Skip to main content

Advertisement

Log in

Therapeutic Strategies for Parkinson’s Disease: The Ancient Meets the Future—Traditional Chinese Herbal Medicine, Electroacupuncture, Gene Therapy and Stem Cells

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

In China, it has been estimated that there are more than 2.0 million people suffering from Parkinson’s disease, which is currently becoming one of the most common chronic neurodegenerative disorders during recent years. For many years, scientists have struggled to find new therapeutic approaches for this disease. Since 1994, our research group led by Drs. Ji-Sheng Han and Xiao-Min Wang of Neuroscience Research Institute, Peking University has developed several prospective treatment strategies for the disease. These studies cover the traditional Chinese medicine—herbal formula or acupuncture, and modern technologies such as gene therapy or stem cell replacement therapy, and have achieved some original results. It hopes that these data may be beneficial for the research development and for the future clinical utility for treatment of Parkinson’s disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Lang AE, Lozano AM (1998) Parkinson’s disease. First of two parts. N Engl J Med 339:1044–1053

    Article  PubMed  CAS  Google Scholar 

  2. Zhang ZX, Roman GC, Hong Z, Wu CB, Qu QM, Huang JB, Zhou B, Geng ZP, Wu JX, Wen HB, Zhao H, Zahner GE (2005) Parkinson’s disease in China: prevalence in Beijing, Xian, and Shanghai. Lancet 365:595–597

    PubMed  Google Scholar 

  3. Siniscalchi A, Gallelli L, Mercuri NB, Ibbadu GF, De Sarro G (2006) Role of lifestyle factors on plasma homocysteine levels in Parkinson’s disease patients treated with levodopa. Nat Neurosci 9:11–16

    CAS  Google Scholar 

  4. Gao HM, Jiang J, Wilson B, Zhang W, Hong JS, Liu B (2002) Microglial activation-mediated delayed and progressive degeneration of rat nigral dopaminergic neurons: relevance to Parkinson’s disease. J Neurochem 81:1285–1297

    Article  PubMed  CAS  Google Scholar 

  5. Chen BJ (2001) Triptolide, a novel immunosuppressive and anti-inflammatory agent purified from a Chinese herb Tripterygium wilfordii Hook F. Leuk Lymphoma 42:253–265

    Article  PubMed  CAS  Google Scholar 

  6. Qiu D, Kao PN (2003) Immunosuppressive and anti-inflammatory mechanisms of triptolide, the principal active diterpenoid from the Chinese medicinal herb Tripterygium wilfordii Hook f. Drugs R&D 4:1–18

    Article  CAS  Google Scholar 

  7. Zhao G, Vaszar LT, Qiu D, Shi L, Kao PN (2000) Anti-inflammatory effects of triptolide in human bronchial epithelial cells. Am J Physiol Lung Cell Mol Physiol 279:L958–L966

    PubMed  CAS  Google Scholar 

  8. Qiu D, Zhao G, Aoki Y, Shi L, Uyei A, Nazarian S, Ng JC, Kao PN (1999) Immunosuppressant PG490 (triptolide) inhibits T-cell interleukin–2 expression at the level of purine-box/nuclear factor of activated T-cells and NF-kappaB transcriptional activation. J Biol Chem 274:13443–13450

    Article  PubMed  CAS  Google Scholar 

  9. Li FQ, Cheng XX, Liang XB, Wang XH, Xue B, He QH, Wang XM, Han JS (2003) Neurotrophic and neuroprotective effects of tripchlorolide, an extract of Chinese herb Tripterygium wilfordii Hook F, on dopaminergic neurons. Exp Neurol 179:28–37

    Article  PubMed  CAS  Google Scholar 

  10. Zhou HF, Liu XY, Niu DB, Li FQ, He QH, Wang XM (2005) Triptolide protects dopaminergic neurons from inflammation-mediated damage induced by lipopolysaccharide intranigral injection. Neurobiol Dis 18:441–449

    Article  PubMed  CAS  Google Scholar 

  11. Zhou HF, Niu DB, Xue B, Li FQ, Liu XY, He QH, Wang XH, Wang XM (2003) Triptolide inhibits TNF-alpha, IL-1 beta and NO production in primary microglial cultures. Neuroreport 14:1091–1095

    Article  PubMed  CAS  Google Scholar 

  12. Li FQ, Lu XZ, Liang XB, Zhou HF, Xue B, Liu XY, Niu DB, Han JS, Wang XM (2004) Triptolide, a Chinese herbal extract, protects dopaminergic neurons from inflammation-mediated damage through inhibition of microglial activation. J Neuroimmunol 148:24–31

    Article  PubMed  CAS  Google Scholar 

  13. Xue B, Jiao J, Zhang L, Li KR, Gong YT, Xie JX, Wang XM (2007) Triptolide upregulates NGF synthesis in rat astrocyte cultures. Neurochem Res 32:1113–1119

    Article  PubMed  CAS  Google Scholar 

  14. He QH, Zhou HF, Xue B, Niu DB, Wang XM (2003) Neuroprotective effects and mechanism of Tripteryygium Wilforddi Hook F monomer triptolide on glutamate induced PC12 cell line damage. Beijing Da Xue Xue Bao 35:252–255

    PubMed  CAS  Google Scholar 

  15. Gu M, Zhou HF, Xue B, Niu DB, Wang XM (2004) The effect of Chinese Herb Tripterygium Wilfordii Hook F. Monomer T10 on in vitro model of Alzheimer’s disease. Acta Physiol Sin 56:73–78

    CAS  Google Scholar 

  16. Lee KY, Park JS, Jee YK, Rosen GD (2002) Triptolide sensitizes lung cancer cells to TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis by inhibition of NF-kappakB activation. Exp Mol Med 34:462–468

    PubMed  CAS  Google Scholar 

  17. Rajendran PR, Thompson RE, Reich SG (2001) The use of alternative therapies by patients with Parkinson’s disease. Neurology 57:790–794

    PubMed  CAS  Google Scholar 

  18. Shulman LM, Wen X, Weiner WJ, Bateman D, Minagar A, Duncan R, Konefal J (2002) Acupuncture therapy for the symptoms of Parkinson’s disease. Mov Disord 17:799–802

    Article  PubMed  Google Scholar 

  19. Cristian A, Katz M, Cutrone E, Walker RH (2005) Evaluation of acupuncture in the treatment of Parkinson’s disease: a double-blind pilot study. Mov Disord 20:1185–1188

    Article  PubMed  Google Scholar 

  20. Eng ML, Lyons KE, Greene MS, Pahwa R (2006) Open-label trial regarding the use of acupuncture and yin tui na in Parkinson’s disease outpatients: a pilot study on efficacy, tolerability, and quality of life. J Altern Complem Med 12:395–399

    Article  Google Scholar 

  21. Tan LC, Lau PN, Jamora RD, Chan ES (2006) Use of complementary therapies in patients with Parkinson’s disease in Singapore. Mov Disord 21:86–89

    Article  PubMed  Google Scholar 

  22. Liang XB, Liu XY, Li FQ, Luo Y, Lu J, Zhang WM, Wang XM, Han JS (2002) Long-term high-frequency electro-acupuncture stimulation prevents neuronal degeneration and up-regulates BDNF mRNA in the substantia nigra and ventral tegmental area following medial forebrain bundle axotomy. Brain Res Mol Brain Res 108:51–59

    Article  PubMed  CAS  Google Scholar 

  23. Liang XB, Luo Y, Liu XY, Lu J, Li FQ, Wang Q, Wang XM, Han JS (2003) Electro-acupuncture improves behavior and upregulates GDNF mRNA in MFB transected rats. Neuroreport 14:1177–1181

    Article  PubMed  Google Scholar 

  24. Qian ZN, Gu ZL, Pan JX (1985) The effect of acupuncture analgesia on the monamine transmitters in the rat striatum and spinal cord. Zhen Ci Yan Jiu 13:199–121

    Google Scholar 

  25. Liu XY, Zhou HF, Pan YL, Liang XB, Niu DB, Xue B, Li FQ, He QH, Wang XH, Wang XM (2004) Electro-acupuncture stimulation protects DAergic neurons from inflammation-mediated damage in medial forebrain bundle-transected rats. Exp Neurol 189:189–196

    Article  PubMed  CAS  Google Scholar 

  26. Kang JM, Park HJ, Choi YG, Choe IH, Park JH, Kim YS, Lim S (2007) Acupuncture inhibits microglial activation and inflammatory events in the MPTP-induced mouse model. Brain Res 1131:211–219

    Article  PubMed  CAS  Google Scholar 

  27. Jolly D (1994) Viral vector systems for gene therapy. Cancer Gene Ther 1:51–64

    PubMed  CAS  Google Scholar 

  28. Kotin RM, Siniscalco M, Samulski RJ, Zhu XD, Hunter L, Laughlin CA, McLaughlin S, Muzyczka N, Rocchi M, Berns KI (1990) Site-specific integration by adeno-associated virus. Proc Natl Acad Sci USA 87:2211–2215

    Article  PubMed  CAS  Google Scholar 

  29. Samulski RJ, Zhu X, Xiao X, Brook JD, Housman DE, Epstein N, Hunter LA (1991) Targeted integration of adeno-associated virus (AAV) into human chromosome 19. EMBO J 10:3941–3950

    PubMed  CAS  Google Scholar 

  30. Harding TC, Geddes BJ, Murphy D, Knight D, Uney JB (1998) Switching transgene expression in the brain using an adenoviral tetracycline-regulatable system. Nat. Biotechnol. 16:553–555

    Article  PubMed  CAS  Google Scholar 

  31. Massie B, Couture F, Lamoureux L, Mosser DD, Guilbault C, Jolicoeur P, Belanger F, Langelier Y (1998) Inducible overexpression of a toxic protein by an adenovirus vector with a tetracycline-regulatable expression cassette. J Virol 72:2289–2296

    PubMed  CAS  Google Scholar 

  32. During MJ, Kaplitt MG, Stern MB, Eidelberg D (2001) Subthalamic GAD gene transfer in Parkinson disease patients who are candidates for deep brain stimulation. Hum Gene Ther 12:1589–1591

    PubMed  CAS  Google Scholar 

  33. Mandel RJ, Spratt SK, Snyder RO, Leff SE (1997) Midbrain injection of recombinant adeno-associated virus encoding rat glial cell line-derived neurotrophic factor protects nigral neurons in a progressive 6-hydroxydopamine-induced degeneration model of Parkinson’s disease in rats. Proc Natl Acad Sci USA 94:14083–14088

    Article  PubMed  CAS  Google Scholar 

  34. Ma DD, Wang XM, Han JS (2000) NIH 3T3 cells or engineered NIH 3T3 cells stably expressing GDNF can protect primary dopaminergic neurons. Neurol Res 22:538–544

    PubMed  CAS  Google Scholar 

  35. Ma DD, Wang XM, Jing XJ, Wang J, Xiong L, Song H, Wan Y, Xu GH, Sun QL, Dong HW, Wang XH, Han JS (1997) GDNF cDNA engineered NIH 3T3 cells protect primary dopaminergic neurons. Chinese Sci Bull 42:1921–1924

    Article  CAS  Google Scholar 

  36. Ledley FD, Grenett HE, Bartos DP, van Tuinen P, Ledbetter DH, Woo SL (1987) Assignment of human tryptophan hydroxylase locus to chromosome 11: gene duplication and translocation in evolution of aromatic amino acid hydroxylases. Somat Cell Mol Genet 13:575–580

    Article  PubMed  CAS  Google Scholar 

  37. Flotte TR, Ferkol TW (1997) Genetic therapy. Past, present, and future. Pediatr Clin North Am 44:153–178

    Article  PubMed  CAS  Google Scholar 

  38. Xu GH, Ling Y, Wan Y, Wang XM, Han JS (1998) Construction of recombinant adenovirus expressing human tyrosine hydroxylase gene and study of its activityes in vitro. Chinese J Neuroanatomy 14:313–317

    Google Scholar 

  39. Xu GH, Ling Y, Wan Y, Wang XM, Han JS (1999) Development of the recombinant GDNF-adenovirus and observation of its protective effects on primary cultured dopaminergic neurons against neurotoxin MPP+. Chinese J Biochem Mol Biol 15:42–47

    CAS  Google Scholar 

  40. Wang JJ, Niu DB, Zhang T, Wang K, Xue B, Wang XM (2005) A tetracycline-regulatable adeno-associated virus vector for double-gene transfer. Neurosci Lett 378:106–110

    Article  PubMed  CAS  Google Scholar 

  41. Wang JJ, Zhang T, Niu DB, Wang K, Li KR, Xue B, Wang XM (2006) Doxycycline-regulated co-expression of GDNF and TH in PC12 cells. Neurosci Lett 401:142–145

    Article  PubMed  CAS  Google Scholar 

  42. Perlow MJ, Freed WJ, Hoffer BJ, Seiger A, Olson L, Wyatt RJ (1979) Brain grafts reduce motor abnormalities produced by destruction of nigrostriatal dopamine system. Science 204:643–647

    Article  PubMed  CAS  Google Scholar 

  43. Lindvall O, Brundin P, Widner H, Rehncrona S, Gustavii B, Frackowiak R, Leenders KL, Sawle G, Rothwell JC, Marsden CD, Bjőrklund A (1990) Grafts of fetal dopamine neurons survive and improve motor function in Parkinson’s disease. Science 247:574–577

    Article  PubMed  CAS  Google Scholar 

  44. Widner H, Tetrud J, Rehncrona S, Snow B, Brundin P, Gustavii B, Bjőrklund A, Lindvall O, Langston JW (1992) Bilateral fetal mesencephalic grafting in two patients with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). N Engl J Med 327:1556–1563

    PubMed  CAS  Google Scholar 

  45. Freed CR, Breeze RE, Rosenberg NL, Schneck SA, Kriek E, Qi JX, Lone T, Zhang YB, Snyder JA, Wells TH (1992) Survival of implanted fetal dopamine cells and neurologic improvement 12–46 months after transplantation for Parkinson’s disease. N Engl J Med 327:1549–1555

    PubMed  CAS  Google Scholar 

  46. Freed CR, Greene PE, Breeze RE, Tsai WY, DuMouchel W, Kao R, Dillon S, Winfield H, Culver S, Trojanowski JQ, Eidelberg D, Fahn S (2001) Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. N Engl J Med 334:710–719

    Article  Google Scholar 

  47. Vescovi AL, Parati EA, Gritti A, Poulin P, Ferrario M, Wanke E, Frőlichsthal-Schoeller P, Cova L, Arcellana-Panlilio M, Colombo A, Galli A (1999) Isolation and cloning of multipotential stem cells from the embryonic human CNS and establishment of transplantable human neural stem cell lines by epigenetic stimulation. Exp Neurol 156:71–88

    Article  PubMed  CAS  Google Scholar 

  48. Svendsen CN, Clarke DJ, Rosser AE, Dunnett SB (1996) Survival and differentiation of rat and human epidermal growth factor-responsive precursor cells following grafting into the lesioned adult central nervous system. Exp Neurol 137:376–388

    Article  PubMed  CAS  Google Scholar 

  49. Uchida N, Buck DW, He DP, Reitsma MJ, Masek M, Phan TV, Tsukamoto AS, Gage FH, Weissman IL (2000) Direct isolation of human central nervous system stem cells. Proc Natl Acad Sci USA 97:14720–14725

    Article  PubMed  CAS  Google Scholar 

  50. Reynolds BA, Weiss S (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255:1707–1710

    Article  PubMed  CAS  Google Scholar 

  51. Richards LJ, Kilpatrick TJ, Bartlett PF (1992) De novo generation of neuronal cells from the adult mouse brain. Proc Natl Acad Sci USA 89:8591–8595

    Article  PubMed  CAS  Google Scholar 

  52. Studer L, Tabar V, McKay RD (1998) Transplantation of expanded mesencephalic precursors leads to recovery in parkinsonian rats. Nat Neurosci 1:290–295

    Article  PubMed  CAS  Google Scholar 

  53. Carvey PM, Ling ZD, Sortwell CE, Pitzer MR, McGuire SO, Storch A, Collier TJ (2001) A clonal line of mesencephalic progenitor cells converted to dopamine neurons by hematopoietic cytokines: a source of cells for transplantation in Parkinson’s disease. Exp Neurol 171:98–108

    Article  PubMed  CAS  Google Scholar 

  54. Wang X, Lu YY, Zhang HQ, Wang K, He QH, Wang Y, Liu XY, Li LS, Wang XM (2004) Distinct efficacy of pre-differentiated versus intact fetal mesencephalon-derived human neural progenitor cells in alleviating rat model of Parkinson’s disease. Int J Dev Neurosci 22:175–183

    Article  PubMed  CAS  Google Scholar 

  55. Ling ZD, Potter ED, Lipton JW, Carvey PM (1998) Differentiation of mesencephalic progenitor cells into dopaminergic neurons by cytokines. Exp Neurol 149:411–423

    Article  PubMed  CAS  Google Scholar 

  56. Studer L, Csete M, Lee SH, Kabbani N, Walikonis J, Wold B, McKay RD (2000) Enhanced proliferation, survival, and dopaminergic differentiation of CNS precursors in lowered oxygen. J Neurosci 20:7377–7383

    PubMed  CAS  Google Scholar 

  57. Kawasaki H, Mizuseki K, Nishikawa S, Kaneko S, Kuwana Y, Nakanishi S, Nishikawa SI, Sasai Y (2000) Induction of midbrain dopaminergic neurons from ES cells by stromal cell-derived inducing activity. Neuron 28:31–40

    Article  PubMed  CAS  Google Scholar 

  58. Wang X, Li XX, Wang K, Zhou HF, Xue B, Li LS, Wang XM (2004) Forskolin cooperating with growth factor on generation of dopaminergic neurons from human fetal mesencephalic neural progenitor cells. Neurosci Lett 362:117–121

    Article  PubMed  CAS  Google Scholar 

  59. Langston JW (2005) The promise of stem cells in Parkinson disease. J Clin Invest 115:23–25

    PubMed  CAS  Google Scholar 

  60. Takagi Y, Takahashi J, Saiki H, Morizane A, Hayashi T, Kishi Y, Fukuda H, Okamoto Y, Koyanagi M, Ideguchi M, Hayashi H, Imazato T, Kawasaki H, Suemori H, Omachi S, Iida H, Itoh N, Nakatsuji N, Sasai Y, Hashimoto N (2005) Dopaminergic neurons generated from monkey embryonic stem cells function in a Parkinson primate model. J Clin Invest 115:102–109

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by the National Basic Research Program of China (2006C B500700), National Natural Science Foundation of China (30430280, 30472245, 30571704 and 30500255) and Natural Science Foundation of Beijing (kz200510025014).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Xiao-Min Wang.

Additional information

Special issue article in honor of Dr. Ji-Sheng Han.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, X., Liang, XB., Li, FQ. et al. Therapeutic Strategies for Parkinson’s Disease: The Ancient Meets the Future—Traditional Chinese Herbal Medicine, Electroacupuncture, Gene Therapy and Stem Cells. Neurochem Res 33, 1956–1963 (2008). https://doi.org/10.1007/s11064-008-9691-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-008-9691-z

Keywords

Navigation