DOI QR코드

DOI QR Code

Therapeutic Evaluation of a Topical Unani Formulation, Tila-i Muhāsā in Buthūr Labaniyya (Acne Vulgaris): A Randomized, Controlled Clinical Study

  • Azahar, Mohd (Department of Moalajat (Medicine), National Research Institute of Unani Medicine for Skin Disorders (NRIUMSD)) ;
  • Uddin, Qamar (Department of Moalajat (Medicine), National Research Institute of Unani Medicine for Skin Disorders (NRIUMSD)) ;
  • Kazmi, Munawwar Husain (Ilmul Advia (Pharmacology), National Research Institute of Unani Medicine for Skin Disorders (NRIUMSD)) ;
  • Khatoon, Faiza (Department of Moalajat (Medicine), National Research Institute of Unani Medicine for Skin Disorders (NRIUMSD)) ;
  • Husain, Nazim (Department of Moalajat (Medicine), National Research Institute of Unani Medicine for Skin Disorders (NRIUMSD))
  • Received : 2020.04.09
  • Accepted : 2020.04.20
  • Published : 2020.05.29

Abstract

Introduction: Buthūr Labaniyya (Acne vulgaris) is a multifactorial disorder of the pilosebaceous units characterized by non-inflammatory and inflammatory clinical lesions. Several Unani medications have been used for centuries to treat acne. Objectives: Evaluation of safety and efficacy of Tila-i Muhāsā in patients with acne vulgaris Materials and Methods: This clinical study was conducted in patients with acne vulgaris. Patients applied Tila-i Muhāsā or 5% Benzoyl Peroxide (BPO) once daily for 6 weeks. Assessment of efficacy was carried out by Global Acne Grading System (GAGS) and Patient Global Assessment (PGA) scores. In addition, overall severity of acne was evaluated on a 5-point Cook's acne grading scale using photographic standards. Assessment of safety was performed through adverse drug reactions, local dermal tolerability, vital signs, and routine laboratory investigations. Results: A total of 60 patients (30 in each group) completed 6 weeks of treatment. The mean percentage reduction in GAGS score at 6 weeks from baseline in Unani group (66.97%) and BPO group (59.09%) was statistically significant (P<0.0001). After 6 weeks of therapy, the mean percentage reduction in PGA score compared to baseline in Unani group (57.44%) and BPO group (50.23%) was statistically significant (P<0.0001). No serious adverse events were reported in both groups; however, mild adverse events occurred more frequently in BPO group (30%) compared to Unani group (10%). Conclusion: Tila-i Muhāsā was found to be effective and safe in the treatment of acne vulgaris. However, further clinical studies with larger sample size and longer duration of therapy need to be conducted.

Keywords

References

  1. Abiya SE, Odiyi BO, Falarunu LR, Abiya NU. Antimicrobial activity of three medicinal plants against acne-inducing bacteria Propionibacterium acnes. Brazilian Journal of Biological Sciences. 2018; 5(10):277-288. https://doi.org/10.21472/bjbs.051008
  2. Abriham H, Paulos B. In vitro Antioxidant and Antibacterial Activity of Albizia lebbeck (L) Benth Stem Bark. Sci. Technol. Arts Res. J. 2015; 4(2):204-206. https://doi.org/10.4314/star.v4i2.25
  3. Aditi G, Bhandari BS, Rai N. Antimicrobial activity of medicinal plants Azadirachta indica A. Juss, Allium cepa L. and Aloe vera L. Int. J Pharm Tech Res. 2011; 3(2):1059-1065.
  4. Adityan B, Kumari R, Thappa DM. Scoring systems in acne vulgaris. Indian J Dermatol Venereol Leprol. 2009; 75(3):323-326. https://doi.org/10.4103/0378-6323.51258
  5. Ali MT, Haque ST, Kabir ML, Rana S, Haque ME. A comparative study of in vitro antimicrobial, antioxidant and cytotoxicactivity of Albizia lebbeck and Acacia nilotica stem bark. Bulletin of Faculty of Pharmacy, Cairo University. 2018;56:34-38. https://doi.org/10.1016/j.bfopcu.2017.10.002
  6. Ali SS. Unani Adviya Mufarrada, 4th Ed. (New Delhi, India: National Council for Promotion of Urdu Language, Ministry of HRD), pp. 57-58,275-276, 2010.
  7. Anonymous. Standardization of Single Drugs of Unani Medicine, Vol-1,2,3,4. (New Delhi, India: CCRUM, Ministry of Health and Family), pp. 42-46,86-90,262-266,7-12,79-83,262-265,79-83,256-260, 1987.
  8. Anonymous. The Unani Pharmacopoeia of India, Part-I, Vol.-2. (New Delhi, India: Dept. of AYUSH, M/o Health & FW), pp. 57,58,81,82, 2007.
  9. Anonymous. The Unani Pharmacopoeia of India, Part-I, Vol.-4. (New Delhi, India: Dept. of AYUSH, M/o Health & FW), pp. 102,103, 2007.
  10. Anonymous. Standard Unani Medical Terminology. (New Delhi, India: CCRUM, Dept. of AYUSH), pp. 303, 2012.
  11. Antaki D. Tadhkira Uli al-Albab. (New Delhi, India: CCRUM, Ministry of Health & Family Welfare), pp. 87, 2010.
  12. Arzani HMA. Tibb-i Akbar, Translated by Hussain HM. (Deoband, India: Faisal Publications), pp. 697,722.
  13. Arzani HMA. Mizan al-Tibb, Translated by Hakim Kabir al-Din. (New Delhi, India: Idara Kitab al-Shifa), pp. 249, 2001.
  14. Babu NP, Pandikumar P, Ignacimuthu S. Anti-inflammatory activity of Albizia lebbeck Benth., an ethnomedicinal plant, in acute and chronic animal models of inflammation. Journal of Ethnopharmacology. 2009; 125:356-360. https://doi.org/10.1016/j.jep.2009.02.041
  15. Baghdadi IH. Kitab al-Mukhtarat fi'l Tibb, Vol. 4. (New Delhi, India: CCRUM, Dept. of AYUSH, Ministry of Health & Family Welfare), pp. 188-189.
  16. Balakrishnan KP, Narayanaswamy N, Subba P, Poornima EH. Antibacterial activity of certain medicinal plants against acne inducing bacteria. Int J Pharma Bio Sci. 2011; 2(3):476-481.
  17. Barnes LE, Levender MM, Fleischer AB, Feldman SR. Quality of life measures for acne patients. Dermatologic Clinics. 2012; 30(2):293-300. https://doi.org/10.1016/j.det.2011.11.001
  18. Barua CC, Talukdar A, Barua AG, Chakraborty A, Sarma RK, Bora RS. Evaluation of the wound healing activity of methanolic extract of Azadirachta indica (Neem) and Tinospora cordifolia (Guduchi) in rats. Pharmacologyonline. 2010; 1:70-77.
  19. Basak PY, Gultekin F, Kilinc I. The role of the antioxidative defense system in papulopustular acne. J Dermatol. 2001; 28(3):123-127. https://doi.org/10.1111/j.1346-8138.2001.tb00105.x
  20. Benisheikh AAG, Muhammad FM, Kelluri H, Aliyu ZM, Mallam UB, Jibrin MW. Phytochemical Extraction and Antimicrobial Studies on Crude Leaf Extract of Azadirachta indica (Neem) in Semi-Arid Region of Borno State, Nigeria. International Journal of Research & Review. 2019; 6(12):516-522.
  21. Bolognia JL, Schaffer JV, Cerroni L, Callen JP, Cowen EW, . Dermatology, Vol. 1, 4th Edn. (US: Elsevier Limited), pp. 588-603, 2018.
  22. Bowe WP, Patel N, Logan AC. Acne vulgaris: the role of oxidative stress and the potential therapeutic value of local and systemic antioxidants. J Drugs Dermatol. 2012; 11(6):742-746
  23. Chattopadhyay RR, Chattopadhyay RN, Maitra SK. Possible mechanism of anti-inflammatory activity of Azadirachta indica leaf extract. Indian J. Pharmacol. 1993; 25:99-100.
  24. Chattopadhyay RR. Possible biochemical mode of antiinflammatory action of Azadirachta indica A. Juss in rats. Indian Journal of Experimental Biology. 1998; 36(4):418-420.
  25. Chaudhary M, Sharma AK, Kumar R, Chauhan B, Kaushik K, Agarwal V. Comparative Immunomodulator Activity of Leaves and Bark of Albizia lebbeck (Linn.) Benth. Int. J. Res. Dev. Pharm. L. Sci. 2012; 1(1):25-27.
  26. Chulet R, Pradhan P, Sharma KS, Jhajharia KM. Phytochemical screening and antimicrobial activity of Albizia lebbeck, J. Chem. Pharm. Res., 2010; 2(5): 476-484.
  27. Cook CH, Centner RL, Michaels SE. An Acne Grading Method Using Photographic Standards. Archives of Dermatology. 1979; 115(5):571-575. https://doi.org/10.1001/archderm.1979.04010050005003
  28. Das AK, Ahmed F, Bachar SC, Kundu J, Dev S. Antiinflammatory effect of Albizzia lebbeck (Benth.) Bark. Online Journal of Biological Science. 2003; 3:685-687. https://doi.org/10.3923/jbs.2003.685.687
  29. Dinda A, Das D, Ghosh G, Kumar S. Analgesic and antiinflammatory activity of hydro-alcoholic extract of Azadirachta indica Leaf. Pharmacologyonline. 2011; 3:477-484.
  30. Doshi A, Zaheer A, Stiller MJ. A comparison of current acne grading systems and proposal of a novel system. International Journal of Dermatology. 1997; 36(6):416-418. https://doi.org/10.1046/j.1365-4362.1997.00099.x
  31. Durrani FR, Chand N, Jan M, Sultan A, Durrani Z, Akhtar S. Immunomodulatory and growth promoting effects of Neem leaves infusion in broiler chicks. Sarhad J. Agric. 2008; 24:655-659.
  32. Ganaie AA, Mishra RP, Allaie AH. Antioxidant activity of some extracts of Iris ensata. J Pharmacogn Phytochem. 2018; 7(2):230-235.
  33. Ganguli NB, Bhatt RM. Mode of Action of active principles from stem bark of Albizia lebbeck. Indian J Experiment Biol. 1993; 31:125-129.
  34. Ghani N. Khazain al Advia. (New Delhi, India: Idara Kitab al-Shifa), pp. 242-3,370-1,482-5,595-6,616-9,720-1,800-1, 2010.
  35. Ghimeray AK, Jin CW, Ghimire BK, Cho DH. Antioxidant activity and quantitative estimation of azadirachtin and nimbin in Azadirachta indica A. Juss grown in foothills of Nepal. Afr. J. Biotechnol. 2009; 8(13):3084-3091.
  36. Ghonmode WN, Balsaraf OD, Tambe VH, Saujanya KP, Patil AK, Kakde DD. Comparison of the antibacterial efficiency of Neem leaf extracts, grape seed extracts and 3% sodium hypochlorite against E. feacalis - an in vitro study. J Int Oral Health. 2013; 5(6):61-66.
  37. Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, Klaus Wolff K. Fitzpatrick's Dermatology in General Medicine, 8th Edn. (US: McGraw-Hill Companies), pp. 897-917, 2012.
  38. Goodman G. Acne and Acne Scarring - the case for active and early intervention. Australian Family Physician. 2006; 35(7):503-504.
  39. Goodman GJ. Post-acne scarring: A short review of its pathophysiology. Australas. J. Dermatol. 2001; 42:84-90. https://doi.org/10.1046/j.1440-0960.2001.00487.x
  40. Grange PA, Chereau C, Raingeaud J, Nicco C, Weill B, et al. Production of Superoxide Anions by Keratinocytes initiates P. acnes-induced Inflammation of the Skin. PLoS Pathogens. 2009; 5(7):1-14.
  41. Griffiths C, Barker J, Bleiker T, Chalmers R, Creamer D. Rook's Textbook of Dermatology, 9th Edn. (US: John Wiley & Sons, Ltd.), pp. 90.1-50, 2016.
  42. Hakim MA. Bustan al Mufradat Jadid. (New Delhi, India: Idara Kitab al-Shifa), pp. 85,106,129,176,286,335-7, 2002.
  43. Ibn Sina. Al Qanun fi'l Tibb. (New Delhi, India: Idara Kitab al-Shifa), pp. 1420,1432, 2010.
  44. Ingham E. The immunology of Propionibacterium acnes and acne. Curr Opin Infect Dis. 1999; 12(3):191-197. https://doi.org/10.1097/00001432-199906000-00006
  45. Jain A, Basal E. Inhibition of Propionibacterium acnes-induced mediators of inflammation by Indian herbs. Phytomedicine. 2003; 10(1):34-38. https://doi.org/10.1078/094471103321648638
  46. Kabiruddin HM. Bayad-i Kabir, Vol. 2, 15th Edn. (Gujrat, India: Shaukat Book Depot), p. 126, 1977.
  47. Kamlesh JW, Lakhotiya CL, Umekar MJ. Formulation and Evaluation of Cream of Azadirachta indica leaves extracts on Skin Renewal rate. Int. J. ChemTech Res. 2009; 1(1):88-95.
  48. Kaur G, Alam MS, Athar M. Nimbidin suppresses functions of macrophages and neutrophils: relevance to its anti-inflammatory mechanisms. Phytotherapy Research. 2004; 18(5):419-424. https://doi.org/10.1002/ptr.1474
  49. Khare CP. Indian Medicinal Plants - An Illustrated Dictionary, New York, USA: Springer Verlag, Berlin Heidelberg), pp. 30,75,76,336, 2007.
  50. Mahfuzul Hoque MD, Bari ML, Inatsu Y, Juneja VK, Kawamoto S. Antibacterial activity of guava (Psidium guajava L.) and neem (Azadirachta indica A. Juss.) extracts against foodborne pathogens and spoilage bacteria. Foodborne Pathog Dis. 2007; 4(4):481-488. https://doi.org/10.1089/fpd.2007.0040
  51. Maragathavalli S, Brindha S, Kaviyarasi NS, Annadurai B, Gangwar SK. Antimicrobial activity in leaf extract of Neem (Azadirachta indica Linn.). Int. J. Sci. Nat., 2012; 3:110-113.
  52. Mosaddek ASM, Rashid MMU. A comparative study of the antiinflammatory effect of aqueous extract of Neem leaf and dexamethasone. Bangladesh J. Pharmacol. 2008; 3(1):44-47.
  53. Osunwoke EA, Olotu EJ, Allison TA, Onyekwere JC. The wound healing effects of aqueous leave extracts of Azadirachta indica on wistar rats. J. Nat. Sci. Res. 2013; 3(6):181-186.
  54. Papadakis MA, McPhee SJ, Rabow MW. Current Medical Diagnosis & Treatment. 58th Edn. (US: McGraw-Hill Education), pp. 134-136, 2019.
  55. Patel P, Bhalodia Y, Gohil T, Malavia S, Devmurari V. In-vitro antioxidant activity of Azadirachta indica leaves. J Advances Pharmacy Healthcare Res. 2011; 1(3):22-7.
  56. Patterson JW, Hosler GA. Weedon's Skin Pathology. 4th Edn. (USA: Churchill Livingstone, Elsevier Ltd.), pp. 459-461, 2016.
  57. Pramanik K., Bhattacharya P, Chatterjee TK, Mandal SC. Antiinflammatory activity of methanol extract of Albizzia lebbeck (Mimosaceae) bark. Eur Bulletin Drug Res. 2005; 13:71-75.
  58. Ralston SH, Penman ID, Strachan MWJ, Hobson RP. Davidson's Principles and Practice of Medicine. 23rd Edn. (Edinburgh, Scotland: Elsevier Ltd.), pp. 1241-1243, 2018.
  59. Rashid RB, Chowdhury R, Jabbar A, Hasan CM, Rashid MA. Constituents of Albizia lebbeck and antibacterial activity of an isolated flavone derivatives. Saudi Pharm. J., 2003; 11(1-2):52-56.
  60. Ray A, Banerjee BD, Sen P. Modulation of humoral and cell-mediated immune responses by Azadirachta indica (Neem) in mice. Indian J Exp Biol. 1996; 34(7):698-701.
  61. Razi ABMZ. Kitab al-Hawi fi'l Tibb. Vol. 23. (Aligarh, India: Saba Publishers), pp. 36-37, 1994.
  62. Renu S, Rakha NK, Sandeep G, Mishra SK. Effect of Neem (Azadirachta indica) leaf extract administration on immune responses of broiler chickens. J. Immunol. Immunopathol. 2003; 5:47-50.
  63. Sadekar RD, Kolte AY, Barmase BS, Desai VF. Immunopotentiating effects of Azadirachta indica (Neem) dry leaves powder in broilers, naturally infected with IBD virus, Ind J Exp Biol. 1998; 36(11):1151-1153.
  64. Saha A, Ahmed M. The analgesic and anti-inflammatory activities of the extract of Albizia lebbeck in animal model. Pak. J. Pharm. Sci. 2009; 22(1):74-77.
  65. Salem MZM, Aly H, Gohar Y, El-Sayed AW. Biological activity of extracts from Morus alba L., Albizzia lebbeck (L.) Benth. and Casuarina glauca Sieber against the Growth of some Pathogenic Bacteria. Int J Agri Food Res. 2013; 2(1):9-22.
  66. Sarmiento WC, Maramba CC, Gonzales MLM. An in vitro study on the antibacterial effect of Neem (Azadirachta indica) leaf extracts on methicillin-sensitive and methicillinresistant Staphylococcus aureus. PIDSP Journal. 2011; 12(1):40-45.
  67. Schumacher M, Cerella C, Reuter S, Dicato M, Diederich M. Anti-inflammatory, pro-apoptotic, and anti-proliferative effects of a methanolic neem (Azadirachta indica) leaf extract are mediated via modulation of the nuclear factor-${\kappa}B$ pathway. Genes and Nutrition. 2011; 6(2):149-160. https://doi.org/10.1007/s12263-010-0194-6
  68. Sehgal VN. Textbook of Clinical Dermatology. 5th Edn. (New Delhi, India: Jaypee Brothers Medical Publishers), pp. 12-16, 2011.
  69. Sina I. Al-Qanun fi'l Tibb, Urdu Translation by Hakim Ghulam Hasnayn Kinturi. Vol. IV. (New Delhi, India: Idara Kitab al-Shifa), pp. 1420, 1432, 2010.
  70. Sithisarn P, Supabphol R, Gritsanapan W. Antioxidant activity of siamese neem tree. J Ethnopharmacol. 2005; 99(1):109-112. https://doi.org/10.1016/j.jep.2005.02.008
  71. Suruse PB, Bodele SB, Duragkar NJ, Saundankar YG. In-Vitro Evaluation of Antioxidant Activity of Albizia lebbeck Bark. Int. J. Biol. Sci. Ayur. Res. 2013; 1(1):6-17.
  72. Tasnim J, Saha A, Ahmed S, Sultana N, Muslim T, Rahman MA: Biological Studies of the Bark of Albizia Lebbeck (L.) Benth. Int J. Pharm Sci Res. 2014; 5(11):4969-4974.
  73. Upadhyay SN, Dhawan S, Garg S, Talwar GP. Immunomodulatory effects of Neem (Azadirachta indica) oil. Int. J. Immunopharmacol. 1992; 14(7):1187-1193. https://doi.org/10.1016/0192-0561(92)90054-O
  74. van der Nat JM, Klerx JP, van Dijk H, de Silva KT, Labadie RP. Immunomodulatory activity of an aqueous extract of Azadirachta indica stem bark. J Ethnopharmacol. 1987; 19(2):125-131. https://doi.org/10.1016/0378-8741(87)90036-5
  75. Vos T, Allen C, Arora M, Barber RM, Bhutta ZA, . Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016; 388(10053):1545-1602. https://doi.org/10.1016/S0140-6736(16)31678-6
  76. Wadher KJ, Lakhotiya CL, Umekar MJ. Skin renewal effect of different extracts of leaves of Azadirachta indica. Int. J. PharmTech Res. 2009; 1(4):1350-1353.
  77. Wagay JI, Jain K. Phytochemical Analysis and Antimicrobial Activity of Iris kashmiriana and Iris ensata Extracts against Selected Microorganisms, J Drug Delivery & Therapeutics, 2018; 8(6):28-34. https://doi.org/10.22270/jddt.v8i6.1975
  78. Williams HC, Dellavalle RP, Garner S. Acne vulgaris. Lancet. 2012; 379(9813):361-372. https://doi.org/10.1016/S0140-6736(11)60321-8
  79. Wolff K, Johnson RA, Saavedra AP. Fitzpatrick's Color Atlas and Synopsis of Clinical Dermatology. 7th Edn. (New York, USA: McGraw-Hill Education), pp. 2-7, 2013.
  80. Yerima MB, Jodi SM, Oyinbo K, Maishanu HM, Farouq AA, Junaidu AU. Effect of Neem extracts (Azadirachta indica) on bacteria isolated from adult mouth. J. Basic & Appl. Sci. 2012; 20:64-67.
  81. Zeind CS, Carvalho MG. Applied Therapeutics: the clinical use of drugs. 11th Edn. (Philadelphia, US: Wolters Kluwer Health), pp. 824-831, 2018.
  82. Zia-Ul-Haq M, Ahmad S, Qayum M, Sezai E. Compositional studies and antioxidant potential of Albizia lebbeck (L.) Benth. pods and seeds, Turk J. Biol., 2013; 37:25-32.