Citation: Shuyu Wang, Yue Chai, Jinxin Shi, Pengcheng Dai, Ruizhi Yu, Hongming Shao, Wenxin Ding, Lijuan Xu, Runhui Liu, Chunlin Zhuang. Shikonin ameliorates ulcerative colitis by inhibiting necroptosis via targeting HSPA8[J]. Chinese Chemical Letters, ;2026, 37(10): 112111. doi: 10.1016/j.cclet.2025.112111 shu

Shikonin ameliorates ulcerative colitis by inhibiting necroptosis via targeting HSPA8

The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Second Military Medical University, Shanghai 200433, China

lyliurh@126.com

zclnathan@163.com

Received Date: 25 October 2025
Revised Date: 12 November 2025
Accepted Date: 13 November 2025
Available Online: 13 November 2025

Figures(5)

Ulcerative colitis (UC) is a pressing clinical issue currently lacking effective therapeutic approaches. Here we conducted a screening on the natural compounds from traditional Chinese medicine to identify a potent lead, shikonin (SHK), applying a necroptosis cell model. The potency for treating UC was confirmed in a dextran sulfate sodium (DSS)-induced UC mouse model. Leveraging a photo-affinity labeling approach, heat shock protein family A member 8 (HSPA8), a key negative regulator of necroptosis, was identified as the direct target of SHK. The in vivo protection of SHK were validated through targeting HSPA8 based on necroptosis pathway. As a result, targeting HSPA8 by SHK or activate HSPA8 significantly impairs necroptosis signaling and mitigates UC. Our findings not only define HSPA8 as a novel therapeutic target for UC but also highlight SHK as a promising lead for treatment of this symptom.
- Ulcerative colitis,
- Shikonin,
- Necroptosis,
- HSPA8,
- Target
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