AMPK 활성화를 통한 목통의 항산화 효과
Akebiae Caulis Inhibits Oxidative Stress through AMPK Activation
2
조회
0
다운로드
8
인용
0
참고문헌
키워드
초록
Akebiae Caulis is a galenical originated from Akebia quinata Decaisne species. It is commonly used in the treatment of oposiuria, inflammation, nociceptive and fever. Here, we investigated the effect of Akebiae Caulis extract (ACE) to protect hepatocyte against the malfunction of mitochondria and apoptosis. Arachidonic acid (AA)+iron promoted excessive reactive oxygen species (ROS) production and exerted a deleterious effect on mitochondria. Treatment with ACE protected hepatocytes from AA+iron-induced cytotoxicity, as shown by alterations in the protein levels related with apoptosis such as poly(ADP-ribose) polymerase, pro-caspase 3, Bcl-XL and Bcl-2. Moreover, AA+iron-induced H₂O₂ production, GSH depletion and mitochondrial dysfunction were alleviated by ACE pretreatment. As a potential molecular mechanism for the ACE-mediated cytoprotection, phosphorylation of AMP-activated protein kinase (AMPK), a key regulator in determining cell survival or death, was increased by ACE. Moreover, ACE treatment enhanced inactive phosphorylation of glycogen synthase kinase-3β (GSK3β), downstream substrate kinase of AMPK. More importantly, ACE prevented a decrease in the GSK3β phosphorylation derived by AA+iron, which might contribute to mitohondiral protection and cell survival. To further identify essential compounds in Akebiae Caulis for the protection of AA+iron-mediated cytotoxicity, we found that betulin in combination with hederagenin protected from AA+iron-induced mitochondrial dysfunction. Betulin+hederagenin treatment also increased inactive phosphorylation of GSK3β in common with ACE. These results suggest that ACE protected hepatocytes against oxidative stress and mitochondrial dysfunction, which is mediated with inactive GSK3β phosphorylation downstream of AMPK.
Abstract
Akebiae Caulis is a galenical originated from Akebia quinata Decaisne species. It is commonly used in the treatment of oposiuria, inflammation, nociceptive and fever. Here, we investigated the effect of Akebiae Caulis extract (ACE) to protect hepatocyte against the malfunction of mitochondria and apoptosis. Arachidonic acid (AA)+iron promoted excessive reactive oxygen species (ROS) production and exerted a deleterious effect on mitochondria. Treatment with ACE protected hepatocytes from AA+iron-induced cytotoxicity, as shown by alterations in the protein levels related with apoptosis such as poly(ADP-ribose) polymerase, pro-caspase 3, Bcl-XL and Bcl-2. Moreover, AA+iron-induced H₂O₂ production, GSH depletion and mitochondrial dysfunction were alleviated by ACE pretreatment. As a potential molecular mechanism for the ACE-mediated cytoprotection, phosphorylation of AMP-activated protein kinase (AMPK), a key regulator in determining cell survival or death, was increased by ACE. Moreover, ACE treatment enhanced inactive phosphorylation of glycogen synthase kinase-3β (GSK3β), downstream substrate kinase of AMPK. More importantly, ACE prevented a decrease in the GSK3β phosphorylation derived by AA+iron, which might contribute to mitohondiral protection and cell survival. To further identify essential compounds in Akebiae Caulis for the protection of AA+iron-mediated cytotoxicity, we found that betulin in combination with hederagenin protected from AA+iron-induced mitochondrial dysfunction. Betulin+hederagenin treatment also increased inactive phosphorylation of GSK3β in common with ACE. These results suggest that ACE protected hepatocytes against oxidative stress and mitochondrial dysfunction, which is mediated with inactive GSK3β phosphorylation downstream of AMPK.
참고문헌 (39)
- 김연숙, "돼지감자잎 추출물의 항산화 활성 및 간세포 보호 효과", 한국식품영양과학회지, 40(11), pp.1525~1531 (2011), 한국식품영양과학회
- 오정민, "인간 간암 세포주인 SK-Hep-1에서 Stearic Acid에 의한 산화적 스트레스 및 항산화효소의 발현변화 평가", 약 학 회 지, 56(1), pp.14~19 (2012), 대한약학회
- 양정민, "HeLa cell에서 山藥의 항산화 작용을 통한 세포보호효과에 대한 연구", 대한한방부인과학회지, 21(2), pp.97~107 (2008), 대한한방부인과학회
- 이소연, "산화스트레스가 유도된 인체 간암세포 (HepG2)에서 Sulforaphane과 Diallyl Sulfide, Capsaicin, Gingerol의 항산화효과 비교연구", Journal of Nutrition and Health, 44(6), pp.488~497 (2011), 한국영양학회
- 장주리, "도라지 부탄올 추출물의 항산화 및 nitric oxide 생성 저해 효과", 한국식품저장유통학회지, 18(1), pp.65~71 (2011), 한국식품저장유통학회
- 김인혜, "Alloxan에 의한 HIT-T15 세포 손상에 대한 쑥갓주정추출물의 세포보호효과", 한국식품영양학회지, 25(1), pp.123~131 (2012), 한국식품영양학회
- Galaris, D., "Oxidative stress and iron homeostasis: mechanistic and health aspects", Crti Rev Clin Lab Sci, 45(1), pp.1~23 (2008)
- Neufeld, E. J, "Oral chelators deferasirox and deferiprone for transfusional iron overload in thalassemia major: new data, new questions", Blood, 107(9), pp.3436~3441 (2006)
- 최철수, "Zinc와 Arachidonic Acid가 고 Fructose 식이로 유도된 인슐린 저항성에 미치는 영향", 한국식품영양과학회지, 38(4), pp.415~422 (2009), 한국식품영양과학회
- Claria, J, "Regulation of cell proliferation and apoptosis by bioactive lipid mediators", Recent Pat Anticancer Drug Discov, 1(3), pp.369~382 (2006)
- Monjazeb, A. M., "Inhibitors of arachidonic acid metabolism act synergistically to signal apoptosis in neoplastic cells", Prostaglandins Leukot Essent Fatty Acids, 73(6), pp.464~474 (2005)
- Nakanishi, M., "Roles of cPLA2a and arachidonic acid in cancer", Biochim Biophys Acta, 1761(11), pp.1335~1343 (2006)
- Balboa, M. A., "Oxidative stress and arachidonic acid mobilization", Biochim Biophys Acta, 1761(4), pp.385~391 (2006)
- Choi, S. H., "AMPK-mediated GSK3β inhibition by isoliquiritigenin contributes to protecting mitochondria against iron-catalyzed oxdative stress", Biochemical Pharmacol, 79(9), pp.1352~1362 (2010)
- Shin, S. M., "Inhibition of arachidonic acid and iron-induced mitochondrial dysfunction and apoptosis by oltipraz and novel 1,2-dithiole-3thione congeners", Mol Pharmacol, 75(1), pp.242~253 (2009)
- Lee, S. M., "Study on application of Lignum akebiae main blended prescription from Dongeuybogam", Korean J Orient Med Prescr, 13(1), pp.195~213 (2005)
- Oh, S. H., "Protection of betulin against cadmium-induced apoptosis in hepatoma cells", Toxicology, 220(1), pp.1~12 (2006)
- 박찬성, "한약재 추출물의 항산화작용 및 아질산염 소거작용", 한국식품저장유통학회지, 12(6), pp.631~636 (2005), 한국식품저장유통학회
- 고인호, "동충하초 추출물과 백삼추출물 투여가 방사선을 조사한 생쥐 간에서의 glutathione함량에 미치는 영향", 한국방사선학회논문지, 6(2), pp.99~106 (2012), 한국방사선학회[DOI]
- Kode, A., "Resveratrol induces glutathione synthesis by activation of Nrf2 and protects against cigarette smoke-mediated oxidative stress in human lung epithelial cells", Am J Physiol Lung Cell Mol Physiol, 294(3), pp.L478~L488 (2008)
- Zamzami, N., "Measurement of membrane permeability and the permeability transition of mitochondria", Methods Cell Biol, 80, pp.327~340 (2007)
- 하주헌, "생체 에너지 대사 조절에서 AMPK의 역할", Endocrinology and Metabolism, 25(1), pp.9~17 (2010), 대한내분비학회
- 고성호, "산화성 손상을 받은 N18D3세포에서 Epigallocatechin gallate가 Phosphoinositide 3-kinase", Akt 및 Glycogen synthase kinase-3경로에 미치는 효과, 2003, pp.13(1), 29~39[DOI]
- Wang, J., "Macranthoside B, a hederagenin saponin extracted from Lonicera macranthoides and its anti-tumor activities in vitro and in vivo", Food Chem Toxicol, 47(7), pp.1716~1721 (2009)
- Han, B. J., "Effects of the water extract of Akebia (Akebia quinata Decaisne) on the growth of Clostridium perfringens and intestinal microorganisms", Kor J Appl Microbiol Biotechnol, 23(6), pp.633~640 (1995)
- 장귀영, "열처리와 추출방법에 따른 몇 가지 약초의 항산화 활성", 한국식품영양과학회지, 41(7), pp.914~920 (2012), 한국식품영양과학회[DOI]
- Kim, J. G., "Antioxidative activity and antimicrobial activity of extracts from medicinal plants (Akebia quinate Decaisn, Scirusfluviatilis A. Gray, Gardenia jasminoides for. grandiflora Makino)", J Agric Life Sci, 37(4), pp.69~75 (2003)
- Devasagayam, T. P., "Free radicals and antioxidants in human health: current status and future prospects", J Assoc Physicians India, 52, pp.794~804 (2004)
- 윤주호, "강황이 수종의 암세포에 미치는 영향", 대한한방내과학회지, 27(2), pp.429~443 (2006), 대한한방내과학회
- 조일영, "다이옥신이 미토콘드리아 내막의 전위차 변화 및 ROS 생성에 미치는 영향", 환경독성보건학회지, 24(1), pp.33~41 (2009), 환경독성보건학회
- 남정원, "HepG2 간암세포에서 아라키돈산에 의한 세포사멸기전에 미치는 NADPH 산화효소의 역할", 약 학 회 지, 56(2), pp.80~85 (2012), 대한약학회[DOI]
- Wu, S. B., "Role of AMPK-mediated adaptive responses in human cells with mitochondrial dysfunction to oxidative stress.", Biochem Biophys Acta, 1840(4), pp.1331~1344 (2014)
- 박창석, "근육세포 내 Glucose 농도와 AICAR에 의한 단백질 합성 저해", 한국동물자원과학회지, 54(5), pp.369~373 (2012), 한국동물자원과학회
- 최형철, "AMP-activated protein kinase 활성화 물질과 생체기능조절", Endocrinology and Metabolism, 27(2), pp.109~115 (2012), 대한내분비학회[DOI]
- 남주영, "安胎에 활용되는 山藥의 신경세포주에 대한 안전성 및 항산화효과에 대한 연구", 대한한방부인과학회지, 19(4), pp.61~76 (2006), 대한한방부인과학회
- Jang, H. J., "Structure activity relationship of oleanane disaccharides isolated from Akebia quinata versus cytotoxicity against cancer cells and NO inhbition", Biol Pharm Bull, 27(5), pp.744~747 (2004)
- Miura, N., "Protective effects of triterpene compounds against the cytotoxicity of cadmium in HepG2 cells", Mol Pharmacol, 56(6), pp.1324~1328 (1999)
- 안성준, "The Antibacterial Effect of Hederagenin Monodesmosides on Anaerobes in the Saliva", Journal of Oral Medicine and Pain, 27(3), pp.321~331 (2002), 대한안면통증∙구강내과학회
- Szuster-Ciesielska, A., "Betulin and betulinic acid attenuate ethanol-induced liver stellate cell activation by inhibiting reactive oxygen species (ROS), cytokine (TNF-α, TGF-β) production and by influencing intracellular signaling", Toxicology, 280(3), pp.152~163 (2011)