Toona sinensis inhibits LPS-induced inflammation and migration in vascular smooth muscle cells via suppression of reactive oxygen species and NF-κB signaling pathway.
Toona sinensis is one of the most popular vegetarian cuisines in Taiwan and it has been shown to possess antioxidant, antiangiogenic, and anticancer properties. In this study, we investigated the antiatherosclerotic potential of aqueous leaf extracts from Toona sinensis (TS; 25-100 μg/mL) and its major bioactive compound, gallic acid (GA; 5 μg/mL), in LPS-treated rat aortic smooth muscle (A7r5) cells. We found that pretreatment with noncytotoxic concentrations of TS and GA significantly inhibited inflammatory NO and PGE2 production by downregulating their precursors, iNOS and COX-2, respectively, in LPS-treated A7r5 cells. Furthermore, TS and GA inhibited LPS-induced intracellular ROS and their corresponding mediator, p47(phox). Notably, TS and GA pretreatment significantly inhibited LPS-induced migration in transwell assays. Gelatin zymography and western blotting demonstrated that treatment with TS and GA suppressed the activity or expression of MMP-9, MMP-2, and t-PA. Additionally, TS and GA significantly inhibited LPS-induced VEGF, PDGF, and VCAM-1 expression. Further investigation revealed that the inhibition of iNOS/COX-2, MMPs, growth factors, and adhesion molecules was associated with the suppression of NF-κB activation and MAPK (ERK1/2, JNK1/2, and p38) phosphorylation. Thus, Toona sinensis may be useful for the prevention of atherosclerosis.
Institute of Nutrition, China Medical University, Taichung, Taiwan.
Hsin-Ling
HL
Yang
Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.
Pei-Jane
PJ
Huang
Institute of Nutrition, China Medical University, Taichung, Taiwan.
Yi-Ru
YR
Liu
Department of Cosmeceutics, College of Pharmacy, China Medical University, Taichung, Taiwan.
K J Senthil
KJ
Kumar
Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan.
Li-Sung
LS
Hsu
School of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan.
Te-Ling
TL
Lu
Department of Food Science and Technology, Ta-Jen University, Ping-Tung County, Taiwan.
Yi-Chen
YC
Chia
Department of Medico Pharmaceutical Science, Nihon Pharmaceutical University, Komuro, Inamachi, Kita-Adachigun,Saitama, Japan.
Tokuko
T
Takajo
Department of Medico Pharmaceutical Science, Nihon Pharmaceutical University, Komuro, Inamachi, Kita-Adachigun,Saitama, Japan.
Anzai
A
Kazunori
Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan ; Department of Cosmeceutics, College of Pharmacy, China Medical University, Taichung, Taiwan.
You-Cheng
YC
Hseu
D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects; D005136:Eye Proteins / Q000378:metabolism; D005707:Gallic Acid / Q000494:pharmacology; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy*; D008070:Lipopolysaccharides; D020935:MAP Kinase Signaling System / Q000187:drug effects; D029582:Meliaceae / Q000737:chemistry*; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D019255:NADPH Oxidases / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015843:Serpins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000099174:Pigment Epithelium-Derived Factor
D051546:Cyclooxygenase 2; D015232:Dinoprostone; D005136:Eye Proteins; D005707:Gallic Acid; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D019255:NADPH Oxidases; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B; D009414:Nerve Growth Factors; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D015843:Serpins; D010959:Tissue Plasminogen Activator; D042461:Vascular Endothelial Growth Factor A; D000099174:Pigment Epithelium-Derived Factor; C000606206:Nfkbia protein, rat; C489691:Ptgs2 protein, rat; C060505:neutrophil cytosolic factor 1