Hepatoprotective effect of cryptotanshinone from Salvia miltiorrhiza in d-galactosamine/lipopolysaccharide-induced fulminant hepatic failure |
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Institution: | 1. Leuven Lung Transplant Group, Department of Chronic Diseases, Metabolism & Ageing, KU Leuven, Leuven, Belgium;2. Department of Pathology, Erasmus Medical Centre, Rotterdam, The Netherlands;3. Department of Imaging and Pathology, University Hospitals Leuven, Leuven, Belgium;4. IBiTech–bioMMeda, Department of Electronics and Information Systems, Ghent University, Ghent, Belgium;5. Department of Thoracic Surgery, University Hospitals Leuven, Leuven, Belgium;1. Biotec BetaGlucans AS, 9019 Tromsø, Norway;2. Drug Transport and Delivery Research Group, Department of Pharmacy, Faculty of Health Sciences, University of Tromsø The Arctic University of Norway, 9037 Tromsø, Norway |
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Abstract: | Cryptotanshinone from Salvia miltiorrhiza Bunge was investigated for hepatoprotective effects in d-galactosamine (GalN)/lipopolysaccharide (LPS)-induced fulminant hepatic failure. Cryptotanshinone (20 or 40 mg/kg) was orally administered 12 and 1 h prior to GalN (700 mg/kg)/LPS (10 μg/kg) injection. The increased mortality and TNF-α levels by GalN/LPS were declined by cryptotanshinone pretreatment. In addition, cryptotanshinone attenuated GalN/LPS-induced apoptosis, characterized by the blockade of caspase-3, -8, and -9 activation, as well as the release of cytochrome c from the mitochondria. In addition, cryptotanshinone significantly suppressed JNK, ERK and p38 phosphorylation induced by GalN/LPS, and phosphorylation of TAK1 as well. Furthermore, cryptotanshinone significantly inhibited the activation of NF-κB and suppressed the production of proinflammatory cytokines. These findings suggested that hepatoprotective effect of cryptotanshinone is likely associated with its anti-apoptotic activity and the down-regulation of MAPKs and NF-κB associated at least in part with suppressing TAK1 phosphorylation. |
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Keywords: | Cryptotanshinone Fulminant hepatic failure Apoptosis NF-κB |
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