Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 
Users Online: 576 | Home Print this page Email this page Small font size Default font size Increase font size


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2013  |  Volume : 33  |  Issue : 2  |  Page : 119-122

Evaluation of a Unani polyherbal formulation (Tiryaqe wabai) as an immunostimulator in elderly persons


Departments of Tahaffuzi wa Samaji Tib National Institute of Unani Medicine, Bengaluru, Karnataka, India

Date of Web Publication18-Aug-2014

Correspondence Address:
Zar Nigar
National Institute of Unani Medicine, Bengaluru, Karnataka
India
Login to access the Email id

Source of Support: This study was funded by National Institute of Unani Medicine, Bengaluru., Conflict of Interest: None


DOI: 10.4103/0257-7941.139054

Clinical trial registration IEC/ IV/ 14/ TST

Rights and Permissions
  Abstract 

Background and Aims: Elderly subjects have a dysregulation of immune response mainly due to the changes in cell - mediated immunity. Due to their weakened immune response, the elderly are at increased risk of infection and related complications. In Unani medicine Tiryaq wabai was used for the prevention of epidemic diseases during outbreaks, but it has not been explored scientifically so far. The study was aimed to evaluate the immune-stimulating effect of Tiryaq wabai in elderly.
Materials and Methods: A randomized placebo controlled trial was conducted at National Institute of Unani Medicine Hospital, Bangalore. Thirty immunocompromised elderly persons were selected on the basis of clinical examination considering parameters like history of recurrent infection, unexplained weight loss, persistent diarrhea etc. They were randomly assigned,
20 in test and 10 in the control group. Tiryaq wabai was given to test group 500 mg orally thrice in a week for 45 days. Placebo was given orally to the control group at a dose of 500 mg thrice in a week for 45 days. Response was assessed by total leucocyte count (TLC), lymphocyte percentage, absolute lymphocyte count (ALC), CD4 and CD8 count. The results were analyzed statistically using Graph Pad InStat 3.
Results: The test drug showed statistically significant increase in TLC (P < 0.001), lymphocyte percentage (P < 0.001),
ALC (P < 0.001), CD4 count (P < 0.001) in comparison to control group, but increase in CD8 count was not statistically significant. No major adverse effect was observed throughout the study.
Conclusion: The findings outlined above indicate immune- stimulating activity of Tiryaq wabai and supports its use in conditions where immunostimulation is required and thus is suggestive of therapeutic usefulness.

Keywords: Aging, immune-senescence, T-lymphocytes, Unani medicine


How to cite this article:
Nigar Z, Itrat M. Evaluation of a Unani polyherbal formulation (Tiryaqe wabai) as an immunostimulator in elderly persons. Ancient Sci Life 2013;33:119-22

How to cite this URL:
Nigar Z, Itrat M. Evaluation of a Unani polyherbal formulation (Tiryaqe wabai) as an immunostimulator in elderly persons. Ancient Sci Life [serial online] 2013 [cited 2019 Nov 18];33:119-22. Available from: http://www.ancientscienceoflife.org/text.asp?2013/33/2/119/139054


  Introduction Top


Aging is a process of bodily change with time, leading to increased susceptibility to disease, and ultimately to death. This is reflected in the rise in age specific death rates in the population. After the age of 30 years, gradually there are structural and functional changes in the body. By the age of 50-60 years these changes get manifested clinically like decreased energy, vision, memory, locomotion or exertional dyspnea, reduction in homeostasis and immunity. [1] Of 6 billion people in the world 600 million are elderly and are expected to increase to >1.2 billion by 2025. [2] In India, the population of elderly has risen from 6.5% in 1991 to 7.7% in 2001 and will be 12% in 2025. [3] With advances in modern medical research techniques, research on age-related illnesses has become intense. Various biological therapies have been introduced in biotechnology and biopharmaceutical sectors for altered immune functions in elderly such as monoclonal antibodies, interferon, interleukins, several types of colony stimulating factors, restoration of the thymus, telomerase gene therapy. Many of these therapies have side-effects such as chills, fever, loss of appetite, nausea, vomiting, and diarrhea. [4]

The process of aging is attributed mostly to the excessive oxidants produced in the body. Reactive oxidant species and immune dysfunction are major causes of age-related diseases, [5],[6],[7] immune-senescence, attributed partly to the reduction in number of T-lymphocytes and loss of their functions. Such loss increases the prevalence of infectious diseases in the elderly. [6],[7] The maintenance of antioxidant and immune fitness is a rational approach to preventive health care. The importance of disease prevention is recognized by Unani medicine through experience accumulated over centuries. Tiryaq wabai is a well-documented and well-known drug in Unani system of medicine for its wide use for prophylaxis during epidemics of cholera, plague and other epidemic diseases. Tiryaq wabai was used by Avicenna and Galen in healthy persons as well as in patients during epidemics. [8],[9] Tiryaq wabai was selected for immune-stimulating study for two reasons. First, Unani descriptions were correlated with the immune-stimulating activity, therapeutically Tiryaq wabai is indicated for prevention of epidemic diseases during epidemics. The second basis for its selection were scientific reports regarding immune modulating, and antioxidant activity or related pharmacological actions and therapeutic effects of the ingredients of this formulation. Tiryaq wabai consists of three ingredients Sibr (Aloe barbadensis), Zaafran (Crocus sativus) and Mur (Commiphora myrrh) in the ratio of 2:1:1. [9] Antioxidant and immune-stimulating effect of A. barbadensis,[10],[11],[12] C. myrrha[13] and C. sativus[14] has already been established in animal models.


  Materials and methods Top


This study was a randomized placebo controlled trial designed to evaluate the immunostimulating effect of Tiryaq wabai in elderly persons. After taking ethical clearance from the Institutional Ethical Committee of National Institute of Unani Medicine (NIUM) Bangalore (IEC/IV/14/TST), the study was carried out over a period of 12 months from April 2010 to March 2011 in NIUM hospital. After obtaining informed consent, 30 immunocompromised elderly persons were selected and randomly assigned into two groups, 20 in test and 10 in the control group. Test group was treated with Tiryaq wabai 500 mg 3 times a week for 45 days, while in the placebo group, roasted wheat flour was given in the dose of 500 mg 3 times a week for 45 days. Persons of either sex of ≥ 60 years with two or more signs of immunodeficiency like (i) history of recurrent infection, (ii) unexplained weight loss, (iii) persistent diarrhea, (iv) persistent thrush in mouth, (v) 2 or more months on oral antibiotics with little effect were included in the study. Persons below the age of 60 years, receiving immunosuppressive drugs, uncontrolled diabetes and hypertension, chronic obstructed pulmonary disease, ischemic heart disease were excluded from the study. The subjects were strictly advised to stick to the usual dietary habits until the completion of the study. The response was measured by the assessment of total leucocyte count (TLC) every 15 th day up to 45 days and lymphocyte percentage, absolute lymphocyte count (ALC), CD4 count, CD8 count, pre- and post-treatment. Safety of the treatment was assessed by renal function test and liver function test before and after treatment. The data was analyzed by computerized statistical package Graph Pad InStat version 3 (GraphPad Software, Inc. 7825 Fay Avenue, Suite 230, La Jolla, CA 92037 USA). Analysis of variance one-way for the intra-group comparison and Tukey Kraman multiple comparison tests were used for inter-group comparison.


  Results Top


Characteristics of the subjects before the start of the trial have been presented in [Table 1]. Study population comprised of 73.33% males and 26.66% [8] females. About 63.34% subjects had mixed dietary habits, whereas 36.66% [11] were vegetarians.

In this study, immune-stimulating effect of Tiryaq wabai was evaluated. The response was measured by the assessment of TLC every 15 th day [Table 2], lymphocyte percentage, ALC, CD4 count and CD8 count before and after treatment [Table 3]. TLC, lymphocyte percentage, ALC and CD4 count showed a significant increase after treatment with respect to 0 day test and 45 th day control CD8 count also showed increase, but the difference was not statistically significant.
Table 1: Characteristics of the subjects


Click here to view
Table 2: Effect of Tiryaq wabai on TLC (mean±SD) in elderly persons


Click here to view
Table 3: Effect of Tiryaqe wabai on lymphocytes %, ALC, CD4 count and CD8 count in elderly persons


Click here to view



  Discussion Top


Age associated changes in cell mediated immunity strongly depend on thymic functions. As an individual ages, the thymus undergoes a progressive involution and the output of new cells fall significantly. This results in decreased concentration of naοve T-cells in peripheral blood and lymph nodes. In the elderly, there is a decrease in the diversity and functional integrity of both CD4 and CD8 T-cell subsets, which contribute to decreased ability to respond adequately to repeated infection. Production and maintenance of the diverse peripheral T-cell repertoire are critical to the normal function of the immune system. [15] Animal studies have shown that A. barbadensis increases the proliferation of T-lymphocytes in involuted thymus. Gonzalez et al. 1990 found that newly weaned mice treated with 30 mg water extract of Aloe subcutaneously showed greater proliferation of T-lymphocytes at thymus cortex that delayed fat infiltration of the involution at that level. [16] Reynolds and Dweck 1999 and Turner 2004 found immune modulating activities of the polysaccharides in A. barbadensis and suggest that these effects occur via activation of macrophage cells to generate nitric oxide, secrete cytokines and present cell surface markers. Acemannan, a polysaccharide stimulates antigenic response of human lymphocytes as well as the formation of all types of leukocytes from both spleen and bone marrow in irradiated mice. Lectin found in Aloe acts as mitogenic factor to stimulate lymphocyte proliferation and growth. Lectin enables the cells to recognize foreign cells and to stimulate macrophages for endocytosis. [17],[18]

Said found that C. myrrh significantly increases all types of leucocytes during different stages of healing. On microscopic examination of blood smear from C. myrrh treated rats with skin injury, Said found an elevated count of middle sized lymphocytes and neutrophils with well-defined nuclear lobules and rich granular cytoplasm. Furthermore, in spleen and lymph nodes, he also found an increased thickness of lymphatic sheath around the arterioles in the white pulp that was associated with high density of the medium sized lymphocytes in the secondary lymphoid follicles of the lymph nodes with engorged sinusoids. [19] C. myrrh helped to maintain the relative rise of leukocyte count throughout the healing period. Bani 2011 found that all animal models treated with alcoholic extract of C. sativus at graded dose level from 1.56 to 50 mg/kg body weight showed significant modulation of immune reactivity. Alcoholic extract of C. sativus increases Direct- type hypersensitivity reaction (DTH) in mice. [20] Increase in DTH reaction in response to antigen revealed the immune stimulatory effect of alcoholic extract of C. sativus on T-lymphocytes and accessory cell types required for expression of reaction.

In this study, increase in TLC, lymphocyte percentage, absolute lymphocytes and CD4 cell count after the use of Tiryaq wabai is supported by animal studies showing an increase in all types of leucocytes after the use of C. myrrh and A. barbadensis in separate studies. Aloe also increases proliferation of lymphocytes at thymus cortex and stimulates macrophages for endocytosis. C. sativus increases DTH reaction in mice as mentioned above. DTH reactions are mediated by T-cells and monocyte/macrophages rather than by antibodies. Delayed hypersensitivity is a major mechanism of defense against various intracellular pathogens including Mycobacteria, fungi and certain parasites.

Leukocytes are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Neutrophils, basophils, and eosinophils are granulocyte leucocytes; these cells contain granules in their cytoplasm. These granules are membrane-bound enzymes that act primarily in the digestion of endocytosed particles. Neutrophils/polymorphonuclear defend against bacterial or fungal infection and other very small inflammatory processes that are usually first responders to microbial infection. Neutrophils are very active in phagocytizing bacteria. Basophils are chiefly responsible for allergic and antigen response by releasing the chemical histamine causing vasodilatation. Eosinophils deal with parasitic infections. These are also the predominant inflammatory cells in allergic reactions. [21] Monocyte and macrophages are vital to the regulation of immune responses and the development of inflammation; Macrophages function in both nonspecific defense (innate immunity) as well as specific defense mechanisms (adaptive immunity) of vertebrate animals. Their role is to phagocytose, or engulf and then digest cellular debris and pathogens, either as stationary or as mobile cells by producing powerful chemical substances (monokines) including enzymes, complement proteins, and regulatory factors such as interleukin-1. They also stimulate lymphocytes and other immune cells to respond to pathogens. They are specialized phagocytic cells that attack foreign substances, infectious microbes and cancer cells through destruction and ingestion. [22] Increased proliferation of T-lymphocytes at thymus cortex results in an increased number of naοve CD4 T-cells in peripheral blood. Naïve CD4 T-cells respond to newly encountered antigens and once activated, provide help to cognate B-cells. These interactions are essential to germinal center formation and high affinity antibody generation. [23] CD4 T-cells (helper T-cells) coordinate the immune response and play a central role in immune protection. They help B-cells to make antibodies, to induce macrophages to develop enhanced microbicidal activity, to recruit neutrophils, eosinophils, and basophils to the sites of infection and inflammation, and through production of cytokines and chemokines and to orchestrate the full panoply of immune responses. [24] Safety parameters were found within normal range before and after treatment in both groups. Thus, our drug may be considered to be safe. This study suggests that Tiryaq wabai has immunostimulating capabilities and provides direct evidence for the immunostimulating effects of Tiryaq wabai in humans.

The overall effect of the test drug was found quite encouraging in the treatment of immunocompromised elderly persons. No clinically significant side effects were observed in the test group and overall compliance to the treatment was found excellent. The findings outlined above indicate immune-stimulating activity of Unani test drug Tiryaq wabai and suggest its use in conditions where immune-stimulation is required and thus is suggestive of its therapeutic usefulness. Such plant based immune-stimulant may have application in the treatment of immunodeficiency diseases, allergic manifestation, and combinational therapy with antibiotics and as a vaccine adjuvant.


  Acknowledgments Top


We are extremely thankful to Prof. M. A. Jafri, Director, National Institute of Unani Medicine for providing basic facilities to carry out this work. We are also thankful to Dr. Ghulamuddin Sofi, Lecturer, Department of Ilmul Advia, NIUM, Bangalore for statistical analysis and Dr. Jayaram N, Pathologist, Anand Diagnostics, for his crucial contribution regarding cytometery examination not available in other laboratories.

 
  References Top

1.Suhami RL, Moxham J. Text Book of Medicine. 4 th ed. New York: Churchill Livingstone; 2004. p. 183-5.  Back to cited text no. 1
    
2.Park K. Textbook of Preventive and Social Medicine. 20 th ed. Jabalpur: Banarsidas Bhanot; 2007. p. 512.  Back to cited text no. 2
    
3.Kumar V. Geriatric medicine. In: Shah SN, editor. API Textbook of Medicine. Mumbai: API; 2003. p. 1459-62.  Back to cited text no. 3
    
4.Fülöp T, Larbi A, Hirokawa K, Mocchegiani E, Lesourds B, Castle S, et al. Immunosupportive therapies in aging. Clin Interv Aging 2007;2:33-54.  Back to cited text no. 4
    
5.Moskovitz J, Yim MB, Chock PB. Free radicals and disease. Arch Biochem Biophys 2002;397:354-9.  Back to cited text no. 5
    
6.Hakim FT, Flomerfelt FA, Boyiadzis M, Gress RE. Aging, immunity and cancer. Curr Opin Immunol 2004;16:151-6.  Back to cited text no. 6
    
7.Ko KM, Leung HY. Enhancement of ATP generation capacity, antioxidant activity and immunomodulatory activities by Chinese Yang and Yin tonifying herbs. Chin Med 2007;2:3.  Back to cited text no. 7
    
8.Ismail J. Zakhira khuarzam shahi. Vol. 5 New Delhi: Kitab al Shifa; 2010. p. 94.  Back to cited text no. 8
    
9.Kabeeruddin M. Bayaze Kabeer. Lahore: Siddiqui Publications; 1921. p. 12, 36.  Back to cited text no. 9
    
10.Moss RW. Cancer Therapy-The Independent Consumer Guide to Non-toxic Treatment and Prevention. New York: Equinox Press;1996. p. 126-7.  Back to cited text no. 10
    
11.Singh S, P. K. Sharma, N. Kumar, R. Dudhe Biological activities of Aloe vera. Int J Pharm Technol 2010;l2:259-80.  Back to cited text no. 11
    
12.Hamman JH. Composition and applications of Aloe vera leaf gel. Molecules 2008;13:1599-616.  Back to cited text no. 12
[PUBMED]    
13.Assimopoulou AN, Zlatanos SN, Papageorgiou VP. Anti-oxidant activity of natural resins and bio-active triterpenes in oil substrates. Food Chem 2005;92:721-7.  Back to cited text no. 13
    
14.Bakshi H, Sam S, Islam T, Singh P, Sharma M. The free radical scavenging and the lipid peroxidation inhibition of crocin isolated from Kashmiri saffron (Crocus sativus) occurring in northern part of India International Journal of PharmTech Research CODEN (USA): IJPRIF 2009;1:1317-21.  Back to cited text no. 14
    
15.Khazen W, M'bika JP, Tomkiewicz C, Benelli C, Chany C, Achour A, et al. Expression of macrophage-selective markers in human and rodent adipocytes. FEBS Lett 2005;579:5631-4.  Back to cited text no. 15
    
16.Haffor AS. Effect of Commiphora molmol on leukocytes proliferation in relation to histological alterations before and during healing from injury. Saudi J Biol Sci 2010;17:139-46.  Back to cited text no. 16
[PUBMED]    
17.Steinmann GG. Changes in the human thymus during aging. Curr Top Pathol 1986;75:43-88.  Back to cited text no. 17
[PUBMED]    
18.Tte. Cor. Mario González-Quevedo Rodríguez, Dr. Gonzalo Abín Montalván, Dr. Nelson Merino García, Lic. José de la Paz Naranjo Lic. Miguel Alonso González Effect of Aloe barbadensis on the thymus gland involution of mice. Rev Club Med Mil 1990;28:88-92.  Back to cited text no. 18
    
19.Reynolds T, Dweck AC. Aloe vera leaf gel: A review update. J Ethnopharmacol 1999;68:3-37.  Back to cited text no. 19
    
20.Turner CE, Williamson DA, Stroud PA, Talley DJ. Evaluation and comparison of commercially available Aloe vera L. products using size exclusion chromatography with refractive index and multi-angle laser light scattering detection. Int Immunopharmacol 2004;4:1727-37.  Back to cited text no. 20
    
21.Bani S, Pandey A, Agnihotri VK, Pathania V, Singh B. Selective Th2 upregulation by Crocus sativus: A neutraceutical spice. Evid Based Complement Alternat Med 2011;2011:1-9.  Back to cited text no. 21
    
22.Gartner LP, Hiatt JL. Color Textbook of Histology. 5 th ed. Philadelphia, PA: Saunders Elsevier; 2007. p. 225.  Back to cited text no. 22
    
23.Lefebvre JS, Haynes L. Aging of the CD4 T-cell compartment. Open Longev Sci 2012;6:83-91.  Back to cited text no. 23
    
24.Zhu J, Paul WE. CD4 T-cells: Fates, functions, and faults. Blood 2008;112:1557-69.  Back to cited text no. 24
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]


This article has been cited by
1 Skin Aging Remedies in Traditional Persian Medicine
Laila Shirbeigi,Maryam Iranzadasl,Parvin Mansouri,Somayeh Hejazi,Jale Aliasl
Journal of Skin and Stem Cell. 2015; 2(1)
[Pubmed] | [DOI]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Materials and me...
Results
Discussion
Acknowledgments
References
Article Tables

 Article Access Statistics
    Viewed1541    
    Printed42    
    Emailed0    
    PDF Downloaded75    
    Comments [Add]    
    Cited by others 1    

Recommend this journal