Traditional Chinese medicines with caspase-inhibitory activity

Clinical evidence indicates that traditional Chinese medicine (TCM) drugs can reduce stroke-inflicted brain damage. To date, the molecular basis of the apparent neuroprotective effects of these TCM drugs remains largely obscure. Several lines of evidence indicate that the activation of cell death programs leads to the loss of neurons during the reperfusion phase of ischemic stroke. In particular, activation of caspases (cysteinyl aspartate-specific proteinases) is a critical step in neuronal apoptosis. Using nuclear magnetic resonance (NMR) and fluorescence assays, we screened a collection of 58 TCM drugs that are commonly used in stroke therapy for caspase inhibitory activity. We found that aqueous extracts of Lianqiao (Fructus Forsythiae) and Shouwuteng (Caulis Polygoni multiflori) blocked the activity of the initiator caspase-8 as well as the effector caspase-3 and caspase-7 in a dose-dependent manner with an IC 50≤10 μg/ml. Identification of caspase inhibitory activity of these TCM drugs, allows the formulation of testable hypotheses and design of further investigations aimed at the elucidation of the molecular basis of TCM stroke therapy. © 2005 Elsevier GmbH. All rights reserved.