Kaempferol‐3‐ O ‐rutinoside exerts cardioprotective effects through NF‐ κ B/NLRP3/Caspase‐1 pathway in ventricular remodeling after acute myocardial infarction

Abstract

Ventricular remodeling (VR) after acute myocardial infarction (AMI) is the main pathogenesis of chronic heart failure (CHF). Kaempferol-3-O-rutinoside (KR) is the flavonoid glycoside with the highest content in Lu'an GuaPian tea, which has good pharmacological activities. However, the mechanism of KR against VR after AMI remains unclear. Molecular docking was used to predict the targets of KR on the NLRP3/Caspase-1 signaling pathway. Histological changes in the myocardium were visualized using HE staining, Masson staining. Cardiomyocyte apoptosis was detected using TUNEL. Immunohistochemistry was used to examine NLRP3, Caspase-1 p20, and GSDMD. IL-1β level in serum was detected using ELISA. Finally, the expressions of NF-κB p65, NLRP3, ASC, Caspase-1 p20, GSDMD, and IL-1β were measured using RT-PCR and Western blotting. Our results showed that KR had a good binding activity with NLRP3, Caspase-1, and GSDMD, significantly improved cardiac function, alleviated cardiac pathological changes, reduced the excessive deposition of myocardial interstitial collagen, and inhibited cardiomyocyte apoptosis in AMI rats. Furthermore, KR could decrease the IL-1β level and inhibit the expressions of NF-κB p65, NLRP3, ASC, Caspase-1 p20, GSDMD, and IL-1β. Our study suggests that KR can prevent and treat VR after AMI, and the protective effect is related to its regulatory NF-κB/ NLRP3/Caspase-1 signaling pathway. Practical applicationsKaempferol-3-O-rutinoside is present in Carthamus tinctorius L., Nymphaea candida, Afgekia mahidoliae and green tea, which has good pharmacological activities against liver injury, cerebral ischemia/reperfusion injury, dementia, hyperglycemia, and myocardial infarction. Our previous study found that kaempferol-3-O-rutinoside had an obvious anti-inflammatory effect, and could significantly improve the cell survival rate of H9c2 myocardium inflammatory injury induced by LPS. In this study, kaempferol-3-O-rutinoside significantly improved cardiac function, alleviated cardiac pathological changes, reduced the excessive deposition of myocardial interstitial collagen, and inhibited cardiomyocyte apoptosis in AMI rats. Furthermore, kaempferol-3-O-rutinoside

Lactoferrin alleviates Western diet-induced cognitive impairment through the microbiome-gut-brain axis

“…As a result, numerous neuroin ammation processes further exacerbate the pathological processes that cause cognitive impairment [40]. The in ammatory signaling pathway NF-κB/NLRP3/caspase-1 is activated in a variety of cells [39,41]. In this study, NF-κB/NLRP3 in ammasome activation was found to be involved in neuroin ammation caused by WD feeding.…”

Pretreatment of kaempferol-3-O-rutinoside protects H9c2 cells against LPS-induced inflammation through the AMPK/SIRT1 pathway

“…Previous research has demonstrated that KR could decrease the protein expression levels of TLR4, MyD88, and NF-κB in LPS-induced H9c2 cell injury, indicating that it inhibits inflammatory response through TLR4/MyD88/NF-κB signaling pathway (Hua et al, 2021). Our latest finding has indicated that KR could decrease IL-1β level and inhibited the expression levels of NF-κB, NLRP3, ASC, Caspase-1 p20, GSDMD, and IL-1β, suggesting that the protective effect of KR was related to regulating the NF-κB/NLRP3/Caspase-1 signaling pathway (Hua et al, 2022). Thus, our studies found that KR is closely related to NF-κB.…”

“…Previous studies have found that KR improves hemodynamics and cardiac function, reduces myocardial fibrosis and cardiomyocyte apoptosis, and decreases excessive release of inflammatory factors by inhibiting nuclear factor kappa B-oligomerization domain-like receptor family pyrin domain-containing 3-caspase-1 (NF-κB/NLRP3/Caspase-1) signaling pathway. The myocardial protective effect of KR is related to its regulation of NF-κB/NLRP3/Caspase-1 signaling pathway (Hua et al, 2022). However, the activation of NF-κB is regulated by the upstream AMPK-silent mating type information regulation 2 homolog 1 (sirtuin) (SIRT1) signaling pathway, which leads to myocardial cell damage (Chen et al, 2018).…”

Major quality regulation network of flavonoid synthesis governing the bioactivity of black wolfberry

“…For instance, rutin prevents tau pathology and neuroinflammation associated with Alzheimer's disease and attenuates doxorubicin‐induced cardiotoxicity through mediating cell apoptosis (Ma et al ., 2017; Sun et al ., 2021). K3R improves the inflammatory responses in lipopolysaccharide‐stimulated RAW264.7 cells through the NF‐κB pathway and exerts cardioprotective effects through alleviating cell apoptosis in ventricular remodeling after acute myocardial infarction (Hwang et al ., 2019; Hua et al ., 2022). Here, QH fruit contained higher levels of K3R and rutin, which effectively alleviated H 2 O 2 ‐induced cell apoptosis and inflammatory responses, supporting their importance in the medicinal activity of black wolfberry.…”