MATERIALS AND METHODS: The effects of mitragynine on the mRNA and protein expression of COX-1 and COX-2 and the production of prostaglandin E(2) (PGE(2)) were investigated in LPS-treated RAW264.7 macrophage cells. Quantitative RT-PCR was used to assess the mRNA expression of COX-1 and COX-2. Protein expression of COX-1 and COX-2 were assessed using Western blot analysis and the level of PGE(2) production was quantified using Parameter™ PGE(2) Assay (R&D Systems).
RESULTS: Mitragynine produced a significant inhibition on the mRNA expression of COX-2 induced by LPS, in a dose dependent manner and this was followed by the reduction of PGE(2) production. On the other hand, the effects of mitragynine on COX-1 mRNA expression were found to be insignificant as compared to the control cells. However, the effect of mitragynine on COX-1 protein expression is dependent on concentration, with higher concentration of mitragynine producing a further reduction of COX-1 expression in LPS-treated cells.
CONCLUSIONS: These findings suggest that mitragynine suppressed PGE(2) production by inhibiting COX-2 expression in LPS-stimulated RAW264.7 macrophage cells. Mitragynine may be useful for the treatment of inflammatory conditions.
Objectives: This study aimed to predict the actions of 10 compounds in I. batatas leaves, which are YGM-0a [cyanidin 3-0-sophoroside-5-0-glucosede], YGM-0f [cyanidin 3-O-(2-0-(6-0-(E)-p-coumaroyl-β-D-glucopyranosyl)-β-D-glucopyranoside)-5-0-β-D-glucopyranoside], YGM-1a [cyanidin 3-(6,6'-caffeylp-hydroxybenzoylsophoroside) -5-glucoside], YGM-1b [cyanidin 3-(6,6'-dicaffeylsophor-oside)-5-glucoside], YGM-2 [cyanidin 3-(6-caffeylsophoroside)-5-glucoside], YGM-3 [cyanidin 3-(6,6'-caffeyl-ferulylsophoroside)-5-glucoside], YGM-4b [peonidin 3-(6,6'-dicaffeylsophoroside)-5- glucoside], YGM-5a [peonidin 3-(6,6'-caffeylphydroxybenzo-ylsophoroside)-5-gluco-side], YGM-5b [cyanidin 3-6-caffeylsophoroside)-5-glucosede], and YGM-6 [peonidin 3-(6,6'-caffeylferulylsophoroside)-5-glucoside] as LOX inhibitors, and also predict the stability of ligand-LOX complex.
Materials and Methods: The compounds were screened through docking studies using PLANTS. Also, the molecular dynamics simulation was conducted using GROMACS at 310K.
Results: The results showed that the most significant binding affinity toward LOX was shown by YGM-0a and YGM-0a, and the LOX complex in molecular dynamics simulation showed stability for 20 ns.
Conclusion: Based on Docking Studies and Molecular Dynamics Simulation of I. Batatas Leaves compounds, YGM-0a was shown to be the most probable LOX inhibitor.
METHODS: A total of 165 patients with cardiovascular disease who were treated with 75-150 mg daily dose of aspirin and 300 healthy volunteers were recruited. DNA was extracted from the blood samples and genotyped for COX-1 (A-842G), UGT1A6 (UGT1A6*2 and UGT1A6*3) and CYP2C9 (CYP2C9*3; A1075C) using allele specific polymerase chain reaction (AS-PCR).
RESULTS: Variants UGT1A6*2,*3 and CYP2C9*3 were detected in relatively high percentage of 22.83%, 30.0% and 6.50%, respectively; while COX-1 (A-842G) was absent. The genotype frequencies for UGT1A6*2 and *3 were significantly different between Indians and Malays or Chinese. The level of bilirubin among patients with different genotypes of UGT1A6 was significantly different (p-value < 0.05). In addition, CYP2C9*3 was found to be associated with gastritis with an odd ratio of 6.8 (95 % Cl OR: 1.39 - 33.19; P = 0.033).
CONCLUSION: Screening of patients with defective genetic variants of UGT1A6 and CYP2C9*3 helps in identifying patients at risk of aspirin induced gastritis. However, a randomised clinical study of bigger sample size would be needed before it is translated to clinical use.