Qiu Fan, Zhang Yu-Qing
School of Biology and Basic Medical Sciences, Soochow University, RM702-2303, No. 199, Renai Road, Dushuhu Higher Edu. Town, Suzhou, People's Republic of China.
Nutr Metab (Lond). 2019 Jan 31;16:10. doi: 10.1186/s12986-019-0335-x. eCollection 2019.
Mulberry () branch bark powder have showed effective hypoglycemic activity in our previous research. This study aims to explore the mechanism of protect effect on diabetes mice of mulberry branch bark as food supplement based on non-targeted GC-MS metabolomics' platform.
Animal model of double diabetes was established with high fat diet and Streptozotocin injection. Mice were fed with mulberry branch bark powder (MBBP) for five weeks to study its therapeutic effect. The metabolite feature of diabetes model and treatment group mice were characterized using a gas chromatography-mass spectrometry-based metabolomics, complemented with the biochemical evaluation, histological inspection, immunohistochemistry observations and enzyme protein detection.
A panel of endogenous metabolites were revealed that are relevant to disturbed metabolic processes among groups. The serum metabolic profiles were significantly different between the model group and treatment group. The manner of MBBP treatment showed to be significantly dose dependent and 20% MBBP treatment gain a relatively greater benefit than others. The metabolic disorders in model group include enhanced activation of the sorbitol pathway and galactose metabolite, increased activities of gluconeogenesis, fatty acid oxidation, proteins catabolism and attenuated activities of pentose phosphate pathway, glycolysis and aerobic oxidation pathways, internal synthesis of cholesterol, inositol production. MBBP treatment ameliorate these abnormal metabolize as revealed by differential metabolites comparing with that of model mice, such as decreasing the accumulation of ketone body, enhancing NADPH biosynthesis, partially reversing oxidative stress and energy metabolism disturbance.
Mulberry branch bark had a re-balancing effect on the disturbed metabolic pathways in the diabetic mice. Based on the metabolic pathways network, oral administration of MBBP could ameliorate the hyperglycemia and hyperlipidemia symptoms in a global scale and restore the abnormal metabolic state to a near normal level in a dose dependent pattern.
在我们之前的研究中，桑（）枝皮粉已显示出有效的降血糖活性。本研究旨在基于非靶向气相色谱 - 质谱代谢组学平台，探索桑枝皮作为食品补充剂对糖尿病小鼠保护作用的机制。
通过高脂饮食和注射链脲佐菌素建立双糖尿病动物模型。给小鼠喂食桑枝皮粉（MBBP）五周以研究其治疗效果。使用基于气相色谱 - 质谱的代谢组学对糖尿病模型和治疗组小鼠的代谢物特征进行表征，并辅以生化评估、组织学检查、免疫组织化学观察和酶蛋白检测。
揭示了一组与各组间代谢过程紊乱相关的内源性代谢物。模型组和治疗组之间的血清代谢谱有显著差异。MBBP治疗方式显示出明显的剂量依赖性，20% MBBP治疗组比其他组获得了相对更大的益处。模型组的代谢紊乱包括山梨醇途径和半乳糖代谢物的激活增强、糖异生、脂肪酸氧化、蛋白质分解代谢的活性增加以及磷酸戊糖途径、糖酵解和有氧氧化途径、胆固醇内合成、肌醇生成的活性减弱。与模型小鼠相比，通过差异代谢物揭示，MBBP治疗改善了这些异常代谢，例如减少酮体积累、增强NADPH生物合成、部分逆转氧化应激和能量代谢紊乱。
桑枝皮对糖尿病小鼠紊乱的代谢途径具有重新平衡作用。基于代谢途径网络，口服MBBP可在全球范围内改善高血糖和高血脂症状，并以剂量依赖模式将异常代谢状态恢复到接近正常水平。
