Natural products as Nrf2 modulators for ferroptosis inhibition in renal disease therapy: Recent progress and future prospects

Ruimin Tian; Shan Guo; Shudong Chen; Jiaqi Wu; Aoyang Long; Ran Cheng; Xiaowan Wang; Lihua Huang; Chuang Li; Wei Mao; Peng Xu; Lili Yu; Hudan Pan; Liang Liu

doi:10.1016/j.phymed.2024.156342

Natural products as Nrf2 modulators for ferroptosis inhibition in renal disease therapy: Recent progress and future prospects

Phytomedicine. 2024 Dec 24:136:156342. doi: 10.1016/j.phymed.2024.156342. Online ahead of print.

Authors

Ruimin Tian¹, Shan Guo², Shudong Chen², Jiaqi Wu³, Aoyang Long², Ran Cheng², Xiaowan Wang⁴, Lihua Huang⁴, Chuang Li⁴, Wei Mao⁵, Peng Xu⁵, Lili Yu⁶, Hudan Pan⁷, Liang Liu⁸

Affiliations

¹ State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau 999078, China; The Second Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, China.
² The Second Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
³ State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau 999078, China; The Second Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
⁴ The Second Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, China.
⁵ The Second Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, China; Chinese Medicine Guangdong Laboratory (Hengqin Laboratory), Guangdong-Macao In-Depth Cooperation Zone in Hengqin, 519000, China.
⁶ State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau 999078, China.
⁷ State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Chinese Medicine Guangdong Laboratory (Hengqin Laboratory), Guangdong-Macao In-Depth Cooperation Zone in Hengqin, 519000, China. Electronic address: [email protected].
⁸ State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau 999078, China; State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Chinese Medicine Guangdong Laboratory (Hengqin Laboratory), Guangdong-Macao In-Depth Cooperation Zone in Hengqin, 519000, China. Electronic address: [email protected].

PMID: 39742572
DOI: 10.1016/j.phymed.2024.156342

Abstract

Background: The transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2, NFE2L2) is a pivotal regulator of redox balance, metabolism, protein homeostasis and inflammation. Nrf2 is critically involved in both ferroptosis and renal diseases, and may serve as a significant target for many natural products in the treatment of renal diseases. However, a comprehensive overview on this topic is still lacking.

Purpose: To review the protective or therapeutic effects of natural products regulating Nrf2-related ferroptosis against various renal diseases.

Methods: We systematically searched the electronic databases involving PubMed, Web of Science, Google Scholar, China National Knowledge Internet (CNKI), Wanfang Database and VIP Database. To ensure a comprehensive exploration, keywords including Nrf2, ferroptosis, natural products, phytochemicals, renal disease, kidney disease, kidney injury and nephropathy were employed.

Results: Ferroptosis is deeply implicated in various kinds of renal diseases, notably including cisplatin-induced acute kidney injury, sepsis-associated acute kidney injury, renal ischemia/reperfusion injury, diabetic nephropathy, kidney stones and renal fibrosis. Nrf2 plays a regulatory role on many important genes related to iron metabolism, antioxidant system and lipid metabolism, thereby modulating ferroptosis. More than twenty natural products exert renoprotective effects by inhibiting ferroptosis via the regulation of Nrf2. This review presents a comprehensive overview of recent advancements in elucidating the ferroptosis involvement in renal diseases, the role of Nrf2 in regulating ferroptosis, and summarizes the renoprotective natural products as Nrf2 modulators for ferroptosis inhibition.

Conclusion: Through the comprehensive insights, this review clarifies the protective or therapeutic effects of natural products as Nrf2 modulators for ferroptosis inhibition in renal disease therapy, in the pursuit of providing new research ideas and directions for the treatment of renal diseases. Further drug development aimed at discovering more natural products and optimizing their utilization for disease treatment is necessary.

Keywords: Ferroptosis; Kidney disease; Natural products; Nrf2; Renal disease.