Anti-Septic Functions of Cornuside against HMGB1-Mediated Severe Inflammatory Responses

Abstract

High mobility group box 1 (HMGB1) is acknowledged to have critical functions; therefore, targeting this protein may have therapeutic effects. One example is potential antiseptic activity obtained by suppressing HMGB1 secretion, leading to the recovery of vascular barrier integrity. Cornuside (CN), which is a product extracted from the fruit of Cornusofficinalis Seib, is a natural bis-iridoid glycoside with the therapeutic effects of suppressing inflammation and regulating immune responses. However, the mechanism of action of CN and impact on sepsis is still unclear. We examined if CN could suppress HMGB1-induced excessive permeability and if the reduction of HMGB1 in response to LPS treatment increased the survival rate in a mouse model of sepsis. In human endothelial cells stimulated by LPS and mice with septic symptoms of cecal ligation and puncture (CLP), we examined levels of proinflammatory proteins and biomarkers as an index of tissue damage, along with decreased vascular permeability. In both LPS-treated human umbilical vein endothelial cells (HUVECs) and the CLP-treated mouse model of sepsis, we applied CN after the induction processes were over. CN suppressed excessive permeability and inhibited HMGB1 release, leading to the amelioration of vascular instability, reduced mortality, and improved histological conditions in the CLP-induced septic mouse model. Overall, we conclude that the suppressed release of HMGB1 and the increased survival rate of mice with CLP-induced sepsis caused by CN may be an effective pharmaceutical treatment for sepsis.

Identification of the Main Chemical constituents and mechanism of Renshen Guben oral liquid against Renal Fibrosis

“…[ 16 – 18 ], paeonol [ 19 , 20 ], gallic acid [ 21 ], loganin [ 22 ] and pachymic acid [ 23 ] showed activities in kidney fibrosis and other kidney diseases. Cornuside [ 24 ], loganic acid [ 25 ] and rehmannioside A [ 26 ] have anti-inflammatory activities, which further proved that the key constituents in the “constituents-targets-pathways” network may be used as the pharmacodynamic material basis of RSGB in the treatment of renal fibrosis.…”

Cornuside protects against ischemic stroke in rats by suppressing the IL-17F/TRAF6/NF-κB pathway via the brain-gut axis

“…Cornuside administration has been used in several neurodegenerative-like diseases. For example, cornuside inhibits neuroin ammation and oxidative stress, improves neuronal damage, and attenuates cognitive dysfunction in mice [21,29]. However, there are no studies on the application of cornuside in the treatment of ischemic stroke.…”

Is rosuvastatin protective against sepsis-associated encephalopathy? A secondary analysis of the SAILS trial

“…[19] The protective effect of statins was also recently highlighted in severe sepsis cases. [20] Almog et al [21] conducted a prospective cohort study in 2004 and found that prior statin therapy was associated with a lower rate of severe sepsis. Statin also showed a long-term protective eff ect in bacteraemic patients, reducing the 180-d mortality rate.…”