Depresyon ve anksiyetede Ashwagandha bitkisinin klinik uygulamaları

Year 2024, Volume: 49 Issue: 3, 818 - 833, 30.09.2024

Havanur Güllü , Olcay Kıroğlu

https://doi.org/10.17826/cumj.1460207

Abstract

Ashwagandha, geleneksel Hint tıbbında uzun süredir kullanılan adaptogenik bir bitkidir ve son yıllarda modern tıpta dikkat çekmektedir. Ashwagandha, adaptogen özellikleri sayesinde vücutta dengeyi sağlama yeteneği ile bilinmektedir. Anksiyete ve depresyon, modern toplumda giderek artan bir halk sağlığı sorunudur. Ashwagandha'nın içerdiği biyoaktif bileşenler, özellikle withanolid, sinir sistemini etkileyen bir dizi biyolojik mekanizma üzerinden anksiyete ve depresyonun hafifletilmesine katkıda bulunabilir. Bu durum, nörotransmitterlerin düzenlenmesi, anti-inflamatuar etkiler ve stresle başa çıkma mekanizmalarını destekleme yoluyla gerçekleşebilir. Ashwagandha'nın, geleneksel antidepresan ve anksiyolitik ilaçlara kıyasla daha az yan etkiye neden olması ve doğal bir adaptogen olarak geniş bir etki mekanizmasına sahip olması, gelecekteki potansiyel terapötik seçenekleri açısından önemli bir avantaj sunmaktadır. Literatürdeki birçok araştırma, Ashwagandha'nın bu alanlarda potansiyel bir doğal yardımcı olarak rol oynayabileceğini öne sürmektedir. Ancak, bu potansiyeli tam anlamıyla değerlendirebilmek için daha fazla klinik çalışma ve uzun vadeli etki analizlerine ihtiyaç duyulmaktadır. Bu derleme, Ashwagandha'nın anksiyete ve depresyonla mücadeledeki etkinliği konusunda mevcut literatürü değerlendirerek, gelecekteki araştırmalara yönelik bir temel oluşturmayı amaçlamaktadır.

Keywords

Anksiyete, depresyon, Ashwagandha

Ethical Statement

ETİK KURUL BELGESİ GEREK OLMADIĞI BEYAN EDİLMİŞTİR

Clinical applications of Ashwagandha plant in depression and anxiety

Abstract

Ashwagandha is an adaptogenic herb that has been long used in traditional Indian medicine and has garnered attention in modern medicine in recent years. Known for its ability to restore balance in the body due to its adaptogenic properties, Ashwagandha is believed to offer potential benefits in addressing anxiety and depression, which are growing public health concerns in modern society. The bioactive components found in Ashwagandha, particularly withanolides, may contribute to reducing symptoms of anxiety and depression through various biological mechanisms that affect the nervous system. This can involve the regulation of neurotransmitters, anti-inflammatory effects, and support for stress coping mechanisms. The fact that Ashwagandha tends to cause fewer side effects compared to conventional antidepressants and anxiolytic drugs, along with its broad mechanism of action as a natural adaptogen, presents a significant advantage in terms of potential future therapeutic options. Many studies in the literature suggest that Ashwagandha could serve as a natural adjunct in these areas. However, more clinical trials and long-term effect analyses are necessary to fully evaluate this potential. This review aims to lay the groundwork for future research by assessing current literature on the effectiveness of Ashwagandha in addressing anxiety and depression.

Keywords

Anxiety, depression, Ashwagandha

References

• Ferrari AJ, Somerville AJ, Baxter AJ, Norman R, Patten SB, Vos T et al. Global variation in the prevalence and incidence of major depressive disorder: a systematic review of the epidemiological literature. Psychol Med. 2013;43:471-81.
• Craske MG, Stein MB, Eley TC, Milad MR, Holmes A, Rapee RM et al. Anxiety disorders. Nat Rev Dis Primers. 2017;4:17024.
• American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th edition. Arlington, American Psychiatric Publishing, 2013.
• Javaid SF, Hashim IJ, Hashim MJ, Stip E, Samad MA, Ahbabi AA. Epidemiology of anxiety disorders: global burden and sociodemographic associations. Middle East Curr Psychiatry. 2023;30:44.
• Garber J, Brunwasser S, Zerr A, Schwartz K, Sova K, Weersing V. Treatment and prevention of depression and anxiety in youth: test of cross-over effects. Depress Anxiety. 2016;33:939-59.
• Sarris J. Herbal medicines in the treatment of psychiatric disorders: 10-year updated review. Phytother Res. 2018;32:1147-62.
• Sarris J, Ravindran A, Yatham L, Marx W, Rucklidge J, McIntyre R et al. Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Task force. World J Biol Psychiatry. 2022;23:424-55.
• Speers A, Cabey K, Soumyanath A, Wright K. Effects of Withania somnifera (Ashwagandha) on stress and the stress- related neuropsychiatric disorders anxiety, depression, and insomnia. Curr Neuropharmacol. 2021;19:1468-95.
• Panossian A, Efferth T, Shikov A, Pozharitskaya O, Kuchta K, Mukherjee P et al. Evolution of the adaptogenic concept from traditional use to medical systems: Pharmacology of stress- and aging-related diseases. Med Res Rev. 2021;41:630-703.
• Alam N, Hossain M, Khalil M, Moniruzzaman M, Sulaiman S, Gan S. Recent advances in elucidating the biological properties of Withania somnifera and its potential role in health benefits. Phyto Chem Rev. 2012;11:97-112.
• Paul S, Chakraborty S, Anand U, Dey S, Nandy S, Ghorai M et al. Withania somnifera (L.) Dunal (Ashwagandha): A comprehensive review on ethnopharmacology, pharmacotherapeutics, biomedicinal and toxicological aspects. Biomed Pharmacother. 2021;143:112175.
• Tetali S, Acharya S, Ankari A, Nanakram V, Raghavendra A. Metabolomics of Withania somnifera (L.) dunal: Advances and applications. J Ethnopharmacol. 2021;267:113469.
• Chatterjee S, Srivastava S, Khalid A, Singh N, Sangwan R, Sidhu O et al. Comprehensive metabolic fingerprinting of Withania somnifera leaf and root extracts. Phytochemistry. 2010;71:1085-94.
• Kuboyama T, Tohda C, Zhao J, Nakamura N, Hattori M, Komatsu K. Axon- or dendritepredominant outgrowth induced by constituents from Ashwagandha. Neuroreport. 2002;13:1715-20.
• Kuboyama T, Tohda C, Komatsu K. Neuritic regeneration and synaptic reconstruction induced by withanolide A. Br J Pharmacol. 2005;144:961-71.
• Kuboyama T, Tohda C, Komatsu K. Withanoside IV and its active metabolite, sominone, attenuate Abeta(25-35)-induced neurodegeneration. Eur J Neurosci. 2006;23:1417-26.
• Kuboyama T, Tohda C, Komatsu K. Effects of Ashwagandha (roots of Withania somnifera) on neurodegenerative diseases. Biol Pharm Bull. 2014;37:892-7.
• Alam N, Hossain M, Mottalib M, Sulaiman S, Gan S, Khalil M. Methanolic extracts of Withania somnifera leaves, fruits and roots possess antioxidant properties and antibacterial activities. BMC Complement Altern Med. 2012;12:175.
• Kaushik M, Kaul S, Wadhwa R, Yanagisawa M, Urade Y. Triethylene glycol, an active component of Ashwagandha (Withania somnifera) leaves, is responsible for sleep induction. PLoS One. 2017;12:e0172508.
• Gupta G, Rana A. Protective effect of Withania somnifera dunal root extract against protracted social isolation induced behavior in rats. Indian J Physiol Pharmacol. 2007;51:345-53.
• Gupta G, Rana A. Effect of Withania somnifera Dunal in ethanol-induced anxiolysis and withdrawal anxiety in rats. Indian J Exp Biol. 2008;46:470-5.
• Bhattacharya S, Bhattacharya A, Sairam K, Ghosal S. Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: an experimental study. Phytomedicine. 2000;7:463-9.
• KrishnaRaju A, Somepalli V, Thanawala S, Shah R. Efficacy and anti-inflammatory activity of Ashwagandha sustained-release formulation on depression and anxiety induced by chronic unpredictable stress: in vivo and in vitro studies. J Exp Pharmacol. 2023;15:291305.
• Majeed M, Nagabhushanam K, Murali A, Vishwanathan D, Mamidala R, Mundkur L. A standardized Withania somniferra (Linn.) root extract with piperine alleviates the symptoms of anxiety and depression by increasing serotonin levels: a double-blind, randomized, placebo-controlled study. J Integr Complement Med. 2023.
• Remenapp A, Coyle K, Orange T, Lynch T, Hooper D, Hooper S et al. Efficacy of Withania somnifera supplementation on adult's cognition and mood. J Ayurveda Integr Med. 2022;13:100510.
• Andrade C, Aswath A, Chaturvedi S, Srinivasa M, Raguram R. A double-blind, placebo controlled evaluation of the anxiolytic efficacy of an ethanolic extract of Withania somnifera. Indian J Psychiatry. 2000;42:295-301.
• Nuss P. Anxiety disorders and GABA neurotransmission: a disturbance of modulation. Neuropsychiatr Dis Treat. 2015;11:165-75.
• Sonar V, Fois B, Distinto S, Maccioni E, Meleddu R, Cottiglia F et al. Ferulic acid esters and withanolides: in search of Withania somnifera GABAA receptor modulators. J Nat Prod. 2019;82:1250-57.
• Mehta A, Binkley P, Gandhi S, Ticku M. Pharmacological effects of Withania somnifera root extract on GABAA receptor complex. Indian J Med Res. 1991;94:312-5.
• Bassareo V, Talani G, Frau R, Porru S, Rosas M, Kasture S et al. Inhibition of morphine- and ethanol-mediated stimulation of mesolimbic dopamine neurons by Withania somnifera. Front Neurosci. 2019;13:545.
• Candelario M, Cuellar E, Reyes-Ruiz J, Darabedian N, Feimeng Z, Miledi R et al. Direct evidence for GABAergic activity of Withania somnifera on mammalian ionotropic GABAA and GABAρ receptors. J Ethnopharmacol. 2015;171:264-72.
• Fedoce A, Ferreira F, Bota R, Bonet-Costa V, Sun P, Davies K. The role of oxidative stress in anxiety disorder: cause or consequence? Free Radic Res. 2018;52:737-50.
• Mohanty R, Das S, Singh N, Patri M. Withania somnifera leaf extract ameliorates benzo[a]pyrene-induced behavioral and neu romorphological alterations by improving brain antioxidant status in zebrafish (Danio rerio). Zebrafish. 2016;13:188-96.
• Kumar A, Kalonia H. Protective effect of Withania somnifera Dunal on the behavioral and biochemical alterations in sleep disturbed mice (Grid over water suspended method). Indian J Exp Biol. 2007;45:524-8.
• Kaur T, Kaur G. Withania somnifera as a potential candidate to ameliorate high fat diet induced anxiety and neuroinflammation. J Neuroinflammation. 2017;14:201.
• Antony B, Anu Aravind A, Benny M, Gupta N, Joseph B, Sebastian A. Bioactivity guided fractionation and purification of anti depressant molecule from ashwagandha (Withania somnifera). Curr Bioact Compd. 2020;16:681-6.
• Jayanthi M, Prathima C, Huralikuppi J, Suresha R, Dhar M. Anti-depressant effects of Withania somnifera fat (Ashwagandha Ghrutha) extract in experimental mice. Int J Pharma Bio Sci. 2012;3:33-42.
• Shah P, Trivedi N, Bhatt J, Hemavathi K. Effect of Withania somnifera on forced swimming test induced immobility in mice and its interaction with various drugs. Indian J Physiol Pharmacol. 2006;50:409-15.
• Dey A, Chatterjee S, Kumar V. Triethylene glycol-like effects of Ashwagandha (Withania somnifera (L.) Dunal) root extract devoid of withanolides in stressed mice. Ayu. 2018;39:230-8.
• Shreevathsa M, Ravishankar B, Dwivedi R. Anti depressant activity of Mamsyadi Kwatha: An Ayurvedic compound formulation. Ayu. 2013;34:113-7.
• Naß J, Abdelfatah S, Efferth T. Induction of stress resistance and extension of lifespan in Chaenorhabditis elegans serotonin-receptor knockout strains by withanolide A. Phytomedicine. 2021;84:153482.
• Tripathi A, Dey S, Singh R, Dey P. Alterations in the sensitivity of 5(th) receptor subtypes following chronic Asvagandha treatment in rats. Anc Sci Life. 1998;17:169-81.
• Chandrasekhar K, Kapoor J, Anishetty S. A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults. Indian J Psychol Med. 2012;34:255-62.
• Gannon J, Brar J, Rai A, Chengappa K. Effects of a standardized extract of Withania somnifera (Ashwagandha) on depression and anxiety symptoms in persons with schizophrenia participating in a randomized, placebo-controlled clinical trial. Ann Clin Psychiatry. 2019;31:123-9.
• Lopresti A, Smith S, Malvi H, Kodgule R. An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: A randomized, double-blind, placebo-controlled study. Medicine (Baltimore). 2019;98:e17186.
• Bhatt S, Nagappa A, Patil C. Role of oxidative stress in depression. Drug Discov Today. 2020;25:1270-6.
• Priyanka G, Anil Kumar B, Lakshman M, Manvitha V, Kala Kumar B. Adaptogenic and immunomodulatory activity of ashwagan dha root extract: an experimental study in an equine model. Front Vet Sci. 2020;7:541112.
• Bhatnagar M, Sharma D, Salvi M. Neuroprotective effects of Withania somnifera dunal: A possible mechanism. Neurochem Res. 2009;34:1975-83.
• Tandon N, Yadav S. Safety and clinical effectiveness of Withania somnifera (Linn.) Dunal root in human ailments. J Ethnopharmacol. 2020;255:112768.
• Singh N, Bhalla M, de Jager P, Gilca M. An overview on ashwagandha: a Rasayana (rejuvenator) of Ayurveda. Afr J Tradit Complement Altern Med. 2011;8:208-13.
• Venkataraghavan S, Seshadri C, Sundaresan TP, Revathi R, Rajagopalan V, Janaki K. The comparative effect of milk fortified with Aswagandha and Aswagandha and Punarnava in children- a double blind study. J. Res. Ayur. 1980;1:370-85.
• Kuppurajan K, Rajagopalan SS, Sitaraman R, Rajagopalan V, Janaki K, Revathi R et all. Effect of Aswagandha (Withania somnifera Dunal) on the process of ageing in human volunteers. J. Res. Ayur. 1980;1:247-58.
• Dongre S, Langade D, Bhattacharyya S. Efficacy and safety of Ashwagandha (Withania somnifera) root extract in improving sexual function in women: a pilot study. BioMed Res. Int. 2015;2015:284154.
• Prabu PC, Panchapakesan S. Prenatal developmental toxicity evaluation of Withania somnifera root extract in Wistar rats. Drug Chem Toxicol. 2015;38:50–6.
• Kelgane SB, Salve J, Sampara P, Debnath K. Efficacy and tolerability of Ashwagandha root extract in the elderly for improvement of general well-being and sleep: a prospective, randomized, double-blind, placebo-controlled study. Cureus. 2020;12:e7083.
• Gómez AA, Fernandez-Lazaro D, Adams DP, Monserdà-Vilaró A, Fernandez-Lazaro CI. Effects of Withania somnifera (Ashwagandha) on hematological and biochemical markers, hormonal behavior, and oxidant response in healthy adults: a systematic review. Curr Nutr Rep. 2023;12:465-77.
• Vaidya V, Gothwad A, Ganu G, Girme A, Modi S, Hingorani L. Clinical safety and tolerability evaluation of Withania somnifera (L.) Dunal (Ashwagandha) root extract in healthy human volunteers. J Ayurveda Integr Med. 2023;15:100859.
• Kumar S, Bouic PJ, Rosenkranz B. Investigation of CYP2B6, 3A4 and β-esterase interactions of Withania somnifera (L.) dunal in human liver microsomes and HepG2 cells. J Ethnopharmacol. 2021;270:113766.
• Haron M, Dale O, Martin K, Avula B, Chittiboyina A, Khan I et al. Evaluation of the herb-drug interaction potential of commonly used botanicals on the us market with regard to PXR- and AhR-mediated influences on CYP3A4 and CYP1A2. J Diet Suppl. 2023;20:763-76.
• Siwek M, Woroń J, Wrzosek A, Gupało J, Chrobak AA. Harder, better, faster, stronger? Retrospective chart review of adverse events of interactions between adaptogens and antidepressant drugs. Front Pharmacol. 2023;14:1271776.