Background/Purpose:

Commercial curcumin (CU), derived from food spice turmeric, has been widely studied as a potential therapeutic for a variety of oncological and inflammatory conditions. Commercial CU has been found to be safe in very high doses in clinical trials. Turmeric (TU) has been shown to ameliorate human refractory lupus nephritis. Lack of solubility and bioavailability has hindered CU’s therapeutic efficacy in human diseases. Previous studies have used CU solubilized in organic solvents or as CU powder supplemented in animal feed. We have solubilized CU with heat/pressure in water, obtaining up to 36-fold increase in solubility. We hypothesized that this ultrasoluble CU, as well as ultrasoluble TU will ameliorate systemic lupus erythematosus (SLE) and Sjogren’s Syndrome (SS)-like disease in MRL-lpr/lprmice, a well-studied animal model for both SLE and SS.

Methods:

Eighteen female MRL-MpJ (6-week old) and 18 female MRL-lpr/lpr  (6-week) mice were used. Female MRL-lpr mice develop SLE-like disease at the 10^th week and die at an average age of 17 weeks.  MRL-MpJ mice, used as control, develop SLE-like disease around 47 weeks and typically die at 73 weeks). Six mice of each strain received autoclaved water (lpr-water or MpJ-water group), water with ultrasoluble CU (lpr-CU or MpJ-CU group) or water with ultrasoluble TU (lpr-TU or MpJ-TU group) in water bottle.

Results:

By 14 weeks of age, 4/6 lpr-water group developed severe SLE-like disease with lymphadenopathy (in 5/6 mice), urinary cell casts and proteinuria. lpr-CU and lpr-TU mice had significantly reduced proteinuria, lymphadenopathy and no urinary cell casts. Sera (1:80 dilution, bleed 3) from 6/6 lpr-water group were positive for ANA, weakly positive in lpr-CU and negative in lpr-TU mice. Anti-dsDNA was positive by week 8 in lpr-water and lpr-CU, but not in lpr-TU mice. Significant levels of anti-RNP and anti-Sm autoantibodies developed by 8th week in lpr-water group, but not in lpr-CU and lpr-TU groups (these groups developed antibodies only by 10^th week). 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 SLE-like illness.  CU or TU treatment inhibited lymphadenopathy significantly compared to water treated mice (p=0.03 and p=0.02 respectively). Average lymph node weights were 248±1147, 99±330 and 49±67.49 mg respectively for lpr-water, lpr-CU and lpr-TU groups. TUNEL assay showed that lymphocytes in lymph nodes of TU and CU treated mice underwent apoptosis. Salivary gland histopathology studies show significantly reduced cellular infiltration in lpr-CU and lpr-TU groups, compared to lpr-water group, while there was a trend towards reduced kidney damage in lpr-CU and lpr-TU groups. Severe tail skin lesions occurred in lpr-water group (2 mice) and not in the lpr-CU and lpr-TU groups (week 24). Surprisingly, as seen with MRL-lpr mice, MpJ-water group developed autoantibodies by 8^th bleed (but at levels lower than lpr-water group).  MpJ-CU and MpJ-TU groups did not develop autoantibodies at this time, as observed in lpr-CU and lpr-TU mice. 

Conclusion:

Ultrasoluble CU/TU could prove useful as a therapeutic intervention in SLE and SS.

« Back to 2015 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/significantly-reduced-lymphadenopathy-salivary-gland-infiltrates-and-proteinuria-in-mrl-lprlpr-mice-treated-with-ultrasoluble-curcuminturmeric-increased-survival-with-curcumin-treatment/