Evaluation of antidepressant effects and safety of Lavendula angustifolia aqueous and total crude leaf extracts in Wistar albino rats.

Abstract

Introduction: Depression continues to be a major problem in Ugandan population and communities’ use medicinal plants like L. angustifolia (Lavandula angustifolia) for its treatment.Objective: To establish the antidepressant effects and safety of L. angustifolia aqueous and total crude leaf extracts in depression-induced Wistar albino rats. Methods: An experimental laboratory-based study was conducted. Total of 48 Wistar albino rats (male -24 and female -24) were used for antidepressant effects. Group-I (negative control) received tap water, while Group II (positive control) received escitalopram 10mg/kg, Group- III, received aqueous extract of 200mg/kg bwt and IV received aqueous extract of 1000mg/kg bwt administered orally an hour prior to the FST. Group V received Total crude 200mg/kg bwt and Droup VI received Total crude 1000mg/kg bwt. Depression in rats was induced by subjecting them to several manipulations of Chronic Unpredictable Stress (CUS) from 1-5 weeks. Inability of animals to feel pleasure (anhedonia) or a distaste to drink sucrose solution (sweetened water) was evaluated using Sucrose Preference Test (SPT) while, antidepressant effects was determined using forced swim test (FST). Duration in minutes of immobility, swimming, and climbing or struggling period was recorded. Most active dose extract (1000mg/kg bwt aqueous) was used for safety studies. For acute toxicity study, up and down method was used on 30 Swiss albino mice and according to the OECD guideline 425, no further test was done and was declared safe. For sub- acute toxicity study, 1000mg/kg bwt of aqueous leaf extract was administered orally to the 12 rats (6 test groups and 6 control) for 28 days and blood samples were drowned from tail vein on days 0, 7, 14 ,21 and 28 to determine any hematological alterations in procalcitonin levels, neutrophil, lymphocyte, monocyte, eosinophil, basophil counts plus RBCs, MCV, HGB, HCT, MCH, MCHC, RDW-CV, platelets and biochemistry studies; serum Total bilirubin, AST, ALT, total protein, creatinine, urea and Histopathological changes in the organs (liver, kidney and the brain), levels were also identified. one way ANOVA was used to compare (p<0.005) mean differences between the control and the extract treated rats. Results: The percentage of sucrose preference in chronic mild stress group was 19.2% (24) compared to 66% (198) of the unstressed groups (p<0.005). Administration of L. angustifolia (1000mg/kg body weight) showed a significant (p<0.005) reduction in mean immobility time 6.8±0.53 (minutes) as compared to 5.56±0.24 (minutes) of the control and 1 minute in stressed animals compared to 3 minutes of normal animals in the FST; the effect of which was comparable to that of the synthetic antidepressant escitalopram. No change in the locomotion activity observed. For acute toxicity study, no death was recorded. Hematological parameters such as PCT, neutrophil, monocyte, lymphocyte, eosinophil and basophils count had statistically significant (p<0.005) difference compared to the control RBC values; RBCs, MCV, HGB, HCT, MCH, MCHC, RDW-CV and PLATELET counts had statistically significant (p<0.005) difference compared to the control, slight increase in platelet count was observed. Biochemical parameters such as AST, ALT, had no statistically significant (p<0.005) difference compared to the control, though there was slight significant (p<0.005) increase in total protein values, creatinine and urea level values as compared to the controls and no histopathological changes were detected in the organs. Conclusion: Findings show that 1000mg/kg bwt aqueous extract dose produced antidepressant effects similar to Escitalopram. No death was recorded within 24 hours at 5000mg/kg bwt limit dose. No major organ derangement noted except marked irregular vacuoles (glycogen degeneration) in hepatocytes and focal portal mononuclear inflammation.