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Title: An appraisal of the antidiabetic and hypolipidaemic activities of thiazolidin-4-ones with nicotinamide moiety in animal models
Researcher: Anoop Kishore
Guide(s): Kutty, N Gopalan
Rao, C Mallikarjuna
Keywords: Pharmaceutical Sciences
Nicotinamide moiety
Pharmacological evaluation
Upload Date: 25-Oct-2013
University: Manipal University
Completed Date: July, 2013
Abstract: The current study involves detailed pharmacological evaluation of four thiazolidine-4-one derivatives of nicotinic acid (NAT1-4), which have shown dual hypolipidaemic and anti-hyperglycaemic activities in preliminary studies. The in-vivo models included streptozotocin-induced, High-sucrose-diet (HSD) and High-fat-diet (HFD) fed mice models of diabetes. Mechanistic studies included effects on DPP-IV inhibition, glucose uptake, AMPK activation and expression of mediators like PPAR-and#945;/and#947;, NFand#61547;B, COX-II, Bax etc. NAT1-4 significantly lowered elevated blood glucose levels in HFD and HSD models and NAT-1and3 improved the insulin levels in HSD model. The elevated lipids levels in HFD and HSD models were decreased by NAT-1and3. Interestingly, all treatment (NAT 1-4) groups markedly increased HDL-cholesterol levels in both the models. Also, the molecules did not show any adverse effects on renal or liver functions. In in-vitro experiments, none of the drugs showed DPP-IV inhibition or AMPK activation but all drugs increased glucose uptake by hemi-diaphragm. NAT-1-4 alone and in combination with insulin increased glucose uptake in myotubes and pre-adipocytes. NAT-2,3and4 increased the levels of PPAR-and#945;/and#947; in the nuclear fractions of myotubes and pre-adipocytes. In RAW cells, NAT-3and4 reduced the levels of NFand#61547;B but none of the treatments had any effect on the COX-II expression, ROS and nitrite generation. NAT-1 increased and NAT-4 decreased the expression of BAX in LPS treated L6 myotubes. In conclusion, the drugs have shown effective glucose and lipid lowering effects in different in-vivo models and are found to increase translocation of transcription factors PPAR and#945;andand#947; and inhibition of NFand#61547;B expression which may have contributed to their anti-diabetic and hypolipidaemic activities.
Pagination: 101p.
Appears in Departments:Manipal College of Pharmaceutical Sciences

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01_ title.pdfAttached File220.42 kBAdobe PDFView/Open
02_certificate.pdf200.82 kBAdobe PDFView/Open
03_abstract.pdf192.76 kBAdobe PDFView/Open
04_declaration.pdf192.16 kBAdobe PDFView/Open
05_acknowledgement.pdf187.55 kBAdobe PDFView/Open
06_contents.pdf205.01 kBAdobe PDFView/Open
07_list_of_tables.pdf201.23 kBAdobe PDFView/Open
08_ list_of_figures.pdf189.98 kBAdobe PDFView/Open
09_list of abbreviations.pdf188.43 kBAdobe PDFView/Open
10_chapter 1.pdf411.54 kBAdobe PDFView/Open
11_chapter 2.pdf526.97 kBAdobe PDFView/Open
12_chapter 3.pdf1.61 MBAdobe PDFView/Open
13_chapter 4.pdf287.71 kBAdobe PDFView/Open
14_chapter 5.pdf2.35 MBAdobe PDFView/Open
15_chapter 6.pdf343.5 kBAdobe PDFView/Open
16_summary.pdf465.75 kBAdobe PDFView/Open

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