Kaempferol Attenuates Myocardial Ischemic Injury via Inhibition of MAPK Signaling Pathway in Experimental Model of Myocardial Ischemia‐Reperfusion Injury

Abstract

Kaempferol (KMP), a dietary flavonoid, has antioxidant, anti-inflammatory, and antiapoptotic effects. Hence, we investigated the effect of KMP in ischemia-reperfusion (IR) model of myocardial injury in rats. We studied male albino Wistar rats that were divided into sham, IR-control, KMP-20 + IR, and KMP 20 per se groups. KMP (20 mg/kg; i.p.) was administered daily to rats for the period of 15 days, and, on the 15th day, ischemia was produced by one-stage ligation of left anterior descending coronary artery for 45 min followed by reperfusion for 60 min. After completion of surgery, rats were sacrificed; heart was removed and processed for biochemical, morphological, and molecular studies. KMP pretreatment significantly ameliorated IR injury by maintaining cardiac function, normalizing oxidative stress, and preserving morphological alterations. Furthermore, there was a decrease in the level of inflammatory markers (TNF-α, IL-6, and NFκB), inhibition of active JNK and p38 proteins, and activation of ERK1/ERK2, a prosurvival kinase. Additionally, it also attenuated apoptosis by reducing the expression of proapoptotic proteins (Bax and Caspase-3), TUNEL positive cells, and increased level of antiapoptotic proteins (Bcl-2). In conclusion, KMP protected against IR injury by attenuating inflammation and apoptosis through the modulation of MAPK pathway.

The protective effect of kaempferol on heart via the regulation of Nrf2, NF‐κβ, and PI3K/Akt/GSK‐3β signaling pathways in isoproterenol‐induced heart failure in diabetic rats

“…In contrast, treatment with KF reduced the serum cardiac markers due to decreased leakage of these markers into serum (Vishwakarma et al, 2018). The current study was supported by the previous reports, which indicated that KF treatment caused the decrease in cell damage and increase in cell integrity and thereby decreases the serum cardiac injury markers in ISO-induced cardiac toxicity in rats (Suchal et al, 2016). The results of the present study are also in agreement with reports of the earlier study which suggested that KF treatment decreased creatine kinase and LDH in MI-induced rats (Zhou, Ren et al, 2015).…”

“…In addition to these enzymes, GR and GST provide GSH to neutralize the toxic electrophiles (Giacco & Brownlee, 2010). The present study results are in par with previous studies, where reduced MDA levels with increased SOD, CAT, and GPx activity levels were observed in KF-treated ISO-induced cardiac toxicity in rats (Suchal et al, 2016). Recently, a few other studies showed that KF treatment reduced the LPO and bought back antioxidant enzymes like SOD, CAT, GPx, and GST in liver, kidney, and heart of diabetic rats (Al-Numair, Chandramohan, Veeramani, & Alsaif, 2015) and ISO-induced myocardial injury rats (Zhou, Ren et al, 2015).…”

“…Moreover, GSK‐3β plays a vital role in glycogen metabolism and insulin resistance (Wang et al, ). Furthermore, another study observed that treatment of KF inhibit the active p38MAPK and activation of ERK1/ERK2 in myocardial ischemia–reperfusion injury rats (Suchal et al, ). The activation of PI3K/AKT/GSK‐3β and ERK/MAPK pathways can effectively inhibit the ROS by regulating the expression of Bcl‐2 family.…”

N-Acetylcysteine Influence on Oxidative Stress and Cardiac Remodeling in Rats During Transition from Compensated Left Ventricular Hypertrophy to Heart Failure

“…Experimental studies have shown that the mitogen-activated protein kinase (MAPK) signaling pathway is involved in myocardial response to oxidative stress in several conditions [41-43]. MAPK includes four subfamilies, three of which have been well characterized: extracellular regulated kinase (ERK 1/2), c-jun N-terminal kinase (JNK), and p38-MAPK.…”

“…MAPK includes four subfamilies, three of which have been well characterized: extracellular regulated kinase (ERK 1/2), c-jun N-terminal kinase (JNK), and p38-MAPK. After oxidative stress increase, MAPK downstream signaling may lead to myocardial hypertrophy and fibrosis [6, 41, 42, 44]. We therefore evaluated MAPK protein expression and observed that p-ERK and p-JNK were lower in AS-NAC than AS.…”