Antidepressant-like Property of Jobelyn

▼ Objectives: The purpose of this investigation was to evaluate whether Jobelyn ® (JB) possesses anti-depressant-like property in the mouse forced swimming test (FST), tail suspension test (TST) and yohimbine-induced lethality test (YLT) in aggregated mice. Methods: Mice were given JB (10–100 mg/kg, p.o.) daily for 7 days and then subjected to FST, TST, YLT and open fi eld test. The parameters assessed in both FST and TST were the time (s) spent in active movement (struggling time), fi rst occurrence of immobility (s) and the duration of immobility (s). In the YLT, the mortality rate was recorded 24 h after yohimbine (35 mg/kg, i.p.) administration. In the open fi eld test, the number of line crosses and total distance travelled (m) were measured for 10 min in the open fi eld chamber. Results: JB signifi cantly (p < 0.05) decrease the duration of immobility both in the FST and TST, which suggests antidepressant-like property. JB signifi cantly (p < 0.05) prolonged the time spent in active swimming and delayed the fi rst occurrence of immobility, indicating endurance promoting eff ect. It potentiated the toxic eff ect of yohimbine, which further suggests antidepressant-like activity and facilitation of both serotonergic and noradrenergic neurotransmissions. However, JB did not signifi cantly increase the locomotor activity in the open-fi eld test. Conclusions: Jobelyn ® has antidepressant-like activity, which may be related to the stimulation of serotonergic and noradrenergic pathways. The ability of Jobelyn ® to delay the onset of immobility and to prolong the struggling time support its use as energizer in general body weakness or exhaustion. 2 DrugRes/2013-06-0332/22.8.2013/MPS Original Article DrugRes/2013-06-0332/22.8.2013/MPS Umukoro S et al. Antidepressant Property of Jobelyn ® ... Drug Res 2013; 63: 1–5 ■ Proof copy for correction only. All forms of publication, duplication or distribution prohibited under copyright law. ■ therapeutic usefulness in central nervous system disorders [ 4 – 7 ] . Although previous studies have confi rmed the anti-anaemic eff ect of JB [ 1 , 2 ] , several other medicinal claims especially in central nervous system disorders are yet to be verifi ed scientifi cally. This present study which describes the antidepressant property of JB is a part of our ongoing investigations on the psychopharmacological activities of this unique herbal formulation in experimental animals. It is well recognized that a high levels of sustained stress is associated with the natural course of several illnesses especially depression [ 8 ] . Prolonged intense stress produced lowered mood and depletion of monoamines that played crucial role in the regulation of emotion and behavior [ 8 , 9 ] . Thus, a common neurochemical abnormality particularly noradrenergic system/ serotonergic system exist between depressions and prolonged psychosocial stress [ 8 – 10 ] . Furthermore, depressed individuals and those under prolonged intense stress exhibit low tolerance to frustration and are more prone to exhaustion [ 8 , 11 ] . The use of JB as an energizer in the state of exhaustion and relieve of stress suggest that it might contain psychopharmacologically active compounds with anti-depressant property. Thus, this present investigation was carried out to evaluate whether Jobelyn ® has anti-depressant-like property in rodent models predictive of endogenous depression in humans. Materials and Methods ▼ Experimental animals Male albino Swiss mice (20–22 g) were obtained from the Central Animal House, University of Ibadan. The animals were housed in plastic cages at room temperature and they had free access to commercial food pellets and water ad libitum. They were acclimatized for at least one week before use for all experiments. The study was carried out in accordance with the ethical guidelines of the University of Ibadan for the care and use of laboratory animals for experimental studies. Drugs and treatment Imipramine (IM) hydrochloride (Sigma-Aldrich, St. Louis, USA), yohimbine (Sigma, USA) and Jobelyn ® (Health Forever Products Ltd, Lagos, Nigeria) were used in the study. All drugs were dissolved in distilled water immediately before use and were given orally. The doses of 10, 50 and 100 mg/kg of JB used in the study were selected based on the results obtained from preliminary investigations. All the experimental procedures were started on day 7, 60 min after treatment. Experimental Procedures ▼ Forced swim test (FST) The forced swim test is the most widely used test to evaluate depression-like behavior exhibited by mice [ 12 ] . The FST was carried out according to the method of Porsolt et al. [ 13 ] . Mice (6/group) were forced to swim individually in a glass jar (height: 20 cm, diameter: 10 cm) fi lled with water (depth: 15 cm) at a temperature of 25 ± 2 °C for 6 min. The duration of immobility (s) was recorded during the last 4 min of a 6 min observation period. A mouse was judged to be immobile when it remained fl oating in an upright position with the head above the water level. In addition, the struggling time (s) and fi rst occurrence of immobility (s) were also measured. Struggling time was defi ned as the total time spent swimming with active limb motions during the 6 min test. Latency of immobility was defi ned as the duration from the start of the experiment to the fi rst appearance of 4-limb immobility. Tail suspension test (TST) The TST was carried out according to the method previously described [ 14 – 16 ] . Mice (6/group) were individually suspended by the tail to a cord of about 50 cm in length stretched between 2 metal retort-stands at a height of 70 cm. After the initial 2 min period of vigorous motor activity, the mice became still and the immobility time (s) was measured with a stopwatch for a period of 4 min. Mice were considered immobile when they hung passively and completely motionless [ 14 ] . In addition, the struggling time (s) and fi rst occurrence of immobility (s) were also measured. Struggling time was defi ned as the total time spent with active limb movements during the 6 min test. Latency of immobility was defi ned as the duration from the start of the experiment to the fi rst appearance of 4-limb immobility. Yohimbine lethality test The antidepressant eff ect of JB was further evaluated utilizing the potentiation of yohimbine-induced lethality test in mice, as previously described [ 17 ] . Mice (10/group) received JB, 60 min before i.p. injection of yohimbine (35 mg/kg) and were immediately placed in cages. The numbers of death in each group were recorded 24 h after yohimbine administration. Eff ect of Jobelyn on spontaneous motor activity (SMA) The open fi eld test was employed to screen the eff ect of JB on SMA in mice. Mice (6 per group) were given JB (10–100 mg/kg, p.o.), IM (25 mg/kg, p.o.), or vehicle (10 ml/kg, p.o.) 60 min before each animal was placed in the center of an open fi eld chamber (72 cm × 72 cm × 36 cm). The number of line crosses and total distance travelled (m) for 10 min were recorded [ 18 ] . Statistical analysis The data were expressed as mean ± S.E.M. The data were analyzed with Graph Pad Prism software version 4.03. Statistical analysis of data was done by One-way ANOVA, followed by Tukey post-hoc test. A level of p < 0.05 was considered as statistically signifi cant. Results ▼ Eff ects of Jobelyn ® on the performance of mice in the forced swim test The eff ect of JB on performance of mice in the forced swim test, as measured by the fi rst occurrence of immobility, duration of immobility and struggling time are presented in ● ▶ Table 1 . Oneway ANOVA showed that there were signifi cant diff erences between treatment groups: fi rst occurrence of immobility [F (10, 55) = 77.14, p ≤ 0.05], duration of immobility [F (10, 55) = 142.9, p < 0.05] and struggling time [F (10, 55) = 112.5, p < 0.05]. Post-hoc analysis showed that JB (10, 50 and 100 mg/kg, p.o.) produced a signifi cant decrease in the period of immobility when compared with control. Furthermore, JB signifi cantly prolonged the struggling time and also delayed the fi rst occurrence of immobility in comparison with control ( ● ▶ Table 1 ). 3 DrugRes/2013-06-0332/22.8.2013/MPS Original Article Res/2013-06-0332/22.8.2013/MPS Umukoro S et al. Antidepressant Property of Jobelyn ® ... Drug Res 2013; 63: 1–5 ■ Proof copy for correction only. All forms of publication, duplication or distribution prohibited under copyright law. ■ Eff ects of Jobelyn ® on the performance of mice in the tail suspension test ● ▶ Table 2 showed the eff ects of JB on tail suspension test, as measured by fi rst occurrence of immobility, duration of immobility and struggling time in mice. One-way ANOVA reveals that there were signifi cant diff erences between treatment groups: fi rst occurrence of immobility [F (10, 55) = 281.3, p < 0.05], duration of immobility [F (10, 55) = 390.8, p < 0.05] and struggling time [F (10, 55) = 196.7, p < 0.05]. Post-hoc analysis showed that the JB (10, 50 and100 mg/kg) and IM treated groups were signifi cantly diff erent (p < 0.05) when compared with control. JB signifi cantly (p < 0.05) shortened the duration of immobility in the tail suspension test, which indicates antidepressant eff ect. Jobelyn ® potentiates lethality induced by yohimbine in aggregated mice The eff ect of JB (10, 50 and 100 mg/kg, p.o.) on yohimbineinduced lethality are depicted in ● ▶ Fig. 1 . Post-hoc analysis showed that JB (10–50 mg/kg, p.o.) signifi cantly (p < 0.05) potentiated the lethal eff ect of yohimbine (35 mg/kg, i.p.), which was comparable to that of IM. However, at a dose of 100 mg/kg, JB did not signifi cantly (p > 0.05) potentiate the toxic eff ect of yohimbine in mice ( ● ▶ Fig. 1 ). Although, JB (10 mg/kg, 50 mg/kg) signifi cantly potentiated the lethal eff ect of yohimbine, it did not produce any toxic symptoms or death in mice when given alone. Eff ect of Jobelyn ® on spontaneous motor activity ● ▶ Table 3 indicates the eff ects of JB on locomotor activity in the open fi eld test, as measured by the number of line crosses and total distance travelled (m). One-way ANOVA indicated that there were no signifi cant diff erences in motor activity of the animals when treated with daily doses of JB (10–100 mg/kg, p.o.) for 7 days as compared with control: number of line crosses [F(10, 55) = 4.11, p > 0.05] and total distance travelled [F(10, 55) = 4.14, p > 0.05]. Discussion ▼ The results of this study revealed that JB reduced the duration of immobility in the forced swim and tail suspension tests in mice, indicating antidepressant-like eff ect. JB also increase the ability of the animals to copy with the aversive situations, as shown by increase in struggling time and delay in the fi rst occurrence of immobility in the FST and TST. The FST and TST are stress models widely used as valid behavioral paradigms for the evaluation of antidepressant drugs in rodents [ 13 , 14 ] . In both tests, rodents are exposed to an aversive situation from which there is no escape, and will, after periods of agitation, cease attempts to escape and become immobile [ 13 , 14 ] . Thus, the appearance of immobility indicates a state of exhaustion, lowered mood (hopelessness) or despairs and antidepressant drugs are known to decrease the period of immobility in rodents [ 12 , 19 ] . However, the anti-immobility eff ect of JB was not associated with central nervous system stimulation, as it did not signifi cantly increase the SMA in the open-fi eld test. This further suggests that the anti-immobility activity exhibited by JB refl ects a true antidepressant-like eff ect. The YLT was further used to validate the antidepressant-like property of JB. The potentiation of yohimbine-induced lethality in aggregated mice has served as an additional paradigm for the routine screening of compounds with antidepressant activity [ 17 ] . Thus, the fi ndings that JB enhanced the lethal eff ect of yohimbine further suggest that it may have antidepressant-like property. Table 1 Eff ect of Jobelyn ® on performance of mice in the forced swimming