4.5 Article

In-vitro and in-vivo assessment of the anti-diabetic, analgesic, and anti-inflammatory potenstials of metal-based carboxylates derivative

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HELIYON
卷 9, 期 8, 页码 -

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CELL PRESS
DOI: 10.1016/j.heliyon.2023.e19160

关键词

Carrageenan Histamine Arachidonic acid; alpha-Amylase; alpha-Glucosidase; Hot plate

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In this research, an amide based metal carboxylate compound was identified as an anti-diabetic analgesic and anti-inflammatory agent. The compound showed inhibition against diabetic enzymes and demonstrated analgesic and anti-inflammatory effects in vivo. The molecular docking study suggested its potential inhibitory effect on the COX-2 receptor.
In the current research work, an amide based metal carboxylate chemical ([((5-((5-(2-hydroxyethyl)4-methylthiazol-3-ium-3-yl)methyl)-2-methylpyrimidin-4-yl)amino)bis((4-((4-methoxy- 2-nitrophenyl)amino)-4-oxobutanoyl)oxy)zinc]) was identified as anti-diabetic analgesic and anti-inflammatory. The identified chemical(MT-1) was tested for acute toxicity (the MT-1 was fund safe), antidiabetic analgesic, and anti-inflammatory potentials. The in-vitro study was conducted for antidiabetic enzyme inhibition (alpha-amylase and a-glucosidase) and the in-vivo studies included analgesic (acetic acid-induced writing and hot plate model) and anti-inflammatory (carrageenan etc induced edema) effects. The tested compound showed 88.63% (IC50 = 3.23 mu g/ml) and 89.10%(IC50 = 5.10 mu g/ml) against alpha-amylase and alpha-glucosidase respectively. A significant (p < 0.001) analgesic effect was noted by MT-1 in acetic acid-induced animal models with a percent effect of 86.00, 60.,06, and 55.29 at the tested doses of 20, 1,0, and 5 mg/kg respectively. In the case of the hot plate model, the MT-1 showed a significant (p < 0.001) effect with maximum percent prolongation in latency observed after 60 min.08, 22.2,9, and 11.61) against 20, 1,0, and 5 mg/kg. The analgesic effect in the hot plate model was significantly (p < 0.01) reversed by the injection of naloxone (0.125 mg/kg). The paw edema induced by carrageenan, histamine, bradykinin, arachidonic acid, and PGE2 was significantly antagonized with percent attenuation of 34.09, 33.57, 34.60, 34.14, and 48.04 respectively. Furthermore, to predict the interactions between the MT-1 compound and COX-2 molecular docking was carried out and the result was compared with the standard compound. The docking score of MT-1 was predicted as 6.30 while that of Diclofenac was predicted as 6.82. Both compounds made several hydrogen bond interactions with the active site of the COX-2 enzyme. The docking study revealed the potent inhibitory potential of the compound MT-1 against the COX-2 receptor.

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