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Triptolide protects dopaminergic neurons from inflammation-mediated damage induced by lipopolysaccharide intranigral injection.
Neurobiol Dis. 2005 Apr; 18(3):441-9.ND

Abstract

Converging lines of evidence suggest that neuroinflammatory processes may account for the progressive death of dopaminergic neurons in Parkinson's disease (PD). Therefore, anti-inflammatory strategies have attracted much interest for their potential to prevent further deterioration of PD. Our previous study showed that triptolide, a traditional Chinese herbal compound with anti-inflammatory and immunosuppressive properties, protected dopaminergic neurons from lipopolysaccharide (LPS)-induced damage in primary embryonic midbrain cell cultures. To examine further if triptolide can protect dopaminergic neurons from inflammation-mediated damage in vivo, microglial activation and injury of dopaminergic neurons were induced by LPS intranigral injection, and the effects of triptolide treatment on microglial activation and survival ratio and function of dopaminergic neurons were investigated. Our results demonstrated that microglial activation induced by a single intranigral dose of 10 mug of LPS reduced the survival ratio of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the substantia nigra pars compacta (SNpc) to 29% and the content of dopamine (DA) in striatum to 37% of the non-injected side. Intriguingly, treatment with triptolide of 5 mug/kg for 24 days once per day dramatically improved the survival rate of TH-ir neurons in the SNpc to 79% of the non-injected side. Meanwhile, treatment with triptolide of 1 or 5 mug/kg for 24 days once per day significantly improved DA level in striatum to 70% and 68% of the non-injected side, respectively. Complement receptor 3 (CR3) immunohistochemical staining revealed that triptolide treatment potently inhibited LPS-elicited deleterious activation of microglia in SNpc. The excessive production of cytokines, such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta, was significantly abolished by triptolide administration. These results, together with our previous data in vitro, highly suggest the effectiveness of triptolide in protecting dopaminergic neurons against inflammatory challenge.

Authors+Show Affiliations

Neuroscience Research Institute, Peking University, 38 Xueyuan Road, Beijing 100083, P.R. China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15755670

Citation

Zhou, Hui-Fang, et al. "Triptolide Protects Dopaminergic Neurons From Inflammation-mediated Damage Induced By Lipopolysaccharide Intranigral Injection." Neurobiology of Disease, vol. 18, no. 3, 2005, pp. 441-9.
Zhou HF, Liu XY, Niu DB, et al. Triptolide protects dopaminergic neurons from inflammation-mediated damage induced by lipopolysaccharide intranigral injection. Neurobiol Dis. 2005;18(3):441-9.
Zhou, H. F., Liu, X. Y., Niu, D. B., Li, F. Q., He, Q. H., & Wang, X. M. (2005). Triptolide protects dopaminergic neurons from inflammation-mediated damage induced by lipopolysaccharide intranigral injection. Neurobiology of Disease, 18(3), 441-9.
Zhou HF, et al. Triptolide Protects Dopaminergic Neurons From Inflammation-mediated Damage Induced By Lipopolysaccharide Intranigral Injection. Neurobiol Dis. 2005;18(3):441-9. PubMed PMID: 15755670.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Triptolide protects dopaminergic neurons from inflammation-mediated damage induced by lipopolysaccharide intranigral injection. AU - Zhou,Hui-Fang, AU - Liu,Xian-Yu, AU - Niu,Dong-Bin, AU - Li,Feng-Qiao, AU - He,Qi-Hua, AU - Wang,Xiao-Min, PY - 2004/03/31/received PY - 2004/11/28/revised PY - 2004/12/10/accepted PY - 2005/3/10/pubmed PY - 2005/5/18/medline PY - 2005/3/10/entrez SP - 441 EP - 9 JF - Neurobiology of disease JO - Neurobiol Dis VL - 18 IS - 3 N2 - Converging lines of evidence suggest that neuroinflammatory processes may account for the progressive death of dopaminergic neurons in Parkinson's disease (PD). Therefore, anti-inflammatory strategies have attracted much interest for their potential to prevent further deterioration of PD. Our previous study showed that triptolide, a traditional Chinese herbal compound with anti-inflammatory and immunosuppressive properties, protected dopaminergic neurons from lipopolysaccharide (LPS)-induced damage in primary embryonic midbrain cell cultures. To examine further if triptolide can protect dopaminergic neurons from inflammation-mediated damage in vivo, microglial activation and injury of dopaminergic neurons were induced by LPS intranigral injection, and the effects of triptolide treatment on microglial activation and survival ratio and function of dopaminergic neurons were investigated. Our results demonstrated that microglial activation induced by a single intranigral dose of 10 mug of LPS reduced the survival ratio of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the substantia nigra pars compacta (SNpc) to 29% and the content of dopamine (DA) in striatum to 37% of the non-injected side. Intriguingly, treatment with triptolide of 5 mug/kg for 24 days once per day dramatically improved the survival rate of TH-ir neurons in the SNpc to 79% of the non-injected side. Meanwhile, treatment with triptolide of 1 or 5 mug/kg for 24 days once per day significantly improved DA level in striatum to 70% and 68% of the non-injected side, respectively. Complement receptor 3 (CR3) immunohistochemical staining revealed that triptolide treatment potently inhibited LPS-elicited deleterious activation of microglia in SNpc. The excessive production of cytokines, such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta, was significantly abolished by triptolide administration. These results, together with our previous data in vitro, highly suggest the effectiveness of triptolide in protecting dopaminergic neurons against inflammatory challenge. SN - 0969-9961 UR - https://www.unboundmedicine.com/medline/citation/15755670/Triptolide_protects_dopaminergic_neurons_from_inflammation_mediated_damage_induced_by_lipopolysaccharide_intranigral_injection_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0969-9961(04)00294-3 DB - PRIME DP - Unbound Medicine ER -