Neuritogenic activity of coumarins from Clausena harmandiana

Coumarins have been identified from natural sources, especially green plants such as Clausena harmandiana. Antioxidant activity of the plant was assayed using 1,1-diphenyl-2-pricrylhydrazyl (DPPH) and Thiobarbituric Acid Reactive Substances (TBARS) methods while its neuritogenic effects was assessed on cultured P19 neurons. Nordentatin, isolated from the root bark of C. harmandiana, showed more potent antioxidant and inhibition of lipid peroxidation than its derivatives, dentatin and xanthoxyletin. Nordentatin with IC₅₀ > 10 mM and viability of 82.74 ± 24.54% showed no neurotoxicity while dentatin and xanthoxyletin expressed neurotoxicity at 1 nM (viability 62.28 ± 12.11% and 43.02 ± 10.31%, respectively). Phase-contrast micrographs showed that nordentatin promoted the outgrowth of the neurites of the neurons. The neurons treated with the extracts displayed significantly more branching numbers of the neurites than the control (p < 0.05), indicating that nordentatin was a remarkable natural neuritogen.