Neuroprotective effects of carnosic acid on neuronal cells under ischemic and hypoxic stress.
Ischemia/hypoxia induces oxidative stress which is associated with neurodegenerative diseases. The present study investigated protective mechanism of carnosic acid (CA) on ischemia/reperfusion and hypoxia-induced neuronal cell injury. The results showed that CA reduced 52% of the infarct volume from brains under ischemia/reperfusion in vivo and protected the PC12 cells from hypoxic injury in vitro. CA (1.0 µM) enhanced cell viability, prevented lactic dehydrogenase (LDH) release, scavenged reactive oxygen species (ROS), increased superoxide dismutase activity, and attenuated Ca(2+) release, lipid peroxidation, and prostaglandin E2 production in hypoxic PC12 cells. In addition, CA also reduced nitric oxide (NO) and interleukine (IL)-1 and IL-6 production from activated BV-2 microglia. Furthermore, its effect on hypoxia-induced mitogen-activated protein kinases (MAPKs) signaling pathway and caspase-3 was examined. Extracellular signal-regulated protein kinases, c-jun NH2-terminal kinase, and p38 MAPK were activated during hypoxia. CA inhibited MAPKs, caspase-3, and COX-2 activation and correlated well with the diminished LDH release and apoptosis (TUNEL) in PC12 cells under hypoxia. Taken together, CA protected neuronal cells under ischemia/hypoxia through scavenging or reducing of ROS and NO, inhibiting COX-2 and MAPK pathways by anti-inflammatory and anti-oxidative properties.
Chien-Wei
CW
Hou
Yu-Tzy
YT
Lin
Yi-Ling
YL
Chen
Ya-Hui
YH
Wang
Jui-Ling
JL
Chou
Ling-Yin
LY
Ping
Kee-Ching
KC
Jeng
D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
D045784:Abietanes; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D002118:Calcium; D053148:Caspase 3; D051546:Cyclooxygenase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D007375:Interleukin-1; D015850:Interleukin-6; D048031:JNK Mitogen-Activated Protein Kinases; D018696:Neuroprotective Agents; D009569:Nitric Oxide; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D048051:p38 Mitogen-Activated Protein Kinases; D000093242:Interleukin-6 Inhibitors; C489691:Ptgs2 protein, rat; C505410:Casp3 protein, rat; C018381:salvin