Deshetty Uma Maheswari, Tamatam Anand, Patil Mahantesh Mallikarjun
Nutrition, Biochemistry & Toxicology Division, Defence Food Research Laboratory, Mysore, India.
J Food Biochem. 2021 Jul 9:e13863. doi: 10.1111/jfbc.13863.
Motion sickness (MS) occurs due to contradicting vestibular and visual inputs to the brain causing nausea and vomiting. Antidopaminergic drugs being effective in reducing MS create a path for effective therapy against MS by regulating dopamine levels. We aimed to evaluate the role of the striatum and brainstem dopamine and dopamine D2 receptor (DRD2) in MS and the efficacy of menthol (MNT) to modulate dopamine and DRD2 in vitro and in vivo for possible amelioration of MS. Evaluation of efficacy of MNT to inhibit dopamine release from PC12 cells and anti-MS efficacy in BALB/c mice model was performed. Dopamine, DRD2 expression in PC12 cells, mice striatum, and brainstem were detected using HPLC-ECD, RT-PCR, and Western blot analysis, respectively. DRD2 expression increased in calcium ionophore-treated PC12 cells compared with control cells. Pretreatment with 50 μg/ml menthol decreased dopamine and DRD2 expression. Similarly, dopamine and DRD2 levels in mice striatum and brainstem of MS group (rotation induced) increased significantly compared with control group NC (no rotation). Pretreatment with menthol at 50 mg/kg concentration (rotation induced) showed decreased dopamine and DRD2 expression, thus indicating ameliorative effect on MS. Hence, we suggest that increased striatum and brainstem dopamine and DRD2 levels might lead to MS symptoms, and menthol could be used as a potent herbal alternative medicine for MS. PRACTICAL APPLICATIONS: Antidopaminergic drugs being effective in reducing motion sickness (MS) creates a path for effective therapy against MS by regulating dopamine levels. Increased striatum and brainstem dopamine and Dopamine D2 receptor (DRD2) levels might lead to the MS symptoms induced by rotation stimulation in mice model. Menthol showed a prophylactic effect on rotation-induced MS by reducing striatal and brainstem dopamine levels, DRD2 mRNA, and protein expression. Menthol could be used as an herbal alternative to antidopaminergics to minimize the associated adverse effects.
晕动病(MS)是由于传入大脑的前庭和视觉信息相互矛盾,从而导致恶心和呕吐。抗多巴胺能药物对减轻晕动病有效,通过调节多巴胺水平为晕动病的有效治疗开辟了一条途径。我们旨在评估纹状体和脑干中的多巴胺及多巴胺D2受体(DRD2)在晕动病中的作用,以及薄荷醇(MNT)在体外和体内调节多巴胺和DRD2的功效,以期改善晕动病。对薄荷醇抑制PC12细胞释放多巴胺的功效以及在BALB/c小鼠模型中的抗晕动病功效进行了评估。分别使用高效液相色谱-电化学检测法(HPLC-ECD)、逆转录-聚合酶链反应(RT-PCR)和蛋白质免疫印迹分析检测PC12细胞、小鼠纹状体和脑干中的多巴胺、DRD2表达。与对照细胞相比,经钙离子载体处理的PC12细胞中DRD2表达增加。用50μg/ml薄荷醇预处理可降低多巴胺和DRD2表达。同样,与未旋转的对照组NC相比,旋转诱导的晕动病组小鼠纹状体和脑干中的多巴胺和DRD2水平显著升高。以50mg/kg浓度的薄荷醇进行预处理(旋转诱导)可使多巴胺和DRD2表达降低,从而表明对晕动病有改善作用。因此,我们认为纹状体和脑干中多巴胺及DRD2水平升高可能导致晕动病症状,薄荷醇可作为治疗晕动病的一种有效的草药替代药物。实际应用:抗多巴胺能药物对减轻晕动病有效,通过调节多巴胺水平为晕动病的有效治疗开辟了一条途径。纹状体和脑干中多巴胺及多巴胺D2受体(DRD2)水平升高可能导致小鼠模型中旋转刺激诱发的晕动病症状。薄荷醇通过降低纹状体和脑干中的多巴胺水平、DRD2 mRNA及蛋白表达,对旋转诱发的晕动病显示出预防作用。薄荷醇可作为抗多巴胺能药物的草药替代品,以尽量减少相关不良反应。