(OR32-01-24) Dietary 23-Hydroxy Ursolic Acid Reduces the Severity and Incidence of Acute Experimental Autoimmune Encephalomyelitis (EAE) in a Murine Model of Multiple Sclerosis

Objectives: 23-Hydroxy ursolic acid (23-OH UA) is a potent atheroprotective and anti-obesogenic phytochemical, with anti-inflammatory and inflammation resolving properties. In this study, we examined whether dietary 23-OH UA protects mice against the acute onset and progression of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS).

Methods: Female C57BL/6 mice were fed either a defined low-calorie maintenance diet (MD) or an MD supplemented with 0.2 % wgt/wgt 23-OH UA for 5 weeks prior to actively inducing EAE and during the 30 days post-immunization. After 5 weeks (day 0) on MD or MD supplemented with 23-OH UA, EAE was actively induced by subcutaneous injection with 100 mg of mouse MOG_35-55 emulsified in 50 µL of complete Freund's adjuvant (CFA) containing 5 mg/ml Mycobacterium tuberculosis H37Ra. 200 ng of Bordetella pertussis toxin was administered intraperitoneally (i.p.) on day 0 and day 2 after immunization. Mice were weighed and clinically scored daily for 30 days.On day 30, splenocytes were isolated and plated on ELISPOT plates pre-coated with anti-IL-17 or anti-IFN-γ antibodies, restimulated with MOG_35-55 and subsequently stained and analyzed using a Series 2 ImmunoSpot analyzer.

Results: We observed no difference in the onset of EAE between both groups of mice, but ataxia and EAE disease severity were suppressed by 52% and 48%, respectively, and disease incidence was reduced by over 49% in mice that received 23-OH UA in their diet. Furthermore, disease-associated weight loss was strikingly ameliorated in 23-OH UA-fed mice. ELISPOT analysis showed no significant differences in frequencies of T cells producing IL-17 or IFN-γ between 23-OH UA fed mice and control mice, suggesting that 23-OH UA does not appear to regulate peripheral T-cell responses. 

Conclusions: Our findings demonstrate that dietary 23-OH UA may represent an effective oral adjunct therapy for the prevention and treatment of relapsing-remitting MS.

Funding Sources: This project was supported by institutional support to R.A. and with funding from grant NS117742 from the National Institute of Health (T.G.F.), and support from the Jesse H. & Mary Jones Gibbs Endowed Chair (T.G.F).