Effects of an Aqueous Extract of Asparagus cochinchinensis on the Regulation of Nerve Growth Factor in Neuronal Cells

신경세포에서 신경성장인자(nerve growth factor)의 조절에 미치는 천문동(Asparagus cochinchinensis) 열수추출물의 영향

  • Received : 2016.01.07
  • Accepted : 2016.03.15
  • Published : 2016.05.30


Asparagus cochinchinensis is a medical plant that has long been used to treat fever, cough, kidney disease, breast cancer, inflammatory disease and brain disease in northeast Asian countries. Although several studies have been conducted on the anti-neuroinflammatory effects of A. cochinchinensis, the correlation between these effects and nerve growth factor (NGF) has not yet been examined. In this study, we investigated the effects of an aqueous extract of A. cochinchinensis (AEAC) on the secretion and action mechanism of NGF in neuronal cells. The concentration of the NGF protein in the supernatant collected from cultured cells increased significantly in B35 cells treated with AEAC in comparison with the vehicle-treated group without any specific cytotoxicity. Furthermore, the mRNA expression of NGF showed a very similar pattern to its protein concentration. To examine the bioactivity of NGF secreted from B35 cells, undifferentiated PC12 cells were cultured in an AEAC-conditioned medium and neuritic outgrowth was observed. The dendrite length of PC12 cells in the AEAC-treated group was significantly higher than that in the vehicle-treated group. Moreover, the level of the downstream effectors p-TrkA and p-ERK of the high-affinity NGF receptor was significantly higher in the AEAC-treated group, while the expression of the downstream effectors of the low-affinity NGF receptor was significantly lower in the same group. These results suggest that AEAC may contribute to the regulation of NGF expression and secretion in neuronal cells; it is therefore an excellent candidate for further investigation as a therapeutic drug for neurodegenerative diseases.


Asparagus cochinchinensis;B35 cells;NGF;NGF receptor;PC12 cells


  1. Barde, Y. A. 1989. Trophic factors and neuronal survival. Neuron 2, 1525-1534.
  2. Choi, S. I., Goo, J. S., Kim, J. E., Hwang, I. S., Lee, H. R., Lee, Y. J., Son, H. J., Lee, J. S. and Hwang, D. Y. 2012. Effects of Red Liriope platyphylla on NGF seretion ability, NGF receptor signaling pathway and γ-secretase components in NSE/hAPPsw transgenic mice expressing Alzheimer′s disease. Lab. Anim. Res. 28, 155-163.
  3. Choi, S. I., Park, J. H., Her, Y. K., Lee, Y. K., Kim, J. E., Nam, S. H., Goo, J. S., Jang, M. J., Lee, H. S., Son, H. J., Lee, C. Y. and Hwang, D. Y. 2010. Effects of water extract of Liriope platyphylla on the mRNA expression and protein secretion of nerve growth factors. Kor. J. Med. Crop Sci. 18, 291-297.
  4. Cong, P. Z. and Keman, S. 2000. Handbook of analytical Chemistry—Mass Volume, pp. 296-298, 2nd ed., Chemical Industry Publishing House: Beijing, China.
  5. Cragg, G. M. and Newman, D. J. 2005. Drug discovery and development from natural products: the way forward. The 11th NAPRECA Symposium Book of Proceedings. August 9-12. Antananarivo, Madagascar.
  6. Efange, S. M. N. 2002. Natural products: a continuing source of inspiration for the medical chemist, pp. 61-69. In: Iwu, M. M., Wootton, J. C. (eds), Ethnomedicine and drug discovery: Advances in Phytomedicine. Elsevier Science: Amsterdam, The Netherlands.
  7. Freund-Michel, V. and Frossard, N. 2008. The nerve growth factor and its receptors in airway inflammatory diseases. Pharmacol. Ther. 117, 52-76.
  8. Gong, Y. H. 1986. 13C NMR chemical shifts of natural organic compounds, pp. 252, 2nd ed., Yunnan Science and Technology Publishing House: Kunming, China
  9. Hur, J. Y., Lee, P. J., Kim, J. M., Kim, A. J., Kim, H. C. and Kim, S. Y. 2004. Induction of nerve growth factor by butanol fraction of Liriope platyphylla in C6 and primary astrocyte cells. Biol. Pharm. Bull. 27, 1257-1260.
  10. Hur, J. Y., Lee, P. J., Moon, E. J., Kang, I. S., Kim, S. H., Oh, M. S. and Kim, S. Y. 2009. Neurite outgrowth induced by spicatoside A, a steroidal saponin, via the tyrosine kinase A receptor pathway. Eur. J. Pharmacol. 620, 9-15.
  11. Jung, K. H., Choi, H. L., Park, S. J., Lee, G. H., Kim, M. R., Min, J. K., Min, B. I. and Bae, H. S. 2014. The effects of the standardized herbal formula PM014 on pulmonary inflammation and airway responsiveness in a murine model of cockroach allergen-induced asthma. J. Ethnopharmacol. 155, 113-122.
  12. Kim, H. M., Lee, E. H., Lim, T. K., Jung, J. A. and Lyu, Y. S. 1998. Inhibitory effect of Asparagus cochinchinensis on tumor necrosis factor-alpha secretion from astrocytes. Int. J. Immunopharmacol. 20, 153-162.
  13. Koo, H. N., Jeong, H. J. and Choi, J. Y. 2000. Inhibition of tumor necrosis factor-a-induced apoptosis by Asparagus cochlnchinensis in HepG2 cells. J. Ethnopharmacol. 73, 137-143.
  14. Lee, D. Y., Choo, B. K., Yoon, T. S., Cheon, M. S., Lee, H. W., Lee Y. A. and Kim, H. K. 2009. Anti-inflammatory effects of Asparagus cochinchinensis extract in acute and chronic cutaneous inflammation. J. Ethnopharmacol. 121, 28-34.
  15. Lee, J. H., Lim, H. J., Lee, C. W., Son, K. H., Son, J. K., Lee, S. K. and Kim, H. P. 2015. Methyl protodioscin from the roots of Asparagus cochinchinensis attenuates airway inflammation by inhibiting cytokine production. Evid. Based Complement Alternat. Med. 2015, 640846.
  16. Liang, Z. Z., Aquino, R., De Simone, F., Dini, A., Schettino, O. and Pizza, C. 1988. Oligo furo stanosides from Asparagus cochinchinensis. Planta Med. 54, 344–346.
  17. Li, M., Fei, Y. and Wang, J. K. 2005. Studies on pharmacologic effects of Radix asparagi. LiShiZhen Med. Mater Med. Res. 16, 580-582.
  18. Li, P., Matsunaga, K. and Ohizumi, Y. 2000. Nerve growth factor-potentiating compounds from Picrorhizae rhizoma. Biol. Pharm. Bull. 23, 890-892.
  19. Li, X. N., Chu, C., Cheng, D. P., Tong, S. Q. and Yan, J. Z. 2012. Norlignans from Asparagus cochinchinensis. Na Prod. Commun. 7, 1357-1358.
  20. Liu, Y. Z., Qu, F. Y. and Zhang, P. X. 2001. Effect of chloroform extract of Tiandong on the brain antioxidation of D-galatose-induced senile mice. Heilongjiang Med. Pharm. 24, 7-8.
  21. Luo, J., Long, Q. D., Li, C. X., Li, L. and Huang, N. H. 2000. Inhibitory effects of ALWB and ACM on mice bearing tumor. J. GuiYang Med. Coll. 25, 15-16.
  22. Luo, J., Long, Q. D., Li, C. X., Li, L., Huang, N. H., Nie, M. and Tang, P. X. 1998. Comparison of antitussive, expectorant and anti-asthmatic effect between ALWB and ACM. J. GuiYang Med. Coll. 23, 132-134.
  23. Lv, B. and Liu, W. Z. 2004. Aspartate treatment of hemodialysis patients with hypertension in 22 cases. J. Tradit Chin. Med. 19, 43-44.
  24. Nam, S. H., Choi, S. I., Goo, J. S., Kim, J. E., Lee, Y. K., Hwang, I. S., Lee, H. R., Lee, Y. J., Lee, H. G., Choi, Y. W. and Hwang, D. Y. 2011. LP-M, a novel butanol-extracts isolated from Liriope platyphylla, could induce the neuronal cell survival and neuritic outgrowth in hippocampus of mice through Akt/ERK activation on NGF signal pathway. J. Life Sci. 21. 1234-1243.
  25. Newman, D. J. 2008. Natural products as leads to potential drugs: an old process or the new hope for drug discovery? J. Med. Chem. 51, 2589-2599.
  26. Ni, J. M., Zhao, R. and Wang, R. 1992. Comparison on amino acid content in prepared and unprepared Asparagus cochinchinensis. Chin. Tradit. Herb Drugs 23, 182-183.
  27. Park, S. C., Kim, S. E., Oh, D. M., Shim, K. M., Jeong, M. J., Lim, S. C., Nah, S. Y., Park, S. H., Kang, S. S., Moon, C. J., Kim, J. C., Kim, S. H. and Bae, C. S. 2009. Effect of Korean red ginseng extract in a steroid-induced polycystic ovary murine model. Arch. Pharm. Res. 32, 347-352.
  28. Qu, F. Y., Wei, X. D., Li, S. L., Wang, Y. M. and Bai, S. G. 1999. Experimental study of Asparagus cochinchinensis delay aging. Acta Chin. Med. Pharm. 2, 68-70.
  29. Salim, K. N., McEwen, B. S. and Chao, H. M. 1997. Ginsenoside Rb1 regulates ChAT, NGF and trkA mRNA expression in the rat brain. Brain Res. Mol. Brain Res. 47, 177-182.
  30. Shen, Y., Chen, H. S. and Wang, Q. 2007. Studies on chemical constituents of Asparagus cochinchinensis(II). J. Second Med. Univ. 28, 1241-1244.
  31. Shen, Y., Xu, C. l., Xuan, W. D., Li, H. L., Liu, R. H., Xu, X. K. and Chen, H. S. 2011. A new furostanol saponin from Asparagus cochinchinensis. Arch. Pharm. Res. 34. 1587-1591.
  32. Singleton, V. L. and Rossi, J. A. 1965. Colorimetry of total phenolics with phosphomolybdic-phosphotungstic acid reagents. Am. J. Enol. Vitic. 16, 144-158.
  33. Tenji, K. and Junzo, S. 1979. Studies on the constituents of Asparagi Radix. I. On the structures of furostanol oligosides of Asparagus cochinchinensis (Lour.) Merr. Chem. Pharm. Bull. 27, 3086-3094.
  34. Theonen, H., Bandtlow, C. and Heuman, R. 1987. The physiological function of nerve growth factor in the central nervous system: comparison with the periphery. Rev. Physiol. Biochem. Pharmacol. 109, 146-178.
  35. Tsui-Pierchala, B. A. and Ginty, D. D. 1999. Characterization of an NGF-P-TrkA retrograde-signaling complex and age-dependent regulation of TrkA phosphorylation in sympathetic neurons. J. Neurosci. 19, 8207-8218.
  36. Tuszynski, M. H., Gabriel, K., Gage, F. H., Shur, S., Meyer, S. and Rosetti, A. 1996. Nerve growth factor delivery by gene transfer induces differential outgrowth of sensory, motor and noradrenergic neurites after adult spinal cord injury. Exp. Neurol. 137, 157-173.
  37. Wen, J. Y., Li, Y., Ding, S. S. and Li, Q. H. 1993. Nine Pharmacological screening of medicinal plants of China Liliaceae asparagus. J. Acta Acad Med. Shanghai 20, 107-111.
  38. Xiao, P.G. 2002. Modern chinese material medica, pp. 150, 2nd ed., Chemical Industry Press: Beijing, China.
  39. Xiong, D. S., Yu, L. X., Yan, X., Guo, C. and Xiong, Y. 2011. Effects of root and stem extracts of Asparagus cochinchinensis on biochemical indicators related to aging in the brain and liver of mice. Am. J. Chin. Med. 39, 719-726.
  40. Xu, C. L., Chen, H. S. and Tan, X. Q. 2005. Studies on the active constituents of Asparagi radix. Nat. Prod. Res. Dev. 17, 128-130.
  41. Yang, M. H. 1981. Steroidal sapogenins of dioscorea. Chin Tradit Herb Drugs. 12, 43-44.
  42. Yang, Y. C., Huang, S. Y. and Shi, J. G. 2002. Two new furostanol glycosides from Asparagus cochinchinensis. Chin. Chem. Lett. 13, 11850-11880.
  43. Yu, F. R., Lian, X. Z. and Guo, H. Y. 2006. Effect of lucid asparagus extract on the regulation of blood sugar. Chin. J. Clin. Rehabil. 10, 57-59.
  44. Zhao, Y. J., Meng, X. L., Li, X. L. and Qu, F. Y. 2005. Influence of Radix asparagi nano-pharmaceutics on NOS, NO, LPF of aging mice. Chin. Wild. Plant Resour. 24, 49-51.
  45. Zhishen, J., Mengcheng, T. and Jianming, W. 1999. The determination of flavonoid contents in mulberry and their scavenging effects on superoxide radicals. Food Chem. 64, 555-559.
  46. Zhu, G. L., Hao, Q., Li, R. T. and Li, H. Z. 2014. Steroidal saponins from the roots of Asparagus cochinchinensis. Chin. J. Nat. Med. 12, 213-217.
  47. Freund-Michel, V. and Frossard, N. 2008. The nerve growth factor and its receptors in airway inflammatory diseases. Pharmacol. Ther. 117, 52-76.

Cited by

  1. Quercetin promotes gastrointestinal motility and mucin secretion in loperamide-induced constipation of SD rats through regulation of the mAChRs downstream signal vol.56, pp.1, 2018,
  2. Asparagus cochinchinensis stimulates release of nerve growth factor and abrogates oxidative stress in the Tg2576 model for Alzheimer’s disease vol.18, pp.1, 2018,
  3. Anti-Inflammatory Response and Muscarinic Cholinergic Regulation during the Laxative Effect of Asparagus cochinchinensis in Loperamide-Induced Constipation of SD Rats vol.20, pp.4, 2019,