Attenuation of Endoplasmic Reticulum Stress-Mediated Liver Damage by Mulberry Leaf Diet in Streptozotocin-Induced Diabetic Rats

  • Rejina Afrin
    Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan
  • Somasundaram Arumugam
    Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan
  • Mir Imam Ibne Wahed
    Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan
  • Vigneshwaran Pitchaimani
    Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan
  • Vengadeshprabhu Karuppagounder
    Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan
  • Remya Sreedhar
    Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan
  • Meilei Harima
    Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan
  • Hiroshi Suzuki
    Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan
  • Shizuka Miyashita
    Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan
  • Takashi Nakamura
    Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan
  • Kenji Suzuki
    Department of Gastroenterology, Niigata University of Graduate School of Medicine and Dental Sciences, Niigata City 951-8510, Japan
  • Masahiko Nakamura
    Department of Cardiology, Yamanashi Prefectural Central Hospital, Kofu Yamanashi 400-8506, Japan
  • Kazuyuki Ueno
    Department of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan
  • Kenichi Watanabe
    Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan

書誌事項

公開日
2016-01
資源種別
journal article
DOI
  • 10.1142/s0192415x16500063
公開者
World Scientific Pub Co Pte Lt

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説明

<jats:p> Endoplasmic reticulum stress (ERS) plays a crucial role in the development of insulin resistance and diabetes mellitus. Although antidiabetic use of mulberry leaves (MLs) has been popular due to their many anti-oxidative flavonoid compounds and free radical scavenging effects, ML’s effects on ERS in experimental diabetic hepatocyte injury remain unknown. To investigate how ML affect ERS in diabetic liver, Sprague–Dawley (SD) rats were assigned to induce diabetes by a single intraperitoneal injection of streptozocin (STZ; 55 mg/kg) and fed with either normal chow or a diet containing 25% mulberry leaf powder diet (MLD) and examined for 56 days. We observed that MLD improved the rats’ morphological and histopathological changes. Levels of ERS markers such as phosphorylated double-stranded RNA-dependent protein kinase-like endoplasmic reticulum kinase (PERK) and X-box binding protein 1 (XBP1) and the protein expression of glucose regulated protein 78 (GRP78) were significantly higher in the diabetic liver compared to normal liver. MLD for 8 weeks significantly reduced all of these markers. MLD also significantly decreased hepatocyte apoptosis, hepatic macrophage recruitment, cellular infiltration, and CCAAT/enhancer–binding protein homologous protein (CHOP), tumor necrosis factor receptor associated factor 2 (TRAF2), interleukin 1[Formula: see text] (IL-1[Formula: see text]) and sterol regulatory element binding protein isoform 1c (SREBP 1c) levels in diabetic liver. These results may suggest that MLs can preserve hepatic function in experimental diabetes by modulating ERS mediated apoptosis and liver damage. </jats:p>

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