Suppression of Dynamical Network Biomarker Signals at the Predisease State (Mibyou) before Metabolic Syndrome in Mice by a Traditional Japanese Medicine (Kampo Formula) Bofutsushosan
Suppression of Dynamical Network Biomarker Signals at the Predisease State (Mibyou) before Metabolic Syndrome in Mice by a Traditional Japanese Medicine (Kampo Formula) Bofutsushosan
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DOI：
10.1155/2020/9129134
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发表时间：
2020-08-04
影响因子：
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通讯作者：
Aihara, Kazuyuki
中科院分区：
文献类型：
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作者：
Koizumi, Keiichi;Oku, Makito;Aihara, Kazuyuki
随着代谢综合征发病率的增加，迫切需要开发新的治疗策略。一个有前途的方法是把重点放在代谢综合征之前的疾病前状态（所谓的Mibyouin传统日本医学）作为一个先发制人的医疗目标。最近，我们成功地检测代谢综合征前的疾病状态，使用一种称为动态网络生物标志物（DNB）理论的数学理论。检测到的疾病前状态的特征在于，在5周龄的TSOD（Tsumura-Suzuki Obese Diabetes）小鼠（一种公认的代谢综合征模型）的总共24，217个基因中，有147个DNB基因。在TSOD小鼠中，疾病前状态的时间比代谢综合征的发作早得多，据报道大约在8-12周龄。在本研究中，我们调查了TSOD小鼠的疾病前状态是否可以通过口服Kampo配方，bofutsushosan（BTS）来抑制，该配方通常用于治疗日本代谢综合征的肥胖患者，从3至7周龄。我们发现BTS在5周龄及以后全面抑制DNB基因的预警信号。具体地，与未处理对照组相比，147个DNB基因中的134个基因的标准偏差在5周龄时降低，其中80个基因显示出超过50%的降低。此外，在7周龄时，BTS治疗组的体重和血糖水平显著低于未治疗对照组。我们的研究结果表明BTS的一种新机制;它抑制了DNB基因在代谢综合征前的疾病前状态的波动，从而防止了随后向代谢综合征的转变。总之，本研究首次基于科学评估证明了汉方对代谢综合征的预防和预防作用。
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-calledMibyouin 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 onMibyoubefore metabolic syndrome for the first time based on scientific evaluation.