Hesperetin attenuates sepsis-induced intestinal barrier injury by regulating neutrophil extracellular trap formation via the ROS/autophagy signaling pathway

Abstract

Hesperetin (HES), one of the major flavonoids that has various biological activities, such as anti-inflammatory and antioxidant activities, may preserve the intestinal barrier during sepsis.

Neutrophil extracellular traps regulating tumorimmunity in hepatocellular carcinoma

“…PMA promotes cell death by increasing chromatin loosening and incorporating the nuclear envelope into organelles, a process that occurs within a few hours ( 39 , 40 ). This process involves four key steps: (1) enhanced plasma membrane permeability, (2) accelerated disintegration of the nuclear envelope and cytoskeleton, (3) assembly of antimicrobial proteins onto chromatin scaffolds, and (4) decondensation of chromatin ( 41 ). In vitro experiments using isolated neutrophils treated with PMA have provided valuable mechanistic insights into lytic NET formation ( Figure 1 ), demonstrating that neutrophil activation is accompanied by the assembly and activation of a multicomponent nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and ROS ( 51 – 53 ).…”

“…In addition, G protein-coupled receptors (GPCRs) ( 54 ), CXC chemokine receptors (CXCRs) ( 55 ), toll-like receptors (TLRs) ( 56 , 57 ), and cytokine receptors contribute to this process. Hydrogen peroxide (H 2 O 2 ) is a robust oxidant generated by NADPH oxidase during the reduction of molecular oxygen through electron transfer, and it plays a crucial role in both NET and ROS generation ( 41 ). The correlation between neutrophil metabolism and ROS generation has been highlighted in mechanistic studies ( 58 , 59 ).…”

Hesperetin blocks poxvirus replication with a low tendency to select for drug‐resistant viral variants

“…Hesperetin (C 16 H 14 O 6 ) is the aglycone form of the flavanone glycoside hesperidin (C 28 H 34 O 15 ). It is a naturally occurring flavonoid found in citrus fruits such as oranges, grapes, and lemons and possesses antioxidant and anti‐inflammatory properties by regulating various host signaling pathways 22–24 . Recent studies have demonstrated the antiviral activity of hesperetin against herpes simplex virus type 1 (HSV‐1), poliovirus type 1, parainfluenza virus type 5, respiratory syncytial virus (RSV), influenza A virus, chikungunya virus (CHIKV), Zika virus (ZIKV), severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), yellow fever virus (YFV), Sindbis virus, and dengue virus (DENV) 25–32 .…”

“…It is a naturally occurring flavonoid found in citrus fruits such as oranges, grapes, and lemons and possesses antioxidant and anti-inflammatory properties by regulating various host signaling pathways. [22][23][24] Recent studies have demonstrated the antiviral activity of hesperetin against herpes simplex virus type 1 (HSV-1), poliovirus type 1, parainfluenza virus type 5, respiratory syncytial virus (RSV), influenza A virus, chikungunya virus (CHIKV), Zika virus (ZIKV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), yellow fever virus (YFV), Sindbis virus, and dengue virus (DENV). [25][26][27][28][29][30][31][32] In this study, we extended the antiviral efficacy of hesperetin against poxviruses, besides providing insights into its potential mechanisms of action.…”

Mechanism of electro-acupuncture in alleviating intestinal injury in septic mice via polyamine-related M2-macrophage polarization

“…As a result, blood flow is often redirected to vital organs such as the brain, lungs, and heart, which can cause ischemia, hypoxia, and reperfusion injury in the intestinal mucosa. During this process, a large amount of oxygen free radicals are produced, which can disrupt the formation and distribution of tight junctions between cells and cause damage to the intestinal epithelium ( 10 – 12 ). Simultaneously, the compromised intestinal microenvironment, weakened intestinal motility, and inadequate intestinal nutrition result in intestinal barrier dysfunction and increased permeability ( 13 , 14 ).…”