Thymoquinone attenuates liver fibrosis via PI3K and TLR4 signaling pathways in activated hepatic stellate cells

Bai, Ting; Lian, Li-Hua; Wu, Yan-Ling; Wan, Ying; Nan, Ji‐Xing

doi:10.1016/j.intimp.2012.12.020

Cited by 105 publications

(78 citation statements)

References 35 publications

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“…NF-κB p65 is a central signaling factor for hepatic fibrosis in control of the generation of PICs [38]. As the critical molecules, PI3K/Akt/mTOR pathway mediate protein expression and proliferation through the inhibition of DNA synthesis in HSCs [39] and play the critical role in transmitting signaling in hepatic fibrosis [40]. The suppression of mTOR/p70S6K signaling results in the inhibition of type I collagen accumulation and HSC proliferation [41].…”

Section: Discussionmentioning

confidence: 99%

Astragaloside Alleviates Hepatic Fibrosis Function via PAR2 Signaling Pathway in Diabetic Rats

Wang

Xiang

et al. 2017

Cell Physiol Biochem

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Background/Aims: Astragaloside (AGS) extracted from radix astragalin (Huangqi) has been considered to be beneficial to liver diseases. In this study, we examined the role played by AGS in alleviating hepatic fibrosis function via protease-activated receptor-2 (PAR2) mechanisms. We hypothesized that AGS affects PAR2 signaling pathway thereby improving hepatic function in rats with hepatic fibrosis induced by carbon tetrachloride (CCl₄). We further hypothesized that AGS attenuates impaired hepatic function evoked by CCl₄ to a greater degree in diabetic animals. Methods: ELISA and Western Blot analysis were used to examine PAR2 signaling pathway in diabetic CCl₄-rats and non-diabetic CCl₄-rats. Results: AGS inhibited the protein expression of PAR2 and its downstream pathway PKA and PKCɛ in CCl₄-rats. Notably, the effects of AGS were greater in CCl₄-rats with diabetes. AGS also significantly attenuated the CCl₄-induced upregulations of pro-inflammatory cytokines, namely interleukin-1β, interleukin-6 and tumor necrosis factor-α accompanied with decreases of collagenic parameters such as hexadecenoic acid, laminin and hydroxyproline. Additionally, AGS improved the CCl₄-induced exaggerations of liver index and functions including alanine aminotransferase, aspartate aminotransferase. Moreover, TGF-β1, a marker of hepatic fibrosis, was increased in CCl₄-rats and AGS inhibited increases in TGF-β1 induced by CCl₄. Conclusions: AGS alleviates hepatic fibrosis by inhibiting PAR2 signaling expression and its effects are largely enhanced in diabetic animals. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of hepatic fibrosis; and results of our study are likely to shed light on strategies for application of AGS because it has potentially greater therapeutic effectiveness for hepatic fibrosis in diabetes.

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Section: Discussionmentioning

confidence: 99%

Astragaloside Alleviates Hepatic Fibrosis Function via PAR2 Signaling Pathway in Diabetic Rats

Wang

Xiang

et al. 2017

Cell Physiol Biochem

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“…PI3K/AKT and mitogen-activated protein kinase/ERK are important signaling pathways for numerous cellular functions, including proliferation, survival, adhesion and migration (17)(18)(19)(20)(21)(22). It has been reported that pretreatment of cells with TNFR2 neutralizing antibody could effectively block the activation of PI3K/AKT and ERK signal pathway in cholangiocarcinoma cells (11).…”

Section: Discussionmentioning

confidence: 99%

Tumor necrosis factor receptor 2 promotes growth of colorectal cancer via the PI3K/AKT signaling pathway

Zhao

Liu

2016

Oncology Letters

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Abstract. Tumor necrosis factor receptor 2 (TNFR2) is the receptor for tumor necrosis factor α (TNF-α). TNFR2 differs from tumor necrosis factor 1 (TNFR1) in various ways and is mainly expressed in hematopoietic and endothelial cells. However, studies about its functions in tumors are limited. The contributions of TNFR2 in colorectal cancer (CRC) remain unknown. In the present study, it was found that TNFR2 was positively associated with Ki67 expression in CRC tissues using immunohistochemistry (IHC), and western blot analysis found that Ki67 was upregulated by overexpressing TNFR2 in SW1116 cells and inhibited by silencing TNFR2 in HT29 cells. Methyl thiazolyl tetrazolium assay found that growth of SW1116 cells overexpressing TNFR2 was significantly increased compared with the control group and that the growth of HT29 cells subsequent to silencing TNFR2 was significantly decreased compared with the control group. Clone formation assay found that more clones were formed in SW1116 cells overexpressing TNFR2 than the control group, and less clones formed in HT29 cells subsequent to silencing TNFR2 than the control group. In addition, western blot analysis found that phosphorylation of protein kinase B (AKT) was activated subsequent to overexpressing TNFR2 in SW1116 cells, and inhibited following silencing of TNFR2 in HT29 cells. Additionally, treatment using LY294002 significantly abrogated the promotion of Ki67 expression, growth and clone formation abilities induced by TNFR2 overexpression in SW1116 cells. All the results suggest that TNFR2 can significantly promote CRC growth via the phosphoinositide 3-kinase/AKT signaling pathway; this provides evidential support for taking TNFR2 as a new target for CRC treatment.

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“…(Ranunculaceae) is a medicinal plant also known as black caraway, black cumin, Habbatul Barakah or and Kalonji seed, is widely used in the treatment of various ailments such as bronchial asthma, cough, diarrhoea, abdominal pain, and dyslipidemia [9]. N. sativa oil (NSO] exhibits pharmacological activities including the ability to act as a chelating agent [10], antioxidant and antiinflammatory [11], immunomodulatory and antitumor substances [12].…”

Section: Introductionmentioning

confidence: 99%

Protective Effect of Nigella Sativa (Black Caraway (Oil on Oral Dichlorvos Induced Hematological, Renal and Nonspecific Immune System Toxicity in Wistar Rats

Ajao

Sansa

Imam

et al. 2017

IJT

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Thymoquinone attenuates liver fibrosis via PI3K and TLR4 signaling pathways in activated hepatic stellate cells

Cited by 105 publications

References 35 publications

Astragaloside Alleviates Hepatic Fibrosis Function via PAR2 Signaling Pathway in Diabetic Rats

Astragaloside Alleviates Hepatic Fibrosis Function via PAR2 Signaling Pathway in Diabetic Rats

Tumor necrosis factor receptor 2 promotes growth of colorectal cancer via the PI3K/AKT signaling pathway

Protective Effect of Nigella Sativa (Black Caraway (Oil on Oral Dichlorvos Induced Hematological, Renal and Nonspecific Immune System Toxicity in Wistar Rats

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