Casticin attenuates liver fibrosis and hepatic stellate cell activation by blocking TGF-β/Smad signaling pathway

Zhou, Ling; Dong, Xiaoying; Wang, Linlin; Shan, Lanlan; Li, Ting; Xu, Wei; Ding, Yan; Lai, Mingqiang; Lin, Xiaojun; Dai, Meng; Bai, Xiaochun; Jia, Chunhong; Zheng, Hongliang

doi:10.18632/oncotarget.17453

Cited by 45 publications

(28 citation statements)

References 41 publications

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“…And accordant with our results, several studies that relied on low levels of casticin exerted different effects such as scavenging ROS or blocking TGFβ/Smad signaling (Lee et al, ; Zhou et al, ). This discordance may be due to the different reactions triggered by different concentration of casticin in cells.…”

Section: Discussionsupporting

confidence: 91%

Casticin prevents DSS induced ulcerative colitis in mice through inhibitions of NF‐κB pathway and ROS signaling

Yin

et al. 2018

Phytotherapy Research

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Casticin, a compound purified from the Chinese herb Viticis Fructus, has been proven effective in preventing tumor progression in previous studies. Ulcerative colitis (UC) is a common inflammatory bowel disease that affects millions of people worldwide, but no effective and safe drugs are available. In this study, we aimed to study how did casticin affect UC by evaluating its effects on dextran sulfate sodium (DSS)-induced colitis in mice. Our data suggested that casticin attenuated body weight loss, colon length shortening, and pathological damage in the colon of DSS-treated mice. Casticin decreased reactive oxygen species level and chemocytokines (IL-1β, IL-6, TNF-α) productions in colon tissue. The decreased reactive oxygen species level and suppressed proinflammatory cytokines productions were also confirmed in casticin-treated LPS-stimulated RAW264.7 cells and hydrogen peroxide-treated CACO-2 cells in vitro. Mechanistically, casticin treatment prevented the profound activation of AKT signaling caused by DSS administration. And casticin inhibited the productions of proinflammatory chemocytokines through downregulating AKT/NF-κB pathway in macrophages. Meanwhile, data revealed that casticin increased expressions of endogenous antioxidants peroxiredoxin 3 and MnSOD were through activation in FOXO3α signaling by downregulating AKT signaling in colon epithelium cells. Our findings demonstrated that casticin alleviated DSS-induced UC by increasing the antioxidant enzyme peroxiredoxin 3 and MnSOD expressions, and decreasing the production of proinflammatory chemocytokines through inhibition of AKT signaling.

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Section: Discussionsupporting

confidence: 91%

Casticin prevents DSS induced ulcerative colitis in mice through inhibitions of NF‐κB pathway and ROS signaling

Yin

et al. 2018

Phytotherapy Research

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“…Previous studies have reported the involvement of the TGF-β1/Smad pathway in fibrosis diseases. For example, Zhou et al revealed that casticin attenuated liver fibrosis by blocking the TGF-β/Smad signaling pathway (36). A study by Choi et al reported that capsaicin was able to ameliorate hepatic fibrosis by inhibiting the TGF-β1/Smad pathway via peroxisome proliferator-activated receptor-γ activation (37).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑326 inhibits endometrial fibrosis by regulating TGF‑β1/Smad3 pathway in intrauterine adhesions

2018

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Intrauterine adhesion (IUA), characterized by endometrial fibrosis, may lead to infertility and recurrent pregnancy loss. At present, there is no ideal therapy for IUA. Recent findings have revealed that microRNAs (miRNAs) have a decisive role in the regulation of fibrosis. The aim of the present study was to investigate the molecular mechanism of miRNAs in endometrial fibrosis. The present study compared the expression profiles of miRNAs between endometrial tissues from patients with IUA and normal endometrial tissues using microarray analysis. Validation of miR‑326 level in endometrial tissues was performed using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). Subsequently, the effects of miR‑326 on fibrotic markers including α‑smooth muscle actin (α‑SMA), collagen type I α 1 chain (COL1A1), transforming growth factor‑β1 (TGF‑β1) and fibronectin (FN), were evaluated in endometrial tissues and endometrial stromal cells (ESCs) from patients with IUA. Additional bioinformatics analysis, luciferase reporter assays, RT‑qPCR and western blotting were performed to identify target genes. Additionally, the expression levels of TGF‑β1, p‑Smad3 and Smad3 were quantified to determine whether the anti‑fibrotic role of miR‑326 was associated with the activity of the TGF‑β1/Smad3 signaling pathway. The present study determined that miR‑326 was downregulated in endometrial tissues from patients with IUA and miR‑326 levels were inversely correlated with the expression of TGF‑β1, α‑SMA, COL1A1 and FN. Additional findings revealed that overexpression of miR‑326 inhibited endometrial fibrosis by downregulating these pro‑fibrotic genes. TGF‑β1, an important pro‑fibrogenic mediator, was identified as a direct target of miR‑326. Additionally, overexpression of miR‑326 blocked the activation of the TGF‑β1/SMAD family member 3 (Smad3) signaling pathway by suppressing the expression of TGF‑β1 in ESCs from patients with IUA. The findings of the present study indicated that miR‑326 inhibited endometrial fibrosis by suppressing the TGF‑β1/Smad3 signaling pathway, suggesting that miR‑326 may be a prognostic biomarker and therapeutic target for IUA.

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“…The cytokines cause reflective pathological changes in the advancement of hepatotoxicity. [50][51][52] Frequently, we found that CCl 4 suggestively expanded TNF-α, IL-1β, and IL-6 expression. 53,54 Interestingly, Met or Lut, especially in combination, expressively decreased the downstreaming inflammatory cascade.…”

Section: Discussionmentioning

confidence: 66%

“…Prior studies have referenced that CCl 4 worsens successions of inflammatory responses in the nearby zone of hepatic tissues by invigorating generation of inflammatory cytokines. The cytokines cause reflective pathological changes in the advancement of hepatotoxicity . Frequently, we found that CCl 4 suggestively expanded TNF‐α, IL‐1β, and IL‐6 expression .…”

Section: Discussionmentioning

confidence: 75%

Combination of metformin and luteolin synergistically protects carbon tetrachloride‐induced hepatotoxicity: Mechanism involves antioxidant, anti‐inflammatory, antiapoptotic, and Nrf2/HO‐1 signaling pathway

Yang¹,

Yang²,

Jiangmei³

2019

BioFactors

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Liver diseases are one of the fatal disorders due to the vital role of the liver. Carbon tetrachloride (CCl4) is the most perceived chemical substance utilized in developing models of hepatic damage. Metformin (Met) is a potent antidiabetic and redox modulatory agent that has shown anticancer and protective effects on various organs. Therefore, addition of therapy with natural antioxidative agents or herbal extracts shows defensive impacts against different injuries inside the body. Luteolin (Lut) can be found in several customary Chinese remedies. It has been reported for various pharmacological actions such as antitumor, antioxidative, and anti‐inflammatory impacts. Here, the liver injury rat model was established using CCl4 (1.00 mL/kg body weight) in vivo. The protective roles of Met and Lut separately or in combination were observed in hepatotoxicity induced by CCl4. The result was shown that both Met and Lut, while individually used, were normally active in diminishing CCl4‐caused hepatotoxicity. The combination of two drugs performed synergistically to improve liver damage caused by CCl4, as shown by the considerably improved liver dysfunction. Met and Lut showed highly antioxidative effects on CCl4‐treated rats moderately by increasing the activities and expression of the antioxidant enzymes. Along with this, a combination of Met and Lut significantly suppressed inflammatory responses, which is evidenced by the reduced level of inflammatory cytokines together with interleukin 1 beta (IL‐1β), tumor necrosis factor alpha (TNF‐α), and interleukin 6 (IL‐6). Additionally, CCl4‐agitated apoptosis was intensely reduced by Met and Lut through reducing cleaved caspase‐3 and Bax (pro‐apoptotic factor) while increasing Bcl‐2 (antiapoptotic factor) signaling pathways. Cotreatments of Met and Lut upregulated nuclear factor erythroid 2‐related factor 2 (NRF2) and heme oxygenase‐1 (HO‐1) expression in the CCl4‐intoxicated rat's liver. The above result recommended that combination of Met and Lut may have a substantial potential and synergizing impact against CCl4‐induced hepatotoxicity.

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Casticin attenuates liver fibrosis and hepatic stellate cell activation by blocking TGF-β/Smad signaling pathway

Cited by 45 publications

References 41 publications

Casticin prevents DSS induced ulcerative colitis in mice through inhibitions of NF‐κB pathway and ROS signaling

Casticin prevents DSS induced ulcerative colitis in mice through inhibitions of NF‐κB pathway and ROS signaling

MicroRNA‑326 inhibits endometrial fibrosis by regulating TGF‑β1/Smad3 pathway in intrauterine adhesions

Combination of metformin and luteolin synergistically protects carbon tetrachloride‐induced hepatotoxicity: Mechanism involves antioxidant, anti‐inflammatory, antiapoptotic, and Nrf2/HO‐1 signaling pathway

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