Passiflora cincinnata Extract Delays the Development of Motor Signs and Prevents Dopaminergic Loss in a Mice Model of Parkinson's Disease

Abstract

Passiflora cincinnata Masters is a Brazilian native species of passionflower. This genus is known in the American continent folk medicine for its diuretic and analgesic properties. Nevertheless, few studies investigated possible biological effects of P. cincinnata extracts. Further, evidence of antioxidant actions encourages the investigation of possible neuroprotective effects in animal models of neurodegenerative diseases. This study investigates the effect of the P. cincinnata ethanolic extract (PAS) on mice submitted to a progressive model of Parkinson's disease (PD) induced by reserpine. Male (6-month-old) mice received reserpine (0.1 mg/kg, s.c.), every other day, for 40 days, with or without a concomitant treatment with daily injections of PAS (25 mg/kg, i.p.). Catalepsy, open field, oral movements, and plus-maze discriminative avoidance evaluations were performed across treatment, and immunohistochemistry for tyrosine hydroxylase was conducted at the end. The results showed that PAS treatment delayed the onset of motor impairments and prevented the occurrence of increased catalepsy behavior in the premotor phase. However, PAS administration did not modify reserpine-induced cognitive impairments. Moreover, PAS prevented the decrease in tyrosine hydroxylase immunostaining in the substantia nigra pars compacta (SNpc) induced by reserpine. Taken together, our results suggested that PAS exerted a neuroprotective effect in a progressive model of PD.

Figure 1

Schematic representation of the neuroprotective evaluation of PAS administration in mice.

Figure 2

Effects of repeated administration of Passiflora cincinnata extract (25 mg/kg) and reserpine (0.1 mg/kg) on catalepsy behavior of mice. (a) Entire treatment analysis, (b) basal phase, (c) premotor phase, and (d) motor phases. Data are expressed as mean ± SEM. ^∗p < 0.05 RES/CTR compared to CTR/CTR; ^#p < 0.05 RES/PAS compared to CTR/CTR; and ⁺p < 0.05 RES/CTR compared to RES/PAS (repeated measures ANOVA followed by Tukey's post hoc test).

Figure 3

Effects of repeated administration of Passiflora cincinnata extract (25 mg/kg) and reserpine (0.1 mg/kg) on oral movements of mice. (a) Twitching and (b) vacuous chewing. Data are expressed as mean ± SEM. ^∗p < 0.05 RES/CTR compared to CTR/CTR; ^#p < 0.05 RES/PAS compared to CTR/CTR (repeated measures ANOVA followed by Tukey's post hoc test).

Figure 4

Effects of repeated administration of Passiflora cincinnata extract (25 mg/kg) and reserpine (0.1 mg/kg) on mice exploration of the aversive and nonaversive arms in plus-maze discriminative avoidance task. (a) Training session and (b) test session. Data are expressed as mean ± SEM. ^∗p < 0.05 and ^#p = 0.07 compared to aversive arm (paired-samples t-test).

Figure 5

Effects of repeated administration of Passiflora cincinnata extract (25 mg/kg) and reserpine (0.1 mg/kg) on (a) total distance travelled, (b) time spent in central zone, and (c) average speed of mice in open field. Data are expressed as mean ± SEM. ^∗∗p < 0.01 and ^∗∗∗p < 0.005 compared to control (one-way ANOVA followed by Tukey's post hoc test).

Figure 6

Effects of repeated administration of Passiflora cincinnata extract (25 mg/kg) and reserpine (0.1 mg/kg) on (a) TH+ cells of SNpc and (b) relative optical density (ROD) of dorsal striatum, both normalized by CTR values. Data are expressed as mean ± SEM. ^∗p < 0.05 compared to CTR/CTR. ^#p < 0.05 compared to RES/CTR. (one-way ANOVA followed Tukey's post hoc test). Magnification 100x (a) and 40x (b), black bold lines are scale bars, corresponding to 200 μm.