Exploring the Therapeutic Benefits of Silymarin Herbal Extract as a Supplement to Pulmonary Tuberculosis Treatment: A Comprehensive Review from Laboratory to Clinical Trials
DOI:
https://doi.org/10.35790/msj.v6i2.51870Abstract
Abstract: Indonesia is ranked second in the number of tuberculosis (TB) cases with an incidence rate of 300 per 1000 population. A combination of antibiotics with a minimum six-month-administration regimen is an effective first line of TB treatment. Silymarin (Sm) is a plant extract which is known to have hepatoprotective and anti-microbial effects. This literature review aimed to discuss the potential of Sm in pulmonary TB treatment, starting from laboratory studies to clinical trials in humans. Studies on the use of Sm in tuberculosis literatures were obtained from a rapid systematic search in Pubmed and ScienceDirect databases. Supporting articles were searched based on specific keywords with inclusion criteria. The in vitro test showed immunomodulatory and bactericidal capacities of Sm against Mycobacterium tuberculosis. The in vivo test of Sm administration showed that Sm was able to increase the percentage of macrophage cells expressing the cytokines NF-κB and IFN-β. Sm had a bactericidal effect at levels >50 μM. The hepatoprotective character of Sm could prevent the increase in liver enzymes in mice receiving anti-TB drugs. Clinical trials showed that administration of Sm could prevent anti-tuberculosis drug hepatoxicity. In conclusion, silymarin has the potential to be an adjuvant therapy for the treatment of anti-TB drug-sensitive or resistant tuberculosis, as well as protection against the hepatotoxic properties of anti-TB drugs.
Keywords: tuberculosis; silymarin; supplementation therapy; antituberculosis therapy
References
Glaziou P, Floyd K, Raviglione MC. Global epidemiology of tuberculosis. Semin Respir Crit Care Med. 2018;39(3):271–85. Doi: 10.1055/s-0038-1651492
Furin J, Cox H, Pai M. Tuberculosis. Lancet. 2019;393(10181):1642–56. Doi:10.1016/S0140-6736(19)30308-3
MacNeil A, Glaziou P, Sismanidis C, Maloney S, Floyd K. Global epidemiology of tuberculosis and progress toward achieving global targets - 2017. MMWR Morb Mortal Wkly Rep. 2019;68(11):263–6. Doi: 10.15585/mmwr.mm6811a3
Ministry of Health Republic of Indonesia. National Guidelines for Medical Services for the Management of Tuberculosis [In Indonesia]. Jakarta: Ministry of Health Republic of Indonesia; 2020. p. 1–156.
World Health Organization. WHO consolidated guidelines on tuberculosis. Module 4: Treatment - Drug-Resistant Tuberculosis Treatment, 2022 Update. Geneva: World Health Organization; 2022.
Munro SA, Lewin SA, Smith HJ, Engel ME, Fretheim A, Volmink J. Patient adherence to tuberculosis treatment: a systematic review of qualitative research. PLoS Med. 2007;4(7):e238. Doi: 10.1371/journal.pmed.0040238
Karumbi J, Garner P. Directly observed therapy for treating tuberculosis. Cochrane Database Syst Rev. 2015;2015(5):CD003343. Doi: 10.1002/14651858.CD003343.pub4
Perwitasati DA, Setiawan D, Nguyen T, Pratiwi A, Fauziah LR, Saebrinah E, et al. Investigating the relationship between knowledge and hepatotoxic effects with medication adherence of TB patients in Banyumas Regency, Indonesia. Int J Clin Pract. 2022;2022:4044530. Available from: https: //doi.org/10.1155/2022/4044530
Karimi G, Vahabzadeh M, Lari P, Rashedinia M, Moshiri M. “Silymarin”, a promising pharmacological agent for treatment of diseases. Iran J Basic Med Sci. 2011;14(4):308–17. Available from: https:// pubmed.ncbi.nlm.nih.gov/23492971/
Vargaz-Mendoza N, Madrigal-Santillan E, Morales-Gonzalez A, Esquivel-Soto J, Esquivel-Chirino C, Gonzalez-Rubio M, et al. Hepatoprotective effect of silymarin. World J Hepatol. 2014;6(3):144–9. Doi: 10.4254/wjh.v6.i3.144
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Syst Rev. 2021;10(1):89. Doi: 10.1186/s13643-021-01626-4
Eminzade S, Uras F, Izzetin F V. Silymarin protects liver against toxic effects of anti-tuberculosis drugs in experimental animals. Nutr Metab (Lond). 2008;5:18. Doi: 10.1186/1743-7075-5-18
Rodriguez-Flores EM, Mata-Espinosa D, Barrios- Payan J, Marquina-Castillo B, Castanon-Arreola M, Hernandez-Pando R. A significant therapeutic effect of silymarin administered alone, or in combination with chemotherapy, in experimental pulmonary tuberculosis caused by drug-sensitive or drug-resistant strains: in vitro and in vivo studies. PLoS One. 2019;14(5):e0217457. Doi: 10.1371/journal.pone.0217457
Luangchosiri C, Thakkinstian A, Chitphuk S, Stitchantrakul W, Petraksa S, Sobhonslidsuk A. A Double-blinded randomized controlled trial of silymarin for the prevention of antituberculosis drug-induced liver injury. BMC Complement Altern Med. 2015;15:334. Doi: 10.1186/s12906-015-0861-7
Marjani M, Baghei P, Dizaji MK, Bayani PG, Fahimi F, Tabarsi P, et al. Evaluation of hepatoprotective effect of silymarin among under treatment tuberculosis patients: a randomized clinical trial. Iran J Pharm Res. 2016;15(1):247–52. Available from: https://pubmed.ncbi.nlm.nih.gov/27610165/
Heo E, Kim DK, Oh SH, Lee JK, Park JH, Chung HS. Effect of prophylactic use of silymarin on anti-tuberculosis drugs induced hepatotoxicity. Tuberc Respir Dis (Seoul). 2017;80(3):265–9. Doi: 10.4046/trd.2017.80.3.265
Talebi A, Soltani R, Khorvash F, Jouabadi SM. The effectiveness of silymarin in the prevention of anti-tuberculosis drug-induced hepatotoxicity: a randomized controlled clinical trial. Int J Prev Med. 2023;14:48. Doi: 10.4103/ijpvm.ijpvm_81_22
Gu J, Tang S, Tan S, Wu Q, Zhang X, Liu C, et al. An open-label, randomized and multi-center clinical trial to evaluate the efficacy of silibinin in preventing drug-induced liver injury. Int J Clin Exp Med. 2015;8(3):4320–7. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4443182/
Zhang S, Pan H, Peng X, Lu H, Fan H, Zheng X, et al. Preventive use of a hepatoprotectant against anti-tuberculosis drug-induced liver injury: a randomized controlled trial. J Gastroenterol Heaptol. 2016;31(2):409–16. Available from: https://doi.org/10.1111/jgh.13070
Bannwart C, Nakaira-Takahagi E, Golim MA, de Medeiros LT, Romao M, Weel IC, et al. Downregulation of nuclear factor-kappa B (NF-Kappab) pathway by silibinin in human monocytes challenged with Paracoccidioides brasiliensis. Life Sci. 2010;86(23–24):880–6. Doi: 10.1016/j.lfs.2010.04.005
Ramappa V, Aithal GP. Hepatotoxicity related to anti-tuberculosis drugs: mechanisms and management. J Clin Exp Hepatol. 2013;3(1):37–49. Available from: https:// www.ncbi.nlm.nih.gov/pmc/articles/ PMC3940184/
Vivekanandan L, Sheik H, Singravel S, Thangavel S. Ameliorative effect of silymarin against linezolid-induced hepatotoxicity in methicillin-resistant Staphylococcus aureus (MRSA) Infected Wistar rats. Biomed Pharmacother. 2018;108:1303–12. Doi: 10.1016/j.biopha.2018.09.133
Javed S, Kohli K, Ali M. Reassessing bioavailability of silymarin. Altern Med Rev. 2011;16(3):239–49. Available from: https://pubmed.ncbi.nlm.nih.gov/21951025/
Abenavoli L, Capasso R, Milic N, Capasso F. Milk thistle in liver diseases: past, present, future. Phytother Res. 2010;24(10):1423–32. Doi: 10.1002/ptr.3207
Abenavoli L, Izzo AA, Milic N, Cicala C, Santini A, Capasso R. Milk thistle (Silybum marianum): a concise overview on its chemistry, pharmacological, and nutraceutical uses in liver diseases. Phytother Res. 2018;31(11):2202–13. Doi: 10.1002/ptr.6171
Calani L, Brighenti F, Bruni R, Del Rio D. Absorption and metabolism of milk thistle flavanolignans in humans. Phytomedicine. 2012;20(1):40–6. Doi: 10.1016/j.phymed.2012.09.004
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