title: Significantly reduced lymphadenopathy, salivary gland infiltrates and proteinuria in MRL-lpr/lpr mice treated with ultrasoluble curcumin/turmeric: increased survival with curcumin treatment.
abstract: OBJECTIVE
  Commercial curcumin (CU), derived from food spice turmeric (TU), has been widely studied as a potential therapeutic for a variety of oncological and inflammatory conditions. Lack of solubility/bioavailability has hindered curcumin's therapeutic efficacy in human diseases. We have solubilised curcumin in water applying heat/pressure, obtaining up to 35-fold increase in solubility (ultrasoluble curcumin (UsC)). We hypothesised that UsC or ultrasoluble turmeric (UsT) will ameliorate systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS)-like disease in MRL-lpr/lpr mice.
  
  
  METHODS
  Eighteen female MRL-lpr/lpr (6 weeks old) and 18 female MRL-MpJ mice (6 weeks old) were used. Female MRL-lpr/lpr mice develop lupus-like disease at the 10th week and die at an average age of 17 weeks. MRL-MpJ mice develop lupus-like disease around 47 weeks and typically die at 73 weeks. Six mice of each strain received autoclaved water only (lpr-water or MpJ-water group), UsC (lpr-CU or MpJ-CU group) or UsT (lpr-TU or MpJ-TU group) in the water bottle.
  
  
  RESULTS
  UsC or UsT ameliorates SLE in the MRL-lpr/lpr mice by significantly reducing lymphoproliferation, proteinuria, lesions (tail) and autoantibodies. lpr-CU group had a 20% survival advantage over lpr-water group. However, lpr-TU group lived an average of 16 days shorter than lpr-water group due to complications unrelated to lupus-like illness. CU/TU treatment inhibited lymphadenopathy significantly compared with lpr-water group (p=0.03 and p=0.02, respectively) by induction of apoptosis. Average lymph node weights were 2606±1147, 742±331 and 385±68 mg, respectively, for lpr-water, lpr-CU and lpr-TU mice. Transferase dUTP nick end labelling assay showed that lymphocytes in lymph nodes of lpr-CU and lpr-TU mice underwent apoptosis. Significantly reduced cellular infiltration of the salivary glands in the lpr-TU group compared with the lpr-water group, and a trend towards reduced kidney damage was observed in the lpr-CU and lpr-TU groups.
  
  
  CONCLUSIONS
  These studies show that UsC/UsT could prove useful as a therapeutic intervention in SLE/SS.
authors.affiliation: Department of Medicine , University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma , USA ; Oklahoma Medical Research Foundation , Arthritis & Clinical Immunology Program , Oklahoma City, Oklahoma , USA ; Department Veterans Affairs Medical Center, Oklahoma City, Oklahoma, USA.
authors.forename: Biji T
authors.initials: BT
authors.lastname: Kurien
authors.affiliation: Department of Medicine , University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma , USA ; Oklahoma Medical Research Foundation , Arthritis & Clinical Immunology Program , Oklahoma City, Oklahoma , USA.
authors.forename: Valerie M
authors.initials: VM
authors.lastname: Harris
authors.affiliation: Department of Medicine , University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma , USA ; Oklahoma Medical Research Foundation , Arthritis & Clinical Immunology Program , Oklahoma City, Oklahoma , USA.
authors.forename: Syed M S
authors.initials: SM
authors.lastname: Quadri
authors.affiliation: Oklahoma Medical Research Foundation , Arthritis & Clinical Immunology Program , Oklahoma City, Oklahoma , USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Coutinho-de Souza
authors.affiliation: Department of Medicine , University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma , USA ; Oklahoma Medical Research Foundation , Arthritis & Clinical Immunology Program , Oklahoma City, Oklahoma , USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Cavett
authors.affiliation: Department of Medicine , University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma , USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Moyer
authors.affiliation: Department of Medicine , University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma , USA.
authors.forename: Bilal
authors.initials: B
authors.lastname: Ittiq
authors.affiliation: Oklahoma Medical Research Foundation , Arthritis & Clinical Immunology Program , Oklahoma City, Oklahoma , USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Metcalf
authors.affiliation: Oklahoma School of Science and Mathematics, Oklahoma City, Oklahoma, USA ; University of Oklahoma , Norman, Oklahoma , USA.
authors.forename: Husayn F
authors.initials: HF
authors.lastname: Ramji
authors.affiliation: Oklahoma School of Science and Mathematics, Oklahoma City, Oklahoma, USA.
authors.forename: Dat
authors.initials: D
authors.lastname: Truong
authors.affiliation: Oklahoma Medical Research Foundation , Arthritis & Clinical Immunology Program , Oklahoma City, Oklahoma , USA.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Department of Medicine , University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma , USA ; Oklahoma Medical Research Foundation , Arthritis & Clinical Immunology Program , Oklahoma City, Oklahoma , USA ; Department Veterans Affairs Medical Center, Oklahoma City, Oklahoma, USA.
authors.forename: Kristi A
authors.initials: KA
authors.lastname: Koelsch
authors.affiliation: Haus Bioceuticals , Oklahoma City, Oklahoma , USA.
authors.forename: Mike
authors.initials: M
authors.lastname: Centola
authors.affiliation: Haus Bioceuticals , Oklahoma City, Oklahoma , USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Payne
authors.affiliation: Christian Medical College , Vellore, Tamil Nadu , India.
authors.forename: Debashish
authors.initials: D
authors.lastname: Danda
authors.affiliation: Department of Medicine , University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma , USA ; Oklahoma Medical Research Foundation , Arthritis & Clinical Immunology Program , Oklahoma City, Oklahoma , USA ; Department Veterans Affairs Medical Center, Oklahoma City, Oklahoma, USA.
authors.forename: R Hal
authors.initials: RH
authors.lastname: Scofield
keywords: Autoantibodies; Autoimmunity; Sjøgren's Syndrome; Systemic Lupus Erythematosus; Treatment