The Chinese herbal medicine indigo naturalis (IN) shows promising potential for treating autoimmune inflammatory diseases. However, its clinical application is limited by vascular toxicity. Using Mendelian randomization analysis, we conducted the first systematic study of IN’s target-specific vascular risks, revealing causal links between IN exposure and various vascular disorders. Importantly, our findings identify urate as a mediator between IN exposure and deep vein thrombosis outcome. This study provides genetic insights into safety implications for clinical translation study of IN for anti-inflammation applications and guides biomarker monitoring in related trials.

The authors have declared no competing interest.

Jie Liu extends sincere gratitude to Fenji postdoctoral program in Shenzhen Bay Lab of Guang Dong Province of China. The authors acknowledge financial supports from the IDEATION Programme of the Hong Kong Science & Technology Parks Corporation (Partner-23-159). The methodological suggestions from Dr. ZHENG Ping are strongly appreciated.

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