Chronic oral administration of Passiflora incarnata extract has no abnormal effects on metabolic and behavioral parameters in mice, except to induce sleep

Abstract

Although the number of prescriptions and dependence on sleeping pills are increasing, the associations with unexpected abnormal behaviors and metabolic diseases caused by the overuse of sleeping pills are not well understood. In particular, such as abnormal eating-behavior and the occurrence of metabolic disorders caused by psychological unstable states are reported. For this reason, herbal medicine, which has not had such side effects in recent years, is attracting attention as an alternative medicine/food for sleeping inducer. We have used ethanol extracts from Passiflora incarnata (PI) to steadily obtain positive effects on sleep and brain microenvironment. However, as mentioned earlier, sleep-inducing efficacy can only be used safely if the behavioral and metabolic abnormalities do not appear. Thus, in this study, we used Phenomaster equipment to continuously monitor the movement, feeding, water consumption, gas changes, etc. in C57BL/6 mice at a dose of 500 mg/kg/day for 5 consecutive days with PI extract group compared with the control group. Before sacrifice, differences in body composition of mice were also compared. Monitoring of 24 h/5 days through the equipment showed no change in PI-treated group in anything except for significant decrease in blood melatonin levels and activity after PI administration. Taken together, the statistically insignificance of any behavioral and metabolic phenomenon produced by repeated treatment of PI are not only expected to have an accurate sleep effect, but are also free of side effects of the prescribed sleeping pills. This study has given us greater confidence in the safety of the PI extracts we use for sleep-inducer.

Keywords: Behavioral abnormality; Insomnia; Metabolic abnormality; Passiflora incarnata; Sleep-inducer.

Fig. 1

GABA activation and sleep-related hormone levels by repeated oral PI extract administration. a Hippocampal and hypothalamic calretinin expressions were analyzed by Western blotting. Significant increases in expression were observed in the PI-treated group, shown by the relative expression of the proteins at the hippocampus and hypothalamus in the control (Veh) and experimental groups (PI 500). b Changes in body weight, and changes in sleeping-related hormones in animals after repeated PI extract administration. There was no change in body weight between the two groups. Serum levels of melatonin and serotonin were increased in the PI group. Serum serotonin tended to increase in the PI-treated group, but was not statistically significant, and melatonin showed a significant increase. The error bar represent mean ± standard error (SE). (^***, P < 0.0005; ns, non-significant)

Fig. 2

Real-time changes in feed and water intake over 24 h by light cycles between Veh- and PI 500-treated animals. a Veh and PI extract (500 mg/kg) were administered 2 h before the lights were turned off. However, there was a significant decrease or declining trend in both feed and water intake in the PI 500 group 2–4 h before the lights were turned on. b After the lights were turned off, both the food intake and water consumption were increased in both groups, but no difference in volume between the two was found. (AUC; area under curve). The error bar represents mean ± standard error (SE). ZT stands for zeitgeber time. (^*, P < 0.05; ns, non-significant)

Fig. 3

Real-time changes in RER, EE and activity over 24 h by light cycles between Veh- and PI 500-treated animals. a Real-time change tracking of RER, EE and activity over 24 h in mice treated with vehicle and PI extract. b The area under curve (AUC) demonstrated by bar graphs during dark cycle and 24 h in RER, EE and activity in Veh and PI 500 mice. The vehicle and PI extract were administered orally 2 h before lights- off. EE and activity showed statistical significance between the groups. The error bar represents mean ± standard error (SE). ZT stands for zeitgeber time. (^***, P < 0.0005; ^**, P < 0.005; ^*, P < 0.05; ns, non-significant)

Fig. 4

Body composition after repeated oral administration of Veh and PI extract. a Body compositions of fat, free body fluid and lean mass (gram). b Body composition ratio (%) by fat, free body fluid and lean. There was no significant index change caused by chronic PI administration for 5 days. The error bar represents mean ± standard error (SE) (ns, non-significant)