OBJECTIVETo investigate the hypothesis that anti-obesity action of bofu-tsusho-san (TJ-62) works via activating the brown adipose tissue thermogenesis and inhibiting the phosphodiesterase activity.DESIGNMSG obese mice and lean controls were fed a diet including 1.4% or 4.7% TJ-62 of weight of food for 8 weeks. Another group of MSG obese mice were fed with 1-ephedrine (1-E) + d-pseudoephedrine (d-PE) of equivalent amounts as contained in TJ-62 (4.7%) for 8 weeks. Yet another group of MSG obese mice were further supplemented with Glycyrrhizae Radix (GR) extract + Forsythiae Fructus (FF) extract + Schizonepetae Spica (SS) extract (that inhibited phosphodiesterase activity) of amounts contained in TJ-62 (4.7%) for 8 weeks.MEASUREMENTSThe following were measured: The concentration of ephedrine and its congeners in TJ-62; the inhibitory effect of TJ-62 on phosphodiesterase activity; body weight; food intake; retroperitoneal white adipose tissue (RWAT) weight; interscapular brown adipose tissue (IBAT) weight; mitochondrial protein content in IBAT; cytochrome c oxidase activity in IBAT; guanosine-5'-diphosphate (GDP) binding in IBAT mitochondria.RESULTSOne gram of TJ-62 contained 3.33 mg of 1-E and 0.73 mg of d-PE. One mg of TJ-62 was equivalent to 2.5 mg of caffeine in the inhibitory effect on phosphodiesterase activity. After feeding with TJ-62, GDP binding was significantly increased in a dose dependent manner. Body weight and RWAT weight decreased in both MSG obese mice and lean controls. Food intake was not changed by TJ-62. Feeding with 1-E + d-PE produced responses of about 70% of those of TJ-62. These responses were, furthermore, enhanced by the addition of the three extracts to the levels that were similar to those produced by TJ-62.CONCLUSIONBofu-tsusho-san (TJ-62) works via activating the BAT thermogenesis and inhibiting the phosphodiesterase activity in mice.