Discussion
The findings from this investigation suggest that the roots extract of Z. nummularia displays significant in vivo sedative-hypnotic, antipyretic, and analgesic effects. The open field test is one of the commonly used behavioral test protocol for screening of sedative and anxiolytic activity of substances in laboratory animals (de la Peña et al. 2013), whereas the phenobarbitone-induced sleeping time test (Inganakal et al. 2012) is employed for the assessment of hypnotic properties. The roots extract significantly reduced the movement of mice in the open field test apparatus implying the tranquilizing nature of its components. While the precise mechanistic of therapeutic role is not known, several probable causes were formulated. The allosteric modulation of γ-aminobutyric acid (GABA) receptors in mice brain might be the underlying mechanism (Shrestha et al. 2012). The prolongation of the sleeping duration suggested the hypnotic properties of the extract. The effect could have been mediated by the induction of central nervous system (CNS) depressant activity by the bioactive components of the extract (Ya’u et al. 2011). In this investigation, the crude extracts showed remarkable sedative-hypnotic effect which varied upon fractionation. The chloroform fraction was most potent followed by ethyl acetate whereas the hexane fraction did not produce significant results. From the results, it could be assumed that the sedative-hypnotic constituents of Z. nummularia roots are mostly concentrated in chloroform and ethyl acetate fractions. Results revealed that Z. nummularia root extract elicits antipyretic effects in yeast-induced hyperthermia in the murine models. Chloroform fractions proved to be the most active fraction followed by ethyl acetate, suggesting the presence of pharmacologically important components in them.
The acetic acid-induced writhing test is considered very effective in detecting antinociceptive effects of various extracts. Its sensitivity is much higher than other methods (hot plate, tail flick, carrageenan-induced paw edema, formalin-induced paw licking, etc.) used for this purpose (Ramirez et al. 2010). The abdominal constrictions and the resultant painful sensations provoked by the acid has been attributed to the perturbation and interplay of bradykinin, prostaglandins, interleukin-1β (IL-1β), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) (Ribeiro et al. 2000). The Z. nummularia root extract at the doses of 50–100 mg/kg, moderated the abdominal constrictions in a dose-dependent manner. One possible mechanism of this action could be the diminished production of prostaglandin E2 (PGE2) (Ying et al. 2014). The extract could be interfering with both central (opioid and cholinergic pathways) and peripheral (COX-2) pathways in eliciting the anti-inflammatory effects (Sawada et al. 2014). The chloroform fraction was the most effective followed by the ethyl acetate fraction in reducing pain and sensitivity. It indicates the accumulation of the antinociceptive constituents in these fractions.
Anxiety and sleep interruptions have become the norm of current stressful living (Han et al. 2012). Also, the instances of depression, suicidal attempts are soaring (Cash and Bridge 2009). Reliance on the prescription drugs is not free of side effects. The frequent intake aggregates the metabolic system in long term, becomes ineffective and overdose proves fatal. Opioid analgesics (buprenorphine, fentanyl, codeine, ativan, dextropropoxyphene, methadone, oxycodone, carisoprodol, etc.) overdose-caused death cases are rising dramatically (Paulozzi et al. 2012). The deadly combination opioid, benzodiazepines, and/or alcohol use poses huge risk of morbidity (Gudin et al. 2013). On the other hand, CAM are naturally sourced, thus pose lower genotoxicity compared to chemicals. In this regard, Z. nummularia root extract merits further investigation. Isolation of the functional constituents and their structural elucidation warrants impetus. In a preliminary screening study, the phytochemicals alkaloids (ziziphines), carbohydrates, saponins, flavonoids, anthocyanins, and tannins were found in the ethanolic extract of Z. oenoplia (Suksamrarn et al. 2005; Rao et al. 2012). These components might be instrumental in inducing the tested biological responses. The hypnotic efficacy of Z. jujuba Mill. jujubosides has been correlated to the impact on circadian rhythm and the serotonergic system (Cao et al. 2010). Further studies on the therapeutic importance of this plant might provide affordable medication to large section population in the developing countries. However, possible health risks must be verified for broader remedial applications.