Thymoquinone Research Articles

Enhancing Gentamicin Antibacterial Activity by Co-Encapsulation with Thymoquinone in Liposomal Formulation

Background and Purpose. Gentamicin (GEN) is a broad-spectrum antibiotic that cannot be prescribed freely because of its toxicity. Thymoquinone (THQ), a phytochemical, has antibacterial, antioxidant, and toxicity-reducing properties. However, its hydrophobicity and light sensitivity make it challenging to utilize. This incited the idea of co-encapsulating GEN and THQ in liposomes (Lipo-GEN-THQ). Method. Lipo-GEN-THQ were characterized using the zeta-potential, dynamic light scattering, Fourier transform infrared spectroscopy, and transmission electron microscope (TEM). The liposomes’ stability was evaluated under different storage and biological conditions. Lipo-GEN-THQ’s efficacy was investigated by the minimum inhibitory/bactericidal concentrations (MICs-MBCs), time–kill curves, and antibiofilm and antiadhesion assays. Bacterial interactions with the empty and GEN-THQ-loaded liposomes were evaluated using TEM. Results. The Lipo-GEN-THQ were spherical, monodispersed, and negatively charged. The Lipo-GEN-THQ were relatively stable and released GEN sustainably over 24 h. The liposomes exhibited significantly higher antibacterial activity than free GEN, as evidenced by the four-fold lower MIC and biofilm eradication in resistant E. coli strain (EC-219). TEM images display how the empty liposomes fused closely to the tested bacteria and how the loaded liposomes caused ultrastructure damage and intracellular component release. An antiadhesion assay showed that the Lipo-GEN-THQ and free GEN (0.125 mg/L) similarly inhibited Escherichia coli (EC-157) adhesion to the A549 cells (68% vs. 64%). Conclusions. The Lipo-THQ-GEN enhanced GEN by combining it with THQ within the liposomes, reducing the effective dose. The reduction in the GEN dose after adding THQ may indirectly reduce the toxicity and aid in developing an enhanced and safer form of GEN.

Dietary supplementation with thymoquinone inhibits rotenone induced developmental toxicity in Drosophila melanogaster: Focus on ovary and larval development

Pesticide exposure has been associated with various health conditions like asthma, Parkinson’s disease, Alzheimer’s disease, genetic disorders, epigenetic changes, oxidative stress, and hormonal disruption. Recent evidence suggests that infants are more vulnerable to pesticides (such as rotenone) than adults. Although the disease has already been clinically characterized, no treatment has yet been developed to improve pathology or prevent developmental toxicity. Therefore, the purpose of this study was to investigate whether thymoquinone (TQ) from Nigella sativa seeds could ameliorate rotenone (ROT)-induced developmental damage in both Drosophila melanogaster ovary and third instar larvae. Female adult wild-type flies and third instar larvae (72 ± 2 h after egg laying) were exposed to ROT and/or TQ through food for 48 and 24 h respectively. Results indicate that co-exposure of TQ inhibits ROT-induced increased oxidative stress and alleviates abnormal antioxidant enzyme activities. Further, TQ alters developmental gene expression (Bacoid, Oscar, Nanos, and Gurken), impedes mitochondrial dysfunction, and reduces apoptosis in ROT induced ovary. In addition, TQ changes ROT induced abnormal crawling behaviour, cholinergic dysfunction, and dopamine depletion to normal levels in third instar larvae. Also, TQ reduces pupation and emergence time in ROT induced third instar larvae. The above findings demonstrate that ROT exposure during early developmental stages is inevitable, and TQ supplementation prevents developmental toxicity in the Drosophila ovary and third instar larvae. A diet enriched TQ provides a ray of hope in preventing ROT induced developmental toxicity.

Thymoquinone Abrogates Acrylamide-Induced Cerebellar Toxicity via Modulation of Nuclear Factor Erythroid 2-Related Factor 2/Nuclear Factor Kappa B Signaling, Oxidative Neuroinflammation, and Neuroapoptosis in Rats.

Acrylamide (ACR) is an obligate human neurotoxicant ubiquitously produced and found in foods processed at high temperature. There is an increasing public health concern regarding its probable carcinogenic potential. Its prevailing toxicity mechanism is oxidative inflammation and apoptosis. Herein, we explored whether thymoquinone (TQ), a bioactive quinone in Nigella sativa seed, could mitigate ACR-induced cerebellar toxicity in rats. Our study design featured four rat groups: control, TQ (5 mg/kg bw), ACR (50 mg/kg bw), and TQ + ACR (5 mg/kg + 50 mg/kg). After 14 days of respective treatments, cerebellar homogenate was used to estimate acetylcholinesterase activity (AchE) activity, antioxidant enzymes (catalase [CAT], superoxide dismutase [SOD], and glutathione peroxidase [GPx]), malondialdehyde (MDA), inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-α, IL-4, and IL-10), nuclear factor kappa B (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), caspase-3, and caspase-9. The level of DNA damage by fragmentation and histopathological lesions was also determined in the cerebellum. The rat exposure to ACR caused significant decreases in the cerebellar activities of AchE, CAT, SOD, and GPx, IL-4, IL-10, and expression of Nrf2, whereas the levels of MDA, IL-6, TNF-α, caspase-3, and caspase-9 were prominently increased compared with the control. ACR induced significant DNA fragments and cerebellar lesions when compared with the control. Contrarily, TQ treatment inhibited the depression of CAT, SOD, and GPx activities and reversed the MDA level and expression of Nrf2/NF-κB, cytokines, and caspases. These effects were confirmed by reduced DNA damage and cerebellar histopathological lesions in comparison with the ACR. TQ afforded neuroprotection via its antioxidant, anti-inflammatory, and antiapoptotic mechanisms in rats.

Thymoquinone Effects on the Expression of p62 Gene in Cisplatin-Induced Testicular Damage in Mice

Background: Cisplatin (CPN) is widely used for the management of various malignant tumors. Objectives: This study investigated the effects of Thymoquinone (TQN) on the expression of the p62 gene in CPN-induced testicular damage in mice. Methods: Histomorphometry, testis injury scores, expression of p62, and protein levels of LC3-II were assessed. Results: Cisplatin induced histological changes, increased p62 expression (P < 0.01), and reduced LC3-II levels (P < 0.001). Thymoquinone pretreatment decreased p62 expression while increasing LC3-II protein levels. Thymoquinone significantly reversed the testicular injury scores and improved histomorphometric parameters. Conclusions: The results indicate that TQN enhances autophagy and improves testicular tissue in CPN-intoxicated mice.

Efficacy of Thymoquinone and Hesperidin in Attenuating Cardiotoxicity from 5-Fluorouracil: Insights from In Vivo and In Silico Studies.

5-Fluorouracil (5-FU) is widely used in chemotherapy but poses serious risks of cardiotoxicity, which can significantly affect treatment outcomes. Identifying interventions that can prevent these adverse effects without undermining anticancer efficacy is crucial. This study investigates the efficacy of Thymoquinone (TQ) and Hesperidin (HESP) in preventing cardiotoxicity induced by 5-FU in Wistar rats and elucidates the molecular interactions through docking studies. We employed an experimental design involving multiple groups of Wistar rats exposed to 5-FU, with and without the concurrent administration of TQ and HESP. Cardiac function markers, oxidative stress indicators, and inflammatory markers were assessed. Additionally, molecular docking was used to analyze the interaction of TQ and HESP with key inflammatory proteins. Treatment with TQ and HESP not only lowered levels of cardiac enzymes but also improved antioxidant capacity and reduced inflammation in cardiac tissues. Notably, the combination of TQ and HESP provided more significant protective effects than either agent alone. Molecular docking supported these findings, showing effective binding of TQ and HESP to inflammatory targets. TQ and HESP demonstrate potential as protective agents against cardiotoxicity in 5-FU-treated rats, with their combined use offering enhanced protection. These findings suggest a viable strategy for reducing cardiac risks associated with 5-FU chemotherapy.

Systemic Codelivery of Thymoquinone and Doxorubicin by Targeted Mesoporous Silica Nanoparticle Sensitizes Doxorubicin-Resistant Breast Cancer by Interfering between the MDR1/P-gp and miR 298 Crosstalk.

Multi drug resistance (MDR) in breast carcinoma still poses a significant impairment to successful chemotherapy. As the arsenal of anticancer agents increases with improved preclinical methods, the growth of therapeutic drug combinations is now unprecedented. The malignancies addressed by mono drugs often fail to limit cancer progression, resulting in resistant cancer, thereby offering combinatorial therapies a terrific edge over monodrug regimes. However, the selection of drug combinations required enough preliminary evidence for their synergistic effect. The fundamental mechanisms of MDR to chemotherapeutics are associated with the overexpression of membrane efflux pumps, alternations in drug targets, and increased drug metabolism. Unfortunately, it is very difficult for drugs to overcome resistance produced on their own or by another different drug action. In this context, herein, we report a simple delivery system for coencapsulation and intracellular codelivery of dual-drug thymoquinone (TQ) and doxorubicin (DOX) to resensitize DOX-resistant MDA MB231 cell line (231 R). The 231 R cell line developed in our lab showed an enhanced expression of the ATP-binding cassette (ABC) transporters P-gp1/MDR-1 and a declined miR-298 expression. The present delivery system is based on amine-functionalized mesoporous silica nanoparticles (MSNs), in which the side chain amine functional group was used to react with the carbonyl group of TQ, which acts as a pro-drug system (TQ-MSN) to release TQ and DOX simultaneously. DOX was encapsulated later into the above TQ-MSN by a simple diffusion method. The drugs containing MSNs were further coated with a hyaluronic acid-conjugated PEG-PLGA polymer (HA@TQ-DOX-MSN). This simple nanostrategy interferes with the MDR-1/miR-298 cross-talk, thereby allowing a significant reduction in drug efflux from the cell and highlighting a promising nanotechnology-based combinatorial delivery approach in managing breast cancer chemoresistance.

Developing and applying a single strategy for improved intestinal permeability of diverse and complex phytomolecules: nanoformulations of rutin, quercetin, thymoquinone provide proof-of-concept

Purpose: The clinical use of phytomolecules is restricted due to low oral bioavailability that may be attributed to their poor intestinal permeability owing to their complex structure, poor aqueous solubility and low biological stability. Rutin (RT), quercetin (QU), thymoquinone (TQ) are such potent and therapeutically versatile phytomolecules that await maximal utilization. Here we report a single strategy for enhanced intestinal permeation of diverse phytomolecules. Method: A simple idea with easy-to-apply method was developed that involved preparing nanoparticles of the phytomolecules RT, QU, TQ using eudragit matrix (RT-PNP, QU-PNP, TQ-PNP) and encapsulated in HPMC grade capsule shell. The PNPs were evaluated for particle characteristics, encapsulation efficiency, in vitro release kinetics, and intestinal permeability. Result: The average particle sizes of RT-PNP, QU-PNP, TQ-PNP were 446 ± 0.152, 39.6 ± 0.006 and 186 ± 0.513 nm, polydispersity indices were < 0.5 with negative zeta potential. The % release of respective phytomolecule from RT-PNP, QU-PNP, TQ-PNP was significantly higher (p<0.05) at pH 6.8 than pH 1.2. PNPs followed higuchi kinetics with non-Fickian diffusion mechanisms. The apparent intestinal permeability (Papp) of RT-PNP, QU-PNP, TQ-PNP were 14.45 ± 4.85, 12.96 ± 1.73 and 30.87 ± 8.75 µg/cm2, respectively, significantly (P <0.5) greater vs RT, QU, TQ, respectively. CLSM confirmed significantly higher (p<0.05) intestinal permeation of RT-PNP, QU-PNP, TQ-PNP vs RT, QU, TQ, respectively. Conclusion: Developed PNPs appear to be a good approach to increase the permeability of hydrophobic phytomolecules.

Comparison of The Effectiveness of Thymoquinone, St. John Wort Oil and Silver Sulfadiazine in Experimental Burn Wounds.

We aimed to compare the effectiveness of thymoquinone (TQ), most important bioactive component of black cumin, St. John wort (SJW) oil, a traditional medicinal plant used in burns, and silver sulfadiazine (AgSD), well-known anti-inflammatory agent used in modern medicine, in an experimental burn rat-model. 63 Wistar-Albino rats were randomly divided into 9 groups (n=7). TQ, SJW were administered topically and systemically but AgSD was applied topically. Epithelialization, inflammatory cell response, granulation tissue, vascularization, and fibrosis were evaluated. Malondialdehyde (MDA), total antioxidant status (TAS), total oxidant status (TOS), vitamin E, 8-hydroxy-deoxyguanosine (8-OHdG), coenzyme Q10 (CoQ10) were analyzed in serum. Topical TQ accelerated theepithelialization, enabled granulation, vascularization and fibrosis in wounds (P=0.001). Topical and systemic TQ increased Vitamin-E levels (P=0.003) but reduced TOS and 8-OHdG levels (P=0.001). Topical SJW reduced granulation and vascularization. Topical and systemic SJW decreased TOS, MDA and 8-OHdG levels (P=0.001), but increased TAS (P=0.001), and Vitamin-E levels (P=0.003). Topical AgSD reduced TOS, 8-OHdG, MDA levels (P=0.001). Topical and systemic TQ demonstrated significant advantages in accelerating wound healing process, while also enhancing antioxidant defenses and reducing oxidative damage. SJW oil, particularly in topical application, improved epithelialization and antioxidant status but showed less efficacy in systemic use. AgSD, while effective in reducing oxidative stress, was less successful in promoting wound healing and appeared to delay granulation and fibrosis. TQ offers superior protective and healing benefits, SJW is effective locally but less so systemically, and AgSD should be used cautiously, potentially combined with antioxidants to mitigate its negative impact on wound healing.

Therapeutic Effect of Thymoquinone on Melatonin, Ferritin, and Renal Function in Renal Ischemia/Reperfusion Injury in Rats

Objective: Ischemia/reperfusion (I/R) injury is the period of tissue or organ damage that develops after the tissue's blood flow is restored. The extent of damage varies according to the severity of tissue and cell damage. Thymoquinone (TQ) has a wide therapeutic spectrum. The effect of thymoquinone on melatonin and ferritin in I/R can regulate renal function by combining these two mechanisms to improve damage. Therefore, the effect of thymoquinone on melatonin and ferritin levels in renal I/R as well as its regulatory role in renal functions have been investigated. Methods: Thirty-six male Sprague Dawley rats were included in the study (250-300 g, 8-10 weeks). The rats were randomly assigned to 6 groups with 6 animals in each group. Groups; 1- Control, 2- Sham, 3- Solvent, 4- Renal ischemia/reperfusion injury (I/R), 5- I/R+ Thymoquinone (TQ) (5 mg/kg/day), 6- TQ (5 mg/kg/day). The dorsal region of the rats was surgically opened, and the left renal artery was clamped for 30 minutes and then reperfused for 24 hours. TQ (i.p) was applied to the treatment groups for 15 days. At the end of the experiment, blood samples were taken from all groups, and kidney function tests (Na+, K+, Creatinine, urea, BUN) were performed. Melatonin and ferritin levels were analyzed by the ELISA method from kidney tissue samples. Results: Data showed that short-term TQ treatment was effective on serum K+ (P = 0.010) and melatonin and ferritin levels in kidney tissue. Melatonin and iron activity, which were normal in healthy groups, melatonin decreased and ferritin increased significantly in the I/R group. TQ treatment positively regulated the dysregulation of these two molecules in I/R. Conclusion: TQ may contribute to the healing of the damage by improving the K+ levels, which indicates the insufficiency of kidney functions in I/R damage. Melatonin and ferritin, as interacting molecules in I/R, are regulated by TQ, indicating that they may contribute to the management of I/R damage.

Pilot scale manufacturing of black seed oil-loaded alginate beads; process development, and stability of thymoquinone

The approach of ionic gelation was employed at the pilot scale of the 50 kg batch size to manufacture black seed oil (BSO)-loaded alginate (ALG) beads as a natural source supplementing the main bioactive compound of BSO, i.e., thymoquinone (TQ). The BSO-ALG emulsion was prepared by initially emulsifying BSO with alginate solution at the pilot scale in two stages. The final emulsion was then dripped through 12 units of 3D-printed multi-nozzles into a curing bath containing Ca2+. The dripping flow rate was scaled up to 288 mL/min through the 3D-printed multi-nozzles (22-gauge). The characteristics of pilot scale BSO-ALG beads were similar to those produced at the lab scale; the beads were spherical with a size of 1.84–1.94 mm. The mechanical strength and loss on drying ranged from 143.6 to 172 g and 77.85–81.96 %, respectively. The production yield and encapsulation efficiency were 77.53–83.65 % and 95.36–97.9 %, respectively. Furthermore, the emulsification process did not affect TQ stability, while the curing process reduced TQ concentration from 1.51 % to 1.03 % w/w. Additionally, a substantial drop in TQ concentration in the encapsulated BSO was observed after the drying process, where it reached 0.23 % w/w. Finally, the stability of BSO-ALG beads in both wet and dried forms under real-time and accelerated conditions for 3 months revealed that beads were stable in terms of their organoleptic characteristics, size and sphericity, and loss on drying. Findings from this study enable the large-scale manufacturing of encapsulated BSO and similar bioactive compounds in ALG beads for the first time. These findings are valuable for advancing microencapsulation through ionic gelation and enhancing food preservation and safety.

Prospects for the Use of Thymoquinone (a Component of Nigella sativa) in the Prevention and Therapy of Neuropathologies

Black cumin and its component thymoquinone (TQ) are known as drugs with a wide range of pharmacological activities: immunomodulating, anti-inflammatory, antimicrobial, antiviral, antineoplastic properties. These drugs also have neuroprotective properties in neurodegenerative diseases (Alzheimer's, Parkinson's), ischaemia, epilepsy, encephalomyelitis, traumatic brain injury. The main mechanisms of action are antioxidant activity increased expression of neuroprotective genes and proteins with decreased activity of pro-inflammatory cytokines and the NF-кB pathway, which plays a key role in neuroinflammation. A separate section is devoted to the effects of black cumin and TQ on the course of depression, a common and socially significant illness. Reduced signs of depression and increased levels of a neuroprotective factor belonging to the neutrophin family (BDNF), a characteristic marker of depression, were described in 54 depressed patients. The review discusses the prospects for prevention and therapy with these drugs in central nervous system pathology.

Development of Mitoxantrone-Loaded Quercetin Nanoparticles for Breast Cancer Therapy with Potential for Synergism with Bioactive Natural Products

Nanoparticle (NP)-based drug delivery systems have caused a paradigm shift in cancer treatment by enabling drug targeting, sustaining drug release, and reducing systemic toxicity of chemotherapy. Here we developed a novel NP formulation for the anticancer drug mitoxantrone (MTZ) by loading it into an emerging nanomaterial derived from the plant polyphenol quercetin (QCT). QCT was partially oxidized to produce amphiphilic oxQCT which was co-assembled with poly(ethylene glycol) (PEG) and MTZ by nanoprecipitation to form MTZ NPs. The optimal NPs exhibited an average diameter of 128 nm, a polydispersity index of 0.22, and a drug loading efficiency of 76%. While only a small fraction of the loaded drug was released at physiologic pH, a significantly higher fraction was released at acidic pH. The anticancer activity of MTZ NPs was assessed in MCF-7 and MDA-MB-231 breast cancer cell lines, alone and in combination with the bioactive natural products curcumin (CUR) and thymoquinone (TQ). In cell viability assays, MTZ NPs were slightly less potent than free MTZ, most likely due to their sustained release properties, but their cytotoxicity was greatly enhanced in the presence of TQ (in MCF-7 cells) as well as CUR (in MDA-MB-231 cells). The results were corroborated by apoptosis assays such as mitochondrial membrane potential measurement, acridine orange/ethidium bromide staining, in addition to caspase activity assays. The assays revealed that the NPs’ proapoptotic effect was enhanced in the presence of CUR or TQ, depending on the cell line. Our work presents a promising nanocarrier platform for MTZ with the potential to enhance its bioactivity against breast cancer when combined with bioactive natural products.

Stereological and biochemical effects of thymoquinone on ovarian tissue toxicity induced by silver nanoparticles in NMRI mice: An experimental study.

The toxicity of silver nanoparticles (AgNPs) has been proven in the female reproductive system. Thymoquinone (TQ) is a natural antioxidant and bioactive component of Nigella sativa. We evaluated the efficacy of TQ on ovarian tissue following toxicity induced by AgNPs in female mice. 24 female NMRI mice (5-6 wk, an average weight of 33 gr) were randomly divided into 4 groups (n = 6/each): control, AgNPs (500 mg/kg, gavage), TQ (2.5 mg/kg, intraperitoneal injection), and TQ+AgNPs. Mice were treated every day for 35 days. Serum levels of malondialdehyde (MDA), total antioxidant capacity (TAC), luteinizing hormone, and follicle-stimulating hormone were measured. The optical disector and stereological techniques were utilized to estimate the follicular count, their volume at different developmental stages, and the structure of ovarian tissue. In the AgNPs group, the serum concentrations of TAC (p = 0.01), luteinizing hormone (p 0.001), follicle-stimulating hormone, the volume of corpus luteum (p 0.001), and the number of follicles decreased significantly compared to the control group. Nevertheless, AgNPs significantly increased the MDA level. In the TQ+AgNPs group compared to the AgNPs group, a significant decrease in MDA level (p 0.001) and a significant improvement in TAC (p = 0.03), and hormonal levels, the number of primary, preantral, and antral follicles (p = 0.04), and the volume of corpus luteum (p = 0.01) were observed. TQ improved the number of follicles by reducing oxidative stress and lipid peroxidation in AgNPs-damaged ovarian tissue.

Ameliorative Effects of Thymoquinone against Chemotherapy-Induced Testicular Damage in Experimental Animals: A Systematic Review.

Chemotherapeutic drugs have demonstrated effectiveness in treating various neoplastic conditions; however, they can also have detrimental effects on male gonadal function and fertility. Consequently, interest has grown in identifying novel approaches that can mitigate chemotherapy-induced testicular damage. Thymoquinone (TQ), the chief active component of the volatile oil of Nigella sativa (NS), has a wide range of therapeutic properties, including antioxidant, anti-inflammatory and anti-apoptotic effects. The aim of this systematic review was to identify experimental animal studies that have evaluated the protective effects of TQ against testicular complications associated with chemotherapy. In accordance with the preferred reporting items for systematic review and meta-analyses (PRISMA) guidelines, a thorough search was performed across several databases (PubMed, EBSCOhost, Sage and Scopus) to identify experimental studies published from 2010 to May 2022 that focused on rodent models and compared the effects of TQ versus other chemotherapeutic drugs. Eight studies met the inclusion criteria, comparing TQ with methotrexate (MTX), 6-mercaptopurine (6-MP), cyclophosphamide (CPA), bleomycin (BL), doxorubicin (DOX) or busulfan (BUS). The results of these studies consistently demonstrated that TQ significantly improved sperm parameters, the levels of oxidative stress (OS) markers, apoptosis markers, and hormones and testicular histopathology, indicating that TQ has protective effects against chemotherapy-induced damage. TQ mitigated chemotherapy-induced testicular toxicity by decreasing lipid peroxidation and enhancing the activity of antioxidant enzymes within chemotherapy-treated testes. These findings highlight the potential of TQ as a therapeutic agent that can ameliorate testicular complications associated with chemotherapy, thereby providing a basis for further research and potential therapeutic applications.

5-Fluorouracil in Combination with Calcium Carbonate Nanoparticles Loaded with Antioxidant Thymoquinone against Colon Cancer: Synergistically Therapeutic Potential and Underlying Molecular Mechanism.

Colon cancer is the third most common cancer worldwide, with high mortality. Adverse side effects and chemoresistance of the first-line chemotherapy 5-fluorouracil (5-FU) have promoted the widespread use of combination therapies. Thymoquinone (TQ) is a natural compound with potent antioxidant activity. Loading antioxidants into nano delivery systems has been a major advance in enhancing their bioavailability to improve clinical application. Hence, this study aimed to prepare the optimal TQ-loaded calcium carbonate nanoparticles (TQ-CaCO3 NPs) and investigate their therapeutic potential and underlying molecular mechanisms of TQ-CaCO3 NPs in combination with 5-FU against colon cancer. Firstly, we developed purely aragonite CaCO3 NPs with a facile mechanical ball-milling method. The pH-sensitive and biocompatible TQ-CaCO3 NPs with sustained release properties were prepared using the optimal synthesized method (a high-speed homogenizer). The in vitro study revealed that the combination of TQ-CaCO3 NPs (15 μM) and 5-FU (7.5 μM) inhibited CT26 cell proliferation and migration, induced cell apoptosis and cell cycle arrest in the G0/G1 phase, and suppressed the CT26 spheroid growth, exhibiting a synergistic effect. Finally, network pharmacology and molecular docking results indicated the potential targets and crucial signaling pathways of TQ-CaCO3 NPs in combination with 5-FU against colon cancer. Therefore, TQ-CaCO3 NPs combined with 5-FU could enhance the anti-colon cancer effects of 5-FU with broader therapeutic targets, warranting further application for colon cancer treatment.

Determination of the Effect of Thymoquinone on DNA Damage in Kidney Cells Treated to High Glucose Depending on Time and Dosage by Comet Assay

The purpose of this study was to assess the anti-genotoxic potential of thymoquinone (TQ) against DNA damage in NRK-52E cells treated with high glucose using the comet assay technique single cell gel electrophoresis method. Cells were propagated by regular passages in in vitro conditions. TQ proliferative concentration (10μM) and IC25 (3rd-hour: 550 mM, 12th-hour: 240 mM, 24th-hour: 200 mM) and IC50 (3rd-hour: 760 mM, 12th-hour: 400 mM, 24th-hour: 280 mM) values for each hour of high glucose and were determined separately with MTT method. At these concentrations, the cells were divided into control(C), Thymoquinone (TQ), high glucose(G) and high glucose plus thymoquinone (GT) groups; It was incubated with the indicated substances for 3, 12, 24 hours. DNA damage was evaluated by applying the comet assay protocol and the results were calculated as DNA damage index (DDI). While DDI levels were observed to be significantly higher (p<0.05) in all groups administered high glucose compared to the control, a significant decrease was determined in all groups in which TQ was added along with high glucose. It was determined that high concentrations of glucose had genotoxic effects on kidney cells, and TQ administration together with high glucose, depending on concentration and time, had a significant effect on reducing DNA damage. However, it was concluded that the application of only thymoquinone significantly increased the DDI value compared to the control, and this was a data worth investigating in future studies. Additionally, TQ inhibited DNA damage. These results demonstrated the importance of TQ against nephrotic syndrome with its high antioxidant properties.

Assessment of Phytochemical Properties of Nigella sativa Seeds Essential Oil and Its Potential Antimicrobial Activity against Staphylococcus aureus in the Context of Safety Profiles and Therapeutic Applications in Neurosurgical Interventions

This comprehensive study explored the phytochemical properties of Nigella sativa L (N. sativa L) seeds essential oil using gas chromatography-mass spectrometry (GC-MS) analysis, with a specific focus on its potential compound Thymoquinone (TQ) exhibiting antimicrobial activity against Staphylococcus aureus (S. aureus) in the context of neurosurgical interventions.The study employs a meticulous methodology, encompassing the preparation of N. sativa essential oil, qualitative phytochemical screening, quantitative GC-MS analysis, and the antimicrobial analysis, employing Disc Diffusion, Minimum Inhibitory Concentration (MIC), and Minimum Bactericidal Concentration (MBC) evaluations to demonstrate the substantial inhibitory and bactericidal effects against Staphylococcus aureus (S.aureus}. comprehensive assessment of antimicrobial activity.The qualitative analysis reveals the presence of alkaloids, flavonoids, phenols, tannins, cardiac glycosides, steroids, saponins, and terpenoids, underscoring the multifaceted pharmacological potential of the essential oil. The quantitative GC-MS analysis provides a detailed breakdown of the chemical composition under different extraction conditions, showcasing the complexity of N. sativa essential oil. The study thoroughly compares the antimicrobial efficacy of N. sativa essential oil with various antibiotics, employing Disc Diffusion, MIC, and MBC analyses. N. sativa demonstrates substantial inhibitory effects, with a 29 mm zone comparable to Gentamycin. The MIC and MBC values align with established antibiotics, indicating similar bacteriostatic and bactericidal properties. Despite slightly lower potency than Vancomycin and Methicillin, N. sativa exhibits considerable antimicrobial effectiveness. This study contributes valuable insights into the phytochemical composition of N. sativa seeds essential oil and its potential as an antimicrobial agent in the context of neurosurgical interventions paves the way for future research.

Nano-based formulations of thymoquinone are new approaches for psoriasis treatment: a literature review.

Psoriasis, a persistent immune-mediated inflammatory skin condition, affects approximately 2-3% of the global population. Current treatments for psoriasis are fraught with limitations, including adverse effects, high costs, and diminishing efficacy over time. Thymoquinone (TQ), derived from Nigella sativa seeds, exhibits promising anti-inflammatory, antioxidant, and immunomodulatory properties that could prove beneficial in managing psoriasis. However, TQ's hydrophobic nature and poor bioavailability have hindered its usefulness as a therapeutic agent. Recent research has strategically addressed these challenges by developing nano-thymoquinone (nano-TQ) formulations to enhance delivery and efficacy in treating psoriasis. Preclinical studies employing mouse models have demonstrated that nano-TQ effectively mitigates inflammation, erythema, scaling, epidermal thickness, and cytokine levels in psoriatic lesions. Various nano-TQ formulations, including nanoemulsions, lipid vesicles, nanostructured lipid carriers, and ethosomes, have been explored to improve solubility, facilitate skin penetration, ensure sustained release, and achieve site-specific targeting. Although clinical trials are currently scarce, the outcomes from in vitro and animal models are promising. The potential co-delivery of nano-TQ with other anti-psoriatic agents also presents avenues for further investigation.

Thymoquinone reversed doxorubicin resistance in U87 glioblastoma cells via targeting PI3K/Akt/mTOR signaling.

Natural compounds such as thymoquinone (TQ) have recently gained increasing attention in treating glioblastoma (GBM). However, the effects of TQ in reversing drug resistance are not completely understood. Therefore, we aimed to examine TQ impacts on GBM cells with doxorubicin (DOX) resistance and the involvement of the PI3K/Akt/mTOR pathway. GBM cancer U87 and U87/DOX (resistant cells) cells were exposed to DOX and TQ, and cell proliferation was assessed by the MTT assay. ELISA was applied to evaluate cell apoptosis. The expression of apoptotic mediators such as Caspase-3, Bax, Bcl-2 and PI3K, Akt, mTOR, P-gp, and PTEN was assessed via qRT-PCR and western blot. We found that a combination of TQ and DOX suppressed dose-dependent cell growth capacity in cells and increased the cytotoxic effects of DOX in resistant cells. In addition, TQ treatment increased DOX-mediated apoptosis in U87/DOX cell lines via modulating the pro- and anti-apoptotic markers. A combination of TQ and DOX upregulated PTEN and downregulated PI3K, Akt, and mTOR, suppressing this signal transduction in resistant cells. In conclusion, we showed TQ potentiated doxorubicin-mediated antiproliferative and pro apoptotic function DOX-resistant glioblastoma cells, which is mediated by targeting and suppressing PI3K/Akt/mTOR signal transduction.

The anti-neoplastic impact of thymoquinone from Nigella sativa on small cell lung cancer: In vitro and in vivo investigations.

Malignant and aggressive, small cell lung cancer (SCLC) constitutes about 15% of all diagnosed lung cancer cases. With primary therapeutic options such as chemotherapy accompanied by debilitating side effects, interest has been soaring in the therapeutic competencies of herbs. The pharmacological driving force behind the beneficial properties of Nigella sativa is the quinone, thymoquinone (TQ). The anti-cancer effects of TQ on different cancers have been extensively studied. Nonetheless, only one paper in the entire National Center for Biotechnology Information (NCBI) database describes its effects on SCLC. A more detailed investigation is required. The current study examined the impact of TQ in vitro on five SCLC cell lines and in vivo in a nude mouse xenograft model. The following in vitro effects of TQ on SCLC were evaluated: (a) cell viability; (b) apoptosis; (c) cell cycle arrest; (d) intracellular reactive oxygen species (ROS) levels, and (e) protein expression in concomitant signaling pathways. For the in vivo effects of TQ on SCLC, (a) tumor volume was measured, and (b) selected protein expression in selected concomitant signaling pathways was determined by Western blotting. In general, TQ reduced cell viability, induced apoptosis and cell cycle arrest, depleted ROS, and altered protein expression in associated signaling pathways. Furthermore, TQ exhibited a tumor-suppressive effect in an H446 SCLC xenograft model. The cytotoxic impact of TQ arising from anti-cancer mechanisms was elucidated. The positive results obtained in this study warrant further investigation.