%0 Journal Article
%T Systems-Based Metabolomics and Network Pharmacology Reveal MAOA-Dependent Anti-Ferroptotic Mechanisms of Curcumin in Acute Kidney Injury
%A Katerina Dimitrova
%A Todor Slavov
%J Pharmaceutical Sciences and Drug Design
%@ 3062-4428
%D 2023
%V 3
%N 1
%R 10.51847/HSkwD6pl4L
%P 98-116
%X Acute kidney injury (AKI) remains a major global health concern due to its considerable morbidity and mortality. Increasing evidence points to ferroptosis as a dominant pathological process in AKI, and suppression of monoamine oxidase A (MAOA) as well as 5-hydroxytryptamine signaling has been linked to protection against this form of cell death. Curcumin (Cur), the principal polyphenolic constituent of Curcuma longa, has shown renal protective activity in AKI models, yet the molecular basis through which it influences ferroptotic pathways has not been clearly defined. This study investigates how Cur modulates ferroptosis during AKI. A folic acid–induced mouse model of AKI and erastin/RSL-3–triggered ferroptosis in HK-2 cells were utilized to evaluate the renoprotective effects of Cur. Nuclear magnetic resonance (NMR) metabolomics combined with network pharmacology was applied to identify metabolic disruptions and potential Cur-related targets. Molecular docking and enzymatic assays were employed to determine Cur’s interaction with MAOA.

Cur treatment improved renal function in vivo, evidenced by reduced serum creatinine and blood urea nitrogen levels, and enhanced survival of HK-2 cells undergoing ferroptotic stress in vitro. Mechanistic analyses revealed that Cur mitigates ferroptosis primarily by inhibiting MAOA activity, thereby influencing the metabolic processing of 5-hydroxy-L-tryptophan. These findings suggest, for the first time, that Cur may act as a functional inhibitor of MAOA to counteract ferroptosis in AKI, offering a new mechanistic rationale for its potential therapeutic value.
%U https://galaxypub.co/article/systems-based-metabolomics-and-network-pharmacology-reveal-maoa-dependent-anti-ferroptotic-mechanism-ow70vcsztqst6l6