Pterostilbene alleviated NAFLD via AMPK/mTOR signaling pathways and autophagy by promoting Nrf2

Shen, Bingyu; Wang, Yeling; Cheng, Jiaqi; Peng, Yi; Zhang, Qiaoling; Li, Zheng; Zhao, Lilei; Deng, Xuming; Feng, Hailan

doi:10.1016/j.phymed.2022.154561

Cited by 36 publications

(12 citation statements)

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“…37 The role of Nrf2 in liver steatosis, inflammation, fibrosis, as well as related therapeutic strategies has been recently summarized by Bukke et al 38 Besides, the studies that the natural plants components alleviate NAFLD via AMPK/Nrf2 pathway have been reported extensively. 36,39,40 In this study, the downregulation in the relative protein level of p-AMPK/AMPK, Nrf2, and HO-1 in HFD-feeding rats was restored by the treatment of PMS, suggesting that PMS activated the AMPK/Nrf2 pathway in HFD-induced NAFLD rats. Zeng et al 28 have reported that PMS promotes the activation of Nrf2/HO-1 pathway in hypoxia/reoxygenation-induced injury.…”

Section: Conflict Of Interest Statementsupporting

confidence: 50%

“…Nrf2 plays an important role in neutralizing oxidative stress and conserving redox homeostasis in the cell through the generation of cytoprotective and antioxidant enzymes, such as HO‐1 and NQO1 37 . The role of Nrf2 in liver steatosis, inflammation, fibrosis, as well as related therapeutic strategies has been recently summarized by Bukke et al 38 Besides, the studies that the natural plants components alleviate NAFLD via AMPK/Nrf2 pathway have been reported extensively 36,39,40 . In this study, the downregulation in the relative protein level of p‐AMPK/AMPK, Nrf2, and HO‐1 in HFD‐feeding rats was restored by the treatment of PMS, suggesting that PMS activated the AMPK/Nrf2 pathway in HFD‐induced NAFLD rats.…”

Section: Discussionmentioning

confidence: 64%

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Plantamajoside modulates immune dysregulation and hepatic lipid metabolism in rats with nonalcoholic fatty liver disease viaAMPK/Nrf2 elevation

Wu,

Zhaori,

Mei

et al. 2023

The Kaohsiung J of Med Scie

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Nonalcoholic fatty liver disease (NAFLD) is a hepatic metabolic syndrome with a rapidly increasing prevalence globally. Plantamajoside (PMS), a phenylethanoid glycoside component extracted from Plantago asiatica, has various biological properties. However, its effect on NAFLD remains unknown. The study aimed to explore the effect and mechanism of PMS on NAFLD in the high‐fat diet (HFD)‐feeding rats. PMS induced a decrease in body and liver weight, and the amelioration in the blood lipid parameters and pathological symptoms in HFD‐feeding rats. The increase in the serum concentrations and the relative protein expressions of proinflammatory factors was decreased by the PMS treatment in HFD‐induced NAFLD rats. Additionally, PMS reduced the excessive lipid vacuoles, and modified the relative expressions of proteins involved in the fatty acid synthesis and uptake in HFD‐feeding rats. Mechanically, the downregulation of AMPK/Nrf2 pathway in HFD‐feeding rats was restored by the PMS treatment. Inhibition of AMPK pathway reversed the PMS‐induced the increase in the level of inflammatory factors, pathological symptoms, excessive lipid vacuoles, and the relative expression of proteins involved in the fatty acid synthesis and uptake. Collectively, PMS ameliorated immune dysregulation and abnormal hepatic lipid metabolism by activating AMPK/Nrf2 pathway in rats with NAFLD.

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Section: Conflict Of Interest Statementsupporting

confidence: 50%

Section: Discussionmentioning

confidence: 64%

Plantamajoside modulates immune dysregulation and hepatic lipid metabolism in rats with nonalcoholic fatty liver disease viaAMPK/Nrf2 elevation

Wu,

Zhaori,

Mei

et al. 2023

The Kaohsiung J of Med Scie

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“…The Nrf2-ARE is the most critical antioxidant signaling pathway in biological organisms ( Dai et al, 2022 ; Guo et al, 2022 ; Jiang et al, 2022 ; Qiu et al, 2022 ; Shen et al, 2022a ; Yan et al, 2022 ). So far, accumulating evidence has shown that a large amount of natural active substances activate Nrf2-mediated antioxidant signaling pathway and regulate the expression of cytoprotective enzymes, thus playing an important role in preventing antioxidant damage ( Eggler et al, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

Characterization of tangeretin as an activator of nuclear factor erythroid 2-related factor 2/antioxidant response element pathway in HEK293T cells

Liang

et al. 2023

Current Research in Food Science

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“…Furthermore, we performed Oil Red O staining on mouse liver tissue (Figure E) and found that Britanin could alleviate lipid accumulation in the liver. Numerous studies demonstrated that the AMPK/SREBP1c pathway plays a key role in the regulation of hepatic lipid accumulation in NAFLD mice. , To further investigate the inhibitory effect of Britanin on hepatic lipid accumulation, we examined the phosphorylation levels of AMPK and the expression levels of SREBP1c. The results demonstrated that Britanin inhibited AMPK phosphorylation and reduced SREBP1c expression (Figure F,G).…”

Section: Resultsmentioning

confidence: 99%

Integrated Pharmaco-Bioinformatics Approaches and Experimental Verification To Explore the Effect of Britanin on Nonalcoholic Fatty Liver Disease

Dou,

Zhu,

Xie

et al. 2024

ACS Omega

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Nonalcoholic fatty liver disease (NAFLD) is a prevalent global liver disorder, posing substantial health risks. Britanin, a bioactive sesquiterpene lactone extracted from Inula japonica, has demonstrated antidiabetic, hypolipidemic, and hepatoprotective attributes. Nonetheless, the precise impact of Britanin on NAFLD and the intricate biological mechanisms underpinning this interaction remain unexplored. We integrated computer-aided methods to unearth shared biological targets and signaling pathways associated with both Britanin and NAFLD. A network was constructed by compiling putative targets associated with Britanin and NAFLD, followed by a stringent screening of key targets and mechanisms through protein–protein interaction analysis along with GO and KEGG pathway enrichment analyses. Molecular docking was integrated as an evaluation tool, culminating in the identification of HO-1 as the pivotal therapeutic target, showcasing a satisfactory binding affinity. The primary mechanism was ascribed to biological processes and pathways linked to oxidative stress, as evidenced by the outcomes of enrichment analyses. Of these, the AMPK/SREBP1c pathway assumed centrality in this mechanism. Furthermore, in vivo experiments substantiated that Britanin effectively curtailed NAFLD development by ameliorating liver injury, modulating hyperlipidemia and hepatic lipid accumulation, and alleviating oxidative stress and apoptosis. In summary, this study demonstrates the potential of Britanin as a promising therapeutic drug against NAFLD.

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Pterostilbene alleviated NAFLD via AMPK/mTOR signaling pathways and autophagy by promoting Nrf2

Cited by 36 publications

References 50 publications

Plantamajoside modulates immune dysregulation and hepatic lipid metabolism in rats with nonalcoholic fatty liver disease viaAMPK/Nrf2 elevation

Plantamajoside modulates immune dysregulation and hepatic lipid metabolism in rats with nonalcoholic fatty liver disease viaAMPK/Nrf2 elevation

Characterization of tangeretin as an activator of nuclear factor erythroid 2-related factor 2/antioxidant response element pathway in HEK293T cells

Integrated Pharmaco-Bioinformatics Approaches and Experimental Verification To Explore the Effect of Britanin on Nonalcoholic Fatty Liver Disease

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