Background Curcumin is the bioactive component of turmeric and has been used as a nutraceutical for centuries in Eastern medicine to suppress inflammation. Although many molecular targets have been identified in vitro, the inability to successfully translate curcumin clinically results from inadaquete bioavailability. Specifically, curcumin is not absorbed well in the intestinal tract due to its limited solubility and is metabolized rapidly. A pharmacological research team at Ohio State recently developed a novel formulation of nano-emulsified curcumin (NEC), which was shown to enhance bioavailability by 10.5-fold. Using this compound, our laboratory demonstrated that orally administered NEC suppresses inflammatory responses by inhibiting macrophage infiltration using several models of acute inflammation. Currently, orally administered NEC is being evaluated in a human clinical trial at Ohio State investigating inflammation associated with carcinogenesis in clinically obese patients with breast cancer.
Objectives To determine the therapeutic potential of NEC in the treatment of chronic inflammation, NEC was supplied to drinking water in an animal model of lupus nephritis.
Methods NZM2410 mice spontaneously develop severe glomerulonephritis at 22-40 weeks of age and are commonly used as an animal model of lupus nephritis. Mice were supplied approximately 40 mg/kg/day NEC in their water bottles ad libitum beginning at 18 weeks of age. Overall health was assessed weekly by weight measurements and kidney function was gauged by weekly blood urea nitrogen (BUN) testing from serum isolated following submandibular bleeding. Endpoint removal criteria was defined by a threshold of 20% weight loss and a BUN level reaching above 50 mg/dL.
Results Increased BUN levels positively correlated with the loss of weight in each mouse during disease progression. While only 62% of the mice in the control group had maintained BUN levels under 50 mg/dL and not lost more than 20% body weight at the 40 week time point, none of the mice receiving NEC met the increased BUN level or weight loss criteria throughout the duration of the study.
Conclusions Daily intake of NEC can mitigate the pathology associated with glomerulonephritis in this model, which suggests that NEC does indeed have therapeutic potential in treating the chronic inflammation associated with lupus nephritis as well as other autoimmune diseases. Ongoing work on this project will include proinflammatory cytokine analysis and immunohistochemical evaluation of glomerular infiltrates.
Young, N.A., et al., Oral Administration of Nano-Emulsion Curcumin in Mice Suppresses Inflammatory-Induced NFkappaB Signaling and Macrophage Migration. PLoS One, 2014. 9(11): p. e111559.
Acknowledgements Funding for this work was provided through the Wexner Medical Center at The Ohio StateUniversity.
Disclosure of Interest None declared