Apigenin’s Health Benefits in Kidney Disease: Pharmacological Insights and Future Perspectives

ABSTRACT

The incidence of kidney diseases is increasing globally, posing a serious threat to human health. Studies have shown that apigenin, a natural dietary flavonoid with multiple bioactivities, may be effective in protecting the kidneys and treating a variety of kidney diseases. This review collates and discusses the available evidence on the therapeutic effects of apigenin on common kidney diseases. In addition, the specific molecular mechanisms by which apigenin exerts its renoprotective effects are described, which informs further research and clinical nutritional applications of apigenin in the field of renal diseases.

GRAPHICAL ABSTRACT

KEYWORDS:

• Kidney disease
• natural compounds
• apigenin
• molecular mechanism
• nephroprotective

Acknowledgments

This study was sponsored by the National Natural Science Foundation of China (32371185); the Shanghai Science and Technology Plan Project (23010504200); the “Shuguang Program” (20SG50) funded by Shanghai Education Development Foundation and Shanghai Municipal Education Commission; the Shanghai Talent Development Fund (2020125); the Key Lab of Exercise and Health Sciences of Ministry of Education (Shanghai University of Sport) (2022KF001); and the Shanghai Key Lab of Human Performance (Shanghai University of Sport) (NO. 11DZ2261100).

Disclosure statement

No potential conflict of interest was reported by the author(s).

CRediT author statement

Jiabin Wu: Conceptualization, Data curation, Writing-Original draft preparation. Wei Dai: Data curation, Writing-review & editing, Validation. Ke Li: Writing-review & editing, Validation. Xianyi Ding: Writing-review & editing, Investigation. Haoyang Gao: Writing-review & editing, Validation. Wenhong Wang: Supervision, Project administration, Writing-review & editing. Weihua Xiao: Funding acquisition, Project administration, Supervision, Writing-review & editing. All authors read and approved the final manuscript.

Notes

1 Abbreviation: AKI, acute kidney injury; CKD, chronic kidney disease; DN, diabetic nephropathy; UAN, hyperuricemic nephropathy; RIRI, renal ischemia-reperfusion injury; RF, renal fibrosis; RCC, renal cell carcinoma; KS, kidney stones; MSCs, mesenchymal stem or stromal cells; ESRD, end-stage renal disease; RASS, renin – angiotensin – aldosterone system; SGLT2i, sodium-glucose transporter 2 inhibitors; VRA, vasopressin receptor antagonists; BCS, Biopharmaceutics Classification System; PAL, phenylalanine ammonia-lyase; C4H, cinnamic acid-4-hydroxylase; 4CL, 4-coumaric acid-coenzyme A ligase; CHS, chalcone synthase; CHI, chalcone isomerase; FS, flavonoid synthase; NADPH, nicotinamide adenine dinucleotide phosphate; ER, endoplasmic reticulum; FMO, flavin-containing monooxygenase; ROS, reactive oxygen species; TGF-β1, transforming growth factor-β1; Col, collagen; FN, fibronectin; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor kappa-B; TNF-α, tumor necrosis factor-α; IL, interleukin; Bcl-2, B-cell lymphoma-2; IFN-γ, interferon-γ; USF2, upstream stimulating factor 2; SOD, superoxide dismutase; IDH2, isocitrate dehydrogenase 2; Sirt3, sirtuin 3; Nrf2, nuclear factor erythroid2-related factor 2; HO-1, heme oxygenase-1; PI3K, phosphoinositide 3-kinase; Akt, protein kinase B; GSH, glutathione; CAT, catalase; MDA, malondialdehyde; HUA, hyperuricemia; UA, uric acid; URAT1, uric acid transporter 1; GLUT9, glucose transporter 9; PO, potassium oxybate; α-SMA, α-smooth muscle actin; JAK2, janus kinase 2; STAT3,signal transducer and activator of transcription 3; SOCS3, signal of cytokine signaling 3; TLR4, toll-like receptor 4; ICAM-1, intercellular cell adhesion molecule-1; CXCL12, C-X-C motif chemokine ligand 12; PKM2, Pyruvate kinase isozyme type M2; HIF-1α, hypoxia-inducible factor-1α; GSK3β, glycogen synthase kinase-3 beta; DOCA, deoxycorticosterone acetate; TRPV4, transient receptor potential vanilloid 4; AMPK, AMP-activated protein kinase; ERK, extracellular regulated protein kinases; MET, mesenchymal to epithelial transition; 5-FU, 5-Fluorouracil; GPX, glutathione peroxidase; CP, cisplatin; MTX, methotrexate; iNOS, inducible nitric oxide synthase; DOX, doxorubicin; NLRP3, NOD-like receptor thermal protein domain associated protein 3; GNT, Gentamicin; KIM-1, kidney injury molecule-1; NGAL, neutrophil gelatinase-associated lipocalin; LPO, lipid peroxide; Imp, Imipenem; OATs, organic anion-transporting proteins; CsA, cyclosporin A; NiONPs, nickel oxide nanoparticles; FOXO3a, forkhead rhabdomyosarcoma-like 1; IkB, inhibitory kappa B; MSNs, mesoporous silica nanoparticles; MWCNTs, multi-walled carbon nanotube; EDF, Edifenphos; APCs, antigen-presenting cells; COX-2, cyclooxygenase 2; c-FLIP, cellular FLICE-like inhibitory protein; HC, hypercholesterolaemia; IS, indoxyl sulfate; GSK-3β, glycogen synthase kinase-3 β; PbAc, lead acetate; HRSD, Hamilton rating scale for depression; NDBs, nucleotide-binding domains; ABC, ATP-binding cassette.

Additional information

Funding

This study was sponsored by the National Natural Science Foundation of China [32371185]; the Shanghai Science and Technology Plan Project [23010504200]; the “Shuguang Program” [20SG50] funded by Shanghai Education Development Foundation and Shanghai Municipale Education Commission; the Shanghai Talent Development Fund [2020125]; the Key Lab of Exercise and Health Sciences of Ministry of Education (Shanghai University of Sport) [2022KF001]; and the Shanghai Key Lab of Human Performance (Shanghai University of Sport) [NO. 11DZ2261100].