Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/046185

FREEZE DRIED EXTRACTS OF Bidens biternata (Lour.) Merr. And Sheriff. SHOW SIGNIFICANT ANTIDIARRHEAL ACTIVITY IN -VIVO MODELS OF DIARRHEA

Dennis G Kinuthia·Anne W Muriithi·Peter Waweru Mwangi
View original source ↗Export metadata ↓

Abstract

Ethnopharmacological relevance of the studyDiarrhea remains one of the main killers of children aged below five years. Traditional antidiarrheal remedies form a potentially viable source of novel low cost efficacious antidiarrheal remedies in low resource settings. There is therefore a pressing to scientifically evaluate these remedies.\n\nAim of the studyThis study aimed to investigate the in vivo and in vitro antidiarrheal activity of Bidens biternata a herb species used in traditional Ayurvedic medicine in the management of diarrhea.\n\nMaterials and MethodsIn the castor oil test twenty (20) adult Sprague-Dawley rats were randomized to the negative control (normal saline), positive control (5 mg/kg loperamide), (200 mg/kg Bidens biternata extract) and (400 mg/kg Bidens biternata extract) groups (n=5 in each group). Castor oil (4 ml/kg) was then administered to the animals one hour after administration of the respective treatments after which the total mass of fecal output excreted after four (4) hours was determined.\n\nIn the charcoal meal test fifteen (15) Sprague Dawley rats were randomized to the negative control (normal saline 5 ml/kg orally), the positive control (atropine sulphate 0.1 mg/kg i.p) and test (400 mg/kg Bidens biternata extract) groups (n=5). Charcoal meal was then administered via oral gavage to each rat thirty (30) minutes after the administration of the various treatments. The distance covered by the charcoal meal from the pylorus was then determined after sacrifice of the animals.\n\nIn the enteropooling test twenty (20) Sprague-Dawley rats were randomized to the negative control (5% v/v ethanol in normal saline), positive control (5 mg/kg loperamide) and test (400 mg/kg Bidens biternata extract) groups and prostaglandin E2 (PGE2) (100g/kg) administered immediately after the treatments. The animals were then sacrificed half an hour later and the volume of the small intestine contents determined. The effects of different concentrations of Bidens biternata extract (0.5. 1.0, 2.0, 3.0 and 5.0 mg/ml) on jejunal contraction were investigated and a dose-response curve constructed using the experimental data after which The ED50 dose determined. The effect of tamsulosin (1 adrenergic blocker), yohimbine (2 adrenergic blocker), propranolol ({beta} adrenergic blocker) and naloxone ( opioid blocker) on the contractile activity of the extract were also investigated.\n\nThe experimental data were expressed as mean {+/-} standard error of mean (SEM) and then analyzed using one way ANOVA followed by Tukeys post hoc test in cases of significance (set at p<0.05).\n\nResultsThe freeze dried extracts of Bidens biternata had significant antidiarrhealeffects in the castor oil induced diarrhea model (p=0.0075) with maximal activity being observed at the 400mg/kg dosage level (1.66{+/-} 0.81g vs. 4.54 {+/-} 0.51 g negative control, p=0.01). Bidens biternata extract had significant effects on intestinal motility in the charcoal meal test compared to the control group (43.61 {+/-} 4.42% vs. 60.54 {+/-} 3.33%: p= 0.02). Bidens biternata extract had a significant effect on PGE2 induced enteropooling (3.06 {+/-} 0.07 ml vs. 4.74 {+/-} 0.10 ml; p<0.001).\n\nThe freeze dried extracts of Bidens biternata had a significant negative effect on the contractility of the isolated rabbit jejunum (p<0.001). The effects of the extract were significantly attenuated by tamsulosin (53.94 {+/-} 4.20% vs. 80.57 {+/-} 4.09%; p=0.0067) and naloxone (53.94 {+/-} 4.20% vs. 73.89 {+/-} 7.26 %; p=0.0358). Yohimbine (p=0.4598) and propranolol (p=0.5966) however did not have any significant effect on the contractile activity of the extract.\n\nConclusionsThe freeze dried extract of Bidens biternata possess significant antidiarrhealactivity in both in vitro and in vivo models which appears to be mediated by modulating both the intestinal motility as well as the secretory activity. The results of this study also validate its traditional use as an antidiarrheal remedy.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=196 SRC=\"FIGDIR/small/046185_ufig1.gif\" ALT=\"Figure 1000\">\nView larger version (15K):\norg.highwire.dtl.DTLVardef@1251d73org.highwire.dtl.DTLVardef@1b08654org.highwire.dtl.DTLVardef@430f4forg.highwire.dtl.DTLVardef@a210cc_HPS_FORMAT_FIGEXP M_FIG C_FIG

Source connections

Explore related subjects

Pharmacology and ToxicologyPreprint

Keep this discovery

BibTeXRIS

Dennis G Kinuthia, Anne W Muriithi, Peter Waweru Mwangi. 2016-03-29. FREEZE DRIED EXTRACTS OF Bidens biternata (Lour.) Merr. And Sheriff. SHOW SIGNIFICANT ANTIDIARRHEAL ACTIVITY IN -VIVO MODELS OF DIARRHEA. https://doi.org/10.1101/046185

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2016

Harnessing Big Data for Systems Pharmacology

Systems pharmacology aims to holistically understand genetic, molecular, cellular, organismal, and environmental mechanisms of drug actions through developing mechanistic or predictive models. Data-driven modeling plays a central role in systems pharmacology, and has already enabled biologists to generate novel hypotheses. However, more is needed. The drug response is associated with genetic/epigenetic variants and environmental factors, is coupled with molecular conformational dynamics, is affected by possible off-targets, is modulated by the complex interplay of biological networks, and is dependent on pharmacokinetics. Thus, in order to gain a comprehensive understanding of drug actions, systems pharmacology requires integration of models across data modalities, methodologies, organismal hierarchies, and species. This imposes a great challenge on model management, integration, and translation. Here, we discuss several upcoming issues in systems pharmacology and potential solutions to them using big data technology. It will allow systems pharmacology modeling to be findable, accessible, interoperable, reusable, reliable, interpretable, and actionable.

Pharmacology and Toxicology↗
bioRxiv2016

Insights into the binding mode of MEK type-III inhibitors. A step towards discovering and designing allosteric kinase inhibitors across the human kinome

Protein kinases are critical drug targets for treating a large variety of human diseases. Type-I and type-II kinase inhibitors frequently exhibit off-target toxicity or lead to mutation acquired resistance. Two highly specific allosteric type-III MEK-targeted drugs, Trametinib and Cobimetinib, offer a new approach. Thus, understanding the binding mechanism of existing type-III kinase inhibitors will provide insights for designing new type-III kinase inhibitors. In this work we have systematically studied the binding mode of MEK-targeted type-III inhibitors using structural systems pharmacology and molecular dynamics simulation. Our studies provide detailed sequence, structure, interaction-fingerprint, pharmacophore and binding-site information on the binding characteristics of MEK type-III kinase inhibitors. We propose that the helix-folding activation loop is a hallmark allosteric binding site for type-III inhibitors. Subsequently we screened and predicted allosteric binding sites across the human kinome, suggesting other kinases as potential targets suitable for type-III inhibitors. Our findings will provide new insights into the design of potent and selective kinases inhibitors.\n\nAuthor SummaryHuman protein kinases represent a large protein family relevant to many diseases, especially cancers, and have become important drug targets. However, developing the desired selective kinase-targeted inhibitors remain challenging. Kinase allosteric inhibitors provide that opportunity, but, to date, few have been designed other than MEK inhibitors. To more efficiently develop kinase allosteric inhibitors, we systematically studied the binding mode of the MEK type-III allosteric kinase inhibitors using structural system pharmacology and molecular dynamics approaches. New insights into the binding mode and mechanism of type-III inhibitors were revealed that may facilitate the design of new prospective type-III kinase inhibitors.

Pharmacology and Toxicology↗
bioRxiv2016

Clinically-weighted transcriptomic signatures for protein kinase inhibitor associated cardiotoxicity

Cardiotoxicity (CT) involving diminished cardiac contractility and heart failure is a major adverse event associated with otherwise efficacious protein kinase inhibitors (KIs). Here, we sought to develop clinically-weighted transcriptomic signatures to predict risk of CT and to better understand the biological processes associated with CT risk. We obtained transcriptome-wide response profiles in four human primary cardiomyocyte cell lines that were treated with 22 different KIs using mRNA sequencing with 3 digital gene expression. The FDA Adverse Event Reporting System was used to derive relative risk scores for four types of CT for different KIs. We used elastic net regression to associate these transcriptomic profiles with KI-associated risk scores for CT subtypes to obtain clinically-weighted transcriptomic signatures, which showed good predictive properties (cross-validation R2 >0.87). Our clinically-weighted transcriptomic signatures for KI-associated CT may be of relevance in early drug development for the prediction of KI-associated CT.

Pharmacology and Toxicology↗