The effect of sanguinarine on human peripheral blood neutrophil viability and functions

Abstract

Human polymorphonuclear cell (PMN) viability, morphology, adherence, chemotaxis, oxidative metabolism, degranulation and phagocytosis were evaluated following treatment with sanguinarine (SANG). SANG was noncytotoxic to PMNs at all concentrations tested (0.31-200 microM). SANG entered the PMNs rapidly without altering the membrane fluidity and localized in the nuclear matrix. SANG (1.56-6.21 microM) inhibited chemotaxis, chemokinesis and adhesion in a dose-dependent manner, with a complete inhibition at 6.2 microM concentration. Concentrations of SANG up to 1.56 microM did not affect PMN oxidative burst; however, higher concentrations were found to inhibit basal as well as PMA-induced superoxide anion generation. The effect of SANG was time- and dose-dependent, and could be reversed if the PMNs were exposed to 12.5 microM or lower concentrations of SANG for less than 5 min. Autologous serum increased the tolerance of PMNs to SANG. Exogenous Ca2+ or Mg2+ did not alter the SANG-mediated inhibition of PMN functions. Treatment of PMNs with 3.12 microM or higher concentrations of SANG also resulted in inhibition of PMN degranulation and phagocytosis. The results suggest that SANG-mediated inhibition of PMN functions, without cytolysis or resultant release of inflammatory mediators, may have clinical implications.

Studies with sanguinarine like alkaloids as feed additive in broiler diets

“…In parallel, it is possible to speculate that sanguinarine activity as an anti-inflammatory substance may play a role in the partial improvements obtained in the broilers of Study 1. For instance, antiinflammatory activity has been largely demonstrated with various QBA´s, including sanguinarine (Lenfeld et al, 1981;Agarwal et al, 1991). In pig intestines, this activity is expected to be caused mostly by contact, since the bulk of these alkaloids are excreted in the feces, and only a very small proportion is absorbed (Kosina et al, 2004).…”

“…Natural compounds extracted from plants, such as quaternary benzo [c]phenanthridine alkaloids (QBA) sanguinarine and chelerythrine, are known to have antimicrobial (Eisenberg et al, 1991;Mewton et al, 2002;Colombo & Bosisio, 1996), anti-inflammatory (Lenfeld et al, 1981;Tanaka et al, 1993), and immunomodulatory (Agarwal et al, 1991;Chaturvedi et al, 1997) effects. Sanguinarine has been incorporated into swine, bovine, and poultry diets to reduce amino acid degradation, increase feed intake, and promote growth (Tschirner, 2004;Susenberth & Wolffran, 2003).…”

Sanguinarine (Pseudochelerythrine) Is a Potent Inhibitor of NF-κB Activation, IκBα Phosphorylation, and Degradation

“…In human peripheral blood neutrophils, sanguinarine has been shown to inhibit PMA-induced oxidative bursts and generation of superoxide anions (5,17). Also, sanguinarine has been shown to have antioxidative activity against spontaneous oxidation (40).…”

“…This benzophenanthridine alkaloid is a structural homologue of chelerythrine, which is a potent inhibitor of protein kinase C (2). Sanguinarine has been shown to display antitumor (3) and antiinflammatory properties in animals (4) and to inhibit neutrophil function, including degranulation and phagocytosis in vitro (5). It is also a potent inhibitor of Na-K-dependent ATPase (6)(7)(8) and cholinesterase (9).…”

“…Sanguinarine exhibits antimicrobial, anti-inflammatory, and antioxidant properties (5,(11)(12)(13)(14)(15)(16)(17). Since anti-inflammatory compounds like aspirin and glucocorticoid have been shown to inhibit activation of NF-B (18 -20), we investigated the effect of sanguinarine on activation of NF-B induced by a wide variety of agents including TNF.…”