EMERGING MECHANISMS AND POTENTIAL ANTIDEPRESSANT ACTION OF MEDICINAL PLANTS

EMERGING MECHANISMS AND POTENTIAL ANTIDEPRESSANT ACTION OF MEDICINAL PLANTS

Jitendra Gupta ^*, Reena Gupta and Krishna Kumar Varshney

Institute of Pharmaceutical Research, GLA University, Chaumuhan, Mathura - 281406, Uttar Pradesh, India.

ABSTRACT: Depression is a common heterogeneous, debilitating and life-threatening mood disorder affecting different segments of the community. Several chemical and synthetic medicines as standard are being employed to treat depression and may lead to complete recovery in only 50% of clinically depressed patients but causes many adverse effects. Thus, scientists are increasing their interest in research towards the utility of medicinal plants for antidepressant activity. Several medicinal plants and its derived medicinal products have been reported to exert antidepressant action in different animal models by the combined effect of their phytoconstituents. In the brain, the alteration in level of various endogenous molecules likes noradrenaline (NA), acetylcholine (Ach), serotonin (5-HT), dopamine, glucocorticoid, γ-aminobutyric acid (GABA), corticotrophin-releasing hormone (CRH) and hippocampal volume are responsible for depression. Therefore, most medicinal plants through synaptic regulation of serotonin, noradrenaline, and dopamine, overcome the altered level of monoamines in the brain and also reinforcing antioxidant defense mechanism, regulate hypothalamic-pituitary-adrenal axis activity and reducing inflammatory mediators. So, herbal medicines are widely used in contrast to allopathic or synthetic medicines globally because of their least side effects and wide therapeutic applications. The present review aims to highlight the medicinal plants and their antidepressant mechanism involved in the treatment of depression by animal model studies.

Depression, Endogenous molecules, Medicinal plants, Phytoconstituents

INTRODUCTION: In the present world, there is several life-threatening neurological disorders such as Alzheimer’s, epilepsy, multiple sclerosis, Parkinson’s disease, brain tumor, etc. Besides them, there are certain disorders such as mood swing, anxiety, and depression, which may not be life-threatening, but at the same time, degrade the quality of life.

One of the mood disorders, depression is an extensive medical condition which not only affect mental health but also have an impact on physical health resulting in feeling of sadness or emptiness, insomnia, alopecia, risk of heart attack, constricted blood vessels, uncontrollable thoughts of suicide, lower interest in sex, feeling of tiredness, trouble in taking decisions and weakened immune system etc.

According to World Health Organization (WHO) statics, the depressive disorder is the third most disabling disorder worldwide, affecting 1% to 2% of teenagers and 0.9% to 42% of elderly patients in the Europid population. Over 36 percent of the worldwide population attempt suicide due to bipolar disorder or major depression.

Depression is of various kinds’ namely major depression, persistent depression, postpartum depression, psychotic depression, seasonal depression, and Bipolar disorder.

Persistent Depressive Disorder: It is also known by the name dysthymia, and such a depression lasts for a minimum of two years. The symptoms vary in severity, and their occurrence could sometimes be serious while at other times it may be less severe, but altogether if only the symptoms persist for two consecutive years, this could be characterized as a persistent depressive disorder.

Postpartum Depression: It is much more serious than the “Baby blues” experienced by perturbating mothers. The postpartum depression makes it very tough for the recent mothers to fulfill their childcare and also their own routinely activities due to their extreme emotions of anxiety, sorrow, and lassitude.

Psychotic Depression: This kind of depression is a combination of depression with any form of psychosis such as delusions, hallucinations, and even suicidal thoughts. People in such condition are most commonly found in delusions of poverty or illness.

Seasonal Affective Disorder: This can more easily be understood as winter depression as its onset is in winters due to lesser intensity of sunlight and thrusts during spring and summer. This kind of depression has symptoms like social withdrawal, more sleep, and weight gain.

Bipolar Disorder: Although, bipolar disorder is not a part of the depression, a person with bipolar disorder experience rise and fall in moods. The mood variation could be extremely irritable known to be mania and less intense as hypomania. These mood swings match the characteristics of depression and so included in the list of depressions.

Risk of Endogenous Bioactive Molecules for Depression: With the advancements in studies related to depression, researchers have established some new aspects to be considered in depression. These include an increased level of corticotropin-releasing hormone (CRH); increase in the level of gamma-aminobutyric acid (GABA); unrestricted glucocorticoid activity in psychotic depression; elevation in acetylcholine activity; and loss in hippocampal volume. These outcomes lead to the development of newer hypothesis in the study regarding depressions.

1. Norepinephrine: Norepinephrine is a catecholamine which is synthesized from tyrosine. Norepinephrine is found in the brain, plasma, sympathetic nervous system, and heart tissues. The process of synthesis of norepinephrine is: tyrosine converts to L-dopa under the action of tyrosine hydroxylase and this L-dopa in the presence of dopa decarboxylase turns into dopamine which then finally converts into norepinephrine by the activity of dopamine beta-hydroxylase ¹.

Norepinephrine is further translated into epinephrine in adrenal tissues via phenyl-n-methyltransferase ². CNS do not have much specific role to play in the samples of norepinephrine collected from urine or plasma whereas there are previously established studies that showed 20-30% of 3-hydroxy-4-hydroxyphenyl glycol (MHPG) is obtained from brain ³.

It has been reported that in depressed patients, specifically bipolar and the subgroup of unipolar depressives, their urinary MHPG levels were lesser when compared with healthy individuals. On assigning both bipolar and unipolar depressives into two groups each I and II, investigators reported a similar pattern of MHPG levels in both categories, i.e., low MHPG levels were reported in group I than group II ^{4, 5}.

But there were some cases of unipolar patients that reported an increase in MHPG ⁶ and urinary free cortisol levels ⁷. The level of catecholamine and MHPG in cerebrospinal fluid (CSF), urine or plasma is always higher in cases of manic or euthymic bipolar patients in comparison to bipolar depression patients ^{8, 9}. Altogether, this previous study helped to understand the fact that norepinephrine levels play an etiological role in mood disorders. These data revealed that depression exists in two forms- a norepinephrine depression, marked by low levels of MHPG ¹⁰ and another, a serotonin depression ¹¹ marked by the high levels of MHPG.

Tyrosine Hydroxylase / Locus Coeruleus:  Tyrosine hydroxylase or locus coeruleus act as the nucleus of the Norepinephrine system in brain ¹². The post-mortem studies of depressed patients or suicide ¹³ casualties reported upregulated activity of tyrosine hydroxylase ¹⁴ in brain pointing towards chronic stress. There were other studies which produced a contradictory report such as there were cases that reported a decrease in NE in neurons in suicidal victims ¹⁵, whereas in other studies NE transporter sites were reduced, but NE level in neurons was sufficient in numbers ¹⁶. When putting together, these studies concluded an alteration of NE in suicide victims but cannot produce any convincing pattern of NE alterations.

Norepinephrine and Adrenoceptor: The production and release of NE are regulated by presynaptic α₂ receptors by acting as thermostats. Studies have shown an elevated activity of α₂ in platelets of depressed patients ¹⁷. The receptor activity of α₂ could be computed by monitoring the response of cAMP in regard with agonists since these receptors are bound to adenylate cyclase second messenger system in such a way that their agonist inhibits cAMP formation ^{18, 19}. It has been documented that stimulation of postsynaptic α₂ adrenoceptor inhibits hypothalamic-pituitary-adrenal axis function ²⁰; the abnormally increased cortisol response to yohimbine (indole alkaloid, α_2-antagonist) suggests a relative sub sensitivity of postsynaptic α₂ adrenoceptor in depression ¹⁸.

2. Serotonin: Serotonin or 5-hydroxytryptamine (5-HT), a monoamine neurotransmitter, have a significance role in appetite and mood Fig. 1. It is synthesized within the raphe from amino acid L-tryptophan in the brain, but it does not cross the blood-brain barrier by itself, but its metabolite 5-hydroxy indole acetic acid (5-HIAA) is present in a measurable amount in CSF.

Serotonin metabolism is regulated by monoamine oxidase (MAO). The interest to study about serotonin was established because low CSF 5-HIAA levels were found in hospitalized depressives (depressive patients) who have attempted suicide ²¹ by violent methods such as hanging and also the antisocial personalities who have improper impulse control ^{22, 23}. With recent advancements, a link between low serotonin level and difficulties in impulse control have been established stating the suicidal nature of antisocial subjects if depressed ²⁴.

FIG. 1: CAUSES OF DEPRESSION DUE TO POST-SYNOPTICALLY INSUFFICIENT 5-HT

Serotonin and Serotonergic Receptors: There have been several 5-HT receptors (both presynaptic and postsynaptic) studied in depressed patients, among which 5-HT_1A and 5-HT_2A became the center of attraction. 5-HT_2A receptors are found post-synoptically in the frontal cortex and also in platelets ^{25, 26}. Increased binding sites in suicidal patients have been reported ^27, but they are not considered as diagnosis (diagnostic feature) for the cognitive aspect of major depression ²⁸.

5-HT_2A receptors are part of phosphoinositide second messenger system. When this receptor is activated by agonists, phosphatidylinositol 4,5-bisphosphate get hydrolyzed to form diacylglycerol and 1, 4, 5-triphosphate in the presence of phospholipase C. This phosphoinositide system is studied in suicide victim’s brain. It was reported that phorbol 13, 14-dibutyrate binding with protein kinase C (activated by diacylglycerol) in the prefrontal cortex was lesser in teenage suicide victims ²⁹, also decrease in the levels of beta-1 isozyme was found ³⁰. On studying number and activity of 5-HT_1A receptors in post-mortem brain, it was found that in some cases there was an increase in 5-HT_1A Bmax in non-violent suicide victims while in some other suicide victims the cases failed to establish any difference in 5-HT_1A receptors activity ³¹.

3. Dopamine: Although, dopamine is a precursor of NE and is also widely present in the brain, but still NE remains the center in the etiologic study of depression. The levels of CSF DA are reported to increase in depressive patients ^32, but levels of CSA homo-vanillic acid (HVA), which is a metabolite of CSF DA decreased ^{32, 33}. DOPAC levels linked with suicidal nature of depressives were found to decrease when compared with controls ^{34, 35}. Increased levels of CSF HVA and CSF DA are found in an association with symptoms of psychotics, agitation in major depression, and delusional depression. Data collected from preclinical studies have shown that DA activities and metabolism in some particular brain parts could be altered by HPA axis activity ^{36, 37}.

4. GABA (Gamma-Amino Butyric Acid): GABA has become a topic of interest, due to the wide use of anticonvulsants in mood disorders. It is an inhibitory neurotransmitter which regulates activities of both norepinephrine and dopamine and also balances the threshold of seizures. GABA receptors are categorized into forms GABA_A and GABA_B, which are associated with chloride channels and calcium channels, respectively. GABA_B receptors present in the frontal cortex are upregulated by antidepressants and mood stabilizers in case of the rat.

These GABA_B agonists mark an increase in cAMP response to norepinephrine and also a decrease in β-adrenergic response to TCA. The low levels of plasma GABA are linked to unipolar depression and alcoholism ^{38, 39, 40}.

5. Neuroendocrine Systems: The neuroendocrine system was initially considered for investigating activities of neurotransmitters like norepinephrine and serotonin, in cases of depression but with the time the focus has diverted to investigate the roles played by the axes in the pathogenesis of diseases. The three axes to be focused in cases of major depression includes HPA, HPT, and HGH Fig. 2.

Hypothalamic-Pituitary-Adrenal (HPA) Axis: There is several evidence that points towards abnormalities in HPA Axis during the depression. An increase in both serum cortisol and their precursor’s level was observed in depressive patients ^{41, 42} especially during the evening and overnight ¹⁰, when the axis is supposed to be dormant and is also believed to cause suicidal ideations ³⁷. The levels of cortisol are high throughout day and night in patients with severe depression conditions or in cases of major depression, which also indicates a very high-stress level of patients ¹⁰.

FIG. 2: ROLE OF NEUROIMMUNE AND NEURO-ENDOCRINE SYSTEM IN DEPRESSION. (‘+’ ACTIVATE, ‘-’ INHIBIT)

A study conducted based on types of patients revealed that outpatients with mild and nonpsychotic disorders showed lesser cases of non-suppression and were also at a lesser risk for relapse when compared with psychotically depressed patients. Studies have shown that in depressed patients’ level of corticotropic releasing hormone (CRH) in CSF or plasma remains high due to their blunt responses to adrenocorticotropic hormone (ACTH) ^{43, 44}. Imaging techniques have shown that the size of pituitary ⁴⁵ and adrenal gland⁴⁶ increases during the depression, and it reduces to normal with the recovery of patient ⁴⁶.

FIG. 3: FEEDBACK MECHANISM OF NENEURAL CIRCULATORY SYSTEM OF HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS. (‘+’ ACTIVATE, ‘-’ INHIBIT)

In suicide victims’ number of arginine vasopressin (AVP) neurons and serum AVP is increased, which also became a cause for increasing CRH stimulation of ACTH ^47-49. Besides hypothalamus CRH is also present in extrahypothalamic region such as amygdala where it has a particular role to play in fear responses and if it gets over activated, it leads to panic and depressions ^{50, 51}. Low levels of ACTH are also found in patients of atypical depression and post-traumatic stress disorder (burn out syndromes) Fig. 3. The data proves that, HPA axis over activity and under activity both accounts for various depressive subtypes ⁵².

Hypothalamic-Pituitary- Thyroid (HPT) Axis: The major reason for considering the hypothalamic-pituitary-thyroid (HPT) axis is the overlapping of major depression symptoms with hypothyroidism ⁵³. In studies conducted on depressives, an elevation in CSF thyrotropin-releasing hormone (TRH) was reported which should be followed by blunted thyroid-stimulating hormone (TSH) response ⁵⁴ as the TRH levels of pituitary remained low, and this was experienced in around 25% of cases of major depression ⁵⁵. The depressed patients were diagnosed with type III and type IV subclinical hypothyroidism which is characterized by normal level of T3, T4, and TSH but are observed by elevated responses of TSH to TRH and also the presence of antithyroid antibodies ^{53, 55}.

These data have led to a conclusion that patients with symptomless autoimmune thyroiditis and positive antibodies are reported to be depressive patients ⁵⁶. Some data revealed elevation in both central TRH activity and subtle forms of hypothyroidism (suggestive of low T3 and TRH activity) has a significant potential role in major depression ⁵⁵.

Human Growth Hormone (HGH): Growth hormone is synthesized in the anterior pituitary and regulated by growth hormone-releasing factor (GRF) which stimulates the release of GH and somatostatin, which inhibits its release. Somatostatin is also considered as a neurotransmitter and is found in extra-hypothalamic regions, and it is known that all major neurotransmitters involved in mood disorders affect growth hormone release ⁵⁷. Nocturnal growth hormone levels increase in depression, while daylight-stimulated growth hormone levels increase in both unipolar and bipolar depressions ⁵⁸. Growth hormone response to GRF has blunted in depression ^59, and also the CSF levels of somatostatins are low in cases of depression ⁶⁰.

6. Homocysteine: Elevated level of plasma homocysteine (>15mcmol/L) may lead to major depressive disorder. Several studies have documented the evidence for the association between elevated level of homocysteine and depression ⁶¹. It is relevant to notice that folate deficiency was observed in up to one-third of patients with severe depression unlike of their ages, but this topic also has a conflicting result, due to the fact that most studies evaluating homocysteine levels are performed in elderly patients and there is an increase in both homocysteine levels and depression onset with aging.

The folate deficiency being primary or secondary to depression makes no difference, since its low level are meant to limit the response to antidepressants. There are a number of studies that supports the efficacy of folate replacement therapy in improving mental state recovery and showed antidepressant function of s-adenosyl methionine, probably via the one-carbon metabolism pathway which produces methyl groups required for the synthesis of serotonin ⁶², dopamine, and norepinephrine which imbalance in the patients with depression and psychiatric disorder ⁶³.

Phytochemicals against Depression: Besides, autoimmune and cardiovascular diseases phytochemicals derived from herbs also help to reduce the risk of neurodegenerative disease. Polyphenols such as curcumin, ferulic acid, and resveratrol are known to possess anti-inflammatory and antioxidant properties, but they have also known to show neuroprotective effects in symptoms of depression.

Carvacrol: Carvacrol is a monoterpene phenol obtained from oregano and thyme and is known for it's anti-inflammatory, analgesic, antiarthritic, anti-allergic, anticarcinogenic, antidiabetic, cardio-protective, gastroprotective, hepatoprotective, and neuroprotective properties ⁶⁴.

Dong et al., showed that when carvacrol is co-administered with compounds that undergo CYP2A6-mediated metabolism ⁶⁵ in oral dose (12.5-50mg/kg) induced anti-depressant effect that was regulated by a dopaminergic pathway in mice ⁶⁶. Oral administration of carvacrol was reported to produce a raise in 5-HT and dopamine in hippocampus and prefrontal cortex ⁶⁷.

Curcumin: The major active constituent of Curcuma longa is curcumin, which is a yellow colored natural phenol widely known as Oriental medicine since historical time, but nowadays its medicinal potential is under study. It has been reported that curcumin supplements have shown antidepressant potential in improving damage caused in behavioral abnormalities in open field and passive step-down avoidance in depressant models ⁶⁸.

Also, a decrease in immobility time in forced swimming test and improvement of bilateral olfactory bulbectomy-induced alteration of 5-HT, noradrenaline, and dopamine in hippocampus were also observed when treated with curcumin. Kulkarni et al., came to a conclusion that curcumin elevated 5-HT levels in mice and when co-administered with other antidepressants like fluoxetine, venlafaxine, and bupropion, it produced synergistic effects ⁶⁹.

Curcumin has also been reported to rehabilitate the biochemical and behavioral changes occurred due to chronic stress ⁶⁹. Antidepressant activity of curcumin could be related to the elevation of hippocampal brain-derived neurotrophic factors which are deeply indicated in the pathophysiology of depression ^{70, 71}.

Ferulic Acid: It is a phytochemical that is known for it's anti-inflammatory ⁷², anti-tumour ⁷³, anti-diabetic ⁷⁴, neuroprotective ^75, and anti-oxidant ⁷⁶ properties. Oral administration of ferulic acid reduced stress-induced abnormal behaviors in mouse depression model and also increased phosphorylation of CREB and brain-derived neuro-trophic factor mRNA hippocampal levels ^{71, 77}.

Quercetin: Quercetin is a non-specific protein kinase enzyme inhibitor that is known to inhibit depression-like behaviors occurring due to the over activity of the hypothalamic-pituitary-adrenal (HPA) axis in mice ^{71, 78}.

Resveratrol: Resveratrol is a natural phenol found widely in grapes and red wine. Trans-resveratrol is found to show antidepressant activity due to its interaction with the monoaminergic system by increasing levels of 5-HT/noradrenaline in mouse brain. Resveratrol is capable of inhibiting chronic stress-induced depression-like behavior ^{71, 79}.

Yohimbine: Yohimbine is an indoloquinolizidine alkaloid derived from the bark of African tree Pausinystalia johimbe. Despite parallel MHPG response in control and depressed patients, the response to yohimbine was significantly greater in depressed patients than in controls. Since there is evidence that stimulation of postsynaptic alpha 2-adrenergic receptors inhibit HPA axis function and the abnormally increased cortisol response to the alpha 2-antagonist yohimbine suggests a relative sub-sensitivity of postsynaptic alpha 2-adrenergic receptors in depression ¹⁸.

Pharmacological Impact of Antidepressant Action of Medicinal Herbs:

Aloysia polystachya: The hydroalcoholic extracts of leaves of Aloysia polystachya at various doses produce antidepressant activity in Forced Swim Test (FST) conducted on female rats. Its anti-depressant property is due to the presence of bioactive constituents such as thujone and carjone⁸⁰.

Aloysia triphylla: Aloysia triphylla belongs to family Verbenaceae. Two active constituent hesperidin and artemitin are known to show therapeutic activities such as anti-inflammatory actions, anti-oxidant properties, and also tonic effect upon nervous system such as in rescuing from depression ⁸¹.

Aniba riparia: Aniba riparia belonging to family Lauraceae is found to possess anti-depressant activity at various doses due to the presence of riparin III in tail suspension test and forced swim test conducted on mice ⁶⁶.

Bacopa monnieri: Brahmi is found to reduce depression score in demented and non-demented elders due to the presence of saponins like bacopasides VI-VIII, bacopaside I and II and bacopasaponsin C. Its ability to treat neurodegenerative disease was taken into consideration due to its nootropic and cholinergic property ^{82, 83}.

Berberis aristate: Daruhaldi is known to show anti-depressant activity in forced swim test conducted on mice by enhancing brain serotonin, noradrenaline, and dopamine levels. All this is believed to be due to the presence of an isoquinoline berberine ⁸⁴.

Camellia sinensis: The aqueous extract of leaves of Camellia sinensis is found to show anti-depressant like activity in male mice during forced swim test ⁸⁵.

Cinnamomum verum: Cinnamon, a plant from Lauraceae family, is known to possess anti-depressant, anti-viral, anti-microbial and anti-oxidant properties. The major constituents that contribute to these therapeutic activities are cinnamaldehyde ⁸⁶ and proanthocyanidins ⁷¹.

Citrus aurantium: The studies have reported that essential oils of Citrus aurantium could be considered as the choice of treatment for depression over the chemical drugs due to the positive and no side effects produced in depression cases ⁸⁷.

Echium amoneum: The petals of Echium amoneum contains phenolic compounds such as sanding, defending, and rosmarinic acid that is reported to show anti-depressant, analgesics, anti-oxidant, and anti-bacterial properties ⁸⁸.

Hippophae salicifolia: This medicinal herb is known from early times as a potent prophylactic and health promotive agent. Its bioactive contents such as ellagic acid, vitamin C, and coumarins are known to provide neuroprotective properties such as anti-depressant activity, control of appetite, sleep, memory, and learning ⁸⁹.

Hypericum perforatum: St. John’s Wort is a medicinal plant well known for its anti-depressant property. Its extract, named as WS 5570, is in markets of Germany applied in acute term treatment of mild to moderate major depression. The actual mechanism of Hypericum perforatum remains unknown, but their in-vitro and in-vivo studies have demonstrated that they act by elevating brain serotonin levels, upregulation of 5-HT2 receptors and by inhibition of serotonin reuptake ^{90, 91}.

Lavandula angustifolia: Lavender essential oil is well known for its aromatherapy as a relaxant, but the inhalation of its major constituent linalool is also known to possess anti-depressant, anxiolytic, and anti-conflict effects ⁹².

Melissa officinalis: In Iranian folk medicine, the Lemon balm is used for treating nervousness, lack of energy, and depression in young girls. The major constituents of lemon balm are citronellal, geranial, citral, rosmarinic acid, flavoglychoside acids and three terpinenes ⁹³.

Morinda officinalis: The ethanolic extract of Morinda officinalis shows anti-depressant activity by upregulating serotonin levels in rodent models of depression in learned helplessness test and forced swim test ⁹⁴.

Nyctanthes arbortristis: The hydroalcoholic leaf extract of night Jasmine is found to demonstrate anti-depressant activity in depression models of rodents in forced swim test and learned helplessness test ^{95, 96}.

Ocimum sanctum: Tulsi, the sacred herb is blessed with the number of therapeutic properties, and a recent study concluded that its root extract had shown anti-depressant activity in mice when tested in forced swim test and tail suspension Test.

The dopamine and serotonin systems are believed to be involved in the anti-depressant property of tulsi ^{97, 98}.

Oenothera biennis: The seeds of Oenothera biennis are employed in the production of evening Primerose oil. This oil has shown considerable anti-depressant property in a rodent model of Chronic Fatigue Syndrome ⁹⁹.

Salix aegyptiaca: In Iranian folk medicine, musk willow plant flower is of great therapeutic importance. Each plant possesses single-sex i.e.; the plant is either male or female. The distillates of male flowers of the plant are used in the treatment of depression, anemia, vertigo, and various cardiovascular diseases ¹⁰⁰.

Tinospora cordifolia: The dried stem extract of Tinospora cordifolia demonstrated anti-depressant activity in anti-depressant models such as tail suspension test and forced swim test with the involvement of monoaminergic and GABAergic system ¹⁰¹.

Valeriana officinalis: The root extract of Valerian officinalis showed anti-depressant, anxiolytic, and sedative properties due to the presence of active constituents such as valenol, valepotriates, and baldrinals valerenic ¹⁰².

Viola odorata: Sweet violet is the herbal plant of Iranian folk medicine belonging to the family Violaceae whose flower is useful in treating depression, sleeping disorders, and as a blood pressure-lowering agent ¹⁰³.

Withania somnifera: W. somnifera also known as Indian ginseng belonging to the family Solanaceae is found to show anti-depressant effect by targeting serotonergic system in rodent behavior test studies such as open field test, forced swim test, tail suspension test and learned helplessness test ^104-108.

Zingiber officinale: Other than the established uses of ginger, a recent study showed that hydro-alcoholic extract of rhizome of ginger when administered orally caused depletion in immobility period of rats in forced swim test and tail suspension test hence leading to the conclusion that they possess anti-depressant properties ^{109, 110}.

Some other plants have antidepressant activity showed in Table 1.

TABLE 1: APPLICATION OF MEDICINAL PLANTS IN TREATMENT OF DEPRESSION

CONCLUSION: The new concept of looking for drugs from natural sources has been put to use as an anti-depressant and has gained world-wide interest during the last decades. Such advancement in the world of pharmaceuticals will be of great fortune for developing nations. This review enlists certain medicinal plants that could be positively included in anti-depressant therapy. Medicinal plants and their active constituents can be associated with decreasing risk of depressive disorders.

Active constituents like carvacrol, curcumin, ferulic acid, quercetin, and yohimbine obtained from plant sources are considered to be potent antidepressants. The world needs to shift itself towards the drugs obtained from natural sources to avoid expensive synthetic medicine as well as the side effects like insomnia due to reboxetine, seizures due to amoxapine, G.I. Distress due to paroxetine etc. experienced due to intake of synthetic anti-depressants.

The easier availability, lesser side effects, and cost-effectiveness of drugs obtained from medicinal plants make them more desirable therapeutic agents. The outcome of the study is an aid to recognize and choose effective and safer approaches in the treatment of depression. The need of the hour is to clinically investigate and precisely calculate the role played by these medicinal plants in cure and management of depression ^121-122.

ACKNOWLEDGEMENT: The author, thanks GLA University, for providing the necessary facility to accomplish the work.

CONFLICTS OF INTEREST: The author(s) confirm that this article content has no conflict of interest.

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     Gupta J, Gupta R and Varshney KK: Emerging mechanisms and potential antidepressant action of medicinal plants. Int J Pharm Sci & Res 2020; 11(1): 1-13. doi: 10.13040/IJPSR.0975-8232.11(1).1-13.

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