Kaempferol attenuates LPS-induced inflammatory responses in H9c2 cells through involvement of the IL-6/JAK2/STAT3 pathway

BACKGROUND: Kaempferol (Kae), a flavonoid compound, has shown considerable potential in preventing and treating cardiovascular diseases and ameliorating myocardial damage. However, its underlying mechanisms remain complex and require further elucidation. This study investigated the protective effects of Kae pretreatment against lipopolysaccharide (LPS)-induced inflammatory responses in H9c2 cardiomyocytes through the interleukin-6 (IL-6)/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway, aiming to establish a theoretical foundation for Kae development and clinical application. METHODS: Initially, potential targets were identified through network pharmacology and molecular docking. The protective efficacy of Kae against CS was then preliminarily validated in vivo via histopathological analysis (hematoxylin and eosin staining). Finally, an LPS-induced CS model was constructed in H9c2 cardiomyocytes to elucidate the underlying mechanisms in vitro. RESULTS: Network pharmacology analysis indicated that Kae may exert anti-CS effects via modulation of the IL-6/JAK2/STAT3 signaling pathway. In vivo experiments demonstrated that Kae significantly ameliorated histopathological changes, including disorganized myocardial fibers and inflammatory cell infiltration. Compared with the model group, serum levels of tumor necrosis factor alpha (TNF-α), IL-6, and interleukin-1β (IL-1β) were significantly decreased, along with reduced mRNA expression of these cytokines in cardiac tissue. In vitro, LPS stimulation significantly elevated the levels of TNF-α, IL-6, and IL-1β, and increased phosphorylated Janus kinase 2 (p-JAK2) and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) expression compared with the control group (P < 0.01). Kae pretreatment significantly reduced these inflammatory mediators and downregulated p-JAK2 and p-STAT3 expression compared with the LPS group (P < 0.01). Additionally, Kae pretreatment increased superoxide dismutase activity while decreasing malondialdehyde content and nitric oxide production (P < 0.05). CONCLUSION: Kae pretreatment demonstrated a protective effect against the LPS-induced inflammatory response in H9c2 cells. This protective effect potentially involves regulating the IL-6/JAK2/STAT3 signaling pathway.