Effects of syringic acid on chronic MPTP/probenecid induced motor dysfunction, dopaminergic markers expression and neuroinflammation in C57BL/6 mice

Karamkolly Raghavan Rekha , Govindasamy Pushpavathi Selvakumar , Ramu Inmozhi Sivakamasundari
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引用次数: 33

Abstract

Syringic acid (SA) is a naturally occurring O-methylated trihydroxybenzoic acid present in wine and released as a breakdown product of malvidin, a primary plant pigment (an anthocyanidin). In this study, the neuroprotective efficacy of syringic acid (SA) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and probencid (MPTP/p) induced mouse model of PD was investigated. The C57BL/6 mice were given 10 doses of MPTP/p for five consecutive weeks with 3.5 day interval. Administration of MPTP/p led to reduced motor coordination, neurochemicals and tyrosine hydroxylase (TH), dopamine transporter (DAT) and vesicular monoamine transporter-2 (VMAT2) expression. In addition, increased oxidative stress markers and the expression of inflammatory markers, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and cyclooxygenase-2 (COX-2). Pre-oral treatment with SA (20 mg/kg) was found to improve the MPTP/p-induced impaired motor functions by restoring the catecholamine content and antioxidant enzymes level. In addition, it ameliorated the expressions of TH, DAT and VMAT2 and also significantly attenuated MPTP/p-induced increased inflammatory markers expressions. These results partially explain the pharmacological efficacy of SA as a potential therapeutic agent for the treatment of MPTP/p-induced mice model of PD, together with its neuroprotective effect and reduce the progression of PD.

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丁香酸对慢性MPTP/丙戊酸所致C57BL/6小鼠运动功能障碍、多巴胺能标志物表达及神经炎症的影响
丁香酸(SA)是一种天然存在的o -甲基化三羟基苯甲酸,存在于葡萄酒中,是一种主要植物色素(花青素)的分解产物。本研究研究了丁香酸(SA)对1-甲基-4-苯基-1,2,3,6-四氢吡啶和probencid (MPTP/p)诱导的PD小鼠模型的神经保护作用。连续5周给予C57BL/6小鼠10剂MPTP/p,间隔3.5 d。MPTP/p导致运动协调性、神经化学物质和酪氨酸羟化酶(TH)、多巴胺转运蛋白(DAT)和囊泡单胺转运蛋白-2 (VMAT2)表达降低。此外,氧化应激标志物和炎症标志物如肿瘤坏死因子-α (TNF-α)、白细胞介素-1β (IL-1β)和环氧化酶-2 (COX-2)的表达增加。口服前给予SA (20 mg/kg)可通过恢复儿茶酚胺含量和抗氧化酶水平改善MPTP/p诱导的运动功能受损。此外,它还改善了TH、DAT和VMAT2的表达,并显著减弱了MPTP/p诱导的炎症标志物的表达。这些结果部分解释了SA作为潜在治疗剂治疗MPTP/p诱导的小鼠PD模型的药理作用,以及其神经保护作用和减缓PD的进展。
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