Tanshinone IIA ameliorates myocardial ischemia/reperfusion injury in rats by regulation of NLRP3 inflammasome activation and Th17 cells differentiation

Purpose: Tanshinone IIA is a well-known lipophilic active constituent refined from traditional Chinese medicines, danshen. It has been previously demonstrated to possess various biological properties, including anti-inflammatory, antioxidant, promoting angiogenesis effect and so on. However, the mechanism of tanshinone IIA on myocardial ischemia-reperfusion injury (MI/RI) remains unclear. In this study, we investigated the effect of tanshinone IIA on MI/RI. Methods: MI/RI rat models were set up. Echocardiographic evaluation and hematoxylin and eosin staining were performed to analyze the cardiac function and morphology of MI/RI. Western blot was conducted for the detection of protein expression of pyrin domain containing 3 (NLRP3) and caspase-1 in heart tissues. Flow cytometry and real-time polymerase chain reaction were used for the detection of proinflammatory cytokines and Th17 cells differentiation. Results: We found that tanshinone IIA alleviated the myocardial damage of MI/RI, ameliorated the overall and local inflammatory reaction, and produced a cardioprotective effect by inhibiting of NLRP3 inflammasome activation and Th17/Treg cells differentiation. Conclusions: Our results highlighted the cardio-protective effect of tanshinone IIA on MI/RI and uncovered its underlying mechanism related to the NLRP3 inflammasome inhibition and the modulation of Th17/Treg cells differentiation.

Mitigating effect of tanshinone IIA on ventricular remodeling in rats with pressure overload-induced heart failure

Abstract Purpose To investigate the effect of tanshinone IIA (TIIA) on ventricular remodeling in rats with pressure overload-induced heart failure. Methods Pressure overload-induced heart failure model (abdominal aortic coarctation) was established in 40 rats, which were divided into model and 5, 10 and 20 mg/kg TIIA groups. Ten rats receiving laparotomy excepting abdominal aortic coarctation were enrolled in sham-operated group. The 5, 10 and 20 mg/kg TIIA groups were treated with 5, 10 and 20 mg/kg TIIA, respectively, for 8 weeks. Results Compared with model group, in 20 mg/kg TIIA group the left ventricular ejection fraction, left ventricular fractional shortening, left ventricular systolic pressure, ±maximum left ventricular pressure rising and dropping rate, and myocardial B-cell lymphoma-2 and cleaved cysteinyl aspartate specific proteinase-3 protein levels were increased, respectively (P<0.05), and the left ventricular end diastolic diameter, left ventricular end systolic diameter, left ventricular end diastolic pressure, heart weight index, left ventricular weight index, serum B-type brain natriuretic peptide, interleukin 6 and C-reactive protein levels and myocardial B-cell lymphoma-2 associated X protein level were decreased, respectively (P<0.05). Conclusion TIIA may alleviate ventricular remodeling in rats with pressure overload-induced heart failure heart by reducing inflammatory response and cardiomyocyte apoptosis.(AU)

Salvianolic acid A alleviates the renal damage in rats with chronic renal failure

Purpose:To investigate the protective effects of salvianolic acid A (SAA) on renal damage in rats with chronic renal failure (CRF).Methods:The five-sixth nephrectomy model of CRF was successfully established in group CRF (10 rats) and group CRF+SAA (10 rats). Ten rats were selected as sham-operated group (group S), in which only the capsules of both kidneys were removed. The rats in group CRF+SAA were intragastrically administrated with 10 mg/kg SAA for 8 weeks. The blood urine nitrogen (BUN), urine creatinine (Ucr), creatinine clearance rate (Ccr), and serum uperoxide dismutase (SOD) and malondialdehyde (MDA) were tested. The expressions of transforming growth factor-β1 (TGF-β1), bone morphogenetic protein 7 (BMP-7) and Smad6 protein in renal tissue were determined.Results:After treatment, compared with group CRF, in group CRF+SAA the BUN, Scr, serum MDA and kidney/body weight ratio were decreased, the Ccr and serum SOD were increased, the TGF-β1 protein expression level in renal tissue was decreased, and the BMP-7 and Smad6 protein levels were increased (all P < 0.05).Conclusion:SAA can alleviate the renal damage in CRF rats through anti-oxidant stress, down-regulation of TGF-β1 signaling pathway and up-regulation of BMP-7/Smad6 signaling pathway.(AU)

Alternariol 9-methyl ether from the endophytic fungus Alternaria sp. Samif01 and its bioactivities

One bioactive compound, identified as alternariol 9-methyl ether, was isolated from the crude extract of the endophytic fungus Alternaria sp. Samif01 residing in the roots of Salvia miltiorrhiza Bunge. Alternariol 9-methyl ether was active against bacteria with minimum inhibitory concentration values ranging from 25 to 75 µg/mL and median inhibitory concentration (IC50) values ranging from 16.00 to 38.27 µg/mL. The IC50 value of alternariol 9-methyl ether against spore germination of Magnaporthe oryzae was 87.18 µg/mL. Alternariol 9-methyl ether also showed antinematodal activity against Bursaphelenchus xylophilus and Caenorhabditis elegans with IC50 values of 98.17 µg/mL and 74.62 µg/mL, respectively. This work is the first report on alternariol 9-methyl ether and its biological activities from the endophytic fungus Alternaria sp. Samif01 derived from S. miltiorrhiza Bunge. The results indicate the potential of Alternaria sp. Samif01 as a source of alternariol 9-methyl ether and also support that alternariol 9-methyl ether is a natural compound with high potential bioactivity against microorganisms. (AU)

The c-jun N-terminal kinases (JNK) / mitogen-activated protein kinase (MAPK) is responsible for the protection of tanshinol (Danshensu) upon H2 O2 -induced L6 rat myoblast cell injury

Background: Promoting L6 rat myoblast cell (L6 RMC) survival in the pro-apoptotic environment is critical to myoblastcell replacement for skeletal muscle degenerative disease therapy. Tanshinol (Danshensu), one of the principal bioactivecomponents in salvia miltiorrhiza bunge, has been used widely in skeletal muscle system (SMS) diseases treatment andserves as an antioxidant to protect myoblast cells against oxidative stress. The present study was undertaken to investigatethe protective effects of Tanshinol on L6 RMC injury induced by hydrogen peroxide (H2O2). After challenge with 100 µMH2O2 for 1h, loss of cell viability and excessive apoptotic cell death were observed in cultured L6 RMC, tanshinol treatmentconferred protective effects against the loss of cellular viability in a concentration-dependent manner.Materials, Methods & Results: L6 rat myoblast cells (L6 RMC) were maintained DMEM containing 4.5 g/L glucose andsupplemented with 10% (v/v) fetal bovine serum (FBS), 100 U/mL penicillin and 100 µg/mL streptomycin on tissue culturefl asks in a 37°C humidifi ed atmosphere of 95% air and 5% CO2. Cells were subcultured every 2-3 days. The cells werestained with SABC-Cy3 fl uorescence and measured by counting the nuclei. L6 RMC viability was determined by MTTassay in 96-well plates. The cells were counter-stained with H & E staining and Hoechst 33342 fl uorescent staining. Cellcycle phase distribution and apoptosis rates were detected by fl ow cytometry. Western blot were repeated three times, andqualitatively similar results were obtained. L6 RMC were pretreated with Tanshinol 375, 187.5, 93.75 mg/mL for 24 h,followed by treatment of 1000, 500, 100 µM H2O2 for 1h (P < 0.05) with viability by MTT method. Tanshinol 187.5 mg/mL pretreatment was protected in L6 RMC from H2O2-induced apoptosis with H&E staining and Hoechst 33342 fl uorescent...(AU)

The c-jun N-terminal kinases (JNK) / mitogen-activated protein kinase (MAPK) is responsible for the protection of tanshinol (Danshensu) upon H2 O2 -induced L6 rat myoblast cell injury

Background: Promoting L6 rat myoblast cell (L6 RMC) survival in the pro-apoptotic environment is critical to myoblastcell replacement for skeletal muscle degenerative disease therapy. Tanshinol (Danshensu), one of the principal bioactivecomponents in salvia miltiorrhiza bunge, has been used widely in skeletal muscle system (SMS) diseases treatment andserves as an antioxidant to protect myoblast cells against oxidative stress. The present study was undertaken to investigatethe protective effects of Tanshinol on L6 RMC injury induced by hydrogen peroxide (H2O2). After challenge with 100 µMH2O2 for 1h, loss of cell viability and excessive apoptotic cell death were observed in cultured L6 RMC, tanshinol treatmentconferred protective effects against the loss of cellular viability in a concentration-dependent manner.Materials, Methods & Results: L6 rat myoblast cells (L6 RMC) were maintained DMEM containing 4.5 g/L glucose andsupplemented with 10% (v/v) fetal bovine serum (FBS), 100 U/mL penicillin and 100 µg/mL streptomycin on tissue culturefl asks in a 37°C humidifi ed atmosphere of 95% air and 5% CO2. Cells were subcultured every 2-3 days. The cells werestained with SABC-Cy3 fl uorescence and measured by counting the nuclei. L6 RMC viability was determined by MTTassay in 96-well plates. The cells were counter-stained with H & E staining and Hoechst 33342 fl uorescent staining. Cellcycle phase distribution and apoptosis rates were detected by fl ow cytometry. Western blot were repeated three times, andqualitatively similar results were obtained. L6 RMC were pretreated with Tanshinol 375, 187.5, 93.75 mg/mL for 24 h,followed by treatment of 1000, 500, 100 µM H2O2 for 1h (P < 0.05) with viability by MTT method. Tanshinol 187.5 mg/mL pretreatment was protected in L6 RMC from H2O2-induced apoptosis with H&E staining and Hoechst 33342 fl uorescent...