Phytochemical screening and evaluation of the anti-diarrhoea properties of Diodia sarmentosa leaves in castor oil-induced diarrhoea in albino rats

Purpose This study aims to report the phytochemical screening and anti-diarrhoea properties of methanol extract of Diodia sarmentosa Swartz (DSS) leave (at 200, 400 and 600 mg/kg) in albino rats. Design/methodology/approach Three types of diarrhoea models (castor oil-induced diarrhoea, castor oil-induced gastrointestinal motility and castor oil-induced enteropooling), as well as an assay for serum and faecal electrolyte concentrations, were used. Acute toxicity study and phytochemical screening of the extract were carried out using standard techniques. Findings The percentage inhibition of diarrhoea by DSS 200, 400 and 600 mg/kg was obtained as 25.7%, 55% and 84.6%, respectively, compared with loperamide that had 87.6% inhibition. DSS dose dependently modulated the number and frequency of defecation, the weight of the faeces of the diarrhoea rats, the distance that was travelled by charcoal meal, mean differences in the full lengths of the intestines and the distance travelled by charcoal meal, weight and volume of intestinal contents, serum and faecal concentrations of potassium, sodium, chloride, magnesium, bicarbonate, iron and zinc relative to the negative control and in a manner akin to loperamide (for the extract at 600 mg/kg). DSS or loperamide attenuated the loss of calcium in the faeces of the rats. DSS possesses anti-diarrhoea properties, which may be attributed to the phytochemicals in it. Finally, the study showed the safety in the usage of DSS. Originality/value DSS exerted its anti-diarrhoea action in castor oil-induced diarrhoea rats, by modulating their intestinal secretory and motile activity in a manner akin to loperamide (for DSS at 600 mg/kg).

Cytoprotective Compounds Interfere with the Nutraceutical Potential of Bread Supplemented with Green Coffee Beans

The proliferation and motile activity of prostate epithelial (Pnt2) and cancer cells (DU-145; PC-3) in the presence of bioavailable compounds from green coffee beans (GCB), wholemeal wheat bread (WMWB), and its GCB-fortified variant were analyzed. The considerable cytostatic and anti-invasive activity of GCB extracts was correlated with its phenolic contents. WMWB extract contained significantly lower levels of phenolics but still displayed relatively high cytostatic activity. However, the cytostatic properties of WMWB compounds were hardly augmented by 3% GCB flour supplementation. The cytoprotective activity of the WMWB compounds exerts a negative impact on the cytostatic activity of GCB compounds. These data confirm the relatively high chemopreventive potential of GCB. However, they also indicate that subtle interactions between bioavailable compounds in GCB and WMWB can negatively affect the nutraceutic potential of the fortified bread. Apparently, gastrointestinal processing differentially regulates the availability of individual compounds and affects the balance between the cytostatic and cytoprotective activity of the whole product. Our data show that comprehensive research is necessary before the fortification of a specific carrier with a specific supplement can be recommended.

Cryo-EM Reveals the Structural Basis of Microtubule Depolymerization by Kinesin-13s

SummaryKinesin-13s constitute a distinct group within the kinesin superfamily of motor proteins that promotes microtubule depolymerization and lacks motile activity. The molecular mechanism by which the kinesins depolymerize microtubules and are adapted to perform a seemingly very different activity from other kinesins is still unclear. To address this issue we obtained near atomic resolution cryo-electron microscopy (cryo-EM) structures of Drosophila melanogaster kinesin-13 KLP10A constructs bound to curved or straight tubulin in different nucleotide states. The structures show how nucleotide induced conformational changes near the catalytic site are coupled with kinesin-13-specific structural elements to induce tubulin curvature leading to microtubule depolymerization. The data highlight a modular structure that allows similar kinesin core motor-domains to be used for different functions, such as motility or microtubule depolymerization.

The human cytoplasmic dynein interactome reveals novel activators of motility

In human cells, cytoplasmic dynein-1 is essential for long-distance transport of many cargos, including organelles, RNAs, proteins, and viruses, towards microtubule minus ends. To understand how a single motor achieves cargo specificity, we identified the human dynein interactome by attaching a promiscuous biotin ligase (‘BioID’) to seven components of the dynein machinery, including a subunit of the essential cofactor dynactin. This method reported spatial information about the large cytosolic dynein/dynactin complex in living cells. To achieve maximal motile activity and to bind its cargos, human dynein/dynactin requires ‘activators’, of which only five have been described. We developed methods to identify new activators in our BioID data, and discovered that ninein and ninein-like are a new family of dynein activators. Analysis of the protein interactomes for six activators, including ninein and ninein-like, suggests that each dynein activator has multiple cargos.

The Human Cytoplasmic Dynein Interactome Reveals Novel Activators of Motility

ABSTRACTIn human cells, cytoplasmic dynein-1 is essential for long-distance transport of many cargos, including organelles, RNAs, proteins, and viruses, towards microtubule minus ends. To understand how a single motor achieves cargo specificity, we identified the human dynein interactome or “transportome” by attaching a promiscuous biotin ligase (“BioID”) to seven components of the dynein machinery, including a subunit of the essential cofactor dynactin. This method reported spatial information about the large cytosolic dynein/dynactin complex in living cells. To achieve maximal motile activity and to bind its cargos, human dynein/dynactin requires “activators”, of which only five have been described. We developed methods to identify new activators in our BioID data, and discovered that ninein and ninein-like are a new family of dynein activators. Analysis of the protein interactomes for six activators, including ninein and ninein-like, suggests that each dynein activator has multiple cargos.