Magnolol attenuates sepsis-induced gastrointestinal dysmotility in rats by modulating inflammatory mediators.
OBJECTIVE
To investigate the protective effects of magnolol on sepsis-induced inflammation and intestinal dysmotility.


METHODS
Sepsis was induced by a single intraperitoneal injection of lipopolysaccharide (LPS). Male Wistar rats were randomly assigned to one of three treatment groups: magnolol prior to LPS injection (LPS/Mag group); vehicle prior to LPS injection (LPS/Veh group); vehicle prior to injection of saline (Control/Veh). Intestinal transit and circular muscle mechanical activity were assessed 12 h after LPS injection. Tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), monocyte chemoattractant protein-1 (MCP-1) and inducible nitric oxide synthase (iNOS) mRNA in rat ileum were studied by RT-PCR 2 h after LPS injection. Nuclear factor-kappaB (NF-kappaB) activity in the intestine was also investigated at this time using electrophoretic mobility shift assay. In addition, antioxidant activity was determined by measuring malondialdehyde (MDA) concentration and superoxide dismutase (SOD) activity in the intestine 2 h after LPS injection.


RESULTS
Magnolol significantly increased intestinal transit and circular muscle mechanical activity in LPS-treated animals. TNF-alpha, MCP-1 and iNOS mRNA expression in the small intestine were significantly reduced after magnolol treatment in LPS-induced septic animals, compared with untreated septic animals. Additionally, magnolol significantly increased IL-10 mRNA expression in septic rat ileum. Magnolol also significantly suppressed NF-kappaB activity in septic rat intestine. In addition, magnolol significantly decreased MDA concentration and increased SOD activity in rat ileum.


CONCLUSIONS
Magnolol prevents sepsis-induced suppression of intestinal motility in rats. The potential mechanism of this benefit of magnolol appears to be modulation of self-amplified inflammatory events and block of oxidative stress in the intestine.
Yang
Tie-Cheng
TC
Intensive Care Unit and Medical Department of Infection, Beijing Friendship Hospital, Capital Medical University, No. 95, Yong An Road, Beijing 100050, China. zsw401106@sina.com.
Zhang
Shu-Wen
SW
Sun
Li-Na
LN
Wang
Hong
H
Ren
Ai-Min
AM
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D018932:Chemokine CCL2 / Q000378:metabolism; D004195:Disease Models, Animal; D005767:Gastrointestinal Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology*; D005769:Gastrointestinal Motility / Q000187:drug effects; D007082:Ileum / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology / Q000627:therapeutic use*; D008070:Lipopolysaccharides; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001713:Biphenyl Compounds; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D018836:Inflammation Mediators; D017705:Lignans; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C005498:magnolol; D016753:Interleukin-10; D008315:Malondialdehyde; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase