Autophagy via AMPK Activation

et al. 2022

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Although the red pepper and its seeds have been studied for metabolic diseases, the effects and potential mechanisms of red pepper seed extract (RPS) on hepatic lipid accumulation are not yet completely understood. This study aimed to evaluate the inhibitory effect of RPS on hepatic lipid accumulation via autophagy. C57BL/6 mice were fed a high-fat diet (HFD) or a HFD supplemented with RPS. RPS treatment inhibited hepatic lipid accumulation by suppressing lipogenesis, inducing hepatic autophagic flux, and activating AMPK in HFD-fed mice. To investigate the effect of RPS on an oleic acid (OA)-induced hepatic steatosis cell model, HepG2 cells were incubated in a high-glucose medium and OA, followed by RPS treatment. RPS treatment decreased OA-induced lipid accumulation and reduced the expression of lipogenesis-associated proteins. Autophagic flux dramatically increased in the RPS-treated group. RPS phosphorylated AMPK in a dose-dependent manner, thereby dephosphorylated mTOR. Autophagy inhibition with 3-methyladenine (3-MA) antagonized RPS-induced suppression of lipogenesis-related protein expressions. Moreover, the knockdown of endogenous AMPK also antagonized the RPS-induced regulation of lipid accumulation and autophagy. Our findings provide new insights into the beneficial effects of RPS on hepatic lipid accumulation through the AMPK-dependent autophagy-mediated downregulation of lipogenesis.

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“…Schisandra chinensis is a widely used natural compound of traditional Chinese medicine which can inhibit proliferation of tumor tissue as well as prevent memory deficiency [18]. Schisandrin B is a bioactive compound of Schisandra chinensis, and recent studies have shown that Schisandrin B can provide antioxidant, anti-inflammatory, anti-immune, and cardioprotective effects, its biosafety has also been proven [18][19][20][21]. As an empirical traditional Chinese medicine, Schisandrin B may have some complex mechanism of action which has not been elucidated, but recent studies have found the related pathway of Schisandrin B.…”

Section: Introductionmentioning

confidence: 99%

Schisandrin B Alleviates Diabetic Cardiac Autonomic neuropathy Induced by P2X7 Receptor in Superior Cervical Ganglion via NLRP3

Zhang

Guo

et al. 2023

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Diabetic cardiovascular autonomic neuropathy (DCAN) is a common complication of diabetes mellitus which brings about high mortality, high morbidity, and large economic burden to the society. Compensatory tachycardia after myocardial ischemia caused by DCAN can increase myocardial injury and result in more damage to the cardiac function. The inflammation induced by hyperglycemia can increase P2X7 receptor expression in the superior cervical ganglion (SCG), resulting in nerve damage. It is proved that inhibiting the expression of P2X7 receptor at the superior cervical ganglion can ameliorate the nociceptive signaling dysregulation induced by DCAN. However, the effective drug used for decreasing P2X7 receptor expression has not been found. Schisandrin B is a traditional Chinese medicine, which has anti-inflammatory and antioxidant effects. Whether Schisandrin B can decrease the expression of P2X7 receptor in diabetic rats to protect the cardiovascular system was investigated in this study. After diabetic model rats were made, Schisandrin B and shRNA of P2X7 receptor were given to different groups to verify the impact of Schisandrin B on the expression of P2X7 receptor. Pathological blood pressure, heart rate, heart rate variability, and sympathetic nerve discharge were ameliorated after administration of Schisandrin B. Moreover, the upregulated protein level of P2X7 receptor, NLRP3 inflammasomes, and interleukin-1β in diabetic rats were decreased after treatment, which indicates that Schisandrin B can alleviate the chronic inflammation caused by diabetes and decrease the expression levels of P2X7 via NLRP3. These findings suggest that Schisandrin B can be a potential therapeutical agent for DCAN.

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Schisandrin B mitigates hepatic steatosis and promotes fatty acid oxidation by inducing autophagy through AMPK/mTOR signaling pathway

Cited by 69 publications

References 54 publications

Effect of Isoquercitrin on Free Fatty Acid-Induced Lipid Accumulation in HepG2 Cells

Effect of Isoquercitrin on Free Fatty Acid-Induced Lipid Accumulation in HepG2 Cells

Red Pepper Seeds Inhibit Hepatic Lipid Accumulation by Inducing Autophagy via AMPK Activation

Schisandrin B Alleviates Diabetic Cardiac Autonomic neuropathy Induced by P2X7 Receptor in Superior Cervical Ganglion via NLRP3

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