Work

Kaixuan Qibi granules attenuate myocardial fibrosis through BRD4 blockade regulated by the NF-κB/NLRP3 signaling pathway

Year: 2025

Type: article

Abstract: Background and aim Kaixuan Qibi granules (KXGs) have exhibited favorable therapeutic outcomes in addressing a wide range of ailments. They have established their efficacy as a traditional Chinese medicine formulation, particularly for cardiovascular and cerebrovascular diseases associated with myocardial fibrosis (MF). Targeting of bromodomain-containing protein 4 (BRD4) represents an efficacious strategy for addressing inflammation (a pivotal factor in MF progression). However, revealing the inhibitory impact of KXGs on BRD4 in MF development is elusive. We investigated the impact of KXGs on MF and elucidated the regulatory mechanism of BRD4 in MF by KXGs in vitro and in vivo . Experimental procedure Induction of an in vivo model of MF was achieved in C57BL/6 mice by intraperitoneal administration of isoproterenol (ISO) over 21 days. After administering different doses of KXGs and fosinopril (FOS) via oral gavage for 21 days, metabolite levels, myofibril accumulation, and collagen deposition were assessed using standardized assays. To simulate an inflammatory reaction in vitro , mouse monocyte–macrophage leukemia (RAW264.7) cells were stimulated with lipopolysaccharide (LPS). The intervention effect of KXGs on BRD4 and the nuclear factor-kappa B/NOD-like receptor protein 3 (NF-κB/NLRP3) pathway was evaluated using western blotting and immunofluorescence methods. Results In this study, we observed a notable reduction in the extent of fibrotic tissue accompanied by organized collagen following treatment with KXGs. KXGs exhibited a significant regulatory effect on metabolite levels while also inhibiting BRD4-related pathways and the inflammatory response. Later, KXGs exhibited downregulation the expression of BRD4, phosphorylated-NF-κB p65 (p-NF-κB p65), NF-κB p65, NLRP3, ASC, caspase-1, and interleukin-1β (IL-1β) in both in vitro and in vivo models of MF development. Conclusion KXGs attenuated MF progression by modulating the NF-κB/NLRP3 signaling pathway through inhibition of BRD4 activity.

Source: Journal of Traditional and Complementary Medicine

DOI: 10.1016/j.jtcme.2025.03.001