Skip to main content
SpringerLink
Log in

Biochanin A Protects Against Lipopolysaccharide-Induced Damage of Dopaminergic Neurons Both In Vivo and In Vitro via Inhibition of Microglial Activation

  • Original Article
  • Published:
Neurotoxicity Research Aims and scope Submit manuscript

Abstract

Neuroinflammation has been reported to be involved in the pathogenesis of Parkinson’s disease (PD). Inhibition of microglia-mediated neuroinflammation might be a potential strategy for PD treatment. Biochanin A, is an O-methylated isoflavone, classified as a kind of phytoestrogens due to its chemical structure that is similar to mammalian estrogens. It has been found to possess antifibrotic, antiapoptotic, and antioxidant effects. In the present study, we investigated the neuroprotective effects of biochanin A on lipopolysaccharide (LPS)-induced dopaminergic neurons damage both in vivo and in vitro and the related molecular mechanisms. The results showed that biochanin A treatment for 21 days significantly attenuated the behavioral dysfunction of PD rats, prevented dopaminergic neurons damage, and inhibited activation of microglia in the LPS-induced PD rats. Furthermore, biochanin A decreased the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the serum, and inhibited the phosphorylation of ERK, JNK, p38 in the substantia nigra of PD rats. In vitro test, biochanin A also inhibited primary microglial activation and protected dopaminergic neurons, decreased the content of nitric oxide, IL-1β, and TNF-α in supernatants, and inhibited the reactive oxygen species production. Taken together, these results suggest that biochanin A exerts protective effects on LPS-induced PD rats, and the mechanisms may be associated with the inhibition of inflammatory response and the MAPK signaling pathway.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

Similar content being viewed by others

References

  • Breikaa RM, Algandaby MM, El-Demerdash E, Abdel-Naim AB (2013) Multimechanistic antifibrotic effect of biochanin A in rats: implications of proinflammatory and profibrogenic mediators. PLoS One 8(7):e69276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carta AR, Frau L, Pisanu A, Wardas J, Spiga S, Carboni E (2011) Rosiglitazone decreases peroxisome proliferator receptor-gamma levels in microglia and inhibits TNF-alpha production: new evidences on neuroprotection in a progressive Parkinson’s disease model. Neuroscience 194:250–261

    Article  CAS  PubMed  Google Scholar 

  • Chen HQ, Jin ZY, Li GH (2007) Biochanin A protects dopaminergic neurons against lipopolysaccharide- induced damage through inhibition of microglia activation and proinflammatory factors generation. Neurosci Lett 417(2):112–117

    Article  CAS  PubMed  Google Scholar 

  • Collins LM, Toulouse A, Connor TJ, Nolan YM (2012) Contributions of central and systemic inflammation to the pathophysiology of Parkinson’s disease. Neuropharmacology 62(7):2154–2168

    Article  CAS  PubMed  Google Scholar 

  • Dou W, Zhang J, Ren G, Ding L, Sun A, Deng C, Wu X, Wei X, Mani S, Wang Z (2014) Mangiferin attenuates the symptoms of dextran sulfate sodium-induced colitis in mice via NF-κB and MAPK signaling inactivation. Int Immunopharmacol 23(1):170–178

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Frank-Cannon TC, Alto LT, McAlpine FE, Tansey MG (2009) Does neuroinflammation fan the flame in neurodegenerative diseases? Mol Neurodegener 16(4):47

    Article  Google Scholar 

  • Gao HM, Hong JS (2008) Why neurodegenerative diseases are progressive: uncontrolled inflammation drives disease progression. Trends Immunol 29(8):357–365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gao HM, Liu B, Zhang W, Hong JS (2003) Critical role of microglial NADPH oxidase derived free radicals in the in vitro MPTP model of Parkinson’s disease. FASEB J 17:1954–1956

    CAS  PubMed  Google Scholar 

  • Hefti F, Melamed E, Sahakian BJ, Wurtman RJ (1980) Circling behavior in rats with partial, unilateral nigro-striatal lesions: effect of amphetamine, apomorphine, and DOPA. Pharmacol Biochem Behav 12(2):185–188

    Article  CAS  PubMed  Google Scholar 

  • Hoban DB, Connaughton E, Connaughton C, Hogan G, Thornton C, Mulcahy P, Moloney TC, Dowd E (2013) Further characterisation of the LPS model of Parkinson’s disease: a comparison of intra-nigral and intra-striatal lipopolysaccharide administration on motor function, microgliosis and nigrostriatal neurodegeneration in the rat. Brain Behav Immun 27(1):91–100

    Article  CAS  PubMed  Google Scholar 

  • Iancu R, Mohapel P, Brundin P, Paul G (2005) Behavioral characterization of a unilateral 6-OHDA-lesion model of Parkinson’s disease in mice. Behav Brain Res 162(1):1–10

    Article  CAS  PubMed  Google Scholar 

  • Jankovic J (2008) Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry 79(4):368–376

    Article  CAS  PubMed  Google Scholar 

  • Jeohn GH, Kong LY, Wilson B, Hudson P, Hong JS (1998) Synergistic neurotoxic effects of combined treatments with cytokines in murine primary mixed neuron/glia cultures. J Neuroimmunol 85(1):1–10

    Article  CAS  PubMed  Google Scholar 

  • Kim WG, Mohney RP, Wilson B, Jeohn GH, Liu B, Hong JS (2000) Regional difference in the susceptibility to lipopolysaccharide-induced neurotoxicity in the rat brain: role of microglia. J Neurosci 20(16):6309–6316

    CAS  PubMed  Google Scholar 

  • Kreutzberg GW (1996) Microglia: a sensor for pathological events in the CNS. Trends Neurosci 19(8):312–318

    Article  CAS  PubMed  Google Scholar 

  • Le W, Rowe D, Xie W, Ortiz I, He Y, Appel SH (2001) Microglial activation and dopaminergic cell injury: an in vitro model relevant to Parkinson’s disease. J Neurosci 21(21):8447–8455

    CAS  PubMed  Google Scholar 

  • Li YY, Huang SS, Lee MM, Deng JS, Huang GJ (2015) Anti-inflammatory activities of cardamonin from Alpinia katsumadai through heme oxygenase-1 induction and inhibition of NF-κB and MAPK signaling pathway in the carrageenan-induced paw edema. Int Immunopharmacol 25(2):332–339

    Article  PubMed  Google Scholar 

  • Liu B, Du L, Hong JS (2000a) Naloxone protects rat dopaminergic neurons against inflammatory damage through inhibition of microglia activation and superoxide generation. J Pharmacol Exp Ther 293(2):607–617

    CAS  PubMed  Google Scholar 

  • Liu M, Bing G (2011) Lipopolysaccharide animal models for Parkinson’s disease. Parkinsons Dis 2011:327089

    PubMed  PubMed Central  Google Scholar 

  • Liu B, Jiang JW, Wilson BC, Du L, Yang SN, Wang JY, Wu GC, Cao XD, Hong JS (2000b) Systemic infusion of naloxone reduces degeneration of rat substantia nigral dopaminergic neurons induced by intranigral injection of lipopolysaccharide. J Pharmacol Exp Ther 295(1):125–132

    CAS  PubMed  Google Scholar 

  • Lu X, Bing G, Hagg T (2000) Naloxone prevents microglia-induced degeneration of dopaminergic substantia nigra neurons in adult rats. Neuroscience 97(2):285–291

    Article  CAS  PubMed  Google Scholar 

  • McGeer PL, Itagaki S, Boyes BE, McGeer EG (1988) Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson’s and Alzheimer’s disease brains. Neurology 38(8):1285–1291

    Article  CAS  PubMed  Google Scholar 

  • Qian L, Flood PM, Hong JS (2010) Neuroinflammation is a key player in Parkinson’s disease and a prime target for therapy. J Neural Transm. 117(8):971–979

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tai W, Ye X, Bao X, Zhao B, Wang X, Zhang D (2013) Inhibition of Src tyrosine kinase activity by squamosamide derivative FLZ attenuates neuroinflammation in both in vivo and in vitro Parkinson’s disease models. Neuropharmacology 75:201–212

    Article  CAS  PubMed  Google Scholar 

  • Tan JW, Tham CL, Israf DA, Lee SH, Kim MK (2013) Neuroprotective effects of biochanin A against glutamate-induced cytotoxicity in PC12 cells via apoptosis inhibition. Neurochem Res 38(3):512–518

    Article  CAS  PubMed  Google Scholar 

  • Tansey MG, Goldberg MS (2010) Neuroinflammation in Parkinson’s disease: its role in neuronal death and implications for therapeutic intervention. Neurobiol Dis 37(3):510–518

    Article  CAS  PubMed  Google Scholar 

  • Wang X, Chen S, Ma G, Ye M, Lu G (2005) Genistein protects dopaminergic neurons by inhibiting microglial activation. NeuroReport 16(3):267–270

    Article  CAS  PubMed  Google Scholar 

  • Wang W, Tang L, Li Y, Wang Y (2015) Biochanin A protects against focal cerebral ischemia/reperfusion in rats via inhibition of p38-mediated inflammatory responses. J Neurol Sci 348(1–2):121–125

    Article  CAS  PubMed  Google Scholar 

  • Wu WY, Wu YY, Huang H, He C, Li WZ, Wang HL, Chen HQ, Yin YY (2015) Biochanin A attenuates LPS-induced pro-inflammatory responses and inhibits the activation of the MAPK pathway in BV2 microglial cells. Int J Mol Med 35(2):391–398

    CAS  PubMed  Google Scholar 

  • Zhang Y, Guo J, Zeng L, Zhang J, Hui Y, Liu J, Qing X, Sun X, Guo G (2011) Tert-butyl-2(4,5-dihydrogen-4,4,5,5-tetramethyl-3-O-1H-imidazole-3-cationic-1-oxyl-2-pyrrolidine-1-carboxylic ester displays novel cytotoxicity through reactive oxygen species-mediated oxidative damage in MCF-7 and MDA-MB-231 cells. Chem Biol Interact 192(3):287–297

    Article  CAS  PubMed  Google Scholar 

  • 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(3):441–449

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China (NSFC) fund (Grant No. 31171650) and the Natural Science Foundation of Anhui Province Education Department (Grant No. KJ2014A115) and the Natural Science Foundation of Anhui Province (Grant No. 1508085MH186).

Author information

Author notes

    Authors and Affiliations

    1. Department of Pharmacology, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, People’s Republic of China

      Jun Wang, Wang-Yang Wu, Huan Huang, Wei-Zu Li & Yan-Yan Yin

    2. School of Food Science and Engineering, Hefei University of Technology, 193 Tunxi Road, Hefei, 230009, Anhui, People’s Republic of China

      Jun Wang, Wang-Yang Wu & Han-Qing Chen

    Authors
    1. Jun Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Wang-Yang Wu
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Huan Huang
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Wei-Zu Li
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Han-Qing Chen
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Yan-Yan Yin
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding authors

    Correspondence to Han-Qing Chen or Yan-Yan Yin.

    Ethics declarations

    Conflict of interest

    The authors declare no conflict of interest.

    Additional information

    J. Wang and W.-Y. Wu these authors contributed equally to this work.

    Electronic supplementary material

    Below is the link to the electronic supplementary material.

    Supplementary material 1 (DOCX 801 kb)

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Wang, J., Wu, WY., Huang, H. et al. Biochanin A Protects Against Lipopolysaccharide-Induced Damage of Dopaminergic Neurons Both In Vivo and In Vitro via Inhibition of Microglial Activation. Neurotox Res 30, 486–498 (2016). https://doi.org/10.1007/s12640-016-9648-y

    Download citation

    • Received:

    • Revised:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s12640-016-9648-y

    Keywords

    Search

    Navigation