从玛咖“性温味甘健脾”研究玛咖多糖促进能量代谢及免疫调控机制

Maca is native to South America, and is known as South American Ginseng because it has a variety of biological activities including physical strength enhancement, immune regulation and so on. Maca has been successfully introduced into China and planted, and used with a variety of traditional Chinese medicinal materials. However, there has been lack of theoretical basis on the issue of Chinese medicine property of maca. We have analyzed the Chinese and foreign literatures and established a literature database of maca. Chinese medicine property of maca combined with traditional Chinese medicine theory and conducted experimental verification have been proposed. Maca polysaccharides were screened as the main active ingredient of maca with warm, sweet and strengthening spleen property. Spleen deficiency model have been established, Ginseng, a major strengthen spleen herb, as control. Then study of hot and heat property indexes of maca powder and polysaccharides and mitochondrial energy metabolism enzymes were explored. Furthermore, methods of analyzing the mitochondrial, glycolytic functionality and metabolic phenotype of hepatocyte and spleen cells by seahorse XF technology were designed. The mechanism of enhancing immunity of maca was investigated by immune cytokines, bone marrow stem cell apoptosis proteins and lymphocyte proliferation and typing based on the sweet and strengthening spleen property of maca. As well as, effective material fundamentals and mechanisms of maca were revealed based on metabolomics technology screening of metabolites and analysis pathway. This study aims to measure the Chinese medicine property based on syndromes, to reveal the correlation between property and effects. It is of great significance for guiding the reasonable maca application compatibility of traditional Chinese medicinal materials. It makes full use of the latest scientific and technological achievements and reveals the clinical application of scientific connotation of traditional Chinese medicine theory.

玛咖原产南美，具有增强体力、调节免疫等多种生物活性被誉为南美人参，已在我国成功引种并与多种中药配伍应用，但缺乏中药药性理论依据。我们分析玛咖中外文献建立数据库，结合中医药理论提出其中药药性并实验验证，筛选出玛咖多糖为性温味甘健脾的主要活性成分。本研究采用脾虚证模型，以补脾要药人参为对照，从性温考察玛咖、玛咖多糖对脾虚证寒热药性指标及肝、脾线粒体能量代谢酶的影响，用SeahorseXF能量分析系统测肝、脾细胞线粒体呼吸和糖酵解通路；从味甘健脾考察对功效指标的影响，研究免疫细胞因子、骨髓干细胞凋亡蛋白的变化及淋巴细胞增殖与分型；用代谢组学技术筛选代谢标志物并分析通路；从整体、组织、细胞、分子不同层次探讨玛咖影响能量代谢增强体力、调控免疫的物质基础和作用机制。本研究“以证测性”探讨“性效相关”，对积极引导玛咖与中药配伍合理应用现实而迫切，对深入揭示中药药性理论科学内涵、指导临床应用具有意义。

玛咖原产南美，具有增强体力、调节免疫等多种生物活性被誉为南美人参，已在我国成功引种并与多种中药配伍应用，但缺乏中药药性理论依据。课题组前期研究结合中医药理论首次提出玛咖中药药性，筛选出玛咖多糖为“性温味甘健脾”的主要活性成分。.本研究运用中医证候模型及中药药性最新研究成果，通过“以证测性，性效相关”研究玛咖“性温味甘”药性及“甘温健脾”功效。通过建立环磷酰胺致脾虚证模型，从性温考察玛咖、玛咖多糖对脾虚证寒热药性指标及肝、脾线粒体能量代谢酶的影响，玛咖多糖可以增强小鼠体重、促进脾虚小鼠温度趋向性、调节线粒体ATP酶，促进能量代谢酶NADH、SDH和VDAC的表达，玛咖多糖是玛咖“甘温”的物质基础，通过激发线粒体能量代谢酶的活性，氧化磷酸化产生的 ATP 推动机体的各项生命运动，体现了“性温味甘”药物的补益作用。从味甘健脾考察对中医功效指标的影响，从外周血淋巴细胞、脾脏细胞通过多个层面、多种方法研究玛咖多糖对脾虚证小鼠的免疫调节作用，其机制在于抑制淋巴细胞凋亡、促进机体Th1/Th2细胞亚群恢复平衡；运用代谢组学分析和相关性分析技术，玛咖多糖调节甘油磷脂代谢和磷酸戊糖通路促进能量代谢，基于Keap1-Nrf2通路揭示了抗氧化、改善能量代谢的作用机制。.本项目从改善脾虚小鼠能量代谢和免疫调节作用，将玛咖“性温味甘健脾”客观存在的宏观效应深入到物质基础和作用机制层次，多方位建立了天然药用资源现代研究成果与中药药性理论及现代研究方法的内在关联，阐释了“甘温健脾”中医功效的科学内涵。本项目为建立以中药性能为核心的玛咖中药标准提供科学依据，有助于玛咖控制质量并指导与中药配伍应用。项目研究成果为团队荣获中华中医药学会科学技术奖，中国国际促进会《外来中药标准建立的指南》团体标准的发布提供支撑、发挥示范作用，为新的药用资源科学合理进入中医临床提供理论及实验依据，对于深入阐释中药药性理论科学内涵指导临床应用具有引领意义。