Paeoniflorin improves myocardial injury via p38 MAPK/NF-KB p65 inhibition in lipopolysaccharide-induced mouse

Abstract

Background: Paeoniflorin (Pae) is an active compound with a variety of pharmacological effects. This aim was to investigate how Pae protects against myocardial injury and to explore its potential mechanism. Methods:We established a BALB/c mouse model that was intraperitoneal injection (i.p.) of RvE1 (25 µg/kg) or Pae (20 mg/kg) for 3 days, and then treated with lipopolysaccharide (LPS, 10 mg/kg, i.p.).The mice were randomly divided into the sham group, the LPS group, the LPS + RvE1 group, the LPS + Pae group (n=8). Cardiac dysfunction was detected by HE staining and ELISA assay. The oxidative stress, mitochondrial membrane potential (MMP), mitochondrial permeability transition pore (mPTP) and apoptosis were assessed. Furthermore, western blotting (WB) assay were employed to analyze the protective mechanisms. Results: Pae improved LPS-induced cardiac function and impeded apoptosis. Pae significantly reduced the release of inflammatory cytokines such as interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and IL-1β. Furthermore, Pae decreased malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS), and increased superoxide dismutase (SOD). In addition, Pae attenuated the mPTP opening and MMP depolarization. Notably, Pae treatment inhibited the activation of p38 MAPK and NF-κB p65. Conclusions: It was confirmed that Pae alleviated LPS-induced myocardial injury. Pae might be as a new drug candidate for myocardial ischaemic complications.

ALKBH5 Stabilized N6-Methyladenosine—Modified LOC4191 to Suppress E. coli-Induced Apoptosis

“…Numerous studies have demonstrated that the MAPK pathway is a classical pathway for apoptosis, with broad regulatory effects on various infectious diseases [48,[58][59][60]. Furthermore, the MAPK pathway has been widely confirmed to collaborate with NF-κB [61][62][63]. P65 is a crucial nuclear transcription factor [60,[64][65][66][67], and p38 has the ability to activate p65 and trigger apoptosis [60,68,69].…”

Neogambogic acid relieves myocardial injury induced by sepsis via p38 MAPK/NF-κB pathway

“…LPS, as endotoxin in Gram-negative bacteria, stimulates cardiac apoptosis and secretion of pro-inflammatory factors [ 13 ]. Therefore, LPS was widely used in the establishment of in vivo model of sepsis induced cardiomyopathy [ 14 ]. Results in this study also showed that LPS induced cardiac injury with up-regulation of biomarkers, including LDH, CK-MB and cTnI.…”

“…Increasing evidence has shown that p38 MAPK/NF-κB is involved in inflammation, and sustained activation of p38 MAPK/NF-κB was positively associated with cardiac injury [ 14 ]. LPS stimulated activation of p38 MAPK/NF-κB signaling, and inactivation of p38 MAPK/NF-κB signaling alleviated LPS-induced cardiac insufficiency [ 21 ].…”

Mitochondria-endoplasmic reticulum contacts in sepsis-induced myocardial dysfunction

“…In addition, LPS treatment results in a reduction of BAP31 levels in cardiomyocytes, while melatonin treatment restores BAP31 expression; BAP31 knockdown attenuates the beneficial effects of melatonin on mitochondrial function and ER homeostasis under LPS stress ( Zhang et al, 2020c ). Several studies have shown that p38 MAPK plays an essential role in SIMD, but the main focus of these studies is on its effect on the NF-κB inflammatory signaling pathway ( Wang et al, 2021d ; Rocca et al, 2021 ; Shyni et al, 2021 ), whether p38 MAPK plays a role in SIMD through the mechanism of Gp78 affecting the degradation of Mfn1 and Mfn2 deserves further investigation.…”