title: Antroquinonol differentially modulates T cell activity and reduces interleukin-18 production, but enhances Nrf2 activation, in murine accelerated severe lupus nephritis.
abstract: OBJECTIVE
  Accelerated severe lupus nephritis (ASLN), with an acute onset of severe clinical manifestations and histopathologic renal lesions, may represent transformation of mild LN to a severe form of glomerulonephritis. Abnormal activation of T and B cells and/or oxidative stress may play a major role in the pathogenesis of ASLN. This study tested the hypothesis that antroquinonol, a purified compound and major effective component of Antrodia camphorata with antiinflammatory and antioxidant activities, might prevent the transformation of mild LN into higher-grade (severe) nephritis in a murine lupus model.
  
  
  METHODS
  Experimental ASLN was induced in (NZB×NZW)F1 mice by twice weekly intraperitoneal injections of Salmonella-type lipopolysaccharide (LPS). Starting 2 days after the first dose of LPS, mice were treated daily with antroquinonol, administered by gavage, for different durations up to 5 weeks.
  
  
  RESULTS
  Antroquinonol administration significantly ameliorated the proteinuria, hematuria, impairment of renal function, and development of severe renal lesions, especially cellular crescent formation, neutrophil infiltration, fibrinoid necrosis, and T cell proliferation in the glomerulus, as well as periglomerular interstitial inflammation. Mechanistic analyses revealed that antroquinonol 1) inhibited T cell activation/proliferation, but enhanced Treg cell suppression and reduced renal production of interleukin-18 (IL-18); 2) inhibited production of reactive oxygen species and nitric oxide, but increased activation of Nrf2 in the kidney; and 3) suppressed renal inflammation via blocking of NF-κB activation.
  
  
  CONCLUSIONS
  Antroquinonol may have therapeutic potential for the early treatment of ASLN via its differential regulation of T cell function and lowering of IL-18 production, but also via the promotion of Nrf2 activation.
authors: Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, and Development Center for Biotechnology, Taipei, Taiwan, Republic of China.
authors: Pei-Yi
authors: PY
authors: Tsai
authors: Shuk-Man
authors: SM
authors: Ka
authors: Jia-Ming
authors: JM
authors: Chang
authors: Jenn-Haung
authors: JH
authors: Lai
authors: Ming-Shen
authors: MS
authors: Dai
authors: Huei-Lin
authors: HL
authors: Jheng
authors: Mao-Tien
authors: MT
authors: Kuo
authors: Peini
authors: P
authors: Chen
authors: Ann
authors: A
authors: Chen
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D018450:Disease Progression; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D007074:Immunoglobulin G / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008814:Mice, Inbred NZB; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis*; D010936:Plant Extracts / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D004365:Drugs, Chinese Herbal; D007074:Immunoglobulin G; D020382:Interleukin-18; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D010936:Plant Extracts; D014451:Ubiquinone; C545357:antroquinonol