HESPERETIN INHIBITS ANG II-INDUCED CARDIOMYOCYTE HYPERTROPHY VIA THE NLRP3/NF-&#x0039a;B SIGNALLING PATHWAY

FU Ying; WANG Xin-xing; LIU Hui

Acta Nutrimenta Sinica ›› 2026, Vol. 48 ›› Issue (2) : 180-186.

HESPERETIN INHIBITS ANG II-INDUCED CARDIOMYOCYTE HYPERTROPHY VIA THE NLRP3/NF-ΚB SIGNALLING PATHWAY

FU Ying^1,2, WANG Xin-xing², LIU Hui¹

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Abstract

Objective To investigate the effect of hesperetin (Hst) on cardiomyocyte hypertrophy and explore the underlying mechanism. Methods An in vitro model of cardiomyocyte hypertrophy was established by treating H9c2 cells with different concentrations of angiotensin II (Ang II). Hst at concentrations ranging from 40 to 680 μmol/L was used for intervention. Cell viability was assessed using the cell counting kit-8 (CCK-8) to ultimately select adequate concentrations for the following experiments. Wheat germ agglutinin (WGA) staining and Western blot were employed to detect changes in cell surface area and expression of myocardial hypertrophy markers in H9c2 cells. Western blot was also used to measure the protein expression levels of phosphorylated RELA (p-p65), inhibitor of kappa B alpha (IκBα), and NOD-like receptor pyrin domain-containing protein 3 (NLRP3). Enzyme-linked immunosorbent assay (ELISA) was performed to determine the expression levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). Results Compared with the control group, treatment with 1 μmol/L Ang II produced the most significant hypertrophic effect in H9c2 cells (P<0.05). In the Ang II group, the protein expression levels of NLRP3 and p-p65 were significantly increased, while IκBαwas degraded and its expression decreased (P<0.05). The expression levels of downstream inflammatoryfactors TNF-α, IL-1β, and IL-6 were also significantly elevated (P<0.05). Compared with the Ang II group, Hst intervention reduced cardiomyocyte surface area (P<0.05) and decreased the expression levels of hypertrophy markers ANP and β-MHC (P<0.05). The protein expression levels of NLRP3 and p-p65 were downregulated (P<0.05), while IκBα degradation was attenuated and its expression increased (P<0.05). The expression levels of downstream inflammatory factors TNF-α, IL-1βand IL-6 were significantly reduced (P<0.05). Conclusion Hst significantly inhibits Ang II-induced cardiomyocyte hypertrophy, potentially through suppression of the NLRP3/NF-κB signaling pathway and downstream inflammatory cytokine expression.

Key words

hesperetin / cardiac hypertrophy / NLRP3 / NF-κB / inflammatory factors

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FU Ying, WANG Xin-xing, LIU Hui. HESPERETIN INHIBITS ANG II-INDUCED CARDIOMYOCYTE HYPERTROPHY VIA THE NLRP3/NF-ΚB SIGNALLING PATHWAY[J]. Acta Nutrimenta Sinica. 2026, 48(2): 180-186

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