Abstract

The novel strategy against ischemic stroke in metabolic syndrome (MetS) targeting at oxidative stress and inflammation has gained attention due to the limitation of the current therapy. Due to the antioxidant and anti-inflammation of the combined extract of Oryza sativa and Anethum graveolens, the cerebroprotective effect against cerebral ischemia in MetS condition has been focused. Since no data were available, this study was set up to determine the effects of the combined extract of Oryza sativa L. and Anethum graveolens Linn. against ischemic stroke in the animal model of metabolic syndrome. The possible underlying mechanism was also further investigated. Male Wistar rats (180-220 g) were fed with high-carbohydrate high-fat diet (HCHF diet) to induce metabolic syndrome-like condition. Then, MetS rats were subjected to reperfusion injury at the right middle cerebral artery. The combined extract of O. sativa and A. graveolens (OA extract) at doses of 0.5, 5, and 50 mg/kg BW was fed once daily for 21 days. Neurological assessment was performed every 7 days throughout the experimental period. At the end of study, brain infarction volume, neuron and glial fibrillary acidic protein- (GFAP-) positive cell density, the oxidative stress status, the expressions of proinflammatory cytokines (NF-κB, IL-6), and eNOS in the cortical area together with the expression of VCAM-1 and the histological changes of common carotid artery were determined. It was found that OA extract decreased brain infarction, neurological score, oxidative stress status, and inflammatory mediators but increased eNOS expression in the cortical area; the increased VCAM-1 and intima-media thickness together with the reduction of lumen diameter of common carotid artery of MetS eats with MCAO were also mitigated by OA extract. These data suggest the cerebroprotective effect of OA, and the underlying mechanism may occur partly via the improvement of oxidative stress status, inflammation, and brain blood supply.

Highlights

  • Nowadays, the prevalence of metabolic syndrome, an important noncommunicating disease, is continually rising and it is regarded as the critical health problem in both the developed and developing countries

  • metabolic syndrome (MetS) rats which subjected to middle cerebral artery occlusion (MCAO) and received vehicle showed an increase in the neurological score throughout the study period (p value < 0:001 all; compared to the high-carbohydrate high-fat (HCHF)+sham operation group)

  • The neurological scores throughout the study period of MetS rats with MCAO were improved by the combined extract of O. sativa and A. graveolens at doses of 0.5, 5, and 50 mg/kg BW (p value < 0:001 all; compared to HCHF+MCAO+vehicle)

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Summary

Introduction

The prevalence of metabolic syndrome, an important noncommunicating disease, is continually rising and it is regarded as the critical health problem in both the developed and developing countries. Since MetS is an important cause of atherosclerosis, a key pathophysiological factor of ischemic stroke [5], the prevalence of ischemic stroke in MetS increases. Stroke in MetS often induces poor outcomes [6] and produces both financial and psychological burdens for the country. Despite increasing their importance, the effective pharmacological agents which can effectively prevent and treat cerebral ischemia with MetS are still in an unsatisfaction level.

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