Mangiferin prevents hepatocyte epithelial-mesenchymal transition in liver fibrosis via targeting HSP27-mediated JAK2/STAT3 and TGF-ß1/Smad pathway.

Hepatocytes has been confirmed to undergo EMT and can be converted into myofibroblasts during hepatic fibrogenesis. However, the mechanism of hepatocyte EMT regulation in hepatic fibrosis, particularly through HSP27 (human homologue of rodent HSP25), remains unclear. Mangiferin (MAN), a compound extracted from Mangifera indica L, has been reported to attenuate liver injury. This study aimed to investigate the mechanisms underlying HSP27 inhibition and the anti-fibrotic effect of MAN in liver fibrosis. Our results revealed that the expression of HSP27 was remarkably increased in the liver tissues of patients with liver cirrhosis and CCl4 -induced fibrotic rats. However, HSP27 shRNA treatment significantly alleviated fibrosis. Furthermore, MAN was found to inhibit CCl4 - and TGF-ß1-induced liver fibrosis and reduced hepatocyte EMT. More importantly, MAN decreased HSP27 expression to suppress the JAK2/STAT3 pathway, and subsequently blocked TGF-ß1/Smad signaling, which were consistent with its protection against CCl4 -induced EMT and liver fibrosis. Together, these results suggest that HSP27 may play a crucial role in hepatocyte EMT and liver fibrosis by activating JAK2/STAT3 signaling and TGF-ß1/Smad pathway. The suppression of HSP27 expression by MAN may be a novel strategy for attenuating the hepatocyte EMT in liver fibrosis.

Anti-inflammatory and neuroprotective effects of natural cordycepin in rotenone-induced PD models through inhibiting Drp1-mediated mitochondrial fission.

Accumulating evidences suggest that inflammation-mediated neurons dysfunction participates in the initial and development of Parkinson's disease (PD), whereas mitochondria have been recently recognized as crucial regulators in NLRP3 inflammasome activation. Cordycepin, a major component of cordyceps militaris, has been shown to possess neuroprotective and anti-inflammatory activity. However, the effects of cordycepin in rotenone-induced PD models and the possible mechanisms are still not fully understood. Here, we observed that motor dysfunction and dopaminergic neurons loss induced by rotenone exposure were ameliorated by cordycepin. Cordycepin also reversed Drp1-mediated aberrant mitochondrial fragmentation through increasing AMPK phosphorylation and maintained normal mitochondrial morphology. Additionally, cordycepin effectively increased adenosine 5'-triphosphate (ATP) content, mitochondrial membrane potential (MMP), and reduced mitochondrial ROS levels, as well as inhibited complex 1 activity. More importantly, cordycepin administration inhibited the expression of NLRP3 inflammasome components and the release of pro-inflammatory cytokine in rotenone-induced rats and cultured neuronal PC12 cells. Moreover, we demonstrated that the activation of NLRP3 inflammasome within neurons could be suppressed by the mitochondrial division inhibitor (Mdivi-1). Collectively, the present study provides evidence that cordycepin exerts neuroprotective effects partially through preventing neural NLRP3 inflammasome activation induced by Drp1-dependent mitochondrial fragmentation in rotenone-injected PD models.

[Efffect of baicalin on antipyresis and influence on cytokine].

OBJECTIVE: To study the antipyretic effect of baicalin in inhibiting yeast-induced fever in rats and the influence on inflammatory cytokine, then explore the possible mechanism of baicalin in inhibiting yeast-induced fever in rats. METHODS: Rat modles of pyrexia were established by subcutaneous injection of yeast (2 g x kg(-1)); the rats of were divided into the normal control, model, baicalin high, medium and low-dose group and the effect of baicalin on the changes of the rats' temperature were observed. Dual antibody ELISA method was used to test the changes of IL-6, IL-1beta and TNF-alpha contents in in serum , hypothalamus and cerebral spinal fluid (CSF). Then analyze the correlation between the inhibition ratio of temperature heighten on three different dose of baicalin and the inhibition ratio of the contents heighten on IL-6, IL-1beta and TNF-alpha. RESULT: The high dose of baicalin significantly inhibited the yeast-induced fever of rats, and decresesed IL-6, IL-1beta and TNF-alpha contents in serum, hypothalamus and CSF. The inhibition ratio of temperature heighten of baicalin had direct correlation with the inhibition ratio of the heighten on IL-1beta content in serum, hypothalamus and CSF (r = 0.873, P < 0.05), also dose TNF-alpha (r = 0.862, P < 0.01). CONCLUSION: Baicalin may have obvious antipyretic effect by decreasing the increasing contents of IL-1beta and TNF-alpha in rats.