Lin He, Teng Houlei, Wu Wei, Li Yong, Lv Guangfu, Huang Xiaowei, Yan Wenhao, Lin Zhe
College of Pharmacy, Changchun University of Chinese Medicine, Changchun, China.
Changzhou Deze Drug Research Co., Ltd, Changzhou, China.
BMC Pharmacol Toxicol. 2020 Aug 6;21(1):59. doi: 10.1186/s40360-020-00438-x.
Non-alcoholic fatty liver is one of the most common comorbidities of diabetes. It can cause disturbance of glucose and lipid metabolism in the body, gradually develop into liver fibrosis, and even cause liver cirrhosis. Mangiferin has a variety of pharmacological activities, especially for the improvement of glycolipid metabolism and liver injury. However, its poor oral absorption and low bioavailability limit its further clinical development and application. The modification of mangiferin derivatives is the current research hotspot to solve this problem.
The plasma pharmacokinetic of mangiferin calcium salt (MCS) and mangiferin were monitored by HPLC. The urine metabolomics of MCS were conducted by UPLC-Q-TOF-MS.
The pharmacokinetic parameters of MCS have been varied, and the oral absorption effect of MCS was better than mangiferin. Also MCS had a good therapeutic effect on type 2 diabetes and NAFLD rats by regulating glucose and lipid metabolism. Sixteen potential biomarkers had been identified based on metabolomics which were related to the corresponding pathways including Pantothenate and CoA biosynthesis, fatty acid biosynthesis, citric acid cycle, arginine biosynthesis, tryptophan metabolism, etc. CONCLUSIONS: The present study validated the favorable pharmacokinetic profiles of MCS and the biochemical mechanisms of MCS in treating type 2 diabetes and NAFLD.
非酒精性脂肪性肝病是糖尿病最常见的合并症之一。它可导致体内糖脂代谢紊乱，逐渐发展为肝纤维化，甚至引发肝硬化。芒果苷具有多种药理活性，尤其在改善糖脂代谢和肝损伤方面。然而，其口服吸收差、生物利用度低限制了其进一步的临床开发与应用。芒果苷衍生物的修饰是解决这一问题的当前研究热点。
采用高效液相色谱法监测芒果苷钙盐（MCS）和芒果苷的血浆药代动力学。通过超高效液相色谱-四极杆飞行时间质谱联用仪对MCS进行尿液代谢组学研究。
MCS的药代动力学参数有所变化，其口服吸收效果优于芒果苷。此外，MCS通过调节糖脂代谢对2型糖尿病和非酒精性脂肪性肝病大鼠具有良好的治疗作用。基于代谢组学确定了16种潜在生物标志物，它们与泛酸和辅酶A生物合成、脂肪酸生物合成、柠檬酸循环、精氨酸生物合成、色氨酸代谢等相应途径相关。结论：本研究验证了MCS良好的药代动力学特征以及MCS治疗2型糖尿病和非酒精性脂肪性肝病的生化机制。
