摘要
辣木Moringa oleifera在阿育吠陀医学中被广泛用于治疗头部疾病及改善心神功能,其叶、籽和根皮分别具有vātahara(除风)、sirovirecaka(清脑)、hridya(护养心神)等传统功效。该研究以《鲍威尔写本》记载的Sārasvata方中“sigru”药用部位辨识为目标,系统比较辣木叶、辣木籽和辣木根皮对东莨菪碱(Sco)诱导的学习记忆障碍小鼠的药效差异,并通过多组学技术阐明其分子机制。选用144只雄性ICR小鼠,随机分为空白组,模型组(Sco,2 mg·kg^(-1)),多奈哌齐组(盐酸多奈哌齐片,3 mg·kg^(-1)),辣木叶低、中、高剂量(0.5、1、2 g·kg^(-1))组,辣木籽低、中、高剂量(0.25、0.5、1 g·kg^(-1))组,辣木根皮低、中、高剂量(0.31、0.62、1.24 g·kg^(-1))组。通过被动回避实验和Morris水迷宫评估学习记忆能力,Nissl和HE染色观察海马组织病理变化,结合转录组学和靶向代谢组学筛选差异基因与代谢物,采用MetaboAnalyst 6.0及O_(2)PLS方法筛选关键靶点和通路。结果表明,辣木叶(1 g·kg^(-1))显著改善Sco诱导小鼠的学习记忆障碍,优于辣木籽(0.25 g·kg^(-1))和辣木根皮(1.24 g·kg^(-1)),表现为行为学指标改善、海马神经元损伤减轻及乙酰胆碱酯酶(AChE)活性降低。转录组学和代谢组学分析揭示,辣木叶通过上调突触囊泡循环通路中微管蛋白α-1C(Tuba1c)表达,支持突触囊泡运输,增强谷氨酸(Glu)、多巴胺和乙酰胆碱(ACh)释放,通过Tuba1c-Glu关联保护神经元结构;辣木籽作用于多巴胺能突触通路,通过多巴胺D2受体基因(Drd2)-ACh关联促进记忆巩固;辣木根皮涉及可卡因成瘾通路,通过腺苷A2A受体基因(Adora2a)-多巴胺代谢产物3,4-二羟基苯乙酸(DOPAC)调节多巴胺代谢,但其与学习记忆关联较弱。综上,辣木叶在药效及机制上优于辣木籽和辣木根皮,提示《鲍威尔写本》中Sārasvata方“sigru”可使用辣木叶,为西域古文献中辣木药用部位的辨识提供科学依据。
Moringa oleifera,widely utilized in Ayurvedic medicine,is recognized for its leaves,seeds,and velamen possessing traditional effects such as vatahara(wind alleviation),sirovirecaka(brain clearing),and hridya(mental nourishment).This study aims to identify the medicinal part of'sigru'in the Sarasvata ghee formulation as described in the Bower Manuscript,while investigating the ameliorative effects of different medicinal parts of M.oleifera on learning and memory deficits in mice and elucidating the underlying molecular mechanisms.A total of 144 male ICR mice were randomly assigned to the following groups:control,model(scopolamine hydrobromide,Sco,2 mg·kg^(-1)),donepezil(donepezil hydrochloride,Don,3 mg·kg^(-1)),M.oleifera leaf low-,medium-,and high-dose groups(0.5,1,2 g·kg^(-1)),M.oleifera seeds low-,medium-,and high-dose groups(0.25,0.5,1 g.kg^(-1)),and M.oleifera velamen low-,medium-,and high-dose groups(0.31,0.62,1.24 g·kg').Learning and memory abilities were assessed using the passive avoidance test and Morris water maze.Nissl and HE staining were employed to examine histopathological changes in the hippocampus.Transcriptomics and targeted metabolomics were used to screen differential genes and metabolites,with MetaboAnalyst 6.0 and O_(2)PLS methods applied to identify key disease-related targets and pathways.Results demonstrated that M.oleifera leaf(1 g·kg^(-1))significantly ameliorated Sco-induced learning and memory deficits,outperforming M.oleifera seeds(0.25 g·kg^(-1))and M.oleifera velamen(1.24 g·kg^(-1)).This was evidenced by improved behavioral performance,reversal of neuronal damage,and reduced acetylcholinesterase(AChE)activity.Multi-omics analysis revealed that M.oleifera leaf upregulated Tubalc gene expression through the synaptic vesicle cycle,enhancing glutamate(Glu),dopamine(DA),and acetylcholine(ACh)release via Tubalc-Glu associations for neuroprotection.M.oleifera seeds targeted the dopaminergic synapse pathway,promoting memory consolidation through Drd2-ACh associations.M.oleifera velamen was associated with the cocaine addiction pathway,modulating dopamine metabolism via Adora2a-DOPAC,with limited relevance to learning and memory.In conclusion,M.oleifera leaf exhibits superior efficacy and mechanistic advantages over M.oleifera seeds and velamen,suggesting that the'sigru'in the Sarasvata ghee formulation is likely M.oleifera leaf,providing scientific evidence for its identification in ancient texts.
作者
王志昊
冯淑怡
李涛
周婉萍
王锦玉
刘洋
张琳
谢媛媛
黄秀兰
李志勇
黄璐琦
WANG Zhi-hao;FENG Shu-yi;LI Tao;ZHOU Wan-ping;WANG Jin-yu;LIU Yang;ZHANG Lin;XIE Yuan-yuan;HUANG Xiu-lan;LI Zhi-yong;HUANG Lu-qi(School of Basic Medical Sciences,Shanxi University of Chinese Medicine,Jinzhong 030619,China;State Key Laboratory for Quality Assurance and Sustainable Use of Authentic Medicinal Materials,Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Bejing 100700,China;Medical Experiment Center,China Academy of Chinese Medical Sciences,Bejing 100700,China;Guangdong Pharmaceutical University,Guangzhou 510006,China;College of Traditional Chinese Medicine,Shandong University of Traditional Chinese Medicine,Ji'nan 250355,China;School of Pharmacy,Minzu University of China,Beijing 100081,China;China Academy of Chinese Medical Sciences,Beijing 100700,China)
出处
《中国中药杂志》
北大核心
2025年第13期3793-3802,共10页
China Journal of Chinese Materia Medica
基金
国家自然科学基金面上项目(82374146)
中央本级重大增减支项目(2060302)。
关键词
辣木
学习记忆障碍
多目标优化
转录组学
靶向代谢组学
Moringa oleifera
learning and memory impairment
multi-objective optimization
transcriptomics
targeted metabolomics
作者简介
王志昊,硕士研究生,E-mail:y13572573172@163.com;通信作者:黄璐琦,研究员,博士生导师,E-mail:huangluqi01@126.com;通信作者:李志勇,研究员,硕士生导师,E-mail:lizhiyong7899@sina.com。
