Protective effects of flavonoids from Coreopsis tinctoria Nutt. on experimental acute pancreatitis via Nrf-2/ARE-mediated antioxidant pathways. (5th October 2018)

• Record Type: Journal Article
• 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
• Is Part Of: Journal of ethnopharmacology. Volume 224(2018)
• Page Start: 261
• Page End: 272
• Publication Date: 2018-10-05
• Subjects: AP acute pancreatitis -- AREs antioxidant response elements -- BCA bicinchoninic acid protein -- BPI base peak intensity -- CER Caerulein -- C1-C6 compounds 1–6 -- DM diabetes mellitus -- EtOH ethanol -- GPx glutathione peroxidase -- H&E haematoxylin and eosin -- HO-1 haeme oxygenase-1 -- HRP horseradish peroxidase -- H2-DCFDA 2, 7-dichlorodi-hydrofluorescein diacetate -- IHC immunohistochemistry -- IL-6 Interleukin-6 -- Keap1 Kelch-like ECH-associated protein 1 -- MeOH methanol -- MPO myeloperoxidase -- NaT taurocholic acid sodium salt hydrate -- NF-kB nuclear factor kappa B -- Nrf2 nuclear factor erythroid 2-related factor 2 -- PI propidium iodide -- ROS reactive oxygen species -- SOD superoxide dismutase -- TFE total flavonoids extraction -- TLCS taurolithocholic acid 3-sulfate disodium salt; (2R, 3R)-taxifolin 7-O-β-D-glucopyranoside -- (2S)-flavanomarein -- (2S)-eriodictyol 7-O-β-D-glucopyranoside -- (2S)-flavanocorepsin -- Maritimein -- Marein; Coreopsis tinctoria -- Flavonoids -- Acute pancreatitis -- Oxidative stress -- Nrf2 -- Antioxidant enzymes; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2018.06.003
• Languages: English
• ISSNs: 0378-8741

Abstract

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 μg/kg) at hourly interval in mice or retrograde infusion of taurolithocholic acid 3-sulfate disodium salt (TLCS; 5 mM, 50 μL) 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 1–6 (C1 -C6 ) exhibited different capacities in reducing necrotic cell death pathway activation with 0.5 mM C1, (2 R, 3 R)-taxifolin 7-O- β -D-glucopyranoside, having the best effect. C1 also significantly reduced NaT-induced ROS production and ATP depletion. C1 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. C1 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 C1 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. Graphical abstract: fx1