Soshiho-tang protects LPS-induced acute liver injury by attenuating inflammatory response

Abstract

Soshiho-tang (SSHT) has traditionally been used to treat gastrointestinal disorders. In this experiment, we investigated the protective effect of SSHT on inflammatory liver injury in lipopolysaccharide (LPS)-sensitized mice. Male C57BL/6J mice aged 6 weeks were randomly placed in 6 groups (n = 5): normal mice (CTR), LPS-sensitized mice (LPS), LPS-sensitized mice treated with dexamethasone (DEX) and LPS-sensitized mice treated with 0.05, 0.55, and 5.55 g/kg of SSHT (SSHT 0.05, SSHT 0.55, and SSHT 5.55). Various doses of SSHT was given once a day for 7 days. After 2 h of LPS injection, the liver tissue was collected. SSHT pretreatment recovered hemorrhage of liver tissues in LPS-induced acute liver injury. The expressions of MAP Kinase, NF-κB, IκBα, p-IκBα, COX-2, and iNOS protein levels were markedly decreased by SSHT-treated liver tissues. Additionally, SSHT pretreatment significantly regulated the expressions of MCP-1, TNF-α, and IL-6 cytokines. These results suggest the potential of SSHT on the protection of acute liver injury.

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References

  1. 1.

    Losser MR, Payen D (1996) Mechanism of liver damage. Semin Liver Dis 16(4):357–367

    CAS  PubMed  Google Scholar 

  2. 2.

    Asrani SK, Devarbhavi H, Eaton J, Kamath PS (2019) Burden of liver diseases in the world. J Hepatol 70(1):151–171

    PubMed  Google Scholar 

  3. 3.

    Goodman ZD (2007) Grading and staging systems for inflammation and fibrosis in chronic liver diseases. J Hepatol 47(4):598–607

    PubMed  Google Scholar 

  4. 4.

    Koyama Y, Brenner DA (2017) Liver inflammation and fibrosis. J Clin Invest 127(1):55–64

    PubMed  PubMed Central  Google Scholar 

  5. 5.

    Sostres C, Gargallo CJ, Lanas A (2013) Nonsteroidal anti-inflammatory drugs and upper and lower gastrointestinal mucosal damage. Arthritis Res Ther 15(Suppl 3):S3

    PubMed  PubMed Central  Google Scholar 

  6. 6.

    Lee JK, Kim JH, Shin HK (2011) Therapeutic effects of the oriental herbal medicine Sho-saiko-to on liver cirrhosis and carcinoma. Hepatol Res 41(9):825–837

    PubMed  Google Scholar 

  7. 7.

    Inada Y, Watanabe K, Kamiyama M, Kanemitsu T, Clark WS, Lange M (1990) In vitro immunomodulatory effects of traditional Kampo medicine (sho-saiko-to: SST) on peripheral mononuclear cells in patients with AIDS. Biomed Pharmacother 44(1):17–19

    CAS  PubMed  Google Scholar 

  8. 8.

    Ono M, Miyamura M, Kyotani S, Saibara T, Ohnishi S, Nishioka Y (2000) Effect of Sho-saiko-to extract on HGF and TGF-beta levels of intraorgans in liver-injured rats after partial hepatectomy. J Pharm Pharmacol 52(1):111–118

    CAS  PubMed  Google Scholar 

  9. 9.

    Jeon WY, Shin HK, Shin IS, Kim SK, Lee MY (2015) Soshiho-tang water extract inhibits ovalbumin-induced airway inflammation via the regulation of heme oxygenase-1. BMC Complement Altern Med 15:329

    PubMed  PubMed Central  Google Scholar 

  10. 10.

    Shimizu I, Ma YR, Mizobuchi Y, Liu F, Miura T, Nakai Y, Yasuda M, Shiba M, Horie T, Amagaya S, Kawada N, Hori H, Ito S (1999) Effects of Sho-saiko-to, a Japanese herbal medicine, on hepatic fibrosis in rats. Hepatology 29(1):149–160

    CAS  PubMed  Google Scholar 

  11. 11.

    Yang P, Zhou W, Li C, Zhang M, Jiang Y, Jiang R, Ba H, Li C, Wang J, Yin B, Gong F, Li Z (2016) Kupffer-cell-expressed transmembrane TNF-alpha is a major contributor to lipopolysaccharide and D-galactosamine-induced liver injury. Cell Tissue Res 363(2):371–383

    CAS  PubMed  Google Scholar 

  12. 12.

    Kong Q, Yuan M, Ming T, Fang Q, Wu X (2020) Song X (2020) Expression and regulation of tumor necrosis factor-α-induced protein-8-like 2 is associated with acute lung injury induced by myocardial ischemia reperfusion in diabetic rats. Microvasc Res 22:104009

    Google Scholar 

  13. 13.

    Zhang JX, Feng WJ, Liu GC, Ma QQ, Li HL, Gao XY, Liu HZ, Piao GC, Yuan HD (2020) Corosolic acid attenuates hepatic lipid accumulation and inflammatory response via AMPK/SREBPs and NF-κB/MAPK signaling pathways. Am J Chin Med 24:1–17

    CAS  Google Scholar 

  14. 14.

    Hamesch K, Borkham-Kamphorst E, Strnad P, Weiskirchen R (2015) Lipopolysaccharide-induced inflammatory liver injury in mice. Lab Anim 49(1 suppl):37–46

    CAS  PubMed  Google Scholar 

  15. 15.

    Rolando N, Wade J, Davalos M, Wendon J, Philpott-Howard J, Williams R (2000) The systemic inflammatory response syndrome in acute liver failure. Hepatology 32(4 Pt 1):734–739

    CAS  PubMed  Google Scholar 

  16. 16.

    Sen S, Williams R, Jalan R (2002) The pathophysiological basis of acute-on-chronic liver failure. Liver 22(suppl 2):5–13

    PubMed  Google Scholar 

  17. 17.

    Tu C, Gao D, Li XF, Li CY, Li RS, Zhao YL, Li N, Jia GL, Pang JY, Cui HR, Ma ZJ, Xiao XH, Wang JB (2015) Inflammatory stress potentiates emodin-induced liver injury in rats. Front Pharmacol 6:233

    PubMed  PubMed Central  Google Scholar 

  18. 18.

    Ker YB, Peng CC, Chang WL, Chyau CC, Peng RY (2014) Hepatoprotective bioactivity of the glycoprotein, antrodan, isolated from Antrodia cinnamomea mycelia. PLoS ONE 9(4):e93191

    PubMed  PubMed Central  Google Scholar 

  19. 19.

    Arias-Salvatierra D, Silbergeld EK, Acosta-Saavedra LC, Calderon-Aranda ES (2011) Role of nitric oxide produced by iNOS through NF-κB pathway in migration of cerebellar granule neurons induced by lipopolysaccharide. Cell Signal 23(2):425–435

    CAS  PubMed  Google Scholar 

  20. 20.

    Poligone B, Baldwin AS (2001) Positive and negative regulation of NF-kappaB by COX-2: roles of different prostaglandins. J Biol Chem 276(42):38658–38664

    CAS  PubMed  Google Scholar 

  21. 21.

    Lee HY, Noh HJ, Gang JG, Xu ZG, Jeong HJ, Kang SW, Choi KH, Han DS (2002) Inducible nitric oxide synthase (iNOS) expression is increased in lipopolysaccharide (LPS)-stimulated diabetic rat glomeruli: effect of ACE inhibitor and angiotensin II receptor blocker. Yonsei Med J 43(2):183–192

    CAS  PubMed  Google Scholar 

  22. 22.

    Han J, Lee JD, Bibbs L, Ulevitch RJ (1994) A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. Science 265(5173):808–811

    CAS  PubMed  Google Scholar 

  23. 23.

    Wen Z, Lei Z, Yao L, Jiang P, Gu T, Ren F, Liu Y, Gou C, Li X, Wen T (2016) Circulating histones are major mediators of systemic inflammation and cellular injury in patients with acute liver failure. Cell Death Dis 7(9):e2391

    CAS  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Leonard EJ, Skeel A, Yoshimura T (1991) Biological aspects of monocyte chemoattractant protein-1 (MCP-1). Adv Exp Med Biol 305:57–64

    CAS  PubMed  Google Scholar 

  25. 25.

    Hu DN, Bi M, Zhang DY, Ye F, McCormick SA, Chan CC (2014) Constitutive and LPS-induced expression of MCP-1 and IL-8 by human uveal melanocytes in vitro and relevant signal pathways. Invest Ophthalmol Vis Sci 55(9):5760–5769

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Alexander JJ, Jacob A, Cunningham P, Hensley L, Quigg RJ (2008) TNF is a key mediator of septic encephalopathy acting through its receptor, TNF receptor-1. Neurochem Int 52(3):447–456

    CAS  PubMed  Google Scholar 

  27. 27.

    Couper KN, Blount DG, Riley EM (2008) IL-10: the master regulator of immunity to infection. J Immunol 180(9):5771–5777

    CAS  PubMed  Google Scholar 

  28. 28.

    Fattori E, Cappelletti M, Costa P, Sellitto C, Cantoni L, Carelli M, Faggioni R, Fantuzzi G, Ghezzi P, Poli V (1994) Defective inflammatory response in interleukin 6-deficient mice. J Exp Med 180(4):1243–1250

    CAS  PubMed  Google Scholar 

  29. 29.

    Tanaka T, Narazaki M, Kishimoto T (2014) IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol 6(10):a016295

    PubMed  PubMed Central  Google Scholar 

  30. 30.

    Jung HW, Seo UK, Kim JH, Leem KH, Park YK (2009) Flower extract of Panax notoginseng attenuates lipopolysaccharide-induced inflammatory response via blocking of NF-kappaB signaling pathway in murine macrophages. J Ethnopharmacol 122(2):313–319

    PubMed  Google Scholar 

  31. 31.

    Kim DH, Chung JH, Yoon JS, Ha YM, Bae SJ, Lee EK, Jung KJ, Kim MS, Kim YJ, Kim MK, Chung HY (2013) Ginsenoside Rd inhibits the expressions of iNOS and COX-2 by suppressing NF-κB in LPS-stimulated RAW264.7 cells and mouse liver. J Ginseng Res 37(1):54–63

    CAS  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Dong Q, Chu F, Wu C, Huo Q, Gan H, Li X, Liu H (2016) Scutellaria baicalensis Georgi extract protects against alcohol-induced acute liver injury in mice and affects the mechanism of ER stress. Mol Med Rep 13(4):3052–3062

    CAS  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Cui L, Feng L, Zhang ZH, Jia XB (2014) The anti-inflammation effect of baicalin on experimental colitis through inhibiting TLR4/NF-kappaB pathway activation. Int Immunopharmacol 23:294–303

    CAS  PubMed  Google Scholar 

  34. 34.

    Choi YY, Kim MH, Hong J, Kim SH, Yang WM (2013) Dried ginger (Zingiber officinalis) inhibits inflammation in a lipopolysaccharide-induced mouse model. Evid Based Complement Alternat Med 2013:914563

    PubMed  PubMed Central  Google Scholar 

  35. 35.

    Zhan R, Xia L, Shao J, Wang C, Chen D (2018) Polysaccharide isolated from Chinese jujube fruit (Zizyphus jujuba cv. Junzao) exerts anti-inflammatory effects through MAPK signaling. J Funct Food 40:461–470

    CAS  Google Scholar 

  36. 36.

    Yoshida T, Abe K, Ikeda T, Matsushita T, Wake K, Sato T, Sato T, Inoue H (2007) Inhibitory effect of glycyrrhizin on lipopolysaccharide and d-galactosamine-induced mouse liver injury. Eur J Pharmacol 576(1–3):136–142

    CAS  PubMed  Google Scholar 

  37. 37.

    Huang W, Wang Y, Jiang X, Sun Y, Zhao Z, Li S (2017) Protective effect of flavonoids from Ziziphus jujuba cv. Jinsixiaozao against acetaminophen-induced liver injury by inhibiting oxidative stress and inflammation in mice. Molecules 22(10):1781

    PubMed Central  Google Scholar 

  38. 38.

    Su T, Tan Y, Tsui MS, Yi H, Fu XQ, Li T, Chan CL, Guo H, Li YX, Zhu PL, Tse AKW, Cao H, Lu AP, Yu ZL (2018) Metabolomics reveals the mechanisms for the cardiotoxicity of Pinelliae Rhizoma and the toxicity-reducing effect of processing. Sci Rep 6:34692

    Google Scholar 

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Acknowledgements

This work was supported by a grant of the National Development Institute of Korean Medicine (NIKOM) funded by the Korean Ministry of Health and Welfare (MOHW), Republic of Korea, and a National Research Foundation of Korea Grant funded by the Korean government (NRF-2019R1I1A2A01063598).

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Correspondence to Woong Mo Yang.

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Jin, S.C., Kim, M.H., Jo, S.Y. et al. Soshiho-tang protects LPS-induced acute liver injury by attenuating inflammatory response. J Nat Med (2020). https://doi.org/10.1007/s11418-020-01421-w

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Keywords

  • Soshiho-tang
  • Liver inflammation
  • LPS
  • Acute liver injury
  • Anti-inflammation