Aug 2026· Renal Failure· Vol 48· 0 citations· 70 references
Medicine
TL;DR
This review summarizes recent advances in the use of natural products for the treatment of renal fibrosis, with a particular focus on their underlying molecular mechanisms, current status of clinical translation, and the challenges that remain.
Abstract
Abstract Renal fibrosis represents a shared pathological endpoint that drives the progression of chronic kidney disease (CKD) toward end-stage kidney disease (ESKD). Although current therapies can delay CKD progression, they have limited capacity to reverse established fibrotic remodeling, underscoring the need for mechanism-oriented anti-fibrotic interventions. Plant-derived preparations have long attracted attention because of their multi-component, multi-target, and multi-pathway pharmacological profiles. More recently, advances in separation, purification, and pharmacological evaluation have redirected research interest from crude extracts toward defined bioactive natural products. A growing body of evidence suggests that flavonoids, alkaloids, terpenoids, glycosides, polyphenols, quinones, and other natural products may exert anti-fibrotic effects by targeting key pathological processes, including inflammation, oxidative stress, mitochondrial dysfunction, metabolic reprogramming, autophagy dysregulation, epigenetic regulation, and regulated cell death. This review summarizes recent advances in the use of natural products for the treatment of renal fibrosis, with a particular focus on their underlying molecular mechanisms, current status of clinical translation, and the challenges that remain.
This review examines emerging mechanisms that govern kidney fibrogenesis, with emphasis on therapeutic tractability, and considers how experimental models can improve target prioritization and drug development, and summarizes repurposed drugs, pathway-targeted agents, receptor-directed strategies and cell-based approaches under preclinical or clinical evaluation.
Future directives necessitate rigorous botanical authentication, pharmacokinetic/pharmacodynamic profiling, and adoption of human-relevant models, such as induced pluripotent stem cell-derived cardiomyocytes, to bridge the bench-to-bedside gap.
Tian-Tian Long, Juncheng Ma, Wei-Jun Hu et al.· International Journal of Mol...· 0 citations
This review uses Tangshen formula, a classic traditional Chinese medicine (TCM) for DKD, to detail TCM's protective mechanisms and concisely summarizes the DKD-related preclinical progress of other TCMs over 5 years.
Li Jiang, Shuang Guo, Yufei Zhang et al.· Seminars in Nephrology· 0 citations
This review systematically examines the mechanisms of metabolic reprogramming in different renal cell types and highlights their contribution to renal injury, highlighting the ability of natural products to confer renal protection by modulating key regulatory nodes of metabolic reprogramming.
Wenru Wang, Han Zhu, Keqin Zhao et al.· Journal of Translational Int...· 0 citations
Hyperuricemia (HUA) is a common metabolic disorder with rising global prevalence and is closely linked to gout, chronic kidney disease, and cardiovascular complications. Current Western drugs are limited by single-target mechanisms and adverse effects, whereas traditional Chinese medicine (TCM) is proposed to offer multi-component and multi-target therapeutic effects. This review critically synthesizes recent advances in TCM for HUA, focusing on how natural products modulate uric acid production (XOD/ADA), renal/intestinal excretion (URAT1, GLUT9, ABCG2, OATs), inflammation (NLRP3/NF-κB), and gut microbiota via the gut–kidney axis. We propose a four-tier hierarchical framework—purified metabolites, extracts, single botanical drugs, and formulas—that bridges molecular precision with systemic effects: metabolites serve as mechanistic probes, extracts and single botanical drugs achieve multi-component effects, and formulas enable network regulation. This framework helps deconstruct complex TCM interventions into testable, multi-target strategies. Beyond summarizing mechanisms, we critically examine methodological flaws in preclinical studies (acute models, prophylactic dosing, intraperitoneal injection) that limit translational validity, and highlight the pervasive gap between correlative findings (e.g., transporter expression, microbiota shifts) and causal evidence. We also address the under-appreciated safety profile of anti-HUA TCM, including potential organ toxicity and herb–drug interactions. By critically examining limitations, this review aims to provide a realistic, systems-level perspective to guide future mechanistic and translational research.
Hong Li, Siqi You, Xiaoping Luo et al.· Frontiers in Pharmacology· 0 citations
Diabetic nephropathy (DN), a major microvascular complication of diabetes mellitus, is a leading cause of end-stage renal disease and represents a significant threat to global public health. Currently, clinical management primarily relies on hypoglycemic, antihypertensive, and lipid-lowering agents. Although these therapies can slow the progression of DN, their overall efficacy remains limited due to adverse side effects, poor target specificity, and the multifactorial pathogenesis of the disease. Natural products, predominantly derived from medicinal plants, possess diverse chemical scaffolds and are characterized by multi-target pharmacological actions and broad therapeutic potential. These compounds exert beneficial effects through modulation of key pathological processes, including oxidative stress, inflammatory responses, autophagy, ferroptosis, and renal fibrosis. A literature search was conducted in PubMed and Web of Science for articles published between 2017 and 2025 using keywords including "diabetic nephropathy", "diabetic kidney disease", "natural products", "polyphenols", "phenolic acids", "flavonoids", "flavonols", "flavones", "isoflavones", "iridoids", "saponins", "triterpenoids", "lignans", "stilbenes", "curcuminoids", "quinones", "alkaloids", "phenylethanoid glycosides", "autophagy", "ferroptosis", "NLRP3 inflammasome", "NF-κB", "Nrf2", "PI3K/Akt", "TGF-β/Smad", and "mechanisms". The pharmacological mechanisms of major natural product classes in DN are summarized, covering oxidative stress, inflammation, autophagy, and ferroptosis pathways. In contrast to existing reviews, this study categorizes anti-diabetic nephropathy natural products by chemical scaffold and offers a preliminary structure-activity relationship (SAR) analysis, thereby elucidating the potential link between structural features and pharmacological mechanisms. This provides a new research direction for future target identification and the development of novel anti-diabetic nephropathy agents.
