title: Therapeutic effect of ent-kaur-16-en-19-oic acid on neutrophilic lung inflammation and sepsis is mediated by Nrf2.
abstract: Kaurenoic acid (ent-kaur-16-en-19-oic acid: KA) is a key constituent found in the roots of Aralia continentalis Kitagawa (Araliaceae), a remedy to treat patients with inflammatory diseases in traditional Asian medicine. Since KA activates Nrf2, a key anti-inflammatory factor, at the cellular level, we explored a possible therapeutic usage of KA against neutrophilic inflammatory lung disease such as acute lung injury (ALI). Intraperitoneal (i.p.) injection of lipopolysaccharide (LPS) to C57BL/6 mice induced lung inflammation as in ALI. 2 h after i.p. LPS, intratracheal (i.t.) delivery of KA (0.3, 3, or 30 μg/kg body weight) improved lung structure and significantly suppressed neutrophil infiltrations to mouse lungs, with concomitant reduction of myeloperoxidase activity and of the expression of pro-inflammatory cytokine genes. While activating Nrf2 and expressing Nrf2-dependent genes in mouse lungs, KA did not significantly suppress neutrophil lung inflammation in Nrf2 KO mice. In a mouse model of sepsis, a major cause of ALI, single i.t. KA (3 μg/kg) 2 h after the onset of sepsis significantly decreased the mortality of mice. Together, these results suggest that KA has a therapeutic potential against inflammatory lung disease, the effect of which is associated with Nrf2 activation.
authors.affiliation: School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea.
authors.forename: Kyun Ha
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Pulmonary and Critical Care Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Ruxana T
authors.initials: RT
authors.lastname: Sadikot
authors.affiliation: School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea. Electronic address: mjoo@pusan.ac.kr.
authors.forename: Myungsoo
authors.initials: M
authors.lastname: Joo
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000276:immunology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D004224:Diterpenes / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage; D051379:Mice; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000276:immunology*; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; C014341:argyrophilic acid
keywords: Anti-inflammation; Kaurenoic acid; Neutrophilic lung inflammation; Nrf2; Sepsis