Authors Du, Dan; Yao, Linbo; Zhang, Rui; Shi, Na; Shen, Yan; Yang, Xinmin; Zhang, Xiaoying; Jin, Tao; Liu, Tingting; Hu, Liqiang; Xing, Zhihua; Criddle, David N.; Xia, Qing; Huang, Wei; Sutton, Robert
Journal JOURNAL OF ETHNOPHARMACOLOGY , OCT 5 2018,:224
DOI 10.1016/j.jep.2018.06.003 PubMed 29870787
Abstract Ethnopharmacological relevance: Oxidative stress is a prominent feature of clinical acute pancreatitis (AP). Coreopsis tinctoria has been used traditionally to treat pancreas disorders like diabetes mellitus in China and Portugal and its flavonoid-rich fraction contain the main phytochemicals that have antioxidant and anti-inflammatory activities.Aim of the study: To investigate the effects of flavonoids isolated from C. tinctoria on experimental AP and explore the potential mechanism.Materials and methods: LC-MS based online technique was used to analyse and isolate targeted flavonoids from C. tinctoria. Freshly isolated mouse pancreatic acinar cells were treated with taurocholic acid sodium salt hydrate (NaT, 5 mM) with or without flavonoids. Fluorescence microscopy and a plate reader were used to determine necrotic cell death pathway activation (propidium iodide), reactive oxygen species (ROS) production (H2-DCFDA) and ATP depletion (luminescence) where appropriate. AP was induced by 7 repeated intraperitoneal caerulein injections (50 mu g/kg) at hourly interval in mice or retrograde infusion of taurolithocholic acid 3-sulfate disodium salt (TLCS; 5 mM, 50 mu L) into the pancreatic duct in mice or infusion of NaT (3.5%, 1 mL/kg) in rats. A flavonoid was intraperitoneally administered at 0, 4, and 8 h after the first caerulein injection or post-operation. Disease severity, oxidative stress and antioxidant markers were determined.Results: Total flavonoids extract and flavonoids w1-6 (C1-C6) exhibited different capacities in reducing necrotic cell death pathway activation with 0.5 mM Cl, (2 R,3 R)-taxifolin 7-O-beta-D-glucopyranoside, having the best effect. Cl also significantly reduced NaT-induced ROS production and ATP depletion. Cl at 12.5 mg/kg and 8.7 mg/kg (equivalent to 12.5 mg/kg for mice) significantly reduced histopathological, biochemical and immunological parameters in the caerulein-, TLCS- and NaT-induced AP models, respectively. Cl administration increased pancreatic nuclear factor erythroid 2-related factor 2 (Nrf2) and Nrf2-medicated haeme oxygenase-1 expression and elevated pancreatic antioxidant enzymes superoxide dismutase and glutathione peroxidase levels.Conclusions: Flavonoid Cl from C. tinctoria was protective in experimental AP and this effect may at least in part be attributed to its antioxidant effects by activation of Nrf2-mediated pathways. These results suggest the potential utilisation of C. tinctoria to treat AP.
Species covered 两色金鸡菊 Coreopsis tinctoria
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