Gallic Acid, the Active Ingredient of Terminalia bellirica, Enhances Adipocyte Differentiation and Adiponectin Secretion

  • Makihara Hiroko
    Department of Molecular Pharmacology and Neurobiology, Graduate School of Medicine, Yokohama City University Biological Science and Nursing, Graduate School of Medicine, Yokohama City University
  • Koike Yuka
    Division of Pharmacognosy and Phytochemistry, Department of Medicinal Chemistry, Showa University
  • Ohta Masatomi
    Department of Pharmacognosy and Phytochemistry, Meiji Pharmaceutical University
  • Horiguchi-Babamoto Emi
    Faculty of Pharmacy, Musashino University
  • Tsubata Masahito
    Research and Development Division, Toyo Shinyaku Co., Ltd.
  • Kinoshita Kaoru
    Department of Pharmacognosy and Phytochemistry, Meiji Pharmaceutical University
  • Akase Tomoko
    Biological Science and Nursing, Graduate School of Medicine, Yokohama City University
  • Goshima Yoshio
    Department of Molecular Pharmacology and Neurobiology, Graduate School of Medicine, Yokohama City University
  • Aburada Masaki
    Faculty of Pharmacy, Musashino University
  • Shimada Tsutomu
    Department of Hospital Pharmacy, University Hospital, Kanazawa University

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  • Gallic Acid, the Active Ingredient of <i>Terminalia bellirica</i>, Enhances Adipocyte Differentiation and Adiponectin Secretion

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Visceral obesity induces the onset of metabolic disorders such as insulin resistance and diabetes mellitus. Adipose tissue is considered as a potential pharmacological target for treating metabolic disorders. The fruit of Terminalia bellirica is extensively used in Ayurvedic medicine to treat patients with diseases such as diabetes mellitus. We previously investigated the effects of a hot water extract of T. bellirica fruit (TB) on obesity and insulin resistance in spontaneously obese type 2 diabetic mice. To determine the active ingredients of TB and their molecular mechanisms, we focused on adipocyte differentiation using mouse 3T3-L1 cells, which are widely used to study adipocyte physiology. We show here that TB enhanced the differentiation of 3T3-L1 cells to mature adipocytes and that one of the active main components was identified as gallic acid. Gallic acid (10–30 µM) enhanced the expression and secretion of adiponectin via adipocyte differentiation and also that of fatty acid binding protein-4, which is the target of peroxisome proliferator-activated receptor gamma (PPARγ), although it does not alter the expression of the upstream genes PPARγ and CCAAT enhancer binding protein alpha. In the PPARγ ligand assay, the binding of gallic acid to PPARγ was undetectable. These findings indicate that gallic acid mediates the therapeutic effects of TB on metabolic disorders by regulating adipocyte differentiation. Therefore, TB shows promise as a candidate for preventing and treating patients with metabolic syndrome.

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