Murakami Satoshi, Tasaka Yuichi, Takatori Shingo, Tanaka Akihiro, Kawasaki Hiromu, Araki Hiroaki
Division of Pharmacy, Ehime University Hospital.
Department of Clinical Pharmacy, College of Pharmaceutical Sciences, Matsuyama University.
Biol Pharm Bull. 2018;41(6):864-868. doi: 10.1248/bpb.b17-00878.
Ulcerative colitis (UC) is a refractory disease that causes chronic inflammation or ulceration in the mucosa of the large intestine with multiple relapses. Although several drugs, including 5-aminosalicylic acid, steroids, immunosuppressants, and infliximab, are used for UC therapy, patients suffer from side effects of these drugs, and a new safer therapeutic agent is desired. Eucommia ulmoides OLIV. leaf extract (ELE) has an anti-inflammatory effect. Therefore, we examined the effect of ELE on UC using a chronic dextran sulfate sodium (DSS)-induced colitis model in mice. Chronic DSS-induced colitis was triggered by alternately repeating 5 days' DSS and 7 days' water administration in mice for 29 d. The severity of DSS-induced colitis was evaluated by daily body weight and bloody stool score, and colon length and myeloperoxidase (MPO) activity in colon tissue on day 29. ELE (3 or 9%) was administered in combination by feeding for 29 d, and the effect on colitis was evaluated. The mice given DSS exhibited chronic colitis symptoms with body weight loss, increased bloody stool score and MPO activity, and shortened colon length. Administration of 3 or 9% ELE suppressed the body weight loss, bloody stool score, colon shortening, and MPO activity in a dose-dependent manner. Histological analysis showed that the ELE-treated mice had less damages and leukocyte infiltration in the mucosal layer of the large intestine compared to DSS alone group. These results suggested that ELE has the potential to prevent the development of DSS-induced colitis and a therapeutic effect on UC in a safe manner.
溃疡性结肠炎（UC）是一种难治性疾病，可导致大肠黏膜慢性炎症或溃疡，并多次复发。尽管包括5-氨基水杨酸、类固醇、免疫抑制剂和英夫利昔单抗在内的几种药物用于UC治疗，但患者会遭受这些药物的副作用，因此需要一种新的更安全的治疗药物。杜仲叶提取物（ELE）具有抗炎作用。因此，我们使用慢性葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎模型研究了ELE对UC的影响。慢性DSS诱导的结肠炎是通过在小鼠中交替重复给予5天DSS和7天水，持续29天来引发的。通过每日体重和血便评分，以及第29天结肠组织的结肠长度和髓过氧化物酶（MPO）活性来评估DSS诱导的结肠炎的严重程度。通过喂食给予ELE（3%或9%）联合用药29天，并评估其对结肠炎的影响。给予DSS的小鼠表现出慢性结肠炎症状，体重减轻、血便评分增加、MPO活性升高以及结肠长度缩短。给予3%或9%的ELE以剂量依赖的方式抑制了体重减轻、血便评分、结肠缩短和MPO活性。组织学分析表明，与单独使用DSS的组相比，ELE治疗的小鼠大肠黏膜层的损伤和白细胞浸润较少。这些结果表明，ELE有可能预防DSS诱导的结肠炎的发展，并以安全的方式对UC产生治疗作用。
