Project supported by the National Natural Science Foundation of China (No 30123005) and the Ministry of Science and Technology of China (No 2004CB518907).
Effects of huperzine A on secretion of nerve growth factor in cultured rat cortical astrocytes and neurite outgrowth in rat PC12 cells1
Article first published online: 23 MAY 2005
Acta Pharmacologica Sinica
Volume 26, Issue 6, pages 673–678, June 2005
How to Cite
TANG, L.-l., WANG, R. and TANG, X.-c. (2005), Effects of huperzine A on secretion of nerve growth factor in cultured rat cortical astrocytes and neurite outgrowth in rat PC12 cells. Acta Pharmacologica Sinica, 26: 673–678. doi: 10.1111/j.1745-7254.2005.00130.x
- Issue published online: 23 MAY 2005
- Article first published online: 23 MAY 2005
- Received 2004-12-27; Accepted 2005-03-15
- huperzine A;
- nerve growth factor;
- neurite outgrowth;
- acetylcholinesterase inhibitors
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.