Neferine ameliorates nonalcoholic steatohepatitis through regulating AMPK pathway

Wang, Mingyue; Zhang, Shao-Shi; An, Meng-Fei; Xia, Yue-Fei; Fan, Mao-Si; Sun, Ze-Rui; Zhang, Lijuan; Zhao, Yunli; Sheng, Jun

doi:10.1016/j.phymed.2023.154798

Cited by 12 publications

(8 citation statements)

References 57 publications

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“…Previous researches have been shown that Nef had a powerful anti-inflammatory and neuroprotective effects [15][16][17] : so we tried to figure out the protective evidence of Nef on blood-brain barrier in cerebral I/R instead of neuroprotection. Our study using multiple methods to indicates that Nef repairs disruptive BBB to alleviated brain injury in cerebral I/R.…”

Section: Discussionmentioning

confidence: 99%

Neferine inhibits BMECs pyroptosis and maintains blood–brain barrier integrity in ischemic stroke by triggering a cascade reaction of PGC-1α

Zheng,

Zhu,

Qiu

et al. 2024

Sci Rep

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Blood–brain barrier disruption is a critical pathological event in the progression of ischemic stroke (IS). Most studies regarding the therapeutic potential of neferine (Nef) on IS have focused on neuroprotective effect. However, whether Nef attenuates BBB disruption during IS is unclear. We here used mice underwent transient middle cerebral artery occlusion (tMCAO) in vivo and bEnd.3 cells exposed to oxygen–glucose deprivation/reoxygenation (OGD/R) injury in vitro to simulate cerebral ischemia. We showed that Nef reduced neurobehavioral dysfunction and protected brain microvascular endothelial cells and BBB integrity. Molecular docking, short interfering (Si) RNA and plasmid transfection results showed us that PGC-1α was the most binding affinity of biological activity protein for Nef. And verification experiments were showed that Nef upregulated PGC-1α expression to reduce mitochondrial oxidative stress and promote TJ proteins expression, further improves the integrity of BBB in mice. Intriguingly, our study showed that neferine is a natural PGC-1α activator and illustrated the mechanism of specific binding site. Furthermore, we have demonstrated Nef reduced mitochondria oxidative damage and ameliorates endothelial inflammation by inhibiting pyroptosis to improve BBB permeability through triggering a cascade reaction of PGC-1α via regulation of PGC-1α/NLRP3/GSDMD signaling pathway to maintain the integrity of BBB in ischemia/reperfusion injury.

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Section: Discussionmentioning

confidence: 99%

Neferine inhibits BMECs pyroptosis and maintains blood–brain barrier integrity in ischemic stroke by triggering a cascade reaction of PGC-1α

Zheng,

Zhu,

Qiu

et al. 2024

Sci Rep

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“…LMH cells originate from the liver, an essential organ for lipid synthesis, and the synthesis of TC and TG is an important indicator to reflect the lipid synthesis status of LMH cells [ 1 , 2 , 8 , 9 , 10 ]. Abnormal synthesis of TG and TC in liver cells can lead to various diseases, such as fatty liver syndrome and hyperlipidaemia [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

“…AMPK is the molecular switch of energy regulation in the organism, and the organism’s life processes, such as glucose metabolism, protein synthesis, and lipid metabolism, are regulated by AMPK [ 8 , 9 , 10 ]. When AMPK is activated, ATP-consuming life activities, such as lipid and protein synthesis, will be inhibited [ 8 , 9 , 10 ].…”

Section: Discussionmentioning

confidence: 99%

“…When exogenous substances activate AMPK, catabolic life activities in cells are enhanced to increase the ATP supply, and anabolic life activities are inhibited to reduce energy consumption [8]. Numerous studies have shown that when AMPK is activated, the synthesis of cholesterol and TG in cells is inhibited [8][9][10]. Hwang et al (2013) reported that S-Allyl cysteine (SAC) can activate AMPK to reduce triglyceride (TG) accumulation in HepG2 cells [9].…”

Section: Introductionmentioning

confidence: 99%

“…Hwang et al (2013) reported that S-Allyl cysteine (SAC) can activate AMPK to reduce triglyceride (TG) accumulation in HepG2 cells [9]. reported that neferine (NEF) could reduce the accumulation of total cholesterol (TC) and TG in the livers of non-alcoholic fatty liver disease model mice by activating AMPK [10]. At present, there are few studies on the AMPK pathway in LMH cells and a study of AMPK and lipid metabolism in LMH cells has not been reported.…”

Section: Introductionmentioning

confidence: 99%

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Resveratrol and (-)-Epigallocatechin-3-gallate Regulate Lipid Metabolism by Activating the AMPK Pathway in Hepatocytes

Wang,

An,

Rajput

et al. 2024

Biology

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The purpose of this study was to explore the effects of Res and EGCG on cell growth, cellular antioxidant levels, and cellular lipid metabolism in hepatocytes. In this experiment, leghorn male hepatoma (LMH) cells were used as hepatocytes. The results showed that 6.25–25 μM Res and EGCG had no adverse effects on cell viability and growth. Meanwhile, with the increasing dosage of Res and EGCG, the contents of total cholesterol (TC), total glyceride (TG), and malondialdehyde (MDA) in hepatocytes decreased significantly (p < 0.05), while the contents of glutathione peroxidase (GSH-Px), total superoxide dismutase (T-SOD), and catalase (CAT) increased significantly (p < 0.05). In addition, western blot results showed that Res and EGCG could significantly increase the expression of p-AMPK protein and reduce the expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) protein in hepatocytes (p < 0.05). Moreover, q-PCR results showed that with the increase in Res and EGCG, the expression of cholesterol- and fatty acid synthesis-related genes decreased significantly (p < 0.05). In conclusion, Res and EGCG can increase the antioxidant capacity of hepatocytes and reduce the synthesis of TC and TG in hepatocytes by activating AMPK, thereby regulating lipid metabolism in hepatocytes.

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Neferine alleviates acute kidney injury by regulating the PPAR-α/NF-κB pathway

Xiong,

Zhong,

Chen

et al. 2024

Clin Exp Nephrol

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Neferine ameliorates nonalcoholic steatohepatitis through regulating AMPK pathway

Cited by 12 publications

References 57 publications

Neferine inhibits BMECs pyroptosis and maintains blood–brain barrier integrity in ischemic stroke by triggering a cascade reaction of PGC-1α

Neferine inhibits BMECs pyroptosis and maintains blood–brain barrier integrity in ischemic stroke by triggering a cascade reaction of PGC-1α

Resveratrol and (-)-Epigallocatechin-3-gallate Regulate Lipid Metabolism by Activating the AMPK Pathway in Hepatocytes

Neferine alleviates acute kidney injury by regulating the PPAR-α/NF-κB pathway

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