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Published on: May 22, 2018
Triptolide inhibits amyloid-β production and protects neural cells by inhibiting CXCR2 activity
Ju Wang1, Zi-Qi Shi, Xiaojun Xu
1Department of Pharmacognosy, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
Abstract:
Triptolide, a biologically active natural product from Tripterygium wilfordii, protects neurons from inflammation-mediated damage. Our results showed for the first time that triptolide inhibited the expression of CXCR2 and presenilin in a neuroblastoma cell line SHSY5Ysw. Moreover, triptolide potently inhibited amyloid-β1-42 production with IC50 value of 30 pM in HEK293sw cells or 2 nM in SHSY5Ysw cells, respectively. We also demonstrated that triptolide prevented primary cortical neurons from chemokine CXCL1-induced cytotoxicity. Therefore, our study indicates that the neural protective effect of triptolide is largely mediated by inhibiting CXCR2 activity.
Insights
Triptolide, a natural compound, protects neurons by inhibiting CXCR2 and reducing amyloid-beta production. This neuroprotective effect is linked to its ability to block CXCR2 activity.
Area of Science:
- Neuroscience
- Pharmacology
- Natural Products Chemistry
Background:
- Inflammation-mediated neuronal damage is a key factor in neurodegenerative diseases.
- Tripterygium wilfordii yields triptolide, a compound with known biological activities.
- The specific mechanisms underlying triptolide's neuroprotective effects require further elucidation.
Purpose of the Study:
- To investigate the neuroprotective mechanisms of triptolide.
- To determine the effect of triptolide on CXCR2 and presenilin expression in neuronal cells.
- To evaluate the impact of triptolide on amyloid-beta production and neuronal cytotoxicity.
Main Methods:
- Utilized neuroblastoma cell line SHSY5Ysw and HEK293sw cells.
- Assessed the expression of CXCR2 and presenilin.
- Measured amyloid-beta 1-42 production using IC50 values.
- Examined the protection of primary cortical neurons against CXCL1-induced cytotoxicity.
Main Results:
- Triptolide inhibited the expression of CXCR2 and presenilin in SHSY5Ysw cells.
- Triptolide potently inhibited amyloid-beta 1-42 production with low IC50 values (30 pM in HEK293sw, 2 nM in SHSY5Ysw).
- Triptolide demonstrated neuroprotective effects by preventing primary cortical neurons from chemokine CXCL1-induced damage.
Conclusions:
- Triptolide exhibits significant neuroprotective properties.
- The inhibition of CXCR2 activity is a primary mechanism for triptolide's neuroprotective effects.
- Triptolide's ability to reduce amyloid-beta production and protect neurons from inflammatory damage suggests therapeutic potential.
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