Bowman-Birk Inhibitor Concentrate: A Novel Therapeutic Agent for Patients with Active Ulcerative Colitis

Abstract

Bowman-Birk inhibitor concentrate (BBIC), a soy extract with high protease inhibitor activity, is efficacious in the treatment of colitis in mice and has been used in numerous clinical trials. A randomized, double blind, placebo-controlled trial was performed to investigate the safety and possible benefits of BBIC in patients with active ulcerative colitis. The Sutherland Disease Activity Index (SDAI) was used to assess disease activity, response (Index decrease > or = 3), and remission (Index < or = 1 with no rectal bleeding) in patients receiving 12 weeks of therapy. The Index scores of patients receiving BBIC decreased more than those of the patients receiving placebo (P = 0.067). Beneficial trends were observed in the rates of remission (P = 0.082) and clinical response (P = 0.22). No severe adverse events were observed. This trial suggests a potential benefit over placebo for both achieving clinical response and induction of remission in patients with active ulcerative colitis without apparent toxicity.

Bowman-Birk inhibitors in lentil: Heterologous expression, functional characterisation and anti-proliferative properties in human colon cancer cells

“…On the other hand, many reports highlight the involvement of BBI proteins, in particular the chymotrypsin inhibitor site, to prevent or suppress carcinogen-induced transformation in vitro and carcinogenesis in animal model systems (Chen, Huang, Lin-Shiau, & Lin, 2005;Clemente & Domoney, 2006;Clemente, Gee, Johnson, Mackenzie, & Domoney, 2005;Kennedy, 1998Kennedy, , 2008Maki, Paterson, & Kennedy, 1994). In this sense, soybean extracts enriched in BBI have attained investigational new drug status by the US Food and Drug Administration, and trials to evaluate BBI as an anti-carcinogenic agent in human populations have been ongoing for over a decade with encouraging clinical efficacy and minimal toxicity (Armstrong et al, 2000;Kennedy, 2005;Lichtenstein, Deren, Katz, Kennedy, & Ware, 2002;Malkowicz et al, 2001). In this context, the anti-inflammatory properties of soybean BBI, likely via inhibition of target proteases, such as leukocyte elastase, cathepsin G and mast cell chymase released from inflammation-mediating cells, have also been reported (Ware, Wan, Newberne, & Kennedy, 1999).…”

Molecular engineering of a small trypsin inhibitor based on the binding loop of horsegram seed Bowman-Birk inhibitor

“…This result suggests a potential application as a therapeutic agent for ulcerative colitis. BBIC is efficacious with high trypsin and chymotrypsin inhibitor activity without any apparent toxicity for both achieving clinical response and induction of remission in patient with active ulcerative colitis 20 . A leech derived tight binding tryptase inhibitor, (K i = 1.4 nM) of 46 amino acids differs from BBI in its size 45 .…”

“…BBIC was effectively used in the remission of active ulcerative colitis without any apparent toxicity in humans 20 . Mung bean BBI has been shown to inhibit the NS3 protease integral to the virus life cycle that causes Dengue hemorrhagic fever 21 .…”

Bowman-Birk Inhibitors from Legumes: Utilisation in Disease Prevention and Therapy

“…Given the lack of toxicity as well as the reported anti-inflammatory properties in animals, the potential for BBIC to benefit patients with ulcerative colitis has been evaluated. In a randomized double-blind placebo-controlled trial, a dose of 800 chymotrypsin inhibitor units (CIU) per day over a three-month treatment period was associated with a clinical response and induction of remission, as assessed by the Sutherland Disease Activity Index score [59], in patients with ulcerative colitis, without apparent toxicity [9]. Approximately 50 % of patients responded clinically and 36 % showed remission of disease.…”

“…In light of the Food and Drug Administration (FDA) approval for trials of Bowman-Birk inhibitors (BBI) concentrate (BBIC), a protein extract of soybean (Glycine max) enriched in BBI, as an 'Investigational New Drug', human trials have been completed in patients with benign prostatic hyperplasia [5], oral leukoplakia [6][7][8] and ulcerative colitis [9] (Table 1). Although, in most of these cases, the intrinsic ability of BBI to inhibit serine proteases has been related to beneficial health properties, the mechanisms of action and the identity of their therapeutic targets are largely unknown.…”