👤 Anantha Krishnan Dhanabalan

This study reported the profiling and the in-silico analysis of the therapeutic potential of proteins/peptides (for Alzheimer disease) isolated from Tinospora cordifolia, Evolvulus alsinoides, Centella asiatica and Convolvulus pluricaulis. The proteins/peptides were extracted by using four different pH based buffer solutions. The trypsin digested proteins/peptides were analyzed by LC-MS/MS based peptide mass fingerprinting which showed the presence of high number of proteins/peptides involved in regulating the oxidative stress. The sequential purification with 10 kDa and 3 kDa cut-off ultrafiltration membranes for buffer based extracted proteins/peptides was performed. The evaluation of crude and these filtrates revealed the highest antioxidant potential for 3 kDa cut-off filtrate of 0.1 M Tris HCl buffer (pH 8.0) from FRAP, DPPH, ABTS and NOS assays. The presence of peptides in 3 kDa cut-off filtrates was detected by HPLC, identified by MALDI-TOF MS and the fragmentation pattern was obtained by LC-MS/MS. The in-silico docking study revealed that the identified peptides showed the highest binding affinity against the Alzheimer targets (BACE1, nAChR, Aβ, AChE, GSK-3β, JNK). Thus, the findings of this study provided the preliminary evidence for the antioxidant and neuroprotective potential of the selected medicinal plants, by supporting their relevance in delaying the onset of neurodegeneration and highlighting their prospects for drug development. Show less

The drug target protein β-secretase 1 (BACE1) is one of the promising targets in the design of the drugs to control Alzheimer's disease (AD). Patients with neurodegenerative diseases are increasing in number globally due to the increase in the average lifetime. Neuro modulation is the only remedy for overcoming these age related diseases. In recent times, marine bioactive compounds are reported from Phaeophyceae (Brown Algae), Rhodophyta (Red Algae) and Chlorophyta (Green Algae) for neuro-modulation. Hence, an important attempt is made to understand the binding and stability of the identified bioactive compounds from the above marine algae using BACE1 as the molecular target. The docking study shows that the bioactive compound Fucotriphlorethol A ( - 17.27 kcal/mol) has good binding affinity and energy compared to other compounds such as Dieckol ( - 16.77 kcal/mol), Tetraphlorethol C ( - 15.12 kcal/mol), 2-phloroeckol ( - 14.98 kcal/mol), Phlorofucofuroeckol ( - 13.46 kcal/mol) and the co-crystal ( - 8.59 kcal/mol). Further, molecular dynamics simulations studies had been carried out for β-secretase 1 complex with Fucotriphlorethol A and Phlorofucofuroeckol for 100 ns each. Results are compared with that of the co-crystal inhibitor. Molecular dynamics simulations studies also support the stability and flexibility of the two bioactive compounds Fucotriphlorethol A and Phlorofucofuroeckol with BACE1. The online version contains supplementary material available at 10.1007/s40203-024-00210-7. Show less