Detection of Bowman-Birk Inhibitor and Anti-Bowman-Birk Inhibitor Antibodies in Sera of Humans and Animals Treated With Bowman-Birk Inhibitor Concentrate

Abstract

The Bowman-Birk inhibitor (BBI) is a soybean-derived serine protease inhibitor with anticarcinogenic activities. BBI, in the form of BBI concentrate (BBIC), is currently being evaluated in clinical trials as a human cancer-preventive agent. In the present study, an enzyme-linked immunosorbent assay was used to measure BBI concentrations in serum samples collected from human subjects and animals treated with BBIC. The results demonstrate that the serum BBI concentration was higher than the baseline level for the patients after treatment with BBIC at 100-800 chymotrypsin-inhibitor units/day for 0.5, 1, 2, 4, and 6 mo. The increase in serum BBI concentration was also observed in dogs treated with BBIC at 100-1,000 mg/kg/day for 52 wk, and the increase was dose dependent. The results also indicate that anti-BBI antibodies were present in animals and the serum levels of anti-BBI antibodies increased significantly in mice treated with BBIC at 100-1,000 mg/kg/day for 15 and 26 wk. The increase in the serum level of anti-BBI antibodies in dogs treated with BBIC was not statistically significant, and no increase in the serum level of anti-BBI antibodies was observed in human subjects after BBIC treatment. These results suggest that orally ingested BBI is absorbed by human subjects and animals and that some animals develop antibodies to BBI in response to treatment with BBIC.

Structural aspects of legume proteins and nutraceutical properties

“…Maintenance of the native conformation of the inhibitory domain after processing and during gastrointestinal digestion has been hypothesized to be essential for protective antiproliferative effect of BBI towards colon cancer. These inhibitors have been recovered in an intact form in the liver, kidney and lung after ingestion (Wan, Serota, Ware, Crowell, & Kennedy, 2002). However, the mechanism responsible for their bioactivity is still under debate.…”

Cloning, yeast expression, purification and biological activity of a truncated form of the soybean 7S globulin α′ subunit involved in Hep G2 cell cholesterol homeostasis

“…However, an increasing number of animal and plant (poly)peptides are being claimed to play relevant regulatory functions, often attributed to anti-oxidant, antiproliferative and anti-inflammatory effects [17]. As far as soybean is concerned, experimental evidence clearly indicates the possibility that peptides and even small compact proteins, such as the BowmanBirk inhibitor, may be adsorbed [18], thus eliciting a number of effects, including anticancer, anti-inflammatory, radioprotective ones [19]. Other peptides have been shown to exert hypotensive effects [20].…”

Role of pulses in nutraceuticals

“…Animal models have clearly shown that these inhibitors are absorbed after oral administration and are found in liver, kidney and lung in an intact form (Wan et al, 2002).…”

“…Bowman-Birk inhibitors have been found in an intact form in several organs after ingestion (Wan et al, 2002), but the mechanism responsible for their bioactivity needs to be further elucidated. Intrinsic structural features, such as stabilization by disulfide bridges and presence of hydrophobic patches, have long been claimed to be responsible for low digestibility of seed storage proteins from both pulses and cereals (Semino et al, 1985;Nielsen et al, 1988;Deshpande and Damodaran, 1989;Shewry and Halford, 2002).…”