IMMUNOMODULATORY EFFECTS OF TINOSPORA CORDIFOLIA LOTION ON INTERLEUKIN-1, INTERLEUKIN-6 AND INTERLEUKIN-8 LEVELS IN SCABIES-INFECTED PEDIATRIC PATIENTS: A SINGLE BLIND, RANDOMIZED TRIAL
Abstract
Scabies is a contagious, parasitic skin infestation caused by Sarcoptes scabiei mite, which has the ability to regulate the host’s inflammatory and immune responses. It is a serious community health problem in many less-developed countries. A randomized, controlled, parallel, pilot clinical study was performed to investigate the immunomodulatory effect of the formulated Tinospora lotion in clinically diagnosed scabies-infected patients through Enzyme-Linked Immunosorbent Assay (ELISA) for Interleukin-1, Interleukin-6 and Interleukin-8 using blood serum samples. The pediatric patients were treated with Tinospora and Permethrin lotions for three consecutive days for two weeks. Blood extraction was performed before and after the second and fourth week of treatment period. Tinospora lotion significantly reduced the Interleukin-1 (IL-1) and Interleukin-6 (IL-6) levels from Day 14 to Day 28 (p=0.0002) comparable to Permethrin lotion (p<0.050). Permethrin efficiently decreased Interleukin-8 (IL-8) levels than Tinospora at Day 14 (p=0.0155). Down regulation of Interleukin 1, 6, and 8 levels in scabies infestation inhibits hyperkeratosis and infiltration of inflammatory cells into scabietic lesion. The modulation effect of the Tinospora lotion on interleukin levels reinforces its anti-scabies activity.
Keywords:
Immunomodulatory, interleukin, scabies, TinosporaDOI
https://doi.org/10.25004/IJPSDR.2014.060307References
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2. Morgan M, Arlian L. Response of Human Skin Equivalents to Sarcoptes scabiei. Journal of Medical Entomology 2010; 47 (5): 877-883.
3. Vorou R, Remoudaki HD, Maltezou HC. Nosocomial scabies- Review. Journal of Hospital Infection 2007; 65: 9-14.
4. Laurel Elder B, Arlian L, Morgan M. Modulation of human dermal microvascular endothelial cells by Sarcoptes scabiei in combination with proinflammatory cytokines, histamine, and lipid-derived biologic mediators. Cytokine 2009; 47: 103-111.
5. De Padua LS, Lugod GC, Pancho JV. Handbook on Philippine Medicinal Plants. Documentation and Information Section, Office of the Director of Research, University of the Philippines, Los Banos, Laguna, Phil.,1977 pp. 89-94.
6. Salazar N, Sabordo N, Romero R, Montalban C, Acacio M, Tarrayo M. Tinospora rumphii Boerl (Makabuhay) in the Treatment of Scabies. Phil. J. Microbiol. Infect. Dis. 1987; 16: 25-29.
7. Reyes JM, King-Ismael D, Llamasares A, Ochoa MT. Phase I and Phase II Clinical Trial on the Efficacy and Safety of Tinospora rumphii Boerl. (Makabuhay) Lotion for the Treatment of Scabies. UST Department of Dermatology, Manila, Philippines, 2008.
8. Sohni Y, Kaimal P, Bhatt R. The antiamoebic effect of a crude drug formulation of herbal extracts against Entamoeba histolytica in-vitro and in-vivo. Journal of Ethnopharmacology 1995; 45: 43-52.
9. Goel HC, Prasad J, Singh S , Sagar R, Agrawal PK, Bala M. Radioprotective Potential of a Herbal Extract of Tinospora cordifolia. Journal Radiation Research 2004; 45(1): 61-68.
10. Bishayi B, Roychowdhury S, Ghosh S, Sengupta M. Hepatoprotective and immunomodulatory properties of Tinospora cordifolia in CCl4 intoxicated mature albino rats. Journal Toxicological Science 2002; 27(3): 139-146.
11. Bisset N, Nwaiwu J. Quaternary Alkaloids of Tinospora Species. Planta Medica 1983; 48: 275-79.
12. Thippeswamy G, Sheela ML, Salimath B. Octacosanol isolated from Tinospora cordifolia downregulates VEGF gene expression by inhibiting nuclear translocation of NFκB and its DNA binding activity. European Journal of Pharmacology 2008; 588: 141-150.
13. Desai V, Ramkrishnan R, Chintalwar G, Sainis KB. G1-4A, an Immunomodulatory polysaccharide from Tinospora cordifolia, modulates macrophage responses and protects mice against lipopolysaccharide induced endotoxic shock. International Immunopharmacology 2007; 7: 1375-1386
14. Nair PKR, Rodriguez S, Ramachandran R, Alamo A, Melnick S, Escalon E, Garcia P, Wnuk S, Ramachandran C. Immune stimulating properties of a novel polysaccharide from the medicinal plant Tinospora cordifolia. International Immunopharmacology 2004; 4:1645-1659.
15. Raghu R, Sharma D, Ramakrishnan R, Khanam S, Chintalwar G, Sainis K. Molecular events in the activation of β cells and macrophages by a non-microbial TLR4 agonist, G1-4A from Tinospora cordifolia. Immunology Letters 2009; 123: 60-71.
16. Manjrekar PN, Jolly CI, Narayanan S. Comparative studies of the Immunomodulatory activity of Tinospora cordifolia and Tinospora sinensis. Fitoterapia 2000; 71: 254-257.
17. Castillo A, Osi M, Ramos JDA, De Francia J, Dyjunco M, Quilala P. Efficacy and safety of Tinospora cordifolia lotion in Sarcoptes scabiei var hominis infected pediatric patients: A single blind randomized controlled trial. Journal of Pharmacology and Pharmacotherapeutics 2013; 4 (1): 39-46.
18. Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behavior Research Methods 2007; 39: 175-191.
19. Rivera EF, Sison EM, Aligui G. A Comparative Study of The Efficacy of Crotamiton and Tinospora rumphii in the Treatment of Scabies in Children. Journal of Phil. Medical Assoc.1983; 58: 265-67.
20. Meinking T, Burkhart CN, Burkhart CG. Dermatology. Vol.1, London, Mosby, 2003, pp. 1321-1324.
21. Margeli A, Skenderi K, Tsironi M, Hantzi E, Matalas A, Vrettou C, Kanavakis E, Chrousos G, Papassotiriou I. Dramatic Elevations of Interleukin-6 and Acute–Phase Reactants in Athletes Participating in the Ultradistance Foot Race Spartathlon: Severe Systemic Inflammation and Lipid and Lipoprotein Changes in Protracted Exercise. The Journal of Clinical Endocrinology & Metabolism 2005; 90(7): 3914-3918.
22. Pledge D, Grosset JF, Onambélé-Pearson G. Is there a morning-to-evening difference in the acute IL-6 and cortisol responses to resistance exercise? Cytokine 2011; 55: 318–323.
23. Akbar H, Idrees M, Butt S, Awan Z, Sabar MF, Rehaman I, Hussain A, Saleem S. High baseline interleukine-8 level is an Independent risk factor for the achievement of sustained virological response in chronic HCV patients. Infection, Genetics and Evolution 2011; 11: 1301–1305.
24. Bergstrom F, Reynolds S, Johnstone M, Pike R, Buckle A, Kemp D, Fischer K, Blom A. Scabies Mite Inactivated Serine Protease Paralogs Inhibit the Human Complement System. The Journal of Immunology 2009; 182: 7809-7817.
25. Mika A, Reynolds SL, Mohlin FC, Willis C, Swe PM. Novel Scabies Mite Serpins Inhibit the Three Pathways of the Human Complement System. PLoS ONE 2012; 7(7): e40489. doi:10.1371/journal.pone.0040489.
26. Henderson C, Goldbach-Mansky R. Monogenic IL-1 mediated autoinflammatory and immunodeficiency syndromes: Finding the right balance in response to danger signals. Clinical Immnunology 2010; 135: 210-222.
27. Takeda K, Akira S. Toll-like receptors in innate immunity. International Immunology 2005; 17(1): 1-14.
28. Wilder RL. Interleukin-6 in autoimmune and inflammatory diseases. Ann Intern Med.1998; 128: 127-137.
29. Neurath M, Finotto S. IL-6 signaling in autoimmunity, chronic inflammation, and inflammation-associated cancer. Cytokine & Growth Factor Reviews 2011; 22: 83-89.
30. Akdis M, Burgler S, Crameri R, Eiwegger T, Fujita H, Gomez E, Klunker S, Meyer N, O’Mahony L, Palomares O, Rhyner C, Quaked N, Schaffartzik A, Van De Veen W, Zeller S, Zimmermann M, Akdis C, MD. Interleukins, from 1 to 37, and interferon-γ: Receptors, functions, and roles in diseases. Journal of Allergy and Clinical Immunol. 2011; 127:701-21.
31. Singh SK, Dimri U, Sharma MC, Swarup D, Sharma B. Determination of oxidative status and apoptosis in peripheral blood of dogs with sarcoptic mange. Veterinary Parasitology 2011; 178: 330-338.
32. Goldbach-Mansky R, Kastner D. Autoinflammation: The Prominent role of IL-1 in monogenic autoinflammatory diseases and implications for common illnesses. Journal of Allergy Clinical Immunology 2009; 124: 1141-1149.
33. Wu S, Gao J, Thai Dinh Q, Chen C, Fimmel S. IL-8 production and AP-1 transactivation induced by UVA inhuman keratinocytes: Roles of d-α-tocopherol. Molecular Immunology 2008; 45: 2288-2296.
34. Marino M, Scuderi F, Provenzano C, Scheller J, Rose-John S, Bartoccioni E. IL-6 regulates MCP-1, ICAM-1 and IL-6 expression in human myoblasts. Journal of Neuroimmunology 2008; 196: 41-48.
35. Romano M, Sironi M, Toniatti C, Polentarutti N, Fruscella P, Ghezzi P, Faggioni R, Luini W, van Hinsbergh V, Sozzani S, Bussolino F, Poli V, Ciliberto G, Mantavani A. Role of IL-6 and Its Soluble Receptor in Induction of Chemokines and Leukocyte Recruitement. Immunity 1997; 6: 315-325.
36. Premanath R, Lakshmidevi N. Studies on Anti-oxidant activity of Tinospora cordifolia (Miers.) Leaves using in vitro models. Journal of American Science 2010; 6 (10): 736-743.
37. Sharma U, Bala M, Kumar N, Singh B, Munshi R, Bhalerao S. Immunomodulatory active compounds from Tinospora cordifolia. Journal of Ethnopharmacology 2012; 14: 918-926.
38. Cbakrabortyl B, Sbarma GD, Sengupta M. Immunomodulatory Properties of Tinospora cordifolia in Carbon Tetrachloride Intoxicated Swiss Albino Mice. Assam University Journal of Science & Technology: Biological Sciences 2009; 4 (1): 35-39.
39. Aranha I, Clement F, Venkatesh Y. Immunostimulatory properties of the major protein from the stem of the Ayurvedic medicinal herb, guduchi (Tinospora cordifolia). Journal of Ethnopharmacology 2012; 139 (2):366-372.
40. Thatte UM, Rao SG, Dahanukar SA. Tinospora cordifolia induces colony stimulating activity in serum. Journal of Postgraduate Medicine 1994; 40(4): 202-203.
41. Purandare H, Supe A. Immunomodulatory role of Tinospora cordifolia as an adjuvant in surgical treatment of diabetic foot ulcers: A prospective randomized controlled study. Indian Journal of Medical Sciences 2007; 61:347-55.
42. Padmanabhan P, Jangle SN. Evaluation of DPPH Radical Scavenging Activity and Reducing Power of Four Selected Medicinal Plants and Their Combinations. International Journal of Pharmaceutical Sciences and Drug Research 2012; 4(2): 143-146.
43. Ranawat LS, Patel J. Antioxidant and Hepatoprotective Activity of Ethanolic Extracts of Bark of Zanthoxylum armatum DC in Paracetamol-Induced Hepatotoxicity. International Journal of Pharmaceutical Sciences and Drug Research 2013; 5(3): 120-124.
44. Chakraborthy GS. Antioxidant Activity of the Successive Extracts of Aesculus indica Leaves. International Journal of Pharmaceutical Sciences and Drug Research 2009; 1(2): 121-123.
2. Morgan M, Arlian L. Response of Human Skin Equivalents to Sarcoptes scabiei. Journal of Medical Entomology 2010; 47 (5): 877-883.
3. Vorou R, Remoudaki HD, Maltezou HC. Nosocomial scabies- Review. Journal of Hospital Infection 2007; 65: 9-14.
4. Laurel Elder B, Arlian L, Morgan M. Modulation of human dermal microvascular endothelial cells by Sarcoptes scabiei in combination with proinflammatory cytokines, histamine, and lipid-derived biologic mediators. Cytokine 2009; 47: 103-111.
5. De Padua LS, Lugod GC, Pancho JV. Handbook on Philippine Medicinal Plants. Documentation and Information Section, Office of the Director of Research, University of the Philippines, Los Banos, Laguna, Phil.,1977 pp. 89-94.
6. Salazar N, Sabordo N, Romero R, Montalban C, Acacio M, Tarrayo M. Tinospora rumphii Boerl (Makabuhay) in the Treatment of Scabies. Phil. J. Microbiol. Infect. Dis. 1987; 16: 25-29.
7. Reyes JM, King-Ismael D, Llamasares A, Ochoa MT. Phase I and Phase II Clinical Trial on the Efficacy and Safety of Tinospora rumphii Boerl. (Makabuhay) Lotion for the Treatment of Scabies. UST Department of Dermatology, Manila, Philippines, 2008.
8. Sohni Y, Kaimal P, Bhatt R. The antiamoebic effect of a crude drug formulation of herbal extracts against Entamoeba histolytica in-vitro and in-vivo. Journal of Ethnopharmacology 1995; 45: 43-52.
9. Goel HC, Prasad J, Singh S , Sagar R, Agrawal PK, Bala M. Radioprotective Potential of a Herbal Extract of Tinospora cordifolia. Journal Radiation Research 2004; 45(1): 61-68.
10. Bishayi B, Roychowdhury S, Ghosh S, Sengupta M. Hepatoprotective and immunomodulatory properties of Tinospora cordifolia in CCl4 intoxicated mature albino rats. Journal Toxicological Science 2002; 27(3): 139-146.
11. Bisset N, Nwaiwu J. Quaternary Alkaloids of Tinospora Species. Planta Medica 1983; 48: 275-79.
12. Thippeswamy G, Sheela ML, Salimath B. Octacosanol isolated from Tinospora cordifolia downregulates VEGF gene expression by inhibiting nuclear translocation of NFκB and its DNA binding activity. European Journal of Pharmacology 2008; 588: 141-150.
13. Desai V, Ramkrishnan R, Chintalwar G, Sainis KB. G1-4A, an Immunomodulatory polysaccharide from Tinospora cordifolia, modulates macrophage responses and protects mice against lipopolysaccharide induced endotoxic shock. International Immunopharmacology 2007; 7: 1375-1386
14. Nair PKR, Rodriguez S, Ramachandran R, Alamo A, Melnick S, Escalon E, Garcia P, Wnuk S, Ramachandran C. Immune stimulating properties of a novel polysaccharide from the medicinal plant Tinospora cordifolia. International Immunopharmacology 2004; 4:1645-1659.
15. Raghu R, Sharma D, Ramakrishnan R, Khanam S, Chintalwar G, Sainis K. Molecular events in the activation of β cells and macrophages by a non-microbial TLR4 agonist, G1-4A from Tinospora cordifolia. Immunology Letters 2009; 123: 60-71.
16. Manjrekar PN, Jolly CI, Narayanan S. Comparative studies of the Immunomodulatory activity of Tinospora cordifolia and Tinospora sinensis. Fitoterapia 2000; 71: 254-257.
17. Castillo A, Osi M, Ramos JDA, De Francia J, Dyjunco M, Quilala P. Efficacy and safety of Tinospora cordifolia lotion in Sarcoptes scabiei var hominis infected pediatric patients: A single blind randomized controlled trial. Journal of Pharmacology and Pharmacotherapeutics 2013; 4 (1): 39-46.
18. Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behavior Research Methods 2007; 39: 175-191.
19. Rivera EF, Sison EM, Aligui G. A Comparative Study of The Efficacy of Crotamiton and Tinospora rumphii in the Treatment of Scabies in Children. Journal of Phil. Medical Assoc.1983; 58: 265-67.
20. Meinking T, Burkhart CN, Burkhart CG. Dermatology. Vol.1, London, Mosby, 2003, pp. 1321-1324.
21. Margeli A, Skenderi K, Tsironi M, Hantzi E, Matalas A, Vrettou C, Kanavakis E, Chrousos G, Papassotiriou I. Dramatic Elevations of Interleukin-6 and Acute–Phase Reactants in Athletes Participating in the Ultradistance Foot Race Spartathlon: Severe Systemic Inflammation and Lipid and Lipoprotein Changes in Protracted Exercise. The Journal of Clinical Endocrinology & Metabolism 2005; 90(7): 3914-3918.
22. Pledge D, Grosset JF, Onambélé-Pearson G. Is there a morning-to-evening difference in the acute IL-6 and cortisol responses to resistance exercise? Cytokine 2011; 55: 318–323.
23. Akbar H, Idrees M, Butt S, Awan Z, Sabar MF, Rehaman I, Hussain A, Saleem S. High baseline interleukine-8 level is an Independent risk factor for the achievement of sustained virological response in chronic HCV patients. Infection, Genetics and Evolution 2011; 11: 1301–1305.
24. Bergstrom F, Reynolds S, Johnstone M, Pike R, Buckle A, Kemp D, Fischer K, Blom A. Scabies Mite Inactivated Serine Protease Paralogs Inhibit the Human Complement System. The Journal of Immunology 2009; 182: 7809-7817.
25. Mika A, Reynolds SL, Mohlin FC, Willis C, Swe PM. Novel Scabies Mite Serpins Inhibit the Three Pathways of the Human Complement System. PLoS ONE 2012; 7(7): e40489. doi:10.1371/journal.pone.0040489.
26. Henderson C, Goldbach-Mansky R. Monogenic IL-1 mediated autoinflammatory and immunodeficiency syndromes: Finding the right balance in response to danger signals. Clinical Immnunology 2010; 135: 210-222.
27. Takeda K, Akira S. Toll-like receptors in innate immunity. International Immunology 2005; 17(1): 1-14.
28. Wilder RL. Interleukin-6 in autoimmune and inflammatory diseases. Ann Intern Med.1998; 128: 127-137.
29. Neurath M, Finotto S. IL-6 signaling in autoimmunity, chronic inflammation, and inflammation-associated cancer. Cytokine & Growth Factor Reviews 2011; 22: 83-89.
30. Akdis M, Burgler S, Crameri R, Eiwegger T, Fujita H, Gomez E, Klunker S, Meyer N, O’Mahony L, Palomares O, Rhyner C, Quaked N, Schaffartzik A, Van De Veen W, Zeller S, Zimmermann M, Akdis C, MD. Interleukins, from 1 to 37, and interferon-γ: Receptors, functions, and roles in diseases. Journal of Allergy and Clinical Immunol. 2011; 127:701-21.
31. Singh SK, Dimri U, Sharma MC, Swarup D, Sharma B. Determination of oxidative status and apoptosis in peripheral blood of dogs with sarcoptic mange. Veterinary Parasitology 2011; 178: 330-338.
32. Goldbach-Mansky R, Kastner D. Autoinflammation: The Prominent role of IL-1 in monogenic autoinflammatory diseases and implications for common illnesses. Journal of Allergy Clinical Immunology 2009; 124: 1141-1149.
33. Wu S, Gao J, Thai Dinh Q, Chen C, Fimmel S. IL-8 production and AP-1 transactivation induced by UVA inhuman keratinocytes: Roles of d-α-tocopherol. Molecular Immunology 2008; 45: 2288-2296.
34. Marino M, Scuderi F, Provenzano C, Scheller J, Rose-John S, Bartoccioni E. IL-6 regulates MCP-1, ICAM-1 and IL-6 expression in human myoblasts. Journal of Neuroimmunology 2008; 196: 41-48.
35. Romano M, Sironi M, Toniatti C, Polentarutti N, Fruscella P, Ghezzi P, Faggioni R, Luini W, van Hinsbergh V, Sozzani S, Bussolino F, Poli V, Ciliberto G, Mantavani A. Role of IL-6 and Its Soluble Receptor in Induction of Chemokines and Leukocyte Recruitement. Immunity 1997; 6: 315-325.
36. Premanath R, Lakshmidevi N. Studies on Anti-oxidant activity of Tinospora cordifolia (Miers.) Leaves using in vitro models. Journal of American Science 2010; 6 (10): 736-743.
37. Sharma U, Bala M, Kumar N, Singh B, Munshi R, Bhalerao S. Immunomodulatory active compounds from Tinospora cordifolia. Journal of Ethnopharmacology 2012; 14: 918-926.
38. Cbakrabortyl B, Sbarma GD, Sengupta M. Immunomodulatory Properties of Tinospora cordifolia in Carbon Tetrachloride Intoxicated Swiss Albino Mice. Assam University Journal of Science & Technology: Biological Sciences 2009; 4 (1): 35-39.
39. Aranha I, Clement F, Venkatesh Y. Immunostimulatory properties of the major protein from the stem of the Ayurvedic medicinal herb, guduchi (Tinospora cordifolia). Journal of Ethnopharmacology 2012; 139 (2):366-372.
40. Thatte UM, Rao SG, Dahanukar SA. Tinospora cordifolia induces colony stimulating activity in serum. Journal of Postgraduate Medicine 1994; 40(4): 202-203.
41. Purandare H, Supe A. Immunomodulatory role of Tinospora cordifolia as an adjuvant in surgical treatment of diabetic foot ulcers: A prospective randomized controlled study. Indian Journal of Medical Sciences 2007; 61:347-55.
42. Padmanabhan P, Jangle SN. Evaluation of DPPH Radical Scavenging Activity and Reducing Power of Four Selected Medicinal Plants and Their Combinations. International Journal of Pharmaceutical Sciences and Drug Research 2012; 4(2): 143-146.
43. Ranawat LS, Patel J. Antioxidant and Hepatoprotective Activity of Ethanolic Extracts of Bark of Zanthoxylum armatum DC in Paracetamol-Induced Hepatotoxicity. International Journal of Pharmaceutical Sciences and Drug Research 2013; 5(3): 120-124.
44. Chakraborthy GS. Antioxidant Activity of the Successive Extracts of Aesculus indica Leaves. International Journal of Pharmaceutical Sciences and Drug Research 2009; 1(2): 121-123.
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01-07-2014
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“IMMUNOMODULATORY EFFECTS OF TINOSPORA CORDIFOLIA LOTION ON INTERLEUKIN-1, INTERLEUKIN-6 AND INTERLEUKIN-8 LEVELS IN SCABIES-INFECTED PEDIATRIC PATIENTS: A SINGLE BLIND, RANDOMIZED TRIAL”. International Journal of Pharmaceutical Sciences and Drug Research, vol. 6, no. 3, July 2014, pp. 204-10, https://doi.org/10.25004/IJPSDR.2014.060307.
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How to Cite
“IMMUNOMODULATORY EFFECTS OF TINOSPORA CORDIFOLIA LOTION ON INTERLEUKIN-1, INTERLEUKIN-6 AND INTERLEUKIN-8 LEVELS IN SCABIES-INFECTED PEDIATRIC PATIENTS: A SINGLE BLIND, RANDOMIZED TRIAL”. International Journal of Pharmaceutical Sciences and Drug Research, vol. 6, no. 3, July 2014, pp. 204-10, https://doi.org/10.25004/IJPSDR.2014.060307.
