Chlorogenic acid ameliorated concanavalin A-induced hepatitis by suppression of Toll-like receptor 4 signaling in mice

Yuan, Yinglin; Gong, Xia; Zhang, Li; Jiang, Rong; Yang, Jian; Wang, Bin; Wan, Jingyuan

doi:10.1016/j.intimp.2017.01.017

Cited by 47 publications

(30 citation statements)

References 48 publications

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“…Accordingly, great attraction is paid to the use of natural products as new therapeutic and preventive drugs against immune-mediated hepatic injury due to their high efficiency, high safety, and low cost. Some compounds of natural products have been investigated to possess protective effects on immune hepatic injury [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Taraxasterol from Taraxacum prevents concanavalin A-induced acute hepatic injury in mice via modulating TLRs/NF-κB and Bax/Bc1-2 signalling pathways

Sang

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Immune hepatic injury is a liver disease closely related to an immune imbalance of T cells and macrophages. Our previous series of studies have demonstrated that taraxasterol isolated from Taraxacum possesses great anti-inflammatory and immunomodulatory effects in vivo and in vitro. In this study, we explored the preventive effects of taraxasterol and its underlying mechanisms on concanavalin A (Con A)-induced acute hepatic injury in mice. It was found that treatment with taraxasterol significantly decreased the Con A-induced increase of liver index, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and hepatic malondialdehyde (MDA) levels, and increased the Con A-induced decrease of hepatic glutathione (GSH) and superoxide dismutase (SOD) production. Taraxasterol also significantly inhibited the release of pro-inflammatory cytokines tumour necrosis factor-a (TNF-a), interleukin-6 (IL-6), IL-1b, interferon-c (IFN-c) and IL-4. In addition, treatment with taraxasterol alleviated the hepatic histopathological injury and apoptosis induced by Con A. Furthermore, taraxasterol dramatically down-regulated the expressions of T toll-like receptor (TLR2), TLR4 and nuclear factor-jappaB (NF-jB) p65, and decreased the expression ratio of Bax/Bc1-2 in hepatic tissues. These findings suggest that taraxasterol prevents Con A-induced acute hepatic injury in mice by inhibiting TLRs/NF-jB inflammatory signalling pathway and promoting Bax/Bc1-2 anti-apoptotic signalling pathway.

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Section: Introductionmentioning

confidence: 99%

Taraxasterol from Taraxacum prevents concanavalin A-induced acute hepatic injury in mice via modulating TLRs/NF-κB and Bax/Bc1-2 signalling pathways

Sang

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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“…As one of the earliest discovered pattern recognition receptors, TLRs are involved in inflammatory response and NF-κB activation [28,31]. Moreover, Con A stimulates the expression of TLR2, TLR4, and TLR9 and downstream pathways in liver tissue, resulting in the release of numerous proinflammatory factors [12,13].…”

Section: Effect Of Serotonin On Intrahepatic Tlr Signalingmentioning

confidence: 99%

“…As one of the earliest identified pattern recognition receptors (PRRs), toll-like receptors (TLRs) have been widely studied and are involved in the regulation of inflammatory and apoptotic responses [11]. Previous studies have shown that Con A can stimulate the expression of TLRs and downstream pathways in liver tissue, leading to the initiation of inflammatory response [12,13]. After binding ligand, TLRs stimulate nuclear factor kappa B (NF-κB) activation and trigger the release of various inflammatory mediators, such as tumor necrosis-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-17 (IL-17) [11,14].…”

Section: Introductionmentioning

confidence: 99%

The Role of Serotonin in Concanavalin A-Induced Liver Injury in Mice

Pang

Jin

et al. 2020

Oxidative Medicine and Cellular Longevity

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Serotonin is involved in the pathological processes of several liver diseases via the regulation of inflammatory response and oxidative stress. We aimed to investigate the role of serotonin in Concanavalin A- (Con A-) induced acute liver injury (ALI). ALI was induced in C57B/6 wild-type (WT) mice and tryptophan hydroxylase 1 (TPH1) knockout mice through tail vein injection of Con A (15 mg/kg body weight). Another group of TPH1 knockout ALI mice was supplied with 5-hydroxytryptophan (5-HTP) in advance to recover serotonin. The blood and liver tissues of mice were collected in all groups. Markedly increased serum levels of serotonin were identified after the injection of Con A. Increased serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and stronger hepatic tissue pathology were detected, suggesting that serotonin could mediate Con A-induced liver damage. Serotonin significantly facilitated the release of serum and intrahepatic inflammatory cytokines, including interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-17A (IL-17A), interferon-gamma (IFN-γ), and tumor necrosis-alpha (TNF-α), after the administration of Con A. In addition, serotonin significantly increased the intrahepatic levels of oxidative stress markers malonaldehyde (MDA), myeloperoxidase (MPO), and nitric oxide (NO) and decreased antioxidant stress indicator glutathione (GSH) in Con A-treated mice. Additionally, serotonin promoted hepatocyte apoptosis and autophagy based on B-cell lymphoma-2 (Bcl-2), Bcl-2-asociated X protein (Bax), and Beclin-1 levels and TUNEL staining. More importantly, serotonin activated nuclear factor kappa B (NF-κB) and upregulated the hepatic expressions of high mobility group protein B1 (HMGB1), toll-like receptor-4 (TLR4), and downstream molecules in Con A-mediated liver injury. Serotonin 2A receptor was upregulated in liver tissue after Con A injection, and serotonin 2A receptor antagonist Ketanserin protected against Con A-induced hepatitis. These results indicated that serotonin has the potential to aggravate Con A-induced ALI via the promotion of inflammatory response, oxidative stress injury, and hepatocyte apoptosis and the activation of hepatic HMGB1-TLR signaling pathway and serotonin 2A receptor.

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“…CGA and its derivatives show inhibition in the fight against hepatitis B and hepatitis C (6,7). After a thorough study of the antimicrobial, antiviral and anti-inflammatory effects of CGA, it has been proved that some important signaling pathways involved in these processes (8)(9)(10). Among them, the value of NF-kB pathway widely recognized.…”

Section: Introductionmentioning

confidence: 99%

Annexin a2 as a target protein for chlorogenic acid in human lung cancer A549 cells

Wang¹,

Du²,

Chen³

2020

Preprint

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Running title：Drug target of chlorogenic acid. AbstractChlorogenic acid, an important active component of coffee with anti-tumor activities, has been found for many years.However, the lack of understanding about its target proteins greatly limits the exploration of its anti-tumor molecular mechanism and clinical application. Here, in vitro and animal experiments showed that chlorogenic acid had a significant inhibitory effect on the proliferation of A549 cells. Using the spontaneous fluorescence characteristic of chlorogenic acid to screen the target proteins cleverly to avoid the problem of chemical modification increasing false positive, we identify and verify annexin A2 (ANXA2) as a covalent binding target of chlorogenic acid in A549 cells.Then, we discover that chlorogenic acid as an inhibitor of the binding of ANXA2 to p50 subunit inhibited the expression of downstream anti-apoptotic genes cIAP1 and cIAP2 of NF-κB signaling pathway in A549 cells in vitro and vivo. Moreover, we find chlorogenic acid hindered the binding of ANXA2 and actin maybe involved in the impediment of tumor cell cycle and migration. Thus, this work demonstrates that chlorogenic acid, as a binding ligand of ANXA2, decrease the expression of NF-κB downstream anti-apoptotic genes, inhibiting the proliferation of A549 cells in vivo and vitro.

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Chlorogenic acid ameliorated concanavalin A-induced hepatitis by suppression of Toll-like receptor 4 signaling in mice

Cited by 47 publications

References 48 publications

Taraxasterol from Taraxacum prevents concanavalin A-induced acute hepatic injury in mice via modulating TLRs/NF-κB and Bax/Bc1-2 signalling pathways

Taraxasterol from Taraxacum prevents concanavalin A-induced acute hepatic injury in mice via modulating TLRs/NF-κB and Bax/Bc1-2 signalling pathways

The Role of Serotonin in Concanavalin A-Induced Liver Injury in Mice

Annexin a2 as a target protein for chlorogenic acid in human lung cancer A549 cells

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