Emodin ameliorated lipopolysaccharide-induced fulminant hepatic failure by blockade of TLR4/MD2 complex expression in D-galactosamine-sensitized mice

Yin, Xinru; Gong, Xia; Jiang, Rong; Kuang, Ge; Wang, Bin; Zhang, Li; Xu, Guohai; Wan, Jingyuan

doi:10.1016/j.intimp.2014.08.018

Cited by 27 publications

(17 citation statements)

References 31 publications

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“…Thus, there is an urgent need for new evidence of the efficiency of herbs in the treatment of liver diseases. Recently, some pure compounds extracted from herbs such as quercetin and emodin have been demonstrated to have favorable protective effects in FHF animal experiments (Peng et al, ; Yin et al, ). In the previous reported studies, pretreatment with Tec showed anti‐inflammatory effects in an acute lung injury model and hepatoprotective effects in chemical and oxidative models (H. U. Lee et al, ; H. W. Lee et al, ; Ma et al, ).…”

Section: Discussionmentioning

confidence: 99%

Tectorigenin protects against experimental fulminant hepatic failure by regulating the TLR4/mitogen‐activated protein kinase and TLR4/nuclear factor‐κB pathways and autophagy

Zhang

Zhao

Fan

et al. 2019

Phytotherapy Research

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Tectorigenin has received attention due to its antiproliferation, anti‐inflammatory, and antioxidant activities. In this study, we investigated the effects of tectorigenin on lipopolysaccharide (LPS)/D‐galactosamine(D‐GalN)‐induced fulminant hepatic failure (FHF) in mice and LPS‐stimulated macrophages (RAW 264.7 cells). Pretreatment with tectorigenin significantly reduced the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), histological injury, apoptosis, and the mortality of FHF mice, by suppressing the production of inflammatory cytokines such as TNF‐α and IL‐6. Tectorigenin also suppressed the activation of the inflammatory response in LPS‐stimulated RAW 264.7 cells. Tectorigenin‐induced protection is mediated through its mitigation of TLR4 expression, inhibition of mitogen‐activated protein kinase (MAPK) and nuclear factor‐κB (NF‐κB) pathway activation, and promotion of autophagy in FHF mice and LPS‐stimulated RAW 264.7 cells. Therefore, tectorigenin has therapeutic potential for FHF in mice via the regulation of TLR4/MAPK and TLR4/NF‐κB pathways and autophagy.

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Section: Discussionmentioning

confidence: 99%

Tectorigenin protects against experimental fulminant hepatic failure by regulating the TLR4/mitogen‐activated protein kinase and TLR4/nuclear factor‐κB pathways and autophagy

Zhang

Zhao

Fan

et al. 2019

Phytotherapy Research

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“…Yin et al showed that emodin could effectively prevent LPS‐induced fulminant hepatic failure, and this beneficial effect might occur by the blockade of TLR4/MD2 complex expression on the cell surface of macrophages, which could lead to the deactivation of the p38 MAPK and NF‐κB signalling pathways and inhibition of TNF‐α production (Yin et al ., ). Similarly, emodin treatment protected against concanavalin A‐induced liver injury by inhibiting the activation of the p38 MAPK and NF‐κB signalling pathways in CD4+ T cells and macrophages, indicating that emodin can be applied as a potential candidate for the prevention and intervention of clinical fulminant hepatic failure (Xue et al ., ).…”

Section: Pharmacologymentioning

confidence: 97%

Emodin: A Review of its Pharmacology, Toxicity and Pharmacokinetics

Dong

Yin

et al. 2016

Phytotherapy Research

513

365

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Emodin is a natural anthraquinone derivative that occurs in many widely used Chinese medicinal herbs, such as Rheum palmatum, Polygonum cuspidatum and Polygonum multiflorum. Emodin has been used as a traditional Chinese medicine for over 2000 years and is still present in various herbal preparations. Emerging evidence indicates that emodin possesses a wide spectrum of pharmacological properties, including anticancer, hepatoprotective, antiinflammatory, antioxidant and antimicrobial activities. However, emodin could also lead to hepatotoxicity, kidney toxicity and reproductive toxicity, particularly in high doses and with long-term use. Pharmacokinetic studies have demonstrated that emodin has poor oral bioavailability in rats because of its extensive glucuronidation. This review aims to comprehensively summarize the pharmacology, toxicity and pharmacokinetics of emodin reported to date with an emphasis on its biological properties and mechanisms of action. Copyright © 2016 John Wiley & Sons, Ltd.

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“…The inflammatory process leads to parenchymal damage, which progresses to fibrosis, liver cancer, and, occasionally, SALF[17]. Metabolites of hepatotoxic drugs bind to a toll-like receptor 4 (TLR4) complex that activates nuclear factor kappa B (NFκB), triggering the production of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6, and modulation of anti-inflammatory cytokines such as IL-10[12,14,17,18]. Furthermore, it can stimulate production of the enzymes cyclooxygenase-2 (COX-2) and iNOS, both of which act as inflammatory mediators[19].…”

Section: Introductionmentioning

confidence: 99%

Protective action of glutamine in rats with severe acute liver failure

Schemitt¹,

Hartmann²,

Colares³

et al. 2019

WJH

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BACKGROUND Severe acute liver failure (SALF) is a rare, but high-mortality, rapidly evolving syndrome that leads to hepatocyte degeneration with impaired liver function. Thioacetamide (TAA) is a known xenobiotic, which promotes the increase of the formation of reactive oxygen species. Erythroid 2-related factor 2 (Nrf2) activates the antioxidant protection of cells. Studies have evidenced the involvement of inflammatory mediators in conditions of oxidative stress. AIM To evaluate the antioxidant effects of glutamine on Nrf2 activation and NFκB-mediated inflammation in rats with TAA-induced IHAG. METHODS Male Wistar rats ( n = 28) were divided into four groups: control, control+glutamine, TAA, and TAA + glutamine. Two TAA doses (400 mg/kg) were administered intraperitoneally, 8 h apart. Glutamine (25 mg/kg) was administered at 30 min, 24 h, and 36 h. At 48 h, blood was collected for liver integrity analysis [aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP)]. The liver was harvested for histology and assessment of oxidative stress [thiobarbituric acid-reactive substances (TBARS), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione (GSH), Nrf2, Kelch-like ECH-associated protein 1 (Keap1), NADPH quinone oxidoreductase1 (NQO1), superoxide dismutase (SOD)] and inflammatory process. RESULTS TAA caused disruption of the hepatic parenchyma, with inflammatory infiltration, massive necrosis, and ballooning degeneration. Glutamine mitigated this tissue damage, with visible regeneration of hepatic parenchyma; decreased TBARS ( P < 0.001), GSH ( P < 0.01), IL-1β, IL6, and TNFα levels ( P < 0.01) in hepatic tissue; and decreased blood levels of AST, ALT, and ALP ( P < 0.05). In addition, CAT, GPx, and GST activities were restored in the glutamine group ( P < 0.01, P < 0.01, and P < 0.001, respectively vs TAA alone). Glutamine increased expression of Nrf2 ( P < 0.05), NQO1, and SOD ( P < 0.01), as well as levels of IL-10 ( P < 0.001), while decreasing expression of Keap1, TLR4, NFκB ( P < 0.001), COX-2 and iNOS, ( P < 0.01), and reducing NO 2 and NO 3 levels ( P < 0.05). CONCLUSION In the TAA experimental model of IHAG, glutamine activated the Nrf2 pathway, thus promoting antioxidant protection, and blunted the NFκB-mediated pathway, reducing inflammation.

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Emodin ameliorated lipopolysaccharide-induced fulminant hepatic failure by blockade of TLR4/MD2 complex expression in D-galactosamine-sensitized mice

Cited by 27 publications

References 31 publications

Tectorigenin protects against experimental fulminant hepatic failure by regulating the TLR4/mitogen‐activated protein kinase and TLR4/nuclear factor‐κB pathways and autophagy

Tectorigenin protects against experimental fulminant hepatic failure by regulating the TLR4/mitogen‐activated protein kinase and TLR4/nuclear factor‐κB pathways and autophagy

Emodin: A Review of its Pharmacology, Toxicity and Pharmacokinetics

Protective action of glutamine in rats with severe acute liver failure

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