Abstract
Mycobacterium tuberculosis (Mtb) is a pathogenic bacterium which causes tuberculosis (TB). TB control programmes are facing threats from drug resistance. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mtb strains need longer and more expensive treatment with many medications resulting in more adverse effects and decreased chances of treatment outcomes. The World Health Organization (WHO) has emphasised the development of not just new individual anti-TB drugs, but also novel medication regimens as an alternative treatment option for the drug-resistant Mtb strains. Many plants, as well as marine creatures (sponge; Haliclona sp.) and fungi, have been continuously used to treat TB in various traditional treatment systems around the world, providing an almost limitless supply of active components. Natural products, in addition to their anti-mycobacterial action, can be used as adjuvant therapy to increase the efficacy of conventional anti-mycobacterial medications, reduce their side effects, and reverse MDR Mtb strain due to Mycobacterium’s genetic flexibility and environmental adaptation. Several natural compounds such as quercetin, ursolic acid, berberine, thymoquinone, curcumin, phloretin, and propolis have shown potential anti-mycobacterial efficacy and are still being explored in preclinical and clinical investigations for confirmation of their efficacy and safety as anti-TB medication. However, more high-level randomized clinical trials are desperately required. The current review provides an overview of drug-resistant TB along with the latest anti-TB medications, drug-induced hepatotoxicity and oxidative stress. Further, the role and mechanisms of action of first and second-line anti-TB drugs and new drugs have been highlighted. Finally, the role of natural compounds as anti-TB medication and hepatoprotectants have been described and their mechanisms discussed.
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Acknowledgements
HKR acknowledges UGC New Delhi for financial assistance in the form of a CRET Research Fellowship. AKS and RK acknowledge CSIR New Delhi for financial assistance in the form of Junior and Senior Research Fellowships. RK also acknowledges Research Associateship of ICMR New Delhi. All the authors gratefully acknowledge UGC-SAP and DST-FIST facilities of the Department of Biochemistry, University of Allahabad, Prayagraj (Allahabad).
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A.K.P. conceptualized the ideas for this review; H.K.R., A.K.S., and R.K. wrote the manuscript and validated the references; A.K.P. critically reviewed and supervised the manuscript writing. All authors have read and approved the manuscript. The authors confirm that no paper mill and artificial intelligence was used.
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Rana, H.K., Singh, A.K., Kumar, R. et al. Antitubercular drugs: possible role of natural products acting as antituberculosis medication in overcoming drug resistance and drug-induced hepatotoxicity. Naunyn-Schmiedeberg's Arch Pharmacol 397, 1251–1273 (2024). https://doi.org/10.1007/s00210-023-02679-z
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DOI: https://doi.org/10.1007/s00210-023-02679-z