ReferenceID 4113

Study on the pharmacodynamic effect of Rhizoma Dioscoreae polysaccharides on cerebral ischemia-reperfusion injury in rats and the possible mechanism

J Ethnopharmacol

Ethnopharmacological relevance: Rhizoma Dioscoreae (RD) is the rhizome of Dioscorea opposita Thunb., a traditional Chinese medicine, which can treat hypertension, diabetes, cerebral vasospasm headache and Alzheimer's dis

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Reference Id
4113
Evidence Id
20703
Core Evidence Id
20703
Source Reference Id
1508
Herb2 Reference Id
HBREF002305
Subject Paper Key
HERB002476_35777608
Pubmed Id
35777608
Doi
10.1016/j.jep.2022.115517
Paper Title
Study on the pharmacodynamic effect of Rhizoma Dioscoreae polysaccharides on cerebral ischemia-reperfusion injury in rats and the possible mechanism
Paper Abstract
Ethnopharmacological relevance: Rhizoma Dioscoreae (RD) is the rhizome of Dioscorea opposita Thunb., a traditional Chinese medicine, which can treat hypertension, diabetes, cerebral vasospasm headache and Alzheimer's disease. Meanwhile, RD is the main component of Liuwei Dihuang pill, a Chinese patent medicine. Rhizoma Dioscoreae polysaccharides (RDPS) are the primary active ingredient of RD. Modern medical research confirmed RDPS has multiple pharmacological effects, including neuroprotection, immunoregulation, antioxidant effect in many organs. The primary ischemia/hypoxia injury and secondary reperfusion injury are mainly caused by oxidative stress, which caused by hypoxia, such as free radical generation, energy metabolism disorder, intracellular calcium overload, excitatory amino acid release and inflammatory reaction. Aim of the study: We have investigated the pharmacodynamic effect of RDPS on cerebral ischemia-reperfusion (IR) injury in rats and the possible mechanism in vitro. Materials and methods: The pharmacodynamic effect of RDPS on IR injury in rats was studied by the construction of the occlusion of middle cerebral artery (MCAO) model, measuring the volume of cerebral infarct area, the content of oxidation index, inflammatory cytokines, and the expression of CaMMKβ in brain tissue. The in vitro study was explored by oxygen-glucose deprivation/glycogen reoxygenation (OGD/R) model, construction of the CaMMKβ interference sequence, measuring the expression of CaMMKβ in BV2 cells before and after inhibition of CaMMKβ, and the influence of RDPS on Nrf2/HO-1 signal pathway, in order to investigate the possible mechanism. Results: Compared with the model group, the present study showed that RDPS with high-dose and low-dose groups could significantly reduce the volume of cerebral infarction. The content of MDA decreased and the activities of GSH and SOD increased in the two dose groups of RDPS. We confirmed that after RDPS treatment, the levels of IL-6, IL-1 β and TNF-α in brain tissue were lower than those in model group, and the expression of CaMMKβ in brain tissue of rats decreased in the model group, but increased in the groups of RDPS. In the in vitro study, compared with the control group, RDPS could regulate the OGD/R-induced apoptosis of BV2 cells and increase the level of CaMMKβ, Nrf2 and HO-1 induced by OGD/R. To our surprise, these therapeutic effects are no longer present after the inhibition of CaMMKβ protein. The activity of BV2 induced by OGD/R could not be enhanced by RDPS after the inhibition of CaMMKβ protein. Conclusions: RDPS has the pharmacodynamic effect in IR injury, which reduce the area of cerebral infarction, up-regulate the activity of anti-oxidant kinase, and down-regulate the inflammatory cytokine. Additionally, RDPS could affect the activation of Nrf2/HO-1 signaling pathway by regulating the expression of CaMMKβ. Our observations justify the RDPS could be a new strategy for IR injury therapy, and the mechanism may be related to the improvement of antioxidant enzyme activity and inhibition of inflammatory reaction.
Journal
J Ethnopharmacol
Publish Year
2022
Experiment Subject
rat; bv2 cells
Experiment Type
Animal Experiment
Phenotype Related
Cerebral Vasospasm Headache; Energy Metabolism Disorder; Ischemia/hypoxia Injury; Ir Injury; Hypertension; Reperfusion Injury; Cerebral Infarction; Diabetes; Alzheimer's Disease
Paper Title Cn
Paper Title En
Study on the pharmacodynamic effect of Rhizoma Dioscoreae polysaccharides on cerebral ischemia-reperfusion injury in rats and the possible mechanism
Bilingual Status
semi_complete