Capsaicin induces de-differentiation of activated hepatic stellate cell

Abstract

Hepatic stellate cells (HSC) play a key role in liver fibrogenesis. Activation of PPARγ and inhibition of fibrogenic molecules are potential strategies to block HSC activation and differentiation. A number of natural products have been suggested to have antifibrotic effects for the de-activation and de-differentiation of HSCs. The purpose of this study was to investigate the in vitro effects of capsaicin on HSC de-activation and de-differentiation. The results demonstrated that capsaicin induced quiescent phenotype in GRX via PPARγ activation. Significant decrease in COX-2 and type I collagen mRNA expression was observed in the first 24 h of treatment. These events preceded the reduction of TGF-β1 and total collagen secretion. Thus, capsaicin promoted down-regulation of HSC activation by its antifibrotic and anti-inflammatory actions. These findings demonstrate that capsaicin may have potential as a novel therapeutic agent for the treatment of liver fibrosis.

Inhibitory effect of dietary capsaicin on liver fibrosis in mice

“…It is consumed worldwide as a food additive, especially in Latin‐American and Asian countries . CPS has several beneficial properties such as anti‐inflammatory and antioxidative . The amount of CPS (0.01%) used in this study is similar to the quantity reported by Li et al.…”

“…TGF‐β1 is the main profibrogenic cytokine related to the activation of HSCs and we have previously shown that CPS strongly affects TGF‐β1 secretion . We show here that CPS does not affect the early responders Smad6 and Smad7, but clearly affects later events (αSMA, Col1a1, and Lox upregulation) following TGF‐β1 stimulation.…”

“…Beneficial characteristics of CPS have been studied for centuries and nowadays this compound is commonly used as an analgesic product . Previously, we reported that CPS could modulate the activation of HSCs in vitro . In the present study, to elucidate a potential beneficial role of CPS during liver fibrosis in vivo, dietary CPS was given to mice that had undergone bile duct ligation (BDL) or received carbon tetrachloride (CCl 4 ) injections.…”

Exogenous expression of caveolin‐1 is sufficient for hepatic stellate cell activation

“…GRX cells represent a heterogeneous population that can be induced to have majority activated or quiescent cells . Here, we showed for the first time that exogenous expression of Cav‐1 (GRX EGFP‐Cav1 ) induced the majority of the GRX population into an activated‐like HSC state.…”

Resveratrol Regulates the Quiescence‐Like Induction of Activated Stellate Cells by Modulating the PPARγ/SIRT1 Ratio

“…On the other hand, culture‐activated HSC can be phenotypically and functionally reversed to a quiescent‐like phenotype by forced expression of PPARγ [Hazra et al, ]. On this premise, it was already demonstrated that PPARγ mRNA expression was increased in GRX quiescent‐like cells [Guimaraes et al, ; Bitencourt et al, ].…”