Amber Hanif Palla
Barret Hodgson University, Pakistan
Title: Pharmacological basis for medicinal use of Flaxseed in IBD
Biography
Biography: Amber Hanif Palla
Abstract
Multi-targeted therapy is the new approach in IBD therapeutics due to its multifactorial etiology and failure to attain remission with currently available options. In the current study, we assess the pharmacological basis of both the extract and oil of Flaxseed use in IBD and compare their activity profile.
HPLC of the extract revealed the presence of polar compounds with peaks resembling quercetin, nicotinic acid and nicotinamide, whereas Flaxseed oil only showed peaks corresponding to non-polar components. Flaxseed oil was more effective in reducing the mortality rate in acetic acid (AA)-induced colitis in BALB/c mice at 500 mg/kg dose as compared to Flaxseed extract (Fs.Cr). Flaxseed oil was more effective in reduing the ulcers, whereas, Fs.Cr was more effective in reducing the inflammatory infiltration and reducing goblet cell depletion and increasing the mucin release. Antispasmodic mechanisms of Fs.Cr were mediated by phosphodiesterase enzyme inhibitory activity (PDEI) as main mechanism, followed by Ca++ antagonist effect, as Fs.Cr dose-dependently inhibited spontaneous, carbachol (CCh) at 3 mg/ml and high K+-induced contractions at 5 mg/ml, in isolated rabbit jejunum with higher potency against CCh, similar to that of papaverine, while verapamil was more potent against high K+. This was also supported by potentiation of isoprenaline concentration-response curves (CRCs) by pretreatment with low doses of Fs.Cr (0.01 and 0.03 mg/ml). Fs.Cr mediated PDEI activity by inhibiting PDE-4 subtype as pre-treatment of Fs.Cr did not potentiate Rolipram (PDE-4 inhibitor) inhibitory activity against CCh-induced contractions, whereas it potentiated the inhibitory effect of Cilostazol (PDE-3 inhibitor) and zaprinast (PDE-5 inhibitor). Subsequent dose dependent increase in cAMP levels (1 and 3 mg/ml) was also evident similar to papaverine (1 mM and 3 mM doses), further supporting its PDEI effect. Flaxseed oil’s main antispasmodic activity was by K+ channel opening (KCO) mechanism (3 mg/ml), followed by a weak PDEI activity as it inhibited CCh-induced contraction at 5 mg/ml. Flaxseed oil was more potent and efficacious bactericidal against enteropathogenic Eschericia.coli (EPEC), enterotoxigenic E.coli (ETEC) and enteroaggregative E.coli (EAEC) which are implicated in IBD, as they killed these microbes at 9 µg/ml and 14 µg/ml, whereas, Fs.Cr was only cidal against EPEC at a 10 times higher dose than of Flaxseed oil (100 µg/ml), whereas, it had a static mechanism against ETEC and EAEC.
Our results indicate that both Flaxseed oil and Fs.Cr have constituents that are effective against IBD model of mice with different activity profile. Hence, Flaxseed as a whole may produce an augmented response.