title: Bofu-tsu-shosan, an oriental herbal medicine, exerts a combinatorial favorable metabolic modulation including antihypertensive effect on a mouse model of human metabolic disorders with visceral obesity.
abstract: Accumulating evidence indicates that metabolic dysfunction with visceral obesity is a major medical problem associated with the development of hypertension, type 2 diabetes (T2DM) and dyslipidemia, and ultimately severe cardiovascular and renal disease. Therefore, an effective anti-obesity treatment with a concomitant improvement in metabolic profile is important for the treatment of metabolic dysfunction with visceral obesity. Bofu-tsu-shosan (BOF) is one of oriental herbal medicine and is clinically available to treat obesity in Japan. Although BOF is a candidate as a novel therapeutic strategy to improve metabolic dysfunction with obesity, the mechanism of its beneficial effect is not fully elucidated. Here, we investigated mechanism of therapeutic effects of BOF on KKAy mice, a model of human metabolic disorders with obesity. Chronic treatment of KKAy mice with BOF persistently decreased food intake, body weight gain, low-density lipoprotein cholesterol and systolic blood pressure. In addition, both tissue weight and cell size of white adipose tissue (WAT) were decreased, with concomitant increases in the expression of adiponectin and peroxisome proliferator-activated receptors genes in WAT as well as the circulating adiponectin level by BOF treatment. Furthermore, gene expression of uncoupling protein-1, a thermogenesis factor, in brown adipose tissue and rectal temperature were both elevated by BOF. Intriguingly, plasma acylated-ghrelin, an active form of orexigenic hormone, and short-term food intake were significantly decreased by single bolus administration of BOF. These results indicate that BOF exerts a combinatorial favorable metabolic modulation including antihypertensive effect, at least partially, via its beneficial effect on adipose tissue function and its appetite-inhibitory property through suppression on the ghrelin system.
authors.affiliation: Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Azushima
authors.forename: Kouichi
authors.initials: K
authors.lastname: Tamura
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Wakui
authors.forename: Akinobu
authors.initials: A
authors.lastname: Maeda
authors.forename: Masato
authors.initials: M
authors.lastname: Ohsawa
authors.forename: Kazushi
authors.initials: K
authors.lastname: Uneda
authors.forename: Ryu
authors.initials: R
authors.lastname: Kobayashi
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Kanaoka
authors.forename: Toru
authors.initials: T
authors.lastname: Dejima
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Fujikawa
authors.forename: Akio
authors.initials: A
authors.lastname: Yamashita
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Toya
authors.forename: Satoshi
authors.initials: S
authors.lastname: Umemura
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D029001:Herbal Medicine / Q000379:methods*; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D008659:Metabolic Diseases / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D024101:Mitochondrial Proteins / Q000378:metabolism; D056128:Obesity, Abdominal / Q000188:drug therapy* / Q000378:metabolism; D000071256:Uncoupling Protein 1
chemical_list: D004365:Drugs, Chinese Herbal; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604371:UCP1 protein, human; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; C098310:bofu-tsusho-san