Nasal Treatment of Standardized Centella Asiatica Leaves Extract Ameliorates Chronic Unpredictable Mild Stress in Laboratory Rats

Objective: To assess the effectiveness of nasal solution of Centella asiatica leaves standardized to triterpenoids (INDCA-NS) in preventing “chronic unpredictable mild stress” (CUMS) in rats. Methods: The study involved six groups of twelve rats each, with five groups receiving CUMS induction and one group without CUMS, serving as a vehicle control (VC). The other groups received intranasal administration of saline, buspirone, or INDCA-NS (10,30 and 100 µg/rat/day, 2.5, 7.5, and 10 µg/nostril/twice daily) from day 35 to day 49. Behavioral parameters were assessed using the marble burying test, Y-maze, Morris water maze, sucrose preference test, and resident intruder test on days 0, 35, 42, and 49, respectively. The levels of stress-related biomarkers, cortisol and “brain-derived neurotrophic factor” (BDNF) in the hypothalamus were measured using ELISA kits. The data was analyzed with analysis of variance followed by pairwise comparisons, with significance set at P < 0.05. Results: CUMS induction led to a significant increase in anxiety, anhedonia, aggression, and stress markers, as well as a reduction in working and spatial memory parameters (vs. VC). INDCA-NS and BUS administration for 14 days resulted in dose-dependent and significant prevention of CUMS-induced anxiety, working memory, anhedonia, and aggression, but not Morris’s water maze parameters and BDNF levels. Conclusion: Subacute intranasal INDCA-NS showed chronic stress-preventive potential in rats, indicated by the prevention of anxiety, anhedonia, and aggression in CUMS-induced rats, probably through cortisol reduction.