Understanding Vascular Toxicity of Indigo Naturalis in Anti-Inflammatory Applications: Mendelian Randomization and Co-localization Study

Background: Indigo naturalis (IN), a traditional Chinese herbal medicine, shows promising potential for treating autoimmune inflammatory diseases. However, its clinical translation and application are being limited by concerns regarding vascular toxicity. Methods: Mendelian randomization (MR) and colocalization analyses were conducted to systematically investigate the target-specific vascular risks associated with IN. Results: Causal associations were identified between four targets of IN and multiple vascular disorders, including deep vein thrombosis (DVT) (OR = 1.001, 95% CI = 1.003-1.000, P = 0.008), among others. Notably, urate was identified as a mediator between IN and DVT, exhibiting a mild mediation effect (7.3%, P = 0.048). Conclusion: For the first time, the causal effects of IN on vascular toxicity were demonstrated using MR. This study provides insights into the safety implications of IN for anti-inflammatory applications, which would facilitate evidence-based research on IN and its clinical translation.