Development of a psoriatic-like skin inflammation rat model using imiquimod as an inducing agent.

OBJECTIVE: The present investigation was undertaken to develop a psoriatic-like skin inflammation rat model using imiquimod (IMQ) as an inducing agent. MATERIALS AND METHODS: The hairs of the back dorsal portion of the Wistar rats were removed and 80, 100, and 120 mg of IMQ cream (5% w/w) for 10 consecutive days was applied to different groups of rats. Further, psoriasis area severity index was used for calculating the psoriatic score, which included scoring of erythema, scaling, and thickening. Various biochemical parameters, pro-inflammatory cytokines, vascular endothelial growth factor (VEGF), and histopathological examination were also performed. RESULTS: The results demonstrated signs of erythema, scaling, and thickening on group applied with 120 mg and 100 mg of IMQ along with ear thickening. Biochemical evaluation revealed a significant increase in the granulation tissue weight followed by significant decrease in the levels of collagen and hexosamine. The antioxidant parameters superoxide dismutase and catalase were found to decline, while nitric oxide and lipid peroxidation were significantly elevated in skin lesions, also supported by increased pro-inflammatory cytokines expression, i.e., interleukin (IL)-1 ß, IL-6, IL-17, tumor necrosis factor-α, and VEGF. Histopathological studies revealed a disturbed natural structure along with increased epidermal proliferation, abnormal differentiation with increased number of keratinocytes in the psoriatic skin tissue. CONCLUSION: From the overall study, we have successfully developed a psoriatic-like skin inflammation rat model for the first time on Wistar strain using IMQ as an inducing agent.

The potency of eriosematin E from Eriosema chinense Vogel. against enteropathogenic Escherichia coli induced diarrhoea using preclinical and molecular docking studies.

The main objective of the present study was to evaluate the potential of eriosematin E (ECM) isolated from the roots of Eriosema chinense against enteropathogenic Escherichia coli (EPEC) induced diarrhoea. ECM isolated from the bioactive chloroform fraction of E. chinense was subjected to antidiarrhoeal evaluation on rats against diarrhoea, induced by the oral suspension of EPEC. The study included evaluation of behavioral parameters for 6 h and up to 24 h of induction, followed by estimation of water content, the density of EPEC in stools and evaluation of various blood parameters. Further, the colonic and small intestinal tissues were subjected to biochemical estimations, antioxidant evaluation, determination of ion concentration, Na+/K+ -ATPase activity, pro-inflammatory cytokines assessment and histopathology. Finally, the impact of ECM on Na+/K+-ATPase was studied through molecular docking studies. Significant antidiarrhoeal potential of ECM was demonstrated at 5 and 10 mg/kg, p.o., however, ECM at 10 mg/kg, p.o. was found to be more effective, as confirmed through higher % protection, density of EPEC in stools and water content of stools. ECM also significantly increased the level of WBC, Hb, platelets and revealed restoration of altered antioxidants, pro-inflammatory cytokines (IL-1ß and TNF-α) status and also reactivated the suppressed Na+/K+-ATPase activity, which was also confirmed through docking studies showing H-bonding of hydroxyl group of ECM with amino acids Asp 190, Asn 167 and Glu 169 thus, maintaining proper electrolyte balance and also prevented epithelial tissue damage. The overall effect of ECM may be attributed to the decline in the elevated level of cytokines, inhibition in nitric oxide production and reactivation of Na+/K+-ATPase activity resulting in reduced intestinal secretion.