Ginsenoside Rb1 attenuates angiotensin II-induced abdominal aortic aneurysm through inactivation of the JNK and p38 signaling pathways.
BACKGROUND
Abdominal aortic aneurysm (AAA), a life-threatening vascular disease, accounts for approximately 10% of the morbidity in people over 65 years old. No satisfactory approach is available to treat AAA. Ginsenosides Rb1 and Rg1 are primary ingredients of Panax notoginseng for the treatment of cardiovascular diseases, but their impact on AAA is unknown.


RESULTS
An AAA model was established using an Ang II infusion in ApoE(-/-) mice. After continuous stimulation of Ang II for 28 days, suprarenal aortic aneurysms developed in 77% mice and 12% mice died suddenly due to AAA rupture. Administration of ginsenoside Rb1 (20 mg/kg/day), but not ginsenoside Rg1, significantly reduced the incidence and mortality of AAA. Ginsenoside Rb1 treatment dramatically suppressed Ang II-induced diameter enlargement, extracellular matrix degradation, matrix metalloproteinase (MMP) production, inflammatory cell infiltration, and vascular smooth muscle cell (VSMC) dysfunction. Mechanistic studies indicated that the protective effects of ginsenoside Rb1 were associated with the inactivation of JNK and p38 MAPK signaling pathways. A specific activator of JNK and p38, anisomycin, nearly abolished ginsenoside Rb1-driven suppression of MMP secretion by VSMCs.


CONCLUSIONS
Ginsenoside Rb1, as a potential anti-AAA agent, suppressed AAA through inhibiting the JNK and p38 signaling pathways.
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, PR China.
Xiao-Jing
XJ
Zhang
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, PR China.
Chengwei
C
He
Center for Intestinal and Liver Inflammation Research, Stanley Manne Children's Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Ke
K
Tian
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, PR China.
Peng
P
Li
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, PR China.
Huanxing
H
Su
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, PR China. Electronic address: jbwan@umac.mo.
Jian-Bo
JB
Wan
D000804:Angiotensin II; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001012:Aorta, Abdominal / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control*; D001019:Aortic Rupture / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects; D004195:Disease Models, Animal; D020536:Enzyme Activators / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism; D036145:Ginsenosides / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000187:drug effects; D066253:Vascular Remodeling / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D001057:Apolipoproteins E; D020536:Enzyme Activators; D036145:Ginsenosides; D018836:Inflammation Mediators; D047428:Protein Kinase Inhibitors; D000804:Angiotensin II; C442759:ginsenoside Rb1; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
Abdominal aortic aneurysm; Ginsenoside Rb1; Ginsenoside Rb1 (PubChem CID: 9898279); Ginsenoside Rg1 (PubChem CID: 441923); JNK; NF-κB; p38