Phillyrin Relieves Lipopolysaccharide-Induced AKI by Protecting Against Glycocalyx Damage and Inhibiting Inflammatory Responses

Abstract

Damage to the integrity of heparin sulfate (HS) in the endothelial glycocalyx is an important factor of glomerular filtration barrier dysfunction, which is the basic pathological feature of acute kidney injury (AKI). AKI is a common clinical critical illness with few drugs options offering effective treatment. Phillyrin (Phil), the main pharmacological component of Forsythia suspensa, possesses a wide range of pharmacological activities. However, the effects of Phil on lipopolysaccharide (LPS)-induced AKI have yet to be reported. The aim of the present study is to analyze the effects of Phil on HS damage and inflammatory signaling pathways in LPS-induced AKI. Results revealed that Phil reduces pathological changes and improves renal function in LPS-induced AKI. Further analysis indicated that Phil effectively protects against glycocalyx HS degradation in LPS-stimulated EA.hy926 cells in vitro and LPS-induced AKI mice in vivo. The protective effect of Phil on HS damage may be associated with the isolate's ability to suppress the production of reactive oxygen species, and decrease expression levels of cathepsin L and heparanase in vitro and in vivo. In addition, ELISA and Western blot results revealed that Phil inhibits the activation of the NF-κB and MAPK signaling pathways and decreases the levels of inflammatory cytokines (IL-1β, IL-6, and TNF-α) in LPS-induced ARDS mice. In general, protection against endothelial glycocalyx HS damage and inhibition of inflammatory responses by Phil may be used as treatment targets for LPS-induced AKI.

Phillyrin Mitigates Apoptosis and Oxidative Stress in Hydrogen Peroxide-Treated RPE Cells through Activation of the Nrf2 Signaling Pathway

“…Vah. It has a wide range of pharmacological properties such as anti-inflammatory, antioxidation, and antiendotoxin effects [ 39 ]. Phillyrin produces good results in the clinical treatment of dry AMD, although its underlying mechanism has not been fully elucidated [ 40 – 42 ].…”

Endothelial glycocalyx degradation is associated with early organ impairment in polytrauma patients

“…EG coats the luminal surface of glomerular capillaries, therefore its integrity is essential for glomerular filtration barrier function. Study in mice showed the protection against glycocalyx HS degradation is associated with reduction of LPS-induced AKI [ 27 ]. In addition, tests in mice demonstrated inhibition of the syndecan-4 shedding process attenuated diabetes-induced kidney injury in the early stage [ 28 ].…”

Chinese herbal medicine: Fighting SARS-CoV-2 infection on all fronts

“…2 E) ( Xia et al, 2010 ). Literature shows that phillyrin exhibits promising pharmacological properties against lung inflammation ( Zhong et al, 2013 ), traumatic brain injury ( Jiang et al, 2020 ) and acute kidney injury ( Zhang et al, 2020b ). Yang et al recently revealed that phillyrin could effectively inhibit the replication of SARS-CoV-2 in Vero E6 cells at an IC 50 of 63.90 μg/mL with a low toxicity profile (SI = 30.66) by inhibiting activation of the nuclear factor kappa B (NF-κB) signaling pathway ( Ma et al, 2020d ).…”