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Significantly reduced lymphadenopathy, salivary gland infiltrates and proteinuria in MRL-lpr/lpr mice treated with ultrasoluble curcumin/turmeric: increased survival with curcumin treatment
  1. Biji T Kurien1,2,3,
  2. Valerie M Harris1,2,
  3. Syed M S Quadri1,2,
  4. Patricia Coutinho-de Souza2,
  5. Joshua Cavett1,2,
  6. Amanda Moyer1,
  7. Bilal Ittiq1,
  8. Angela Metcalf2,
  9. Husayn F Ramji4,5,
  10. Dat Truong4,
  11. Ramesh Kumar2,
  12. Kristi A Koelsch1,2,3,
  13. Mike Centola6,
  14. Adam Payne6,
  15. Debashish Danda7 and
  16. R Hal Scofield1,2,3
  1. 1Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
  2. 2Oklahoma Medical Research Foundation, Arthritis & Clinical Immunology Program, Oklahoma City, Oklahoma, USA
  3. 3Department Veterans Affairs Medical Center, Oklahoma City, Oklahoma, USA
  4. 4Oklahoma School of Science and Mathematics, Oklahoma City, Oklahoma, USA
  5. 5University of Oklahoma, Norman, Oklahoma, USA
  6. 6Haus Bioceuticals, Oklahoma City, Oklahoma, USA
  7. 7Christian Medical College, Vellore, Tamil Nadu, India
  1. Correspondence to Dr R Hal Scofield; hal-scofield{at}omrf.ouhsc.edu

Abstract

Objectives 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.

  • Autoantibodies
  • Autoimmunity
  • Sjøgren's Syndrome
  • Systemic Lupus Erythematosus
  • Treatment

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