Gran B, Tabibzadeh N, Martin A, Ventura E S, Ware J H, Zhang G X, Parr J L, Kennedy A R, Rostami A M
Division of Clinical Neurology, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, UK.
Mult Scler. 2006 Dec;12(6):688-97. doi: 10.1177/1352458506070769.
Available treatments for multiple sclerosis (MS) require frequent injections and have significant side effects. Proteases generated during inflammation are involved in the induction of tissue damage during inflammatory demyelination in the central nervous system (CNS). The Bowman-Birk Inhibitor (BBI), a soy-derived protease inhibitor with anti-carcinogenic and anti-inflammatory properties, has been shown to be well tolerated in clinical trials for pre-cancerous conditions, such as oral leukoplakia and the inflammatory disease, ulcerative colitis. We hypothesized that BBI may modulate experimental autoimmune encephalomyelitis (EAE), an animal model of MS. The BBI concentrate (BBIC), a soybean extract enriched in BBI, was administered to myelin basic protein (MBP)-immunized Lewis rats by gastric gavage in different treatment regimens, during the induction or the effector phase of disease. BBIC significantly delayed disease onset and suppressed disease severity, clinically and pathologically, in all treatment protocols. Both in vitro and ex vivo, BBIC inhibited MBP-specific proliferation of lymph node cells. BBIC reduced the activity of matrix metalloproteinase (MMP)-2 and -9 in spleen cell supernatants and was detected in the CNS of treated rats. BBIC suppresses EAE, it can be administered orally, and it is safe and relatively inexpensive. It may have a therapeutic role in patients with MS.
目前用于治疗多发性硬化症（MS）的方法需要频繁注射且有显著的副作用。炎症过程中产生的蛋白酶参与中枢神经系统（CNS）炎症性脱髓鞘期间的组织损伤诱导。鲍曼-伯克抑制剂（BBI）是一种源自大豆的蛋白酶抑制剂，具有抗癌和抗炎特性，在针对癌前病症（如口腔白斑病）和炎症性疾病溃疡性结肠炎的临床试验中已显示出良好的耐受性。我们推测BBI可能调节实验性自身免疫性脑脊髓炎（EAE），一种MS的动物模型。在疾病的诱导期或效应期，以不同的治疗方案通过胃管向用髓鞘碱性蛋白（MBP）免疫的Lewis大鼠施用富含BBI的大豆提取物BBI浓缩物（BBIC）。在所有治疗方案中，BBIC在临床和病理上均显著延迟疾病发作并抑制疾病严重程度。在体外和离体实验中，BBIC均抑制淋巴结细胞的MBP特异性增殖。BBIC降低了脾细胞上清液中基质金属蛋白酶（MMP）-2和-9的活性，并且在接受治疗的大鼠的CNS中被检测到。BBIC可抑制EAE，可口服给药，且安全且相对便宜。它可能对MS患者具有治疗作用。
