title: Cycloastragenol mediates activation and proliferation suppression in concanavalin A-induced mouse lymphocyte pan-activation model.
abstract: BACKGROUND
  Cycloastragenol (CAG) is a molecule isolated from various species in the genus Astragalus. Although the regulatory activity of Astragalus on immune system has been investigated, the effect of CAG on activated lymphocytes is poorly understood.
  
  
  OBJECTIVE
  We aimed to biologically address the possible anti-inflammation potential of CAG on concanavalin A (Con A)-mediated mouse lymphocyte pan-activation model.
  
  
  METHODS
  Mouse lymphocytes were obtained from spleens and subjected to Con A for 24 h. Herein, the cells were treated with different concentrations of CAG. Cell viability was assayed by MTT. Pretreated by CAG and stimulated by Con A, the expression of CD69 and CD25, Th1/Th2/Th17 cytokines, cell cycle, proliferation and intracellular Ca2+concentration ([Ca2+]i) were analyzed by flow cytometry.
  
  
  RESULTS
  The results declared that CAG significantly downregulated both CD69 and CD25 expressed on Con A activated CD3 + T cells' surface, as well as inhibiting proliferation of activated lymphocytes. In addition, CAG blocked the Con A-induced mitogenesis, exhibiting lymphocyte G0/G1-phase cell-cycle arrest with significant reduction of cells in S and G2/M phases. Meanwhile, pretreated by CAG, a significant decline in [Ca2+]iwas observed. Furthermore, CAG significantly inhibited the production of Th1 cytokines IFN-γ, TNF, IL-2, Th2 cytokines IL-4, IL-6, IL-10 and Th17 cytokine IL-17 A on Con A-activated lymphocytes.
  
  
  CONCLUSIONS
  Our results reinforce that CAG has important anti-inflammatory activity by inhibiting lymphocytes activation, proliferation and cytokines expression, and shows, that this effect may be related to reduction of overall intracellular Ca2+overload.
authors.affiliation: a Linyi Key Laboratory for Immunopharmacology and Immunotoxicology of Natural Medicine , Lunan Pharmaceutical Group Corporation , Linyi , China.|b State Key Laboratory of Generic Pharmaceutical Technology for Chinese Medicine , Lunan Pharmaceutical Group Corporation , Linyi , China.|c Center for New Drug Pharmacology , Lunan Pharmaceutical Group Corporation , Linyi , PR China.
authors.forename: Chenghong
authors.initials: C
authors.lastname: Sun
authors.affiliation: a Linyi Key Laboratory for Immunopharmacology and Immunotoxicology of Natural Medicine , Lunan Pharmaceutical Group Corporation , Linyi , China.|b State Key Laboratory of Generic Pharmaceutical Technology for Chinese Medicine , Lunan Pharmaceutical Group Corporation , Linyi , China.|c Center for New Drug Pharmacology , Lunan Pharmaceutical Group Corporation , Linyi , PR China.
authors.forename: Mingmin
authors.initials: M
authors.lastname: Jiang
authors.affiliation: b State Key Laboratory of Generic Pharmaceutical Technology for Chinese Medicine , Lunan Pharmaceutical Group Corporation , Linyi , China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: a Linyi Key Laboratory for Immunopharmacology and Immunotoxicology of Natural Medicine , Lunan Pharmaceutical Group Corporation , Linyi , China.|b State Key Laboratory of Generic Pharmaceutical Technology for Chinese Medicine , Lunan Pharmaceutical Group Corporation , Linyi , China.|c Center for New Drug Pharmacology , Lunan Pharmaceutical Group Corporation , Linyi , PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.affiliation: b State Key Laboratory of Generic Pharmaceutical Technology for Chinese Medicine , Lunan Pharmaceutical Group Corporation , Linyi , China.
authors.forename: Guimin
authors.initials: G
authors.lastname: Zhang
authors.affiliation: a Linyi Key Laboratory for Immunopharmacology and Immunotoxicology of Natural Medicine , Lunan Pharmaceutical Group Corporation , Linyi , China.|b State Key Laboratory of Generic Pharmaceutical Technology for Chinese Medicine , Lunan Pharmaceutical Group Corporation , Linyi , China.|c Center for New Drug Pharmacology , Lunan Pharmaceutical Group Corporation , Linyi , PR China.
authors.forename: Bingyuan
authors.initials: B
authors.lastname: Du
authors.affiliation: a Linyi Key Laboratory for Immunopharmacology and Immunotoxicology of Natural Medicine , Lunan Pharmaceutical Group Corporation , Linyi , China.|b State Key Laboratory of Generic Pharmaceutical Technology for Chinese Medicine , Lunan Pharmaceutical Group Corporation , Linyi , China.|c Center for New Drug Pharmacology , Lunan Pharmaceutical Group Corporation , Linyi , PR China.
authors.forename: Yushan
authors.initials: Y
authors.lastname: Ren
authors.affiliation: a Linyi Key Laboratory for Immunopharmacology and Immunotoxicology of Natural Medicine , Lunan Pharmaceutical Group Corporation , Linyi , China.|b State Key Laboratory of Generic Pharmaceutical Technology for Chinese Medicine , Lunan Pharmaceutical Group Corporation , Linyi , China.|c Center for New Drug Pharmacology , Lunan Pharmaceutical Group Corporation , Linyi , PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: a Linyi Key Laboratory for Immunopharmacology and Immunotoxicology of Natural Medicine , Lunan Pharmaceutical Group Corporation , Linyi , China.|b State Key Laboratory of Generic Pharmaceutical Technology for Chinese Medicine , Lunan Pharmaceutical Group Corporation , Linyi , China.|c Center for New Drug Pharmacology , Lunan Pharmaceutical Group Corporation , Linyi , PR China.
authors.forename: Jingchun
authors.initials: J
authors.lastname: Yao
mesh_terms: D000818:Animals; D027883:Astragalus Plant / Q000737:chemistry; D020013:Calcium Signaling / Q000187:drug effects* / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects*; D003208:Concanavalin A / Q000494:pharmacology*; D016207:Cytokines / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D012502:Sapogenins / Q000737:chemistry / Q000494:pharmacology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D016207:Cytokines; D012502:Sapogenins; D003208:Concanavalin A; C061014:cycloastragenol
keywords: Ca2+; Cycloastragenol; anti-inflammation; lymphocytes; proliferation