Hao-Yu Feng,1,2,* Yi-Qi Wang,2,* Jianhua Yang,3,4 Hua Miao,1,2 Ying-Yong Zhao,1,2 Xiaojuan Li1 

1School of Pharmaceutical Sciences, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3Department of Pharmacy, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 4Xinjiang Key Laboratory of Clinical Drug Research, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Ying-Yong Zhao, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China, Tel/Fax +86 571 61768528, Email zyy@nwu.edu.cn Xiaojuan Li, School of Pharmaceutical Sciences, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310001, People’s Republic of China, Email 20093002@zcmu.edu.cn

Abstract: Renal diseases including acute kidney injury (AKI) and chronic kidney disease (CKD) has become a significant public health concern due to its high morbidity and mortality. Rheum officinale Baill (Polygonaceae) exhibits diuretic, renoprotective, lipid-lowering, anti-inflammatory, and antifibrotic properties. Accumulating evidence has highlighted the anthraquinones in R. officinale as key components contributing to its renoprotective effects. The available information on R. officinale was searched by several electronic database such as PubMed, Web of Science, Springer, ScienceDirect, etc. This review summarizes the anthraquinones and their renoprotective effects in R. officinale, evaluating its clinical potential for managing renal disease including AKI and CKD. Studies demonstrate that R. officinale contains bioactive components such as anthraquinones, stilbenes, phenylbutazones, and tannins. This review discusses the renoprotective effects of R. officinale, including improvements in renal function, reduction of podocyte damage, and inhibition of renal fibrosis. These effects are mediated through the regulation of pro-inflammatory (IκB/NF-κB and Keap1/Nrf2), pro-fibrotic (TGF-β 1/Smad and Wnt/β-catenin), AMP-activated protein kinase and phosphoinositide 3-kinase signaling pathways in AKI and CKD. Additional mechanisms include modulation of anti-ageing Klotho expression, autophagy, and apoptosis. These findings expand the understanding of the therapeutic effects on AKI and CKD of R. officinale and provide valuable information on its clinical application in traditional Chinese medicine. This review presents a concept-driven therapeutic strategy for renal disease management.

Keywords: acute kidney injury, chronic kidney disease, Rheum officinale, anthraquinones, oxidative stress and inflammation, TGF-β/Smad