Protective effects of asiaticoside on septic lung injury in mice.
Asiaticoside (AS), a major triterpenoid saponin component isolated from Centella asiatica, has been described to exhibit antioxidant and anti-inflammatory activities. The present study aimed to determine the protective effects and the underlying mechanisms of AS on septic lung injury induced by cecal ligation and puncture (CLP). Mice were pretreated with the AS (45 mg/kg) or AS as well as GW9662 at 1h before CLP, the survival, lung injury, inflammatory mediators and signaling molecules, and Peroxisome proliferator-activated receptor-γ (PPAR-γ) were determined 24 h after CLP. The results showed that AS significantly decreased CLP-induced the mortality, lung pathological damage, the infiltration of mononuclear, polymorphonuclear (PMN) leucocytes and total proteins. Moreover, AS inhibited CLP-induced the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB), the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) protein in lung tissues, and the production of serum tumor necrosis factor (TNF-α) and interleukin-6 (IL-6). Interestingly, the expression of PPAR-γ protein in lung tissue was up-regulated by AS. Furthermore, GW9662 (the inhibitor of PPAR-γ) significantly reversed these beneficial effects of AS in septic mice. These findings suggest that AS could effectively protect from septic lung injury induced by CLP and the underlying mechanisms might be related to up-regulation of PPAR-γ expression to some extent, which inhibits MAPKs and NF-κB pathway.
Zhang
Li-na
LN
Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Yixueyuan Road 1, Yuzhong District, Chongqing 400016, China.
Zheng
Jia-jia
JJ
Zhang
Li
L
Gong
Xia
X
Huang
Hai
H
Wang
Chang-dong
CD
Wang
Bin
B
Wu
Meng-jiao
MJ
Li
Xiao-hui
XH
Sun
Wen-juan
WJ
Liu
Ying-ju
YJ
Wan
Jing-yuan
JY
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000302:isolation & purification / Q000627:therapeutic use*; D000975:Antioxidants / Q000008:administration & dosage / Q000302:isolation & purification / Q000627:therapeutic use*; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D028041:Centella / Q000737:chemistry; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D055370:Lung Injury / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D047495:PPAR gamma / Q000096:biosynthesis; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D014315:Triterpenes / Q000008:administration & dosage / Q000302:isolation & purification / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D016207:Cytokines; D047495:PPAR gamma; D014315:Triterpenes; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C004446:asiaticoside