Anti-fibrotic effects of phenolic compounds on pancreatic stellate cells

Abstract

BackgroundPancreatic fibrosis is a prominent histopathological characteristic of chronic pancreatitis and plausibly a dynamic process of transition to the development of pancreatic ductal adenocarcinoma. Conversely, the activation of pancreatic stellate cells (PSCs) has been recently suggested as the key initiating step in pancreatic fibrosis. As natural polyphenols had been largely applied in complementary therapies in the past decade, in this study, we aimed to investigate which groups of phenolic compounds exert promising inhibitory actions on fibrogenesis as there are few effective strategies for the treatment of pancreatic fibrosis to date.MethodsWe examined the anti-fibrotic effects of a variety of herbal constituents using a cellular platform, the LTC-14 cells, which retained essential characteristics and morphologies of primary PSCs, by means of various biochemical assays including cell viability test, real-time polymerase chain reaction and Western blotting analysis.ResultsAmong a number of commonly used herbal constituents, we found that the application of rhein, emodin, curcumin and resveratrol significantly suppressed the mRNA and protein levels of several fibrotic mediators namely alpha-smooth muscle actin, type I collagen and fibronectin in LTC-14 cells against transforming growth factor-beta stimulation. Though the values of cytotoxicity varied, the mechanism of the anti-fibrotic action of these four phenolic compounds was principally associated with a decrease in the activation of the nuclear factor-kappaB signaling pathway.ConclusionsOur findings suggest that the mentioned phenolic compounds may serve as anti-fibrotic agents in PSC-relating disorders and pathologies, particularly pancreatic fibrosis.

Role of Gut‐Derived Endotoxin on Type I Collagen Production in the Rat Pancreas After Chronic Alcohol Exposure

“…Even so, it remains challenging to model alcohol‐related fibrosis in rodent models and there is a need to more fully determine the exact individual and collective roles of EtOH, its metabolic products, or endotoxin on the initiation or aggravation of pancreatic fibrosis. Col1 has been confirmed as the major component of extracellular matrix in the pancreas of human ACP and animal models of alcohol‐related pancreatitis (Lin et al., ; Masamune et al., ). Although a little aniline blue‐stained collagen was detected in periacinar and perilobular regions (data not shown) where PSCs could be detected, the vast majority of Col1 was only found in PSCs and 3.1‐fold increase in Col1A1 protein was detected in the pancreas of 10‐week EtOH rats, indicating that Col1 is a more sensitive and specific marker for assessing pancreatic fibrogenesis in 10‐week EtOH rat model.…”

Resveratrol and cancer treatment: updates

“…Tsang et al . and Lin et al . demonstrated that resveratrol can suppress the activation of PSCs, and the suppressive effects are associated with a decrease in NF‐κB activation and Akt phosphorylation.…”

The Role of Plant-derived Products in Pancreatitis: Experimental and Clinical Evidence

“…By producing its characteristic protective mechanisms, resveratrol also exhibited beneficial effects in liver injury associated with severe AP (Sha et al , ,b). Apart from the protection against AP, resveratrol also produced antifibrotic effects on LTC‐14 PSCs, suggesting its use in chronic pancreatic conditions (Lin et al , ).…”

“…Curcumin also protected the PSCs (LTC‐14) from fibrotic effects by inhibiting the mRNA expression of alpha‐smooth muscle actin, type I collagen, etc. (Lin et al , ). By checking the TLR‐4/NF‐κB signaling pathway, curcumin produced protective effects in severe AP (Zhong, ).…”