Protective effects of Angelica keiskei extract against TNF-α-induced oxidative stress and vascular inflammation in human umbilical vein endothelial cells
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Angelica keiskei, a perennial herb from Apiaceae family, has been reported to improve diabetes, inhibit thrombosis, alleviate dyslipidemia, and prevent type 2 diabetes, obesity, and atherosclerosis. In this study, the protective effects of A. keiskei extract (AKE) against tumor necrosis factor-alpha (TNF-α)-induced oxidative stress and vascular inflammation in human umbilical vein endothelial cells (HUVECs) were investigated through cell viability analysis, antioxidant enzyme analysis, western blotting, and immunofluorescence staining. The results demonstrated that pretreatment of Angelica keiskei with AKE significantly inhibited the expression of key adhesion molecules such as E-selectin, ICAM-1 and VCAM-1 induced by TNF-α. AKE also showed a substantial reduction in intracellular reactive oxygen species levels and an increase in antioxidant enzyme activity, indicating potential antioxidant capabilities. This study further explained that AKE interfered with the nuclear factor-kappa B (NF-κB) pathway by inhibiting phosphorylation of IκBα and NF-κB, thereby preventing nuclear translocation. Additionally, AKE selectively inhibited the activation of c-Jun N-terminal kinase (JNK) within the mitogen-activated protein kinase (MAPK) pathway, revealing a specific action mechanism. These findings collectively suggest that AKE possesses multi-faceted protective properties, making it a potential therapeutic agent for inflammatory conditions and early atherosclerosis.
Abstract
Angelica keiskei, a perennial herb from Apiaceae family, has been reported to improve diabetes, inhibit thrombosis, alleviate dyslipidemia, and prevent type 2 diabetes, obesity, and atherosclerosis. In this study, the protective effects of A. keiskei extract (AKE) against tumor necrosis factor-alpha (TNF-α)-induced oxidative stress and vascular inflammation in human umbilical vein endothelial cells (HUVECs) were investigated through cell viability analysis, antioxidant enzyme analysis, western blotting, and immunofluorescence staining. The results demonstrated that pretreatment of Angelica keiskei with AKE significantly inhibited the expression of key adhesion molecules such as E-selectin, ICAM-1 and VCAM-1 induced by TNF-α. AKE also showed a substantial reduction in intracellular reactive oxygen species levels and an increase in antioxidant enzyme activity, indicating potential antioxidant capabilities. This study further explained that AKE interfered with the nuclear factor-kappa B (NF-κB) pathway by inhibiting phosphorylation of IκBα and NF-κB, thereby preventing nuclear translocation. Additionally, AKE selectively inhibited the activation of c-Jun N-terminal kinase (JNK) within the mitogen-activated protein kinase (MAPK) pathway, revealing a specific action mechanism. These findings collectively suggest that AKE possesses multi-faceted protective properties, making it a potential therapeutic agent for inflammatory conditions and early atherosclerosis.
참고문헌 (39)
- Amalia R, "The cytotoxicity and nephroprotective activity of the ethanol extracts of Angelica keiskei Koidzumi stems and leaves against the NAPQI-induced human embryonic kidney(HEK293)cell line", Evid Based Complement Altern Med, 2021, pp.6458265~ (2021)
- Baba K, "Studies on Angelica keiskei"Ashitaba"", Foods & Food Ingredients J Jap, 178, pp.52~60 (1998)
- Beinke S, "Functions of NF-kappaB1 and NF-kappaB2 in immune cell biology", Biochem J, 382, pp.393~409 (2004)
- Chang YL, "Glycyrrhetinic acid inhibits ICAM-1 expression via blocking JNK and NF-κB pathways in TNF-α-activated endothelial cells", Acta Pharmacol Sin, 31, pp.546~553 (2010)
- Collins T, "Endothelial nuclear factor-kappa B and the initiation of the atherosclerotic lesion", Lab Invest, 68, pp.499~508 (1993)
- Cominacini L, "Zofenopril inhibits the expression of adhesion molecules on endothelial cells by reducing reactive oxygen species", Am J Hypertens, 15, pp.891~895 (2002)
- Dimmeler S, "Apoptosis of endothelial cells. Contribution to the pathophysiology of atherosclerosis?", Eur Cytokine Netw, 9, pp.697~698 (1999)
- Falk E, "Pathogenesis of atherosclerosis", J Am Coll Cardiol, 47, pp.C7~C12 (2006)
- Forstermann U, "Oxidative stress in vascular disease : Causes, defense mechanisms and potential therapies", Nat Clin Pract Cardiovasc Med, 5, pp.338~349 (2008)
- Galan M, "Mechanism of endoplasmic reticulum stress-induced vascular endothelial dysfunction", BBA-Mol Cell Res, 1843, pp.1063~1075 (2014)
- Glass CK, "Atherosclerosis : The road ahead", Cell, 104, pp.503~516 (2001)
- Guo J, "Berberine protects human umbilical vein endothelial cells against LPS-induced apoptosis by blocking JNK-mediated signaling", Evid Based Complement Altern Med, 2016, pp.6983956~ (2016)
- Hansson GK, "Inflammation and atherosclerosis", Annu Rev Pathol Mech Dis, 1, pp.297~329 (2006)
- Hoefen RJ, "The role of MAP kinases in endothelial activation", Vasc Pharmacol, 38, pp.271~273 (2002)
- Ismail SM, "Piper sarmentosum attenuates TNF-α-induced VCAM-1 and ICAM-1 expression in human umbilical vein endothelial cells", J Taibah Univ Med Sci, 13, pp.225~231 (2018)
- Jafari M, "Angelica keiskei impacts the lifespan and healthspan of Drosophila melanogaster in a sex and strain-dependent manner", Pharmaceuticals, 16, pp.738~ (2023)
- Kil YS, "Angelica keiskei, an emerging medicinal herb with various bioactive constituents and biological activities", Arch Pharm Res, 40, pp.655~675 (2017)
- Kim SR, "Visfatin enhances ICAM-1 and VCAM-1 expression through ROS-dependent NF-κB activation in endothelial cells", BBA-Mol Cell Res, 1783, pp.886~895 (2008)
- Li H, "Vascular oxidative stress, nitric oxide and atherosclerosis", Atherosclerosis, 237, pp.208~219 (2014)
- Libby P, "Inflammation in atherosclerosis", Circ J, 74, pp.213~220 (2010)
- Lu Y, "Apelin-APJ induces ICAM-1, VCAM-1 and MCP-1 expression via NF-κB", JNK signal pathway in human umbilical vein endothelial cells, 2012, pp.43, 2125~2136
- Ma X, "Inhibitors and activators of SOD, GSH-Px, and CAT", Enzyme Inhib Activ, 29, pp.207~224 (2017)
- Monaco C, "Nuclear factor κB : A potential therapeutic target in atherosclerosis and thrombosis", Cardiovasc Res, 61, pp.671~682 (2004)
- Ogawa H, "Hypotensive and lipid regulatory actions of 4-hydroxyderricin, a chalcone from Angelica keiskei, in stroke-prone spontaneously hypertensive rats", Clin Exp Pharmacol Physiol, 32, pp.19~23 (2005)
- Oh HA, "Analysis of plasma metabolic profiling and evaluation of the effect of the intake of Angelica keiskei using metabolomics and lipidomics", J Ethnopharmacol, 243, pp.112058~ (2019)
- Ohkura N, "Possible antithrombotic effects of Angelica keiskei(Ashitaba)", Die Pharmazie, 73, pp.315~317 (2018)
- Pan W, "Resveratrol protects against TNF-α-induced injury in human umbilical endothelial cells through promoting sirtuin-1-induced repression of NF-KB and p38 MAPK", PloS One, 11, pp.e0147034~ (2016)
- Park J., "The Medicinal Herbs, Teas, and Alcoholic Beverages in Donguibogam, Proven by Patents" (2013), Pureun-Hyeongbok Publisher
- Park JK, "Inhibition of TNF-α-induced ROS generation, VCAM-1 expression and NF-κB activation by chloroform extract of aged black garlic in human umbilical vein endothelial cells", FASEB J, 24, pp.960~963 (2010)
- Rao RM, "Endothelial-dependent mechanisms of leukocyte recruitment to the vascular wall", Circ Res, 101, pp.234~247 (2007)
- Ross R, "Atherosclerosis : An inflammatory disease", N Engl J Med, 340, pp.115~126 (1999)
- Schulze-Osthoff K, "Regulation of NF-κB activation by MAP kinase cascades", Immunobiol, 198, pp.35~49 (1997)
- "Cardiovascular diseases fact sheet"[URL]
- Widmann C, "Mitogen-activated protein kinase : Conservation of a three-kinase module from yeast to human", Physiol Rev, 79, pp.143~180 (1999)
- Wu S, "Potent anti-inflammatory effect of dioscin mediated by suppression of TNF-α-induced VCAM-1, ICAM-1and EL expression via the NF-κB pathway", Biochimie, 110, pp.62~72 (2015)
- Zhang F, "Inhibition of TNF-α induced ICAM-1, VCAM-1 and E-selectin expression by selenium", Atherosclerosis, 161, pp.381~386 (2002)
- Zhang L, "Antioxidant and anti-inflammatory activities of selected medicinal plants containing phenolic and flavonoid compounds", J Agric Food Chem, 59, pp.12361~12367 (2011)
- Zhou Z, "TNFR1-induced NF-κB, but not ERK, p38MAPK or JNK activation, mediates TNF-induced ICAM-1 and VCAM-1 expression on endothelial cells", Cell Signaling, 19, pp.1238~1248 (2007)
- Zhu YP, "Astragalus polysaccharides suppress ICAM-1 and VCAM-1 expression in TNF-α-treated human vascular endothelial cells by blocking NF-κB activation", Acta Pharmacol Sin, 34, pp.1036~1042 (2013)
