Bioactivities of holmium(III) and gadolinium(III) complexes of thymoquinone

Chemotherapeutic agents which are the main stay in cancer treatment are toxic with numerous contrary side effects. A number of chemical, physical, and computational techniques were applied to synthesize and elucidate the structural and functional characterization of the new designed bioligands and their metal complexes. Besides, several biological techniques for developing therapeutics and diagnostics agents of these new designed materials were used. The trivalent holmium(III) and gadolinium(III) metal complexes of thymoquinone (TQ) were synthesized. Toxicities and other bioactivites were undertaken with existing drug combinations and more effective tumor models will be established. The molecular structures of TQ-metal complexes were elucidated based on particular spectral approaches. The NF-kB (nuclear factor kappa-light-chain enhancer of activated B Cells) luciferase, elastase release, superoxide anion (O2•−) generation, and DPPH (1,1-diphenyl-2-picryl hydrazyl) free-radical scavenging activities of TQ and its synthesized complexes were elucidated and discussed. The core research is to use coordination and organometallic chemistry to design new bioligands and binary, ternary, mixed ligand, multi metal multi ligand complexes pursing a bio target continuously with structure-activity relationships (SARS).                     KEY WORDS: Thymoquinone, Holmium, Gadolinium, Bioactivities   Bull. Chem. Soc. Ethiop. 2021, 35(1), 87-96. DOI: https://dx.doi.org/10.4314/bcse.v35i1.

Effect of epigallocatechin-3-gallate on inflammatory mediators release in LPS-induced Parkinson's disease in rats

357-362Degeneration of dopamine (DA)-containing neurons in the substantia nigra of the midbrain causes Parkinson's disease (PD). Although neuroinflammatory response of the brain has long been speculated to play a role in the pathogenesis of this neurological disorder, the mechanism is still poorly understood. The aim of the present study was to examine the effect of epigallocatechin-3-gallate (EGCG) in prevention of inflammatory mediators release and protection of dopaminergic neurons from lipopolysaccharide (LPS)-induced neurotoxicity. A single intraperitoneal injection of LPS (15 mg/kg) in male Sprague Dawley rats resulted in an increase of midbrain content of TNF-, NO and a decrease of DA level at 4, 24 h, 3 and 7 days compared to the control. In addition, LPS reduced the number and the density of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the midbrain at 7 days. Pretreatment with EGCG (10 mg/kg) 24 h before LPS for 7 days decreased TNF- and NO compared to LPS-treated rats. Moreover, it increased DA level and preserved the number and the density of TH-ir neurons compared to LPS group. In conclusion, EGCG was found to have a potential therapeutic effect against LPS-induced neurotoxicity via reducing TNF- and NO inflammatory mediators and preserving DA level in midbrain. </span

Zingerone alleviates the delayed ventricular repolarization and AV conduction in diabetes: Effect on cardiac fibrosis and inflammation.

The study aims to analyse the action of zingerone in diabetes-related cardiac arrhythmias.Diabetes was induced by streptozocin while treatment groups received 20 mg/kg zingerone daily. Following extra seven weeks, electrocardiography, extraction of blood, urine and heart for biochemical analysis, histopathology and immunofluorescence were undertaken.The suppression of QT and QTc prolongation in diabetic rats was indicative of prolonged cardiac repolarisation that was greatly reduced by zingerone treatment. In addition, the reduction in PR interval attested that zingerone improved AV delay in diabetic rats. The fibrogenic transforming growth factor β1 upregulation in diabetic hearts was suppressed by zingerone. The marked glycogen deposition and muscle degeneration seen in diabetic heart sections were also alleviated by zingerone. Furthermore, zingerone prevented the decrease in of the serum anti-inflammatory cytokine adiponectin in diabetics. The heightened levels of oxidative stress markers 8-isoprostane and uric acid in diabetic rats were suppressed. In the diabetic heart, the reduced catalase activity was improved and the excessive expression of angiotensin receptor 1 was inhibited by zingerone.Cardiac delayed repolarisation and AV conduction in rats with diabetes were halted by zingerone. It appears that inhibition of cardiac fibrosis and associated inflammation-oxidative stress signalling underpins the zingerone effect

Zingerone alleviates the delayed ventricular repolarization and AV conduction in diabetes: Effect on cardiac fibrosis and inflammation - Fig 1

<p>The impact of 20 mg/kg zingerone orally administered every day on cardiac ECG parameters QT (A), QTc (B), PR interval (C) and P-duration (D) in rats with diabetes (D) induced with 50 mg/kg streptozotocin and in control rats. (E) are representative cardiac ECG recordings. Expression of values takes the form of mean ± SD for N = 6–8 rats. According to the one-way ANOVA and Newman Keuls’ post-hoc test, by comparison to the control group value and D group value, *P<0.05 and ^#P<0.05, respectively.</p

The impact of 20 mg/kg zingerone orally administered every day on urine 8-isoprostane level and serum uric acid level in rats with diabetes (D) induced with 50 mg/kg streptozotocin and in control rats.

<p>Expression of values takes the form of mean ± SD for N = 6–8 rats. According to the one-way ANOVA and Newman Keuls’ post-hoc test, by comparison to the control group value and D group value, *P<0.05 and ^#P<0.05, respectively.</p

The impact of 20 mg/kg zingerone (Z) orally administered every day on collagen deposition in heart longitudinal (LS) and transverse (TS) sections stained with Masson Trichrome of rats with diabetes (D) induced with 50 mg/kg streptozotocin and in control (C) rats.

<p>Collagen fibres are stained blue. The solid arrows indicate degenerated cardiac muscle fibers, hollow stars indicate patches of fibrous tissue.</p