Antimicrobial peptides (AMPs) are gaining attention as substitutes for antibiotics in order to combat the risk posed by multi-drug resistant pathogens. Several research groups are engaged in design of potent anti-infective agents using natural AMPs as templates. In this study, a library of peptides with high sequence similarity to Myeloid Antimicrobial Peptide (MAP) family were screened using popular online prediction algorithms. These peptide variants were designed in a manner to retain the conserved residues within the MAP family. The prediction algorithms were found to effectively classify peptides based on their antimicrobial nature. In order to improve the activity of the identified peptides, molecular dynamics (MD) simulations, using bilayer and micellar systems could be used to design and predict effect of residue substitution on membranes of microbial and mammalian cells. The inference from MD simulation studies well corroborated with the wet-lab observations indicating that MD-guided rational design could lead to discovery of potent AMPs. The effect of the residue substitution on membrane activity was studied in greater detail using killing kinetic analysis. Killing kinetics studies on Gram-positive, negative and human erythrocytes indicated that a single residue change has a drastic effect on the potency of AMPs. An interesting outcome was a switch from monophasic to biphasic death rate constant of Staphylococcus aureus due to a single residue mutation in the peptide.
Background and aim
Chrysin is a flavonoid found in plant extracts from
Passiflora
species, honey and propolis. It has demonstrated anti-adipogenic activity
in vitro
but there are no studies substantiating the anti-obesity activity of chrysin
in vivo
.
Experimental procedure
The pancreatic lipase (PL) inhibitory potential of chrysin was determined by preliminary
in silico
screening and further confirmed by
in vitro
PL inhibitory assay and oral fat tolerance test (OFTT). The effect of chrysin on acute feed intake and sucrose preference test was determined in normal rats. Obesity was induced by feeding of high fructose diet (HFD) to the rats. The rats were divided into six groups: normal control, HFD control, orlistat and three doses of chrysin (25, 50 and 100 mg/kg body weight). Body weight, body mass index (BMI), abdominal circumference/thoracic circumference (AC/TC) ratio, calorie intake, adiposity index, fecal cholesterol, locomotor activity and histopathology of the adipose tissue of the rats were evaluated.
Results
Chrysin showed good affinity to PL with competitive type of inhibition. It significantly reduced serum triglycerides in OFTT. Chrysin also significantly reduced acute feed intake and sucrose preference in rats. Chrysin significantly decreased the body weight, BMI, AC/TC ratio, adiposity index, calorie intake while it significantly increased the fecal cholesterol and locomotor activity of the rats. Chrysin was found to reduce the size of the adipocytes when compared to the HFD control group.
Conclusion
Thus, chrysin exerted anti-obesity effect by inhibiting PL, reducing sucrose preference, reducing calorie intake and increasing the locomotor activity of rats.
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