Chemopreventive Agents from Nature: A Review of Apigenin, Rosmarinic Acid, and Thymoquinone.

Cancer, a major challenge to global health and healthcare systems, requires the study of alternative and supportive treatments due to the limitations of conventional therapies. This review examines the chemopreventive potential of three natural compounds: rosmarinic acid, apigenin, and thymoquinone. Derived from various plants, these compounds have demonstrated promising chemopreventive properties in in vitro, in vivo, and in silico studies. Specifically, they have been shown to inhibit cancer cell growth, induce apoptosis, and modulate key signaling pathways involved in cancer progression. The aim of this review is to provide a comprehensive overview of the current research on these phytochemicals, elucidating their mechanisms of action, therapeutic efficacy, and potential as adjuncts to traditional cancer therapies. This information serves as a valuable resource for researchers and healthcare providers interested in expanding their knowledge within the field of alternative cancer therapies.

Innovative approach against cancer: Thymoquinone-loaded PHEMA-based magnetic nanoparticles and their effects on MCF-7 breast cancer.

Breast cancer is most common cancer among women in the World. Thymoquinone (TQ) exhibits a wide range of biological activities such as anticancer, antidiabetic, antimicrobial, analgesic, antioxidant, and anti-inflammatory effects. However, its effectiveness in cancer treatment is hindered by its poor bioavailability, attributed to its limited solubility in water. Hence, novel strategies are required to enhance the bioavailability of TQ, which possesses remarkable anticancer characteristics. The aim of this study is to prepare pHEMA-based magnetic nanoparticles carrying TQ (TQ-MNPs) to improve bioavailability, and therapeutic efficacy against breast cancer. For this purpose, TQ-MNPs were synthesized and characterized with Fourier transform infrared spectrophotometer (FTIR), scanning electron microscopy (SEM), dynamic light scattering (DLS), magnetic field using a vibrating sample magnetometer (VSM). The loading capabilities of synthesized magentic nanostructures were evaluated, and release investigations were conducted under experimental conditions that mimic the cellular environment. The findings of the studies indicated that the TQ carrying capacity of MNPs was deemed satisfactory, and the release efficiency was adequate. MNPs and TQ-MNPs showed biocompatibility against HDFa cells. TQ-MNPs showed stronger anti-proliferative activity against MCF-7 breast cancer cells compared to free TQ (p < 0.05). TQ-MNPs induced apoptosis in MCF-7 breast cancer cells.

Computational and in vitro analyses on synergistic effects of paclitaxel and thymoquinone in suppressing invasive breast cancer cells.

BACKGROUND: In the present experiment, we evaluated the impact of thymoquinone (TQ) and paclitaxel (PTX) treatment on MDA-MB-231 cell line growth inhibition via controlling apoptosis/autophagy. MATERIALS AND RESULTS: MDA-MB-231cells were exposed to PTX (0, 25, 50, 75, and 100 nM), TQ (0, 25, 50, 75, and 100 µM), and combinations for 48 h. After the MTT assessment, dose-response curves and IC50 values were calculated, and the combination synergism was evaluated using the Compusyn software. Following the treatment with PTX, TQ, and combinations at IC50 doses, the expression of apoptosis and autophagy genes was assessed in cells. The GraphPad Prism program was used to analyze the data, and Tukey's test at p < 0.05 was then run. PTX, TQ, and their combinations inhibited MDA-MB-231cell proliferation and viability dose-dependently. TQ reduced the effective concentration (IC50) of PTX in co-treatment groups. PTX and TQ showed antagonistic effects when cell proliferation declined above 70%. Antagonistic effects shifted into additive and synergistic effects upon increasing PTX concentration, indicated by diminished cell proliferation below 70%. PTX-TQ co-treatment significantly enhanced P53 and BAX expression while reducing Bcl-2 expression. Also, their combination increased Beclin-1, ATG-5, and ATG-7 expression in treated cells. CONCLUSION: Effective concentrations of TQ and PTX had synergic effects and inhibited breast cancer cells via prompting apoptosis and autophagy in vitro.

Thymoquinone improves experimental autoimmune encephalomyelitis by regulating both pro-inflammatory and anti-inflammatory cytokines.

Introduction Multiple sclerosis (MS) is an autoimmune condition marked by inflammation and the loss of myelin in the central nervous system (CNS). The aim of this research was to understand how Thymoquinone regulate the molecular and cellular processes involved in controlling experimental autoimmune encephalomyelitis (EAE), which is an animal model often used to study MS. Methods Female C57BL/6 mice were split into different groups receiving different doses (low, medium, and high) of Thymoquinone simultaneously with EAE induction. Clinical scores and other measurements were observed daily throughout the 25-day post immunization. We assessed lymphocyte infiltration and demyelination in the spinal cord through histological staining, analyzed T-cell profiles using ELISA, and quantified the expression levels of transcription factors in the CNS using Real-time PCR. Results Thymoquinone prevented the development of EAE. Histological experiments revealed only a small degree of leukocyte infiltration into the CNS. Thymoquinone resulted in a notable reduction in the generation of IFN-γ, IL-17, and IL-6, while simultaneously increasing the production of IL-4, IL-10, and TGF-ß in Th2 and Treg cells. Results from Real-time PCR suggested Treatment with Thymoquinone decreased the expression of T-bet and ROR-γt while increasing the expression of Foxp3 and GATA3. Conclusion These findings showed that Thymoquinone could decrease both disease incidence and severity.

Role of Thymoquinone on sleep restriction and its mitigating effect on leptin-mediated signaling pathway in rat brain.

BACKGROUND: Sleep and stress interact bidirectionally by acting on brain circuits that affect metabolism. Sleep and its alterations have impact on blood leptin levels, metabolic hormone that regulates appetite. Brain expresses the receptors for the peptide hormone leptin produced from adipocytes. The hypothalamic orexin neurons are low during sleep and active when awake, influenced by a complex interaction with leptin. Thymoquinone was found to be the major bioactive component of Nigella sativa. The aim of this study was to study the role of thymoquinone on sleep restriction and its mitigating effect on leptin-mediated signaling pathway in rat brain. METHODS AND RESULTS: 30 adult male Wistar rats were divided into 5 groups with 6 animals in each group: Control; Thymoquinone (TQ); Corn oil; Chronic Sleep restriction (CSR); and CSR + TQ. After 30 days, behavioral analysis, antioxidant, lipid profile, glucose level, liver and kidney function test, neurotransmitters, neuropeptides, and mRNA expression in in vivo studies were also assessed and pharmacokinetic and docking were done for thymoquinone. Thymoquinone has also shown good binding affinity to the target proteins. CSR has induced oxidative stress in the discrete brain regions and plasma. Current study has shown many evidences that sleep restriction has altered the neurobehavioral, antioxidant status, lipid profile, neurotransmitters, neuropeptide levels, and feeding behavior which damage the Orexin-leptin system which regulates the sleep and feeding that leads to metabolic dysfunction. CONCLUSION: The potentiality of Thymoquinone was revealed in in silico studies, and its action in in vivo studies has proved its effectiveness. The study concludes that Thymoquinone has exhibited its effect by diminishing the metabolic dysfunction by its neuroprotective, antioxidant, and hypolipidemic properties.

Effects of thymoquinone and the curcumin analog EF-24 on the activity of the enzyme paraoxonase-1 in human glioblastoma cells U87MG.

The spices and aromatic herbs were used not only in cooking to add flavour and smell to dishes but also for medicinal use. Nigella sativa, also called black cumin, is one of the species that contains an important bioactive component, thymoquinone (TQ), which has antioxidant, anti-inflammatory, antimicrobial, and antidiabetic effects. Curcuma longa, which also includes curcumin, has numerous anti-cancer properties. However, the bioavailability of curcumin is lower than that of its analogs. An analog of curcumin (EF-24), which has better bioavailability than curcumin, is capable of exerting a high anti-cancer effect. In our study, we determined the effects of PON1 enzyme activity on the proliferation and aggressiveness of glioblastoma cancer treated with TQ and EF-24 from lysates of the glioblastoma cell line U87MG. The results were determined as increased PON1 activity after treatment with TQ and EF-24 in the U87MG cell line (p < 0.0001).

Evaluation the effect of dietary vitamin E, sesamin and thymoquinone bioactive compounds on immunological response, intestinal traits and MUC-2 gene expression in broiler Japanese quails (Coturnix japonica).

The current study was performed to determine the effect of dietary vitamin E, sesamin and thymoquinone bioactive lignans derived from sesame and black seed on immunological response, intestinal traits and Mucin2 gene expression in broiler quails. Three hundred and fifty (one days-old) quails were allotted to seven dietary treatments with five replicates as an experimental randomized design study. Treatments were basal diet as a control, control +100 and +200 mg of vitamin E, sesamin and thymoquinone per each kg of diet respectively. At 35 d of age, two quails from each pen were chosen, weighted, slaughtered, eviscerated and lymphoid organ relative weights were measured. Anti-body titers against Newcastle disease (ND), Sheep red blood cell (SRBC), and infectious bronchitis virus (IBV) and Avian influenza (AI) vaccination were determined. The serum activities of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and serum antioxidant activates such as superoxide dismutase (SOD),glutathione peroxidase(GPX), catalase (CAT) and total antioxidant capacity (TAC) were examined. The cell mediated immunity by dinitrochlorobenzene (DNCB) and phytohemagglutinin (PHA) challenges were assessed. The microflora populations of ileum, morphological traits of jejunum and mucin2 gene expression were analyzed. Data showed that the lymphoid organ (thymus, spleen and Bursa) relative weights and antibody titer against HI, AI, SRBC and IB vaccination were increased compared to the control (p ≤ 0.05). Serum activities of ALP, ALT and AST were decreased under influences of dietary treatments (p ≤ 0.05). The serum antioxidant activates of GPX,SOD,CAT and TAC were increased and Increasing in mean skin thickness after DNCB challenge and decrease wing web swelling response to PHA mitojen injection were observed (p ≤ 0.05). Salmonella enterica, E-coli and Coliforms colonies were decrease and Lactobacillus colonies increased instead (p ≤ 0.05). The villus height and surface, crypt depth and goblet cells density were increased compared to the control (p ≤ 0.05). The expression of MUC2 gene increased under influnces of vitamin E, sesamin and thymoquinone supplemented diets (p ≤ 0.05).

Thymoquinone effects on autophagy, apoptosis, and oxidative stress in cisplatin-induced testicular damage in mice.

PURPOSE: In this study, the effect of thymoquinone (TQ) on CP-induced spermatogenesis defects in mice has been investigated. METHODS: Sperm parameters, serum testosterone concentration, histology, Bax/Bcl-2 ratio, and expression of autophagy-related biomarkers have been assessed. Total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI) in testicular tissue were examined for the evaluation of oxidative stress levels. RESULTS: CP has induced histological changes and significantly increased the Bax/Bcl-2 ratio, decreased testosterone concentration, testicular weight, and sperm quality. CP induced oxidative stress by elevating OSI in the testicular tissue (p < 0.05). Expression of the autophagy-inducer genes (ATG7, ATG5, and Beclin-1) and ratio of LC3B/LC3A proteins were significantly decreased, while mTOR expression was increased in the CP group. TQ pretreatment dose-dependently decreased the Bax/Bcl-2 ratio and mTOR gene expression while increasing the expression of ATG5 and ATG7 genes, LC3B/LC3A ratio, and Beclin-1 proteins. TQ could also dose-dependently reverse the histology, testosterone level, and sperm quality of the CP-intoxicated mice. CONCLUSIONS: These findings show that TQ pretreatment can enhance sperm production by inducing autophagy and reducing apoptosis and oxidative stress in the CP-intoxicated mouse testicles.

A Study on Thymoquinone: Antioxidant Capacity and Anticancer Activities in LoVo Colorectal Cancer Cells.

Thymoquinone has antioxidant and anticancer effects. This study investigates the cytotoxic, genotoxic, and apoptotic effects of black seed and its active ingredient, thymoquinone on colorectal cancer cells. The antioxidant content of Black seed methanolic extracts (BSME) with different concentrations (50, 500 and 1000 µg/mL) were determined by the photometric methods. The reactive oxygen production (iROS) of BSME and thymoquinone on colorectal cancer cells (LoVo) and normal epithelial cells (CCD18Co) were analyzed by the fluorometric methods. A luminometric glutathione kit was employed to observe the changes in intracellular glutathione (GSH) levels. Cytotoxicity was determined by the ATP method, genotoxicity was determined by Comet Assay, and the apoptosis was identified by the Acridine Orange/Ethidium Bromide (AO/EB) double dye method. The cytotoxicity was increased by BSME and thymoquinone in LoVo cells in a dose-dependent manner (p<0.001). BSME and thymoquinone also increased iROS, and induced apoptosis and DNA damage (p<0.001). High doses of BSME and thymoquinone on cancer and healthy cells have cytotoxic, genotoxic and apoptotic effects with pro-oxidant effects. Colorectal cancer cells are more sensitive than healthy cells.

Protective effect of thymoquinone nanoemulsion in reducing the cardiotoxic effect of 5-fluorouracil in rats.

5-Fluorouracil (5-FU), which is one of the most widely used chemotherapy drugs, has various side effects on the heart. Thymoquinone (TMQ), the main bioactive component of Nigella sativa, has antioxidant and protective effects against toxicity. In this study, we investigated the protective effect of thymoquinone against cardiotoxicity caused by 5-FU in vitro and in vivo models. H9C2 cells were exposed to 5-FU and TMQ, and cell viability was evaluated in their presence. Also, 25 male Wistar rats were divided into five control groups, 5-FU, 2.5, and 5 mg TMQ in nanoemulsion form (NTMQ) + 5-FU and 5 mg NTMQ. Cardiotoxicity was assessed through electrocardiography, cardiac enzymes, oxidative stress markers, and histopathology. 5-FU induced cytotoxicity in H9c2 cells, which improved dose-dependently with NTMQ cotreatment. 5-FU caused body weight loss, ECG changes (increased ST segment, prolonged QRS, and QTc), increased cardiac enzymes (aspartate aminotransferase [AST], creatine kinase-myocardial band [CK-MB], and lactate dehydrogenase [LDH]), oxidative stress (increased malondialdehyde, myeloperoxidase, nitric acid; decreased glutathione peroxidase enzyme activity), and histological damage such as necrosis, hyperemia, and tissue hyalinization in rats. NTMQ ameliorated these 5-FU-induced effects. Higher NTMQ dose showed greater protective effects. Thus, the results of our study indicate that NTMQ protects against 5-FU cardiotoxicity likely through antioxidant mechanisms. TMQ warrants further research as an adjuvant to alleviate 5-FU chemotherapy side effects.

Evaluating the Protective Effects of Thymoquinone on Methamphetamine-induced Toxicity in an In Vitro Model Based on Differentiated PC12 Cells.

Methamphetamine (Meth) is a highly addictive stimulant. Its potential neurotoxic effects are mediated through various mechanisms, including oxidative stress and the initiation of the apoptotic process. Thymoquinone (TQ), obtained from Nigella sativa seed oil, has extensive antioxidant and anti-apoptotic properties. This study aimed to investigate the potential protective effects of TQ against Meth-induced toxicity by using an in vitro model based on nerve growth factor-differentiated PC12 cells. Cell differentiation was assessed by detecting the presence of a neuronal marker with flow cytometry. The effects of Meth exposure were evaluated in the in vitro neuronal cell-based model via the determination of cell viability (in an MTT assay) and apoptosis (by annexin/propidium iodide staining). The generation of reactive oxygen species (ROS), as well as the levels of glutathione (GSH) and dopamine, were also determined. The model was used to determine the protective effects of 0.5, 1 and 2 µM TQ against Meth-induced toxicity (at 1 mM). The results showed that TQ reduced Meth-induced neurotoxicity, possibly through the inhibition of ROS generation and apoptosis, and by helping to maintain GSH and dopamine levels. Thus, the impact of TQ treatment on Meth-induced neurotoxicity could warrant further investigation.

In Vitro and In Vivo Preventive Effects of Thymoquinone against Breast Cancer: Role of DNMT1.

Breast cancer (BC) is one of the most common cancers in women and is a major cause of female cancer-related deaths. BC is a multifactorial disease caused by the dysregulation of many genes, raising the need to find novel drugs that function by targeting several signaling pathways. The antitumoral drug thymoquinone (TQ), found in black seed oil, has multitargeting properties against several signaling pathways. This study evaluated the inhibitory effects of TQ on the MCF7 and T47D human breast cancer cell lines and its antitumor activity against BC induced by a single oral dose (65 mg/kg) of 7,12-dimethylbenzanthracene (DMBA) in female rats. The therapeutic activity was evaluated in DMBA-treated rats who received oral TQ (50 mg/kg) three times weekly. TQ-treated MCF7 and T47D cells showed concentration-dependent inhibition of cell proliferation and induction of apoptosis. TQ also decreased the expression of DNA methyltransferase 1 (DNMT1) in both cancer cell types. In DMBA-treated animals, TQ inhibited the number of liver and kidney metastases. These effects were associated with a reduction in DNMT1 mRNA expression. These results indicate that TQ has protective effects against breast carcinogens through epigenetic mechanisms involving DNMT1 inhibition.

Nigella sativa and its chemical constituents: pre-clinical and clinical evidence for their potential anti-SARS-CoV-2 effects.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused over 500 million reported cases of COVID-19 worldwide with relatively high morbidity and mortality. Although global vaccination drive has helped control the pandemic, the newer variant of the virus still holds the world in ransom. Several medicinal herbs with antiviral properties have been reported, and one such promising herb is Nigella sativa (NS). Recent molecular docking, pre-clinical, and clinical studies have shown that NS extracts may have the potential to prevent the entry of coronaviruses into the host cell as well as to treat and manage COVID-19 symptoms. Several active compounds from NS, such as nigelledine, α-hederin, dithymoquinone (DTQ), and thymoquinone (TQ), have been proposed as excellent ligands to target angiotensin-converting enzyme 2 (ACE2 receptors) and other targets on host cells as well as the spike protein (S protein) on SARS-CoV-2. By binding to these target proteins, these ligands could potentially prevent the binding between ACE2 and S protein. Though several articles have been published on the promising therapeutic role of NS and its constituents against SARS-CoV-2 infection, in this review, we consolidate the published information on NS and SARS-CoV-2, focusing on pre-clinical in silico studies as well as clinical trials reported between 2012 and 2023.

Variation in the Composition and Quality of Nigella sativa L. Seed Oils-The Underestimated Impact on Possible Health-Promoting Properties.

Nigella sativa L. (black cumin) is one of the most investigated medicinal plants in recent years. Volatile compounds like thymoquinone and unsaponifiable lipid compounds are crucial functional components of this oil. Unfortunately, the composition of oils and their quality indicators are ambiguous both in terms of identified compounds and value ranges. Thirteen oils were extracted with hexane from black cumin seeds grown in India, Syria, Egypt, and Poland and analyzed for their fatty acid composition, unsaponifiable compound content and volatile compounds. Oils were also subjected to quality tests according to standard methods. The fatty acid composition and sterol content/composition were relatively stable among the tested oils. Tocol content varied in the range of 140-631 mg/kg, and among them, ß-tocotrienol and γ-tocopherol prevailed. Oils' volatile compounds were dominated by seven terpenes (p-cymene, α-thujene, α-pinene, ß-pinene, thymoquinone, γ-terpinene, and sabinene). The highest contents of these volatiles were determined in samples from Poland and in two of six samples from India. High acid and peroxide values were typical features of N. sativa L. oils. To sum up, future research on the medicinal properties of black cumin oil should always be combined with the analysis of its chemical composition.

Development and Characterization of Transdermal Patches Using Novel Thymoquinone-L-Arginine-Based Polyamide Nanocapsules for Potential Use in the Management of Psoriasis.

Thymoquinone (TQ) is a phytochemical compound present in Nigella sativa and has potential benefits for treating dermatological conditions such as psoriasis. However, its clinical use is limited due to its restricted bioavailability, caused mainly by its low solubility and permeability. To overcome this, a new transdermal drug delivery system is required. Nanoparticles are known to enhance material solubility and permeability, and hence, this study aimed to synthesize TQ-loaded L-arginine-based polyamide (TQ/Arg PA) nanocapsules incorporated into transdermal patches for prolonged delivery of TQ. To achieve this, Eudragit E polymer, plasticizers, and aloe vera as penetration enhancer were used to develop the transdermal patch. Furthermore, novel TQ/Arg-PA was synthesized via interfacial polymerization, and the resultant nanocapsules (NCs) were incorporated into the matrix transdermal patch. The Arg-PA NCs' structure was confirmed via NMR and FTIR, and optimal TQ/Arg-PA NCs containing formulation showed high entrapment efficiency of TQ (99.60%). Molecular and thermal profiling of TQ/Arg-PA and the transdermal patch revealed the effective development of spherical NCs with an average particle size of 129.23 ± 18.22 nm. Using Franz diffusion cells and synthetic membrane (STRAT M®), the in vitro permeation profile of the prepared patches demonstrated an extended release of TQ over 24 h, with enhanced permeation by 42.64% when aloe vera was employed. In conclusion, the produced formulation has a potential substitute for corticosteroids and other drugs commonly used to treat psoriasis due to its effectiveness, safety, and lack of the side effects typically associated with other drugs.

Thymoquinone: A Promising Therapeutic Agent for the Treatment of Colorectal Cancer.

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and is responsible for approximately one million deaths each year. The current standard of care is surgical resection of the lesion and chemotherapy with 5-fluorouracil (5-FU). However, of concern is the increasing incidence in an increasingly younger patient population and the ability of CRC cells to develop resistance to 5-FU. In this review, we discuss the effects of thymoquinone (TQ), one of the main bioactive components of Nigella sativa seeds, on CRC, with a particular focus on the use of TQ in combination therapy with other chemotherapeutic agents. TQ exhibits anti-CRC activity by inducing a proapoptotic effect and inhibiting proliferation, primarily through its effect on the regulation of signaling pathways crucial for tumor progression and oxidative stress. TQ can be used synergistically with chemotherapeutic agents to enhance their anticancer effects and to influence the expression of signaling pathways and other genes important in cancer development. These data appear to be most relevant for co-treatment with 5-FU. We believe that TQ is a suitable candidate for consideration in the chemoprevention and adjuvant therapy for CRC, but further studies, including clinical trials, are needed to confirm its safety and efficacy in the treatment of cancer.

Thymoquinone attenuates inflammation in C. Albicans keratitis by activating Nrf2/HO-1 signaling pathway and reducing fungal load.

PURPOSE: This study aims to investigate the anti-inflammatory and antifungal properties of thymoquinone (TQ) and elucidate its mechanism of action in the context of C. albicans keratitis. METHODS: Various methods were employed to identify a safe and effective concentration of TQ with antifungal properties, including the determination of the minimum inhibitory concentration (MIC), the cell counting kit-8 (CCK-8) test, and the Draize experiment. The severity of fungal keratitis (FK) was assessed through clinical ratings and slit-lamp imaging. Fungus burden was determined using plate counting and periodic acid Schiff (PAS) staining. Neutrophil infiltration and activity were investigated through immunofluorescence staining (IFS), myeloperoxidase (MPO) analysis, and hematoxylin and eosin (HE) staining. To explore the anti-inflammatory effects of TQ and its mechanism of action, we employed RT-PCR, ELISA, and western blot techniques. RESULTS: TQ effectively controlled fungal growth at a concentration of 50 µg/mL while preserving the integrity of mouse corneas. Human corneal epithelial cells (HCECs) remained unaffected by TQ at concentrations ≤ 3.75 µg/mL. Treatment with TQ led to significant improvements in clinical scores, fungal burden, neutrophil infiltration, and the expression of inflammatory factors compared to the DMSO group. Moreover, TQ demonstrated the ability to reduce the levels of inflammatory factors in HCECs stimulated by C. albicans. Additionally, TQ enhanced the expressions of Nrf2 and HO-1 in mouse corneas. The downregulation of cytokines induced by TQ was reversed upon pretreatment with inhibitors of Nrf2 or HO-1. CONCLUSION: TQ exhibits a protective effect in the context of C. albicans keratitis through multiple mechanisms, including inhibition of C. albicans growth, reduction of neutrophil recruitment, activation of the Nrf2/HO-1 pathway, and limitation of the expression of pro-inflammatory factors.

Potential anticancer properties and mechanisms of thymoquinone in colorectal cancer.

Colorectal neoplasms are one of the deadliest diseases among all cancers worldwide. Thymoquinone (TQ) is a natural compound of Nigella sativa that has been used in traditional medicine against a variety of acute/chronic diseases such as asthma, bronchitis, rheumatism, headache, back pain, anorexia, amenorrhea, paralysis, inflammation, mental disability, eczema, obesity, infections, depression, dysentery, hypertension, gastrointestinal, cardiovascular, hepatic, and renal disorders. This review aims to present a detailed report on the studies conducted on the anti-cancer properties of TQ against colorectal cancer, both in vitro and in vivo. TQ stands as a promising natural therapeutic agent that can enhance the efficacy of existing cancer treatments while minimizing the associated adverse effects. The combination of TQ with other anti-neoplastic agents promoted the efficacy of existing cancer treatments. Further research is needed to acquire a more comprehensive understanding of its exact molecular targets and pathways and maximize its clinical usefulness. These investigations may potentially aid in the development of novel techniques to combat drug resistance and surmount the obstacles presented by chemotherapy and radiotherapy.

Coencapsulation of Gemcitabine and Thymoquinone in Citrem-Phosphatidylcholine Hexosome Nanocarriers Improves In Vitro Cellular Uptake in Breast Cancer Cells.

Lyotropic liquid crystalline nanoassemblies (LLCNs) are internally self-assembled (ISA)-somes formed by amphiphilic molecules in a mixture comprising a lipid, stabilizer, and/or surfactant and aqueous media/dispersant. LLCNs are unique nanoassemblies with versatile applications in a wide range of biomedical functions. However, they comprise a nanosystem that is yet to be fully explored for targeted systemic treatment of breast cancer. In this study, LLCNs proposed for gemcitabine and thymoquinone (Gem-TQ) co-delivery were prepared from soy phosphatidylcholine (SPC), phytantriol (PHYT), or glycerol monostearate (MYVR) in optimized ratios containing a component of citric and fatty acid ester-based emulsifier (Grinsted citrem) or a triblock copolymer, Pluronic F127 (F127). Hydrodynamic particle sizes determined were below 400 nm (ranged between 96 and 365 nm), and the series of nanoformulations displayed negative surface charge. Nonlamellar phases identified by small-angle X-ray scattering (SAXS) profiles comprise the hexagonal, cubic, and micellar phases. In addition, high entrapment efficiency that accounted for 98.3 ± 0.1% of Gem and 99.5 ± 0.1% of TQ encapsulated was demonstrated by the coloaded nanocarrier system, SPC/citrem/Gem-TQ hexosomes. Low cytotoxicity of SPC-citrem hexosomes was demonstrated in MCF10A cells consistent with hemo- and biocompatibility observed in zebrafish (Danio rerio) embryos for up to 96 h postfertilization (hpf). SPC/citrem/Gem-TQ hexosomes demonstrated IC50 of 24.7 ± 4.2 µM in MCF7 breast cancer cells following a 24 h treatment period with the moderately synergistic interaction between Gem and TQ retained (CI = 0.84). Taken together, biocompatible SPC/citrem/Gem-TQ hexosomes can be further developed as a multifunctional therapeutic nanodelivery approach, plausible for targeting breast cancer cells by incorporation of targeting ligands.

Protective role of thymoquinone in hyperlipidemia-induced liver injury in LDL-R-/-mice.

BACKGROUND: Hyperlipidemia, a heterogeneous group of disorders characterized by elevated plasma lipids in the blood, causes severe health problems, leading to fatty liver disease and nonalcoholic fatty liver disease. Thymoquinone, the major active chemical component of Nigella sativa, reportedly exerts a vast array of biological effects. Various studies have reported that Thymoquinone protects against liver injury. AIMS: The aim of this study was to investigate the possible protective effects of Thymoquinone against liver injury in hyperlipidemia-induced LDL-R-/- mice. METHODS: Eight-week-old male LDL-R-/- mice were randomly divided into three groups: a control group fed a normal diet and two groups fed a high-cholesterol diet or high-cholesterol diet mixed with Thymoquinone. All groups were fed different diets for 8 weeks. Blood samples were obtained from the inferior vena cava and collected in serum tubes. The samples were then stored at - 80 °C until used. Longitudinal sections of liver tissues were fixed in 10% formalin and then embedded in paraffin for histological evaluation. The remainder of the liver tissues were snap-frozen in liquid nitrogen for reverse transcription-polymerase chain reaction or western blotting. RESULTS: Our results demonstrated that Thymoquinone administration significantly reduced liver histological alterations by hyperlipidemia. Thymoquinone mitigated hyperlipidemia-induced liver injury as indicated by the suppression of metabolic characteristics, liver biochemical parameters, pyroptosis indicators, a macrophage marker, and the phosphatidylinositide 3-kinase signaling pathway. CONCLUSIONS: Thymoquinone is a potential therapeutic agent for hyperlipidemia-induced liver injury.