Thermogenic, anti-obesity effects of bofu-tsusho-san in MSG-obese mice.
OBJECTIVE
To 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.


METHODS
MSG 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.


METHODS
The 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.


RESULTS
One 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.


CONCLUSIONS
Bofu-tsusho-san (TJ-62) works via activating the BAT thermogenesis and inhibiting the phosphodiesterase activity in mice.
Yoshida
T
T
First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
Sakane
N
N
Wakabayashi
Y
Y
Umekawa
T
T
Kondo
M
M
D000273:Adipose Tissue / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001823:Body Composition / Q000187:drug effects / Q000502:physiology; D001833:Body Temperature Regulation / Q000187:drug effects* / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use*; D004435:Eating / Q000187:drug effects / Q000502:physiology; D003576:Electron Transport Complex IV / Q000032:analysis; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D004809:Ephedrine / Q000097:blood / Q000494:pharmacology; D005260:Female; D006035:Glycyrrhiza; D006153:Guanosine Diphosphate / Q000378:metabolism; D007564:Japan; D051379:Mice; D008813:Mice, Inbred ICR; D008820:Mice, Obese; D008928:Mitochondria / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy* / Q000503:physiopathology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010946:Plants, Medicinal; D012970:Sodium Glutamate / Q000008:administration & dosage; D013997:Time Factors
D004365:Drugs, Chinese Herbal; D010726:Phosphodiesterase Inhibitors; C098310:bofu-tsusho-san; D006153:Guanosine Diphosphate; D003576:Electron Transport Complex IV; D004809:Ephedrine; D012970:Sodium Glutamate