Effect of Crocus sativus extracts and its active constituent safranal on the harmaline-induced tremor in mice

Abstract

Objectives: Due to unsatisfactory response or intolerable side effects of current drugs, treatment of essential tremor remains inadequate. Thus, we aimed to investigate the protective and therapeutic effects of aqueous and ethanolic extracts of Crocus sativus (saffron), and its active consistent, safranal, on the harmaline-induced tremor in mice.

Materials and methods: To induce tremor, harmaline (30 mg/kg) was injected intraperitoneally. Test groups were also given the aqueous and ethanolic extracts of saffron (40, 80, and 160 mg/kg) as well as safranal (0.1, 0.3, and 0.5 ml/kg), intraperitoneally, 10 min before harmaline administration (prophylactic study) or 10 min after the onset of tremors (curative study). The latency of onset, duration, and intensity of tremor were recorded.

Results: The extracts (80 and160 mg/kg) dose dependently attenuated duration of harmaline-induced tremors as did reference drug, propranolol (2 and 5 mg/kg). Only the highest dose of extracts (160 mg/kg) attenuated intensity of harmaline-induced tremors throughout the study. Safranal at the doses of (0.1 and 0.3 ml/kg) but not 0.5 ml/kg attenuated duration and intensity of tremor. Onset of tremor increased with the extracts (80 and 160 mg/kg) in prophylactic study, as the effect observed with propranolol at the dose of 5 mg/kg. Safranal did not affect the latency of tremor.

Conclusion: Both aqueous and ethanolic extracts of saffron and with a less effect, low doses of safranal, have relatively protective and suppressive effects on the harmaline-induced tremor and different constituents of extracts seem to participate in the protective effects against harmaline induced tremor.

Keywords: Crocus sativus; Essential tremor; Harmaline; Safranal.

Figure 1

Effects of A: aqueous extract (Aq Ex, 40, 80, and 160 mg/kg), B: ethanolic extract (Eth Ex, 40, 80, and 160 mg/kg), and C: safranal (0.1, 0.3, and 0.5 ml/kg) on the onset of harmaline-induced tremor. Values are mean±SEM of six mice, *P <0.05 as compared with harmaline alone treated animals by ANOVA followed by post-hoc comparison using Tukey’s test. HR: harmaline. Times in x-line indicate time after harmaline treatment

Figure 2

Effects of A: aqueous extract (Aq Ex, 40, 80, and 160 mg/kg), B: ethanolic extract (Eth Ex, 40, 80, and 160 mg/kg), and C: safranal (0.1, 0.3, and 0.5 ml/kg), on the duration of harmaline-induced tremor in prophylactic study. D, E, and F: effects of aqueous extract (Aq Ex, 40, 80, and 160 mg/kg), ethanolic extract (Eth Ex, 40, 80, and 160 mg/kg), and safranal (0.1, 0.3, and 0.5 ml/kg), respectively on the duration of harmaline-induced tremor in curative study. Values are mean±SEM of six mice, ^P<0.01 and *P<0.001 as compared with harmaline alone treated animals by ANOVA followed by post-hoc comparison using Tukey’s test. HR: harmaline. Times in x-line indicate time after harmaline treatment

Figure 3

Effects of A: aqueous extract (Aq Ex, 40, 80, and 160 mg/kg), B: ethanolic extract (Eth Ex, 40, 80, and 160 mg/kg) of saffron, and C: safranal (0.1, 0.3, and 0.5 ml/kg), on the intensity of harmaline-induced tremor in prophylactic study. Effects of D: aqueous extract (Aq Ex, 40, 80, and 160 mg/kg), E: ethanolic extract (Eth Ex, 40, 80, and 160 mg/kg) of saffron, and F: safranal (0.1, 0.3, and 0.5 ml/kg), respectively on the intensity of harmaline-induced tremor in curative study. Values are mean±SEM of six mice. ∞P<0.05, *P<0.01, #P <0.001 compared with harmaline-alone–treated animals using two-way ANOVA followed by Bonferroni’s post hoc comparison at different time points. HR: harmaline. Times in x-line indicate time after harmaline treatment