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 [3H]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 neurite-bearing 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.
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Project supported by the National Natural Science Foundation of China (No 30123005) and the Ministry of Science and Technology of China (No 2004CB518907).
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Tang, Ll., Wang, R. & Tang, Xc. Effects of huperzine A on secretion of nerve growth factor in cultured rat cortical astrocytes and neurite outgrowth in rat PC12 cells. Acta Pharmacol Sin 26, 673–678 (2005). https://doi.org/10.1111/j.1745-7254.2005.00130.x
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DOI: https://doi.org/10.1111/j.1745-7254.2005.00130.x
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