夏枯草의 간세포에서 항산화 및 미토콘드리아 보호효과
Effect of Prunellae Spica on Oxidative Stress and Mitochondrial Dysfunction in the Hepatocyte
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초록
Prunellae Spica, the herbaceous plant in the genus Prunella, is a traditional herbal medicine and has been reported to have diuretic, anti-bacterial and anti-oxidant effects. However, the mechanism of its action was not clearly identified. In the present study, we investigated the hepatoprotective effect of Prunellae Spica extract (PSE) against the damage of mitochondria and death in hepatocyte induced by oxidative stress. Treatment of arachidonic acid (AA)+iron significantly induced oxidative stress and apoptosis in the hepatocytes. However, PSE protected cells and inhibited apoptosis by altering the protein levels such as poly(ADP-ribose) polymerase and pro-caspase 3. Moreover, AA+iron induced reactive oxygen species production and mitochondrial dysfunction, and Both of them were inhibited by PSE treatment. PSE markedly activated AMP-activated protein kinase (AMPK), an important regulator in cell survival. Furthermore, this activation by PSE was mediated with liver kinase B1, a major upstream kinase that phosphorylates Thr 172 of AMPKα, and this activation was associated with its cell protection, as assessed by an experiment of a chemical inhibitor. In conclusion, this study demonstrate that PSE protects hepatocytes against oxidative stress as mediated with activation of LKB1-dependent AMPK pathway.
Abstract
Prunellae Spica, the herbaceous plant in the genus Prunella, is a traditional herbal medicine and has been reported to have diuretic, anti-bacterial and anti-oxidant effects. However, the mechanism of its action was not clearly identified. In the present study, we investigated the hepatoprotective effect of Prunellae Spica extract (PSE) against the damage of mitochondria and death in hepatocyte induced by oxidative stress. Treatment of arachidonic acid (AA)+iron significantly induced oxidative stress and apoptosis in the hepatocytes. However, PSE protected cells and inhibited apoptosis by altering the protein levels such as poly(ADP-ribose) polymerase and pro-caspase 3. Moreover, AA+iron induced reactive oxygen species production and mitochondrial dysfunction, and Both of them were inhibited by PSE treatment. PSE markedly activated AMP-activated protein kinase (AMPK), an important regulator in cell survival. Furthermore, this activation by PSE was mediated with liver kinase B1, a major upstream kinase that phosphorylates Thr 172 of AMPKα, and this activation was associated with its cell protection, as assessed by an experiment of a chemical inhibitor. In conclusion, this study demonstrate that PSE protects hepatocytes against oxidative stress as mediated with activation of LKB1-dependent AMPK pathway.
참고문헌 (37)
- Beckman, K. B., "The free radical theory of aging matures", Physiol Rev., 78, pp.547~581 (1998)
- Wiseman, H., "Damage to DNA by reactive oxygen and nitrogen species: role in inflammatory disease and progression to cancer", Biochem. J., 313, pp.17~20 (1996)
- Kim, T. S., "Changes in antioxidants and antioxidants enzymes activities of soybean leaves subject to water stress", J. Korean Soc. Agric. Chem. Biol., pp.246~251 (1999)
- 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
- Choi, S. H., "AMPK-mediated GSK3b inhibition by isoliquiritigenin contributes to protecting mitochondria against iron-catalyzed oxidative stress", Biochemical Pharmacology, 79, pp.1352~1362 (2009)
- Larson, R. A., "The antioxidant of higher plants", Phytochemistry, 27, pp.969~978 (1988)
- 양정민, "HeLa cell에서 山藥의 항산화 작용을 통한 세포보호효과에 대한 연구", 대한한방부인과학회지, 21(2), pp.97~107 (2008), 대한한방부인과학회
- Lee, C. H., "Effect of reactive oxygen species against hepatic vascular resistance", Korean Society of Gastroenterology, 513(16), pp.271~272 (2006)
- Park, S. Y., "Effect of Vitamin A on Hepatic Mitochondrial Activity", Kor. J. Vet. Publ. Hlth., 27(1), pp.53~58 (2003)
- Shimizu, T., "Arachidonic acid cascadeintercellular signal transduction", J Neurochem, 55(1), pp.1~15 (1990)
- Balboa, M. A., "Oxidative stressarachidonic acid mobilization", Biochim Biophys Acta, 1761, pp.385~391 (2006)
- Shin, S. M., "Inhibition of arachidonic acid and iron-induced mitochondrial dysfunction and apoptosis by oltipraz and novel 1,2-dithiole-3-thione congeners", Mol Pharmacol, 75, pp.242~253 (2009)
- Gunter, T. E., "Mechanisms by which mitochondria transport calcium", Am J Physiol, 258, pp.755~786 (1990)
- Haworth, R. A., "The Ca2+-induced membrane transition in mitochondria. II. Nature of the Ca2+ trigger site", Arch Biochem Biophys, 195, pp.460~467 (1979)
- Hunter, D. R., "The Ca2+-induced membrane transition in mitochondria. I. The protective mechanisms", Arch Biochem Biophys, 195, pp.453~459 (1979)
- 이종화, "Mitochondrial Permeability Transition Pore와 허혈-재관류 손상으로부터의 심근보호작용", 대한의사협회지, 52(10), pp.1007~1019 (2009), 대한의사협회
- Kim, J. S., "Quantitative determination of ursolic acid from Prunellae herba", Kor J Pharmacogn, 31, pp.416~420 (2000)
- Ryu, S. Y., "Anti-allergic and anti-inflammatory tri-terpenes from the herb of Prunella vulgaris", Planta Med, 66, pp.358~360 (2000)
- Liu, F., "Antioxidative and free radical scavenging activities of selected medicinal herbs", Life Sci, 66, pp.725~735 (2000)
- 유진균, "목단피 물 추출물의 항산화 및 Tyrosinase 억제효과", 한국식품영양과학회지, 38(3), pp.292~296 (2009), 한국식품영양과학회
- 김봉희, "Glucagon과 insulin이 glutathione항상성에 미치는 영향 : 세포신호전달체계 및 glutathione transport system의 역할", 환경독성보건학회지, 22(3), pp.227~234 (2007), 환경독성보건학회
- Sandra, J., "Phytochemical studies of Prunella vulgaris and Prunella grandiflora-Ⅰ. Saponin and triterpene compounds", Dissertations Pharm, 15, pp.333~341 (1963)
- Ronot, X., "Mitochondrial analysis in living cells: the use of rhodamine 123 and flow cytometry", Biology of the Cell, 57(1), pp.1~7 (1986)
- Ljubica Vucicevic, "Compound C induces protective autophagy in cancer cells through AMPK inhibition-independent blockade of Akt", mTOR pathway, 2011, pp.7(1), 40~50
- 조유숙, "기관지천식과 산화 스트레스", 천식 및 알레르기, 28(3), pp.167~174 (2008), 대한천식알레르기학회
- Andreas Daiber, "Crosstalk of mitochondria with NADPH oxidase via reactive oxygen and nitrogen species signalling and its role for vascular function", British Journal of Pharmacology (2015), Wiley-Blackwell[DOI]
- Bernardi, P., "Mitochondrial transport of cations: channels, exchangers, and permeability transition", Physiol Rev., 79, pp.1127~1155 (1999)
- Kokoszka, J. E., "The ADP", ATP translocator is not essential for the mitochondrial permeability transition pore, 2004, pp.427, 461~465
- Kim, J. S., "Reactive oxygen species, but not Ca2+ overloading, trigger pH- and mitochondrial permeability transition-dependent death of adult rat myocytes after ischemia-reperfusion", Am J Physiol, Heart Circ Physiol, 290, pp.2024~2034 (2006)
- Juhaszova, M., "The identity and regulation of the mitochondrial permeability transition pore: where the known meets the unknown", Ann NY Acad Sci., 1123, pp.197~212 (2008)
- Rasola, A., "The mitochondrial permeability transition pore and its involvement in cell death and in disease pathogenesis", Apoptosis, 12, pp.815~833 (2007)
- Hardie, D.G., "Mini review: the AMP-activated protein kinase cascade: the key sensor of cellular energy status", Endocrinol, 144, pp.5179~5183 (2003)
- Stapleton, D., "Mammalian AMP-activated protein kinase subfamily", J Biol Chem, 271, pp.611~614 (1996)
- Winder, W. W., "Cellular energy sensing and signaling by AMP-activated protein kinase", Cell Biochem Biophys, 47, pp.332~347 (2007)
- Ouchi, N., "AMP-activated protein kinase signaling stimulates VEGF expression and angiogenesis in skeletal muscle", Circ Res, 96, pp.838~846 (2005)
- 최형철, "AMP-activated protein kinase 활성화 물질과 생체기능조절", Endocrinology and Metabolism, 27(2), pp.109~115 (2012), 대한내분비학회[DOI]
- Boudeau, J., "LKB1, a protein kinase regulating cell proliferation and polarity", FEBS Lett, 546, pp.159~165 (2003)
