title: Inhibition of pancreatic oxidative damage by stilbene derivative dihydro-resveratrol: implication for treatment of acute pancreatitis.
abstract: Trans-resveratrol is a natural stilbenoid possessing multifarious pharmacological benefits; however, when orally consumed, it is rapidly metabolised by colonic microflora and converted to dihydro-resveratrol. Thus, this microbial metabolite is of great therapeutic relevance. In the present study, upon the oral administration of dihydro-resveratrol (10-50 mg/kg), the severity of acute pancreatitis in the cerulein-treated rats was significantly ameliorated as evidenced by decreased α-amylase activities in the plasma and lessened oedema formation in the pancreatic parenchyma. In addition, the generation of intracellular reactive oxidative products, including malondialdehyde and protein carbonyls, was accordingly reduced, so as the production of pro-inflammatory cytokines. While inhibiting the activities of NADPH oxidase and myeloperoxidase, the depletion of glutathione was considerably restored. Importantly, the attenuation of pancreatic oxidative damage by dihydro-resveratrol was associated with a down-regulation of the nuclear factor-kappaB and phosphatidylinositol 3'-kinase-serine/threonine kinase signalling pathways. Furthermore, we demonstrated that the solubility of dihydro-resveratrol was at least 5 times higher than trans-resveratrol whilst exhibiting a much lower cytotoxicity. Collectively, the current findings accentuate new mechanistic insight of dihydro-resveratrol in pancreatic oxidative damage, and advocate its therapeutic potential for the management of acute pancreatitis, particularly for patients unresponsive to trans-resveratrol due to the lack of proper microbial strains.
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China.|Institute of Research and Continuing Education, Hong Kong Baptist University Shenzhen Research Centre, Shenzhen, China.
authors.forename: Siu Wai
authors.initials: SW
authors.lastname: Tsang
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China.
authors.forename: Yi-Fu
authors.initials: YF
authors.lastname: Guan
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China.|School of Public Health, Jilin University, Changchun, Jilin, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China.
authors.forename: Zhao-Xiang
authors.initials: ZX
authors.lastname: Bian
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China.|Institute of Research and Continuing Education, Hong Kong Baptist University Shenzhen Research Centre, Shenzhen, China.
authors.forename: Hong-Jie
authors.initials: HJ
authors.lastname: Zhang
mesh_terms: D000208:Acute Disease; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D015153:Blotting, Western; D002108:Ceruletide; D016207:Cytokines / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D008856:Microscopy, Fluorescence; D015394:Molecular Structure; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D050050:Protein Carbonylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*; D000516:alpha-Amylases / Q000097:blood / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D013267:Stilbenes; D008315:Malondialdehyde; D002108:Ceruletide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D000516:alpha-Amylases; D000077185:Resveratrol