Effect of safranal, a constituent of saffron, on olanzapine (an atypical antipsychotic) induced metabolic disorders in rat

Abstract

Objectives: Olanzapine, an atypical antipsychotic, causes weight gain and metabolic disorders in humans. Safranal, one of the active components of Crocus sativus (saffron), has been shown to have anti-obesity, lipid and blood pressure lowering and anti-diabetes effects. In this investigation, the effect of safranal on metabolic disorders induced by olanzapine was studied.

Materials and methods: Fourty-two female Wistar rats were divided into 7 groups of 6 animals. The two groups were selected as controls, which received olanzapine and safranal solvents, respectively. The third group treated by olanzapine 5 mg/kg. Groups 4, 5 and 6 treated by olanzapine 5 mg/kg plus safranal (2.5, 5 and 10 mg/kg) and the last group received safranal 10 mg/kg. The injections were performed intraperitoneally for 14 days and on the 15^th day the rats were killed and their serum were collected to measure metabolic factors including glucose, insulin, triglyceride, total cholesterol and HDL cholesterol. Leptin level in plasma was also measured. Mean systolic blood pressure was measured using tail cuff method at the end of study. The rats were weighed every other day and amount of food consumed was measured daily.

Results: Olanzapine significantly elevated body weight, food intake, fasting blood glucose, TG, leptin, and mean systolic blood pressure (MSBP). It also significantly decreased HDL cholesterol blood level. Safranal significantly improved all these complications at three doses.

Conclusion: Based on the results of this study, safranal is thought to be used as an effective combination in controlling metabolic complications caused by olanzapine.

Keywords: Crocus sativus; Metabolic syndrome; Obesity; Olanzapine; Saffron; Safranal.

Figure 1

Investigating the effect of olanzapine 5 mg/kg with safranal and alone on daily weight changes in female rats during 14 days of intraperitoneal administration. For statistical comparison, two-way ANOVA and Tukey-Kramer Post hoc test were used. Comparison with control (*) and comparison with olanzapine (+); P<0.05(+,*), and P<0.01(++), and P<0.001 (+++) (saf: safranal, olan: olanzapine). N=6

Figure 2

Investigating the effect of olanzapine 5 mg/kg with safranal and alone on food intake in female rats during 14 days of intraperitoneal administration. Values are displayed as SEM+Mean. For statistical comparison, one-way ANOVA and Tukey-Kramer test were used. Comparison with control (*) and comparison with olanzapine (+); P<0.001 (+++ , ***) (saf: safranal, olan: olanzapine)

Figure 3

Investigating the effect of olanzapine 5 mg / kg with safranal and alone on mean systolic blood pressure (MSBP) changes in female rats during 14 days of intraperitoneal administration. Values are displayed as SEM+Mean. For statistical comparison, one-way ANOVA and Tukey-Kramer test were used. Comparison with control (*) and comparison with olanzapine (+); P<0.01(++) and P<0.001 (+++ , ***) (saf: safranal, olan: olanzapine)

Figure 4

Investigating the effect of olanzapine 5 mg/kg with safranal and alone on fasting blood sugar (FBS) in female rats during 14 days of intraperitoneal administration. Values are displayed as SEM+Mean. For statistical comparison, one-way ANOVA and Tukey-Kramer test were used. Comparison with control (*) and comparison with olanzapine (+); P<0.001 (+++ , ***) (saf: safranal, olan: olanzapine)

Figure 5

Investigating the effect of olanzapine 5 mg/kg with safranal and alone on insulin serum level in female rats during 14 days of intraperitoneal administration. Values are displayed as SEM+Mean. For statistical comparison, one-way ANOVA and Tukey-Kramer test were used. Comparison with control (*) and comparison with olanzapine (+); P<0.001 (+++ , ***) (saf: safranal, olan: olanzapine)

Figure 6

Investigating the effect of olanzapine 5 mg/kg with safranal and alone on leptin serum level in female rats during 14 days of intraperitoneal administration. Values are displayed as SEM+Mean. For statistical comparison, one-way ANOVA and Tukey-Kramer test were used. Comparison with control (*) and comparison with olanzapine (+); P<0.01(++) and P <0.001 (+++, ***) (saf: safranal, olan: olanzapine)

Figure 7

Investigating the effect of olanzapine 5 mg/kg with safranal and alone on triglyceride serum level in female rats during 14 days of intraperitoneal administration. Values are displayed as SEM+Mean. For statistical comparison, one-way ANOVA and Tukey-Kramer test were used. Comparison with control (*) and comparison with olanzapine (+); P<0.001 (+++ , ***) (saf: safranal, olan: olanzapine)

Figure 8

Investigating the effect of olanzapine 5 mg/kg with safranal and alone on HDL level in female rats during 14 days of intraperitoneal administration. Values are displayed as SEM+Mean. For statistical comparison, one-way ANOVA and Tukey-Kramer test were used. Comparison with control (*) and comparison with olanzapine (+); P<0.01(**) and P<0.001 (+++) (saf: safranal, olan: olanzapine)

Figure 9

Investigating the effect of olanzapine 5 mg/kg with safranal and alone on cholesterol in female rats during 14 days of intraperitoneal administration. Values are displayed as SEM+ Mean. For statistical comparison, one-way ANOVA and Tukey-Kramer test were used