Kaempferol Protects Against Streptozotocin-Induced Diabetic Cardiomyopathy in Rats by Inhibition of the NLRP3/Caspase-1 Signaling Pathway
Year: 2024
Type: article
Abstract: Kaempferol (KPF) attenuates diabetic cardiomyopathy (DCM) in streptozotocin (STZ)-treated rats through its hypoglycaemic and insulin-releasing effects, however, the mechanism of KPF protects against DCM is unclear. This study was to reveal the cardioprotective mechanism of KPF. Molecular docking was used to predict the target of KPF. STZ-induced diabetes mellitus (DM) rats was established. The model rats with successful modeling were randomly divided into DM group, KPF group (10 mg/kg), and metformin (Met) group (120 mg/kg). The CTL group and DM group were gavaged with equal amounts of CMC-Na, and all groups were intervened for eight weeks. The changes of blood glucose in different groups was detected. Hematoxylin-eosin (HE), and Masson staining were used to assess pathological changes. Creatine kinase (CK), and B-type natriuretic peptides (BNP) levels were examined. RT-qPCR was used to detect the mRNA expression levels of toll-like receptor 4 (TLR4), NOD-like receptor protein 3 (NLRP3), cysteinyl aspartate specific proteinase-1 (Caspase-1), and GSDMD-N-terminal domain (GSDMD-N), and Western blot was used to detect the expression of NLRP3, and GSDMD-N. KPF has a good binding affinity with TLR4. KPF could significantly improve the abnormal elevation of blood glucose, mitigate pathological changes, and reduce CK and BNP levels. Further mechanistic studies found that KPF reduced the mRNA expressions of TLR4, NLRP3, Caspase-1, and GSDMD-N, and decreased the protein expressions of NLRP3, and GSDMD-N. In conclusion, the mechanism of KPF protects against DCM is related to the inhibition of the NLRP3/Caspase-1 signaling pathway, providing a novel mechanism for KPF intervention in DCM.
Authors: An-lu Shen, Yong-qin Du, Min Ye, Lan Zhou, Hui-min Ding, Zi-qing Hu, Peng Zhou
Institution: Anhui University of Traditional Chinese Medicine
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W4405320620