Get access

Inhibitory effects of bromelain, a cysteine protease derived from pineapple stem (Ananas comosus), on intestinal motility in mice


Address for Correspondence
Dr Francesca Borrelli and Angelo A. Izzo, Department of Experimental Pharmacology, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy.
Tel: +39 081 678665; fax: +39 081 678403; e-mail:;


Background  Bromelain (BR) is a cysteine protease with inhibitory effects on intestinal secretion and inflammation. However, its effects on intestinal motility are largely unexplored. Thus, we investigated the effect of this plant-derived compound on intestinal contractility and transit in mice.

Methods  Contractility in vitro was evaluated by stimulating the mouse isolated ileum, in an organ bath, with acetylcholine, barium chloride, or electrical field stimulation. Motility in vivo was measured by evaluating the distribution of an orally administered fluorescent marker along the small intestine. Transit was also evaluated in pathophysiologic states induced by the pro-inflammatory compound croton oil or by the diabetogenic agent streptozotocin.

Key Results  Bromelain inhibited the contractions induced by different spasmogenic compounds in the mouse ileum with similar potency. The antispasmodic effect was reduced or counteracted by the proteolytic enzyme inhibitor, gabexate (15 × 10−6 mol L−1), protease-activated receptor-2 (PAR-2) antagonist, N1-3-methylbutyryl-N4-6-aminohexanoyl-piperazine (10−4mol L−1), phospholipase C (PLC) inhibitor, neomycin (3 × 10−3 mol L−1), and phosphodiesterase 4 (PDE4) inhibitor, rolipram (10−6 mol L−1). In vivo, BR preferentially inhibited motility in pathophysiologic states in a PAR-2-antagonist-sensitive manner.

Conclusions & Inferences  Our data suggest that BR inhibits intestinal motility – preferentially in pathophysiologic conditions – with a mechanism possibly involving membrane PAR-2 and PLC and PDE4 as intracellular signals. Bromelain could be a lead compound for the development of new drugs, able to normalize the intestinal motility in inflammation and diabetes.