Herbal Antidepressants : A Comprehensive Review of Plant–Based Therapeutic Agents

Abstract

Depression is a prevalent psychiatric disorder affecting approximately 17% of the global population. Conventional antidepressant therapies often present limitations, including side effects and delayed onset of action, prompting the exploration of alternative treatments. Plant-based drugs have garnered attention due to their diverse phytochemical constituents and multifaceted mechanisms of action. This review synthesizes current research on medicinal plants exhibiting antidepressant properties, highlighting their phytochemical constituents and underlying mechanisms. Key phytochemicals such as flavonoids, alkaloids, saponins, and terpenes have demonstrated antidepressant effects through various pathways, including inhibition of monoamine oxidase, modulation of the hypothalamic-pituitary-adrenal axis, and enhancement of neurotrophic factors While these findings are promising, most studies are preclinical, and further research, including well-designed clinical trials, is necessary to establish efficacy, safety, and standardized dosing. Integrating phytotherapy with conventional treatments may offer a holistic approach to managing depression, but careful consideration of potential interactions and individual patient factors is essential.

Keywords

Depression, antidepressant, phytochemical constituents, flavonoids, alkaloids, saponins, managing depression.

Introduction

 

V.negundo leaves are considered tonic and vermifuge, and are taken combined with long pepper in catarrhal fever.^[5]

V.rotundifolia fruits have been used in folk medicine to treat headaches, colds, migraines, eye pain, female hormone abnormalities, asthma, chronic bronchitis, and gastrointestinal illnesses such as bacterial dysentery and diarrhoea.^[5]

In Asian countries, V.trifolia has been used as an anti-inflammatory and sedative for headache, rheumatism, and the common cold, as well as an anti-trypanosomal agent. The plant is a traditional Chinese medicinal used to treat cancer.^[1]

CHENOPODIUM ALBUM LINN

Bathua is the local name for Chenopodium album, an herbaceous vegetable plant belonging to the Chenopodiaceae family. In Bombay Presidency and other parts of India (Kashmir and Sikkim), it is grown as a pot herb, generally in gardens, but occasionally in the corners of early grain fields. ^[8]

Figure: 11 Leaves of Chenopodium album.

Table 1.2 Scientific Classification of plant.

Kingdom	Plantae,
Subkingdom	Tracheobionta,
Superdivision	Spermatophyta,
Division	Magnoliophyta,
Class	Magnoliopsida,
Subclass	Caryophyllidae,
Order	Caryophyllales,
Family	Chenopodiaceae,
Genus	Chenopodium,
Species	album L.

1. Synonyms: C.album, C.lanceolatum, C.missouriense, C.polymorphum, Chenopodium stevensii, Chenopodium amaranticolor, Chenopodium giganteum, Chenopodium suecicum.
2. Commonly known as:Bathua, lamb’s quarters, wild spinach, fat hen, bathu, pigweed.
3. Parts for Use: Leaves, seeds and roots.

Figure 12:  Seeds of Chenopodium album and Root of Chenopodium album

1. Morphology: C. album, also referred to as Goosefoot or Bathua. It is an upright, green/reddish plant that ranges in height from 0.3 to 3.5 m. Additionally, it is an odourless plant.
2. Stems:Rarely are stems slim, angled, and striped in red or purple and green.
3. Leaves: The size and shape of plant leaves vary greatly. Leaves can occasionally be 15 cm long, toothed, lanceolate, sharp, or irregularly lobulated.
4. Flowers:Flowers feature mealy spikes that become thyrsoid in cultivated species, and they resemble cluster-forming complexes or paniculate flowers.
5. Seeds:Typically, seeds are 1.5 mm in diameter, orbicular, compressed with a sharp edge, and feature a smooth, glossy, fully annular embryo.^[3]

It is 0.3–3 m tall, upright or climbing, mealy or green and reddish, odorless, and frequently has stripes on its stem. Cultivated plants can have leaves that are 15 cm long, oblong, ehombic, deltoid or lanceolate, obtuse or acute, whole, toothed or irregularly lobulate, and have long, thin petioles. The embryo is fully annular. The plant increases hunger. The herb contains aphrodisiac, diuretic, laxative, and anthelmintic properties. Additionally, it is utilized to treat piles, eye conditions, throat issues, abdominal discomfort, and diseases of the heart, blood, and seeds. The leaves contain a lot of albuminoids, other nitrogen-containing chemicItals, and important oil mineral substances, especially potash salts. Hindu doctors advise using the plant to treat splenic enlargement and hepatic diseases.

According to ethnobotanical research conducted in Chikar and its neighboring regions, Chenopodium seeds and leaves are used in traditional medicine to treat hepatic disorders and enlarged spleens. An aqueous preparation of the leaves is also taken orally to treat jaundice.^[8]

 In India, the wild edible plant known as bathua (Chenopodium album) is grown as a green vegetable.In various states, it is typically eaten raw in salads or cooked according to traditional recipes.Proteins, fiber, iron, calcium, vitamins A and C, carotenoids, and vital amino acids like lysine, leucine, and isoleucine are all abundant in C. album leaves.Because of its increased content of several essential minerals, including sodium, zinc, nitrogen, phosphorus, potassium, calcium, magnesium, iron, and manganese, Bathua is regarded as a mineral.It functions as a strong antioxidant that may scavenge free radicals such hydroxyl, superoxide, hydrogen peroxide, and nitric oxide because of its flavonoid (caempferol, quercetin, and isoramnetin) and carotenoid concentrations.Anorexia, cough, dysentery, diarrhea, piles, inflammation, and pain relief are all conditions that can be treated with C. album.Once more, research has shown that it is an antibreast cancer bioagent that increases cell toxicity in human breast cancer cell lines and stops the growth of cells from progressing.^[10]Additionally, bathua has potent antibacterial and antifungal properties against Pseudomonas aeruginosa and Staphylococcus aureus.Consuming vegetables high in fiber but poor in nutrients or phytochemicals, like ordinary cabbage, does not produce the same immune response as consuming vegetables rich in nutrients and phytochemicals, like C. album.When combined to grains and legumes, C.album's diverse amino acid levels would create a nutrient-dense diet that is appropriate for people of all ages. Therefore, it is recommended that GVs like bathua be included in meals in order to improve our nutritional status and fortify our immune systems. Because it tastes nice and is full of bioactive phenolics with strong antioxidant qualities, this plant is best used as a food or medicinal ingredient throughout the winter, particularly in February.^[9]

Crocus Sativus (Saffron)

Originating in green, saffron, botanically known as Crocus sativus L., belongs to the Iridaceae family and was brought to Turkey, Iran, Pakistan, the west Himalayas, Italy, Spain, and Morocco. Its fragrant, golden stigmas are dried and used as a dye and to flavour and color food. Crocin, one of its primary colouring pigments, dissolves readily in water. The primary component responsible for saffron's distinct "bitter" flavour is the glycoside picrocrocin.^[13]

Figure 10 :Flower of Crocus sativus

Its maximum height is 30 cm. The diameter of its corm is 3 cm. The leaves are 2 to 3 mm diameter and up to 20 cm long, either erect or spread. One or two flowers with an orange stigma, yellow anther, and violet calyx.^[13]

One of the priciest spices, saffron has been utilized in traditional medicine. 63% carbohydrates, 12% protein, 10% water, 5% fat, 5% crude fiber, and 5% minerals make up its composition. Dried stigma is the component utilized in phytotherapy. It has vitamins, carotenoids, and flavonoids. The apocarotenoids crocin, picrocrocin, and safranal are examples of active ingredients with antioxidant activity. They can scavenge radicals and modulate enzymes that fight oxidative stress. They also have a pro-apoptotic effect, reduce telomerase activity, and decrease the synthesis of DNA, RNA, and proteins.^[11]

Saffron gets its unique color, flavor, and scent from these same elements. N-acetylcysteine, crocin, and crocetin have all been shown to have antidepressant properties that can help reduce depressive symptoms. The opioid system and the GABAergic system (via GABAA receptors) may be involved in the mechanisms underlying antidepressant action. In animal studies, elevated levels of brain-derived neurotrophic and nerve growth factors were associated with antidepressant effect.^[11]

Saffron extract or its active ingredients have demonstrated a variety of central nervous system effects, including sedative, memory-enhancing, antidepressant, and anticonvulsant properties.^[11]

Saffron can help with major depressive disorder, according to a 2013 meta-analysis, and a 2014 systematic review found that it exhibited antidepressant properties comparable to those of synthetic antidepressants. An update on the usage of saffron for mild to moderate depression in comparison to placebo and synthetic antidepressant therapies was published in 2019 by a recent meta-analysis. The statistical analysis of nine of the eleven randomized controlled clinical trials that were taken into consideration demonstrated that oral administration of saffron preparations in pharmacological doses reduces depression symptoms in comparison to the placebo group and is equivalent to treatment with synthetic antidepressants.^[11]

Safranal, which makes up around 60% of the volatile components of saffron, is the primary fragrance component.^[12]

In clinical trials, 30-200 mg of saffron extract daily was the usual dosage. These studies did not report any notable adverse events in terms of clinically assessed safety. In mice, 4.1 g/kg of saffron administered orally is the acute fatal dose. There have been reports of saffron rates having a teratogenic effect on pregnant saffron field workers. Consequently, using saffron supplements while pregnant is not advised.^[12]

Saffron's toxicological profile raises safety concerns, despite new evidence from recent research supporting its usage in treating depression. However, according to the dosages employed in the clinical trials thus far, saffron may help reduce depression and does not have noticeably more negative effects on non-pregnant people than it would in the absence of treatment.^[12]

Mellisa officinalis (Lemon Balm)

Paper herb Mellisa officinalis, a perennial plant in the Lamiaceae family, is a well-liked herb with a variety of medicinal uses. It is said that a significant amount of active chemicals, such as rosmarinic acid, are what provide lemon balm its overall health benefits. Melissa officinalis possesses antidepressant, antimicrobial, anti-inflammatory, and antioxidant properties. In addition to ophthalmology, gynecology, oncology, gastrointestinal, and cardiology, it can be used to treat sleep disorders, neurodegenerative diseases, and obesity. The literature on Melissa officinalis's chemical makeup and potential use in both medicine and functional foods is included in the review. Additionally, a summary of the herb's adverse effects and contraindications was provided.^[14]

Figure 11:Flower of melissa officinalis L.

It is found natively throughout west Asia and the Mediterranean. Furthermore, it is widely grown in North America and Europe. Mellisa, also known as lemon balm, balm, or common balm mint, is a herb that is prized for its distinctive lemon flavor and scent. Notes on lemon balm date back to ancient times, when Hippocrates and Dioskurides were among the first to describe it. Avicenna (980–1037) suggested it to fortify the heart throughout the Middle Ages, while Paracelsus (1493–1541) made "the elixirs of life" with lemon balm. Melissa officinalis has long been recognized for its ability to prevent baldness, strengthen the weak, and restore youth. Lemon balm leaves, herbs, and essential oil are utilized in herbal medicine. In addition to its medical use, Melissa officinalis is becoming more and more popular as an ingredient in functional foods and supplements because of its many health-promoting qualities. A compilation of the most recent information on lemon balm's medicinal qualities will make it easier to use it in culinary products as well. ^[14]

In Iran, this plant is commonly found in the provinces of Tehran, Golestan, Azarbayjan, Lorestan, and Kermanshah. It is known as "Badranjboyeh." The portions of the plant that are utilized as medicine are the top aerial section and dried or fresh leaves. [17] Lemon balm has long been utilized for a variety of medicinal conditions, including tonic antispasmodic, carminative, diaphoretic, surgical wound dressing, sedative-hypnotic, memory-boosting, and headache relief from stress. Currently, it is used as an antiviral to promote the healing of herpes simplex cold sores and as a sedative-hypnotic. Lemon balm has also been used in Iranian traditional medicine to cure sadness, loss of enthusiasm and energy, and irritability and anxiousness in young girls and women. ^[15]

Melissa officinalis has a lemony scent and flavor and includes volatile oil containing citral. Lemon balm's therapeutic use dates back to "De Media," which was written between 50 and 80 B.C. During the Middle Ages, it was used as a medicinal agent in European nations on the advice of Paracel- sus. It has been presented as a revitalizing component and has been suggested as a successful remedy for disorders of the neurological system. Recent research also suggests that lemon balm has antibacterial, behavioral-modifying, and spasmolytic qualities. Because of its calming properties, lemon balm is said to help with sleep disturbances. It works well to lessen problems of the nerve system.^[16]

Hypericum perforatum (St. John's Wort)

Hypericum perforatum, also known as St. John's wort (SJW), is the most widely used complementary medicine (CM) for depression self-treatment.One It is also frequently used to treat self-described worry and tension. According to a community-based survey conducted in Australia, for instance, about 3% of people sought CAM for anxiety or depression, with SJW being the most common option. Participants frequently sought therapy from multiple CAMs. ^[18]It bears little yellow blooms with five petals and can reach a height of one meter. The plant, which is frequently seen in fields and by the sides of roads, is well-known for its capacity to thrive in a variety of environments, including wetlands and dry pastures. Originally from Europe, this herb is now found in many parts of the world.^[20]

According to a recent Cochrane systematic analysis, SJW was just as effective as prescription antidepressant drugs (AD) and better than a placebo overall for those with mild to moderately severe depressive symptoms. Because SJW has fewer side effects than ADs, it's a viable substitute for pharmaceutical intervention.^[18]

Figure 12: Flower of Hypericum perforatum

For ages, traditional medicine has utilized Hypericum perforatum (St. John's wort) to treat depression. The plant, which grows widely along roadsides and in meadows, is known as St. John's wort because it blooms around the feast day of John the Baptist, which is June 24. When crushed, the bright yellow, five-petaled blossom, which resembles a halo, releases a red liquid that early Christians believed to be the blood of their beloved St. John.^[19]

These days, mild to moderate depression is frequently treated with St. John's wort extract. In terms of energy, it eliminates toxins and heat from the liver while restoring and uplifting the "Vital Spirit." I frequently describe the plant as a mood stabilizer, stress reducer, and neurological adaptogen.^[19]

Numerous bioactive substances, such as hypericin, hyperforin, and flavonoids like quercetin, rutin, and kaempferol, are found in St. John's wort. The primary components thought to be in charge of the antidepressant action are hypericin and hyperforin. A photosensitive substance called hypericin is thought to prevent the brain from reabsorbing some neurotransmitters, including noradrenaline, serotonin, and dopamine. However, it has been demonstrated that hyperforin raises these neurotransmitter levels in the brain, improving mood.^[20]

Another class of naturally occurring bioactive substances included in St. John's wort are flavonoids. It has been demonstrated that flavonoids have several positive health effects, such as anti-inflammatory and antioxidant capabilities. Flavonoids have antioxidant properties because they can scavenge free radicals, which are unstable chemicals that can harm cells and tissues through oxidative damage. The body normally produces free radicals as a byproduct of metabolism, but they can also be created by outside sources like radiation, pollution, and cigarette smoke. Free radicals can harm DNA, proteins, and other cellular constituents when they build up in the body, which can result in a number of health issues like cancer, heart disease, and aging.^[20]

REFERENCES

1. Tiwari. N, Mishra. A Bhatt.G&Chaudhary.A “evaluation of antistress potentials of Negundin A from vitex negundo in acute stress induced mice” European Journal of medicine plant (2015) 1-8.
2. Kothari.s, Minda. S & S. D. Tonpay “anxiolytic and antidepressant activities of methanol extract of aegle marmelos leaves in mice”Indian J PhysiolPharmacol 2010; 54 (4) : 318–328.
3. Sharma K, Akansha, Chauhan E.S “pharmacological and therapeutic potential of vitex negundo (nirgundi): a review” International Journal of Scientific Research and Review 2018;ISSN NO: 2279-543X.
4. Aswar M.K, Abhijeet A. Bidkar1, Kishore N. Gujar 2, Tanay G. Athawale “Anxiolytic like effects of leaves extract of Vitex negundo (L) (fam: -verbaceae) in elevated plus maze test”journal of natural remedies (2012) 141-15.
5. Elayaraja.A, Shaik A.R, Phani K.K, “Anti-anxiety activity of hydro alcoholic extract of Scoparia dulcis Linn. assessed using different experimental anxiety models in rodents” International Journal of Pharmacological Research (2015) ISSN: 2277-3312.
6. Gulhane .H Misra A.K, Reddy P, Pandey.D,Gulhane.R Verma S.K“effects of piper bettle leaves (paan) extract as anti-depressant and anti-anxiety in experimental animals” Mintage journal of Pharmaceutical & Medical Sciences(2015) 12-15.
7. Khanum.F and Razack.S “Anxiety- Herbal Treatment: A Review” Research and Reviews in Biomedicine and Biotechnology (2010), 71-89.
8. Yadav S.K “Antidepressant like effects of hydro ethanolic extract of Chenopodium Album on cums induced depression in mice”, world journal of pharmaceutical research(2021)2125-2137.
9. Sharma. A, Kaur.S, Shri.R, “Evaluation of antidepressant activity of Chenopodium Album extracts and fractions in mice”, international journal of pharmaceutical sciences and research (2021)2707-2715.
10. Singh. S, Gupta.R, “Ethno-pharnacological activities of some important medicinal plants on mental health” Journal of pharmaceutical technology research and management (2024) 1-13.
11. Kenda.M, Glavac N.K, Nagy.M and Dolenc M.S, “Medicinal plants used for anxiety,Depression,or Stress treatment” MDPI journal(2022) 1-19.
12. Hosseinzadeh.H, Motamedshariaty.V and Hadizadeh.F, “antidepressant effect of kaempferol, a constituent of saffron (crocus sativus) petal, in mice and rats” Pharmacologyonline 2 (2007) 367-370.
13. Mahapatra.D, Beniwal.AandDas.M, “Therapeutic Effects of Winter Greens”Just agriculture (2023) 300-305.
14. Emamghoreishi M., Talebianpour M.S., “Antidepressant effect of Melissa officinalis in the forced swimming test” Daru journal of pharmaceutical science(2009) 42-47.
15. Khodaei M.K, NoorbalaA.A, Yarani.R, Emadi.F,Emaratkar.E, Faghihzadeh.S,Parsian.Z, Alijaniha.F, Kamalinejad.M and Naseri.M, “A double-blind, randomized pilot study for comparison of Melissa officinalis L. and Lavandula angustifolia Mill. with Fluoxetine for the treatment of depression” BMC journal (2020) 2-9.
16. Namjou.A, Yazdani.N, abbasi.E and Kopaei M.R, “TheAntidepressantActivity of Matricaria chamomilla andMelissa officinalis Ethanolic Extracts in Non-Reserpinized and Reserpinized Balb/C Mice”Jundishapur journal of microbiology(2018) 1-6.
17. ?wi?der.K, Startek.K, Wijaya C.H, “The therapeutic properties of Lemon balm (Melissa officinalis L.): Reviewing novel findings and medical indications” Journal of Applied Botany and Food Quality (2019) 327-335.
18. Pirotta.M, Willis.K, Carter.M, Forsdike.K, Newton.D, Gunn.J, “Less like a drug than a drug’: The use of St John's wort among people who self-identify as having depression and/or anxiety symptoms “Complementary therapies in medicine (2014) 870-876.
19.  Yance.D, “Antidepressants May Be No More Effective Than Placebo: But What About St. John’s Wort and Other Herbal Medicines” Lancet journal (2019).
20. Rychlewski. P, Kamgar.E, SzkudlarzS.M, Kowalczewski P.Land  Zembrz.J, “Determination of the contents of bioactive compounds in St. John’s wort (Hypericum perforatum): Comparison of commercial and wild samples”deg journal (2023).