β-carotene attenuates calcium oxalate crystal-induced renal injury through suppression of NF-κB-mediated inflammation.

Abstract

Calcium oxalate (CaOx) nephrolithiasis represents the most prevalent form of kidney stone disease and is characterized by persistent renal inflammation and tissue damage. β-Carotene, a naturally occurring carotenoid with well-documented anti-inflammatory properties, has demonstrated beneficial effects in a variety of inflammatory conditions; however, its potential role in CaOx crystal-associated renal injury remains largely unexplored. In this study, the effects of β-carotene on CaOx-induced renal damage were evaluated using both cellular and animal models. In human renal proximal tubular epithelial (HK-2) cells, β-carotene effectively alleviated calcium oxalate monohydrate (COM)-induced injury, decreased kidney injury molecule-1 (KIM-1) expression, and reduced the production of pro-inflammatory mediators, including TNF-α, IL-1β, IL-6, and MCP-1. Similarly, in a glyoxylate-induced nephrocalcinosis mouse model, β-carotene attenuated CaOx crystal accumulation, improved renal histopathological alterations and functional impairment, and suppressed inflammatory responses. To investigate the underlying mechanisms, network pharmacology and molecular docking analyses were conducted. A total of 145 overlapping targets were identified, and enrichment analyses identified NF-κB signaling as one of the candidate pathways potentially involved in the protective effects of β-carotene. Molecular docking analysis suggested favorable binding affinities between β-carotene and several key targets. Experimental validation demonstrated that β-carotene markedly inhibited NF-κB activation in both in vitro and in vivo settings, whereas pharmacological activation of NF-κB partially abolished its beneficial effects. Taken together, these findings indicate that β-carotene ameliorates CaOx crystal-induced renal injury and inflammation, at least in part through suppression of NF-κB signaling, and may offer a potential basis for the development of novel preventive and therapeutic approaches for kidney stone disease.