Cryptotanshinone from Salviae miltiorrhizae radix inhibits sodium-nitroprusside-induced apoptosis in neuro-2a cells.
The root of Salvia miltiorrhiza (Salviae miltiorrhizae radix), a herbal medicine has widely been used for the treatment of pain, miscarriage and oedema. In this study, we evaluated the neuroprotective effect of cryptotanshinone (CRT) from Salviae miltiorrhizae radix on sodium-nitroprusside (SNP)-induced apoptosis in neuro-2a (N2a) cells, and further investigated its action mechanism in signalling pathways. The effects of CRT against SNP-induced toxicity, mitochondrial membrane potential (MMP) changes, and oxidants/antioxidant defences and apoptotic signalling pathways were investigated in N2a cells. Cryptotanshinone significantly inhibited SNP-induced cell toxicity and the generation of reactive oxygen and nitrogen species (RONS), and improved MMP in N2a cells. Cryptotanshinone significantly suppressed SNP-induced peroxidation of lipid and protein, and the expression of Gclc mRNA. In the signalling pathway, CRT effectively blocked SNP-induced activation of NF-κB and ERK1/2 and JNK MAPK pathways through the elevation of Akt and cyclic AMP response element binding protein. Furthermore, CRT remarkably reduced the increase of mitochondrial Bax/Bcl-2 ratio, the release of cytochrome c from mitochondria to cytosol, and the activations of cytosolic procaspase-3 and nuclear inactive poly ADP (adenosine diphosphate)-ribose polymerase by SNP-induced apoptosis. These results indicate that CRT has neuroprotective effects against SNP-induced apoptosis in neuronal cells via the regulation of mitochondrial apoptotic cascades and antiapoptotic cellular signalling pathways.
Oriental Medicine R&D Center, College of Oriental Medicine, Dongguk University, Gyeongju 780-714, Republic of Korea.
Ramalingam
R
Mahesh
Hyo Won
HW
Jung
Gun Woo
GW
Kim
Young Shik
YS
Kim
Yong-Ki
YK
Park
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D003600:Cytosol / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D005721:Glutamate-Cysteine Ligase / Q000235:genetics / Q000378:metabolism; D015227:Lipid Peroxidation; D020935:MAP Kinase Signaling System; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009599:Nitroprusside / Q000009:adverse effects*; D010616:Phenanthrenes / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D027561:Salvia miltiorrhiza / Q000737:chemistry*
D000972:Antineoplastic Agents, Phytogenic; D016328:NF-kappa B; D018696:Neuroprotective Agents; D010616:Phenanthrenes; D012333:RNA, Messenger; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D009599:Nitroprusside; C037886:cryptotanshinone; D053148:Caspase 3; D005721:Glutamate-Cysteine Ligase