Ari Nuswantoro^1,2, Jusak Nugraha³ , Sri Agus Sudjarwo⁴, Purwo Sri Rejeki⁵, Dinasti Aprillia⁶

Abstract

Purpose: To investigate the dual potential of mitragynine as an anti-tuberculosis and immunomodulatory agent by in silico evaluation of its pharmacokinetic properties and binding affinities for Mycobacterium tuberculosis (Mtb) proteins and pro-inflammatory cytokines. Methods: Mitragynine and 7-hydroxymitragynine, the two most abundant alkaloids in kratom leaves, were evaluated for drug likeness and synthetic accessibility. Molecular docking was performed against four Mtb-related proteins (isocitrate lyase, RmlD, BioA, and LdtB) and two inflammatory cytokines (IL-6 and TNF-α), with rifampicin and brazilin used as reference ligands. Results: Mitragynine showed favorable drug-likeness, demonstrating transport and pharmacokinetic properties, high gastrointestinal absorption, and blood-brain barrier permeability. Molecular docking revealed moderate binding affinity to the Mtb targets isocitrate lyase and BioA, though weaker than rifampicin. Notably, mitragynine exhibited stronger binding to IL-6 and TNF-α than brazilin, suggesting a greater immunomodulatory potential. Conclusion: These results position mitragynine as a promising dual-function compound with potential adjunctive therapeutic value for Mtb and inflammation-related pathology. Further studies are warranted to validate these computational findings.