Effects of taraxasterol against ethanol and high-fat diet-induced liver injury by regulating TLR4/MyD88/NF-κB and Nrf2/HO-1 signaling pathways

Li, Zimeng; Lian, Yuanyu; Wei, Riming; Jin, Ling; Cao, Houkang; Zhao, Tanglian; Ma, Xuexiao; Zhong, Mingli; Gao, Ya; Zhang, Kefeng

doi:10.1016/j.lfs.2020.118546

Cited by 20 publications

(14 citation statements)

References 40 publications

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“…HFD displays deleterious impact on hepatic lipid accumulation and lipid homeostasis. 41 WEFL significantly protects against HFD-induced excessive weight gain, liver lipid accumulation, and the elevation of hepatic levels of TG, TC, AST and ALT, and restores the abnormalities of serum lipid transport proteins (i.e. LDL and HDL).…”

Section: Discussionmentioning

confidence: 92%

Water extract ofFerula lehmanni Boiss.prevents high-fat diet-induced overweight and liver injury by modulating the intestinal microbiota in mice

Shi

Wang

et al. 2022

Food Funct.

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Section: Discussionmentioning

confidence: 92%

Water extract ofFerula lehmanni Boiss.prevents high-fat diet-induced overweight and liver injury by modulating the intestinal microbiota in mice

Shi

Wang

et al. 2022

Food Funct.

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“…Myd88 is the most critical effector molecule in the signal transduction of TLRs. When TLRs recognize ligands, it may activate the downstream signaling through MyD88 and finally activate the nuclear factor κ B (NF- κ B) to regulate the expression of corresponding inflammatory cytokines [ 41 , 42 ]. In addition, studies have shown that Nrf2 may regulate the TLR-4/MyD88/NF- κ B signaling pathway in specific pathological processes [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Limonin Inhibits IL‐1β‐Induced Inflammation and Catabolism in Chondrocytes and Ameliorates Osteoarthritis by Activating Nrf2

Jin

Wang

et al. 2021

Oxidative Medicine and Cellular Longevity

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Osteoarthritis (OA), a degenerative disorder, is considered to be one of the most common forms of arthritis. Limonin (Lim) is extracted from lemons and other citrus fruits. Limonin has been reported to have anti-inflammatory effects, while inflammation is a major cause of OA; thus, we propose that limonin may have a therapeutic effect on OA. In this study, the therapeutic effect of limonin on OA was assessed in chondrocytes in vitro in IL-1β induced OA and in the destabilization of the medial meniscus (DMM) mice in vivo. The Nrf2/HO-1/NF-κB signaling pathway was evaluated to illustrate the working mechanism of limonin on OA in chondrocytes. In this study, it was found that limonin can reduce the level of IL-1β induced proinflammatory cytokines such as INOS, COX-2, PGE2, NO, TNF-α, and IL-6. Limonin can also diminish the biosynthesis of IL-1β-stimulated chondrogenic catabolic enzymes such as MMP13 and ADAMTS5 in chondrocytes. The research on the mechanism study demonstrated that limonin exerts its protective effect on OA through the Nrf2/HO-1/NF-κB signaling pathway. Taken together, the present study shows that limonin may activate the Nrf2/HO-1/NF-κB pathway to alleviate OA, making it a candidate therapeutic agent for OA.

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“…The literature data suggest that the Cyp2e1 mRNA expression in the liver of experimental animals chronically treated with ethanol alone [38] and ethanol combined with HFD [39] was up-regulated up to 4-5-fold. In our study, chronic alcohol intoxication for 8 weeks induced pronounced oxidative stress, elevating not only the expression of Cyp2e1 on the mRNA level (2.5 fold), but also iNos encoding the protein that produces reactive nitrogen species involved in the pathogenesis of alcoholic liver injury [40].…”

Section: Discussionmentioning

confidence: 99%

“…Many authors emphasize the important role of the Nrf2/HO-1 pathway in hepatoprotection against ethanol-induced liver damage. Different herbal substances having antioxidant activity, such as the flavonoids quercetin [47], curcumin, and baicalin [48], and the pentacyclic-triterpene compound taraxasterol [39], ameliorate ethanol-induced liver injury via the Nrf2/HO-1 pathway. In this regard, the expression of HO-1 increases as a result of Nrf2 factor activation.…”

Section: Discussionmentioning

confidence: 99%

Chlorogenic Acid Protects against Advanced Alcoholic Steatohepatitis in Rats via Modulation of Redox Homeostasis, Inflammation, and Lipogenesis

et al. 2021

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The aim of this study was to evaluate the therapeutic effects of chlorogenic acid (CGA) in rats with advanced alcoholic steatohepatitis. The rats were fed on a high-fat diet and gavaged with ethanol (4 g/kg) for 8 weeks. The livers of ethanol-treated rats showed steatosis; necrosis and mononuclear infiltration; and significant upregulation of the mRNA expression of the prooxidant (Cyp2e1, iNos), lipogenic (Srebp1, Acc), proinflammatory (Tlr4, Nf-κb, TnfA, Il-1B, and Il-6), and profibrogenic (TgfB, Col1, VegfA) genes. Simultaneously, a downregulation of level of Sod and Nrf2 was observed, which was accompanied by increased serum transaminase, TnfA, and serum and liver triglycerides levels. CGA administration (40 and 80 mg/kg, 8 weeks) to ethanol-fed group reduced the liver expression levels of Cyp2e1 and iNos, whereas it markedly enhanced the expression of Sod, Nrf2, and Ho-1. CGA at both doses downregulated the expressions of lipogenic, proinflammatory, and profibrogenic genes, while the expression of Tlr4 was lowered only after the higher dose of CGA. The higher dose of CGA efficiently prevented the progression of alcohol-induced steatosis and reduced inflammation through regulation of the expression of genes encoding the proteins involved in the Tlr4/Nf-κB signaling pathway and fibrosis. The study revealed hepatoprotective and anti-inflammatory effects of CGA through the regulation of expression of genes encoding Cyp2e1/Nrf2 involved in oxidative stress modulation. These results demonstrate CGA as a therapeutic candidate for the prevention and treatment of alcoholic steatohepatitis.

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Effects of taraxasterol against ethanol and high-fat diet-induced liver injury by regulating TLR4/MyD88/NF-κB and Nrf2/HO-1 signaling pathways

Cited by 20 publications

References 40 publications

Water extract ofFerula lehmanni Boiss.prevents high-fat diet-induced overweight and liver injury by modulating the intestinal microbiota in mice

Water extract ofFerula lehmanni Boiss.prevents high-fat diet-induced overweight and liver injury by modulating the intestinal microbiota in mice

Limonin Inhibits IL‐1β‐Induced Inflammation and Catabolism in Chondrocytes and Ameliorates Osteoarthritis by Activating Nrf2

Chlorogenic Acid Protects against Advanced Alcoholic Steatohepatitis in Rats via Modulation of Redox Homeostasis, Inflammation, and Lipogenesis

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