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Thermogenic, anti-obesity effects of bofu-tsusho-san in MSG-obese mice
T Yoshida1, N Sakane, Y Wakabayashi
1First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
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.
Design:
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.
Measurements:
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.
Conclusion:
Bofu-tsusho-san (TJ-62) works via activating the BAT thermogenesis and inhibiting the phosphodiesterase activity in mice.
Insights
Bofu-tsusho-san (TJ-62) activates brown adipose tissue (BAT) thermogenesis and inhibits phosphodiesterase activity, leading to reduced body weight and white adipose tissue in mice.
Area of Science:
- Pharmacology
- Metabolic Science
- Traditional Chinese Medicine
Background:
- Obesity is a complex metabolic disorder with significant health implications.
- Bofu-tsusho-san (TJ-62) is a traditional herbal medicine used for managing obesity.
- The precise mechanisms underlying TJ-62's anti-obesity effects require elucidation.
Purpose of the Study:
- To investigate the hypothesis that TJ-62's anti-obesity action is mediated by activating brown adipose tissue (BAT) thermogenesis.
- To determine if TJ-62 inhibits phosphodiesterase (PDE) activity.
- To explore the combined effects of ephedrine congeners and PDE-inhibiting extracts in TJ-62.
Main Methods:
- MSG-obese mice and lean controls were administered TJ-62, ephedrine (1-E) + d-pseudoephedrine (d-PE), or TJ-62's constituent extracts for 8 weeks.
- Key measurements included body weight, adipose tissue weights (RWAT, IBAT), mitochondrial function markers (protein content, cytochrome c oxidase activity, GDP binding), and PDE inhibitory activity.
- Chemical analysis quantified ephedrine and congeners in TJ-62 and compared its PDE inhibitory potency to caffeine.
Main Results:
- TJ-62 significantly increased guanosine-5'-diphosphate (GDP) binding in brown adipose tissue (BAT) mitochondria in a dose-dependent manner, indicating enhanced thermogenesis.
- Administration of TJ-62 led to significant reductions in body weight and retroperitoneal white adipose tissue (RWAT) weight in both obese and lean mice.
- The anti-obesity effects of TJ-62 were partially replicated by ephedrine and its congeners and further enhanced by the addition of PDE-inhibiting herbal extracts.
Conclusions:
- Bofu-tsusho-san (TJ-62) exerts its anti-obesity effects through a dual mechanism involving the activation of BAT thermogenesis and the inhibition of phosphodiesterase activity.
- The combination of ephedrine-like compounds and PDE-inhibiting components in TJ-62 contributes synergistically to its metabolic benefits.
- These findings provide a scientific basis for the traditional use of TJ-62 in weight management.