Research articles
ScienceAsia 52 (2026): 1-14 |doi:
10.2306/scienceasia1513-1874.2026.081
Dihydromyricetin inhibits aberrant cGAS-STING signaling
activation and renal fibrosis in diabetic nephropathy by
promoting ubiquitin-mediated STING degradation
Xu Bai, KuiBi Tan*
ABSTRACT: This study aims to investigate whether dihydromirisinide (DHM) can alleviate diabetic nephropathy
(DN) by promoting the ubiquitination and degradation of STING. Network pharmacology analysis indicates that the
cGAS-STING pathway is a potential target. In a streptozotocin-induced DN mouse model, DHM improved renal
function (as evidenced by reduced urine albumin-to-creatinine ratio, creatinine, and urea nitrogen), and alleviated
fibrosis. In high glucose-treated HK-2 cells, DHM decreased the expression of cGAS, and specifically accelerated the
degradation of STING protein through the ubiquitin-proteasome pathway. Mechanistically, DHM enhanced the K48
linked polyubiquitination of STING, leading to its degradation by the proteasome and subsequent inhibition of the
downstream TBK1-IRF3 signaling pathway and of the production of inflammatory factors. In conclusion, DHM inhibits
the cGAS-STING pathway by promoting the K48-ubiquitination and degradation of STING, thereby alleviating renal
damage in DN.
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Department of Nephrology, Ningbo No.2 Hospital, Wenzhou Medical University, Ningbo, Zhejiang 315010 China |
* Corresponding author, E-mail: Tankuibitkb@outlook.com
Received 25 Mar 2026, Accepted 15 Jun 2026
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