Suppression of Dynamical Network Biomarker Signals at the Predisease State (Mibyou) before Metabolic Syndrome in Mice by a Traditional Japanese Medicine (Kampo Formula) Bofutsushosan.

Keiichi Koizumi,Kazuyuki Tobe,Luonan Chen,Yoshiko Igarashi,Makito Oku,Akiko Inujima,Naotoshi Shibahara,Makoto Kadowaki,Kazuyuki Aihara,Shigeru Saito,Shusaku Hayashi

doi:10.1155/2020/9129134

Abstract

Due to the increasing incidence of metabolic syndrome, the development of new therapeutic strategies is urgently required. One promising approach is to focus on the predisease state (so-called Mibyou in traditional Japanese medicine) before metabolic syndrome as a preemptive medical target. We recently succeeded in detecting a predisease state before metabolic syndrome using a mathematical theory called the dynamical network biomarker (DNB) theory. The detected predisease state was characterized by 147 DNB genes among a total of 24,217 genes in TSOD (Tsumura-Suzuki Obese Diabetes) mice, a well-accepted model of metabolic syndrome, at 5 weeks of age. The timing of the predisease state was much earlier than the onset of metabolic syndrome in TSOD mice reported to be at approximately 8–12 weeks of age. In the present study, we investigated whether the predisease state in TSOD mice can be inhibited by the oral administration of a Kampo formula, bofutsushosan (BTS), which is usually used to treat obese patients with metabolic syndrome in Japan, from 3 to 7 weeks of age. We found the comprehensive suppression of the early warning signals of the DNB genes by BTS at 5 weeks of age and later. Specifically, the standard deviations of 134 genes among the 147 DNB genes decreased at 5 weeks of age as compared to the nontreatment control group, and 80 of them showed more than 50% reduction. In addition, at 7 weeks of age, the body weight and blood glucose level were significantly lower in the BTS-treated group than in the nontreatment control group. The results of our study suggest a novel mechanism of BTS; it suppressed fluctuations of the DNB genes at the predisease state before metabolic syndrome and thus prevented the subsequent transition to metabolic syndrome. In conclusion, this study demonstrated the preventive and preemptive effects of a Kampo formula on Mibyou before metabolic syndrome for the first time based on scientific evaluation.

Highlights

Keiichi Koizumi,1,2 Makito Oku,3,4 Shusaku Hayashi,5,6 Akiko Inujima,1,2 Naotoshi Shibahara,1 Luonan Chen,7,8 Yoshiko Igarashi,9 Kazuyuki Tobe,9 Shigeru Saito,10 Makoto Kadowaki,5 and Kazuyuki Aihara8,11
We recently succeeded in detecting a predisease state before metabolic syndrome using a mathematical theory called the dynamical network biomarker (DNB) theory. e detected predisease state was characterized by 147 DNB genes among a total of 24,217 genes in TSOD (Tsumura-Suzuki Obese Diabetes) mice, a well-accepted model of metabolic syndrome, at 5 weeks of age. e timing of the predisease state was much earlier than the onset of metabolic syndrome in TSOD mice reported to be at approximately 8–12 weeks of age
Erefore, in the present study, we attempted to reveal whether the emergence of the predisease state before metabolic syndrome in TSOD mice, which was characterized by the 147 DNB genes, can be prevented by the oral administration of a Kampo formula

Summary

Introduction

Keiichi Koizumi ,1,2 Makito Oku,3,4 Shusaku Hayashi,5,6 Akiko Inujima,1,2 Naotoshi Shibahara,1 Luonan Chen,7,8 Yoshiko Igarashi,9 Kazuyuki Tobe,9 Shigeru Saito,10 Makoto Kadowaki,5 and Kazuyuki Aihara8,11. E detected predisease state was characterized by 147 DNB genes among a total of 24,217 genes in TSOD (Tsumura-Suzuki Obese Diabetes) mice, a well-accepted model of metabolic syndrome, at 5 weeks of age. We investigated whether the predisease state in TSOD mice can be inhibited by the oral administration of a Kampo formula, bofutsushosan (BTS), which is usually used to treat obese patients with metabolic syndrome in Japan, from 3 to 7 weeks of age.

Results

Conclusion