Comparative extracellular and intracellular anti-Mycobacterium tuberculosis activity of three tanshinones from Salvia miltiorrhiza and oral cryptotanshinone efficacy in mice.

Tuberculosis (TB) remains a major global health threat, particularly due to multidrug-resistant (MDR) Mycobacterium tuberculosis (M.tb). Although recent years have seen the introduction of new drugs and shorter regimens for TB, additional chemical scaffolds with activity against drug-resistant and intracellular bacilli are still needed. Tanshinones from Salvia miltiorrhiza represent a natural product scaffold with potential anti-mycobacterial activity. We systematically compared three major tanshinones-Tanshinone I (TAN), Dihydrotanshinone I (DTI), and Cryptotanshinone (CTS)-against M.tb H37Rv and a panel of drug-resistant clinical isolates. Extracellular minimum inhibitory concentrations (MICs) were determined, and intracellular activity was evaluated in M.tb-infected THP-1 macrophages by colony-forming unit (CFU) enumeration after 48 h of treatment. CTS was further evaluated in an acute murine TB infection model via daily oral gavage (25 mg/kg/day) for 28 days starting 14 days post-infection. All three tanshinones inhibited extracellular growth of drug-sensitive and drug-resistant M.tb with MICs in the 5-20 μM range, with DTI showing the lowest extracellular MIC (5 μM). In infected THP-1 macrophages at 48 h, CTS (10 μM; 1 × MIC) reduced intracellular CFU by approximately 1.00 Log