Saeng-Kankunbi-Tang (生肝健脾汤) protects liver against oxidative damage through activation of ERK/Nrf2 pathway

In Woo Lee; Hee Yoon Choi; Ju-Hee Lee; Sun-Dong Park; Seung Mo Kim; Sae Kwang Ku; Rong-jie Zhao; Sang Chan Kim; Young Woo Kim; Hong Sik Choi

doi:10.1007/s11655-016-2466-5

Your Location：

Home >

Browse articles >

Saeng-Kankunbi-Tang (生肝健脾汤) protects liver against oxidative damage through activation of ERK/Nrf2 pathway

Updated：2021-08-27

- Saeng-Kankunbi-Tang (生肝健脾汤) protects liver against oxidative damage through activation of ERK/Nrf2 pathway
- Chinese Journal of Integrative Medicine Vol. 22, Issue 8, Pages: 619-628(2016)
- Affiliations：
  
  1. Department of Internal Oriental Medicine of Hepatology, College of Oriental Medicine, Daegu Haany University,Daegu,Korea
  2. Medical Research Center for Globalization of Herbal Formulation, College of Oriental Medicine, Daegu Haany University,Daegu,Korea
  3. College of Oriental Medicine, Dongguk University,Gyeongju,Korea
  4. School of Mental Health, Jining Medical University,Shandong Province,Jining,China
- Author bio：
- Funds：
  
  Supported by the National Research Foundation of Korea Grant funded by the Korea government (No. 2014R1A2A2A01007375, No. 2012R1A5A2A42671316)
- DOI：10.1007/s11655-016-2466-5
  CLC：
- Published：2016，
  
  Published Online：14 June 2016，
Scan for full text
Lee, I.W., Choi, H.Y., Lee, JH. et al. Saeng-Kankunbi-Tang (生肝健脾汤) protects liver against oxidative damage through activation of ERK/Nrf2 pathway., Chin. J. Integr. Med. 22, 619–628 (2016). https://doi.org/10.1007/s11655-016-2466-5

In Woo Lee, Hee Yoon Choi, Ju-Hee Lee, et al. Saeng-Kankunbi-Tang (生肝健脾汤) protects liver against oxidative damage through activation of ERK/Nrf2 pathway. [J]. Chinese Journal of Integrative Medicine 22(8):619-628(2016)
Lee, I.W., Choi, H.Y., Lee, JH. et al. Saeng-Kankunbi-Tang (生肝健脾汤) protects liver against oxidative damage through activation of ERK/Nrf2 pathway., Chin. J. Integr. Med. 22, 619–628 (2016). https://doi.org/10.1007/s11655-016-2466-5 DOI：

In Woo Lee, Hee Yoon Choi, Ju-Hee Lee, et al. Saeng-Kankunbi-Tang (生肝健脾汤) protects liver against oxidative damage through activation of ERK/Nrf2 pathway. [J]. Chinese Journal of Integrative Medicine 22(8):619-628(2016) DOI： 10.1007/s11655-016-2466-5.

摘要

To investigate the cytoprotective effects of Saeng-kankunbi-tang (生肝健脾汤

SKT)

a herbal prescription consisting of Artemisia capillaris and Alisma canaliculatum

and its underlying mechanism involved. In mice

blood biochemistry and histopathology were assessed in carbon tetrachloride (CCl4)-induced oxidative hepatic injury in vivo. The animal groups included vehicle-treated control

CCl4

SKT 500 mg/(kg day) CCl4+SKT 200 or 500 mg/(kg day). In HepG2 cell

tert-butyl hydroperoxide (tBHP) induced severe oxidative stress and mitochondrial dysfunction in vitro. The cyto-protective effects of SKT were determined by 3-(4

5-dimethylthiazol)-2

5-diphenyltetrazolium bromide (MTT) assay

flfluorescence activated cell sorting analysis and western blotting. The administration of SKT prevented liver damage induced by CCl4 in mice

by inhibition of hepatocyte degeneration and inflflammatory cell infifiltration as well as plasma parameters such as alanine aminotransferase (P<0.01). Moreover

treatment with tBHP induced hepatocyte death and cellular reactive oxygen species production in hepatocyte cell line. However

SKT pretreatment (30–300 μg/mL) reduced this cell death and oxidative stress (P<0.01). More importantly

SKT inhibited the ability of tBHP to induce changes in mitochondrial membrane transition in cell stained with rhodamine 123 P<0.01). Furthermore

treatment with SKT induced extracellular signal-regulated kinases-mediated nuclear factor erythroid-2-related factor 2 (Nrf2) activation as well as the expressions of heme oxygenase 1 and glutamate- cystein ligase catalytic

Nrf2 target genes. SKT has the ability to protect hepatocyte against oxidative stress and mitochondrial damage mediated by Nrf2 activation.

Abstract

To investigate the cytoprotective effects of Saeng-kankunbi-tang (生肝健脾汤

SKT)

a herbal prescription consisting of Artemisia capillaris and Alisma canaliculatum

and its underlying mechanism involved. In mice

blood biochemistry and histopathology were assessed in carbon tetrachloride (CCl4)-induced oxidative hepatic injury in vivo. The animal groups included vehicle-treated control

CCl4

SKT 500 mg/(kg day) CCl4+SKT 200 or 500 mg/(kg day). In HepG2 cell

tert-butyl hydroperoxide (tBHP) induced severe oxidative stress and mitochondrial dysfunction in vitro. The cyto-protective effects of SKT were determined by 3-(4

5-dimethylthiazol)-2

5-diphenyltetrazolium bromide (MTT) assay

flfluorescence activated cell sorting analysis and western blotting. The administration of SKT prevented liver damage induced by CCl4 in mice

by inhibition of hepatocyte degeneration and inflflammatory cell infifiltration as well as plasma parameters such as alanine aminotransferase (P<0.01). Moreover

treatment with tBHP induced hepatocyte death and cellular reactive oxygen species production in hepatocyte cell line. However

SKT pretreatment (30–300 μg/mL) reduced this cell death and oxidative stress (P<0.01). More importantly

SKT inhibited the ability of tBHP to induce changes in mitochondrial membrane transition in cell stained with rhodamine 123 P<0.01). Furthermore

Nrf2 target genes. SKT has the ability to protect hepatocyte against oxidative stress and mitochondrial damage mediated by Nrf2 activation.

关键词

aeng-kankunbi-tangmitochondrianuclear factor erythroid-2-related factor 2oxidative stresslivermouse

Keywords

aeng-kankunbi-tangmitochondrianuclear factor erythroid-2-related factor 2oxidative stresslivermouse

references

Kurzawski M, Dziedziejko V, Urasiska E, Post M, Wójcicki M, Mitkiewski J, et al. Nuclear factor erythroid 2-like 2 (Nrf2) expression in end-stage liver disease. Environ Toxicol Pharmacol 2012;34:87–95.

Rushmore TH, Morton MR, Pickett CB. The antioxidant responsive element. Activation by oxidative stress and identification of the DNA consensus sequence required for functional activity. J Biol Chem 1991;266:11632–11639.

Moi P, Chan K, Asunis I, Cao A, Kan YW. Isolation of NFE2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/ AP1 repeat of the beta-globin locus control region. Proc Natl Acad Sci USA 1994;91:9926–9930.

Tong KI, Kobayashi A, Katsuoka F, Yamamoto M. Two-site substrate recognition model for the Keap1-Nrf2 system: a hinge and latch mechanism. Biol Chem 2006;387:1311–1320.

Hwang SJ, Choi HS, Kim SM, Woo CH. Effects of Saeng kankeonbi tang on prevention of hyperlipidemia and liver damage induced by alcohol. Kor J Herbol 2009;24:9–15.

Hong JH, Lee JW, Park JH, Lee IS. Antioxidative and cytoprotective effects of Artemisia capillaris fractions. Biofactors 2007;31:43–53.

Hong JH, Lee IS. Effects of Artemisia capillaris ethyl acetate fraction on oxidative stress and antioxidant enzyme in high-fat diet induced obese mice. Chem Biol Interact 2009;179:88–93.

Han KH, Jeon YJ, Athukorala Y, Choi KD, Kim CJ, Cho JK, et al. A water extract of Artemisia capillaris prevents 2,2’-azobis(2-amidinopropane) dihydrochloride-induced liver damage in rats. J Med Food 2006;9:342–347.

Choe M, Kim DJ, Lee HJ, You JK, Seo DJ, Lee JH, et al. A study on the glucose-regulating enzymes and antioxidant activities of water extracts from medicinal herbs. J Kor Soc Food Sci Nutr 2008;37:542–547.

Choi JH, Kim DW, Choi JS, Nrutul I, Kim YS, Lee SM. Protective effects of hyperoside against carbon tetrachloride-induced liver damage in mice. J Nat Prod 2011;74:1055–1060.

Lee HS, Jung KH, Hong SW, Park IS, Lee C, Han HK, et al. Morin protects acute liver damage by carbon tetrachloride (CCl4) in rat. Arch Pharm Res 2008;31:1160–1165.

Sung JH, Hwang MR, Kim JO, Lee JH, Kim YI, Kim JH, et al. Gel characterisation and in vivo evaluation of minocycline-loaded wound dressing with enhanced wound healing using polyvinyl alcohol and chitosan. Int J Pharm 2010;392:232–240.

Shin SM, Cho IJ, Kim SG. Resveratrol protects mitochondria against oxidative stress through AMP-activated protein kinase-mediated glycogen synthase kinase-3beta inhibition downstream of poly (ADP-ribose) polymerase LKB1 pathway. Mol Pharmacol 2009;76:884–895.

Choi SH, Kim YW, Kim SG. AMPK-mediated GSK3ß inhibition by isoliquiritigenin contributes to protecting mitochondria against iron-catalyzed oxidative stress. Biochem Pharmacol 2010;79:1352–1362.

Kay HY, Won Yang J, Kim TH, Lee da Y, Kang B, Ryu JH, et al. Ajoene, a stable garlic by-product, has an antioxidant effect through Nrf2-mediated glutamate-cysteine ligase induction in HepG2 cells and primary hepatocytes. J Nutr 2010;140:1211–1219.

Han S, Lee JH, Kim C, Nam D, Chung WS, Lee SG, et al. Capillarisin inhibits iNOS, COX-2 expression, and proinflammatory cytokines in LPS-induced RAW 264.7 macrophages via the suppression of ERK, JNK, and NF-B activation. Immunopharmacol Immunotoxicol 2013;35:34–42.

Cha JD, Moon SE, Kim HY, Cha IH, Lee KY. Essential oil of Artemisia capillaris induces apoptosis in KB cells via mitochondrial stress and caspase activation mediated by MAPK-stimulated signaling pathway. J Food Sci 2009;74:75–81.

Kim MW, Effects of a butanol fraction of Alisma canaliculatum and of selenium on blood glucose levels and lipid metabolism in streptozotocin-induced diabetic rats. Nutrit Sci 2003;5:85–93.

Rao PS, Mangipudy RS, Mehendale HM. Tissue injury and repair as parallel and opposing responses to CCl4 hepatotoxicity: a noveldose-response. Toxicology 1997;118:181–193.

Mizuoka H, Shikata N, Yang J, Takasu M, Inoue K, Tsubura A. Biphasic effect of colchicine on acute liver injury induced by carbon tetrachloride or by dimethylnitrosamine in mice. J Hepatol 1999;31:825–833.

Natarajan SK, Thomas S, Ramamoorthy P, Basivireddy J, Pulimood AB, Ramachandran A, et al. Oxidative stress in the development of liver cirrhosis: a comparison of two different experimental models. J Gastroenterol Hepatol 2006;21:947–957.

Stadtman ER. Protein oxidation and aging. Science 1992;257:1220–1224.

Esposito LA, Melov S, Panov A, Cottrell BA, Wallace DC. Mitochondrial disease in mouse results in increased oxidative stress. Proc Natl Acad Sci USA 1999;96:4820–4825.

Sena LA, Chandel NS. Physiological roles of mitochondrial reactive oxygen species. Mol Cell 2012;48:158–167.

Cadenas E, Davies KJ. Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med 2000;29:222–230.

Cuello S, Ramos S, Mateos R, Martin MA, Mardrid Y, Camara C, et al. Selenium methylselenocysteine protects human hepatoma HepG2 cells against oxidative stress induced by tert-butylhydroperoxide. Anal Bioanal Chem 2007;389:2167–2178.

Hwang YP, Choi JH, Yun HJ, Han EH, Kim HG, Kim JY, et al. Anthocyanins from purple sweet potato attenuate dimethylnitrosamine-induced liver injury in rats by inducing Nrf2-mediated antioxidant enzymes and reducing COX-2 and iNOS expression. Food Chem Toxicol 2011;49:93–99.

Na HK, Kim EH, Jung JH, Lee HH, Hyun JW, Surh YJ. (-)-Epigallocatechin gallate induces Nrf2-mediated antioxidant enzyme expression via activation of PI3K and ERK in human mammary epithelial cells. Arch Biochem Biophy 2008;476:171–177.

Chowdhry S, Nazmy MH, Meakin PJ, Dinkova-Kostova AT, Walsh SV, Tsujita T, et al. Loss of Nrf2 markedly exacerbates nonalcoholic steatohepatitis. Free Radic Biol Med 2010;48:357–371.

Kwak MK, Egner PA, Dolan PM, Ramos-Gomez M, Groopman JD, Itoh K, et al. Role of phase2 enzyme induction in chemoprotection by dithiolethiones. Mutat Res 2001;480:305–315.

Lee YJ, Im JH, Lee DM, Park JS, Won SY, Cho MK, et al. Synergistic inhibition of mesothelioma cell growth by the combination of clofarabine and resveratrol involves Nrf2 downregulation. BMB Rep 2012;45:647–652.

Rosenbaum S, Ringseis R, Hillen S, Becker S, Erhardt G, Reiner G, et al. The stress signalling pathway nuclear factor E2-related factor 2 is activated in the liver of sows during lactation. Acta Vet Scand 2012;5:54–59.

Checker R, Patwardhan RS, Sharma D, Menon J, Thoh M, Bhilwade HN, et al. Schisandrin B exhibits antiinflammatory activity through modulation of the redoxsensitive transcription factors Nrf2 and NFB. Free Radic Biol Med 2012;53:1421–1430.

Cai C, Teng L, Vu D, He JQ, Guo Y, Li Q, et al. The heme oxygenase 1 inducer (CoPP) protects human cardiac stem cells against apoptosis through activation of the extracellular signal-regulated kinase (ERK)/NRF2 signaling pathway and cytokine release. J Biol Chem 2012;287:33720–33732.

Macedo LF, Rogero MM, Guimarães JP, Granato D, Lobato LP, Castro IA. Effect of red wines with different in vitro antioxidant activity on oxidative stress of high-fat diet rats. Food Chem 2013;137:122–129.

FULL TEXT LINK

More>

Views

Downloads

CSCD

Alert me when the article has been cited

Submit

Tools

Publicity Resources

Yishen Jiangzhuo Granules (益肾降浊冲剂) affect tubulointerstitial fibrosis via a mitochondrion-mediated apoptotic pathway

Total triterpene acids, isolated from Corni Fructus, ameliorate progression of renal damage in streptozotocin-induced diabetic rats

Effects of royal jelly supplementation on glycemic control and oxidative stress factors in type 2 diabetic female: A randomized clinical trial

Bear bile powder (熊胆粉) induces apoptosis of human hepatocellular carcinoma cells via mitochondrion-dependent pathway

Impairment of triptolide on liver mitochondria in isolated liver mitochondria and HL7702 cell line

Related Author

No data

Related Institution

Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine

People Hospital Affiliated to Fujian University of Traditional Chinese Medicine

Department of Nephrology, The First Affiliated Hospital, Fujian Medical University

Department of Pharmacy, College of Chemical and Chemistry Engineering, Hu’nan University

Department of Basic Guiyang College of Traditional Chinese Medicine

Address：1 Caochang, xiyuan, Beijing, People's Republic of China Postal code：100091
Tel：010-62886827, 62877592 Fax：010-62874291
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备05067934号-1 京公网安备11010802024621
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰