Combating Tuberculosis with Nature’s Pharmacy: Role of Natural Products in Anti-TB Drug Development

Abstract

Tuberculosis (TB) remains a major global health challenge, further complicated by multidrug-resistant (MDR), extensively drug-resistant (XDR), and latent Mycobacterium tuberculosis infections. Although current therapies are effective in drug-sensitive TB, prolonged treatment duration, toxicity, poor adherence, and emerging resistance highlight the need for safer and more effective alternatives. Natural products represent a valuable source of structurally diverse bioactive compounds with antimycobacterial, resistance-modifying, and host-directed therapeutic potential. This review summarizes recent advances in natural and plant-derived compounds with anti-TB activity. Major natural sources, including medicinal plants, microorganisms, and marine organisms, are discussed along with important bioactive classes such as alkaloids, flavonoids, terpenoids, coumarins, quinones, and peptides. Reported mechanisms include inhibition of cell wall biosynthesis, disruption of energy metabolism, efflux pump modulation, interference with nucleic acid synthesis, and host immunomodulation through autophagy and inflammatory signaling pathways. however, most evidence remains preclinical and heterogeneous in methodology bergenin, berberine, curcumin, resveratrol, quercetin, tetrandrine, calanolide A, ecumicin, and gladiolin. Several compounds have shown encouraging in vitro antimycobacterial activity, while selected candidates demonstrate efficacy in macrophage and animal models or synergistic effects with standard anti-TB drugs. However, robust clinical evidence remains limited. Major translational barriers include poor bioavailability, rapid metabolism, formulation challenges, toxicity concerns, lack of standardization, and insufficient pharmacokinetic/pharmacodynamic validation. Future progress will depend on integrated approaches involving artificial intelligence-guided screening, nanoformulations, synthetic biology, and well-designed preclinical and clinical studies. Natural products may therefore provide valuable leads and adjunct therapies for next-generation TB treatment.