Effect of Curcuma longa Extract as Adjuvant Therapy on IL-6 Serum Levels in Leprosy Type 1 Reaction Patients

Authors

  • Syifa Nurisma Putri Diponegoro University, Semarang
  • Farmaditya Eka Putra Mundhofir Diponegoro University, Semarang
  • Renni Yuniati Diponegoro University, Semarang
  • Noor Wijayahadi Diponegoro University, Semarang
  • Yora Nindita Diponegoro University, Semarang

DOI:

https://doi.org/10.46799/jhs.v5i6.1301

Keywords:

Curcuma longa, Leprosy, Reversal reaction, IL-6

Abstract

Type 1 leprosy reaction / Reversal reaction (RR) is an inflammatory episode in existing leprosy lesions and aggravates the pain rate. Long-term therapy with steroids causes a variety of side effects, so an adjuvant therapy alternative is needed to alleviate steroid use. Curcuma longa rhizome extract has become an anti-inflammatory therapy choice in various previous inflammatory diseases. This study aims to determine the anti-inflammatory effect of Curcuma longa rhizome extract as an adjuvant therapy for reversal reaction patients by analyzing serum levels of IL-6 as a marker of inflammation. The pre and post-test randomized single-blinded controlled trial was conducted on two groups, namely control (RR patients with steroid therapy & placebo) and treatment (steroid therapy & Curcuma longa rhizome extract 1 gram/day). IL-6 serum levels were analyzed from sampling before and after the intervention for one month. The serum levels of IL-6 post-test in the control group were significantly higher than those of the pre-test. The treatment group showed lower serum levels of IL-6 post-test compared to pre-test, although there was no significant difference. Curcuma longa rhizome extract 1 gram/day for one month as adjuvant therapy for patients with type 1 leprosy reaction did not significantly reduce serum IL-6 levels.

References

Aggarwal BB, Gupta SC, & Sung B. (2013). Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers. Br J Pharmacol. , 169(8), 1672-92.

Ashrafizadeh, M., Rafiei, H., Mohammadinejad, R., Afshar, E. G., Farkhondeh, T., & Samarghandian, S. (2020). Potential therapeutic effects of curcumin mediated by JAK/STAT signaling pathway: A review. In Phytotherapy Research (Vol. 34, Issue 8, pp. 1745–1760). John Wiley and Sons Ltd. https://doi.org/10.1002/ptr.6642

Chen, L., Deng, H., Cui, H., Fang, J., Zuo, Z., Deng, J., Li, Y., Wang, X., & Zhao, L. (2018). Inflammatory responses and inflammation-associated diseases in organs. In Oncotarget (Vol. 9, Issue 6). www.impactjournals.com/oncotarget/

Derosa, G., Maffioli, P., Simental-Mendía, L. E., Bo, S., & Sahebkar, A. (2016). Effect of curcumin on circulating interleukin-6 concentrations: A systematic review and meta-analysis of randomized controlled trials. In Pharmacological Research (Vol. 111, pp. 394–404). Academic Press. https://doi.org/10.1016/j.phrs.2016.07.004

Gandhi GR, Neta MTSL, Sathiyabama RG, Quintans J de SS, de Oliveira e Silva AM, & Araújo AA de S, ,. (2018). Flavonoids as Th1/Th2 cytokines immunomodulators: A systematic review of studies on animal models. Phytomedicine., 44, 78–84.

Harr, M. W., Rong, Y., Bootman, M. D., Roderick, H. L., & Distelhorst, C. W. (2009). Glucocorticoid-mediated inhibition of Lck modulates the pattern of T cell receptor-induced calcium signals by down-regulating inositol 1,4,5-trisphosphate receptors. Journal of Biological Chemistry, 284(46), 31860–31871. https://doi.org/10.1074/jbc.M109.005579

Irusen, E., Matthews, J. G., Takahashi, A., Barnes, P. J., Chung, K. F., & Adcock, I. M. (2002). p38 mitogen-activated protein kinase-induced glucocorticoid receptor phosphorylation reduces its activity: Role in steroid-insensitive asthma. Journal of Allergy and Clinical Immunology, 109(4), 649–657. https://doi.org/10.1067/mai.2002.122465

Jamil, S. N. H., Ali, A. H., Feroz, S. R., Lam, S. D., Agustar, H. K., Mohd Abd Razak, M. R., & Latip, J. (2023). Curcumin and Its Derivatives as Potential Antimalarial and Anti-Inflammatory Agents: A Review on Structure–Activity Relationship and Mechanism of Action. In Pharmaceuticals (Vol. 16, Issue 4). MDPI. https://doi.org/10.3390/ph16040609

Kementerian Kesehatan Republik Indonesia. (2023). Profil Kesehatan Indonesia 2021. Kemenkes RI. https://www.kemkes.go.id/id/profil-kesehatan-indonesia-2021

Khan, M. I., Karima, G., Khan, M. Z., Shin, J. H., & Kim, J. D. (2022). Therapeutic Effects of Saponins for the Prevention and Treatment of Cancer by Ameliorating Inflammation and Angiogenesis and Inducing Antioxidant and Apoptotic Effects in Human Cells. International Journal of Molecular Sciences, 23(18). https://doi.org/10.3390/ijms231810665

Luo, Y., Kiriya, M., Tanigawa, K., Kawashima, A., Nakamura, Y., Ishii, N., & Suzuki, K. (2021). Host-Related Laboratory Parameters for Leprosy Reactions. Frontiers in Medicine, 8. https://doi.org/10.3389/fmed.2021.694376

Menteri Kesehatan Republik Indonesia. (2019). Peraturan Menteri Kesehatan Nomor 11 Tahun 2019 tentang Penanggulangan Kusta. Kementerian Kesehatan Republik Indonesia, Art. 11.

N. S, N. A., Muniroh, M., Kusumaningrum, N., P M, F. E., & Yuniati, R. (2023). Clitoria ternatea L. Extract as Adjuvant Therapy on Reducing IL–6 Levels in Reversal Reaction. Biosaintifika: Journal of Biology & Biology Education, 15(1). https://doi.org/10.15294/biosaintifika.v15i1.39808

Nazli, P. A. N., Lubis, S. R., & Khairina. (2021). Correlation between the stress scale with cortisol levels in leprosy patients. Bali Medical Journal, 10(1), 500-4. https://doi.org/10.15562/BMJ.V10I1.2213

Perhimpunan Dokter Spesialis Kulit dan Kelamin Indonesia. (2017). Panduan Praktik Klinis Bagi Dokter Spesialis Kulit dan Kelamin di Indonesia. Perdoski, 80–100.

Piazza, S., Fumagalli, M., Martinelli, G., Pozzoli, C., Maranta, N., Angarano, M., Sangiovanni, E., & Dell’Agli, M. (2022). Hydrolyzable Tannins in the Management of Th1, Th2 and Th17 Inflammatory-Related Diseases. In Molecules (Vol. 27, Issue 21). MDPI. https://doi.org/10.3390/molecules27217593

Pinheiro RO, Schmitz V, Silva BJA, Dias AA, de Souza BJ, & de Mattos Barbosa MG, et al. (2018). Innate immune responses in leprosy. Front Immunol. , 9:518. https://doi.org/10.3389/fimmu.2018.00518

Pinsornsak P, & Niempoog S. (2012). The efficacy of Curcuma Longa L. extract as an adjuvant therapy in primary knee osteoarthritis: a randomized control trial. J Med Assoc Thai, 95(Suppl-1), S51-8.

Putri, A. I., de Sabbata, K., Agusni, R. I., Alinda, M. D., Darlong, J., de Barros, B., Walker, S. L., Zweekhorst, M. B. M., & Peters, R. M. H. (2022). Understanding leprosy reactions and the impact on the lives of people affected: An exploration in two leprosy endemic countries. PLoS Neglected Tropical Diseases, 16(6). https://doi.org/10.1371/journal.pntd.0010476

Quante, T., Yee, C. N., Ramsay, E. E., Henness, S., Allen, J. C., Parmentier, J., Ge, Q., & Ammit, A. J. (2008). Corticosteroids reduce IL-6 in ASM cells via up-regulation of MKP-1. American Journal of Respiratory Cell and Molecular Biology, 39(2), 208–217. https://doi.org/10.1165/rcmb.2007-0014OC

Ramasamy, S., Kumar, A., & Govindharaj, P. (2018). Screening household contacts of children diagnosed with leprosy in a tertiary referral centre, Chhattisgarh State, India. Leprosy Review, 89(2), 117-23. https://doi.org/https://doi.org/10.47276/lr.89.2.117

Saini, C., Siddiqui, A., Ramesh, V., & Nath, I. (2016). Leprosy Reactions Show Increased Th17 Cell Activity and Reduced FOXP3+ Tregs with Concomitant Decrease in TGF-β and Increase in IL-6. PLoS Neglected Tropical Diseases, 10(4), 1–21. https://doi.org/10.1371/journal.pntd.0004592

Simadibrata M, Halimkesuma CC, & Suwita BM. (2017). Efficacy of Curcumin as Adjuvant Therapy to Induce or Maintain Remission in Ulcerative Colitis Patients: an Evidence-based Clinical Review. Acta Med Indones. , 49((4)), 363-8.

Strandberg, K., Palmberg, L., & Larsson, K. (2008). Effect of budesonide and formoterol on Il-6 and Il-8 release from primary bronchial epithelial cells. Journal of Asthma, 45(3), 201–203. https://doi.org/10.1080/02770900801890372

Van Veen, N. H. J., Nicholls, P. G., Smith, W. C. S., & Richardus, J. H. (2016). Corticosteroids for treating nerve damage in leprosy. In Cochrane Database of Systematic Reviews (Vol. 2016, Issue 5). John Wiley and Sons Ltd. https://doi.org/10.1002/14651858.CD005491.pub3

Vilani-Moreno, F. R., Brito-De-Souza, V. N., Ruiz Silva, S. M. U., Almeida Barbosa, A. S. A., Carreira Sartori, B. G., Campanelli, A. P., Barreto, J. A., & Lopes Virmond, M. D. C. (2021). Increased serum levels of interleukin-6 in erythema nodosum leprosum suggest its use as a biomarker. Indian Journal of Dermatology, Venereology and Leprology, 87(2), 190–198. https://doi.org/10.25259/IJDVL_143_20

Wagenaar, I., Post, E., Brandsma, W., Bowers, B., Alam, K., Shetty, V., Pai, V., Husain, S., Sigit Prakoeswa, C. R., Astari, L., Hagge, D., Shah, M., Neupane, K., Tamang, K. B., Nicholls, P., & Richardus, J. H. (2017). Effectiveness of 32 versus 20 weeks of prednisolone in leprosy patients with recent nerve function impairment: A randomized controlled trial. PLoS Neglected Tropical Diseases, 11(10). https://doi.org/10.1371/journal.pntd.0005952

Walker, S. L. (2020). Leprosy reactions. In Scollard DM & Gillis TP (Eds.), The International Textbook of Leprosy (pp. 1–30). London School of Hygiene and Tropical Medicine. https://internationaltextbookofleprosy.org/authors/walker

WHO. (2019). Global leprosy update, 2018 moving towards a leprosy-free world. World Health Organization, 94, 389–412. http://www.who.int/wer

WHO. (2020). Leprosy/Hansen Disease: Management of reactions and prevention of disabilities technical guidance. http://apps.who.int/bookorders.

WHO. (2021). Towards zero leprosy: global leprosy (‎Hansen’s disease)‎ strategy 2021–2030 (WHO, Ed.). https://apps.who.int/iris/handle/10665/340774.

Wine, E., Mack, D. R., Hyams, J., Otley, A. R., Markowitz, J., Crandall, W. V., Leleiko, N., Muise, A. M., Griffiths, A. M., & Turner, D. (2013). Interleukin-6 is associated with steroid resistance and reflects disease activity in severe pediatric ulcerative colitis. Journal of Crohn’s and Colitis, 7(11), 916–922. https://doi.org/10.1016/j.crohns.2012.12.012

Yang, J., Li, X., Sun, Y., Zhang, L., Jin, G., Li, G., Zhang, S., Hou, K., & Li, Y. (2022). Global epidemiology of leprosy from 2010 to 2020: A systematic review and meta-analysis of the proportion of sex, type, grade 2 deformity and age. In Pathogens and Global Health (Vol. 116, Issue 8, pp. 467–476). Taylor and Francis Ltd. https://doi.org/10.1080/20477724.2022.2057722

Yasir, M., Goyal, A., & Sonthalia, S. (2023). Corticosteroid Adverse Effects. [Updated 2023 Jul 3]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK531462/

Yuniati, R., & Agusni, I. (2018). IL-6 Levels in Leprosy Patients with Reversal Reactions. Pakistan Journal of Health & Medical Sciences, 12(3), 1340-2. https://pjmhsonline.com/2018/july_sep/pdf/1340.pdf

Zhang, J., Zheng, Y., Luo, Y., Du, Y., Zhang, X., & Fu, J. (2019). Curcumin inhibits LPS-induced neuroinflammation by promoting microglial M2 polarization via TREM2/ TLR4/ NF-κB pathways in BV2 cells. Molecular Immunology, 116, 29–37. https://doi.org/10.1016/j.molimm.2019.09.020

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Published

2024-06-24