Hachimijiogan, a traditional herbal medicine, modulates adipose cell function and ameliorates diet-induced obesity and insulin resistance in mice

Syota Kagawa; Katsuya Tanabe; Makoto Hiromura; Kakuyou Ogawa; Takayuki Koga; Takahiro Maeda; Kikuko Amo-Shiinoki; Hiroyuki Ochi; Yui Ichiki; Shogo Fukuyama; Saori Suzuki; Natsuki Suizu; Takaaki Ohmine; Sakurako Hamachi; Hiroshi Tsuneki; Shigeru Okuya; Toshiyasu Sasaoka; Yukio Tanizawa; Fumihiro Nagashima

doi:10.3389/fphar.2023.1167934

Hachimijiogan, a traditional herbal medicine, modulates adipose cell function and ameliorates diet-induced obesity and insulin resistance in mice

Front Pharmacol. 2023 May 12:14:1167934. doi: 10.3389/fphar.2023.1167934. eCollection 2023.

Authors

Syota Kagawa¹, Katsuya Tanabe², Makoto Hiromura³, Kakuyou Ogawa⁴, Takayuki Koga⁵, Takahiro Maeda⁶, Kikuko Amo-Shiinoki², Hiroyuki Ochi¹, Yui Ichiki¹, Shogo Fukuyama¹, Saori Suzuki¹, Natsuki Suizu¹, Takaaki Ohmine¹, Sakurako Hamachi¹, Hiroshi Tsuneki⁶, Shigeru Okuya⁷, Toshiyasu Sasaoka⁶, Yukio Tanizawa², Fumihiro Nagashima¹

Affiliations

¹ Department of Natural Products Chemistry, Daiichi University of Pharmacy, Fukuoka, Japan.
² Division of Endocrinology, Metabolism, Hematological Sciences and Therapeutics, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.
³ Department of Pharmaceutics and Biochemistry, Daiichi University of Pharmacy, Fukuoka, Japan.
⁴ Department of Natural Medicine, Daiichi University of Pharmacy, Fukuoka, Japan.
⁵ Department of Hygienic Chemistry, Daiichi University of Pharmacy, Fukuoka, Japan.
⁶ Department of Clinical Pharmacology, University of Toyama, Toyama, Japan.
⁷ Health Administration Centre, Organisation for University Education, Yamaguchi University, Yamaguchi, Japan.

Abstract

Hachimijiogan (HJG) has originally been used to ameliorate a variety of symptoms associated with low ambient temperatures. However, its pharmacological action in metabolic organs remains unclear. We hypothesized that HJG may modulate metabolic function and have a potential therapeutic application to metabolic diseases. To test this hypothesis, we investigated metabolic action of HJG in mice. Male C57BL/6J mice chronically administered with HJG showed a reduction in adipocyte size with increased transcription of beige adipocyte-related genes in subcutaneous white adipose tissue. HJG-mixed high-fat diet (HFD)-fed mice showed alleviation of HFD-induced weight gain, adipocyte hypertrophy, liver steatosis with a significant reduction in circulating leptin and Fibroblast growth factor 21 despite no changes in food intake or oxygen consumption. Feeding an HJG-mixed HFD following 4-weeks of HFD feeding, while a limited effect on body weight, improved insulin sensitivity with a reversal of decreased circulating adiponectin. In addition, HJG improved insulin sensitivity in the leptin-deficient mice without significant effects on body weight. Treatment with n-butanol soluble extracts of HJG potentiated transcription of Uncoupling protein 1 mediated by β3-adrenergic agonism in 3T3L1 adipocytes. These findings provide evidence that HJG modulates adipocyte function and may exert preventive or therapeutic effects against obesity and insulin resistance.

Keywords: adipocyte; insulin resistance; leptin; obesity; traditional herbal medicine.

Grants and funding

This research was funded by Grants-in-Aid for Scientific Research, grant numbers 16K19314 and 21K07332 to SK; 16K09752 and 20K08887 to KT; 18K08516 to SO; and 18K07457 and 21K07382 to FN.