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, m Show more
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. Show less
In the present study, a comparative global high-throughput proteomic analysis strategy was used to identify proteomic differences between estrus and diestrus stage of estrous cycle in dairy cows. Sali Show more
In the present study, a comparative global high-throughput proteomic analysis strategy was used to identify proteomic differences between estrus and diestrus stage of estrous cycle in dairy cows. Saliva was collected from cows during estrus and diestrus, and subjected to LC-MS/MS-based proteomic analysis. A total of 2842 proteins were detected in the saliva of cows, out of which, 2437 and 1428 non-redundant proteins were identified in estrous and diestrous saliva, respectively. Further, it was found that 1414 and 405 salivary proteins were specific to estrus and diestrus, respectively while 1023 proteins were common to both groups. Among the significantly dysregulated proteins, the expression of 56 proteins was down-regulated (abundance ratio <0.5) while 40 proteins were up-regulated (abundance ratio > 2) in estrous compared to diestrous saliva. The proteins, such as HSD17B12, INHBA, HSP70, ENO1, SRD5A1, MOS, AMH, ECE2, PDGFA, OPRK1, SYN1, CCNC, PLIN5, CETN1, AKR1C4, NMNAT1, CYP2E1, and CYP19A1 were detected only in the saliva samples derived from estrous cows. Considerable number of proteins detected in the saliva of estrous cows were found to be involved in metabolic pathway, PI3K-Akt signaling pathway, toll-like receptor signaling pathway, steroid biosynthesis pathway, insulin signaling pathway, calcium signaling pathway, estrogen signaling pathway, oxytocin signaling pathway, TGF-β signaling pathway and oocyte meiosis. On the other hand, proteins detected in saliva of diestrous cows were involved mainly in metabolic pathway. Collectively, these data provide preliminary evidence of a potential difference in salivary proteins at different stages of estrous cycle in dairy cows. Show less