Baicalin relieves inflammation stimulated by lipopolysaccharide via upregulating TUG1 in liver cells
- 32 Downloads
Hepatitis has become a major social, health, and economic problem worldwide. Herein, we tested the beneficial influence of baicalin, a flavonoid extracted from the roots of Scutellaria baicalensis, on human normal liver L-02 and THLE2 cell apoptosis and inflammatory reaction stimulated by lipopolysaccharide (LPS) and possible molecular mechanisms. L-02 and THLE2 cell viability and apoptosis after LPS and/or baicalin treatment were tested using CCK-8 assay and Annexin V-FITC/PI apoptosis kit, respectively. qRT-PCR was used to measure the MCP-1, IL-6, TNF-α, and lncRNA taurine upregulated gene 1 (TUG1) expressions in L-02 and THLE2 cells. sh-TUG1 was transfected to knockdown TUG1. SB203580 was used as inhibitor of p38MAPK pathway, while SP600125 was used as inhibitor of JNK pathway. We discovered that LPS stimulation caused L-02 and THLE2 cell apoptosis and inflammatory reaction. Baicalin relieved the L-02 and THLE2 cell apoptosis and inflammatory reaction stimulated by LPS. Moreover, LPS lowered the TUG1 expression in L-02 cells, while baicalin promoted the TUG1 expression in L-02 and L-02 and THLE2 cells, as well as inactivated p38MAPK and JNK pathways in LPS-stimulated L-02 cells. Besides, knockdown of TUG1 activated p38MAPK and JNK pathways and promoted inflammatory cytokine expression in L-02 cells. In conclusion, this study further affirmed the beneficial influences of baicalin on LPS-stimulated human normal liver cell apoptosis and inflammatory reaction. Baicalin relived liver cell inflammation stimulated by LPS might be via upregulating TUG1 and then inactivating p38MAPK and JNK pathways.
KeywordsHepatitis Baicalin Lipopolysaccharide LncRNA TUG1 p38MAPK pathway JNK pathway
Yanqiu Huang, Aiying Zhao: conceived and designed the experiments.
Yanqiu Huang, Mengyan Sun, Xuefang Yang, Aiyu Ma, Yujie Ma: data collection.
Yanqiu Huang, Aiying Zhao: manuscript writing.
Compliance with ethical standards
Conflict of interest
The authors declare that there is no conflict of interest.
- 4.Ceccarelli S, Panera N, Mina M, Gnani D, De Stefanis C, Crudele A, Rychlicki C, Petrini S, Bruscalupi G, Agostinelli L, Stronati L, Cucchiara S, Musso G, Furlanello C, Svegliati-Baroni G, Nobili V, Alisi A (2015) LPS-induced TNF-alpha factor mediates pro-inflammatory and pro-fibrogenic pattern in non-alcoholic fatty liver disease. Oncotarget 6:41434–41452. https://doi.org/10.18632/oncotarget.5163 CrossRefGoogle Scholar
- 10.Filliol A, Piquet-Pellorce C, Raguenes-Nicol C, Dion S, Farooq M, Lucas-Clerc C, Vandenabeele P, Bertrand MJM, Le Seyec J, Samson M (2017) RIPK1 protects hepatocytes from Kupffer cells-mediated TNF-induced apoptosis in mouse models of PAMP-induced hepatitis. J Hepatol 66:1205–1213. https://doi.org/10.1016/j.jhep.2017.01.005 CrossRefGoogle Scholar
- 13.He P, Wu Y, Shun J, Liang Y, Cheng M, Wang Y (2017) Baicalin ameliorates liver injury induced by chronic plus binge ethanol feeding by modulating oxidative stress and inflammation via CYP2E1 and NRF2 in mice. 2017:4820414. doi: https://doi.org/10.1155/2017/4820414
- 17.Long Y, Wang X, Youmans DT, Cech TR (2017) How do lncRNAs regulate transcription? 3:eaao2110. doi: https://doi.org/10.1126/sciadv.aao2110
- 18.Lopez-Izquierdo R, Udaondo MA, Zarzosa P, Garcia-Ramon E, Garcinuno S, Bratos MA, Orduna A, Rodriguez-Torres A, Almaraz A (2007) Seroprevalence of viral hepatitis in a representative general population of an urban public health area in Castilla y Leon (Spain). Enferm Infecc Microbiol Clin 25:317–323CrossRefGoogle Scholar
- 25.Rorato R, Borges BC, Uchoa ET, Antunes-Rodrigues J, Elias CF, Elias LLK (2017) LPS-induced low-grade inflammation increases hypothalamic JNK expression and causes central insulin resistance irrespective of body weight changes. Int J Mol Sci 18. https://doi.org/10.3390/ijms18071431
- 27.Salaritabar A, Darvishi B, Hadjiakhoondi F, Manayi A, Sureda A, Nabavi SF, Fitzpatrick LR, Nabavi SM, Bishayee A (2017) Therapeutic potential of flavonoids in inflammatory bowel disease: a comprehensive review. World J Gastroenterol 23:5097–5114. https://doi.org/10.3748/wjg.v23.i28.5097 CrossRefGoogle Scholar
- 29.Sinn DH, Cho EJ, Kim JH, Kim DY, Kim YJ, Choi MS (2017) Current status and strategies for viral hepatitis control in Korea. 23:189–195. https://doi.org/10.3350/cmh.2017.0033
- 30.Sowndhararajan K, Deepa P, Kim M, Park SJ, Kim S (2018) Neuroprotective and cognitive enhancement potentials of baicalin: a review 8. doi: https://doi.org/10.3390/brainsci8060104
- 32.Sun SJ, Wu XP, Song HL, Li GQ (2015) Baicalin ameliorates isoproterenol-induced acute myocardial infarction through iNOS, inflammation, oxidative stress and P38MAPK pathway in rat. Int J Clin Exp Med 8:22063–22072Google Scholar
- 35.Yu X, Lan P, Hou X, Han Q, Lu N, Li T, Jiao C, Zhang J, Zhang C, Tian Z (2017) HBV inhibits LPS-induced NLRP3 inflammasome activation and IL-1beta production via suppressing the NF-kappaB pathway and ROS production. J Hepatol 66:693–702. https://doi.org/10.1016/j.jhep.2016.12.018 CrossRefGoogle Scholar
- 36.Zhang EB, Yin DD, Sun M, Kong R, Liu XH, You LH, Han L, Xia R, Wang KM, Yang JS, De W, Shu YQ, Wang ZX (2014) P53-regulated long non-coding RNA TUG1 affects cell proliferation in human non-small cell lung cancer, partly through epigenetically regulating HOXB7 expression. Cell Death Dis 5:e1243. https://doi.org/10.1038/cddis.2014.201 CrossRefGoogle Scholar