INTRODUCTION:

A mental or behavioral disease affects nearly 450 million people worldwide, claims a world health report.¹ A chronic illness is mental depression, which affects a person's emotions, thoughts, physical health, and behaviour. Biological and emotional factors are linked to depressive symptoms. Retardation of thought, action, and hunger are biological signs, whereas enigmatic Ness, apathy, and pessimism, low self-esteem, which includes a sense of guilt, inadequacy, and ugliness, indecision, and a lack of desire are emotional markers.²According to projections, depression will have the second-largest increase in morbidity after cardiovascular illness by the year 2020, placing a huge socioeconomic burden on society.³

There are two types of mental depression: unipolar depression, which is frequent (occurs in about 75% of cases), non-familial, unquestionably linked to stressful life events, and characterized by symptoms of anxiety and agitation. The second form, known as bipolar depression (which accounts for around 25% of instances), has a recognizable pattern, is independent to external stresses, typically manifests in early adulthood, and causes oscillating depression and mania over the course of a few weeks⁴.

Depression: Diagnostic Features and Symptoms:

Extreme sadness is only one aspect of depression. It is a condition that affects the immune system, the peripheral nerve system, cognition, behaviour, and both the brain and body. Depression is seen as an illness, as opposed to a temporary sad mood, because it impairs daily functioning at job, in school, or in relationships.

The mourner views the world as empty or awful, whereas people who are clinically depressed place their sense of emptiness or badness within themselves. This is another way in which depression varies from regular grief.⁵

Symptoms of depression:

Not everyone who is depressed or manic experience every symptom. Some may experience a few symptoms, some many. Also, the severity of symptoms may vary with individuals

1. Persistent sad, anxious or empty mood

2. Feelings of hopelessness, pessimism

3. Feeling of guilt worthlessness, helplessness

4. Loss of interest or pleasure in hobbies and activities that you once enjoyed, including sex

5. Insomnia, early-morning awakening or oversleeping,

6. Appetite and or weight loss or overeating and weight gain,

7. Decreased energy, fatigue, being slowed down

8. Thoughts of death or suicide, suicide attempts ⁶

Epidemiology:

Depression is still an illness that affects many people. The National Comorbidity Survey Replication (NCS-R) study evaluated depression. Major depressive episodes were more common in US adults over the course of a year (8.3%) than during their lifetime (19.2%). The average age of beginning for depression is 26, and it typically begins in the early stages of adulthood. In early and middle age, the distribution of lifetime depression is generally even across the age categories, but it falls in people over 65. Across all age groups, women are much more likely than males to experience depression.⁷

Drug Treatment:

For the initial antidepressant, 50–65% of patients show improvement. No antidepressant has a higher level of effectiveness or faster time to action than any other. The ability to match a patient's symptoms to a side effect profile, the presence of medical and mental health co-morbidity, and previous responses can all influence a decision. Relative costs can also be taken into account (e.g., generics) UMHS preferred agents are Fluoxetine (generic) and citalopram (Celexa ®)⁸

By blocking the enzyme monoamine oxidase, monoamine oxidase inhibitors (MAOIs) prevent the degradation of the monoamine neurotransmitters serotonin, norepinephrine, and dopamine. This results in higher levels of these neurotransmitters in the brain and greater neurotransmission.⁹

Serotonin, norepinephrine, and, to a much lesser extent, dopamine are just a few of the neurotransmitters that are prevented from reuptake by tricyclic antidepressants (TCAs). Selective serotonin reuptake inhibitors (SSRIs), which prevent serotonin from being reabsorbed and hence raise the amount of active serotonin in brain synapses, are currently the most widely used antidepressants. Other cutting-edge antidepressants have various effects on the nerve cell's receptors or norepinephrine reuptake.^10,11

Although SSRIs, MAOIs, and TCAs raise serotonin levels, other medications stop serotonin from binding to 5-HT2A receptors, arguing that it is oversimplified to refer to serotonin as the "happy hormone." In fact, it's typical for patients to feel worse during the first few weeks of treatment since the prior antidepressants accumulate in the circulation and the serotonin level rises. One reason for this is that 5-HT2A receptors evolved as a saturation signal, warning the animal to cease exploring for food, a partner, etc., and to start looking for predators (people who use 5-HT2A antagonists frequently gain weight).¹²

Medicinal Herbs with antidepressant activity:

The antidepressant effects of medicinal plants have been extensively studied in animal models up to this point, but human studies have been far less common. Here are some plants that have been utilised in clinical trials and have demonstrated significant activity in research on animals.

Centella asiatica Linn:

The umbellifere family includes the clonal, perennial herbaceous creeper Centella asiatica (CA) (Apiceae). Initial phytochemical research revealed the presence of phenols, alkaloids, saponins, and terpenoids.¹³ Several investigations have proposed that this plant possess sedative and anxiolytic¹⁴ memory enhancing¹⁵ This herb has also been discovered to have antidepressant properties¹⁶

Momordica charantia:

This plant is also referred to as balsam pear, karela, bitter gourd, and pare. Traditional uses for it include food and medicine and it grows in tropical regions of the Amazon, East Africa, Asia, India, South Africa, and the Caribbean. Alkaloids, flavonoids, glycosides, triterpenoids, steroids, phenols, tannins, oils, and lipids are some of its phytochemicals.^17,18 Additionally, M. charantia has been proven to be an effective herb for treating depression and anxiety. However, there is very little information on this plant's leaves, seeds, and roots as well as its fruit that has undergone a comprehensive biological research.^19,20 Using stress-induced depression models like the FST and TST, the unripe fruit and leaves of M. charantia are assessed for their antidepressant properties.^21,22

Clitoria ternatea:

The perennial herbaceous plant Clitoria ternatea (CT), also called "butterfly pea," has long been utilized in traditional Ayurvedic treatment. The roots are helpful for severe bronchitis, asthma, and chaotic fever because they include laxative, diuretic, anthelmintic, and anti-inflammatory effects.^23,24 There have been reports of Clitoria ternatea nootropic, emetic, and anticonvulsant properties.²⁵ It improves memory, raises acetylcholine levels in rats, and has antidepressant effects.²⁶

Cucurbita pepo:

A cultivated plant belonging to the genus Cucurbita, the species Cucurbita pepo. A strong antidepressant-like effect was seen in mice using Cucurbita pepo extracts in FST, and its efficacy was determined to be comparable to imipramine. All major classes of antidepressant medications can be detected by this test, which is also extremely sensitive and relatively specific. Rats are made to swim against their will in a confined space in the FST. This supposedly reproduces a state resembling human depression in animals by inducing a state of behavioral despair.²⁷

Aegle marmelos:

Aegle marmelos (AM), also known as the bale fruit tree, is a well-known Ayurvedic medicinal tree found throughout India. The tree has a variety of medicinal properties. Several studies on various parts of the plant revealed that the plant has antidiarrheal²⁸, anti-inflammatory, antipyretic, and analgesic properties.²⁹ Methanol leaf extract of Aegle marmelos demonstrated significant anxiolytic and antidepressant activity, which could be attributed to an increase in monoamine levels at post synaptic sites. As a result, Aegle marmelos could be used as a natural psychotherapeutic agent for stress-related disorders such as anxiety and depression.³⁰

Rosmarinus officinalis:

Rosmarinus officinalis, also known as rosemary, grows wild in the majority of Mediterranean countries.³¹ Rosemary has long been used in traditional medicine and has been shown to have high antioxidant activity.³² It has long been known as the herb of remembrance, and it has been reported that using R. Officinalis improves memory.³³

Artemisia absinthium:

Artemisia absinthium (Asteraceae) is commonly used in traditional Iranian medicine. Wormwood (Artemisia absinthium L.) (Asteraceae) is an aromatic-bitter herb that has been used traditionally in Iran. This species has ethnomedical and biological properties such as antifungal activity,³⁴ antimicrobial activity,³⁵ choleretic, antiseptic, balsamic, depurative, digestive, diuretic, emmenagogue, and in the treatment of leukemia and sclerosis.³⁶Its antidepressant activity has also been proven.³⁷

Bacopa monniera:

Bacopa monniera (Family: Scrophulariaceae), also known as Brahmi, is an aquatic herb found throughout the world's warmer regions, including Bangladesh. This plant is widely used in traditional medicine in Bangladesh as a powerful therapeutic agent as a neurological tonic to enhance intellectual development,³⁸ to treat respiratory³⁹, and digestive⁴⁰ disorders. Its antidepressant activity was also found⁴¹

Citrus maxima:

The Citrus maxima Pummel is the common name for Merr. (Rutaceae). It has been used as a sedative in indigenous medicine to treat nervous affections, convulsive cough, hemorrhagic diseases, epilepsy⁴² as well as depression.⁴³

Urtica dioica:

According to the findings of this study, Urtica dioica has a specific antidepressant-like effect in animal models predictive of antidepressant properties, FST and TST. Furthermore, the effect of acute or repeated administration of this extract was comparable to that of the classical antidepressants fluoxetine and haloperidol.⁴⁴

Andrographis paniculate:

Andrographis paniculata (Acanthaceae) is an Indian herbal medicine used to treat fever, cold, laryngitis, diarrhea, and rheumatoid arthritis as an anti-inflammatory and antipyretic.⁴⁵ The behavioral despair model was used to investigate this herbal drug's ability to elevate suppressed mood, which is quite common in today's scenario. The FST and TST results clearly show that this drug has the potential to be quite useful in cases of depression.⁴⁶

Selaginella Bryopteris:

Selaginella bryopteris is a pteridophytic plant in the selaginellaceae family. Sanjeevani booti is its well-known name. Selaginella bryopteris is a lithophyte that grows on tropical hills, specifically the arawali mountain terrain from east to west in India, and the plants grow luxuriantly during rains, displaying a lush green velvety landscape. During the summer, the plants suffer from severe desiccation; the fronds curl and become nearly dead. In this state, they resemble a closed fist and are commonly referred to as punjemeriam or hathazori in Unani. When dry plants are immersed in water, their fronds unfold, turn green, and they resume active life. This plant has been shown to have antidepressant properties.⁴⁷

Plant name	Extract	Animal model	Method of testing	Reference standard	Drug Dose	Reference
Centella asiatica Linn	Ethanolic Extract of Leaves	Male Wister rats	FST HBT	Imipramine (30 mg/kg)	100 mg/kg 300 mg/kg	16
Momordica charantia	Ethanolic Extract of unripe fruit	Swiss albino female mice	FST TST	Imipramine (15 mg/kg)	100 mg/kg 300 mg/kg 500 mg/kg	22
Clitoria ternatea	Ethanolic extract of root	Swiss albino mice and Albino rats of either sex	OFT MCAT	Imipramine (15mg/kg,p.o.)	150 mg/kg 300 mg/kg	26
Cucurbita pepo	Alcoholic and aqueous extract of Seeds	Male albino Wistar rats	FST	Imipramine (30mg/kg)	100mg/ kg	27
Aegle marmelos	Methanolic Extract of Leaves	Male Swiss Albino mice	EPM TST Digital Photo actometer	Imipramine (20mg/kg) and Fluoxetine (20 mg/ Kg).	75 mg/kg 150 mg/kg 300 mg/kg	30
Rosmarinus officinalis	Isolation of salvigenin, rosmanol and cirsimaritin	Male Swiss Albino mice	FST TST	Imipramine (60 mg/kg)	50-200 mg/kg	33
Artemisia absinthium	Methanolic extract of aerial parts	Swiss albino mice of either sex	FST TST	Imipramine (5 and 10 mg/kg)	125 mg/kg 250 mg/kg 500 mg/kg 1000 mg/kg	37
Bacopa monniera	Methanolic extract of leaves	Swiss Albino mice	FST OFT TST	Imipramine hydrochloride (30 mg/kg)	50 mg/kg 100 mg/kg 200 mg/kg	41
Citrus maxima	Aqueous extract of leaves	Swiss albino mice of either sex	FST TST OFT	Fluoxetine (20 mg/kg,i.p.) and Imipramine (30 mg/kg,i.p.)	100 mg/kg 200 mg/kg 300 mg/kg	43
Urtica dioica	Roots and leaves extract	Mice of either sex	FST TST	Fluoxetine (10 mg/kg)	50 mg/kg 100 mg/kg	44
Andrographis paniculate	Ethanolic extract of leaves	Rats of either sex	FST TST	Imipramine (30 mg/kg)	50 mg/kg	46
Selaginella bryopteris	Pet ether, Chloroform Methanol, Ethanol, And aqueous extracts	Swiss albino mice of either sex	HBT Rotarod test	Diazepam (10mg/kg)	250 mg/kg 500 mg/kg	47

CONCLUSION:

The collection of antidepressant herbal plants were tabulated from various journals and reported above as we can conclude that herbal plants are a very rich source of substances that are responsible for increasing antidepressant activity. Marketed antidepressant drugs used to treat depression may cause vomiting, nausea, irritation, insomnia, tremor, blurred vision, urinary retention, and other side effects. To address this, natural medicines with minimal side effects are being used to treat depression.

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Received on 27.02.2023 Modified on 17.04.2023

Res. J. Pharmacognosy and Phytochem. 2023; 15(3):230-234.

DOI: 10.52711/0975-4385.2023.00036