INTRODUCTION:

Depression is kind of psychiatrically ill health¹. Depression refers to the experience of worry, restlessness, nervousness, tension, fearfulness, apprehensiveness, panic, and agitation.²American Psychiatric Association (APA) says that Depression is emotional reaction due to expectation of future risk³. Nowadays modern life style responsible for increase in case of Depression and depression⁴. Most common symptoms of Depression are irritability, uneasiness, rapid or irregular heartbeat, jumpiness, feelings of apprehension, nausea, faintness, and abdomen ache and respiration problems⁵.

Glutamatergic hyperactivity in brain injuries, liable for varied events such as mitochondrial pathology, oxidative stress, and cellular communication that responsible for inflammatory response and ultimately cell death.

Since glutamatergic overactive is related with characteristic of Depression, neuroinflammation and oxidative stress. Therefore overactive glutamatergic system deregulationg in balance of inhibitory/excitatory in the brain is liable for Depression disorder. Presynaptically situated, mGlu_2/3 receptors are present in some brain areas where glutamate hyperactivity is associated with Depression, together with the cortex, amygdale, striatum, thalamus, and hippocampus.⁶

Primary depression affects 4.7% of people worldwide. Because of this, one character out of every 20 suffers from depression. Girls and older people have a higher level of superiority in despair than other populations. Males experience depression at a rate of five to twelve percent, whereas women experience it at a rate of ten to twenty-five percent, or roughly twice as often as men. According to the definition of the American Psychiatric Association, depression is a diverse illness that is typically accompanied by physical, behavioural, and mental symptoms.⁷

There are several medicines available for the treatment of depression, however clinical evaluation of these pills has demonstrated recurrence of the condition and certain side effects similar to drug interactions. Tricyclic antidepressants can treat a number of headache symptoms, including dry mouth, discomfort, constipation, thirst, dizziness, impaired vision, high blood pressure, impairing ability to drive, and sexual dysfunction. MAO is (monoamine oxidase inhibitors) can cause treatment or behavioural stimulation and an increase in the risk of developing postural hypotension. Compared to earlier tricyclic inhibitors and MAO inhibitors, newer antidepressants frequently have less or unique feature side effects and a lower risk of toxicity.⁹

Zingiber officinale origin from eastern ghat or central india. It usually grown in Bihar, Uttarpradesh, Uttaranchal, Madhya Pradesh, Chattisgarh, Jharkhand, Deccan highland and east coast Myanmar and srilanka.¹⁰It contain alkaloids, terpenoids, coumerin, phenyl propanoids tannin and flavoinds.¹¹ Previous studies showed that at dose of 150mg/kg methanolic leaf extract of Zingiber officinale shown significant antidepressanr effect, antidiarrhoeal effect, antimicrobial effect, radioprotective activity, anticancer activity, chemopreventive activity, antipyretic, antigenotoxic activity, ulcer healing potential, diuretic activity, antifertility action and anti-inflammatory effects.¹²

Azadirachta indica found in tropical and semitropical regions like India, Nepal and Pakistan.¹³Previous studies showed that at dose of 10mg/kg, 20mg/kg 50mg/kg, 100mg/kg, 200mg/kg freshly prepared leaf extract of azadiracta indica posses significant anti-Depression activity with compare with standard drug diazepam using elevated plus maze test and open field test¹⁴.

Curcuma longafound almost everywhere in India and its is found in Sri Lanka and other south Asian countries.¹⁵ The phytochemical analysis indicates presence of secondary metabolites like alkaloids, triterpenoid, coumarine and different compounds (mahanimbicine, bicyclomahanimbicine, phebalosin).¹⁶ Previous studies shown that 400mg/kg dose of aqueous extract of Curcuma longahas CNS stimulant activity so it is useful in treatment of Depression disorder but it’s not shown effect on elevated plus maze model.¹⁷

Hibiscus rosasinesisis a tropical plant which is cultivated and grows as weeds. It is growing naturally nearly all over the world¹⁸.The main chemical constituents of China rose are tannins, anthraquinones, quinines, phenols, flavanoides, alkaloids, terpenoids, saponins, cardiac glycosides, protein, free amino acids, carbohydrates, reducing sugars, mucilage, essential oils and steroids.¹⁹Previous studies showed that It is used for treatment of cough, anxiety, diarrhea, asthma, fever, arthritis, dysentery, genitourinary, vomiting, gastric disorder, cardiac disorder, insect, ringworm, snake bite, malaria and scorpion bites.²⁰

MATERIALS AND METHODS:

Plant material: Zingiber officinale, Azadirachta indica, Curcuma longa and Hibiscus rosasinesis were collected from local plant.

Standard drug:

Diazepam tablet I.P were used as a standard drug

Preparation of composite extract:

The collected plants leaves were shade dried at room temperature and reduced its size with help of mechanical grinder, and passed through forty meshes sieved. The powdered leaves were extracted with 80% methanol with the Soxhlet at boiling temperature (60⁰C) for 10h separately. The extract was then evaporated using boiling water bath.^21,22 final composite extract was dark green in color with dried weight 8.33%.

Phytochemical studies:

Stock solution: 1g of the methanolic plant extracts of Zingiber officinale, Azadirachta indica, Curcuma longa and Hibiscus rosasinesis leaves were dissolved in 100ml of methanol.

· Test of glycosides:

Liebermann’s Test: To 2ml of stock solution add 2ml of chloroform and then add 2ml of acetic acid violet to blue to green colaration occur^.23

· Test of saponins and tannins:

The stock solution was dilute with 20ml of water and then agitates for 15min. presence of saponins shown by formation of foam layer. Then 3ml of these extract add some drops of 1percent lead acetate. Presence of tannins shown by formation of yellow precipitate.²¹

· Test for alkaloids:

Wager’s test: to stock solution add wager’s reagent formation of reddish brown precipitate indicate presence of alkaloids.²⁴

Preparation of wager reagent:

Take 0.25gm of iodine and 1.25gm of potassium iodide and dilute with 250ml water.

· Test for flavonoids

Alkaline reagent test: To stock solution add some drop of NaOH solution an intense yellow colour produced, which turns to colorless on addition of few drops of dilute acid, shown presence of flavanoids.²⁴

Animals and drug treatment: The study included 20 rats. They were divided into 5groups and each group contains 4 rats. Group-I serve as control and receive only vehicle. Groups II was treated with Diazepam as positive control (1mg/kg, po). Groups III- V were treated dose of (50, 75,150mg/kg, po). The dose of C.E was prepared at same day of experiment.²⁵

Rotarod test:

Rotarod is explained by Dunham and Miya in 1957. It is generally used for estimation of neuromuscular management in mice. Rotarod generally consists of rod that is coated with polypropylene foam which provide friction and also to prevent mice from slip of the rod. The space between rod and floor is about 15cm.The rod is drive by motor and the rpm can be maintained at 20 rpm in over study. Animals were trained on rotarod for 2min duration of per trial, with trials 3 per day for two days. On third day, mice were given trial before and after treatment of extract²⁶

Actophotometer:

Actophotometer instrument is employed to watch locomotor activity of mice. Animals were placed in a actophotometer that has constant beams of lights, criss-crossing the chamber and falling on matching photoelectrical cells. When the mouse crosses the light beams every interrupted interruption was recorded for 10min. Total photo beam interruptions represent locomotor activity of mice.²⁷

RESULT AND DISCUSSION:

SSRIs class of synthetic drugs are majorly used for treatment of Depression disorder but its causes many adverse effects such as sedation, confusion, fatigue, anterograde amnesia, disinhibition, irritability, local injection site reaction, tremoretc,. Some adverse effect is common while some are severe such as respiratory depression, suicidality, seizures, bradycardia, cardiovascular collapse, syncope etc which is effect patient’s health severely.²⁸To overcome from this; natural medicinal plant considered as alternative or complementary medicines for the treatment of Depression with fewer and no side effects.⁹

Previous studies showed that composite extract (Zingiber officinale, Azadirachta indica, Curcuma longa and Hibiscus rosasinesis) have higher antioxidant content instead of individual plants. Many previous studies showed that plants which contain highly antioxidant properties were highly effective in treatment of Depression disorder due to these in present studies we were take composite extract instead of individual medicinal plants^21.

Presence of alkaloids, glycoside saponin, tannins, and flavanoids shown by above qualitative chemical test. Presence of flavanoids indicates that composite extract of leaves of medicinal plants have antioxidant properties which is helpful to reduce the Depression^29.

The aim of present studies to evaluate antidepressant properties of composite extract of leaves of medicinal plants using model rotarod and actophometer.

Rotarod:

In above studies it’s shown that diazepam and composite extract both are responsible for decreased in time ratfalling of the rod when we compare it with control group. When we studied Table 1 we observed that rat falling time from the rod is decreased after administration of composite extract at different doses its showed that all doses (50mg/kg, 75mg/kg and 150mg/kg) possess significant anxiolytic activity. However 150mg/kg doses showed maximum anxiolytic activity.

Actophometer:

In above studies it’s shown that diazepam and composite extract both are responsible for decreased in locometry activity of rat when we compare it with control group. When we studied Table 2 we observed that rat showes decreased in locometry activity after administration of composite extract at different doses it’s indicate that at all doses (50mg/kg, 75mg/kg and 150mg/kg) possess significant anxiolytic activity. However 150mg/kg doses showed maximum anxiolytic activity.

Table 1: Table for rotarod

S. No	Treatment	Dose	Time of animals remained without falling from rod (sec)
S. No	Treatment	Dose	30 min	60min	90min
1.	Vehicle	Water	171.66 ±3.44	162.08±2.23	157.57±2.65
2.	Diazepam	1mg/kg	163.57±2.33	130.11±3.48**	105.68±2.15***
3.	C.E(50mg/kg)	(50mg/kg)	168.18±1.34	152.79±2.65	145.17±2.29*
4.	C.E(75mg/kg)	(75mg/kg)	175.46±2.68	157.98±1.19*	135.45±2.54**
5.	C.E(150mg/kg)	(150mg/kg)	166.33±2.92	148.48±2.51**	112.08±3.80***

All values are mean ±SEM (n=4); *p< 0.05 when compared to control

Table 2: Table for actophometer

S. No	Treatment	Dose	Locometry activity (number of count)
S. No	Treatment	Dose	Before dose Administration	After 30(min)	After 60(min)
1.	Vehicle	Water	251.55±2.30	250.33±2.18	248.52±2.50
2.	Diazepam	1mg/kg	246.03±3.18	224.02±3.26***	187.02±2.17***
3.	C.E(50mg/kg)	(50mg/kg)	251.82±2.49	247.51±2.40	228.74±1.65***
4.	C.E(75mg/kg)	(75mg/kg)	247.76±2.79	220.40±1.30***	217.60±2.84***
5.	C.E(150mg/kg)	(150mg/kg)	252.65±2.04	229.10±3.58***	186.65±3.22***

All values are mean ±SEM (n=4); *p< 0.05 when compared to control

CONCLUSION:

Our studied shown that composite methanolic extract of medicinal plant have significant anxiolytic effect on exposure to the rotarod and actophotometer test. C.E at doses (50mg/kg, 75mg/kg and 150mg/kg) posse’s an “anxiolytic” activity comparable with the effects of standard drugs diazepam (1mg/kg) while 150mg/kg composite extract showed maximum anxiolytic activity. Methanolic C.E showed significant anxiolytic activity probably due to its antioxidant properties. However further studies are required for better explanations of mechanism of action responsible for anti-Depression activity of composite extract

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Received on 14.08.2023 Modified on 20.09.2023

Asian J. Pharm. Res. 2023; 13(4):233-236.

DOI: 10.52711/2231-5691.2023.00043