Albizia zygia is used in Ghanaian traditional medicine for the management of mental disorders. The present study tested the hypothesis that an extract of the leaves of Albizia zygia AZE may possess antipsychotic and antidepressant properties. The novelty- and apomorphine-induced locomotor and rearing behaviours of AZE in mice were explored in an open-field observational test system. The effects of AZE in apomorphine-induced cage climbing test, extract-induced catalepsy, and haloperidol-induced catalepsy on mice were also investigated. Lastly, the forced swimming and tail suspension tests in mice were employed to screen the possible antidepressant effects of AZE.
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Albizia zygia is used in Ghanaian traditional medicine for the management of mental disorders. The present study tested the hypothesis that an extract of the leaves of Albizia zygia AZE may possess antipsychotic and antidepressant properties. The novelty- and apomorphine-induced locomotor and rearing behaviours of AZE in mice were explored in an open-field observational test system.
The effects of AZE in apomorphine-induced cage climbing test, extract-induced catalepsy, and haloperidol-induced catalepsy on mice were also investigated. Lastly, the forced swimming and tail suspension tests in mice were employed to screen the possible antidepressant effects of AZE. The extract also significantly decreased the frequency and duration of apomorphine-induced climbing activities in mice. However, AZE did not produce any significant antidepressant effects in the test models employed.
The extract of Albizia zygia exhibited an antipsychotic-like activity in mice. The wood obtained from the tree is used for indoor construction, veneer and plywood, boat and ship building, implements e. In the Ghanaian traditional medicine, the leaves of Albizia zygia are used in the management of mental troubles [ 2 ]. In other indigenous African traditional health systems, the bark sap is instilled in the eyes to treat eye infections and the bark decoction is also useful for the treatment of bronchial diseases, malaria, fever, and female sterility [ 3 ].
The pounded bark is applied topically to treat yaws, sores, wounds, and toothache. Leaf decoctions are administered to treat fever and diarrhoea. Ground roots of the plant are added to food to treat cough and as an expectorant. The root bark juice is also used on wounds to promote healing [ 3 ]. In Nigeria, some communities use the plant for the treatment of waist pain [ 4 ] and in Cameroon, decoction of the leaves and stem is used in the treatment of boils, diarrhoea, male sexual impotence, oedema, and fracture [ 5 , 6 ].
Hexane and methanol extract of Albizia zygia has demonstrated in vitro free radical scavenging and antioxidant effects [ 8 ]. The aqueous methanolic stem bark extract of Albizia zygia has been found to possess analgesic activity and low subacute toxicity [ 9 ].
Recently, the antipyretic and analgesic properties of the plant extracts have been demonstrated [ 10 , 11 ]. The drug discovery paradigm involving the investigation of medicinal plants has produced successful results such as the isolation of reserpine from Rauwolfia serpentina which is known to have antipsychotic properties [ 13 — 15 ], in addition to its better known antihypertensive effect.
In our quest to provide pharmacological validation of the traditional use in mental health, the antipsychotic and antidepressant effects of an ethanolic extract of the leaves of Albizia zygia in mice were evaluated. The leaves were air-dried for seven days and powdered. The ethanolic extract was then evaporated to dryness under reduced pressure, labelled as AZE, and stored in a desiccator. AZE was screened for the presence of alkaloids, saponins, tannins, flavonoids, and other phytochemicals using standard qualitative colorimetric methods [ 16 ].
The observation was repeated 24 hours later. The base of the maze has 16 squares 6. The arena of the open field was also designated as i corner one of the four corner squares ; ii periphery the squares along the walls ; or iii centre the 4 inner squares. Rearing behaviour was recorded when a mouse stood on its hind limbs and placed the forelimbs against the wall of the observation cage supported rearing or in free air unsupported rearing.
In addition, the number of times a mouse crosses any of the lines demarcating the base of the maze i. The total frequency and duration spent in the corner and periphery or central portions of the observation set-up by the mice were also recorded. The mice were then placed in the open-field test chamber. A no-apomorphine vehicle group was also included. Also the total frequency and duration the mice spent in the corner, periphery, or central portions of the observation set-up were recorded.
The method as described previously was adopted [ 18 ]. The frequency and duration of climbing were tracked from the recorded video. The set-up used in this test consists of a Perspex rod elevated with support to a height of 3. The time a mouse spent when placed on the rod with its forepaws was recorded. The test ended when the animal removed its forepaws from the rod unto the floor or climbed the rod.
The effect of AZE on haloperidol-induced catalepsy was performed as previously described [ 20 , 21 ]. This procedure was carried out using published methods with modifications [ 22 — 24 ]. With a public domain software JWatcher, version 1. Immobility behaviours floating passively in the water without active movement except for twitches, shivers, or corrective wall-bouncing , swimming behaviours movement of the hind limbs or tail resulting in a propulsive force or swimming motions, more than necessary, to solely maintain their head above water , and climbing behaviours active movements in and out of the water with forepaws, usually directed against the walls of the mice were scored.
The tail suspension test TST was carried out according to previous descriptions with modifications [ 24 , 25 ]. Alkaloids, flavonoids, tannins, saponins, and anthraquinone glycosides were found to be present in AZE. Extract-treated mice at all dose levels showed dose and time dependent sedation which lasted 60 minutes.
The decrease in the frequency of the rearing behaviour was dose-dependent. The decrease in rearing activity by CPZ was dose-dependent, whereas that of the line-crossing was not.
Apomorphine induced a characteristic increase in the total frequency Figure 5 a and duration Figure 5 b of climbing of the wire-meshed cage by the animals. Haloperidol HAL 0. Haloperidol 0. The present study describes an antipsychotic and antidepressant potential of a hydroethanolic extract of the leaves of Albizia zygia AZE in murine models of psychosis and depression.
The experimental procedures were done to rationalise the traditional uses of the plant in mental health. The behavioural effects of Albizia zygia in mice were examined. Mice were used as the experimental subject because they are similar to humans at the anatomical, cellular, biochemical, and molecular level and also share with humans similar brain functions such as anxiety, hunger, circadian rhythm, aggression, memory, sexual behaviour, and other emotional responses [ 26 ].
The findings of this study provide initial evidence that AZE possesses antipsychotic-like effects. However, AZE seem to be devoid of antidepressant-like activity, as seen from the findings of the effects of AZE on the murine models of depression employed. These effects exhibited by AZE do not necessarily suggest an antipsychotic activity, though most antipsychotic agents produce similar effects in animals [ 27 ]. Stimulation of cerebral dopaminergic activity can produce psychosis de novo in some patients and psychosis has long been associated with increased cerebral dopaminergic activity.
This role of dopamine in psychosis is supported by biochemical findings, clinical and imaging studies [ 28 — 31 ]. The clinical efficacy of most antipsychotic drugs, especially those effective against the positive psychotic symptoms such as hallucinations and delusions, may be linked to dopamine D 2 receptor antagonism [ 32 ]. Murine models of psychosis used for screening antipsychotic drugs are based on the neurochemical hypothesis of schizophrenia, involving mainly the neurotransmitters, dopamine and glutamate [ 33 ].
The dopamine-based models usually use apomorphine, a direct dopamine agonist, or amphetamine, a drug that increases the release of dopamine and blocks its reuptake [ 34 ]. In this study, psychosis in the murine models was induced by administration of apomorphine which, being a nonselective dopamine agonist, elicits behavioural responses in animals by activating dopamine D 1 and D 2 receptors in the brain [ 35 , 36 ].
The apomorphine-induced cage climbing test is a widely used test for screening antipsychotic drugs [ 18 , 40 , 42 ]. It has predictive validity for antipsychotic drugs that normalize the hyperactivity and stereotypic behaviour in that almost all antipsychotics dose-dependently antagonize apomorphine-induced cage climbing behaviour of mice [ 42 ].
Mice treated with low doses of apomorphine tend to adopt a vertical position and try to climb walls. Apomorphine induces climbing behaviour in mice by activating both dopamine D 1 and D 2 receptors in the striatum [ 42 ]. Activation of either dopamine D 1 or D 2 receptors does not induce climbing behaviour; instead, activation of both receptors is required to produce climbing behaviour [ 43 ].
Therefore, it follows that antagonism of apomorphine-induced climbing behaviour is achieved by blocking either or both dopamine D 1 and D 2 receptors. Apomorphine induces a peculiar climbing behaviour in mice characterized initially by rearing and then spontaneous climbing activity.
Haloperidol, the reference drug, significantly and dose-dependently reduced the climbing behaviour of mice as expected. Based on these findings, it may be concluded that AZE produces antipsychotic activity which may be mediated through the antagonism of either or both of dopamine D 1 and D 2 receptors in the striatum of the brain.
Catalepsy test in rodents is a predictive tool for detecting the extrapyramidal side effects EPS of antipsychotic drugs [ 44 ]. EPS is a key side effect that is known to account for the discontinuation of antipsychotic drug use in patients [ 45 ]. Consequently, current research for new antipsychotic drug discovery is focused on agents with minimal or no EPS in addition to clinical efficacy [ 45 , 46 ].
Catalepsy in laboratory animals is defined as a failure to correct an externally imposed posture and the test entails measuring the latency for the animal to remove itself from the unfamiliar and uncomfortable position [ 19 , 47 ]. However, this claim can be substantiated following the determination of the incidence of catalepsy after a chronic administration of the AZE. The extract, at the highest dose used in the study, produced a significant increase in haloperidol-induced catalepsy, suggesting it may have the ability to cause this side effect at higher doses.
The forced swimming and tail suspension tests are the two widely used animal models for antidepressant screening. They are quite sensitive and specific to all the major classes of antidepressant drugs [ 22 ]. They are sensitive to both acute and chronic treatments of antidepressants [ 48 ]. In both tests, mice are placed in an inescapable but moderately stressful situation.
Lack of escape related behaviour is considered immobility and it reflects a state of despair which is claimed to produce in the animals a condition similar to depression in humans. This state of despair can be reduced by several agents which are therapeutically effective in human depression [ 48 , 50 ]. Similarly, alkaloids, tannins, saponins, flavonoids, and cardiac glycosides in the stem bark of Albizia zygia have been reported [ 9 ].
The observed neuropharmacological effects of the plant extract could be attributed to the presence of these phytochemical constituents. However, activity-guided characterization of these groups would be needed to comprehend their role in the observed antipsychotic effects.
The extract of Albizia zygia produced antipsychotic-like effects in mice. It, however, did not have any antidepressant effect. These findings support the use of the plant extract in the traditional medicinal management of psychosis in Ghana. The authors declare that there are no conflicts of interest regarding the publication of this paper. Patrick Amoateng Reference no. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Journal overview. Special Issues. Received 30 Jun Accepted 13 Aug
MEPEPE (Albizia zygia)
Albizia zygia DC. Fabaceae Albizia zygia is closely related to Albizia gummifera and Albizia glaberrima, and is often confused with them. Hybrids between this species and A. If you have any useful information about this plant, please leave a comment. Comments have to be approved before they are shown here. If you would like to support this site, please consider Donating. Home Search Contact.
Albizia zygia J.F.Macbr.