Effects of corilagin on alleviating cholestasis via farnesoid X receptor‐associated pathways <i>in vitro</i> and <i>in vivo</i>

Yang, Fan; Wang, Yao; Li, Gang; Xue, Juan; Chen, Zhilin; Jin, Feng; Luo, Lei; Zhou, Xuan; Ma, Qian; Cai, Xin; Li, Huarong; Zhao, Lei

doi:10.1111/bph.14126

Cited by 41 publications

(16 citation statements)

References 62 publications

(71 reference statements)

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“…In vitro , we assessed the viability of RAW264.7 cells pretreated with emodin at different concentrations (3.75, 7.5, 15, 30, 60, 120, 240, and 480 μg/ml) after 24 h. Based on the CCK-8 assay, the 75% viability of emodin concentration was calculated as 65.07 μg/ml. For convenience, we approximated high concentration as 60 μg/ml, middle concentration as 30 μg/ml, and low concentration as 15 μg/ml ( Yang et al, 2018 ). As shown in Figure 1A , the CCK-8 assay showed the viability of RAW264.7 cells.…”

Section: Resultsmentioning

confidence: 99%

“…After 24 h, the cells were harvested to detect the level of the TLR4 downstream signaling molecule TRAF-6 by western blotting to determine the optimal dosage of LPS. RAW264.7 cells were divided into a normal group, a model group, a DEX (0.5 μg/ml, diluted in PBS medium) group ( Yang et al, 2018 ) and emodin (15, 30, and 60 μg/ml, dissolved in DMSO and then diluted in PBS medium to a final DMSO concentration less than 0.1%) groups. After placing the cells in 6-well plates overnight and culturing to 80% density, LPS (1 μg/ml) was added to the wells for 2 h, and then DXM and emodin were added as described above.…”

Section: Methodsmentioning

confidence: 99%

“…Thirty mice were randomly divided into six groups: the normal group, model group, emodin groups (20, 40, and 80 mg/kg/day; Ding et al, 2008 ), and DEX group (1.8 mg/kg/day; Yang et al, 2018 ). Before establishing the ALI model, emodin (20, 40, or 80 mg/kg/day; at a concentration of 1, 2, or 4 mg/ml) and DEX (1.8 mg/kg/d, at a concentration of 90 μg/ml) were intragastrically administered to the mice in corresponding groups for 30 min.…”

Section: Methodsmentioning

confidence: 99%

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Emodin Attenuates Lipopolysaccharide-Induced Acute Liver Injury via Inhibiting the TLR4 Signaling Pathway in vitro and in vivo

et al. 2018

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Aims: Emodin is an anthraquinone with potential anti-inflammatory properties. However, the possible molecular mechanisms and protective effects of emodin are not clear. The objective of this study was to investigate the possible molecular mechanisms and protective effects of emodin on lipopolysaccharide (LPS)-induced acute liver injury (ALI) via the Toll-like receptor 4 (TLR4) signaling pathway in the Raw264.7 cell line and in Balb/c mice.Methods: This study established an inflammatory cellular model and induced an ALI animal model. TLR4 was overexpressed by lentivirus and downregulated by small interfering RNA (siRNA) technology. The mRNA and protein levels of TLR4 and downstream molecules were detected in cells and liver tissue. The tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 levels in supernatant and serum were determined by ELISA. The distribution and expression of mannose receptor C type 1 (CD206) and arginase 1 (ARG1) in the liver were tested by immunofluorescence. Mouse liver function and histopathological observations were assessed.Results: Administration of emodin reduced the protein and/or mRNA levels of TLR4 and its downstream molecules following LPS challenge in Raw264.7 cells and in an animal model. Additionally, emodin suppressed the expression of TNF-α and IL-6 in cell culture supernatant and serum. The inhibitory effect of emodin was also confirmed in RAW264.7 cells, in which TLR4 was overexpressed or knocked down. Additionally, ARG1 and CD206 were elevated in the emodin groups. Emodin also decreased serum ALT and AST levels and alleviated the liver histopathological damage induced by LPS.Conclusion: Emodin showed excellent hepatoprotective effects against LPS-induced ALI, possibly by inhibiting TLR4 signaling pathways.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Emodin Attenuates Lipopolysaccharide-Induced Acute Liver Injury via Inhibiting the TLR4 Signaling Pathway in vitro and in vivo

et al. 2018

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“…This method is an improvement on guidewire-induced injury method that was mentioned in published articles ( 28 , 29 ). According to our previous study ( 30 ), we designed a preliminary experiment to verify the concentrations and mortality curve ( Supplemental Figure 3 ). Then, we treated rats with high (40 mg/kg·day), medium (20 mg/kg·day), or low (10 mg/kg·day) concentrations of corilagin in corilagin groups, aspirin (20 mg/kg·day) in the aspirin group, or physiologic (0.9%) saline in the control group, sham-operation group, and model group, by means of intragastric administration for 1 month.…”

Section: Methodsmentioning

confidence: 99%

Corilagin Ameliorates Atherosclerosis in Peripheral Artery Disease via the Toll-Like Receptor-4 Signaling Pathway in vitro and in vivo

Wang

Chen

et al. 2020

Front. Immunol.

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We investigated if corilagin can ameliorate or reverse atherosclerotic development via the toll-like receptor 4 (TLR4) signaling pathway in vitro and in vivo. Ana-1 cells or mouse peritoneal macrophages (MPMs) were stimulated with oxidized low-density lipoprotein followed by corilagin treatment. TLR4 expression in Ana-1 cells was upregulated by lentiviral transduction and downregulated by small interfering RNA. Peripheral blood mononuclear cells (PBMCs), plasma samples, and femoral arteries were collected from rats exhibiting peripheral artery disease (PAD). mRNA and protein expression of TLR4 and downstream molecules were decreased significantly by corilagin treatment in Ana-1 cells, MPMs, and rat PBMCs, and the reduction remained irrespective of downregulation or upregulation of TLR4 expression in Ana-1 cells. Corilagin also exerted a prominent effect on changes in plasma levels of cytokines and the pathologic manifestation of atherosclerosis in femoral arteries. Corilagin could ameliorate the development of atherosclerotic plaques by inhibiting the TLR4 signaling pathway in monocyte/macrophages and reduce the release of proinflammatory cytokines. This study provides a new therapeutic target and new niche targeting drug to oppose atherosclerosis and reveals the enormous potential of corilagin for control of PAD in humans.

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“…Corilagin, as one of the active ingredients of Erodium stephaniahum, can significantly improve serum liver function indexes of cholestasis rats, and regulate antioxidant and anti-inflammatory mechanisms (Jin et al, 2013). It can also activate FXR, SHP1, SHP2, UGT2B4, BSEP, MRP2, and SULT2A1 expression, down-regulate CYP7A1 and NTCP protein expression to improve cholestasis (Yang et al, 2018). Studies have shown that auraptene, the active ingredient in Citrus reticulata, reduces bile acid synthesis by activating the expression of FXR to reduce CYP7A1 and CYP8B1, and increases bile acid transporters (such as BSEP and MRP2) to increase bile acid transport (Gao et al, 2017).…”

Section: Main Bile Acid Receptor Drugs Fxr Agonistsmentioning

confidence: 99%

Mechanism of Hydrophobic Bile Acid-Induced Hepatocyte Injury and Drug Discovery

Wei

Yan

2020

Front. Pharmacol.

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Cholestatic liver disease is caused by the obstruction of bile synthesis, transport, and excretion in or outside the liver by a variety of reasons. Long-term persistent cholestasis in the liver can trigger inflammation, necrosis, or apoptosis of hepatocytes. Bile acid nuclear receptors have received the most attention for the treatment of cholestasis, while the drug development for bile acid nuclear receptors has made considerable progress. However, the targets regulated by bile acid receptor drugs are limited. Thus, as anticipated, intervention in the expression of bile acid nuclear receptors alone will not yield satisfactory clinical results. Therefore, this review comprehensively summarized the literature related to cholestasis, analyzed the molecular mechanism that bile acid damages cells, and status of drug development. It is hoped that this review will provide some reference for the research and development of drugs for cholestasis treatment in the future.

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Effects of corilagin on alleviating cholestasis via farnesoid X receptor‐associated pathways in vitro and in vivo

Abstract: Corilagin exerts a protective effect in hepatocytes and can prevent the deleterious activities of intrahepatic cholestasis by stimulating FXR-associated pathways.

Cited by 41 publications

References 62 publications

Emodin Attenuates Lipopolysaccharide-Induced Acute Liver Injury via Inhibiting the TLR4 Signaling Pathway in vitro and in vivo

Emodin Attenuates Lipopolysaccharide-Induced Acute Liver Injury via Inhibiting the TLR4 Signaling Pathway in vitro and in vivo

Corilagin Ameliorates Atherosclerosis in Peripheral Artery Disease via the Toll-Like Receptor-4 Signaling Pathway in vitro and in vivo

Mechanism of Hydrophobic Bile Acid-Induced Hepatocyte Injury and Drug Discovery

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