Qiangxin recipe improves doxorubicin-induced chronic heart failure by enhancing KLF5-mediated glucose metabolism

Background: Qiangxin recipe (QXF) is a well-known Chinese herbal medicine commonly used in Asia for thou-sands of years to treat cardiovascular diseases, but its underlying mechanism remains unclear. Purpose: This study aimed to illustrate whether Qiangxin Recipe (QXF) induce glucose metabolism and inhibit cardiomyocyte apoptosis by promoting the activation of the transcription factor Kruppel like factor 5 (KLF5).Material and methods: In vitro experiments, we constructed an H9C2 cardiomyocyte injury model using doxo-rubicin and used RNA-seq data analysis to detect the mechanism of QXF. In in vivo experiments, C57 BL/6 mice injected with doxorubicin (4 mg/kg every 6 days, for 30 days) to construct a CHF mouse model and randomly divided into to the normal control group, Dox group and Dox+QXF group (2.12 g/kg/day, 4.24 g/kg/day, for 30 days). Using Echocardiography, serum biochemical indices BNP, cTnl; and histopathological tests involving HE staining, Tunel staining and Immuno-dual fluorescence colocalization to analyze the therapeutic mechanism of QXF. Results: We verified that the Qiangxin recipe could reverse cardiomyocyte dying through enhancing glucose metabolism and reducing apoptosis to improve CHF. Mechanistically, we discovered that the Qiangxin recipe promoted the activation of transcription factor Kruppel-like factor 5 (KLF5) to induce glucose metabolism and inhibit apoptosis in cardiomyocytes. Further, we identified that KLF5 increased the promoter activity of hexo-kinase 2 (HK2) and B-cell CLL/lymphoma 2 (BCL2) genes, which further enhanced glucose metabolism and inhibited apoptosis of cardiomyocytes. Conclusions: We highlighted the importance of KLF5-mediated signaling pathways in the treatment of CHF as shown by their participation in glucose metabolism and apoptosis in a doxorubicin-induced model of car-diomyocyte injury, as well as show that Qiangxin recipe can be used as a novel targeted therapy for the treatment of CHF. Compared with previous studies, we provide new ideas for the treatment of Doxorubicin-induced CHF from the perspective of energy metabolism.

Automated summary

This study aimed to investigate whether the Qiangxin recipe can induce glucose metabolism and inhibit cardiomyocyte apoptosis by promoting the activation of the transcription factor Kruppel like factor 5 (KLF5). The results showed that the Qiangxin recipe can improve congestive heart failure by enhancing glucose metabolism and reducing apoptosis. The KLF5-mediated signaling pathways play an important role in the treatment of congestive heart failure, and the Qiangxin recipe can be used as a novel targeted therapy.