Isolation and identification of neuroprotective compounds from Morus alba L. root bark against NMDA-induced retinal degeneration

Morus alba L. root bark (MAR) has been used in traditional Chinese medicine and has recently attracted attention for its neuroprotective potential. In this study, 23 compounds were isolated from MAR, including two new compounds (1 and 2) and six new natural products (3-8) present as stereoisomeric mixtures, all characterised by NMR, ECD, and HRESIMS. Bioactivity screening identified five compounds (2, 9, 11, 18, and 19) with significant neuroprotective effects, with compound 19 (EC50 = 0.3 ± 0.12 µM) showing the strongest effect. Under glutamate-induced oxidative stress, compound 19 reduced ROS levels from 2.23-fold to near control levels (1.07-fold) and markedly decreased apoptosis. In an NMDA-induced retinal degeneration mouse model, compound 19 preserved retinal thickness, reduced retinal ganglion cell loss, and suppressed apoptosis-related protein expression. These results significantly expand the phytochemical profile of MAR and highlight compound 19 as a promising glaucoma therapeutic candidate.