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Protective effects of protopanaxatriol on acute liver injury induced by concanavalin A

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Abstract

The purpose of this study was to explore the protective effect of protopanaxatriol (PPT) on acute liver injury induced by concanavalin A (ConA). In this study, mice were randomly separated into four groups. The first group received PBS (i.v.). The second group was given PPT (50 mg/kg body weight, i.p.) for 3 days before PBS (i.v.) injection. The third group received ConA (15 mg/kg body weight, i.v.). The fourth group was administered PPT (50 mg/kg body weight, i.p.) for 3 days before ConA (i.v.) injection. The serum levels of ALT and AST were detected after 20 h of ConA injection. The pathological changes of liver were observed by H/E staining. The expression of inflammatory factors was measured by ELISA and qRTPCR, and the changes of the signaling pathway were detected by western blot. Histopathological changes and blood transaminase elevation indicated significant liver injury after ConA injection. However, PPT pretreatment obviously reversed these changes. The ELISA and qRT-PCR results indicated that PPT preconditioning significantly inhibited the production of inflammatory factors. In addition, this inhibitory effect of PPT was mainly mediated by regulation of the nuclear factor-κB (NF-κB) signaling pathway. The active ingredient of ginseng, PPT, exerts an obvious protective effect on acute liver injury caused by ConA through inhibiting the inflammatory response.

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Abbreviations

ALT:

Alanine aminotransferase (ALT)

AST:

Aspartate aminotransferase (AST)

CCL4 :

Carbon tetrachloride

ConA:

Concanavalin A

H/E:

Hematoxylin and eosin staining

H2O2 :

Hydrogen peroxide

IFN-γ:

Interferon-gamma

IL-1β:

Interleukin-1 beta

IL-6:

Interleukin-6

LPS:

Lipopolysaccharide

NF-κB:

Nuclear factor-κB

PBS:

Phosphate buffer saline

PPT:

Protopanaxitriol

TNF-α:

Tumor necrosis factor-alpha

References

  • Abunab H, Dator WL, Hawamdeh S (2017) Effect of olive leaf extract on glucose levels in diabetes-induced rats: a systematic review and meta-analysis. J Diabetes 9:947–957

    Article  CAS  PubMed  Google Scholar 

  • Carrington DM, Auffret A, Hanke DE (1985) Polypeptide ligation occurs during post-translational modification of concanavalin A. Nature 313:64–67

    Article  CAS  PubMed  Google Scholar 

  • Heneghan MA, Yeoman AD, Verma S, Smith AD, Longhi MS (2013) Autoimmune hepatitis. Lancet 382:1433–1444

    Article  CAS  PubMed  Google Scholar 

  • Hofseth LJ, Wargovich MJ (2007) Inflammation, cancer, and targets of ginseng. J Nutr 137:183S–185S

    Article  CAS  PubMed  Google Scholar 

  • Huu TN, Uto T, Morinaga O, Kim YH, Shoyama Y (2012) Pharmacological effects of ginseng on liver functions and diseases: a minireview. Evid Based Complement Alternat Med 2012:173297

    Google Scholar 

  • Jang S, Lim Y, Valacchi G, Sorn S, Park H, Park NY, Lee M (2012) Preventive effects of protopanaxadiol and protopanaxatriol ginsenosides on liver inflammation and apoptosis in hyperlipidemic apoE KO mice. Genes Nutr 7:319–329

    Article  CAS  PubMed  Google Scholar 

  • Jang KJ, Choi SH, Yu GJ, Hong SH, Chung YH, Kim CH, Yoon HM, Kim GY, Kim BW, Choi YH (2016) Anti-inflammatory potential of total saponins derived from the roots of Panax ginseng in lipopolysaccharide-activated RAW 264.7 macrophages. Exp Ther Med 11:1109–1115

    Article  CAS  PubMed  Google Scholar 

  • Kang KS, Yamabe N, Kim HY, Yokozawa T (2007) Effect of sun ginseng methanol extract on lipopolysaccharide-induced liver injury in rats. Phytomedicine 14:840–845

    Article  CAS  PubMed  Google Scholar 

  • Ki SH, Yang JH, Ku SK, Kim SC, Kim YW, Cho IJ (2013) Red ginseng extract protects against carbon tetrachloride-induced liver fibrosis. J Ginseng Res 37:45–53

    Article  PubMed  PubMed Central  Google Scholar 

  • Knolle PA, Gerken G, Loser E, Dienes HP, Gantner F, Tiegs G, Meyer zum Buschenfelde KH, Lohse AW (1996) Role of sinusoidal endothelial cells of the liver in concanavalin A-induced hepatic injury in mice. Hepatology 24:824–829

    Article  CAS  Google Scholar 

  • Kwok HH, Ng WY, Yang MS, Mak NK, Wong RN, Yue PY (2010) The ginsenoside protopanaxatriol protects endothelial cells from hydrogen peroxide-induced cell injury and cell death by modulating intracellular redox status. Free Radic Biol Med 48:437–445

    Article  CAS  PubMed  Google Scholar 

  • Leung KW, Leung FP, Mak NK, Tombran-Tink J, Huang Y, Wong RN (2009) Protopanaxadiol and protopanaxatriol bind to glucocorticoid and oestrogen receptors in endothelial cells. Br J Pharmacol 156:626–637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li KK, Yang XB, Yang XW, Liu JX, Gong XJ (2012) New triterpenoids from the stems and leaves of Panax ginseng. Fitoterapia 83:1030–1035

    Article  CAS  PubMed  Google Scholar 

  • Lu KH, Weng CY, Chen WC, Sheen LY (2017) Ginseng essence, a medicinal and edible herbal formulation, ameliorates carbon tetrachloride-induced oxidative stress and liver injury in rats. J Ginseng Res 41:316–325

    Article  PubMed  Google Scholar 

  • Mirfeizi M, Mehdizadeh Tourzani Z, Mirfeizi SZ, Asghari Jafarabadi M, Rezvani HR, Afzali M (2016) Controlling type 2 diabetes mellitus with herbal medicines: a triple-blind randomized clinical trial of efficacy and safety. J Diabetes 8:647–656

    Article  CAS  PubMed  Google Scholar 

  • Niranjana Murthy H, Dandin VS, Yoeup Paek K (2014) Hepatoprotective activity of ginsenosides from Panax ginseng adventitious roots against carbon tetrachloride treated hepatic injury in rats. J Ethnopharmacol 158:442–446

    Article  CAS  PubMed  Google Scholar 

  • Oh GS, Pae HO, Choi BM, Seo EA, Kim DH, Shin MK, Kim JD, Kim JB, Chung HT (2004) 20(S)-Protopanaxatriol, one of ginsenoside metabolites, inhibits inducible nitric oxide synthase and cyclooxygenase-2 expressions through inactivation of nuclear factor-kappaB in RAW 264.7 macrophages stimulated with lipopolysaccharide. Cancer Lett 205:23–29

    Article  CAS  PubMed  Google Scholar 

  • Oh KS, Oh BK, Mun J, Seo HW, Lee BH (2011) Salvianolic acid A suppress lipopolysaccharide-induced NF-kappaB signaling pathway by targeting IKKbeta. Int Immunopharmacol 11:1901–1906

    Article  CAS  PubMed  Google Scholar 

  • Oh GS, Yoon J, Lee GG, Oh WK, Kim SW (2015) 20(S)-protopanaxatriol inhibits liver X receptor alpha-mediated expression of lipogenic genes in hepatocytes. J Pharmacol Sci 128:71–77

    Article  CAS  PubMed  Google Scholar 

  • Schumann J, Wolf D, Pahl A, Brune K, Papadopoulos T, van Rooijen N, Tiegs G (2000) Importance of Kupffer cells for T-cell-dependent liver injury in mice. Am J Pathol 157:1671–1683

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shim JY, Kim MH, Kim HD, Ahn JY, YunYS SJY (2010) Protective action of the immunomodulator ginsan against carbon tetrachloride-induced liver injury via control of oxidative stress and the inflammatory response. Toxicol Appl Pharmacol 242:318–325

    Article  CAS  PubMed  Google Scholar 

  • Sumner JB, Howell SF (1936) Identification of hemagglutinin of Jack bean with Concanavalin A. J Bacteriol 32:227–237

  • Tiegs G, Hentschel J, Wendel A (1992) A T cell-dependent experimental liver injury in mice inducible by concanavalin A. J Clin Invest 90:190–203

    Article  Google Scholar 

  • Tripathi YB, Shukla R, Pandey N, Pandey V, Kumar M (2017) An extract of Pueraria tuberosa tubers attenuates diabetic nephropathy by upregulating matrix metalloproteinase-9 expression in the kidney of diabetic rats. J Diabetes 9:123–132

    Article  CAS  PubMed  Google Scholar 

  • Wang Q, Yang F, Miao Q, Krawitt EL, Gershwin ME, Ma X (2016) The clinical phenotypes of autoimmune hepatitis: a comprehensive review. J Autoimmun 66:98–107

    Article  PubMed  Google Scholar 

  • Yue PY, Mak NK, Cheng YK, Leung KW, Ng TB, Fan DT, Yeung HW, Wong RN (2007) Pharmacogenomics and the Yin/Yang actions of ginseng: anti-tumor, angiomodulating and steroid-like activities of ginsenosides. Chin Med 2:6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Z, Li X, Lv W, Yang Y, Gao H, Yang J, Shen Y, Ning G (2008) Ginsenoside Re reduces insulin resistance through inhibition of c-Jun NH2-terminal kinase and nuclear factor-kappaB. Mol Endocrinol 22:186–195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao M, Chen J, Zhu P, Fujino M, Takahara T, Toyama S, Tomita A, Zhao L, Yang Z, Hei M, Zhong L, Zhuang J, Kimura S, Li XK (2015) Dihydroquercetin (DHQ) ameliorated concanavalin A-induced mouse experimental fulminant hepatitis and enhanced HO-1 expression through MAPK/Nrf2 antioxidant pathway in RAW cells. Int Immunopharmacol 28:938–944

    Article  CAS  PubMed  Google Scholar 

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Funding

This study was supported by Shanghai Municipal Planning Commission of Science and Research Foundation (20134429, 20144Y0252), Shanghai University Youth Teacher Training program (ZZjdyx14005). This study was supported by Shanghai Municipal Natural Science Foundation (18ZR1433000). This study was supported by the National Natural Science Foundation of China (No. 81570719, 81670797 81471074, 81770863).

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Author notes

  1. Lina Jin and Xue Fu contributed equally to this work.

Authors and Affiliations

  1. Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, People’s Republic of China

    Lina Jin, Xue Fu, Shuangshuang Yao, Jian Yang, Guang Ning & Zhiguo Zhang

  2. Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

    Lina Jin

Authors
  1. Lina Jin
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  2. Xue Fu
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  3. Shuangshuang Yao
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  4. Jian Yang
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  5. Guang Ning
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  6. Zhiguo Zhang
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Contributions

G.N., Z.Z., and L.J. conceived the project and designed the study; L.J. and X.F. carried out all experiments and participated in the experimental design. L.J., J.Y., and S.Y. participated in the animal study. Z.Z. gave comments in experimental design and manuscript. G.N., Z.Z., and L.J. carried out data interpretation and discussion. L.J., X.F., and Z.Z. wrote the paper. All authors prepared and approved the paper for submission.

Corresponding author

Correspondence to Zhiguo Zhang.

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The authors declare that they have no conflict of interest.

Electronic supplementary material

Fig. S1

PPT treatment reduces Con A-induced liver injury in mice. a. Indices indicating serum ALT and AST levels at 2h and 8 h after ConA injection in mice, and the effects observed in the PPT treatment groups at the same time points. Data are expressed as means ± SE. n=6-8 for each group. ** p < 0.01, ***p <0.001 (for comparisons of specific groups (Veh vs. ConA and ConA vs. PPT + ConA)). b. H&E staining of liver sections. Original magnification ×200. ConA: concanavalin A; PPT: protopanaxatriols; H&E: hematoxylin and eosin. (PDF 596 kb)

Fig. S2

PPT treatment reduced IL-1β and IL-6 expression induced by ConA. Il-1β and Il-6 mRNA expression levels were analyzed via qRT-PCR after ConA injection as described in the “Materials and methods” section. Data are presented as means ± SE. n=6-8 for each group. *p < 0.05, ** p < 0.01, ***p < 0.001 (for comparisons of specific groups, (Veh vs. ConA and ConA vs. PPT + ConA). (PDF 241 kb)

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Jin, L., Fu, X., Yao, S. et al. Protective effects of protopanaxatriol on acute liver injury induced by concanavalin A. Naunyn-Schmiedeberg's Arch Pharmacol 392, 81–87 (2019). https://doi.org/10.1007/s00210-018-1567-4

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  • DOI: https://doi.org/10.1007/s00210-018-1567-4

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