Herbal supplements and anti-tuberculosis therapy: unlocking hidden interactions for better multidrug-resistant tuberculosis management

Tuberculosis (TB), especially in its multidrug-resistant form (MDR-TB), remains a persistent threat to global health despite decades of medical advancements. Standard treatment regimens often involve complex drug combinations, which, while effective, pose a significant risk of drug-drug interactions (DDIs). The growing reliance on complementary and alternative medicine (CAM), particularly herbal supplements, further complicates this landscape by introducing herb-drug interactions (HDIs), many of which are poorly understood or undocumented. These interactions can compromise treatment efficacy, increase toxicity, and hinder patient adherence, particularly in settings where traditional medicine is widely used. This review emphasizes current evidence on the pharmacological interactions between anti-TB/MDR-TB drugs and other conventional medications, as well as commonly used herbal supplements. We explore the pharmacokinetic and pharmacodynamic mechanisms underlying these interactions, with a focus on cytochrome P450-mediated metabolism and modulation of transporter proteins. Highlighted are key interactions involving TB/MDR-TB medication. In addition, the review discusses the emerging role of Network Pharmacology in mapping multi-target interactions, offering new understandings into the potential risks and benefits of integrating herbal medicine into TB care. The potential therapeutic value of select herbs with hepatoprotective and immunomodulatory properties is critically examined alongside safety concerns. By collating and evaluating findings from clinical, pharmacological, and systems-based research, this review aims to guide healthcare professionals in optimizing TB treatment strategies. Emphasis is placed on the need for proactive monitoring, patient education, and culturally sensitive communication regarding herbal use. Integrating evidence-based approaches with traditional practices could enhance treatment outcomes and minimize adverse effects in TB and MDR-TB management.