title: Pharmacological basis for the medicinal use of Linum usitatissimum (Flaxseed) in infectious and non-infectious diarrhea.
abstract: BACKGROUND
  Linum usitatissimum, commonly known as Flaxseed has traditionally been used for the management of diarrhea and gastrointestinal infections. This study was planned to assess pharmacological basis for the medicinal use of Flaxseed in infectious and non-infectious diarrhea.
  
  
  METHODS
  The crude aqueous-methanolic extract of Flaxseed was studied using the in vivo castor oil-induced diarrhea, gut motility and enteropooling assays. Mechanistic basis was further elucidated by testing the inhibitory effect on spontaneously contracting isolated rabbit jejunum preparations, suspended in a 10ml tissue bath containing Tyrode׳ solution, maintained at 37°C and aerated with carbogen. Antibacterial efficacy of the Flaxseed extract was tested against different enteric and non-enteric pathogenic bacteria using in vitro antibacterial assays.
  
  
  RESULTS
  Flaxseed extract reduced the diarrheal score in mice, by 39%, 63.90% and 68.34% at the respective doses of 100, 300 and 500mg/kg. Intestinal secretions were reduced by 24.12%, 28.09% and 38.80%, whereas the intestinal motility was reduced by 31.66%, 46.98% and 56.20% at respective doses of 100, 300 and 500mg/kg. When tested on isolated rabbit jejunum preparations, Flaxseed extract produced a dose-dependent inhibition of both spontaneous and high K(+) (80mM)-induced contractions, and shifted the concentration-response curves of Ca(++) to the right with suppression of the maximum response, similar to that caused by verapamil. Flaxseed extract was found to possess bactericidal activity at the tested concentrations of 12.5mg/ml, against vancomycin-resistant Enterococcus faecalis (100%), Escherichia coli K1 (88.88%), methicillin-resistant Staphylococcus aureus (98.76%), Bacillus cereus (92.64%), Pseudomonas aeruginosa (76.83%) and Salmonella typhi (26.91±3.35%). The concentration of 10mg/ml showed bactericidal effects against all the aforementioned pathogens except Escherichia coli K1, whereas for Pseudomonas aeruginosa and Salmonella typhi, it was bacteriostatic at this concentration.
  
  
  CONCLUSIONS
  Our results indicate that Linum usitatissimum (Flaxseed) extract exhibits antidiarrheal and antispasmodic activities by virtue of its antimotility and antisecretory effects which are mediated possibly through inhibition of Ca(++) channels, though additional mechanism(s) cannot be ruled out. Flaxseed extract proved effective against both enteric and non-enteric pathogens causing diarrhea, thus ensuring wide coverage and rationalizing its medicinal use in both the infectious and non-infectious diarrhea.
authors.affiliation: Department of Biological and Biomedical Sciences, The Aga Khan University Medical College, Karachi 74800, Pakistan.
authors.forename: Amber Hanif
authors.initials: AH
authors.lastname: Palla
authors.affiliation: Department of Biological and Biomedical Sciences, The Aga Khan University Medical College, Karachi 74800, Pakistan.
authors.forename: Naveed Ahmed
authors.initials: NA
authors.lastname: Khan
authors.affiliation: Department of Biological and Biomedical Sciences, The Aga Khan University Medical College, Karachi 74800, Pakistan.
authors.forename: Samra
authors.initials: S
authors.lastname: Bashir
authors.affiliation: Department of Biological and Biomedical Sciences, The Aga Khan University Medical College, Karachi 74800, Pakistan; Department of Pharmacy, College of Health Sciences, Mekelle University, PO Box 1871, Mekelle, Ethiopia.
authors.forename: Najeeb
authors.initials: N
authors.lastname: Ur-Rehman
authors.affiliation: Department of Biological and Biomedical Sciences, The Aga Khan University Medical College, Karachi 74800, Pakistan.
authors.forename: Junaid
authors.initials: J
authors.lastname: Iqbal
authors.affiliation: Department of Biological and Biomedical Sciences, The Aga Khan University Medical College, Karachi 74800, Pakistan; Department of Pharmacy, College of Health Sciences, Mekelle University, PO Box 1871, Mekelle, Ethiopia. Electronic address: anwar.gilani@aku.edu.
authors.forename: Anwarul-Hassan
authors.initials: AH
authors.lastname: Gilani
mesh_terms: D000818:Animals; D000930:Antidiarrheals / Q000737:chemistry / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002368:Castor Oil; D003967:Diarrhea / Q000139:chemically induced / Q000188:drug therapy* / Q000382:microbiology*; D004305:Dose-Response Relationship, Drug; D019597:Flax / Q000737:chemistry*; D005769:Gastrointestinal Motility / Q000187:drug effects; D007583:Jejunum / Q000187:drug effects; D051379:Mice; D008826:Microbial Sensitivity Tests; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D012639:Seeds / Q000737:chemistry*; D014700:Verapamil / Q000494:pharmacology
chemical_list: D000930:Antidiarrheals; D010936:Plant Extracts; D002368:Castor Oil; D014700:Verapamil; D011188:Potassium; D002118:Calcium
keywords: Antidiarrheal; Antisecretory; Antispasmodic; Bactericidal; Ca(++) antagonist; Flaxseed