Protective effect of Xuebijing injection on D-galactosamine- and lipopolysaccharide-induced acute liver injury in rats through the regulation of p38 MAPK, MMP-9 and HO-1 expression by increasing TIPE2 expression

Liu,Ming-Wei; Liu,Rong; Wu,Hai-Yin; Zhang,Wei; Xia,Jing; Dong,Min-Na; Yu,Wen; Wang,Qiang; Xie,Feng-Mei; Wang,Rui; Huang,Yun-Qiao; Qian,Chuan-Yun

doi:10.3892/ijmm.2016.2749

Protective effect of Xuebijing injection on D-galactosamine- and lipopolysaccharide-induced acute liver injury in rats through the regulation of p38 MAPK, MMP-9 and HO-1 expression by increasing TIPE2 expression

Authors:
- Ming-Wei Liu
- Rong Liu
- Hai-Yin Wu
- Wei Zhang
- Jing Xia
- Min-Na Dong
- Wen Yu
- Qiang Wang
- Feng-Mei Xie
- Rui Wang
- Yun-Qiao Huang
- Chuan-Yun Qian
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Affiliations: Department of Emergency Medicine, The First Hospital Affiliated To Kunming Medical University, Kunming, Yunnan 650032, P.R. China, Department of Hepatobiliary Surgery, The First Hospital Affiliated To Kunming Medical University, Kunming, Yunnan 650032, P.R. China, Department of Gastroenterology, The First Hospital Affiliated To Kunming Medical University, Kunming, Yunnan 650032, P.R. China
Published online on: September 23, 2016 https://doi.org/10.3892/ijmm.2016.2749
Pages: 1419-1432
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Xuebijing injection (XBJ) has long been used to treat infectious diseases in China. The therapeutic effect of XBJ is probably associated with anti-inflammatory effects. However, the precise mechanisms responsible for the effects of XBJ remain unknown. The present study was conducted in order to evaluate the protective effects of XBJ in a rat model of D-galactosamine (D-Gal)- and lipopolysaccharide (LPS)‑induced acute liver injury. In the present study, the rats were injected with D-Gal and LPS intraperitoneally to induce acute liver injury. Two hours prior to D-Gal and LPS administration, the treatment group was administered XBJ by intravenous infusion. The effects of XBJ on D-Gal- and LPS-induced expression of tumor necrosis factor (TNF)‑alpha‑induced protein 8-like 2 (TIPE2), nuclear factor-κB (NF-κB), matrix metalloproteinase-9 (MMP-9) and heme oxygenase-1 (HO-1) as well as mitogen-activated protein kinase (MAPK) signaling was examined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot analysis, immunofluorescence, as well as by analysing the serum levels of pro-inflammatory cytokines and the transaminases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Myeloperoxidase (MPO), malondialdehyde (MDA) and superoxide dismutase (SOD) levels in the rat liver tissues were also measured. For histological analysis, hematoxylin and eosin (H&E)-stained liver samples were evaluated. The results showed that XBJ upregulated TIPE2 and HO-1 expression, reduced the expression of NF-κB65 and MMP-9, inhibited the LPS-induced gene expression of c-jun N-terminal kinase (JNK) and p38 MAPK, decreased the generation of pro-inflammatory cytokines [interleukin (IL)-6, IL-13 and TNF-α], inhibited ALT and AST activity, and ameliorated D-Gal- and LPS-induced liver injury. The histological results also demonstrated that XBJ attenuated D-Gal- and LPS-induced liver inflammation. It was found that XBJ may prevent LPS-induced pro-inflammatory gene expression through inhibiting the NF-κB and MAPK signaling pathways by upregulating TIPE2 expression, thereby attenuating LPS-induced liver injury in rats. The marked protective effects of XBJ suggest that it has the potential to be used in the treatment of LPS-induced liver injury.

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1	Nolan JP: The role of intestinal endotoxin in liver injury: a long and evolving history. Hepatology. 52:1829–1835. 2010. View Article : Google Scholar : PubMed/NCBI
2	Kudo H, Takahara T, Yata Y, Kawai K, Zhang W and Sugiyama T: Lipopolysaccharide triggered TNF-alpha-induced hepatocyte apoptosis in a murine non-alcoholic steatohepatitis model. J Hepatol. 51:168–175. 2009. View Article : Google Scholar : PubMed/NCBI
3	Yang SQ, Lin HZ, Lane MD, Clemens M and Diehl AM: Obesity increases sensitivity to endotoxin liver injury: implications for the pathogenesis of steatohepatitis. Proc Natl Acad Sci USA. 94:2557–2562. 1997. View Article : Google Scholar : PubMed/NCBI
4	Peng X, Nie Y, Wu J, Huang Q and Cheng Y: Juglone prevents metabolic endotoxemia-induced hepatitis and neuroinflammation via suppressing TLR4/NF-κB signaling pathway in high-fat diet rats. Biochem Biophys Res Commun. 462:245–250. 2015. View Article : Google Scholar : PubMed/NCBI
5	Sakaguchi S, Takahashi S, Sasaki T, Kumagai T and Nagata K: Progression of alcoholic and non-alcoholic steatohepatitis: common metabolic aspects of innate immune system and oxidative stress. Drug Metab Pharmacokinet. 26:30–46. 2011. View Article : Google Scholar
6	Uesugi T, Froh M, Arteel GE, Bradford BU, Wheeler MD, Gäbele E, Isayama F and Thurman RG: Role of lipopolysaccharide-binding protein in early alcohol-induced liver injury in mice. J Immunol. 168:2963–2969. 2002. View Article : Google Scholar : PubMed/NCBI
7	Su GL, Hoesel LM, Bayliss J, Hemmila MR and Wang SC: Lipopolysaccharide binding protein inhibitory peptide protects against acetaminophen-induced hepatotoxicity. Am J Physiol Gastrointest Liver Physiol. 299:G1319–G1325. 2010. View Article : Google Scholar : PubMed/NCBI
8	Sun H, Gong S, Carmody RJ, Hilliard A, Li L, Sun J, Kong L, Xu L, Hilliard B, Hu S, et al: TIPE2, a negative regulator of innate and adaptive immunity that maintains immune homeostasis. Cell. 133:415–426. 2008. View Article : Google Scholar : PubMed/NCBI
9	Gus-Brautbar Y, Johnson D, Zhang L, Sun H, Wang P, Zhang S, Zhang L and Chen YH: The anti-inflammatory TIPE2 is an inhibitor of the oncogenic Ras. Mol Cell. 45:610–618. 2012. View Article : Google Scholar : PubMed/NCBI
10	Li D, Song L, Fan Y, Li X, Li Y, Chen J, Zhu F, Guo C, Shi Y and Zhang L: Down-regulation of TIPE2 mRNA expression in peripheral blood mononuclear cells from patients with systemic lupus erythematosus. Clin Immunol. 133:422–427. 2009. View Article : Google Scholar : PubMed/NCBI
11	Li HF, Sun ML, Yu YX and Liu XL: Xuebijing alters tumor necrosis factor-alpha, interleukin-1beta and p38 mitogen activated protein kinase content in a rat model of cardiac arrest following cardiopulmonary resuscitation. Neural Regen Res. 6:2573–2576. 2011.
12	Jia P, Wang S, Meng X, Lan W, Luo J, Liao S, Xiao C, Zheng X, Li L, Liu Q, et al: Effects of ionic liquid and nanogold particles on high-performance liquid chromatography-electrochemical detection and their application in highly efficient separation and sensitive analysis of five phenolic acids in Xuebijing injection. Talanta. 107:103–110. 2013. View Article : Google Scholar : PubMed/NCBI
13	Liu YC, Yao FH, Chai YF, Dong N, Sheng ZY and Yao YM: Xuebijing injection promotes M2 polarization of macrophages and improves survival rate in septic mice. Evid Based Complement Alternat Med. 2015:3526422015. View Article : Google Scholar : PubMed/NCBI
14	't Hart NA, van der Plaats A, Leuvenink HG, Wiersema-Buist J, Olinga P, van Luyn MJ, Verkerke GJ, Rakhorst G and Ploeg RJ: Initial blood washout during organ procurement determines liver injury and function after preservation and reperfusion. Am J Transplant. 4:1836–1844. 2004. View Article : Google Scholar : PubMed/NCBI
15	Ben Mosbah I, Alfany-Fernández I, Martel C, Zaouali MA, Bintanel-Morcillo M, Rimola A, Rodés J, Brenner C, Roselló-Catafau J and Peralta C: Endoplasmic reticulum stress inhibition protects steatotic and non-steatotic livers in partial hepatectomy under ischemia-reperfusion. Cell Death Dis. 1:e522010. View Article : Google Scholar
16	Chen P, Chen Y, Wang Y, Cai S, Deng L, Liu J and Zhang H: Comparative evaluation of hepatoprotective activities of geniposide, crocins and crocetin by CCl4-induced liver injury in mice. Biomol Ther (Seoul). 24:156–162. 2016. View Article : Google Scholar
17	Norvell JP: Liver disease after hematopoietic cell transplantation in adults. Transplant Rev (Orlando). 29:8–15. 2015. View Article : Google Scholar
18	Zhu RZ, Xiang D, Xie C, Li JJ, Hu JJ, He HL, Yuan YS, Gao J, Han W and Yu Y: Protective effect of recombinant human IL-1Ra on CCl4-induced acute liver injury in mice. World J Gastroenterol. 16:2771–2779. 2010. View Article : Google Scholar : PubMed/NCBI
19	Qi F, Liang ZX, She DY, Yan GT and Chen LA: A clinical study on the effects and mechanism of Xuebijing injection in severe pneumonia patients. J Tradit Chin Med. 31:46–49. 2011. View Article : Google Scholar : PubMed/NCBI
20	Jiang M, Zhou M, Han Y, Xing L, Zhao H, Dong L, Bai G and Luo G: Identification of NF-κB Inhibitors in Xuebijing injection for sepsis treatment based on bioactivity-integrated UPLC-Q/TOF. J Ethnopharmacol. 147:426–433. 2013. View Article : Google Scholar : PubMed/NCBI
21	Sun ML, Ma DH, Liu M, Yu YX, Cao DB, Ma C, Wang X and Liu XL: Successful treatment of paraquat poisoning by Xuebijing, an injection concocted from multiple Chinese medicinal herbs: a case report. J Altern Complement Med. 15:1375–1378. 2009. View Article : Google Scholar : PubMed/NCBI
22	Liu MW, Wang YH, Qian CY and Li H: Xuebijing exerts protective effects on lung permeability leakage and lung injury by upregulating Toll-interacting protein expression in rats with sepsis. Int J Mol Med. 34:1492–1504. 2014.PubMed/NCBI
23	Gui YG, Chai YF and Yao YM: Effects of Xuebijing injection on tissue factor of monocyte and coagulation parameters in septic rats. Chin J Exp Surg. 27:32–34. 2010.
24	Lu YQ, Gu LH and Huang WD: Effect of Xuebijing injection on peripheral T-lymphocyte subpopulations in patients with severe trauma. Chin J Traumatol. 13:72–76. 2010.PubMed/NCBI
25	Chen T, Guo Q, Wang H, Zhang H, Wang C, Zhang P, Meng S, Li Y, Ji H and Yan T: Effects of esculetin on lipopolysaccharide (LPS)-induced acute lung injury via regulation of RhoA/Rho Kinase/NF-κB pathways in vivo and in vitro. Free Radic Res. 49:1459–1468. 2015. View Article : Google Scholar
26	Brasier AR: The NF-kappaB regulatory network. Cardiovasc Toxicol. 6:111–130. 2006. View Article : Google Scholar
27	Killeen MJ, Linder M, Pontoniere P and Crea R: NF-κβ signaling and chronic inflammatory diseases: exploring the potential of natural products to drive new therapeutic opportunities. Drug Discov Today. 19:373–378. 2014. View Article : Google Scholar
28	Zhang Y and Li J: Carbachol ameliorates lipopolysaccharide-induced intestinal epithelial tight junction damage by down-regulating NF-κβ and myosin light-chain kinase pathways. Biochem Biophys Res Commun. 428:321–326. 2012. View Article : Google Scholar : PubMed/NCBI
29	Liu MW, Su MX, Zhang W, Wang YQ, Chen M, Wang L and Qian CY: Protective effect of Xuebijing injection on paraquat-induced pulmonary injury via down-regulating the expression of p38 MAPK in rats. BMC Complement Altern Med. 14:4982014. View Article : Google Scholar : PubMed/NCBI
30	Hong Z, Cabrera JA, Mahapatra S, Kutty S, Weir EK and Archer SL: Activation of the EGFR/p38/JNK pathway by mitochondrial-derived hydrogen peroxide contributes to oxygen-induced contraction of ductus arteriosus. J Mol Med Berl. 92:995–1007. 2014. View Article : Google Scholar : PubMed/NCBI
31	Murakami K, Suzuki C, Fujii A, Kobayashi F, Nakano A and Kamizono A: Intravenous immunoglobulin preparation prevents the production of pro-inflammatory cytokines by modulating NFκB and MAPKs pathways in the human monocytic THP-1 cells stimulated with procalcitonin. Inflamm Res. 63:711–718. 2014. View Article : Google Scholar : PubMed/NCBI
32	Freundt EC, Bidere N and Lenardo MJ: A different TIPE of immune homeostasis. Cell. 133:401–402. 2008. View Article : Google Scholar : PubMed/NCBI
33	Luan YY, Yao YM, Zhang L, Dong N, Zhang QH, Yu Y and Sheng ZY: Expression of tumor necrosis factor-α induced protein 8 like-2 contributes to the immunosuppressive property of CD4(+)CD25(+) regulatory T cells in mice. Mol Immunol. 49:219–226. 2011. View Article : Google Scholar : PubMed/NCBI
34	Das S, Pandey K, Rabidas VN, Mandal A and Das P: Effectiveness of miltefosine treatment in targeting anti-leishmanial HO-1/Nrf-2-mediated oxidative responses in visceral leishmaniasis patients. J Antimicrob Chemother. 68:2059–2065. 2013. View Article : Google Scholar : PubMed/NCBI
35	McKenzie MJ, Goldfarb A, Garten RS and Vervaecke L: Oxidative stress and inflammation response following aerobic exercise: role of ethnicity. Int J Sports Med. 35:822–827. 2014. View Article : Google Scholar : PubMed/NCBI
36	Cheng CY, Kuo CT, Lin CC, Hsieh HL and Yang CM: IL-1beta induces expression of matrix metalloproteinase-9 and cell migration via a c-Src-dependent, growth factor receptor transactivation in A549 cells. Br J Pharmacol. 160:1595–1610. 2010. View Article : Google Scholar : PubMed/NCBI
37	Jeong S, Ledee DR, Gordon GM, Itakura T, Patel N, Martin A and Fini ME: Interaction of clusterin and matrix metalloproteinase-9 and its implication for epithelial homeostasis and inflammation. Am J Pathol. 180:2028–2039. 2012. View Article : Google Scholar : PubMed/NCBI
38	Chang SJ, Wang TY, Lee YH and Tai CJ: Extracellular ATP activates nuclear translocation of ERK1/2 leading to the induction of matrix metalloproteinases expression in human endometrial stromal cells. J Endocrinol. 193:393–404. 2007. View Article : Google Scholar : PubMed/NCBI
39	Tung WH, Tsai HW, Lee IT, Hsieh HL, Chen WJ, Chen YL and Yang CM: Japanese encephalitis virus induces matrix metallopro-teinase-9 in rat brain astrocytes via NF-κB signalling dependent on MAPKs and reactive oxygen species. Br J Pharmacol. 161:1566–1583. 2010. View Article : Google Scholar : PubMed/NCBI
40	Kolosova I, Nethery D and Kern JA: Role of Smad2/3 and p38 MAP kinase in TGF-β1-induced epithelial-mesenchymal transition of pulmonary epithelial cells. J Cell Physiol. 226:1248–1254. 2011. View Article : Google Scholar :
41	Voloshenyuk TG, Landesman ES, Khoutorova E, Hart AD and Gardner JD: Induction of cardiac fibroblast lysyl oxidase by TGF-β1 requires PI3K/Akt, Smad3, and MAPK signaling. Cytokine. 55:90–97. 2011. View Article : Google Scholar : PubMed/NCBI
42	Zou W, Roth RA, Younis HS, Malle E and Ganey PE: Neutrophil-cytokine interactions in a rat model of sulindac-induced idiosyncratic liver injury. Toxicology. 290:278–285. 2011. View Article : Google Scholar : PubMed/NCBI
43	Liang Y, Hou C, Kong J, Wen H, Zheng X, Wu L, Huang H and Chen Y: HMGB1 binding to receptor for advanced glycation end products enhances inflammatory responses of human bronchial epithelial cells by activating p38 MAPK and ERK1/2. Mol Cell Biochem. 405:63–71. 2015. View Article : Google Scholar : PubMed/NCBI
44	Hanna DM, Tadros MG and Khalifa AE: ADIOL protects against 3-NP-induced neurotoxicity in rats: possible impact of its anti-oxidant, anti-inflammatory and anti-apoptotic actions. Prog Neuropsychopharmacol Biol Psychiatry. 60:36–51. 2015. View Article : Google Scholar : PubMed/NCBI