Yimam Mesfin, Brownell Lidia, Pantier Mandee, Jia Qi
Unigen Inc., Seattle, Washington, USA.
Pharmacognosy Res. 2013 Jul;5(3):139-45. doi: 10.4103/0974-8490.112406.
Rheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune disease. Long-term use of currently available therapies for RA produces adverse effects that limit dosage and duration; hence there is a need for safe and effective alternatives suitable for long term chronic use. UP446, a composition consisting primarily of baicalin from Scutellaria baicalensis Georgi (Family: Lamiaceae) and (+)-catechin from the heartwoods of Acacia catechu (Family: Mimosaceae), has been previously shown to reduce production of eicosanoids and leukotrienes through dual inhibition of cyclooxygenase (COX) and lipoxygenase (LOX) enzymes and to decreased mRNA and protein levels of the proinflammatory cytokines, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α.
To evaluate the likelihood of UP446 in moderating arthritis and its associated symptoms in an experimental animal model of RA.
A RA rat model was induced by injecting Freund's complete adjuvant into left and right hind paw and base of the tail. Animals were administered UP446 (50 mg/kg), ibuprofen (150 mg/kg mg/kg) or vehicle by oral gavage 30 min prior to arthritis induction and each day thereafter for 14 days.
Animals treated with UP446 showed 23.7, 31.9, 33.4, 29.3, and 33.1% reduction in pain sensitivity; 46.0, 36.7, 33.7, 34.8, and 33.4% reduction in ankle diameter on days 3, 5, 7, 9, and 13; respectively; compared to vehicle. Similarly paw edema was significantly reduced with an average of 30% for the first inflammatory reaction period (day 1-8) followed by 37.1 and 33.6% reduction on day 9 and 13.
These data indicate potential benefit of UP446 in alleviating symptoms of RA and support human clinical evaluation of this botanical composition in patients with RA.
类风湿性关节炎(RA)是一种慢性全身性炎症性自身免疫疾病。长期使用目前用于治疗RA的疗法会产生不良反应,限制了用药剂量和疗程;因此,需要有适合长期慢性使用的安全有效的替代药物。UP446是一种主要由黄芩(唇形科)中的黄芩苷和儿茶(豆科)心材中的(+)-儿茶素组成的组合物,先前已表明其通过双重抑制环氧化酶(COX)和脂氧合酶(LOX)来减少类花生酸和白三烯的生成,并降低促炎细胞因子白细胞介素(IL)-1β、IL-6和肿瘤坏死因子(TNF)-α的mRNA和蛋白质水平。
在RA实验动物模型中评估UP446缓解关节炎及其相关症状的可能性。
通过向左右后爪和尾基部注射弗氏完全佐剂诱导建立RA大鼠模型。在诱导关节炎前30分钟,通过口服灌胃给予动物UP446(50mg/kg)、布洛芬(150mg/kg)或赋形剂,此后每天给药,持续14天。
与赋形剂组相比,用UP446治疗的动物在第3、5、7、9和13天疼痛敏感性分别降低了23.7%、31.9%、33.4%、29.3%和33.1%;踝关节直径分别降低了46.0%、36.7%、33.7%、34.8%和33.4%。同样,爪部水肿也显著减轻,在第一个炎症反应期(第1 - 8天)平均减轻30%,在第9天和第13天分别减轻37.1%和33.6%。
这些数据表明UP446在减轻RA症状方面具有潜在益处,并支持对该植物组合物在RA患者中进行人体临床评估。