eupatilin and Arthritis--Rheumatoid

Acid suppressants such as histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) are effective in preventing gastrointestinal (GI) bleeding in nonsteroidal anti-inflammatory drugs (NSAIDs) users. Despite widespread acid suppressant use, there remain concerns about several potential risks of long-term use. Therefore, we investigated whether gastroprotective agents (GPAs) other than acid suppression therapy are effective in preventing NSAID-related GI injury. To this end, we studied 9,133 patients with osteoarthritis or rheumatoid arthritis who used NSAIDs for ≥1 month. A decrease of 2 g/dL or more in the hemoglobin level was considered a GI injury indicator. The GPAs included acid suppressants and other mucoprotective agents. Acid suppressants included PPIs and H2RAs. Other mucoprotective agents included misoprostol, rebamipide, and eupatilin. During a median follow-up period of 27 (range, 4.3-51.3) weeks, occult GI bleeding occurred in 1,191 (13%) patients. A comparison of patients who used GPAs concomitantly with that of nonusers in a multivariable analysis revealed the hazard ratios (HRs; 95% confidence intervals [CIs]) for occult GI bleeding were 0.30 (0.20-0.44), 0.35 (0.29-0.43), 0.47 (0.23-0.95), 0.43 (0.35-0.51), and 0.98 (0.86-1.12) for PPIs, H2RAs, misoprostol, rebamipide, and eupatilin, respectively. Compared to PPI co-treatment, H2RA, misoprostol, rebamipide, and eupatilin co-treatments were associated with occult GI bleeding HRs (95% CIs) of 1.19 (0.79-1.79), 1.58 (0.72-3.46), 1.44 (0.96-2.16), and 3.25 (2.21-4.77), respectively. Our findings suggest that mucoprotective agents, such as rebamipide and misoprostol, as well as acid suppressants, are effective in reducing the risk for GI injury in NSAID users.

Topics: Adult; Aged; Alanine; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Cohort Studies; Female; Flavonoids; Gastrointestinal Agents; Gastrointestinal Hemorrhage; Hemoglobins; Histamine H2 Antagonists; Humans; Male; Middle Aged; Misoprostol; Osteoarthritis; Proton Pump Inhibitors; Quinolones; Treatment Outcome

Eupatilin is the main active component of DA-9601, an extract from Artemisia. Recently, eupatilin was reported to have anti-inflammatory properties. We investigated the anti-arthritic effect of eupatilin in a murine arthritis model and human rheumatoid synoviocytes. DA-9601 was injected into collagen-induced arthritis (CIA) mice. Arthritis score was regularly evaluated. Mouse monocytes were differentiated into osteoclasts when eupatilin was added simultaneously. Osteoclasts were stained with tartrate-resistant acid phosphatase and then manually counted. Rheumatoid synoviocytes were stimulated with TNF-α and then treated with eupatilin, and the levels of IL-6 and IL-1β mRNA expression in synoviocytes were measured by RT-PCR. Intraperitoneal injection of DA-9601 reduced arthritis scores in CIA mice. TNF-α treatment of synoviocytes increased the expression of IL-6 and IL-1β mRNAs, which was inhibited by eupatilin. Eupatilin decreased the number of osteoclasts in a concentration dependent manner. These findings, showing that eupatilin and DA-9601 inhibited the expression of inflammatory cytokines and the differentiation of osteoclasts, suggest that eupatilin and DA-9601 is a candidate anti-inflammatory agent.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Arthritis, Rheumatoid; Cell Differentiation; Cells, Cultured; Collagen Type II; Cytokines; Disease Models, Animal; Drugs, Chinese Herbal; Female; Flavonoids; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Lymph Nodes; Mice; Mice, Inbred DBA; Monocytes; Osteoclasts; Plant Extracts; RNA, Messenger; Synovial Membrane; T-Lymphocytes, Regulatory; Tumor Necrosis Factor-alpha