Gastroprotective effect, wound healing and anti-diabetic potential of two novel dichloro and dibromo schiff base derivatives in SD rats / Kamelia Saremi

Kamelia , Saremi (2021) Gastroprotective effect, wound healing and anti-diabetic potential of two novel dichloro and dibromo schiff base derivatives in SD rats / Kamelia Saremi. PhD thesis, Universiti Malaya.

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      Abstract

      Schiff base derivatives have displayed to possess a broad spectrum of pharmaceutical and biological properties. The present study encompasses an in vitro and in vivo study to evaluate the gastroprotective activity, wound healing potential and anti-diabetic effect of the bromine and chlorine Schiff base derivatives. 2,2'-[1,2-cyclohexanediylbis (nitriloethylidyne)] bis [4-chlorophenol] (CNCP) and 2,2'-[1,2-cyclohexanediylbis (nitriloethylidyne)] bis [4-bromophenol] (CNBP) were synthesized through Schiff base reaction by applying related ketones and diamines as initiators. CNCP and CNBP exhibited strong ferric reducing antioxidant power (FRAP) and possess mild DPPH radical scavenging activity. The safety of these compounds was verified through acute toxicity study exerted no signs of toxicity at 100 and 200 mg/kg. The gastroprotective effect of CNCP and CNBP were investigated against ethanol-induced gastric ulcer in SD rats. The study was performed with normal, ulcer control (5ml/kg of 10% tween 20), treatment group (10 and 20 mg/kg of CNCP and CNBP, respectively) and a reference group (omeperazole, 20 mg/kg). Vast shallow haemorrhagic injury of gastric glandular mucosa was observed in the ulcer group compared to the CNCP and CNBP-treated animals. Histological evaluations showed that these compounds possess stomach epithelial defense effect with an observation of reduction in gastric ulceration, edema and leucocytes penetration of submucosal stratum. Immunostaining of gastroprotective analysis exhibited over-expression of HSP70 protein and down-expression of Bax protein in CNCP and CNBP-treated groups. The gastric protein analysis of treated rats with CNCP and CNBP showed low levels of malondialdehyde (MDA) and high activity of prostaglandin E2 (PGE2), superoxide dismutase (SOD) and catalase (CAT). In the evaluation of wound healing potential, SD rats (male) were subjected into six groups (n=6); negative control (gum acacia), positive control (intrasite gel), and the treatment group (CNCP and CNBP, respectively). Topical treatment on wounded rats with CNCP and CNBP, showed a significant increase of wound closure percentage compared to the negative control. Histological evaluation of the skin sections showed granulation tissues contained more proliferating fibroblast, collagen deposition, angiogenesis, and less inflammatory cells in CNCP (10 mg/ml) and CNBP (20 mg/ml)-treated groups compared to the normal rats. In the treated groups with CNCP and CNBP, the SOD, CAT, and glutathione peroxidase (GPx) activities were found significantly higher, however, the MDA level was shown to be lower than the negative control. At the molecular level, CNCP (10 mg/ml) and CNBP (20 mg/ml) improved wound healing process via down-regulation of Bax and up-regulation of Hsp70 protein. The antidiabetic potential of CNCP and CNBP were evaluated in the STZ-NA-induced type 2 diabetic animal model. Interestingly, increased serum insulin and a significant reduction in fasting blood glucose levels were observed in normal and treated diabetic rats with CNCP and CNBP. Furthermore, the histological observations of the liver, kidney and pancreas of diabetic rats treated with CNCP and CNBP illustrated a significant improvement in structural degeneration. In conclusion, the findings of the present study suggest that CNBP and CNCP are safe to consume and hold great promise for use as preventive and curative agent for anti-diabetic, gastric ulcer and wound healing.

      Item Type: Thesis (PhD)
      Additional Information: Thesis (PhD) - Faculty of Science, Universiti Malaya, 2021.
      Uncontrolled Keywords: Schiff base derivatives; gastroprotective activity; wound healing; HSP70 protein; Anti-diabetic
      Subjects: Q Science > Q Science (General)
      R Medicine > RC Internal medicine
      Divisions: Faculty of Science
      Depositing User: Mr Mohd Safri Tahir
      Date Deposited: 13 Jan 2025 02:45
      Last Modified: 13 Jan 2025 02:45
      URI: http://studentsrepo.um.edu.my/id/eprint/14948

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