Shaji Vineetha, Amrutha S, Pervaje Ravishankar, Abhinand Chandran S, Raju Rajesh, Prasad Thottethodi Subrahmanya Keshava, Modi Prashant Kumar
Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to Be University), Deralakatte, Mangalore, Karnataka, 575018, India.
Sushrutha Ayurveda Hospital, Puttur, 574201, India.
Neurochem Res. 2025 Jun 8;50(3):190. doi: 10.1007/s11064-025-04440-9.
Asparagus racemosus Willd, an Ayurvedic medicine, is known for its antioxidant, antiviral, immune-boosting, and neuro-nutraceutical benefits, particularly in female health. However, its metabolites, mechanisms of action, and target proteins are yet to be fully understood. The present study aimed to identify the metabolite constitution and metabolite-associated proteins in neuroprotective mechanisms in neurodegenerative disease. Mass spectrometry-based untargeted metabolomics and network pharmacology approaches were used to identify metabolites in A. racemosus root extract. In vitro studies, including oxidative stress regulation, neuronal apoptosis, and western blot analysis, were conducted to assess the plant's impact on Alzheimer's disease (AD). We identified 44,014 spectra in positive and negative modes, corresponding to 31,931 non-redundant metabolites at the MS1 level and 5,608 at the MS2 level, from A. racemosus root extract, which include metabolites belonging to phenols, lipids, flavonoids, isoprenoids, and fatty acyls. Novel and known compounds were identified, such as asparagine, sitosterol, arginine, muzanzagenin, pinene, flavone, and kaempferol. Network pharmacology predicted 44 potential human protein targets linked to Alzheimer's disease from these metabolites. These proteins belong to neuromodulator classes, including BACE1, CHRM3, APP, MAP2K1, GSK3B, and TNF, and some of the metabolites of A. racemosus including muzanzagenin interact with BACE1 protein. In vitro validation showed that A. racemosus regulates ROS levels, apoptosis pathways, and BACE1 expression in Alzheimer's disease (AD), highlighting its therapeutic potential. This study integrates network pharmacology and metabolomics, paving the way for clinical research into the neuropharmacological effects of A. racemosus on neurological disorders.
印度人参（Asparagus racemosus Willd）是一种阿育吠陀药物，以其抗氧化、抗病毒、增强免疫力和神经营养益处而闻名，尤其对女性健康有益。然而，其代谢产物、作用机制和靶蛋白尚未完全明确。本研究旨在确定神经退行性疾病神经保护机制中的代谢产物组成和与代谢产物相关的蛋白质。采用基于质谱的非靶向代谢组学和网络药理学方法来鉴定印度人参根提取物中的代谢产物。进行了包括氧化应激调节、神经元凋亡和蛋白质印迹分析在内的体外研究，以评估该植物对阿尔茨海默病（AD）的影响。我们在正负模式下从印度人参根提取物中鉴定出44,014个光谱，在MS1水平对应31,931个非冗余代谢产物，在MS2水平对应5,608个，其中包括酚类、脂质、黄酮类、类异戊二烯和脂肪酰基的代谢产物。鉴定出了新的和已知的化合物，如天冬酰胺、谷甾醇、精氨酸、穆赞扎吉宁、蒎烯、黄酮和山奈酚。网络药理学从这些代谢产物中预测出44个与阿尔茨海默病相关的潜在人类蛋白质靶点。这些蛋白质属于神经调节因子类别，包括β-分泌酶1（BACE1）、毒蕈碱型乙酰胆碱受体M3（CHRM3）、淀粉样前体蛋白（APP）、丝裂原活化蛋白激酶激酶1（MAP2K1）、糖原合成酶激酶3β（GSK3B）和肿瘤坏死因子（TNF），印度人参的一些代谢产物包括穆赞扎吉宁与BACE1蛋白相互作用。体外验证表明，印度人参可调节阿尔茨海默病（AD）中的活性氧水平、凋亡途径和BACE1表达，突出了其治疗潜力。本研究整合了网络药理学和代谢组学，为印度人参对神经疾病神经药理作用的临床研究铺平了道路。
