title: Mulberroside A protects against ischemic impairment in primary culture of rat cortical neurons after oxygen-glucose deprivation followed by reperfusion.
abstract: Mulberroside A is a natural polyhydroxylated stilbene compound present at relatively high abundance in the roots and twigs of Morus alba L. It is known for its nephroprotective, hypoglycemic, and antidiabetic effects. Because its metabolite, oxyresveratrol, possessed purported anti-inflammatory and neuroprotective effects, we proposed that mulberroside A may elicit neuroprotective effects that can be used in the treatment of brain ischemic injury. Therefore, we decided to investigate the pharmacological properties of mulberroside A in primary culture of rat cortical neurons after oxygen-glucose deprivation followed by reperfusion (OGD/R), evaluating its ability to counteract the hypoxia-ischemia impairment. The results showed that mulberroside A elicited neuroprotective effects comparable to nimodipine. The mechanistic studies showed that mulberroside A decreased the expressions of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 and inhibited the activation of NALP3, caspase-1, and nuclear factor-κB and the phosphorylation of extracellular signal-regulated protein kinases, the c-Jun N-terminal kinase, and p38, exhibiting anti-inflammatory antiapoptotic effects. Our results also further demonstrate that the proinflammatory cytokines of IL-1β, IL-6, and TNF-α are promising targets for treatment of cerebral ischemic injury. Although further investigation is required for its development, all of these findings led us to speculate that mulberroside A is a candidate for the treatment of ischemic stroke, which would act as a multifactorial neuroprotectant.
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, China.
authors.forename: Cai-Ping
authors.initials: CP
authors.lastname: Wang
authors.forename: Lu-Zhong
authors.initials: LZ
authors.lastname: Zhang
authors.forename: Gui-Cai
authors.initials: GC
authors.lastname: Li
authors.forename: Yun-wei
authors.initials: YW
authors.lastname: Shi
authors.forename: Jian-Long
authors.initials: JL
authors.lastname: Li
authors.forename: Xiao-Chuan
authors.initials: XC
authors.lastname: Zhang
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Ding
authors.forename: Xin-Miao
authors.initials: XM
authors.lastname: Liang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002352:Carrier Proteins; D020170:Caspase 1 / Q000378:metabolism; D015687:Cell Hypoxia; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004187:Disaccharides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D005947:Glucose / Q000172:deficiency*; D016328:NF-kappa B / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D004187:Disaccharides; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D018696:Neuroprotective Agents; C573346:Nlrp3 protein, rat; D018160:Receptors, Cytoplasmic and Nuclear; D013267:Stilbenes; C420606:mulberroside A; D020170:Caspase 1; D005947:Glucose
keywords: apoptosis; inflammation; ischemia; mulberroside A; neuroprotection