title: Baicalein selectively induces apoptosis in activated lymphocytes and ameliorates concanavalin a-induced hepatitis in mice.
abstract: BACKGROUND
  Insufficient apoptosis in activated lymphocytes contributes to the development of autoimmune hepatitis (AIH). Baicalein (BE), a flavonoid originally isolated from the root of Scutellaria baicalensis Georgi, possesses anti-inflammatory properties. However, whether BE can selectively induce apoptosis in activated lymphocytes and exert therapeutic effect on AIH has not been studied.
  
  
  RESULTS
  The pro-apoptotic properties of BE were evaluated in vitro on different types of immune cells, and in vivo effects of BE were examined in a murine model of Concanavalin A (Con A)-induced hepatitis. In vitro treatment with BE resulted in a higher increase in the level of apoptosis in Con A-stimulated murine splenocytes, Con A-stimulated CD3(+) splenocytes, lipopolysaccharide (LPS)-stimulated CD19(+) splenocytes, and phorbol 12-myristate 13-acetate/ionomycin-stimulated Jurkat T cells, compared with that in unstimulated naïve ones. Murine bone marrow-derived dentritic cells, peritoneal macrophages, and RAW264.7 cells, either stimulated with LPS or unstimulated, were all insensitive to the BE-induced apoptosis. BE treatment also led to a loss of mitochondrial membrane potential, an increase of cytochrome c release from mitochondria to the cytosol, a decrease in the ratio of Bcl-2/Bax, and activation of caspase-9,-3 in Con A-stimulated CD3(+) splenocytes and LPS-stimulated CD19(+) splenocytes, while showing no impact on Fas/FasL expressions and caspase-8 activation. In vivo administration of BE alleviated Con A-induced liver injury, suppressed serum level of TNF-α and IFN-γ, and reduced liver infiltration of mononuclear cells (MNCs). Furthermore, BE treatment increased the incidences of apoptosis in liver-infiltrating MNCs and splenocytes, as well as in CD3(+) and CD19(+) splenocytes. When liver MNCs and splenocytes from BE-treated mice were cultured in vitro for 24 h, they exhibited marked increase in apoptosis compared to vehicle-treated control.
  
  
  CONCLUSIONS
  The present study demonstrates the ability of BE to promote apoptosis in activated lymphocytes through mitochondrial pathway and its potential use in the treatment of AIH.
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Shan
authors.forename: Yaping
authors.initials: Y
authors.lastname: Hua
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.forename: Huawu
authors.initials: H
authors.lastname: Zeng
authors.forename: Runhui
authors.initials: R
authors.lastname: Liu
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhang
authors.forename: Zhenlin
authors.initials: Z
authors.lastname: Hu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003208:Concanavalin A / Q000494:pharmacology*; D005260:Female; D044950:Flavanones / Q000494:pharmacology*; D019693:Hepatitis, Autoimmune / Q000209:etiology / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects; D008934:Mitogens / Q000494:pharmacology; D013154:Spleen / Q000276:immunology
chemical_list: D044950:Flavanones; D008934:Mitogens; D003208:Concanavalin A; C006680:baicalein
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