Nimbolide Reduces Inflammation and Oxidative Stress to Inhibit Disease Progression in Septic Acute Kidney Injury Mice

Yihua Yu; Yangling Li; Ying Gong

doi:10.2478/aite-2026-0023

.blurhash-client-img { display: none !important; }

Nimbolide Reduces Inflammation and Oxidative Stress to Inhibit Disease Progression in Septic Acute Kidney Injury Mice

Archivum Immunologiae et Therapiae Experimentalis

Volume 74 (2026): Issue 1 (January 2026)

By: Yihua Yu, Yangling Li and Ying Gong

Open Access

|Aug 2026

Abstract

The study investigates the protective role of Nimbolide, a natural limonoid, against sepsis-associated acute kidney injury (SA-AKI) and its underlying molecular mechanisms. A murine sepsis model was established via cecal ligation and perforation. Renal histopathological changes were evaluated by hematoxylin and eosin staining, and renal function was assessed based on serum creatinine (Scr) and blood urea nitrogen (BUN) levels. The levels of inflammatory cytokines (interleukin-6 [IL-6], interleukin-1β [IL-1β], tumor necrosis factor-α [TNF-α]) in serum and renal homogenates were quantified by ELISA. Oxidative stress markers (malondialdehyde [MDA], superoxide dismutase [SOD], glutathione [GSH]) in renal tissue were measured using commercial assay kits. Renal cell apoptosis was detected by transferase dUTP nick end labeling (TUNEL) assay. Also, the protein expression and phosphorylation levels of nuclear factor kappa B (NF-κB) p65 and STAT3 in renal tissues were analyzed by Western blotting. Nimbolide treatment markedly attenuated tubular vacuolization and inflammatory cell infiltration, and improved renal function, as demonstrated by reduced serum Scr and BUN levels. Nimbolide also suppressed the levels of the pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) in both serum and renal tissue. Furthermore, Nimbolide decreased MDA levels, increased SOD activity and GSH content, and inhibited renal apoptosis. Mechanistically, these protective effects were associated with the inhibition of NF-κB p65 and STAT3 phosphorylation in the kidneys. Nimbolide protects against SA-AKI by inhibiting activation of the NF-κB/STAT3 pathway, thereby attenuating inflammation, oxidative stress, and apoptosis.

References

Annaldas S, Saifi MA, Khurana A et al. (2019) Nimbolide ameliorates unilateral ureteral obstruction-induced renal fibrosis by inhibition of TGF-β and EMT/Slug signalling. Mol Immunol 112:247–255. https://doi.org/10.1016/j.molimm.2019.06.003
Search in Google Scholar Back to article
Ba J, Lin Y, Zhang J et al. (2025) Nimbolide targeting SIRT1 protects against acetaminophen-induced acute liver injury by regulating oxidative stress and endoplasmic reticulum stress. Pharmacol Res Perspect 13:e70120. https://doi.org/10.1002/prp2.70120
Search in Google Scholar Back to article
Jiang J, Hu B, Chung CS et al. (2020) SHP2 inhibitor PHPS1 ameliorates acute kidney injury by Erk1/2-STAT3 signaling in a combined murine hemorrhage followed by septic challenge model. Mol Med 26:89. https://doi.org/10.1186/s10020-020-00210-1
Search in Google Scholar Back to article
Li N, Lin G, Zhang H et al. (2023) Lyn attenuates sepsis-associated acute kidney injury by inhibition of phospho-STAT3 and apoptosis. Biochem Pharmacol 211:115523. https://doi.org/10.1016/j.bcp.2023.115523
Search in Google Scholar Back to article
Li H, Ren Q, Hu Y et al. (2024) SKLB023 protects against inflammation and apoptosis in sepsis-associated acute kidney injury via the inhibition of Toll-like receptor 4 signaling. Int Immunopharmacol 139:112668. https://doi.org/10.1016/j.intimp.2024.112668
Search in Google Scholar Back to article
Liu AB, Tan B, Yang P et al. (2024) The role of inflammatory response and metabolic reprogramming in sepsis-associated acute kidney injury: Mechanistic insights and therapeutic potential. Front Immunol 15:1487576. https://doi.org/10.3389/fimmu.2024.1487576
Search in Google Scholar Back to article
Lou Y, Shi H, Sha N et al. (2025) Ursodeoxycholic acid protects against sepsis-induced acute kidney injury by activating Nrf2/HO-1 and inhibiting NF-κB pathway. BMC Nephrol 26:45. https://doi.org/10.1186/s12882-025-03977-9
Search in Google Scholar Back to article
Ma Y, Xu S, Meng J et al. (2022) Protective effect of nimbolide against streptozotocin induced gestational diabetes mellitus in rats via alteration of inflammatory reaction, oxidative stress, and gut microbiota. Environ Toxicol 37:1382–1393. https://doi.org/10.1002/tox.23491
Search in Google Scholar Back to article
Mou L, Yang L, Hou S et al. (2023) Structure-activity relationship studies of 2,4,5-trisubstituted pyrimidine derivatives leading to the identification of a novel and potent sirtuin 5 inhibitor against sepsis-associated acute kidney injury. J Med Chem 66: 11517–11535. https://doi.org/10.1021/acs.jmedchem.3c01031
Search in Google Scholar Back to article
Pooladanda V, Thatikonda S, Bale S et al. (2019) Nimbolide protects against endotoxin-induced acute respiratory distress syndrome by inhibiting TNF-α mediated NF-κB and HDAC-3 nuclear translocation. Cell Death Dis 10:81. https://doi.org/10.1038/s41419-018-1247-9
Search in Google Scholar Back to article
Ren Q, Guo F, Tao S et al. (2020) Flavonoid fisetin alleviates kidney inflammation and apoptosis via inhibiting Src-mediated NF-κB p65 and MAPK signaling pathways in septic AKI mice. Biomed Pharmacother 122:109772. https://doi.org/10.1016/j.biopha.2019.109772
Search in Google Scholar Back to article
Şahin N, Bora ES, Çınaroğlu OS et al. (2025) Rho-associated kinase inhibitor fasudil protects from sepsis-induced acute kidney injury in rat via suppressing STAT-3 and NLRP-3 pathway. Curr Issues Mol Biol 47:340. https://doi.org/10.3390/cimb47050340
Search in Google Scholar Back to article
Senousy SR, Ahmed AF, Abdelhafeez DA et al. (2022) Alpha-chymotrypsin protects against acute lung, kidney, and liver injuries and increases survival in CLP-induced sepsis in rats through inhibition of TLR4/NF-κB pathway. Drug Des Devel Ther 16:3023–3039. https://doi.org/10.2147/DDDT.S370460
Search in Google Scholar Back to article
Shu X, Hu Y, Huang C et al. (2021) Nimbolide ameliorates the streptozotocin-induced diabetic retinopathy in rats through the inhibition of TLR4/NF-κB signaling pathway. Saudi J Biol Sci 28:4255–4262. https://doi.org/10.1016/j.sjbs.2021.06.039
Search in Google Scholar Back to article
Teng Y, Huang Y, Yu H et al. (2023) Nimbolide targeting SIRT1 mitigates intervertebral disc degeneration by reprogramming cholesterol metabolism and inhibiting inflammatory signaling. Acta Pharm Sin B 13:2269–2280. https://doi.org/10.1016/j.apsb.2023.02.018
Search in Google Scholar Back to article
Wang X, Li J, Yu B et al. (2026) Nimbolide inhibits NLRP3 inflammasome activation via blocking NEK7-NLRP3 interaction and alleviates sepsis-induced lung injury. Int Immunopharmacol 168(Pt 2):115954. https://doi.org/10.1016/j.intimp.2025.115954
Search in Google Scholar Back to article
Wang HW, Wu MM, Zhu MM et al. (2025) Growth differentiation factor 11 attenuates sepsis-associated acute kidney injury by reducing inflammation and coagulation via PGC-1α/Nrf2 activation. Cell Mol Biol Lett 30:102. https://doi.org/10.1186/s11658-025-00762-2
Search in Google Scholar Back to article
Xia YM, Guan YQ, Liang JF et al. (2024) TAK-242 improves sepsis-associated acute kidney injury in rats by inhibiting the TLR4/NF-κB signaling pathway. Ren Fail 46:2313176. https://doi.org/10.1080/0886022X.2024.2313176
Search in Google Scholar Back to article
Zhang R, Su K, Yang L et al. (2023) Design, synthesis, and biological evaluation of novel P2X7 receptor antagonists for the treatment of septic acute kidney injury. J Med Chem 66:11365–11389. https://doi.org/10.1021/acs.jmedchem.3c00837
Search in Google Scholar Back to article

Articles in this issue

DOI: https://doi.org/10.2478/aite-2026-0023 | Journal eISSN: 1661-4917

Journal RSS Feed

Language: English

Submitted on: Mar 31, 2026

Accepted on: Jul 10, 2026

Published on: Aug 22, 2026

Published by: Hirszfeld Institute of Immunology and Experimental Therapy

In partnership with: Paradigm Publishing Services

Publication frequency: 1 issue per year

Keywords:

Nimbolide,

Sepsis-associated acute kidney injury,

Related subjects:

Basic medical science,

Biochemistry,

Immunology,

Clinical medicine,

Clinical medicine, other,

Clinical chemistry

© 2026 Yihua Yu, Yangling Li, Ying Gong, published by Hirszfeld Institute of Immunology and Experimental Therapy
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Volume 74 (2026): Issue 1 (January 2026)