Magnolol, an active component isolated from the root and stem bark of Magnolia officinalis, has been reported to exhibit antitumour effects, but little is known about its molecular mechanisms of action.
Magnolol inhibited proliferation of human lung squamous carcinoma CH27 cells at low concentrations (10–40 μM), and induced apoptosis at high concentrations (80–100 μM).
Treatment with 80 μM magnolol significantly increased the expression of Bad and Bcl‐XS proteins, whereas it decreased the expression of Bcl‐XL. Overexpression of Bcl‐2 protected CH27 cells against magnolol‐triggered apoptosis.
Magnolol treatment resulted in accumulation of cytosolic cytochrome c and activation of caspase‐9 and downstream caspases (caspase‐3 and ‐6). Pretreatment with z‐VAD‐fmk markedly inhibited magnolol‐induced cell death, but did not prevent cytosolic cytochrome c accumulation.
Magnolol induced a modest and persistent JNK activation and ERK inactivation in CH27 cells without evident changes in the protein levels. The responsiveness of JNK and ERK to magnolol suggests the involvement of these kinases in the initiation of the apoptosis process.
These results indicate that regulation of the Bcl‐2 family, accumulation of cytosolic cytochrome c, and activation of caspase‐9 and caspase‐3 may be the effector mechanisms of magnolol‐induced apoptosis.
British Journal of Pharmacology (2003) 138, 193–201. doi:
Paeonol, an active component of Moutan Cortex, has been recognized as a potential neuroprotective drug. In the present study, an injury model based on glutamate-induced cell death of rat pheochromocytoma cells was used to investigate the neuroprotective potential of paeonol and its mechanism of action. Our findings showed that paeonol dose-dependently prevented glutamate-induced cell death as evidenced by cell viability, lactate dehydrogenase release, and trypan blue exclusion. In addition, flow cytometry of propidium iodide-stained cells revealed that paeonol pretreatment reduced the level of glutamate-induced apoptosis in pheochromocytoma cells. Paeonol was also able to decrease the glutamate-induced injury of mitochondria by normalization of mitochondrial membrane potential and cytochrome c release. The glutamate-induced activity of caspase-3 and p-ERK were dose-dependently reduced by paeonol pretreatments. Taken together, our data suggest that paeonol develops its neuroprotective effect against glutamate neurotoxicity through inhibition of the apoptotic signaling pathway and upregulation of the p-ERK pathway.
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