A standardized combination of Terminalia chebula and Withania somnifera extracts enhances immune function in adults: a pilot randomized, double-blind, placebo-controlled clinical study

Durga Prasad Sadhupati; Rambhakta Lakshmisudha; Karthik Naidu Karjala Chakravarthy; Partha Sarathy Naidana

doi:10.29219/fnr.v68.10297

Durga Prasad Sadhupati Help Hospital, Governorpet, Vijayawada, Andhra Pradesh, India
Rambhakta Lakshmisudha Help Hospital, Governorpet, Vijayawada, Andhra Pradesh, India
Karthik Naidu Karjala Chakravarthy Latha Super Speciality Hospital, Suryaraopet, Vijayawada, Andhra Pradesh, India
Partha Sarathy Naidana Department of Community Medicine, ASR Academy of Medical Sciences, Eluru, Andhra Pradesh, India

DOI: https://doi.org/10.29219/fnr.v68.10297

Keywords: Botanical supplement for immune function, Cell-mediated immunity, Humoral immunity, Randomized clinical trial, Terminalia chebula, Withania somnifera

Abstract

Background: The use of botanical medicine has been demonstrated as a potential strategy to manage or treat a variety of health issues. Terminalia chebula (Retz) fruit and Withania somnifera (L.) Dunal roots are important medicinal herbs described in Ayurveda and traditional therapy for diverse health benefits.

Objective: This pilot study aimed to evaluate the immune function-enhancing potential of a unique blend of T. chebula fruit and W. somnifera root extracts, LN20189, in healthy men and women.

Methods: Forty healthy volunteers (age: 35–60 years) were randomized into two groups receiving either LN20189 (500 mg per day) or a matched placebo over 28 consecutive days. The total T-cell population was the primary efficacy measure in this study. The secondary efficacy measures included counts of CD4, CD8, natural killer (NK) cells, serum levels of interleukin-2 (IL-2), interferon-gamma (IFN-γ), total immunoglobulin-G (IgG), and Immune Function Questionnaire (IFQ) scores. Safety parameter assessments were also conducted.

Results: Post-trial, in LN20189-supplemented subjects, T cells, CD4, NK cells count, and the CD4:CD8 ratio were increased by 9.32, 10.10, 19.91, and 17.43%, respectively, as compared to baseline. LN20189 supplementation increased serum IFN-γ and IgG levels by 14.57 and 27.09% from baseline and by 13.98 and 21.99%, compared to placebo, respectively. Also, the IFQ scores in the LN20189 group were 84.68% (vs. baseline) and 69.44% (vs. placebo) lower at the end of the trial. LN20189 improved the study volunteers’ cellular and humoral immune functions.

Conclusion: In summary, LN20189 supplementation was found tolerable and improved the key cellular and humoral factors of the immune system and helped improve immune function of the trial volunteers.

Downloads

Download data is not yet available.

References

1.
Chaplin DD. Overview of the immune response. J Allergy Clin Immunol 2010; 125(2 suppl 2): S3–23. doi: 10.1016/j.jaci.2009.12.980

2.
Lu RM, Hwang YC, Liu IJ, Lee CC, Tsai HZ, Li HJ, et al. Development of therapeutic antibodies for the treatment of diseases. J Biomed Sci 2020; 27: 1. doi: 10.1186/s12929-019-0592-z

3.
Thakurta A, Pierceall WE, Amatangelo MD, Flynt E, Agarwal A. Developing next generation immunomodulatory drugs and their combinations in multiple myeloma. Oncotarget 2021; 12: 1555–63. doi: 10.18632/oncotarget.27973

4.
Ahmed S, Ding X, Sharma A. Exploring scientific validation of Triphala Rasayana in ayurveda as a source of rejuvenation for contemporary healthcare: an update. J Ethnopharmacol 2021; 273: 113829. doi: 10.1016/j.jep.2021.113829

5.
Peterson CT, Denniston K, Chopra D. Therapeutic uses of triphala in ayurvedic medicine. J Altern Complement Med 2017; 23: 607–14. doi: 10.1089/acm.2017.0083

6.
Das G, Kim DY, Fan C, Gutiérrez-Grijalva EP, Heredia JB, Nissapatorn V, et al. Plants of the genus Terminalia: an insight on its biological potentials, pre-clinical and clinical studies. Front Pharmacol 2020; 11: 561248. doi: 10.3389/fphar.2020.561248

7.
Jokar A, Masoomi F, Sadeghpour O, Nassiri-Toosi M, Hamedi S. Potential therapeutic applications for Terminalia chebula in Iranian traditional medicine. J Tradit Chin Med Sci 2016; 36: 250–4. doi: 10.1016/s0254-6272(16)30035-8

8.
Zhang C, Jiang K, Qu SJ, Zhai YM, Tan JJ, Tan CH. Triterpenoids from the barks of Terminalia chebula. J Asian Nat Prod Res 2015; 17: 996–1001. doi: 10.1080/10286020.2015.1052803

9.
Rahimi VB, Askari VR, Shirazinia R, Soheili-Far S, Askari N, Rahmanian-Devin P, et al. Protective effects of hydro-ethanolic extract of Terminalia chebula on primary microglia cells and their polarization (M1/M2 balance). Mult Scler Relat Disord 2018; 25: 5–13. doi: 10.1016/j.msard.2018.07.015

10.
Kumar R, Arora R, Agarwal A, Gupta YK. Protective effect of Terminalia chebula against seizures, seizure-induced cognitive impairment and oxidative stress in experimental models of seizures in rats. J Ethnopharmacol 2018; 215: 124–31. doi: 10.1016/j.jep.2017.12.008

11.
Kim HJ, Song HK, Park SH, Jang S, Park KS, Song KH, et al. Terminalia chebula Retz. extract ameliorates the symptoms of atopic dermatitis by regulating anti-inflammatory factors in vivo and suppressing STAT1/3 and NF-ĸB signaling in vitro. Phytomedicine 2022; 104: 154318. doi: 10.1016/j.phymed.2022.154318

12.
Bani S, Gautam M, Sheikh FA, Khan B, Satti NK, Suri KA, et al. Selective Th1 up-regulating activity of Withania somnifera aqueous extract in an experimental system using flow cytometry. J Ethnopharmacol 2006; 107: 107–15. doi: 10.1016/j.jep.2006.02.016

13.
Malik F, Singh J, Khajuria A, Suri KA, Satti NK, Singh S, et al. A standardized root extract of Withania somnifera and its major constituent withanolide-A elicit humoral and cell-mediated immune responses by up regulation of Th1-dominant polarization in BALB/c mice. Life Sci 2007; 80: 1525–38. doi: 10.1016/j.lfs.2007.01.029

14.
Gautam M, Diwanay SS, Gairola S, Shinde YS, Jadhav SS, Patwardhan BK. Immune response modulation to DPT vaccine by aqueous extract of Withania somnifera in experimental system. Int Immunopharmacol 2004; 4: 841–9. doi: 10.1016/j.intimp.2004.03.005

15.
Iuvone T, Esposito G, Capasso, F, Izzo AA. Induction of nitric oxide synthatase expression by Withania somnifera in macrophages. Life Sci 2003; 72(14): 1617–25. doi: 10.1016/s0024-3205(02)02472-4

16.
Rasool M, Perumal V. Protective effect of Withania somnifera root powder in relation to lipid peroxidation, antioxidant status, glycoproteins and bone collagen on adjuvant-induced arthritis. Fundam Clin Pharmacol 2007; 21: 157–64. doi: 10.1111/j.1472-8206.2006.00461.x

17.
Speers AB, Cabey KA, Soumyanath A, Wright KM. Effects of Withania somnifera (Ashwagandha) on stress and the stress-related neuropsychiatric disorders anxiety, depression, and insomnia. Curr Neuropharmacol 2021; 19: 1468–95. doi: 10.2174/1570159X19666210712151556

18.
Langade D, Thakare V. Clinical evaluation of the pharmacological impact of ashwagandha root extract on sleep in healthy volunteers and insomnia patients: a double-blind, randomized, parallel-group, placebo-controlled study. J Ethnopharmacol 2021; 264: 113276. doi: 10.1016/j.jep.2020.113276

19.
Mikulska P, Malinowska M, Ignacyk M, Szustowski P, Nowak J, Pesta K, et al. Ashwagandha (Withania somnifera) – current research on the health-promoting activities: a narrative review. Pharmaceutics 2023; 15: 1057. doi: 10.3390/pharmaceutics15041057

20.
Afewerky HK, Ayodeji AE, Tiamiyu BB, Orege JI, Okeke ES, Oyejobi AO, et al. Critical review of the Withania somnifera (L.) Dunal: ethnobotany, pharmacological efficacy, and commercialization significance in Africa. Bull Natl Res Cent 2021; 45: 176. doi: 10.1186/s42269-021-00635-6.

21.
Mukherjee PK, Banerjee S, Biswas S, Das B, Kar A, Katiyar CK. Withania somnifera (L.) Dunal – modern perspectives of an ancient Rasayana from Ayurveda. J Ethnopharmacol 2021; 264: 113157. doi: 10.1016/j.jep.2020.113157

22.
Versprille LJFW, van de Loo AJAE, Mackus M, Arnoldy L, Sulzer TAL, Vermeulen SA, et al. Development and validation of the Immune Status Questionnaire (ISQ). Int J Environ Res Public Health 2019; 16: 4743. doi: 10.3390/ijerph16234743

23.
Mondal S, Varma S, Bamola VD, Naik SN, Mirdha BR, Padhi MM, et al. Double-blinded randomized controlled trial for immunomodulatory effects of Tulsi (Ocimum sanctum Linn.) leaf extract on healthy volunteers. J Ethnopharmacol 2011; 136: 452–6. doi: 10.1016/j.jep.2011.05.012

24.
Głuchowska K, Dzieciątkowski T, Sędzikowska A, Zawistowska-Deniziak A, Młocicki D. The new status of parasitic diseases in the COVID-19 pandemic – risk factors or protective agents? J Clin Med 2021; 10: 2533. doi: 10.3390/jcm10112533

25.
Gopukumar K, Thanawala S, Somepalli V, Rao TSS, Thamatam VB, Chauhan S. Efficacy and safety of ashwagandha root extract on cognitive functions in healthy, stressed adults: a randomized, double-blind, placebo-controlled study. Evid Based Complementary Altern Med 2021; 2021: 8254344. doi: 10.1155/2021/8254344

26.
Nohr LA, Rasmussen LB, Straand J. Resin from the mukul myrrh tree, guggul, can it be used for treating hypercholesterolemia? A randomized, controlled study. Complement Ther Med 2009; 17: 16–22. doi: 10.1016/j.ctim.2008.07.001

27.
Donato F, Raffetti E, Toninelli G, Festa A, Scarcella C, Castellano M. Guggulu and triphala for the treatment of hypercholesterolaemia: a placebo-controlled, double-blind, randomised trial. Complement Med Res 2021; 28: 216–25. doi: 10.1159/000510985

28.
Paudel S, Mishra N, Agarwal R. Phytochemicals as immunomodulatory molecules in cancer therapeutics. Pharmaceuticals 2023; 16: 1652. doi:10.3390/ph16121652

29.
Shokoohi R, Kianbakht S, Faramarzi M, Rahmanian M, Nabati F, Mehrzadi S, et al. Effects of an herbal combination on glycemic control and lipid profile in diabetic women: a randomized, double-blind, placebo- controlled clinical trial. J Evid-Based Integr Med 2017; 22: 798–804. doi: 10.1177/2156587217737683

30.
Belapurkar P, Goyal P, Tiwari-Barua P. Immunomodulatory effects of triphala and its individual constituents: a review. Indian J Pharm Sci 2014; 76: 467–75.

31.
Wu Q, He M, Wang J, Tong T, Yang D, Tang H. The therapeutic mechanism of Chebulae Fructus in the treatment of immunosuppression in Chinese yellow quail on the basis of network pharmacology. Front Vet Sci 2023; 10: 1123449. doi: 10.3389/fvets.2023.1123449

32.
Chandran U, Patwardhan B. Network ethnopharmacological evaluation of the immunomodulatory activity of Withania somnifera. J Ethnopharmacol 2017; 197: 250–6. doi: 10.1016/j.jep.2016.07.080

33.
Verma N, Gupta SK, Tiwari S, Mishra AK. Safety of ashwagandha root extract: a randomized, placebo-controlled, study in healthy volunteers. Complement Ther Med 2021; 57: 102642. doi: 10.1016/j.ctim.2020.102642

34.
Lu W, Mehraj V, Vyboh K, Cao W, Li T, Routy JP. CD4:CD8 ratio as a frontier marker for clinical outcome, immune dysfunction and viral reservoir size in virologically suppressed HIV-positive patients. J Int AIDS Soc 2015; 18: 20052. doi: 10.7448/IAS.18.1.20052

35.
Gojak R, Hadžiosmanović V, Baljić R, Zečević L, Ćorić J, Mijailović Ž. CD4/CD8 ratio as a predictor for the occurrence of metabolic syndrome in HIV/AIDS patients during 6 months of cART therapy. J Med Biochem 2019; 38: 489–95. doi: 10.2478/jomb-2018-0049

36.
Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S. Functions of natural killer cells. Nat Immunol 2008; 9: 503–10. doi: 10.1038/ni1582

37.
Pierce S, Geanes ES, Bradley T. Targeting natural Killer cells for improved immunity and control of the adaptive immune response. Front Cell Infect Microbiol 2020; 10: 231. doi: 10.3389/fcimb.2020.00231

38.
Nigro CL, Macagno M, Sangiolo D, Bertolaccini L, Aglietta M, Merlano MC. NK-mediated antibody-dependent cell-mediated cytotoxicity in solid tumors: biological evidence and clinical perspectives. Ann Transl Med 2019; 7: 105. doi: 10.21037/atm.2019.01.42

39.
McNab F, Mayer-Barber K, Sher A, Wack A, O’Garra A. Type I interferons in infectious disease. Nat Rev Immunol 2015; 15: 87–103. doi: 10.1038/nri3787

40.
Tiralongo E, Wee SS, Lea RA. Elderberry supplementation reduces cold duration and symptoms in air-travellers: a randomized, double-blind placebo-controlled clinical trial. Nutrients 2016; 8: 182. doi: 10.3390/nu8040182

41.
Hawkins J, Baker C, Cherry L, Dunne E. Black elderberry (Sambucus nigra) supplementation effectively treats upper respiratory symptoms: a meta-analysis of randomized, controlled clinical trials. Complement Ther Med 2019; 42: 361–5. doi: 10.1016/j.ctim.2018.12.004

42.
Wieland LS, Piechotta V, Feinberg T, Ludeman E, Hutton B, Kanji S, et al. Elderberry for prevention and treatment of viral respiratory illnesses: a systematic review. BMC Complement Altern Med 2021; 21: 112. doi: 10.1186/s12906-021-03283-5

43.
Dhama K, Sachan S, Khandia R, Munjal A, Iqbal HMN, Latheef SK, et al. Medicinal and beneficial health applications of Tinospora cordifolia (Guduchi): a miraculous herb countering various diseases/disorders and its immunomodulatory effects. Recent Pat Endocr Metab Immune Drug Discov 2017; 10: 96–111. doi: 10.2174/1872214811666170301105101.

44.
Tharakan A, Shukla H, Benny IR, Tharakan M, George L, Koshy S. Immunomodulatory effect of Withania somnifera (Ashwagandha) extract – a randomized, double-blind, placebo controlled trial with an open label extension on healthy participants. J Clin Med 2021; 10: 3644. doi: 10.3390/jcm10163644