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

F Borrelli, R Capasso, B Severino, F Fiorino, G Aviello, G De Rosa, M Mazzella, B Romano, F Capasso, I Fasolino, A A Izzo

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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, N(1) -3-methylbutyryl-N(4) -6-aminohexanoyl-piperazine (10(-4) mol 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.

Original languageEnglish
Pages (from-to)745-e331
JournalNeurogastroenterology and Motility
Volume23
Issue number8
Early online date21 Jun 2011
DOIs
Publication statusPublished - Aug 2011

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Bromelains
Ananas
Gastrointestinal Motility
Cysteine Proteases
PAR-2 Receptor
Type C Phospholipases
Ileum
Gabexate
Croton Oil
Type 4 Cyclic Nucleotide Phosphodiesterase
Phosphodiesterase 4 Inhibitors
Rolipram
Intestinal Secretions
Inflammation
Parasympatholytics
Neomycin
Phytochemicals
Enzyme Inhibitors
Streptozocin
Baths

Keywords

  • Acetylcholine
  • Ananas
  • Animals
  • Barium Compounds
  • Bromelains
  • Caco-2 Cells
  • Chlorides
  • Cholinergic Agonists
  • Croton Oil
  • Diabetes Mellitus, Experimental
  • Electric Stimulation
  • Enzyme Inhibitors
  • Gastrointestinal Motility
  • Gastrointestinal Transit
  • Humans
  • Ileitis
  • Male
  • Mice
  • Muscle Contraction
  • Peptides
  • Receptor, PAR-1
  • Receptor, PAR-2
  • Journal Article

Cite this

Inhibitory effects of bromelain, a cysteine protease derived from pineapple stem (Ananas comosus), on intestinal motility in mice. / Borrelli, F; Capasso, R; Severino, B; Fiorino, F; Aviello, G; De Rosa, G; Mazzella, M; Romano, B; Capasso, F; Fasolino, I; Izzo, A A.

In: Neurogastroenterology and Motility, Vol. 23, No. 8, 08.2011, p. 745-e331.

Research output: Contribution to journalArticle

Borrelli, F, Capasso, R, Severino, B, Fiorino, F, Aviello, G, De Rosa, G, Mazzella, M, Romano, B, Capasso, F, Fasolino, I & Izzo, AA 2011, 'Inhibitory effects of bromelain, a cysteine protease derived from pineapple stem (Ananas comosus), on intestinal motility in mice', Neurogastroenterology and Motility, vol. 23, no. 8, pp. 745-e331. https://doi.org/10.1111/j.1365-2982.2011.01735.x
Borrelli, F ; Capasso, R ; Severino, B ; Fiorino, F ; Aviello, G ; De Rosa, G ; Mazzella, M ; Romano, B ; Capasso, F ; Fasolino, I ; Izzo, A A. / Inhibitory effects of bromelain, a cysteine protease derived from pineapple stem (Ananas comosus), on intestinal motility in mice. In: Neurogastroenterology and Motility. 2011 ; Vol. 23, No. 8. pp. 745-e331.
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abstract = "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, N(1) -3-methylbutyryl-N(4) -6-aminohexanoyl-piperazine (10(-4) mol 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.",
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T1 - Inhibitory effects of bromelain, a cysteine protease derived from pineapple stem (Ananas comosus), on intestinal motility in mice

AU - Borrelli, F

AU - Capasso, R

AU - Severino, B

AU - Fiorino, F

AU - Aviello, G

AU - De Rosa, G

AU - Mazzella, M

AU - Romano, B

AU - Capasso, F

AU - Fasolino, I

AU - Izzo, A A

N1 - © 2011 Blackwell Publishing Ltd.

PY - 2011/8

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N2 - 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, N(1) -3-methylbutyryl-N(4) -6-aminohexanoyl-piperazine (10(-4) mol 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.

AB - 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, N(1) -3-methylbutyryl-N(4) -6-aminohexanoyl-piperazine (10(-4) mol 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.

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KW - Cholinergic Agonists

KW - Croton Oil

KW - Diabetes Mellitus, Experimental

KW - Electric Stimulation

KW - Enzyme Inhibitors

KW - Gastrointestinal Motility

KW - Gastrointestinal Transit

KW - Humans

KW - Ileitis

KW - Male

KW - Mice

KW - Muscle Contraction

KW - Peptides

KW - Receptor, PAR-1

KW - Receptor, PAR-2

KW - Journal Article

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DO - 10.1111/j.1365-2982.2011.01735.x

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VL - 23

SP - 745-e331

JO - Neurogastroenterology and Motility

JF - Neurogastroenterology and Motility

SN - 1365-2982

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