Investigating the Potential Stimulant Effects of Bacopa monnieri in Acute Rapid Eye Movement (REM) Sleep-deprived Mice

Abstract

Introduction: Sleep is a basic physiological process that allows the body to recuperate and replenish energy levels. In today's fast-paced world, many people don't get enough sleep and struggle with daytime grogginess. To combat this, they often rely on stimulants like caffeine, which are associated with side effects like tolerance build-up, anxiety, and cardiovascular problems. Bacopa monnieri, an ayurvedic herb, increases dopamine concentration, and holds potential to counteract and induce wakefulness. Objectives: To study the potential stimulant effects of Bacopa monnieri to improve cognitive and motor function during acute sleep deprivation Methods: The dopamine-degrading enzymatic targets of phytoconstituents of Bacopa monnieri were assessed computationally. The in vivo analysis was conducted on 48 male BALB/c mice randomly divided into groups. Acute sleep deprivation was induced using flowerpot method for two consecutive days followed by a rest day, over the duration of 15 days. Treatment with caffeine (5.7 mg/kg/day) or Bacopa monnieri plant extract (100 mg/kg/day) was administered orally. Behavior assessments were carried out to evaluate levels of anxiety, sociability, social novelty, intrinsic inquisitiveness, recognition memory and motor coordination. Stress levels and renal function were further assessed via biochemical tests along with neuronal and renal histopathology. Results: Molecular docking and PLIP analysis revealed that main phytoconstituents of Bacopa monnieri exhibit stronger binding affinities towards dopamine-degrading enzymes compared to caffeine. Acute sleep deprivation resulted in declined cognition (5.5 ± 1.3, p ≤ 0.05), increased anxiety (7.3 ± 1.8, n.s), impaired motor function (1.8 ± 0.4, n.s), and reduced body weight (78.5 ± 3.3, p < 0.001). Additionally increased cortisol (42.73 ± 8.7, p ≤ 0.05) and urea (84.9 ± 10.2, p ≤ 0.05) levels compared to the control group were seen. Caffeine-treated sleep-deprived group mice exhibited improved cognition (13.0 ± 3.7, n.s), high anxiety (9.1 ± 1.4), improved motor coordination (0.5 ± 0.2, p ≤ 0.05), weight loss (79.0 ± 1.0), accompanied by high cortisol (38.67 ± 2.9) and urea (89.3 ± 3.8) levels. While Bacopa monnieri consumption in sleep deprived mice increased cognition (22.4 ± 3.0, p ≤ 0.01), reduced anxiety (4.7 ± 1.3, p≤ 0.01), improved motor coordination (0.5 ± 0.2, p ≤ 0.05), maintained weight (95.2 ± 3.1, p < 0.001), reduced cortisol (17.17 ± 2.4, p ≤ 0.05) and urea (71.7 ± 4.1) levels compared to sleep-deprived group. Furthermore histopathological analysis supported invigorating stimulation by caffeine and calming stimulation by Bacopa monnieri. xviii Conclusion: Bacopa monnieri holds potential as a nutraceutical stimulant comparable to the effects of caffeine. Additional GCMS analysis of the Bacopa monnieri extract is needed to identify and quantify its phytoconstituents. Moreover, further elucidation of Bacopa monnieri's molecular mechanism contributing to its stimulating effects are required.