Isolation of a novel isoprenylated phenolic compound and neuroprotective evaluation of Dodonaea viscosa extract against cerebral ischaemia-reperfusion injury in rats.

Dodonaea viscosa grows widely in Saudi Arabia, but studies evaluating its neuroprotective activity are lacking. Thus, this study aimed to isolate and identify the secondary metabolites and evaluate the neuroprotective effects of D. viscosa leaves. The isolation and identification of phytochemicals were performed using chromatographic and spectroscopic techniques. The neuroprotective potential of the extract was evaluated against focal cerebral ischaemia-reperfusion injury in rat model. Neurobehavioural deficits in the rats were evaluated, and their brains were harvested to measure infarct volume and oxidative biomarkers. Results revealed the presence of three compounds: a novel isoprenylated phenolic derivative that was elucidated as 4-hydroxy-3-(3'-methyl-2'-butenyl) phenyl 1-O-ß-D-apiosyl-(1''' â†’ 6'')- ß-D-glucopyranoside (named Viscomarfadol) and two known compounds (isorhamnetin-3-O-rutinoside and epicatechin (4-8) catechin). Pre-treatment of the rats with the extract improved neurological outcomes. It significantly reduced neurological deficits and infarct volume; significantly reduced lipid peroxidation, as evidenced by decreased malondialdehyde levels; and significantly elevated antioxidant (superoxide dismutase, catalase, and glutathione) activities. These results indicate that D. viscosa is a promising source of bioactive compounds that can improve neurological status, decrease infarct volume, and enhance antioxidant activities in rats with cerebral ischaemic injury. Thus, D. viscosa could be developed into an adjuvant therapy for ischaemic stroke and other oxidative stress-related neurodegenerative disorders. Further investigations are warranted to explore other bioactive compounds in D. viscosa and evaluate their potential neuroprotective activities.

Effect of C. cyminum and L. sativum on Pharmacokinetics and Pharmacodynamics of Antidiabetic Drug Gliclazide.

BACKGROUND: Numerous herbs are reported to have anti-hyperglycemic activity and are frequently used in combination with prescription drugs to lower the blood glucose levels in diabetic patients, without proper knowledge about the possibility of herb-drug interaction. OBJECTIVES: To investigate the effect of cumin and garden cress on pharmacokinetics (PK) and pharmacodynamics (PD) of gliclazide (GLZ) in nicotinamide-streptozotocin diabetic model. METHODS: Diabetic animals of groups II-IV were treated with GLZ, cumin, 'cumin + GLZ', garden cress and 'garden cress + GLZ'. Herb's treatments were given for two weeks, and GLZ was administered in a single dose. Blood glucose levels (BGLs) were measured at pre-determined time points. Plasma samples of pharmacokinetic study were analyzed using UPLC-MS/MS. GLZ fragment at m/z 324.1>127 was monitored. RESULTS: Cumin and garden cress have shown 15.3% and 15.9% reduction in mean BGL (1-24h) (p-value < 0.001), respectively. GLZ reduced mean BGL by 30.0%, which was significantly better than cumin and garden cress (pvalue <0.05). Concurrently administered "garden cress + GLZ" demonstrated the highest reduction in mean BGL (by 40.46%) and showed a prolonged effect. There was no significant advantage of simultaneously administered 'cumin + GLZ'. Cumin did not affect PK of GLZ. Garden cress has significantly enhanced AUC0-t (by 69.8%, pvalue 0.0013), but other PK parameters Cmax, Tmax, and Kel were close to the control group. CONCLUSION: PK/PD-based herb-drug interaction was observed. Concurrently administered garden cress + GLZ showed improved antidiabetic effect and has enhanced GLZ bioavailability.

Synthesis and in-vitro antifungal activity of 6-substituted-phenyl-2- {[(4'-substituted phenyl-5'-thioxo)-1,2,4-triazol-3-yl]-methyl}-2,3,4,5-tetrahydropyridazin-3-one derivatives.

The synthetic pathway for 6-substituted phenyl-2-[{(4'-substituted phenyl-5'-thioxo)-1,2,4-triazol-3-yl}-methyl]-2,3,4,5-tetrahydropyridazin-3-one compounds was achieved by a sequence of reactions starting from respective aryl hydrocarbons and is illustrated in Scheme 1. All the compounds were tested for their in vitro antifungal activity on five fungal species, namely Candida albicans, Trichophyton rubrum, Aspergillus flavus, Aspergillus niger and Penicillium citrinium. The chloro substituent derivative (compound 5g) showed the highest activity against all the fungal species. The MIC of the standard drug voriconazole was between 0.10 - 0.40 microg/mL against all the fungal species except A. fumigatus. The two electronegative groups of Cl were increasing the activity of 1,2,4-triazole. As we increased the bulky group or aromatic group on benzene ring, there was a decrease of activity as in case of compound 1.