ARTICLE | doi:10.20944/preprints202001.0217.v1
Subject: Biology, Plant Sciences Keywords: antioxidant; Nigella sativa; secondary metabolites; thymoquinone; DNA damage
Online: 19 January 2020 (14:33:58 CET)
Nigella sativa (NS) is an effective medicinal plant possessing noteworthy antioxidant property. In NS, there are more than hundred phyto-chemicals reported, out of which thymoquinone is the utmost active phyto-constituent having sturdy antioxidative property. Thymoquinone is a cyclicdione, when reacts with sodium azide, converts into α-azido ketones i.e its analogs which are handy with extensive range of reactions. Sodium azide induces stress in plants thereby, modulating the antioxidant system. The present investigation was planned to elucidate the effect of sodium azide at different concentrations (5µM, 10µM, 20µM, 50µM, 100µM and 200µM) on its secondary metabolites (mainly thymoquinone) in NS callus culture extract (NSE). The results showed sodium azide effect on thymoquinone content and a concentration dependent boost in antioxidant property. It was also observed that thymoquinone content and percent yield (analyzed by RP-HPLC; Reverse Phase- High Performance Liquid Chromatography) were minimum (0.033±0.006% and 0.420±0.045%, respectively) at 200 µM sodium azide used. Whereas, antioxidant activity (analyzed by DPPH; 2, 2-diphenyl-1-picrylhydrazyl) was found to be maximum (3.873±0.402%) at same dose. Further, analysis was done for inhibition of oxidative DNA damage at different concentrations of sodium azide on NSE, maximum inhibition of DNA damage (0.243±0.017%) was found at 200 µM concentration of sodium azide. When correlated, strong positive correlation was observed between percent yield and percent thymoquinone, antioxidant property and inhibition of DNA damage. Whereas, strong negative correlation was observed between percent yield and antioxidant property, percent thymoquinone and antioxidant property, percent thymoquinone and inhibition of DNA damage. The findings evidently point out that the content of thymoquinone, antioxidant property and inhibition of DNA damage was affected by sodium azide.
ARTICLE | doi:10.20944/preprints202301.0170.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: biopharmaceutical; nephroprotective; oral absorption; self-micellizing solid dispersion; thymoquinone.
Online: 10 January 2023 (03:09:17 CET)
The present study was designed to develop a self-micellizing solid dispersion (SMSD) containing Thymoquinone (TQM), a phytonutrient obtained from Nigella sativa seeds, aiming to improve its biopharmaceutical and nephroprotective functions. The apparent solubility of TQM in polymer solutions was used to choose an appropriate amphiphilic polymer that could be used to make an SMSD system. Based on the apparent solubility, Soluplus® was chosen as an appropriate carrier, and mixing with TQM, SMSD-TQM with different loadings of TQM (5–15%) was made by solvent evaporation and freeze-drying techniques, respectively, and the formulations were optimized. The optimized SMSD-TQM was evaluated in terms of particle size distribution, morphology, release characteristics, pharmacokinetic behavior, and nephroprotective effects in a rat model of acute kidney injury. SMSD-TQM significantly improved the dissolution characteristics (97.8%) of TQM in water within 60 min. Oral administration of SMSD-TQM in rats exhibited a 4.9-fold higher systemic exposure than crystalline TQM. In a cisplatin-induced (6 mg/kg, i.p.) acute kidney-damaged rat model, oral SMSD-TQM (10 mg/kg) improved the nephroprotective effects of TQM based on the results of kidney biomarkers and histological abnormalities. These findings suggest that SMSD-TQM might be efficacious in enhancing the nephroprotective effect of TQM by overcoming biopharmaceutical limitations.
ARTICLE | doi:10.20944/preprints202211.0372.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: biopharmaceutical; nephroprotective; oral absorption; self-micellizing solid dispersion; thymoquinone.
Online: 21 November 2022 (04:43:27 CET)
Nigella sativa's thymoquinone (TQM), a water-insoluble phytonutrient exhibits nephroprotective effects. This study intends to develop a self-micellizing solid dispersion (SMSD) of TQM for better biopharmaceutical and nephroprotective performance. Soluplus®-based SMSD of TQM was created and tested for physicochemical properties, solubility, and pharmacokinetics in rats. Plasma creatinine, blood urea nitrogen (BUN), nephrotoxic indicators, and oxidative stress biomarkers were also tested. During SMSD preparation, TQM was found amorphous, boosting solubility. Minimal band changes between TQM and Soluplus® indicate insignificant drug-carrier interactions. SMSD-TQM generated fine micelles in water, improving TQM's solubility by 97.8% in 60 min. SMSD-TQM was 4.9 times more bioavailable orally in rats than crystalline TQM. In a rat model of acute renal damage by cisplatin (6 mg/kg, i.p.), SMSD-TQM (10 mg-TQM/kg, p.o.) reduced blood creatinine and BUN by 56% and 63.2%, respectively. These findings imply that SMSD-TQM may be a potent dosage option for enhancing TQM's nutrient value.
ARTICLE | doi:10.20944/preprints202208.0364.v1
Subject: Biology, Other Keywords: TMPyP4 1; Thymoquinone 2; cell viability 3; cell adhesion 4; telomerase
Online: 19 August 2022 (10:46:07 CEST)
G‐quadruplexes (G4) are structures formed at the ends of the telomere, these are rich in guanines and were stabilized by molecules that bind to specific sites. TMPyP4 and Thymoquinone (TQ) are small molecules that bind to the G4, they have drawn attention because of their role as telomerase inhibitors. The aim of this study was to evaluate the effects of telomerase inhibitors on cellular proliferation, senescence, and death. Two cell lines LC‐HK2 (NSCLC) and RPE‐1 were treated with TMPyP4 (5μM) and TQ (10μM). Both inhibitors were effective in decreasing telomerase activity. TMPyP4 increased the percentage of cells with membrane damage associated with cell death and decreased the frequency of cells in the S‐phase. TMPyP4 changed the cell adhesion ability and modified the pattern of focal adhesion. TQ acted in a dose‐dependent manner, increasing the frequency of senescent cells, and inducing cell cycle arrest in the G1. In conclusion, the effects of both drugs on LC-HK2 and RPE-1 cell lines were different although both are telomerase inhibitors, because TMPyP4 decreased proteins of cell adhesion and TQ induces a decrease in cell viability.