Phytoconstituents and Immunological Responses in Tuberculosis: Insights Into Network Pharmacology

Pulmonary tuberculosis (TB), caused by the Mycobacterium tuberculosis (MTB) bacterium, remains a significant health problem worldwide, intensified by the emergence of multidrug-resistant (MDR) and highly resistant (XDR) strains. The current treatment protocols, related side effects, and the increasing incidence of drug resistance limit the efficacy of conventional therapeutic strategies. Traditional medicinal constituents rich in diverse phytoconstituents offer multi-target action with reduced toxicity, minimal risk of resistance, and immunomodulatory properties. Network pharmacology (NP), an integrated approach merging systems biology and computational modeling, facilitates understanding complex interactions among phytochemicals, molecular targets, and signaling pathways. Integrating modern pharmacology principles with traditional wisdom, NP provides a logical framework for developing new plant-based anti-TB agents and advancing adjunctive therapies. Combining protein-protein interaction networks, pathway enrichment analyses, multi-combinational data, and molecular docking studies offers insights into how phytoconstituents affect the immune response, block efflux pumps, and reduce resistance. This review provides a detailed analysis of NP-based methods for the identification of active compounds (e.g., alkaloids, flavonoids, terpenoids, polyphenols) and their related molecular targets involved in the pathogenesis of TB, including tumor necrosis factor-alpha (TNF-α), Toll-like receptors (TLR), nucleotide-binding oligomerization domain (NOD)-like receptor, and Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway.