Paeonol alleviates CCl4-induced liver fibrosis through suppression of hepatic stellate cells activation via inhibiting the TGF-β/Smad3 signaling

Wu, Shengwang; Liu, Laicheng; Yang, Sen; Kuang, Ge; Yin, Xinru; Wang, Yuanyuan; Xu, Fangzhi; Xiong, Lingyi; Zhang, Meixia; Wan, Jingyuan; Gong, Xia

doi:10.1080/08923973.2019.1613427

Cited by 20 publications

(17 citation statements)

References 39 publications

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“…49 Wu et al reported that Paeonol alleviated CCl4-induced liver fibrosis in mice models and inhibited the activation of hepatic stellate cells by inhibiting the TGF-β1/Smad3 signaling pathway. 50 In our studies, Paeonol markedly suppressed the phosphorylation of Smad2 and Smad3. Furthermore, our results showed a significant increase in the mesenchymal markers Vimentin and N-Cadherin under TGF-β1 stimulation, which was restrained by Paeonol.…”

Section: Discussionsupporting

confidence: 59%

Paeonol Inhibits Pancreatic Cancer Cell Migration and Invasion Through the Inhibition of TGF-β1/Smad Signaling and Epithelial-Mesenchymal-Transition

Cheng

Chen

Tang

et al. 2020

CMAR

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These authors contributed equally to this workPurpose: Paeonol, a natural product derived from the root of Cynanchum paniculatum (Bunge) K. Schum and the root of Paeonia suffruticosa Andr. (Ranunculaceae) has attracted extensive attention for its anti-cancer proliferation effect in recent years. The present study examined the role of paeonol in suppressing migration and invasion in pancreatic cancer cells by inhibiting TGF-β1/Smad signaling. Methods: Cell viability was evaluated by MTT and colonial formation assay. Migration and invasion capabilities were examined by cell scratch-wound healing assay and the Boyden chamber invasion assay. Western Blot and qRT-PCR were used to measure the protein and RNA levels of vimentin, E-cadherin, N-cadherin, and TGF-β1/Smad signaling. Results: At non-cytotoxic dose, 100 μΜ and 150 μΜ of paeonol showed significant antimigration and anti-invasion effects on Panc-1 and Capan-1 cells (p<0.01). Paeonol inhibited epithelial-mesenchymal-transition by upregulating E-cadherin, and down regulating N-cadherin and vimentin expressions. Paeonol inhibited TGF-β1/Smad signaling pathway by downregulating TGF-β1, p-Smad2/Smad2 and p-Smad3/Smad3 expressions. Further, TGF-β1 attenuated the anti-migration and anti-invasion capacities of paeonol in Panc-1 and Capan-1 cells. Conclusion: These findings revealed that paeonol could suppress proliferation and inhibit migration and invasion in Panc-1 and Capan-1 cells by inhibiting the TGF-β1/Smad pathway and might be a promising novel anti-pancreatic cancer drug.

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Section: Discussionsupporting

confidence: 59%

Paeonol Inhibits Pancreatic Cancer Cell Migration and Invasion Through the Inhibition of TGF-β1/Smad Signaling and Epithelial-Mesenchymal-Transition

Cheng

Chen

Tang

et al. 2020

CMAR

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“…Paeonol, a phenolic compound isolated from Paeonia suffruticosa, has been shown to have a wide range of pharmacological activities including antioxidant and anti-inflammatory properties [9] that may be beneficial in various diseases such as diabetes [10], cancer [11], gastric ulcer [12], liver fibrosis [13], and myocardial infarction [14]. Paeonol has been proven to have a protection against antineoplastic-induced toxicities such as cisplatin-induced nephrotoxicity [15] and epirubicininduced cardiac toxicity [16]; however, to date, this role has not been investigated in MTX-induced cardiac toxicity.…”

Section: Introductionmentioning

confidence: 99%

Paeonol Attenuates Methotrexate-Induced Cardiac Toxicity in Rats by Inhibiting Oxidative Stress and Suppressing TLR4-Induced NF-κB Inflammatory Pathway

Al‐Taher

Morsy

Rifaai

et al. 2020

Mediators of Inflammation

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Methotrexate (MTX) is a commonly used chemotherapeutic agent. Oxidative stress and inflammation have been proved in the development of MTX toxicity. Paeonol is a natural phenolic compound with various pharmacological activities including antioxidant and anti-inflammatory properties. The aim of the present study was to evaluate the protective effect of paeonol against MTX-induced cardiac toxicity in rats and to evaluate the various mechanisms that underlie this effect. Paeonol (100 mg/kg) was administered orally for 10 days. MTX cardiac toxicity was induced at the end of the fifth day of the experiment, with or without paeonol pretreatment. MTX-induced cardiac damage is evidenced by a distortion in the normal cardiac histological structure, with significant oxidative and nitrosative stress shown as a significant increase in NADPH oxidase-2, malondialdehyde, and nitric oxide levels along with a decrease in reduced glutathione concentration and superoxide dismutase activity compared to the control group. MTX-induced inflammatory effects are evidenced by the increased cardiac toll-like receptor 4 (TLR4) mRNA expression and protein level as well as increased cardiac tumor necrosis factor- (TNF-) α and interleukin- (IL-) 6 levels along with increased nuclear factor- (NF-) κB/p65 immunostaining. MTX increased apoptosis as shown by the upregulation of cardiac caspase 3 immunostaining. Paeonol was able to correct the oxidative and nitrosative stress as well as the inflammatory and apoptotic parameters and restore the normal histological structure compared to MTX alone. In conclusion, paeonol has a protective effect against MTX-induced cardiac toxicity through inhibiting oxidative and nitrosative stress and suppressing the TLR4/NF-κB/TNF-α/IL-6 inflammatory pathway, as well as causing an associated reduction in the proapoptotic marker, caspase 3.

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“…Immune cells and cytokines in the liver are involved in the progression of liver fibrosis [31]. Kupffer cells (KCs) are inherent macrophages in the liver that produce cytokines such as TGF-b and IL-6 that promote the activation, proliferation, migration and survival of hepatic stellate cells [32]. We detected expression of TGF-b and IL-6 by real-time PCR.…”

Section: Discussionmentioning

confidence: 99%

Erythropoietin-Modified Mesenchymal Stem Cells Enhance Anti-fibrosis Efficacy in Mouse Liver Fibrosis Model

Wang

et al. 2020

Tissue Eng Regen Med

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BACKGROUND: Mesenchymal stem cell (MSC)-based cell transplantation is an effective means of treating chronic liver injury, fibrosis and end-stage liver disease. However, extensive studies have found that only a small number of transplanted cells migrate to the site of injury or lesion, and repair efficacy is very limited. METHODS: Bone marrow-derived MSCs (BM-MSCs) were generated that overexpressed the erythropoietin (EPO) gene using a lentivirus. Cell Counting Kit-8 was used to detect the viability of BM-MSCs after overexpressing EPO. Cell migration and apoptosis were verified using Boyden chamber and flow cytometry, respectively. Finally, the anti-fibrosis efficacy of EPO-MSCs was evaluated in vivo using immunohistochemical analysis. RESULTS: EPO overexpression promoted cell viability and migration of BM-MSCs without inducing apoptosis, and EPO-MSC treatment significantly alleviated liver fibrosis in a carbon tetrachloride (CCl 4) induced mouse liver fibrosis model. CONCLUSION: EPO-MSCs enhance anti-fibrotic efficacy, with higher cell viability and stronger migration ability compared with treatment with BM-MSCs only. These findings support improving the efficiency of MSCs transplantation as a potential therapeutic strategy for liver fibrosis.

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Paeonol alleviates CCl₄-induced liver fibrosis through suppression of hepatic stellate cells activation via inhibiting the TGF-β/Smad3 signaling

Cited by 20 publications

References 39 publications

<p>Paeonol Inhibits Pancreatic Cancer Cell Migration and Invasion Through the Inhibition of TGF-β1/Smad Signaling and Epithelial-Mesenchymal-Transition</p>

<p>Paeonol Inhibits Pancreatic Cancer Cell Migration and Invasion Through the Inhibition of TGF-β1/Smad Signaling and Epithelial-Mesenchymal-Transition</p>

Paeonol Attenuates Methotrexate-Induced Cardiac Toxicity in Rats by Inhibiting Oxidative Stress and Suppressing TLR4-Induced NF-κB Inflammatory Pathway

Erythropoietin-Modified Mesenchymal Stem Cells Enhance Anti-fibrosis Efficacy in Mouse Liver Fibrosis Model

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