Anti-inflammatory effects of bitongling granules are mediated through the suppression of miR-21/p38 MAPK/TLR4/NF-κB signaling in H9C2 rat cardiac cells exposed to lipopolysaccharides

Purpose: To assess the protective effects of bitongling granules on H9C2 cells exposed to lipopolysaccharides (LPS) in the management of rheumatoid arthritis (RA)-induced myocardial inflammation.Methods: The effects of bitongling granule (BTLG) drug-containing serum were assessed in myocarditis models established in rat cardiac cells. MicroRNA-21 (miR-21) levels were evaluated by qRT-PCR while MTT assays were performed to assess cell viability. ELISA assay was used to evaluate tumor necrosis factor α (TNF-α), interleukin 17 (IL-17) and interleukin 6 (IL-6) levels in cell culture supernatants. Apoptosis was determined by flow cytometry (FCM). Quantitative mitogen-activated protein kinase (MAPK)/p38, toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-kB)/p65 levels were evaluated by western blot and immunofluorescenceResults: BTLG increased cardiac cell activity and exhibited anti-inflammatory effect. It also inhibited LPS-induced H9C2 apoptosis and suppressed p65 NF-κB phosphorylation (p-p65 NF-κB), TLR4, and p38 MAPK phosphorylation (p-p38 MAPK). BTLG also reduced miR-21 expression, and the overexpression of the miR-21 inhibitor in H9C2 suppressed apoptosis. Moreover, p-p38 MAPK, TLR4 and p-p65 NF-κB expression were down-regulated in miR-21 inhibitor transfected H9C2s. The inhibition of p38/TLR4/ NF-κB signaling might have occurred via the suppression of miR-21 by BTLG.Conclusion: The results show that BTLG inhibits the inflammatory reaction involved in p38MAPK/TLR4/ NF-κB signaling pathway and can prevent RA-induced cardiac disease, suggesting that BTLP treatment may be beneficial for the management of arthritic cardiomyopathy

Ginseng-Angelica-Sansheng-Pulvis Boosts Neurogenesis Against Focal Cerebral Ischemia-Induced Neurological Deficiency

BackgroundThe traditional Chinese medicine Ginseng-Angelica-Shanseng-Pulvis (GASP) has been used to treat stroke for 300 years. This present study investigated if it can induce increases in neurogenesis following cerebral ischemic injury.MethodsRats following middle cerebral artery occlusion were orally treated with high, medium, and low doses of a standardized GASP extract.ResultsAfter 14 days, treatment with GASP improved regional blood flow and infarction volume by magnetic resonance imaging scanning, enhanced Ki67+ expression in the subventricular zone, increased brain-derived neurotrophic factor (BDNF) secretion, Nestin, and bone morphogenetic protein (BMP) 2/4 expressions in the hippocampus in a dose-dependent manner. Interestingly, low-dose treatment with GASP downregulated doublecortin and Notch1 expressions in the hippocampus, as well as upregulated glial fibrillary acidic protein expression in the subgranular zone and hairy and enhancer of split (Hes) 5 expression in the hippocampus, while treatment with middle and high doses of GASP reversed these results. Meanwhile, the consumed time was shortened in the basket test and the adhesive removal test and the spending time on exploring novel objects was prolonged by GASP treatment whose effects were more obvious at day 14 post-ischemia.ConclusionOur study demonstrates that treatment with GASP increases neurogenesis and ameliorates sensorimotor functions and recognition memory. We hypothesize that these effects are thought be mediated by an effect on the BMP2/4 pathway and Notch1/Hes5 signal. Due to its beneficial efficacy, GASP can be recognized as an alternative therapeutic agent for ischemic stroke