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