A network pharmacology study on the triterpene saponins from Medicago sativa L. for the treatment of Neurodegenerative diseases.

Neurodegenerative diseases (NDDs) are characterized by progressive and irreversible, is a kind of complex illnesses, and the long-term therapy which is frequently associated with adverse side effects. Medicago sativa L., widely consumed as a vegetable, has the effects of improving memory and relieving central nervous system diseases. However, there are less studies on its specific mechanism for NDDs. In this investigation, we applied a method of network pharmacology, which combined molecular docking and network analysis to decipher the mechanisms of M. sativa in NDDs. The pharmacological system generated 55 triterpene saponins from M. sativa, and predicted 27 potential targets with 100 pathways in the treatment of NDDs. As a result, 13 compounds, 10 target proteins, and 6 signaling pathways were found to play important roles in the treatment of NDDs. In addition, in vitro experiments of isolates confirmed activities for NDDs, which were consistent with the results of network pharmacology prediction. PRACTICAL APPLICATIONS: Medicago sativa L. has been widely consumed as a vegetable, which possesses many nutritional components. As a functional food stuff, M. sativa can improve human health, such as memory improving activities, relieving central nervous system diseases, immunomodulatory, antioxidant, anticancer, and anti-inflammatory. In this article, the mechanism of triterpene saponins from M. sativa against NDDs was successfully predicted by network pharmacology method. The results will serve as a reference of M. sativa against NDDs.

Neuroprotective effects of triterpenoid saponins from Medicago sativa L. against H2O2-induced oxidative stress in SH-SY5Y cells.

Medicago sativa L. is a forage legume plant widely distributed in all continents. Six new triterpenoid saponins, Medicagosides A-F (1-6) and five known ones (7-11) were isolated from M. sativa. Their structures were determined via HRESIMS, 1D and 2D NMR analysis. Biologically, all the isolates displayed neuroprotective activities against H2O2-induced damage in SH-SY5Y cells. Among them, compounds 1, 3-5 and 10 exhibited striking neuroprotective activities at 100 µM, restoring cell viability range from 79.66% to 89.03%, relative to 79.46% (100 µM) of Trolox used as the positive control.