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. 2018 Jul 31;54(4):55.
doi: 10.3390/medicina54040055.

Evaluation of the Sleep-Prolonging Effect of Lagenaria vulgaris and Cucurbita pepo Extracts on Pentobarbital-Induced Sleep and Possible Mechanisms of Action

Vafa Baradaran Rahimi  1   2 , Vahid Reza Askari  3   4 , Amineh Sadat Tajani  5 , Azar Hosseini  6 , Hassan Rakhshandeh  7   8
Affiliations

Evaluation of the Sleep-Prolonging Effect of Lagenaria vulgaris and Cucurbita pepo Extracts on Pentobarbital-Induced Sleep and Possible Mechanisms of Action

Vafa Baradaran Rahimi et al. Medicina (Kaunas). .

Abstract

Introduction: Sleeplessness is the most common sleep disorder. In this study, the hypnotic effect of macerated (HAME) and soxhlet (HASE) extract of Lagenaria vulgaris (fruit and seed) and Cucurbita pepo (fruit) were studied in mice. Methods: Extracts and fractions were administered intra-peritoneally (i.p.) in mice 30 min before the sodium pentobarbital (30 mg/kg, i.p.). Moreover, the influence of flumazenil or naloxone on the hypnotic effects of the extract and its toxic effects were evaluated. Results: The HAME and HASE of C. pepo prolonged the pentobarbital-induced sleep duration at dose of 200 mg/kg. The HAME of L. vulgaris (fruit) at dose of 200 mg/kg increased the sleeping time. The HAME and HASE of L. vulgaris (seed) increased sleep duration at doses of 50 and 100 mg/kg. Besides, flumazenil (2 mg/kg) reversed the effects of both diazepam (P < 0.001 vs. diazepam group), 200 mg/kg of HAME of C. pepo and 50 mg/kg of HAME and HASE of L. vulgaris (seed). All fractions especially ethyl-acetate fraction (EAF) of L. vulgaris (seed) increased the sleep duration. Naloxone reversed the hypnotic effect of HAME and HASE of L. vulgaris (seed). The extracts showed no neurotoxic effects on PC12 and L929 cell lines. Conclusion: The results showed that L. vulgaris (seed and fruit) and C. pepo potentiated pentobarbital hypnosis without toxic influence. The hypnotic effects of L. vulgaris seed was greater than its fruit and C. pepo. The GABA and opioid receptors may play role in the sleep-induction of L. vulgaris seed.

Keywords: Cucurbita pepo; Lagenaria vulgaris; flumazenil; insomnia; naloxone.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Effect of C. pepo extracts on sleep duration in mice. The animals were treated with saline, diazepam (DZP, 3 mg/kg), Hydro-alcoholic maceration extract (HAME) or hydro-alcoholic soxhlet extract (HASE), 30 min before administration of pentobarbital (30 mg/kg, i.p.). Data are expressed as mean ± SD (n = 8). * P < 0.05, ** P < 0.01 and *** P < 0.001 vs. saline. HAME, HASE, ethyl acetate fraction (EAF), N-butanol fraction (NBF), and the water fraction (WF).
Figure 2
Figure 2
Effect of L. vulgaris fruit extracts on sleep duration in mice. The animals were treated with saline, diazepam (DZP, 3 mg/kg), HAME or HASE 30 min before administration of pentobarbital (30 mg/kg, i.p.). Data are expressed as mean ± SD (n = 8). ** P < 0.01 and *** P < 0.001 vs. saline. Hydro-alcoholic maceration extract (HAME), hydro-alcoholic soxhlet extract (HASE), ethyl acetate fraction (EAF), N-butanol fraction (NBF), and the water fraction (WF).
Figure 3
Figure 3
Effect of L. vulgaris seed extracts on sleep duration in mice. The animals were treated with saline, diazepam (DZP, 3 mg/kg), HAME or HASE 30 min before administration of pentobarbital (30 mg/kg, i.p.). Data are expressed as mean ± SD (n = 8). *** P < 0.001 vs. saline. Hydro-alcoholic maceration extract (HAME), hydro-alcoholic soxhlet extract (HASE), ethyl acetate fraction (EAF), N-butanol fraction (NBF), and the water fraction (WF).
Figure 4
Figure 4
Effects of seed fractions of L. vulgaris on sleep duration in mice. The animals were treated with 10% DMSO, saline, diazepam (DZP, 3 mg/kg) or seeds fractions of HASE including: water fraction (WF), ethyl acetate fraction (EAF) or n-butanol fraction (NBF), 30 min before administration of pentobarbital (30 mg/kg, i.p.). Data are expressed as mean ± SD (n = 8). *** P < 0.001 vs. Saline and DMSO (for NBF and EAF). Hydro-alcoholic maceration extract (HAME), hydro-alcoholic soxhlet extract (HASE), ethyl acetate fraction (EAF), N-butanol fraction (NBF), and the water fraction (WF).
Figure 5
Figure 5
Effects of extracts on sleep latency in mice. The animals were treated with saline, diazepam (3 mg/kg), HASE of C. pepo (200 mg/kg) and HASE, water fraction (WF), ethyl acetate fraction (EAF) or N-butanol fraction (NBF) of seeds (50 mg/kg) and HAME of fruit (200 mg/kg) of L. vulgaris. Data are expressed as mean ± SD (n = 8). * P < 0.05 and *** P < 0.001 vs. saline. Hydro-alcoholic maceration extract (HAME), hydro-alcoholic soxhlet extract (HASE).
Figure 6
Figure 6
Effect of flumazenil (FLZ) and naloxone (NLX) on the sleep-prolonging effect of C. pepo. The animals were treated with saline, 3 mg/kg of diazepam (DZP) or 200 mg/kg of HASE before injection of pentobarbital (30 mg/kg, i.p.). Flumazenil (1 mg/kg i.p.) or/and naloxone (5 mg/kg i.p.) were administrated 30 min before diazepam or HASE. Data are expressed as mean ± SD (n = 8). ** P < 0.01 and *** P < 0.001 vs. saline; XX P < 0.01 vs. HASE; oo P < 0.01 vs. diazepam. Hydro-alcoholic maceration extract (HAME), hydro-alcoholic soxhlet extract (HASE), ethyl acetate fraction (EAF), N-butanol fraction (NBF), and the water fraction (WF).
Figure 7
Figure 7
Effect of flumazenil (FLZ) and naloxone (NLX) on the sleep-prolonging effect of L. vulgaris fruit. The animals were treated with saline, 3 mg/kg of diazepam (DZP) or 200 mg/kg of HAME before injection of pentobarbital (30 mg/kg, i.p.). Flumazenil (1 mg/kg i.p.) or/and naloxone (5 mg/kg i.p.) were administrated 30 min before diazepam or HAME. Data are expressed as mean ± SD (n = 8). ** P < 0.01 and *** P < 0.001 vs. saline; oo P < 0.01 vs. diazepam. Hydro-alcoholic maceration extract (HAME), hydro-alcoholic soxhlet extract (HASE), ethyl acetate fraction (EAF), N-butanol fraction (NBF), and the water fraction (WF).
Figure 8
Figure 8
Effect of flumazenil (FLZ) and naloxone (NLX) on the sleep-prolonging effect of L. vulgaris seeds. The animals were treated with saline, 3 mg/kg of diazepam (DZP) or 50 mg/kg of HASE before injection of pentobarbital (30 mg/kg, i.p.). Flumazenil (1 mg/kg i.p.) or/and naloxone (5 mg/kg i.p.) were administrated 30 min before diazepam or HASE. Data are expressed as mean ± SD (n = 8). ** P < 0.01 and *** P < 0.001 vs. saline; XX P < 0.01 and XXX P < 0.001 vs. HASE; oo P < 0.01 vs. diazepam. Values are presented as Mean ± SEM (n = 8). Hydro-alcoholic maceration extract (HAME), hydro-alcoholic soxhlet extract (HASE), ethyl acetate fraction (EAF), N-butanol fraction (NBF), and the water fraction (WF).
Figure 9
Figure 9
The effect of L. vulgaris and C. pepo extracts on the viability of PC12 and L929 cells. Data are mean ± SD (n = 5). (A) hydro-ethanolic macerated extract of L. vulgaris fruit; (B) hydro-ethanolic soxhlet extract of seeds of L. vulgaris; (C) hydro-ethanolic soxhlet extract of C. pepo and (D) 800 µg/mL of water fraction (WF), ethyl acetate fraction (EAF) and n-butanol fraction (NBF) of HASE of L. vulgaris seeds were examined and compared to saline. Hydro-alcoholic maceration extract (HAME), hydro-alcoholic soxhlet extract (HASE).
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