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Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
Traditional Chinese medicines with caspase-inhibitory activity
R Fattorusso1, S Frutos, X Sun
1The Burnham Institute, La Jolla, CA, USA.
Summary
Traditional Chinese Medicine (TCM) drugs show neuroprotective effects against stroke. This study identified Lianqiao and Shouwuteng extracts as inhibitors of caspases, key proteins in neuronal cell death after stroke.
Area of Science:
- Neuroscience
- Pharmacology
- Traditional Chinese Medicine
Background:
- Clinical evidence suggests Traditional Chinese Medicine (TCM) drugs reduce stroke-related brain damage.
- The molecular mechanisms underlying the neuroprotective effects of TCM in stroke remain largely unknown.
- Neuronal loss in ischemic stroke is linked to cell death programs, particularly caspase activation during reperfusion.
Purpose of the Study:
- To screen commonly used TCM drugs for neuroprotective activity relevant to stroke therapy.
- To investigate the caspase inhibitory potential of TCM extracts.
- To identify specific TCM compounds that modulate caspase activity.
Main Methods:
- A collection of 58 TCM drugs used in stroke therapy was screened.
- Nuclear Magnetic Resonance (NMR) and fluorescence assays were employed.
- Aqueous extracts were tested for caspase inhibitory activity.
Main Results:
- Aqueous extracts of Lianqiao (Fructus Forsythiae) and Shouwuteng (Caulis Polygoni multiflori) demonstrated significant caspase inhibitory activity.
- These extracts effectively blocked the activity of initiator caspase-8 and effector caspases-3 and -7.
- Inhibition occurred in a dose-dependent manner with an IC(50) of less than 10 microg/ml.
Conclusions:
- Lianqiao and Shouwuteng possess caspase inhibitory properties, suggesting a molecular basis for their neuroprotective effects in stroke.
- This finding facilitates the development of testable hypotheses for further research into TCM stroke therapies.
- Further investigation is warranted to elucidate the precise mechanisms of TCM in stroke treatment.

