Neurotrophic Effects of Mu Bie Zi (Momordica cochinchinensis) Seed Elucidated by High-Throughput Screening of Natural Products for NGF Mimetic Effects in PC-12 Cells.

摘要: Post-mitotic central nervous system (CNS) neurons have limited capacity for regeneration, creating a challenge in the development of effective therapeutics spinal cord injury or neurodegenerative diseases. Furthermore, therapeutic use human neurotrophic agents such as nerve growth factor (NGF) are due to hampered transport across blood brain barrier (BBB) and large number peripheral side effects (e.g. neuro-inflammatory pain/tissue degeneration etc.). Therefore, there is continued need discovery small molecule NGF mimetics that can penetrate BBB initiate CNS neuronal outgrowth/regeneration. In current study, we conduct an exploratory high-through-put (HTP) screening 1144 predominantly natural/herb products (947 natural herbs/plants/spices, 29 polyphenolics 168 synthetic drugs) ability induce neurite outgrowth PC12 dopaminergic cells grown on rat tail collagen, over 7 days. The data indicate remarkably rare event-low hit ratio with only 1/1144 tested substances (<111.25 µg/mL) being capable inducing dose dependent manner, identified as; Mu Bie Zi, Momordica cochinchinensis seed extract (MCS). To quantify MCS, 36 images (n = 6) (average 340 per image), were numerically assessed length, count/cell min/max length microns (µm) using Image J software. show elongation from 0.07 ± 0.02 µm (controls) 5.5 0.62 (NGF 0.5 μg/mL) 3.39 0.45 (138 where average maximum group extended 3.58 0.42 41.93 3.14 40.20 2.72 Imaging analysis immunocytochemistry (ICC) confirmed MCS had similar influence 3-D orientation/expression 160/200 kD neurofilament, tubulin F-actin. These latent changes associated early rise phosphorylated extracellular signal-regulated kinase (ERK) p-Erk1 (T202/Y204)/p-Erk2 (T185/Y187) at 60 min mild pAKT peaking 5 min, no indication pMEK involvement. findings demonstrate remarkable infrequency polyphenolic constituents exert low concentrations, elucidate unique property do so. Future research will be required delineate depth mechanism action responsible potential application degenerative disease injury.