Xuebijing Injection Mitigates Instant Blood‑Mediated Inflammatory Reaction and Enhances Intrahepatic Islet Transplantation via Target NF‑κB Pathway

Yixiang Zhan¹Yingbo Wang²Boya Zhang³Yijun Zhang²Rui Liang³Jiuxia Yang³Tengli Liu³Xiaoyan Hu³Tianyi You³Na Liu³Yuqi Chen²Qing Liu²Tingsheng Jiang²Zhaoce Liu¹Xiangheng Cai¹Runnan Yang²Yingyi Qi²Peng Sun³Jiaqi Zou³Xuejie Ding³Zhuzeng Yin^4*Shusen Wang^1,3*

• ¹Nankai University School of Medicine, Tianjin, China
• ²The First Central Clinical College, Tianjin Medical University, Tianjin, China
• ³Department of Organ Transplantation Center, Tianjin First Central Hospital, Nankai, China
• ⁴1st Medical Center of Chinese PLA General Hospital, Beijing, China

Intrahepatic islet transplantation is a promising treatment for type 1 diabetes (T1D). However, the outcome is significantly limited by the instant blood-mediated inflammatory reaction (IBMIR), which leads to substantial early islet loss. Due to its multifactorial pathogenesis involving coagulation, inflammation, and apoptosis, there is a critical need for effective, multi-target therapies to mitigate IBMIR and improve graft survival. Xuebijing (XBJ), a clinically approved multi-component herbal medicine known for its anti-inflammatory and organ-protective effects, offers potential to address this challenge. In this study, we evaluated the protecting effects of XBJ, using intrahepatic islet transplantation models in diabetic mice. In vivo, XBJ mitigated IBMIR by reducing thrombosis and inflammatory reaction. The group received XBJ treatment has higher percentage of normoglycemia, and achieved the better graft survival. In other hand, XBJ directly protected islet cells against cytokine-induced apoptosis and dysfunction. Cytokine-stimulated mouse islets and β cells were treated with XBJ to have better viability and function. XBJ restored glucose-stimulated insulin secretion and attenuated cytokine-induced apoptosis. These mechanisms collaboratively contributed to improved islet grafts survival and function. Mechanistically, bulk RNA-sequencing revealed XBJ suppressed NF-κB pathway activation and inhibited pro-inflammatory gene clusters. Molecular docking and Western blot revealed high-affinity interactions between XBJ constituents and NF-κB pathway nodes. XBJ effectively protects islet grafts and improves transplantation outcomes by targeting key inflammatory and apoptotic pathways. These findings support the potential of XBJ as a novel therapy to enhance the outcome of clinical islet transplantation.