Effects of huperzine A on secretion of nerve growth factor in cultured rat cortical astrocytes and neurite outgrowth in rat PC12 cells

Abstract

Aim: To study the effects of huperzine A (HupA) on neuritogenic activity and the expression of nerve growth factor (NGF). Methods: After being treated with 10 µmol/L HupA, neurite outgrowth of PC12 cells was observed and counted under phase-contrast microscopy. Mitogenic activity was assayed by [ 3 H]thymidine incorporation. Cell cytotoxicity was evaluated by lactate dehydrogenase (LDH) release. AChE activity, mRNA and protein expression were measured by the Ellman's method, RT-PCR, and Western blot, respectively. NGF mRNA and protein levels were determined by RT-PCR and ELISA assays. Results: Treatment of PC12 cells with 10 µmol/L HupA for 48 h markedly increased the number of neuritebearing cells, but caused no significant alteration in cell viability or other signs of cytotoxicity. In addition to inhibiting AChE activity, 10 µmol/L HupA also increased the mRNA and protein levels of this enzyme. In addition, following 2 h exposure of the astrocytes to 10 µmol/L HupA, there was a significant up-regulation of mRNA for NGF and P75 low-affinity NGF receptor. The protein level of NGF was also increased after 24 h treatment with HupA. Conclusion: Our findings demonstrate for the first time that HupA has a direct or indirect neurotrophic activity, which might be beneficial in treatment of neurodegenerative disorders such as Alzheimer disease.

Steady and fluctuant methods of inhibition of acetylcholinesterase differentially regulate neurotrophic factors in the hippocampus of juvenile mice

“…In contrast, BDNF and NGF levels did not show any significant changes after the fluctuant inhibition of AChE in HT-treated mice. These results differ from previous studies, which concluded that AChE inhibitors increase neurotrophic factors levels (18,(20)(21)(22). Regarding the contradictory results, it must be noted that the neurotrophic factor levels in the previous studies were measured immediately (4 to 24 h) after administration of AChE inhibitors.…”

Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine1

“…Accumulating evidence indicates that AChE may influence neurite outgrowth through a non-catalytic mechanism [138] . Hence, the effect of HupA on neurite outgrowth may be associated with the level of AChE expression [139] . Neurotrophic factors such as NGF not only promote the survival of responsive neurons but also protect them from oxidative injury.…”

New insights into huperzine A for the treatment of Alzheimer's disease

“…In line with this observation, huperzine A administration was found to enhance the expression and secretion of NGF, as well as increase p75NTR mRNA in primary astrocytes [12] , enhance the non-amyloidogenic pathway by increasing the levels of sAPPα [13] possibly associated with M1 muscarinic ACh receptor mediated pathway [14][15][16] , and reduce the hypoxia ischemiatriggered inflammatory response through α7 nicotinic ACh receptor [17][18][19] . Since previous study has proven that huperzine A had no direct effect on the amplitude or kinetics of nAChRs activation [20] , above cholinergic system-associated beneficial effects of huperzine A administration may mainly act through the enhancement of synaptic ACh level.…”