INTRODUCTION:

Depression, a prevalent mental health disorder, continues on global well-being, affecting millions of individuals across diverse demographics. Depressive disorders are some of the most pervasive, impairing and costly illnesses, having recently been estimated to affect more than 246 million people worldwide.^1,2,3

Although these conditions are classified by subtype and severity, still, they are often characterized by a lack of enjoyment or interest or a depressed mood, often accompanied by symptoms such as, low self-esteem, indecision or difficulty focusing or thinking, exhaustion, psychomotor agitation or retardation, change in appetite, insomnia or hypersomnia, mood swings, and, in the worst cases, frequent thoughts of death or suicidal ideation 1. Depression frequently coexists with other mental health disorders. Peoples who already have an anxiety disorder have a significantly increased risk of developing a depressive disorder.^4,5,6,7 Additionally, there is a higher incidence of cardiovascular, pulmonary, and gastrointestinal issues in patients with anxiety disorders⁸. Psychological and pharmaceutical treatments are available for treating anxiety and related disorders; the decision is based on several patient-related aspects, including the severity of the illness, previous therapy, comorbid disorders, patient desire and motivation etc⁵. Because they are generally safe and better tolerated than other treatments, the first-line pharmacological options are similar to those prescribed for depressive disorders: either selective serotonin reuptake inhibitors (escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) or serotonin and norepinephrine reuptake inhibitors (duloxetine, venlafaxine).^5,8 Moreover, noradrenergic and particular serotonergic antidepressants, tricyclic antidepressants, monoamine oxidase inhibitors, and reversible inhibitors of monoamine oxidase A can be considered.^5,7 Adjunctive short-term therapy may involve benzodiazepines, but only as a short-term therapy because they can lead to dependency, sedation, and cognitive impairment (especially with prolonged use). More recent reports suggest that depression is linked to natural stressors, including changes in serum levels of triglycerides, glucose, cholesterol, and clotting factors.⁹

Neurobiological mechanisms of Depression and anxiety:

Many factors, including psychological, environmental, and biological factors, influence the development of depression. Environmental factors can cause chronic stress, which can lead to depression, work problems, and family disagreements. The onset and maintenance of depression are influenced by multiple neurobiological processes, including neurotrophic factors, brain circuits, and neurotransmitter systems. By understanding the genesis and persistence of depression how these processes combine to affect neuroplasticity, emotional regulation, and reward processing.

Neurotrophic Factors: Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor that is crucial for neurogenesis, synaptic plasticity, and neuron-glial interactions, which are often disturbed in depression. The neurotrophic hypothesis suggests that shortage in these factors contributes to the pathogenesis of depression, indicating potential therapeutic targets.¹⁰

Neural Circuits: The occurrence of depression symptoms is linked to malfunctions in specific brain circuits, particularly those involved in the dorsal raphe nucleus (DRN), nucleus accumbens (NAc), and ventral tegmental area. (VTA)¹¹. Depression is associated with the amygdala, VMPFC, and DLPFC by functional neuroimaging studies, with DLPFC dysfunction being particularly indicative of the illness¹².

Neurotransmitter Systems: Dopamine, glutamate, and gamma-aminobutyric acid (GABA) are neurotransmitters that act on mood and emotional reactions and are exposed to the neurobiological underpinnings of depression. It shows that noninvasive brain stimulation methods that target these neurotransmitters systems can improve depressed symptoms and increase neuroplasticity. While these processes shed light on the complexity of depression, it is important to recognize that personal experiences and contextual elements play a major role in how the illness presents and persists¹³.

Current therapeutic approaches to treat Depression and anxiety and their limitations: According to the World Health Organization (WHO), depression is a leading cause of disability worldwide, with an estimated 280 million people grappling with its debilitating effects as of the most recent global health assessment¹⁴. A variety of pharmacological and non-pharmacological techniques are used in today's therapeutic approaches to treat anxiety and depression. Many techniques seek to treat the intricate neurological foundations of many conditions, such as neuroinflammation and neurotransmitter abnormalities. The main therapeutic modalities now in use are described in the sections that follow.

Pharmacologic agents:

· Antidepressants: Antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs), are often prescribed. Even though some patients may not respond well, they can still provide benefits^15,16.

· Emerging Therapy: In recent decades, the MA (Monoamine) theory of depression has been lost due to the rapid antidepressant effects of sub anesthetic doses of ketamine/esketamine¹⁷. Numerous studies have highlighted the use of anti-inflammatory drugs as potential treatments for major depressive disorder (MDD) due to their ability to reduce depressive symptoms¹⁸.

· Anti-inflammatory agents: Inflammation may be a major factor in the pathophysiology of depression is the foundation of this new therapy strategy. Anti-inflammatory drugs have emphasized as possible major depressive disorder (MDD) treatments because of numerous studies showing how well they reduce depressed symptoms. Anti-inflammatory agents like non-steroidal anti-inflammatory drugs, omega-3 fatty acids, statins, and minocycline have been tried in depression in several RCTs (randomized controlled trials)¹⁹.

· Gamma-aminobutyric acid (GABA) modulators: The primary inhibitory neurotransmitter in the central nervous system, GABA, is crucial for regulating neuronal excitability. Evidence indicates that depression may cause changes to the GABAergic system, which would lead to an imbalance between excitatory and inhibitory neurotransmission²⁰. Brexanolone, a neurosteroid and allosteric modulator of GABA-A receptors, has drawn interest as a potential treatment for depression.

· Psychedelics: The induction of atypical mental states, also referred to as "trips" or "psychedelic experiences," and a perceived "expansion of consciousness" are the primary effects of psychedelics, a subclass of hallucinogenic medications. Many societies have historically used psychedelics for therapeutic, spiritual, and religious purposes. Indigenous peoples have been using drugs like psilocybin-containing mushrooms in rituals for ages ^{21, 22}.

· Probiotics, prebiotics, and anti-inflammatory diet: Recent studies in nutritional psychiatry have brought attention to the possible impact of gut microbes on mental health, particularly the gut-brain axis—the two-way communication between the gut and the brain. Probiotics and prebiotics, two crucial components of this intricate system, have attracted attention due to their potential to lessen the symptoms of depression ²³.

Nanotechnology in mental health management:

An inventive method for treating mental health conditions, including depression, is nanotechnology. Nanotechnology overcomes major drawbacks of conventional pharmacotherapy, including delayed onset and adverse effects, by improving drug delivery mechanisms. Promising approaches to better treatment alternatives are provided by this cutting-edge field.

· Blood-Brain Barrier (BBB) Penetration: Nanoparticles can be engineered to increase the bioavailability of psychotropic drugs, facilitating their passage through the BBB ²⁴.

· Targeted Release: Self-immolative nanocapsules delivering serotonin and catalase straight to the brain provide a promising development in targeted drug delivery systems, especially for improving treatment efficacy in neurological diseases. These nanocapsules are designed to efficiently cross the blood-brain barrier (BBB), enabling targeted therapy that reduces neuroinflammation and enhances mood control ²⁵.

· Personalized Medicine

· Tailored Treatments: The developments in the treatment of depression are possible with personalized medicine, especially when it comes to the use of nanotechnology. By modifying treatments for each patient according to their genetic, biochemical, and environmental characteristics, this method may improve therapy effectiveness and lessen adverse effects²⁶.

Gene Therapy Applications: Gene therapy may provide more individualized and efficient treatment choices by focusing on these genetic components. Due to the limitations of the available pharmaceutical treatments for depression, gene therapy offers a viable alternative. According to research, the pathophysiology of depression is significantly influenced by genetic variables, including serotonin signaling genes and the P11 protein. Despite these advancements, challenges remain regarding the safety and long-term effects of nanotechnology in clinical settings. Continued research is essential to fully realize its potential in mental health management ²⁷.

Plant-derived Nanoparticles:

The use of plant-derived nanoparticles (PDNPs) as innovative therapies for neurological disorders is growing in popularity. These plant-derived nanoparticles boost drug distribution across the blood-brain barrier (BBB) and increase the effective management therapies for diseases including Parkinson's and Alzheimer's. Their main advantages and uses are described in the sections that follow.

· Targeted Action: PDNPs can encapsulate hydrophilic or lipophilic drugs, strengthening their stability and bioavailability²⁸.

Crossing the BBB: In addition to their nanoscale size, therapeutic drugs can be efficiently transported across the blood-brain barrier and delivered to the afflicted areas of the brain^{29, 30}.

· Bioactive Compounds: Compounds possessing anti-inflammatory and antioxidant activities, which include quercetin and curcumin, are frequently found in PDNPs and are essential for the treatment of neurodegenerative illnesses.

· Reduced Toxicity: In addition to their regulated release methods, these nanoparticles are less hazardous than conventional formulations.

Although their potential, issues including mass manufacturing and legal restrictions still need to be solved, therefore further study is required to maximize their clinical uses³¹.

Table:1 Plant-Based Nanotechnology in Depression and Anxiety Management

Herbal Source	Active Constituents	Nanocarrier Type	Therapeutic Action	References
*Curcuma longa* (Turmeric)	Curcumin	Solid Lipid Nanoparticles, Nanoemulsion	Antioxidant, anti-inflammatory, antidepressant	Prasad et al., 2014; Yallapu et al., 2012
*Withania somnifera* (Ashwagandha)	Withanolides	Polymeric Nanoparticles, Liposomes	Adaptogen, anxiolytic	Kulkarni & Dhir, 2008; Devkar et al., 2020
*Bacopa monnieri* (Bramhi)	Bacosides	Nanostructured Lipid Carriers	Cognitive enhancement, anxiolytic	Singh & Dhawan, 1997; Sharma et al., 2020
*Hypericum perforatum* (St. John's Wort)	Hyperforin, Hypericin	Nanoemulsion, SLNs	Antidepressant (SSRI-like)	Butterweck & Schmidt, 2007
*Valeriana officinalis*	Valerenic acid	Liposomes, Nanosuspension	Sedative, anxiolytic	Fernández-San-Martín et al., 2010
*Camellia sinensis* (Green Tea)	EGCG (Epigallocatechin gallate)	Lipid-based Nanoparticles	Neuroprotective, antioxidant	Kuriyama et al., 2006; Fang et al., 2006
*Rhodiola rosea*	Salidroside, Rosavin	Polymeric Nanoparticles	Adaptogen, mood stabilizer	Panossian et al., 2010
*Passiflora incarnata*	Vitexin, Isovitexin	Nanoemulsion	Mild sedative, anxiolytic	Miroddi et al., 2013
*Ginkgo biloba*	Ginkgolides, Bilobalide	Solid Lipid Nanoparticles	Antioxidant, anti-anxiety	Singh et al., 2010
*Ocimum sanctum* (Tulsi)	Eugenol, Rosmarinic acid	Liposomes, Nanoemulsions	Anti-stress, anxiolytic	Mondal et al., 2009; Prakash & Gupta, 2005
*Zingiber officinale* (Ginger)	Gingerols, Shogaols	Niosomes, silver nanoparticles	Neuroprotective, antioxidant	Ali et al., 2018 (J Food Biochem)
*Ficus religiosa* (Peepal)	Flavonoids and Sterols	Extract	Anxiolytic	Bhat et al.,2024

Nanotechnology derived from plants has become a cutting-edge method of treating anxiety and depression. The potential of medication delivery systems based on nanotechnology for the treatment of illnesses of the central nervous system has been brought to light by recent research³². Furthermore, the microbiome and the gut-brain axis have been found to be important determinants of anxiety and depression, paving the door for psychobiotics as possible treatments³³. Intranasal drug delivery of nanomedicines, including plant-derived compounds, has shown promise in the treatment of neuropsychiatric disorders³⁴. In addition, developments in nanotechnology have produced nano-based tools for mental disease diagnosis, opening up new therapeutic options³⁵. Novel drug delivery systems for antidepressant active ingredients have opened up new avenues to enhance the therapeutic efficacy of depression treatment³⁶. Nanotechnology-based strategies have also demonstrated potential in reducing infectious and inflammatory conditions, highlighting the versatility of this approach in addressing various health issues³⁷. Additionally, the potential of medicinal plants to aid in the treatment of stress, anxiety, and depression has been acknowledged³⁸. Irrigation management has been investigated using plant-based solutions and remote sensing technologies, demonstrating the convergence of advances in nanotechnology and plant science³⁹. Furthermore, in an effort to address issues such the poor absorption and metabolism of traditional medications, nano and microemulsions have been studied for the treatment of anxiety and depression. In conclusion, the treatment of anxiety and depression could be completely transformed by combining cutting-edge drug delivery methods with plant-based nanotechnology. In order to enhance the safety, stability, and effectiveness of nanotechnology-based therapies in mental health care, more study is required³⁶. The potential for innovative and successful strategies to treat neuropsychiatric illnesses is highlighted by the investigation of plant-derived chemicals and nanomedicines³⁴.

Innovative Formulations for Managing Depression and Anxiety:

Nutraceuticals are sophisticated medication delivery systems, and precision medicines are just a few of the creative formulations for treating anxiety and depression. Enhancing therapeutic efficacy, increasing bioavailability, and customizing treatments to meet the needs of each patient are the goals of these tactics.

Nutraceutical Ingredients

· Ingredients: Niacin, magnesium, ashwagandha, and St. John's Wort are effective nutraceuticals that have demonstrated promise in reducing anxiety and depressive symptoms⁴⁰.

· Mechanism: By changing neurotransmitter levels and lowering stress reactions, these elements cooperate.

· Advanced Systems for Drug Delivery

Nano and Microemulsions: These formulations can raise the strength of antidepressant medications by up to 20,270 times while also greatly improving their solubility and absorption⁴¹.

Pharmacokinetics: Research on animals has shown improved systemic availability and brain targeting, suggesting the possibility of successful treatment outcomes.

· Methods of Precision Medicine Addressing Stress Hormones: A precision psychiatry approach uses specialized receptor blockers to target individual patient profiles, especially those with hypothalamic-pituitary-adrenocortical (HPA) overactivity⁴².

· Diagnostic Innovations: By identifying those who would benefit from focused therapy, gene-based diagnostics can help replace the "one-size-fits-all" approach.

Despite the potential of these novel formulations, obstacles still stand in the way of their broad adoption and acceptance in clinical practice, calling for more investigation and verification.

Therapeutic Benefits of Plant-Based Nanotechnology in Mental Health Management: Plant-based nanotechnology offers promising therapeutic benefits in mental health management, particularly in treating neurological disorders and depression. This innovative strategy blends the traditional usage of medicinal herbs with modern nanotechnology to optimize drug administration, bioavailability, and efficacy. By encapsulating plant-derived substances within nanoparticles, these systems can efficiently pass physiological barriers, such as the blood-brain barrier, and target specific locations in the brain, hence enhancing therapy outcomes for mental health issues. The therapeutic advantages of plant-based nanotechnology in the management of mental health are covered in detail in the sections that follow.

Enhanced Drug Delivery and Bioavailability:

Plants derived Nanoparticles such as curcumin and quercetin, improve the delivery and stability of therapeutic agents, allowing their better penetration into the central nervous system⁴³. The herbal extracts encapsulated within nanoparticles enhances their bioavailability and targeted delivery, addressing limitations of traditional herbal medicine.

Treatment of Neurological Disorders:

Herbal nanosystems have demonstrated potential effectiveness in treating neurological illnesses by enhancing pharmacokinetics and minimizing side effects of drugs. By delivering therapeutic compounds to the brain selectively, engineered nanoparticles can get beyond the blood-brain barrier⁴³.

Management of Depression:

When nanoparticles formulated with Plant-derived polyphenols, such as berberine and curcumin, have demonstrated antidepressant activity, promoting neuronal cell survival and modulating neurotransmitters. Green synthesized nanoparticles from medicinal plants exhibit considerable efficacy in managing depression, offering an alternative to conventional antidepressants with fewer side effects.

Challenges and Future Perspectives:

Herbal medicines have a long-standing legacy of being used globally for their therapeuticbenefits. Despite the challenges in establishing their pharmacological basis, advancements in biotechnology and nanotechnology are enhancing their efficacy and safety⁴⁴.

The integration of plant-based nanotechnology in managing depression and anxiety presents innovative solutions while also facing significant challenges. This strategy makes use of nanotechnology and plant-derived chemicals' medicinal potential to improve medicine delivery and effectiveness. The main developments, difficulties, and potential directions in this area are described in the sections that follow.

Innovations in Plant-Based Nanotechnology: Polyphenol Efficacy:

Plant polyphenols, such as curcumin and berberine, have shown antidepressant properties and can be formulated into nanoparticles to enhance their bioavailability and therapeutic effects⁴⁵.

Nanoemulsions: These formulations can increase the solubility and brain targeting of antidepressants, improving their absorption and efficacy by up to 20,270-folds³⁸.

Intranasal Delivery: Drug delivery efficiency is increased by using intranasal routes, which enable direct transfer to the brain and avoid the blood-brain barrier^46-50.

Challenges in Implementation Bioavailability Issues: Despite advancements, many antidepressants still face challenges related to low bioavailability and high metabolism^41,48.

CONCLUSION:

Plant-based nanotechnology presents a groundbreaking approach to depression and anxiety management by improving the bioavailability, targeted delivery, and therapeutic potential of natural compounds. This innovative field has the potential to offer safer, more effective and holistic alternatives to conventional pharmacological treatments. With continued research, advancements in nanotechnology could transform mental health care, providing patients with novel, plant-derived therapeutic options that minimize side effects and maximize efficacy.

REFERENCES:

1. American Psychological Association. Clinical practice guideline for the treatment of depression across three age cohorts. Washington (DC): American Psychological Association; 2019.

2. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018; 392:1789–858.

3. Zhao YF, Verkhratsky A, Tang Y, Illes P. Astrocytes and major depression: the purinergic avenue. Neuropharmacology, 2022; 220: 109252.

4. Kircanski K, Joormann J, Gotlib IH. Cognitive aspects of depression. Wiley Interdiscip Rev Cogn Sci. 2012;3(3):301–13.

5. Katzman MA, Bleau P, Blier P, Chokka P, Kjernisted K, Van Ameringen M, et al. Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC Psychiatry. 2014;14(Suppl 1)\:S1.

6. Hu P, Lu Y, Pan B-X, Zhang W-H. New insights into the pivotal role of the amygdala in inflammation-related depression and anxiety disorder. Int J Mol Sci. 2022;23(18):11076.

7. Penninx BW, Pine DS, Holmes EA, Reif A. Anxiety disorders. Lancet. 2021; 397(10277): 914–27.

8. Nasir M, Trujillo D, Levine J, Dwyer JB, Rupp ZW, Bloch MH. Glutamate systems in DSM-5 anxiety disorders: their role and a review of glutamate and GABA psychopharmacology. Front Psychiatry. 2020; 11:548505.

9. Fathinezhad Z, Sewell RDE, Lorigooini Z, Rafieian-Kopaei M. Depression and treatment with effective herbs. Curr Pharm Des. 2019;25(7):738–45.

10. Yasenyavskaya LA, Tsibizova MA, Samotrueva MA. Neurotrophic hypothesis of development of depression. Fiziol Cheloveka. 2024;50(2):142–52. doi:10.31857/s013116462402012

11. Gong W. Research progress on neural circuit mechanisms of depression. BIO Web Conf. 2023; 60:02021. doi:10.1051/bioconf/20236002021

12. Liu YZ, Liu Y, Lin W, He ZH, Zhang DD, Guan Q, et al. The core neural mechanisms underlying depression disorder: a meta-analysis of fMRI studies. Sci Sin Vitae. 2015; 45(12): 1214–23. doi:10.1360/N052015-00164

13. Bulubas L, Mezger E, Keeser D, Padberg F, Brunoni AR. Novel neuromodulatory approaches for depression: neurobiological mechanisms. In: Neuromodulation in psychiatry. 2019. p. 347–60. doi:10.1016/B978-0-12-813333-0.00031-7

14. World Health Organization. Depressive disorder (depression) \[Internet]. Geneva: WHO; 2024 \[cited 2024]. Available from: [https://www.who.int/news-room/fact-sheets/detail/depression] (https://www.who.int/news-room/fact-sheets/detail/depression)

15. Ajmire PP, Mirchapure VG. Exploring the neuropharmacological terrain of depression and anxiety: mechanisms, therapies, and future avenues. Int J Innov Sci Res Technol. 2024; 1065–72. doi:10.38124/ijisrt/ijisrt24sep941

16. Panigrahy A. Therapeutic approaches for treatment and management of depressive disorder: a comprehensive review. Int J Pharm Qual Assur. 2024; 15(2): 1040–7. doi:10.25258/ijpqa.15.2.75

17. Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000;47(4):351–4.

18. Jagtiani A, Khurana H, Malhotra N. Comparison of efficacy of ketamine versus thiopentone-assisted modified electroconvulsive therapy in major depression. Indian J Psychiatry. 2019; 61(3): 258–64.

19. Felger JC, Lotrich FE. Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications. Neuroscience. 2013; 246:199–229.

20. Cutler AJ, Mattingly GW, Maletic V. Understanding the mechanism of action and clinical effects of neuroactive steroids and GABAergic compounds in major depressive disorder. Transl Psychiatry. 2023; 13: 228.

21. Aghajanian G. Serotonin and hallucinogens. Neuropsychopharmacology. 1999; 21(2 Suppl): 16S–23S. doi:10.1016/S0893-133X(98)00135-3

22. Millière R, Carhart-Harris RL, Roseman L, Trautwein FM, Berkovich-Ohana A. Psychedelics, meditation, and self-consciousness. Front Psychol. 2018; 9: 1475. doi:10.3389/fpsyg.2018.01475

23. Saravanan D, Khatoon BS, Winner GJ Sr. Unraveling the interplay: exploring the links between gut microbiota, obesity, and psychological outcomes. Cureus. 2023; 15: e49271.

24. Fond G, Miot S. La nanopsychiatrie: le rôle potentiel des nanotechnologies dans l’avenir de la psychiatrie. Une revue systématique. Encephale. 2013; 39(4): 252–7. doi:10.1016/j.encep.2013.02.002

25. Liu Z, Chen B, Xiang S, Hu S. Self-immolative nanocapsules precisely regulate depressive neuronal microenvironment for synergistic antidepression therapy. J Nanobiotechnol. 2023; 21: 2008–9. doi:10.1186/s12951-023-02008-9

26. Yadav K, Rani A, Tyagi AK, Babu MR. The application of nanotechnology and nanomaterials in depression: an updated review. Precis Nanomed. 2023. doi:10.33218/001c.82215

27. Rehman S, Nabi B, Pottoo FH, Baboota S, Ali J. Nanoparticle based gene therapy approach: a pioneering rebellion in the management of psychiatric disorders. Curr Gene Ther. 2020; 20(3): 164–73. doi:10.2174/1566523220666200607185903

28. Wang R, Zhang Y, Guo Y, Zeng W, Li J, Wu J, et al. Plant-derived nanovesicles: promising therapeutics and drug delivery nanoplatforms for brain disorders. Fundam Res. 2023. doi: 10.1016/j.fmre.2023.09.007

29. Aspatwar A, Nath R, Bhowmik R, Jesudasan R. Herbal-based nanosystems: a novel drug-delivery treatment procedure against neurodegenerative disorders. ChemRxiv [Preprint]. 2024. doi:10.26434/chemrxiv-2024-hh95h-v2

30. Izadi R, Bahramikia S, Akbari V. Green synthesis of nanoparticles using medicinal plants as an eco-friendly and therapeutic potential approach for neurodegenerative diseases: a comprehensive review. Front Neurosci. 2024. doi:10.3389/fnins.2024.1453499

31. Shah N, Kumari M, Sadhu P, Talele C, Rajput HS, Sapra R. Nano-herbal innovations: precision in therapeutic delivery. J Adv Zool. 2024; 45(1). doi:10.17762/jaz. v45i1.2976

32. Sarris J. Disruptive innovation in psychiatry. Ann N Y Acad Sci. 2022; 1512(1): 5–9. doi:10.1111/nyas.14764

33. Kisku A, Nishad A, Agrawal S, Paliwal R, Datusalia AK, Gupta G, et al. Recent developments in intranasal drug delivery of nanomedicines for the treatment of neuropsychiatric disorders. Front Med. 2024; 1–24.

34. Kumar R, Chhikara BS, Gulia K, Chhillar M. Review of nanotheranostics for molecular mechanisms underlying psychiatric disorders and commensurate nanotherapeutics for neuropsychiatry: the mind knockout. Nanotheranostics. 2021; 5(3): 288–308. doi:10.7150/ntno.49619

35. Huang Y, Guo X, Wu Y, Chen X, Feng L, Xie N, et al. Nanotechnology’s frontier in combatting infectious and inflammatory diseases: prevention and treatment. Signal Transduct Target Ther. 2024; 9:34.

36. Yuan S, Ma T, Zhang YN, et al. Novel drug delivery strategies for antidepressant active ingredients from natural medicinal plants: the state of the art. J Nanobiotechnol. 2023; 21: 391. doi:10.1186/s12951-023-02159-9

37. Nurzyńska-Wierda R. Plants with potential importance in supporting the treatment of depression: current trends and research. Pharmaceuticals. 2024; 17(11): 1489. Doi:10.3390/ph17111489

38. Pires PC, Paiva-Santos AC, Veiga F. Nano and microemulsions for the treatment of depressive and anxiety disorders: an efficient approach to improve solubility, brain bioavailability and therapeutic efficacy. Pharmaceutics. 2022; 14(12): 2825. doi:10.3390/pharmaceutics14122825

39. Patel V, Aggarwal K, Dhawan A, Singh B, Shah P, Sawhney A, et al. Protein supplementation: the double-edged sword. Proc (Bayl Univ Med Cent). 2023; 37:118–26.

40. Holsboer F, Ising M. Precision psychiatry approach to treat depression and anxiety targeting the stress hormone system—V1b-antagonists as a case in point. Pharmacopsychiatry. 2024; 57(6): 263–74. doi:10.1055/a-2372-3549

41. Kabra A, Garg R, Brimson JM, Živković J, Almawash S, Ayaz M, et al. Mechanistic insights into the role of plant polyphenols and their nano-formulations in the management of depression. Front Pharmacol. 2022; 13: 1046599. doi:10.3389/fphar.2022.1046599

42. Antunes JL, Amado J, Veiga F, Paiva-Santos AC, Pires PC. Nanosystems, drug molecule functionalization and intranasal delivery: an update on the most promising strategies for increasing the therapeutic efficacy of antidepressant and anxiolytic drugs. Pharmaceutics. 2023; 15(3): 998. doi:10.3390/pharmaceutics15030998

43. Alberto M, Paiva-Santos AC, Veiga F, Pires PC. Intranasal nanoparticles for the treatment of depression and anxiety disorders. Appl Sci Events. 2022; 13853. Doi:10.3390/asec2022-13853

44. Ankit, Harsh Kumar, Kartikey Tiwari, Disha Sharma, Ashutosh Kumar, Shambhu Bhardwaj, Tanu Bhadauriya, Anuradha Verma, Anshika Garg, Babita Kumar. The Legacy and Advancement of Phytotherapeutics. Asian Journal of Pharmaceutical Research. 2025; 15(3): 333-6

45. Mutingwende FP, Kondiah PPD, Ubanako P, Marimuthu T, Choonara YE. Advances in nano-enabled platforms for the treatment of depression. Polymers. 2021; 13(9): 1431. Doi:10.3390/polym13091431

46. Rasad S, Tyagi AK, Aggarwal BB. Curcumin delivery systems: an overview. Phytother Res. 2014; 28(4): 545–58. doi:10.1002/ptr.5021

47. Kulkarni SK, Dhir A. Withania somnifera: an Indian ginseng. Indian J Exp Biol. 2008; 46(7):493–503. Ashok, Aspatwar., Ranajit, Nath., Ratul, Bhowmik., Rajesh, Jesudasan. (2024). Herbal-based nanosystems: A novel drug-delivery treatment procedure against neurodegenerative disorders. doi: 10.26434/chemrxiv-2024-hh95h-v2

48. Atul, Kabra, Ruchika, Garg., James, M., Brimson., Jelena, Živković., Saud, Almawash., Muhammad, Ayaz., Asif, Nawaz., Syed, Shams, ul, Hassan., Simona, Bungau. (2022). Mechanistic insights into the role of plant polyphenols and their nano-formulations in the management of depression. Frontiers in Pharmacology, 13 doi: 10.3389/fphar.2022.1046599

49. Margarida, Alberto, Ana, Cláudia, Paiva-Santos., Francisco, Veiga., Patrícia, C., Pires. (2022). Intranasal Nanoparticles for the Treatment of Depression and Anxiety Disorders. doi: 10.3390/asec2022-13853

50. Fadzai, P, Mutingwende, Pierre, P., D., Kondiah, Philemon, Ubanako., Thashree, Marimuthu., Yahya, E., Choonara. (2021). Advances in Nano-Enabled Platforms for the Treatment of Depression. Polymers, 13(9): 1431-. doi: 10.3390/POLYM13091431

Received on 22.08.2025 Revised on 01.11.2025

Accepted on 23.12.2025 Published on 31.01.2026

Available online from February 07, 2026

Res. J. Pharmacognosy and Phytochem. 2026; 18(1):49-55.

DOI: 10.52711/0975-4385.2026.00008

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.