Neferine, a major alkaloid from the traditional Chinese medicine Lian Zi Xin, alleviates renal fibrosis by targeting GSK3β and β-catenin signaling.

Authors

Jialin Li, Yongzhang Qin, Zhaolong Yu, Pengfei Chen, Xiaocui Huang, Zijian Zhu, Xiansong Fang, Zhiping Liu, Suzhen Wu

Published in

Journal of ethnopharmacology. Pages 122288. Aug 11, 2026. Epub Aug 11, 2026.

Abstract

Neferine (Nef) is the primary bioactive alkaloid of lotus seed germ (Lian Zi Xin), a traditional Chinese medicine long used for 'clearing heart fire' and ' eliminating internal heat, and regulating body fluid metabolism (e.g., promoting diuresis and reducing edema)'. From the perspective of modern medical concepts, 'internal heat' and 'fluid imbalance' often correspond to conditions such as impaired kidney function.
To investigate the protective effects of Nef against renal injury in mice and identify the underlying mechanisms.
In vitro model of diabetic nephropathy (DN) and renal fibrosis were established using high glucose-stimulated mesangial cells and TGF-β1-induced HK-2 cells, respectively. In vivo model of DN and renal fibrosis were established by high-fat diet combined with streptozotocin, and unilateral ureteral obstruction (UUO) , respectively. Nef intervention was applied in both models. Fibrotic markers such as fibronectin (FN), collagen IV (Col IV) and key components of the Wnt/β-catenin pathway were assessed by Western blot and immunohistochemistry. The binding between neferine and target proteins was validated through bioinformatics, pull-down assays, and cellular thermal shift assay (CETSA). The regulatory effects of Nef on GSK3β phosphorylation (Ser9) and β-catenin accumulation were further examined.
Treatment with neferine results in significant downregulation of extracellular matrix components, such as FN and Col IV, along with inhibition of epithelial-mesenchymal transition in both cellular and animal models. At the molecular level, Nef exerts its effects by directly binding to β-catenin and GSK3β, reducing GSK3β phosphorylation at Ser9, which in turn prevents β-catenin accumulation and suppresses Wnt/β-catenin pathway activity.
Nef ameliorates DN and UUO induced renal injury by targeting GSK3β and β-catenin, thereby inhibiting the Wnt/β-catenin signaling pathway. These findings highlight its therapeutic potential for fibrotic kidney diseases.

PMID:
42580543
Bibliographic data and abstract were imported from PubMed on 12 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.