INTRODUCTION:

Depression is a complex, diverse illness that presents with behavioural, physiological, and psychological symptoms. It is believed that depression results from an imbalance in "neurotransmitters," which are substances in the brain that send messages to the body that regulate mood.¹ Animal models of depression are employed to identify new antidepressant medication treatments, to study aspects of the neurobiology of depression, and to study the neuropharmacological mechanisms underlying antidepressant treatments.² Even while many synthetic medications are utilised as standard treatments for patients with clinical depression, their side effects can jeopardise the effectiveness of the therapeutic approach.³

Ayurveda is one of the world’s oldest medical systems. It originated in India and has evolved here over thousands of years.⁴ Ayurveda was the first holistic system of diagnosis and treatment integrating nutrition, hygiene, rejuvenation and herbal medicine. Many Ayurveda formulations with different composition are available in the market as antidepressant formulations. But for many formulations there is no scientific evidence of their effectiveness and their comparable antidepressant activity with clinically proven allopathic medicine. So the present study aims to compare two selected antidepressant Ayurvedic formulations and Fluoxetine in animal models of depression.

MATERIALS AND METHODS:

Animals:

Male Swiss albino mice (20-25g) of two months old were selected for the study. They were housed in groups of six under standard laboratory conditions (temperature-25±1ºC, relative humidity-55±5% and 12.00:12.00h dark:light cycle) with standard pellet diet and water ad libitum. Animals were fasted overnight before the experiment. The experiments were performed during day (9:00-12:00h) and as per the guidelines of the Committee for the Control and Supervision of Experiments on Animals (CCSEA), Government of India. The Institutional Animal Ethics Committee approved the study protocol.

Experimental Design:

Animals are divided into Six groups having 6 animals each. Standard drug is dissolved in vehicle (Simple Syrup) and selected ayurvedic formulations administered orally once daily for seven consecutive days as per the following protocol. The tests were performed on 0^th day and on 8^thday tests were repeated. Selection of doses was done on the basis of body surface area ratio by referring to the standard table of Paget and Barnes.⁵

Group I: Control (Vehicle treated)

Group II: Standard (Fluoxetine 10mg/kg)

Group III: Treated with Low Dose Shankhpuspi syrup 1.8ml/kg (LDSP)

Group IV: Treated with High Dose Shankhpuspi syrup 3.6ml/kg (HDSP)

Group V: Treated with Low Dose Aswagandharista 2.6 ml/kg (LDAG)

Group VI: Treated with High Dose Aswagandharista 5.2ml/kg (HDAG)

Forced Swim Test:⁶

Mice were placed individually in a rectangular glass jar measuring 25×12×25cm, filled with 15cm of water maintained at a temperature between 23-25°C. After 2-3 minutes of intense activity, the mice exhibited periods of immobility, floating passively in the water with minimal movement. During these periods, the animals remained in a slightly hunched, upright position with their noses above the water's surface. The total duration of immobility was recorded using a stopwatch over a 6-minute period.

Tail suspension test⁷:

The tail suspension test (TST) is based on the principle that suspending mice upside down triggers a specific immobility behaviour, which is similar to the symptoms of human depression. Mice were suspended by adhesive tape placed about 1cm from the tip of their tail, with the setup positioned 50cm above the floor. The duration of immobility was recorded during the last 4minutes of a 6 minute observation period. When mice hung passively and remained completely still, considered as immobile and the time of immobility was recorded.

RESULTS:

Effect of Ayurvedic formulations on Tail suspension test:

Vehicle treated group has shown no significant reduction in duration of immobility in TST. There is a significant reduction in duration of immobility in Fluoxetine and other treatment groups. There is a 55.5% reduction in duration of immobility in Fluxetine treated group. 23.1% and 38% reduction in duration of immobility is observed in LDSP and HDSP treated groups respectively. 31.5% and 39.5% reduction in duration of immobility was observed in LDAG and HDAG treated groups.

Figure 1. Effect of drugs on TST

Values given are Mean=SEM. (n=6). *is significantly different from base line values (on 0^th day) * = p<0.01** is p<0.001 ***is p<0.0001.

Effect of Ayurvedic formulations on Forced swim test:

Vehicle treated group has not shown any reduction in duration of immobility in Forced Swim Test. There is a significant reduction in duration of immobility in FST in Fluoxetine and Ayurvedic formulations treated groups. There is a 49.13% reduction in duration of immobility in Fluxetine treated group, 26.7%,36.05% reduction in duration of immobility in LDSP, HDSP treated groups and 21.9%, 33.7 % reduction in immobility of LDAG, HDAG treated groups respectively in FST.

Figure 2. Effect of drugs on FST

Values given are Mean=SEM.(n=6). * is significantly different from base line values (on 0^th day)

* = p<0.01 ** is p<0.001 *** is p<0.0001.

A Dose dependent anti-depressant action is observed for both Ayurvedic formulations and there was no significant difference in their antidepressant action.

DISCUSSION:

Depression is a prevalent, crippling, and even fatal disorder that is becoming more and more widespread. According to the World Health Organisation (WHO), depression ranks as the fourth most common cause of disability globally.⁸Traditional uses of herbal treatments for a variety of illnesses have been extensively documented, both for their safety profile and as a treatment for certain pathological conditions. ⁹

Ayurveda, unani, homeopathy and other alternative, traditional medicinal systems have been used to treat depression in a number of nations. Several of these restorative drugs were tested using scientific models and proved to be successful. ^10-11

The learnt helplessness, chronic mild stress, and social defeat stress models show great specificity, indicating that they can mimic symptoms of depression in humans.¹² The most used experimental model for researching antidepressant activity is the behavioural despair test. In rodents exposed to unavoidable circumstances, causes behavioural despair that is correlated with depression in humans. ¹³

In TST, immobility reflects a state of distress which can be reduced by the agents used to treat human depression. This causes animals to experience behavioural despair, which is said to mimic a state akin to depression in humans.¹⁴ This immobility may therefore be comparable to the clinical findings where people with depression frequently do not exert persistent effort. Animals' behavioural repertoire includes immobility as well. Similar to fluoxetine, both formulations decreased the immobility period in TST. Usually, a drug that stimulates the central nervous system, causing alertness, elevated mood and physical activity can reduce Immobility time in TST.¹⁵

There is evidence that FST shares several characteristics with depression in people, such as increased food intake, irregular sleep patterns, and anhedonia. Low and high doses of ashwagandharista and shankhpuspi shorten the duration of immobility in rodents, and their effects are similar to those of fluoxetine in FST. The immobility time is shortened by medications that block the reuptake of serotonin and norepinephrine. According to earlier research, selective serotonin uptake inhibitors lengthen the swimming duration during the mice's escape behaviour, while selective norepinephrine uptake inhibitors lengthen the climbing time in FST.¹⁶ The two test formulations demonstrated antidepressant activity, with their mechanism potentially involving nonselective inhibition of norepinephrine and serotonin reuptake, as evidenced by the lack of significant difference in swimming and climbing times during the TST.

The antidepressant effects of these Ayurvedic formulations can be attributed to their active ingredients, such as Ashwagandha, Terminalia, and Glycyrrhiza, which have been shown to upregulate BDNF-TrkB signaling, reduce oxidative stress, inhibit MAO-A, interact with the adrenergic and dopaminergic systems of the brain, and alter cortisol levels.17-20 While conventional antidepressants typically function by increasing synaptic concentrations of serotonin and/or norepinephrine²¹, Ayurvedic formulations exhibit a multicomponent and multitargeted approach. This complex nature makes it difficult to attribute their antidepressant effects to a single pharmacological mechanism, highlighting the need for a systems-level understanding of their therapeutic potential. To ensure consistency and efficacy, a combination of qualitative fingerprinting and quantitative multicomponent analysis emerges as a novel and rational strategy for addressing the critical challenges in the quality control of herbal and ayurvedic medicines.²²

CONCLUSION:

The present study investigated the antidepressant effects of two commercially available Ayurvedic formulations, demonstrating their activity comparable to that of the standard drug used for treating depression. Studies involving estimation of central monoamines and their metabolite concentration with varying doses of these formulations would help in establishing their exact mechanism of action. While traditional systems of medicine have shown promising therapeutic potential, they often face challenges related to quality assurance. Implementing rigorous quality control measures and conducting extensive long-term preclinical studies to explore their neurobiological mechanisms would significantly enhance the understanding of their efficacy and safety.

CONFLICT OF INTEREST:

The authors have no conflicts of interest regarding this investigation.

ACKNOWLEDGMENTS:

The authors would like to thank Principal and Management of RBVRR Women's College of Pharmacy for providing facilities to carry out this research.

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Received on 13.04.2025 Revised on 06.08.2025

Accepted on 07.10.2025 Published on 10.04.2026

Available online from April 13, 2026

Asian J. Res. Pharm. Sci. 2026; 16(2):107-110.

DOI: 10.52711/2231-5659.2026.00017

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