EXPLORING PHYTOCHEMICAL CANDIDATES TARGETING SFRP4: A PROMISING APPROACH FOR DIABESITY TREATMENT

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Shazia Anwer Bukhari
Muhammad Farrukh Tahir
Muhammad Masood Ahmad
Muhammad Noman
Aiman Maryam
Mubasher Ahmad
Muhammad Asad
Noor us Saba
Asim Rehman

Keywords

Type 2 Diabetes, Obesity, Wnt Signalling, SFRP4

Abstract

The simultaneous presence of both obesity and diabetes in an individual is known as diabesity. Type 2 diabetes mellitus is a global chronic condition characterized by an increase in blood sugar levels caused by insufficient pancreatic insulin production and in the development of diabetes type 2 obesity plays an important role. Wnt signaling is an evolutionarily conserved system that regulates a wide range of activities during embryonic development, including cell differentiation, proliferation, and growth. Wnt signaling can be influenced by a variety of antagonists. By specifically targeting secreted frizzled-related protein4 (SFRP4) that is released from white adipose tissues and results in the increased production of adipokines into to the blood obesity can be controlled. Therefore, identification of SFRP4 inhibitors from phytochemicals which shows maximum anti-obesity and anti-diabetic activity is necessary. Molecular operating environment (MOE) software was used for protein docking to observe association between protein and compound that can be used as anti-obesity drug. Six to eight-week mice were used in this experiment that were randomly divides into two different studies. For 10-12 weeks, 2 control group was fed on normal diet (ND) while the 12 groups were fed on High fat diet (HFD). After induction of obesity induced diabetes, the mice were treated with the phytochemicals for 3 weeks and their role in reducing blood glucose level and obesity was determined by observing blood glucose level and body weight. The blood sample was collected in properly labeled tubes. Enzyme linked immunosorbent assay (ELISA) was used for quantification and detection of protein in serum. The correlation of body weight reduction and diabetes with SFRP4 level indicates their relation. One-way ANOVA on Graph pad prism was used to compare the mean and standard deviation of each group for identification of their significance level (p < 0.05). The Serum SFRP4 level significantly increased after HFD. Coumarin, Trehalose, Thymol and Ferulic acid showed significant difference to diabetic, non-diabetic and standard treatment group (p < 0.05) while exhibiting non-significant difference among them. In conclusion, treatment of Coumarin, Trehalose, Thymol and Ferulic acid significantly decreased the body weight, glucose level and SFRP4 level. These compounds could be potential candidate to be used as anti-obesity and anti-diabetic drug.

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