Novel polysaccharide identified from Cortinarius purpurascens demonstrated anti-fibrosis effects in cardiac fibroblasts

Abstract

BackgroundMyocardial fibrosis is the primary pathological characteristic of cardiovascular disease, which can cause impaired cardiac function, severe heart failure, arrhythmia, and even sudden cardiac death. Cardiovascular diseases in Inner Mongolia can be prevented by using Cortinarius purpurascens. C. purpurascens polysaccharide (CPP) is the main active component of C. purpurascens. However, the action mechanism of CPP on myocardial fibrosis remain unclear. ObjectivesWe aimed isolate CPPs from purpurascens and to explore the mechanism of CPPs in myocardial fibrosis treatment so as to obtain a new experimental basis for the use of CPPs in the treatment of CVDs. MethodsCPPs were isolated and purified through water extraction, ethanol precipitation, deproteinization, and column chromatography and identified by gel permeation chromatography and Fourier-transformed infrared spectroscopy (FT-IR). The cell model of myocardial fibrosis induced by TGF-β1 was further treated with CPPs of different molecular weights. The expression levels of fibrosis proteins Col I, Col III and α-Smooth muscle actin (α-SMA) were detected by Western blotting, immunofluorescence assay or enzyme-linked immunosorbent assay (ELISA), and the expressions of Snail 1, Snail 2, and Slug were determined qRT-PCR. Western blotting was also performed to evaluate the expression level of TGF-β/Smad signaling-related protein. ResultsWe extracted and purified three CPPs, that TGF-β1 treatment increased the expression of Col I, Col III, α-SMA, and TGF-β/Smad signaling pathway-related proteins, while CPPs treatment significantly decreased the expression of Col I, Col III, and α-SMA proteins. Both the activation of the TGF-β/Smad signaling pathway and the mRNA expression of fibrosis transcriptional regulators such as Snail 1, Snail 2, and Slug were inhibited. ConclusionsCPPs can effectively inhibit the abnormal proliferation of CFs and myocardial fibrosis induced by TGF-β1 in mice. Therefore, CPPs may be worthy of further analyses as a novel therapeutic agent for cardiovascular diseases.