Menthol, a bioactive constituent of Mentha , attenuates motion sickness in mice model: Involvement of dopaminergic system

Abstract

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.

Nutritional and Behavioral Countermeasures as Medication Approaches to Relieve Motion Sickness: A Comprehensive Review

“…Studies involving ginger were inconclusive due to varying ginger doses between trials and study designs. According to Table 2 , nutrient substances such as ginger [ 140 ], Tamazin [ 146 ], Tianxiang formulation [ 139 ], menthol [ 156 ], hesperidin [ 154 ], and vitamin C [ 123 ] can reduce MS through lowering histamine [ 139 , 146 , 148 , 154 ], dopamine [ 148 , 156 ], and acetylcholine levels [ 139 ]. There may be additional mechanisms that contribute to the effectiveness of these substances, but further evaluations are necessary to confirm their impact.…”

“…Hesperidin has been found to decrease histamine levels and downregulates histamine H 1 receptor protein expression and mRNA in the hypothalamus and brainstem [ 154 , 155 ]. Researchers in [ 156 ] also found that the antihistamine activity of hesperidin was almost two times more than that of menthol.…”

Stroboscopic lighting with intensity synchronized to rotation velocity alleviates motion sickness gastrointestinal symptoms and motor disorders in rats

“…Conditioned gaping response that can be elicited during exposure to a context previously paired with nauseant agents or provocative motion can be alleviated by corresponding anti-emetic and anti-MS drugs, making it plausible to serve as a rat model of conditioned nausea (Limebeer et al, 2008;Parker, 2014;Zhou et al, 2017;Qi et al, 2019;Rock et al, 2022). In addition, defecation response and decreased spontaneous locomotion activity were also observed in rats and mice exposed to whole-body rotation (Ossenkopp and Frisken, 1982;Ossenkopp et al, 1994;Yu et al, 2007;Limebeer et al, 2008;Morita et al, 2017;Wang et al, 2017;Deshetty et al, 2021). Balance disorder characterized by the decline in the time taken traversing balance beam was also elicited by passive motion stimulation in both rats and mice (Tung et al, 2014;Zhou et al, 2017;Manno et al, 2020;Zhong et al, 2022).…”