The motor coordination activity of alcoholic extract of Withania coagulans fruits in Swiss albino mice by rota rod test

Introduction

The daytime impairment caused by insomnia is due to the individual experience of trouble with sleep initiation, extent, consolidation, quality, which occurs in spite of adequate opportunity for sleep, thus results in.^[1] The prevalence of insomnia in India is 9% in the general population^[2] compared to 10-30% in the world.^[3], ^[4], ^[5]

There are various drugs like benzodiazepines and barbiturates used for the treatment of insomnia.^[6] However, they do not lack the side effects. The Rota rod test is widely used to evaluate the motor coordination in rodents.^[7] When a mouse is placed on a constant speed rotating rod after ingestion of a central depressant, instead of walking on the rod the animal easily falls from it. This test was first introduced by Dunham and Miya for assaying the drug effects on the motor activity.^[8] Since then, the effects of various central depressants, investigated by this test have been reported.^[9], ^[10], ^[11]

The Solanaceae family covers 84 genera comprising approximately 3,000 species. These species are mainly annual shrubs distributed all over the world. The two genera namely Withania and Physalis play a vital role in the Unani and Ayurvedic systems in the South East Asia. The 23 acknowledged Withania species are extensively scattered in the drier portions of tropical and subtropical zones.^[12], ^[13], ^[14] Out of all these species, the W. coagulans and W. somnifera are financially and curatively important.^[15], ^[16], ^[17] Withania coagulans is a rare species, not found widespread in the territory. This plant is primarily used for the milk coagulation. Though plenty of work has been done to study its antidiabetic activity, not much work is done to evaluate its action on the CNS.^[18], ^[19], ^[20] In 1977 Budhiraja et al. reported CNS depressant effect of this plant.^[21] Thereafter this plant was not much studied for the CNS activity. Thus, it was thought worthwhile to measure the CNS depressant action of this medicinal herb in Swiss albino mice by rota rod test.

Materials and Methods

Results

As observed in the [Table 1], on Day 1 to Day 8 there was no statistically significant difference in endurance time by mice. However, on days 15, 23 and 30 endurance time by mice on rota rod apparatus reduced highly significantly (p<0.001) for all the three doses of 200 mg/kg, 500 mg/kg and 1000 mg/kg of WCFAlcE compared to control. Furthermore, dose response relationship was observed for this reduction for all the three doses. To conclude, this reduction in endurance time by test drug was comparable to that of standard drug diazepam.

Discussion

As observed in [Table 1], on days 15, 23 and 30 endurance time by mice on rota rod apparatus ‘decreased’ highly significantly (p<0.001) for all the three doses of 200 mg/kg, 500 mg/kg and 1000 mg/kg of WCFAlcE compared to control. Furthermore, dose response relationship was observed for this ‘decrease’.

Our study is extraordinary one as there are no other articles reported which have verified the effect of any of the extract of Withania coagulans on mice using Rota rod apparatus. Yet, Withania somnifera (WS) which is a related species to Withania coagulans (WC) having same genus, had been tested for the motor coordination using Rota rod apparatus in middle cerebral artery occluded (MCAO) rodents. It was found that WS had significantly (p<0.05) ‘increased’ the performance of MCAO rodents treated with WS root extract on Rota rod apparatus.^[23] Hence it can be concluded that the different Withanoloides in both the species might be responsible for this activity. The term “Withanolide” composed of “withan” from the genus Withania plus “olide” is biochemical term for a lactone. Today about 400 Withanolides discovered from fifty eight solanaceous species belonging to twenty two genera. Structurally they are steroids built on an ergostane skeleton.^[24]

There are two varieties of rota rod test. First is the constant speed rota rod, and second is accelerating Rota rod.^[25] In our test we used the constant speed Rota rod. But it has few disadvantages. Rod’s diameter can affect the performance of mice,^[26] therefore we used Rota rod of 25 mm diameter. There can be impairment of memory of mice rather than the motor coordination by the test drug,^[27] to eliminate this bias we trained the mice robustly before test. The constant speed rota rod consumes lot of time,^[27] because the time limit needs to be set which declines the sensitivity of this test.^[27] To eradicate this bias, we used the maximum velocity of 25 revolutions per minute on the Rota rod test which had a range of 5 to 25 revolutions per minute. The maximum endurance time of mouse on this apparatus was 38 seconds. This test can estimate the muscle relaxant property of any compound but does not really distinguish between anxiolytics and neuroleptics. Typically, the central depressant medicines have muscle relaxant action. Hence, this test can be valuable to measure the central depressive effect of any medication.^[8]

Though stimulants rise the performance of mice on the rota rod test so that mice take longer time to fall from the rotating rod,^[11] the depressants drop the endurance time of mice on Rota rod so that mice fall early on revolving rod.^[28] To conclude, our test drug WCFAlcEs might have depressant action on mice. Since the effect appeared after 2 weeks, it cannot be used in the acute settings. Therefore it is more suitable for the chronic settings.

Source of Funding

None

Conflict of Interest

None.