Inhibitory functions of maslinic acid, a natural triterpene, on HMGB1-mediated septic responses

Copyright © 2020 Elsevier GmbH. All rights reserved..

BACKGROUND: Maslinic acid (MA), a natural triterpenoid from Olea europaea, prevents oxidative stress and pro-inflammatory cytokine generation. High mobility group box 1 (HMGB1) has been recognized as a late mediator of sepsis, and the inhibition of the release of HMGB1 and the recovery of vascular barrier integrity have emerged as attractive therapeutic strategies for the management of sepsis.

METHODS: We tested the hypothesis that MA induces sirtuin 1 and heme oxygenase-1, which inhibit the release of HMGB1 in lipopolysaccharide (LPS)-stimulated cells, thus inhibiting HMGB1-induced hyperpermeability and increasing the survival of septic mice. MA was administered after LPS or HMGB1 challenge, and the antiseptic activity of MA was determined based on permeability, the activation of pro-inflammatory proteins, and the production of markers for tissue injury in HMGB1-activated human umbilical vein endothelial cells (HUVECs) and a cecal ligation and puncture (CLP)-induced sepsis mouse model.

RESULTS: MA significantly reduced the release of HMGB1 in LPS-activated HUVECs and attenuated the CLP-induced release of HMGB1. Additionally, MA alleviated HMGB1-mediated vascular disruption and inhibited hyperpermeability in mice, and in vivo analysis revealed that MA reduced sepsis-related mortality and tissue injury.

CONCLUSION: Taken together, the present results suggest that MA reduced HMGB1 release and septic mortality and thus may be useful in the treatment of sepsis.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:69

Enthalten in:

Phytomedicine : international journal of phytotherapy and phytopharmacology - 69(2020) vom: 01. Apr., Seite 153200

Sprache:

Englisch

Beteiligte Personen:

Lee, Wonhwa [VerfasserIn]
Lee, Hayeong [VerfasserIn]
Lee, Taeho [VerfasserIn]
Park, Eui Kyun [VerfasserIn]
Bae, Jong-Sup [VerfasserIn]

Links:

Volltext

Themen:

Cytokines
E233J88OHQ
EC 1.14.14.18
EC 3.5.1.-
Endothelium
HMGB1
HMGB1 Protein
HMOX1 protein, human
Heme Oxygenase-1
Journal Article
Lipopolysaccharides
Maslinic acid
SIRT1 protein, human
Sepsis
Sirtuin 1
Triterpenes

Anmerkungen:

Date Completed 03.08.2020

Date Revised 03.08.2020

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.phymed.2020.153200

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM307519910