Muscone improves hypoxia/reoxygenation (H/R)-induced neuronal injury by blocking HMGB1/TLR4/NF-κB pathway via modulating microRNA-142.

Previous reports have indicated that natural muscone has neuroprotective effects against cerebral hypoxia injury; however, little is known in regards to its pharmacological mechanism. In this study, we tried to evaluate the neuroprotective effects and mechanisms of muscone against cerebral hypoxia injury using an in vitro model. The cerebral hypoxia injury cell model was produced by hypoxia/reoxygenation (H/R). The cell viability and apoptosis were measured using the cell counting Kit-8 and the Annexin V-FITC/PI Apoptosis Detection kit, respectively. To screen microRNAs regulated by muscone, we analyzed the gene expression datasets of GSE84216 retrieved from gene expression omnibus (GEO). Here, it was demonstrated that muscone treatment significantly alleviated the cell apoptosis, oxidative stress and inflammation in H/R-exposed neurons. Subsequently, through analyzing GSE84216 from the GEO database, miR-142-5p was markedly upregulated by treatment of muscone in this cell model of cerebral hypoxia injury. Further experiments revealed that downregulation of miR-142-5p eliminated the neuroprotective effects of muscone against H/R induced neuronal injury. Additionally, high mobility group box 1 (HMGB1), an important inflammatory factor, was identified as a direct target of miR-142-5p in neurons. Meanwhile, we further demonstrated that muscone could reduce the expression of HMGB1 by upregulating miR-142-5p expression, which subsequently resulted in the inactivation of TLR4/NF-κB pathway, finally leading to the improvement of cell injury in H/R-exposed neurons. Overall, we demonstrate for the first time that muscone treatment alleviates cerebral hypoxia injury in in vitro experiments through blocking activation of the TLR4/NF-κB signaling pathway by targeting HMGB1, suggesting that muscone may serve as a potential therapeutic drug for treating cerebral hypoxia injury.

Effect of Sini decoction on angiotensin ⠡ transforming growth factor β1 and connective tissue growth factor in rats with myocardial fibrosis-induced banding of the abdominal aorta.

OBJECTIVE: To investigate the effect of Sini decoction on rats with myocardial fibrosis induced by banding the abdominal aorta, and explore the mechanism underlying its actions on angiotensin ¢ò(Ang ¢ò), transforming growth factor-¦Â1 (TGF-¦Â1) and connective tissue growth factor (CTGF). METHODS: Forty-eight male Sprague-Dawley rats were randomly divided into sham operation, model, Captopril, and Sini decoction groups. The models were established by the partial banding of the abdominal aorta according to Doering's method. Eight weeks later, heart weight indexes were calculated; hemodynamic changes of the hearts were tested; changes in myocardial tissue morphology were observed by Masson staining; and myocardial collagen volume fraction was calculated. Enzyme-linked immunosorbent assay was used to measure the concentration of Ang ¢ò in serum. The expression of TGF-ß1 and CTGF were determined by immunohistochemistry and Western blotting. RESULTS: Compared with the sham operation group, the heart weight index, collagen volume fraction of the myocardium, serum levels of Ang ¢ò and the expression of myocardial TGF-ß1 and CTGF in the model group were significantly increased (P < 0.05). Compared with the model group, the heart weight index, collagen volume fraction of the myocardium, serum levels of Ang ¢ò and the expression of myocardial TGF-ß1 and CTGF in all treatment groups were significantly reduced (P < 0.05). CONCLUSION: Sini decoction reduced Ang ¢ò level and inhibited the expression of myocardial TGF-ß1 and CTGF, which may explain the mechanism of its protective effect on myocardium with fibrosis.