The Anti-Arthritis Effect of Olive-Derived Maslinic Acid in Mice is Due to its Promotion of Tissue Formation and its Anti-Inflammatory Effects.

SCOPE: A previous study demonstrated that intake of olive pomace extract containing maslinic acid (MA), a triterpene, effectively prevents and alleviates arthritis in animals and humans. Here, the molecular mechanisms involved in the anti-arthritis effect of MA have been elucidated by determining gene expression changes induced by olive-derived MA intake in collagen antibody-induced arthritis (CAIA) mice. METHODS AND RESULTS: Mice are divided into the untreated (CT), CAIA (CA), and CAIA administered MA (CA + MA) groups. The CA + MA mice are fed MA at a daily dose of 200 mg kg-1 of body weight from day 1. CAIA is then induced on day 8 and evaluated on day 12. Arthritis symptoms are alleviated, and the gene expression of inflammatory cytokines is reduced in the CA + MA group compared with the CA group. A DNA microarray analysis of synovial membranes reveals that MA alters the expression levels of genes related to inflammation, including glucocorticoid responses, immune responses, and the extracellular matrix. CONCLUSIONS: The preventive effect of MA on arthritis is attributable to the promotion of tissue formation as well as suppression of inflammation in the synovium via inactivation of Toll-like receptor signaling and downregulation of leukotrienes through the glucocorticoid receptor. 10 arrays are included. All animal protocols were approved by the Ethical Committee of Nippon Flour Mills Co., Ltd (permission number: 2015-2). Five-week-old male DBA/1J mice were obtained from Japan SLC Inc. (Shizuoka, Japan) and housed under conventional conditions (24°C ± 1°C, 50% ± 10% relative humidity with a 12 h light/dark cycle). The mice were fed the AIN-93G diet, where fat is provided by corn instead of soy, and were provided ad libitum access to the diet and water for 24 h. After a week of acclimatization, the mice were divided into three groups: untreated (CT), CAIA (CA), and CAIA plus MA treatment (CA + MA). MA was suspended in corn oil and orally administered to CA + MA mice daily at a dose of 200 mg/kg of body weight. The other two groups were administrated corn oil instead of MA. CAIA was induced by intraperitoneal injection with 1 mg of a type II collagen mAb (Chondrex, Inc., Redmond, WA, USA) on day 8 and 0.025 mg of LPS (Chondrex) on day 11. Mice were sacrificed on day 12. Five mice selected from the CA and CA + MA groups respectively were used for DNA microarray analysis.