# Medicinal Plants for Major Depressive Disorder

**Authors:** Amanda Gollo Bertollo, Luiza Spohr, Ana Élica Bearzi, Kelli Maria Kreuz, Zuleide Maria Ignácio

PMC · DOI: 10.3390/brainsci16020223 · Brain Sciences · 2026-02-13

## TL;DR

Medicinal plants may help treat depression by affecting brain chemicals and reducing inflammation, but their use needs careful safety monitoring.

## Contribution

This review highlights the mechanisms and safety concerns of medicinal plants for treating Major Depressive Disorder.

## Key findings

- Medicinal plants influence neurotransmitters, neuroplasticity, and the HPA axis to treat MDD.
- Bioactive compounds in plants reduce neuroinflammation and oxidative stress.
- Herb–drug interactions and hepatotoxicity risks must be considered for clinical use.

## Abstract

What are the main findings?
Medicinal plants modulate neurotransmitters, neuroplasticity, and the HPA axis to treat MDD.Some bioactive compounds reduce neuroinflammation and oxidative stress by inhibiting pro-inflammatory cytokines.

Medicinal plants modulate neurotransmitters, neuroplasticity, and the HPA axis to treat MDD.

Some bioactive compounds reduce neuroinflammation and oxidative stress by inhibiting pro-inflammatory cytokines.

What are the implications of the main findings?
Some plants offer promising therapeutic or adjunct alternatives for MDD.Clinical integration requires rigorous attention to safety regarding hepatotoxicity risks and significant herb–drug interactions.

Some plants offer promising therapeutic or adjunct alternatives for MDD.

Clinical integration requires rigorous attention to safety regarding hepatotoxicity risks and significant herb–drug interactions.

Major Depressive Disorder (MDD) is a severe, chronic illness for which conventional treatments often show limited efficacy and side effects, driving a renewed interest in traditional medicinal plants. The therapeutic promise of these plants lies in their multi-targeted action, influencing neurotransmitter systems, modulating neuroinflammation and oxidative stress, impacting neuroplasticity, and regulating the Hypothalamic–Pituitary–Adrenal (HPA) axis. Despite their clinical potential, the use of medicinal plants is associated with challenges, including complex pharmacokinetics, significant adverse effects, and the risk of herb–drug interactions, alongside concerns regarding standardization and quality control. This manuscript aims to examine the therapeutic potential of key medicinal plants for managing MDD, including Hypericum perforatum, Rhodiola rosea, Melissa officinalis, Passiflora incarnata, Valeriana officinalis, and Cannabis sativa. Additionally, the review addresses emerging candidates such as Curcuma longa, Withania somnifera, Panax ginseng and Centella asiatica. By focusing on their mechanisms of action, pharmacokinetics, and associated risks, this review provides a more comprehensive understanding of their role in modern psychiatric care.

## Linked entities

- **Diseases:** Major Depressive Disorder (MONDO:0002009)
- **Species:** Hypericum perforatum (taxon 65561), Rhodiola rosea (taxon 203015), Melissa officinalis (taxon 39338), Passiflora incarnata (taxon 159425), Valeriana officinalis (taxon 19953), Cannabis sativa (taxon 3483), Curcuma longa (taxon 136217), Withania somnifera (taxon 126910), Panax ginseng (taxon 4054), Centella asiatica (taxon 48106)

## Full-text entities

- **Genes:** ABCB1 (ATP binding cassette subfamily B member 1) [NCBI Gene 5243] {aka ABC20, CD243, CLCS, ENPAT, GP170, MDR1}, POMC (proopiomelanocortin) [NCBI Gene 5443] {aka ACTH, CLIP, LPH, MSH, NPP, OBAIRH}, PGP (phosphoglycolate phosphatase) [NCBI Gene 283871] {aka AUM, G3PP, PGPase}, DLG4 (discs large MAGUK scaffold protein 4) [NCBI Gene 1742] {aka MRD62, PSD95, SAP-90, SAP90}, Hcrt (hypocretin) [NCBI Gene 15171] {aka PPOX}, Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, Pomc (pro-opiomelanocortin-alpha) [NCBI Gene 18976] {aka ACTH, BE, Beta-LPH, Clip, Gamma-LPH, Npp}, Bdnf (brain-derived neurotrophic factor) [NCBI Gene 24225], Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Bdnf (brain derived neurotrophic factor) [NCBI Gene 12064], Gsk3b (glycogen synthase kinase 3 beta) [NCBI Gene 56637] {aka 7330414F15Rik, 8430431H08Rik, GSK-3, GSK-3beta, GSK3}, Crh (corticotropin releasing hormone) [NCBI Gene 81648] {aka CRF}, Maoa (monoamine oxidase A) [NCBI Gene 17161] {aka 1110061B18Rik}, Creb1 (cAMP responsive element binding protein 1) [NCBI Gene 12912] {aka 2310001E10Rik, 3526402H21Rik, Creb, Creb-1}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, Htr1a (5-hydroxytryptamine (serotonin) receptor 1A) [NCBI Gene 15550] {aka Gpcr18}, Ntrk2 (neurotrophic tyrosine kinase, receptor, type 2) [NCBI Gene 18212] {aka GP145-TrkB/GP95-TrkB, Tkrb, trk-B, trkB}, NTRK2 (neurotrophic receptor tyrosine kinase 2) [NCBI Gene 4915] {aka DEE58, EIEE58, GP145-TrkB, OBHD, TRKB, trk-B}, Ptgs2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 29527] {aka COX-2, Cox2, PGHS-2, PHS II, Pghs2}, CYP3A4 (cytochrome P450 family 3 subfamily A member 4) [NCBI Gene 1576] {aka CP33, CP34, CYP3A, CYP3A3, CYPIIIA3, CYPIIIA4}, BDNF (brain derived neurotrophic factor) [NCBI Gene 627] {aka ANON2, BULN2}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, UGT1A (UDP glucuronosyltransferase family 1 member A complex locus) [NCBI Gene 7361] {aka GNT1, UGT, UGT1, UGT1A@}, Pgp (phosphoglycolate phosphatase) [NCBI Gene 67078] {aka 1700012G19Rik, AUM, G3PP}, Abat (4-aminobutyrate aminotransferase) [NCBI Gene 81632] {aka Gabat, beta-AlaAT}, Nr3c1 (nuclear receptor subfamily 3, group C, member 1) [NCBI Gene 14815] {aka GR, Grl-1, Grl1}, SYP (synaptophysin) [NCBI Gene 6855] {aka MRX96, MRXSYP, XLID96}, Htr2c (5-hydroxytryptamine (serotonin) receptor 2C) [NCBI Gene 15560] {aka 5-HT-1C, 5-HT-2C, 5-HT1C, 5-HT2C, 5-HT2cR, 5-HTR2C}, Maoa (monoamine oxidase A) [NCBI Gene 29253] {aka Mao}, Crh (corticotropin releasing hormone) [NCBI Gene 12918] {aka CRF, Gm1347}, Nos2 (nitric oxide synthase 2) [NCBI Gene 24599] {aka Nos2a, iNos}, CYP2C19 (cytochrome P450 family 2 subfamily C member 19) [NCBI Gene 1557] {aka CPCJ, CYP2C, CYPIIC17, CYPIIC19, P450C2C, P450IIC19}, Maob (monoamine oxidase B) [NCBI Gene 109731] {aka 6330414K01Rik, MAO-B}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, CYP4F3 (cytochrome P450 family 4 subfamily F member 3) [NCBI Gene 4051] {aka CPF3, CYP4F, CYPIVF3, LTB4H}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}
- **Diseases:** hyperactivity (MESH:D006948), MDD (MESH:D003865), chronic (MESH:D002908), cognitive deficits (MESH:D003072), cerebral hypoxia (MESH:D002534), teratogenicity (MESH:C535542), Depression (MESH:D003866), renal nephropathy (MESH:D007674), neuronal damage (MESH:D009410), sleep deprivation (MESH:D012892), HPA (MESH:D007029), type 2 diabetes mellitus (MESH:D003924), affective disorders (MESH:D019964), liver injury (MESH:D017093), HILI (MESH:D056486), fatigue (MESH:D005221), gastrointestinal (MESH:D005767), tumor (MESH:D009369), neuropsychiatric changes (MESH:D009402), mental disorders (MESH:D001523), insomnia (MESH:D007319), dizziness (MESH:D004244), neuroinflammation (MESH:D000090862), anxiety (MESH:D001007), cytotoxic (MESH:D064420), serotonin syndrome (MESH:D020230), CMS (MESH:D000079225), injury to (MESH:D014947), impairment of liver and cardiac function (MESH:D008107), Inflammatory (MESH:D007249), Parkinson's disease (MESH:D010300), depressive behaviors (MESH:D011596), anhedonia (MESH:D059445)
- **Chemicals:** butanol (MESH:D000440), alcohol (MESH:D000438), alkaloids (MESH:D000470), isorhamnetin (MESH:C047368), indole alkaloids (MESH:D026121), GLU (MESH:D018698), GABA (MESH:D005680), norepinephrine (MESH:D009638), warfarin (MESH:D014859), dopamine (MESH:D004298), N-Methyl-D-Aspartate (MESH:D016202), madecassic acid (MESH:C001669), luteolin (MESH:D047311), cannabinoid (MESH:D002186), heavy metal (MESH:D019216), calcium (MESH:D002118), ROS (MESH:D017382), glycosides (MESH:D006027), AE (MESH:C538178), 5-HT (MESH:D012701), flavonoid (MESH:D005419), valepotriates (MESH:C030127), CBD (MESH:D002185), CPZ (MESH:D002746), vitexin (MESH:C032731), HU-210 (MESH:C062018), fluoxetine (MESH:D005473), ginsenoside Rb1 (MESH:C442759), phospholipid (MESH:D010743), water (MESH:D014867), Endocannabinoid (MESH:D063388), essential oil (MESH:D009822), Hyperforin (MESH:C001654), terpenes (MESH:D013729), LPS (MESH:D008070), lipid (MESH:D008055), sucrose (MESH:D013395), phenolic acids (MESH:C017616), quercitrin (MESH:C012526), cortisol (MESH:D006854), Rhodioloside (MESH:C009172), ginsenoside Rg1 (MESH:C035054), Delta-9-tetrahydrocannabinol (MESH:D013759), quercetin (MESH:D011794), escitalopram (MESH:D000089983), madecassoside (MESH:C093443), valerenic acid (MESH:C037133), sertraline (MESH:D020280), hypericin (MESH:C004965), glucuronates (MESH:D005965), paroxetine (MESH:D017374), asiaticoside (MESH:C004446), withaferin A (MESH:C009684), MDA (MESH:D008315), corticosterone (MESH:D003345), triterpenes (MESH:D014315), piperine (MESH:C008922), Curcumin (MESH:D003474), Ginsenoside Rb3 (MESH:C044463), rosavin (MESH:C529148)
- **Species:** Salix aegyptiaca (species) [taxon 543723], Panax ginseng (Asiatic ginseng, species) [taxon 4054], Drosophila melanogaster (fruit fly, species) [taxon 7227], Passiflora foetida (species) [taxon 159421], Cinnamomum verum (Ceylon cinnamon, species) [taxon 128608], Cannabis sativa (species) [taxon 3483], Curcuma longa (turmeric, species) [taxon 136217], Hypericum perforatum (species) [taxon 65561], Citrus x aurantium (bitter orange, species) [taxon 43166], Mus musculus (house mouse, species) [taxon 10090], Withania somnifera (ashwagandha, species) [taxon 126910], Rattus norvegicus (brown rat, species) [taxon 10116], Viola odorata (species) [taxon 97441], Passiflora caerulea (species) [taxon 159428], Homo sapiens (human, species) [taxon 9606], Rodentia (rodent, order) [taxon 9989], Centella asiatica (Asiatic pennywort, species) [taxon 48106], Valeriana officinalis (common valerian, species) [taxon 19953], Rhodiola rosea (rose-root, species) [taxon 203015], Lavandula angustifolia (lavender, species) [taxon 39329], Passiflora incarnata (species) [taxon 159425], Melissa officinalis (common balm, species) [taxon 39338]
- **Cell lines:** AtT20 — Mus musculus (Mouse), Mouse pituitary gland neoplasms, Cancer cell line (CVCL_2300)

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12938823/full.md

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12938823/full.md

## References

237 references — full list in the complete paper: https://tomesphere.com/paper/PMC12938823/full.md

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Source: https://tomesphere.com/paper/PMC12938823