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PMID:  Nanomedicine (Lond). 2018 07 ;13(13):1567-1582. PMID: 30028248Abstract Title:  Thymoquinone loaded in nanostructured lipid carrier showed enhanced anticancer activity in 4T1 tumor-bearing mice.Abstract:  AIM: To investigate the enhancement of anticancer activity of thymoquinone (TQ) by the use of nanostructured lipid carrier (NLC) in 4T1 tumor-bearing female BALB/c mice.MATERIAL & METHODS: TQ was incorporated into NLC (TQNLC) by using high pressure homogenization. TQNLC and TQ were orally administered to the mice.RESULTS & CONCLUSION: TQNLC and TQ are potential chemotherapeutic drugs as they exhibited anticancer activity. The use of NLC as a carrier has enhanced the therapeutic property of TQ by increasing the survival rate of mice. The antimetastasis effect of TQNLC and TQ to the lungs was evidence by downregulation of MMP-2. TQNLC and TQ induced apoptosis via modulation of Bcl-2 and caspase-8 in the intrinsic apoptotic pathway.

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Posted: December 12, 2018, 3:49 am
PMID:  J Cancer Res Ther. 2018 Jul-Sep;14(5):1023-1028. PMID: 30197342Abstract Title:  Synergistic effect of temozolomide and thymoquinone on human glioblastoma multiforme cell line (U87MG).Abstract:  Aims: Temozolomide (TMZ) is an alkylating agent used for glioblastoma multiforme (GBM) treatment. Nevertheless, resistance to TMZ is a major obstacle to successful treatment of this cancer. The aim of the present study was to investigate the effects of TMZ and thymoquinone (TQ) on U87MG cell line.Materials and Methods: The effect of TMZ and/or TQ on viability and invasion potential of U87MG cells was evaluated using various techniques including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, lactate dehydrogenase activity, cell invasion, migration, and adhesion assays. Enzyme-linked immunosorbent assay and polymerase chain reaction were used to study the expression and secretion of matrix metalloproteinases (MMPs).Results: Combination of TMZ and TQ had a synergistic cytotoxic effect on U87MG cells. TMZ and/or TQ significantly reduced the potential of U87MG cells invasion. In addition, after treating with TMZ and/or TQ, there was a decrease in the levels of matrix matrix metalloproteinase 2 nad 9 (MMP 2 and 9) expression and secretion in U87MG cells.Conclusions: The combination of TMZ and TQ may emerge as a promising strategy for the successful treatment of GBM.

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Posted: December 12, 2018, 2:28 am
PMID:  Saudi Dent J. 2018 Oct ;30(4):348-354. Epub 2018 Jun 11. PMID: 30202173Abstract Title:  Assessment of clinical efficacy of locally delivered 0.2% Thymoquinone gel in the treatment of periodontitis.Abstract:  Objectives: To evaluate the potential benefits of local application of Thymoquinone gel as an adjunctive to scaling and root planing (SRP) in subjects with chronic periodontitis.Material and methods: Twenty subjects with 40 test sites were selected according to inclusion and exclusion criteria. They were further divided into 2 groups. Group I comprised of study subjects (Thymoquinone in addition to SRP) and Group II comprised of control subjects (only SRP). Clinical parameters such as Plaque Index (PI), Gingival Index (GI), Probing Pocket Depth (PPD), Relative Attachment Level (RAL), were monitored at baseline and 6 weeks post operatively. Alkaline phosphatase (ALP) levels in gingival crevicular fluid (GCF) were evaluated at baseline and 6 weeks post operatively using microcapillaries. In addition antimicrobial efficacy of Thymoquinone was evaluated against 3 bacteria using antimicrobial strains.Results: Statistically highly significant reduction was observed in PI, GI and PPD, rise in RAL and GCF ALP level in both the groups at 6 weeks from baseline. On comparison between Group I and Group II, former demonstrated statistically significant reduction in PPD, GCF-ALP levels and rise in RAL but statistically no significant differences were observed in PI and GI at 6 weeks. On microbiological assessment of 0.2% Thymoquinonegel, it was observed to be sensitive against,.Conclusion: Significant changes in clinical and biochemical parameters were achieved in the current study. Hence, it is concluded that intracrevicular application of 0.2% Thymoquinone gel could be a beneficial adjunct to SRP in treating chronic periodontitis.

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Posted: December 12, 2018, 2:20 am
PMID:  Adv Biomed Res. 2018 ;7:121. Epub 2018 Aug 29. PMID: 30211134Abstract Title:  Effects ofExtracts on the Lipid Profile and Uncoupling Protein-1 Gene Expression in Brown Adipose Tissue of Mice.Abstract:  Background: Uncoupling protein-1 (UCP-1) is the index protein of the brown adipose tissue (BAT), used in the obesity studies. We evaluated the effects of thymoquinone (TQ), hydroalcoholic, and hexane extracts of, on thegene expression in BAT, and also on the recovery from oxidative stress, due to a high-fat diet.Materials and Methods: Fifty mice were divided into five groups: the first group was fed with a usual diet and the second, third, fourth, and fifth groups with a high-fat diet, hydroalcoholic extract, hexane extract, and TQ, respectively. After completing the course, the lipid profile, paraoxonase 1 (PON1), serum total antioxidant capacity (TAC), and malondialdehyde (MDA) were measured.expression in BAT was evaluated at the gene and protein level.Results: The weight of mice, receiving TQ, hydroalcoholic, and hexane extracts, was decreased (

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Posted: December 12, 2018, 2:12 am
PMID:  AAPS PharmSciTech. 2018 Sep 14. Epub 2018 Sep 14. PMID: 30218265Abstract Title:  Optimization and Characterization of Thymoquinone-Loaded Liposomes with Enhanced Topical Anti-inflammatory Activity.Abstract:  Thymoquinone, the major constituent of Nigella sativa oil has been found to have a promising topical anti-inflammatory activity; however, exaggerated heat and photo-sensitivity and lipophilicity prevent the best use of this promising product. The present work aimed to formulate an ideal thymoquinone liposomal system for topical delivery. Different liposomal systems were developed using thin film hydration method by applying different cholesterol molar concentrations, different total lipid molar concentrations, and different drug-to-lipid ratios. Morphological characterization of the prepared formulae was performed using polarized light, scanning electron microscope, and transmission electron microscope. The optimized formula (F12) was selected on the basis of enhanced permeation through the skin and was incorporated into chitosan gel for topical application. The gel formulation was clear with suitable skin permeation and exhibited acceptable rheological properties. Using carrageenan-induced paw edema in rats, the developed chitosan gel (F12) showed significant superior in vivo anti-inflammatory activity over the chitosan gel of the TQ (p 

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Posted: December 12, 2018, 1:55 am
PMID:  Neurotoxicology. 2018 Dec ;69:68-76. Epub 2018 Sep 15. PMID: 30227172Abstract Title:  Thymoquinone prevents cisplatin neurotoxicity in primary DRG neurons.Abstract:  Chemotherapy-induced peripheral neuropathy (CIPN) is a substantial, dose-limiting adverse effect that occurs in cancer patients. Cis-dichlorodiamine (II) platinum (CDDP, cisplatin) is a platinum-based chemotherapeutic agent that causes severe acute and chronic peripheral neuropathies in 30% of cancer patients. Thymoquinone (TQ), a leading bioactive constituent of Nigella sativa seeds, has been reported to have antioxidant, anti-inflammatory, anti-neoplastic and neuroprotective properties. Dorsal root ganglia (DRG) include different classes of primary sensory neurons, such as nociceptors, mechanoreceptors, and proprioceptive neurons. Here, we investigated the neuroprotective activity of TQ against cisplatin neurotoxicity in cultured DRG neurons. We prepared neuronal cultures from DRGs of adult mice, pre-treated them with or without varying doses of TQ prior to exposure of cells to cisplatin. The preparations were viewed under the scope before and after the treatment at 24 h, 48 h, and 72 h time points. We analyzed neuronal cell viability and neurite outgrowths, and evaluated morphologic changes of neuronal or non-neuronal cells. TQ significantly increases the ability to extend neurites and neuronal cell viability when compared to the culture conditions which were treated with cisplatin only. Although we provide compelling evidence for the protective activity of TQ against chemotherapy-induced neurotoxicity, further detailed investigations in preclinical settings are warranted for its clinical use.

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Posted: December 12, 2018, 1:23 am
PMID:  Int J Vet Sci Med. 2018 Jun ;6(1):16-21. Epub 2018 Feb 23. PMID: 30255073Abstract Title:  Ameliorative effects of thymoquinone on titanium dioxide nanoparticles induced acute toxicity in rats.Abstract:  Although the nanoparticles had a beneficial activity, it had also adverse effects as a result of generation of oxidative stress. The current study aimed to assess the ameliorative effect of thymoquinone (TQ) on titanium dioxide nanoparticles (TiONPs) induced acute toxicity in male rats. Forty-eight male rats were distributed into four equal groups (12 rats each). Group (1) received single oral dose of TiONPs (300 mg/kg), Group (2) received TiONPs and TQ (20 mg/kg), Group (3) received TQ and group (4) received only the vehicle and served as control group. TiONPs intoxicated group showed increased the level of lipid peroxidation product (LPO), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and decreased the level of antioxidants and testosterone. Vascular and degenerative changes in the liver and testes were observed by light microscopy as well as presence of TiONPs in the lysosomes by electron microscopy. Treatment with TQ revealed improvement of the biochemical parameters, histology and ultrastructure of the liver and testes. It was concluded that acute intoxication of rats with TiONPs induced adverse effect in the liver and testes. Administration of TQ has an ameliorative effect against oxidative stress induced by TiONPs intoxication.

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Posted: December 12, 2018, 1:19 am
PMID:  Cancer Sci. 2018 Dec ;109(12):3865-3873. Epub 2018 Oct 28. PMID: 30259603Abstract Title:  Thymoquinone inhibits the metastasis of renal cell cancer cells by inducing autophagy via AMPK/mTOR signaling pathway.Abstract:  Thymoquinone (TQ, 2-methyl-5-isopropyl-1,4-benzoquinone), a bioactive constituent extracted from the seeds of Nigella sativa, has been proved to exert anti-tumor efficiency in various cancers. Autophagy is a self-digestion phenomenon, and its role in tumor formation and progression remains controversial. In the present study, we investigated the effects of TQ on renal cell cancer (RCC) cell lines (786-O and ACHN) using wound healing assay, transwell assay and western blot analysis. We found that TQ effectively inhibited the metastatic capacity of RCC cells in vitro, which was also verified in a xenograft model. Meanwhile, we observed LC3 puncta and detected the expression of LC3 in TQ-treated RCC cells, and then found that autophagy was induced by TQ in 786-O and ACHN cell lines. In addition, TQ inhibited the migration and invasion as well as the EMT in RCC cells in an autophagy-dependent manner. To further explore the underlying mechanism, we detected the AMPK/mTOR signaling pathway. The results indicated that TQ inhibited the metastasis of RCC cells by inducing autophagy via AMPK/mTOR signaling pathway. In conclusion, our findings provide a novel therapeutic strategy that aims at TQ-induced autophagy in RCC treatment.

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Posted: December 12, 2018, 1:14 am
PMID:  J Basic Clin Physiol Pharmacol. 2018 Oct 1. Epub 2018 Oct 1. PMID: 30269105Abstract Title:  The standardized extract of Nigella sativa and its major ingredient, thymoquinone, ameliorates angiotensin II-induced hypertension in rats.Abstract:  Background This study investigated the effect of hydroalcoholic extract of Nigella sativa (N. sativa) and its active component, thymoquinone (TQ) on hypertension induced by angiotensin II (AngII), the main product of renin-angiotensin system (RAS). Methods Seven animal groups (n=7 for each group) were used as follows: (1) control, (2) AngII (300 ng/kg), (3) AngII+losartan (Los; 10 mg/kg), (4) TQ (40 mg/kg)+AngII, and (5-7) three doses of N. sativa (200, 400, and 600 mg/kg)+AngII. Los and AngII were injected intravenously; TQ and extracts were injected intraperitoneally. In TQ and N. sativa-treated groups, 30 min after injection of the extract and TQ, AngII was injected. Cardiovascular parameters were recorded by power lab system after cannulation of femoral artery. The maximum changes (∆) of systolic blood pressure (SBP), mean arterial pressure (MAP), and heart rate (HR) were calculated and used for statistical analysis. Results AngII significantly increased maximal ∆SBP, ∆MAP, and ∆HR compared with the control (p

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Posted: December 12, 2018, 12:55 am
PMID:  J Cell Biochem. 2018 Sep 30. Epub 2018 Sep 30. PMID: 30269355Abstract Title:  Thymoquinone protects human retinal pigment epithelial cells against hydrogen peroxide induced oxidative stress and apoptosis.Abstract:  Oxidative stress in retinal pigment epithelium (RPE) cells may contribute to the progression of age-related macular degeneration. Thymoquinone (TQ), an active component derived from Nigella sativa, possesses antioxidative effect. However, the role of TQ in RPE cells under oxidative stress condition remains unclear. The present study aimed to examine the protective effect of TQ against hydrogen peroxide (HO)-induced oxidative stress in human RPE cells. Our results showed that TQ improved the cell viability and apoptosis in HO-induced ARPE cells. We also found that the levels of reactive oxygen species and malondialdehyde induced by HOwere reduced after the pretreatment of TQ. In addition, the inhibitory effect of HOon the glutathione (GSH) level and superoxide dismutase activity was markedly attenuated by TQ pretreatment. Moreover, TQ enhanced the activation of Nrf2/heme oxygenase 1 (HO-1) signaling pathway in HO-induced ARPE cells. Knockdown of Nrf2 abolished the protective effect of TQ on HO-induced oxidative damage. These results suggested that TQ protected ARPE cells from HO-induced oxidative stress and apoptosis via the Nrf2/HO-1 signaling pathway.

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Posted: December 12, 2018, 12:51 am
PMID:  J Biochem Mol Toxicol. 2018 Oct 5:e22238. Epub 2018 Oct 5. PMID: 30290066Abstract Title:  Thymoquinone attenuates lead-induced nephropathy in rats.Abstract:  Kidney hazards from lead (Pb) exposure are one of the fastest growing areas of concern in toxicology today. The thymoquinone (TQ) renoprotective effect against Pb-induced nephropathy has not previously been studied. Therefore, adult male Wistar rats were treated with Pb (2000 ppm of Pb acetate in drinking water) and/or TQ (5 mg/kg/day,  per os). All treatments were applied for 5 weeks. The results indicated that Pb exposure produced metal deposition, histopathological changes, functional impairment (significant elevation in plasma urea, uric acid, and creatininelevels), total antioxidant status decrease, and lipid peroxidation stimulation in the kidneys. Interestingly, TQ supplementation remarkably improved the Pb-induced renal adverse effects without significantly reducing the tissue metal accumulation. In conclusion, our data indicate for the first timea protective effect of TQ against Pb-induced nephropathy, most likely through an antioxidant mechanism. On this basis, TQ deserves more consideration and further examination as a potential therapeutic option.

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Posted: December 12, 2018, 12:42 am
PMID:  Sci Rep. 2018 Oct 11 ;8(1):15122. Epub 2018 Oct 11. PMID: 30310156Abstract Title:  Effects of Thymoquinone on radiation enteritis in mice.Abstract:  Radiation enteritis is an old but emerging question induced by the application of radiation. However, no effective drugs for radiation enteritis in clinic. In this study, we found that thymoquinone (TQ) could mitigate intestinal damages induced by irradiation. After exposure to irradiation, TQ-treated improved the irradiated mice survival rate, ameliorated intestinal injury and increased the numbers of intestinal crypts. Furthermore, Lgr5ISCs and their daughter cells, including Vil1enterocytes, Ki67cells and lysozymePaneth cells, were all significantly increased with TQ treatment. In addition, P53,γH2AX, caspase8, caspase9 and caspase3 expression were all reduced by TQ. Our data showed that TQ modulated DNA damages and decreased the apoptosis in the small intestine. TQ might be used for radiation enteritis treatment.

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Posted: December 12, 2018, 12:38 am
PMID:  Inflammation. 2018 Oct 20. Epub 2018 Oct 20. PMID: 30343389Abstract Title:  Role of Thymoquinone in Cardiac Damage Caused by Sepsis from BALB/c Mice.Abstract:  Sepsis is a major health complication causing patient mortality and increased healthcare costs. Cardiac dysfunction, an important consequence of sepsis, affects mortality. We previously reported that thymoquinone (TQ) protected against hyperlipidemia and doxorubicin-induced cardiac damage. This study investigated the possible protective effects of TQ against cardiac damage in septic BALB/c mice. Eight-week-old male BALB/c mice were divided into four groups: control, TQ, cecal ligation and puncture (CLP), and TQ + CLP. CLP was performed after 2-week TQ gavage. After 48 h, we measured the histopathological alterations of the cardiac tissue and the plasma levels of troponin-T (cTnT) and ATP. We evaluated autophagy (p62 and beclin 1), pyroptosis (NLRP3, caspase-1, interleukin [IL]-1β, and IL-18) at thegene and protein levels and IL-6 and tumor necrosis factor-α (TNF-α) at the gene level. Our results demonstrated that TQ administration significantly reduced intestinal histological alterations. TQ inhibited plasma cTnT levels; improved ATP; significantly inhibited p62, NLRP3, caspase-1, IL-1β, IL-18, IL-6, TNF-α, and MCP-1expressions; and increased beclin 1 and IL-10 level. The phosphatidylinositide 3-kinase level was significantly decreased in the TQ + CLP group versus the CLP group. These results suggest that TQ effectively modulates autophagy, pyroptosis, and pro-inflammatory, making it important in the treatment of sepsis-induced cardiac damage.

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Posted: December 12, 2018, 12:25 am
PMID:  J Cell Physiol. 2018 Nov 1. Epub 2018 Nov 1. PMID: 30387147Abstract Title:  Thymoquinone-induced antitumor and apoptosis in human lung adenocarcinoma cells.Abstract:  BACKGROUND: Lung cancer has been associated with the highest cancer-associated mortality rate in the world. Chemotherapeutic management of cancer necessitates introducing new promising agents. Plants represent a rich source of new antineoplastic and chemotherapeutic agents. Thymoquinone (TQ), the main constituent of Nigella sativa (black seed or black cumin), has shown potent antioxidant and anti-inflammatory activities so far. The purpose of the current study was to evaluate the antineoplastic potential of TQ and their underlying mechanisms in A549 cells (human lung cancer cell line).METHOD: The A549 cells were treated with the different concentrations of TQ for three following days. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Necrosis and apoptosis were assessed by fluorescence-activated cell sorter analysis through propidium iodide and annexin V staining and also by assessing caspase-3 and -9 activation. DNA fragmentation was monitored by gel electrophoresis.RESULTS: TQ decreased the viability and increased apoptotic cell death in A549 human lung tumor cells. TQ treatment significantly elevated the Bax/ Bcl-2 ratio in the lung cancer cells. TQ also upregulated p53 expression, another apoptotic modulator in A549 cancer cells. TQ also activated caspase-dependent apoptosis by the activation of caspases-3 and -9.CONCLUSION: Our results proposed that TQ may be a potential new therapeutic agent for the management of lung cancer. TQ promoted apoptosis in A546 lung cancer cells by the activation of p53 and caspase cascade dependent pathways.

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Posted: December 12, 2018, 12:21 am
PMID:  Curr Pharm Biotechnol. 2018 Nov 13. Epub 2018 Nov 13. PMID: 30421672Abstract Title:  Thymoquinone shows the diverse therapeutic actions by modulating multiple cell signaling pathways: single drug for multiple targets.Abstract:  Thymoquinone (TQ), derived from Nigella sativa, has lately been shown as a miracle drug because of it's a wide range of therapeutic effects against various diseases, including cancer, asthma, diabetes, colitis, infectious diseases etc. In the present review, we aimed to decipher the molecular mechanisms of therapeutic action of TQ. Many in vivo and in vitro studies have demonstrated the therapeutic efficacy of TQ against a wide range of diseases. We extensively searched the literature of the therapeutic properties of TQ and its formulations from various online sources, including PubMed, Google Scholar, Scopus and Science Direct. TQ possesses potent anti-inflammatory and immunomodulatory effects by specifically targeting the NF-kB, IL-1β and TNF-α signaling pathways. The anticancer activity of TQ has been primarily shown by altering the expression of signal transducers and activator transcription (STAT3), PTEN and p53 genes. TQ alleviates the hyperglycemia-associated complications, the hepatic or renal ailments through its potential antioxidant and anti-inflammatory properties. Interestingly, the liposome- or nanoparticle-based TQ formulations have shown greater effectiveness against various diseases in animal models. Thus, the understanding of the molecular mechanisms of TQ action may lead to the development of its therapeutic formulations to cure of a wide variety of diseases.

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Posted: December 12, 2018, 12:17 am
PMID:  Oxid Med Cell Longev. 2018 ;2018:7845681. Epub 2018 Oct 30. PMID: 30510626Abstract Title:  Thymoquinone Attenuates Cardiomyopathy in Streptozotocin-Treated Diabetic Rats.Abstract:  Diabetic cardiomyopathy is a diabetic complication due to oxidative stress injuries. This study examined the protecting influence of thymoquinone (TQ) on diabetes-caused cardiac complications. The intracellular means by which TQ works against diabetes-caused cardiac myopathy in rats is not completely understood. In this study, Wistar male rats (= 60) were assigned into four groups: control, diabetic (diabetes induced by IP infusion of streptozotocin, 65 mg/kg), diabetic + TQ (diabetic rats given TQ (50 mg/kg) administered once per day by stomach gavage), and TQ (50 mg/kg) for 12 weeks. TQ supplementation appreciably recovered the cardiac parameters alongside significant declines in plasma nitric oxide concentrations and total superoxidedismutase (T.SOD) activities. Importantly, TQ downgraded expression of cardiac-inducible nitric oxide synthase in addition to significantly upregulating vascular endothelial growth factor and erythropoietin genes and nuclear factor-erythroid-2-related factor 2 (Nrf2) protein. TQ normalized plasma triacylglycerol and low-density lipoprotein-cholesterol and significantly improved the high-density lipoprotein-cholesterol levels. Additionally, TQ administration improved the antioxidant ability of cardiac tissue via significantly increased cardiac T.SOD and decreased cardiac malondialdehyde levels.Oral supplementation with TQ prevented diabetic-induced cardiomyopathy via its inhibitory effect on the E-selectin level, C-reactive protein, and interleukin-6. The TQ protecting effect on the heart tissue was shown by normalization of the plasma cardiac markers troponin I and creatine kinase. Thisexperiment shows the aptitude of TQ to protect cardiac muscles against diabetic oxidative stress, mainly through upregulation of Nrf2, which defeated oxidative damage by improvement of the antioxidant power of cardiac muscle that consequently protected the cardiac muscles and alleviated the inflammatory process.

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Posted: December 12, 2018, 12:10 am
PMID:  Cell Mol Biol (Noisy-le-grand). 2018 11 30 ;64(14):79-83. Epub 2018 Nov 30. PMID: 30511625Abstract Title:  In Vitro evaluation of thymoquinone on apoptosis and oxidative DNA damage in high glucose condition.Abstract:  The study was planned to investigate the effects of thymoquinone (TQ), which is a compound in N. sativa, on caspase dependent apoptosis and oxidative DNA damage in high glucose treated PC12 cells. PC12 cells were treated with high glucose (G1-150 mM, G2-250 mM, G3-350 mM), TQ (20µM), and their combinations. Oxidative DNA damage (8-OHdG (8-Oxo-2'-deoxyguanosine)), and apoptosis (caspase 3, caspase 8, caspase 9 enzymes and M30 protein) parameters were analyzed with ELISA. The 8-OHdG levels decreased in all combination groups compared to the control (p≤0.001). There was nostatistically significant difference between caspase 3 and 9. Caspase 8 in TQ, G3, TQG1, TQG2 groups were higher than the control (p≤0.002). Low M30 levels were observed in TQG1 group (p≤0.002). In conclusion, it was observed that in PC12 cell line treated with the high glucose concentrations, TQ administration had a statistically significant effect on oxidative DNA damage and some apoptotic parameters (caspase 8 and M30 protein).

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Posted: December 11, 2018, 11:58 pm
PMID:  Chem Phys Lipids. 2018 Dec 3. Epub 2018 Dec 3. PMID: 30521787Abstract Title:  Cabazitaxel and Thymoquinone co-loaded Lipospheres as a Synergistic Combination for Breast Cancer.Abstract:  Cabazitaxel as microtubule inhibitor and thymoquinone as HDAC inhibitor affects the important genes like p53, STAT3, Bax, BCL-2, p21 and down regulation of NF-κB are reported for potential activity against breast tumors. However, poor aqueous solubility and permeability hinders the delivery of these drugs to target site. To address the delivery challenges cabazitaxel and thymoquinone co-loaded lipospheres were developed. Lipospheres are the lipid based self-assemblies of particle size below 150 nm were prepared with more than 90% entrapment efficiency for both the drugs. In vitro drug release studies revealed there was a sustained diffusion controlled drug release from liposphere matrix leading to decrease in particle size with increase in zeta potential. Cytotoxicity studies on MCF-7 and MDA-MB-231 cells demonstrated cabazitaxel and thymoquinone as synergistic combination for the treatment of breast cancer which was proved by CompuSyn software. Enhanced efficacy of developed lipospheres can be due to rapid cellular internalization which was observed in confocal laser scanning microscopy. Drastic changes in cancer cell morphology such as nuclear fragmentation were observed upon treatment with these lipospheres in comparison to combination solution as observed in fluorescent imaging which are the hall marks of apoptosis. Cell cycle analysis and apoptosis studies confirmed the increased Sub G1 phase arrest as well as cell death due to apoptosis. Thus, as per observed results, it can be concluded that cabazitaxel and thymoquinone co-loaded lipospheres are the efficient delivery vehicles in management of breast cancer.

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Posted: December 11, 2018, 11:55 pm
PMID:  J Huazhong Univ Sci Technolog Med Sci. 2009 Apr ;29(2):177-81. Epub 2009 Apr 28. PMID: 19399400Abstract Title:  ANG II-AT1 receptor pathway is involved in the anti-fibrotic effect of beta-elemene.Abstract:  To investigate the effects of beta-elemene on the ANG II-AT1 receptor pathway in rats with liver fibrosis, a model of hepatic fibrosis was induced by hypodermical injection of carbon tetrachloride (CCl4) into Wistar male rats. beta-elemene was intraperitonealy administered into the rats for 8 weeks (0.1 mL/100 g body weight per day). Masson staining was used to observe the liver fibrosis of rats and liver functions were measured by enzymatic kinetic analysis. The content of hydroxyproline in liver tissues was detected by specimen alkaline hydrolysis. The level of plasma ANG in blood II plasma was detected by radioimmunoassay. The expression of AT1R in rat liver were measured using reverse transcriptional-polymerase chain reaction and immunohistochemistry respectively. The results showed that beta-elemene could reduce the collagen disposition in liver and inhibit the progression of liver fibrosis. In addition, the levels of plasma ANG II and the expression of hepatic AT1R in rats with liver fibrosis were also suppressed by beta-elemene. It is concluded that the ANG II-AT1 receptor pathway plays an important role in the development of hepatic fibrosis and beta-elemene could down-regulate the levels of plasma ANG II and the expression of hepatic AT1R in rats with liver fibrosis.

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Posted: December 11, 2018, 11:38 pm
PMID:  Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2010 Apr ;18(2):368-71. PMID: 20416170Abstract Title:  [Effects of beta-elemene on proliferation and apoptosis of human multiple myeloma cell RPMI-8226].Abstract:  This study was aimed to investigate the effect of beta-elemene on proliferation and apoptosis of human multiple myeloma cell line RPMI-8226 and its mechanism. The effect of beta-elemene on the growth of human multiple myeloma cell line RPMI-8226 was detected by MTT. The effect of beta-elemene on the apoptosis of RPMI-8226 cells was determined by flow cytometry with Annexin-V/PI staining. The effects of beta-elemene on the expression of BCL-2, caspase-3, DR-4 and NF-kappaB P65 proteins were analyzed by Western blot. The results showed that the beta-elemene obviously inhibited the proliferation of RPMI-8226 cells in both time- and dose-dependent manners. Treatment with 10 - 80 micromol/L beta-elemene for 48 hours induced apoptosis of RPMI-8226 cells in a dose-dependent manner. The expression of caspase-3 and DR-4 proteins in RPMI-8226 cells treated with beta-elemene increased in a time-dependent manner, while expressions of BCL-2 and NF-kappaB P65 proteins decreased. It is concluded that the beta-elemene can inhibit the proliferation of RPMI-8226 cells by inducing the cell apoptosis. Activating the mitochondrial and death receptor pathways of apoptosis and inhibiting the anti-apoptosis pathway may involve in the beta-elemene-induced apoptosis.

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Posted: December 11, 2018, 11:29 pm
PMID:  Cancer Chemother Pharmacol. 2011 Apr ;67(4):799-808. Epub 2010 Jun 19. PMID: 20563582Abstract Title:  Beta-elemene inhibits melanoma growth and metastasis via suppressing vascular endothelial growth factor-mediated angiogenesis.Abstract:  PURPOSE: It was to assess antiangiogenic effect ofβ-elemene in vitro and in vivo, and it was involved in inhibiting melanoma growth and metastasis, as well as to elucidate its intrinsic mechanism.METHODS: Inhibitive effect ofβ-elemene on B16F10 cells was performed by cell proliferation assay. Angiogenesis assays in vitro including rat aortic ring and chick embryo chorioallantoic membrane were used, as well as melanoma growth and metastasis assay in C57BL/6 mice. Vascular endothelial growth factor (VEGF) expression in vitro and in vivo was measured respectively by western blot analysis and enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry analysis of CD34 and VEGF expression in primary melanoma was also presented.RESULTS: β-Elemene inhibited B16BF10 cell proliferation starting from 200 μM, but VEGF from 20 μM. Both 20 and 50 μM β-elemene in vitro inhibited VEGF-induced sprouting vessel of rat aortic ring and microvessel formation of chick embryo chorioallantoic membrane. In vivo, tumor size of primary melanoma in mice intraperitoneally treated with β-elemene was significantly smaller than that of the control; CD34 expression of primary melanoma was also suppressed; and the metastatic melanoma colonies and content of melanin in lung were detected obviously decreased in mice of β-elemene-treated groups. Furthermore, results of VEGF expressing in primary melanoma, serum and lung of mice also disclosed that VEGF was inhibited in vivo.CONCLUSIONS: β-Elemene inhibited melanoma growth and metastasis through suppressing VEGF-mediated angiogenesis. It is a natural potential antiangiogenic agent.

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Posted: December 11, 2018, 11:03 pm
PMID:  Basic Clin Pharmacol Toxicol. 2010 Nov ;107(5):868-76. PMID: 22545969Abstract Title:  Evaluation of cisplatin in combination withβ-elemene as a regimen for prostate cancer chemotherapy.Abstract:  Cisplatin is one of the most potent chemotherapeutic agents for the treatment of many types of solid tumours. Nevertheless, it is not the first-line drug for prostate cancer chemotherapy, because prostate tumour cells exhibit intrinsic and acquired resistance to cisplatin. We have previously demonstrated thatβ-elemene, a novel plant-derived anti-neoplastic with low toxicity, inhibits lung and ovarian carcinoma cell growth in vitro. In the present study, we explored the therapeutically chemosensitizing effect of β-elemene on cisplatin anti-tumour efficacy in androgen-independent prostate cancer cells as well as the underlying mechanism. β-Elemene significantly increased cisplatin cytotoxicity in the androgen-independent prostate carcinoma cell lines DU145 and PC-3. In addition, β-elemene markedly promoted cisplatin-induced apoptotic cell death in both cell lines, as determined by three different apoptosis assays. β-Elemene augmented the cisplatin-induced activation of caspase-3/7/10 and caspase-9, cleavage of caspase-3 and -9, suppression of Bcl-2 and Bcl-X(L) expression, and release of cytochrome c from mitochondria in these cells. Thus, β-elemene enhancement of cisplatin-induced apoptosis via mitochondrial activation of the caspase-mediated apoptotic pathway may account for the augmented anti-cancer potency of cisplatin in prostate cancer. Cisplatin combined with β-elemene as a chemosensitizer or adjuvant warrants further study and may be potentially useful as a first-line treatment of androgen-independent prostate carcinomas.

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Posted: December 11, 2018, 10:52 pm
PMID:  J Mol Neurosci. 2011 May ;44(1):31-40. Epub 2011 Jan 19. PMID: 21246417Abstract Title:  Amelioration of experimental autoimmune encephalomyelitis byβ-elemene treatment is associated with Th17 and Treg cell balance.Abstract:  Experimental autoimmune encephalomyelitis (EAE), an animal mode of multiple sclerosis (MS), was previously considered that is mediated by Th1 cells. However, a number of recent studies provided strong evidence that T helper cells that produce interleukin (IL)-17 (Th17) and anti-inflammatory CD4+ Foxp3+ regulatory T cells (Tregs) play a dominant role in the pathogenesis of EAE.β-elemene is a natural antitumor plant drug with the role of multiple target, and it has been found to pass through the blood-brain barrier easily. It also has been strongly implicated as an immune modulatory agent, but the precise mechanisms of its action are largely unknown. In the present study,we mainly investigated the efficacy and mechanism of β-elemene against EAE in vivo and vitro. The treatment of C57 mice with β-elemene significantly delayed the onset of EAE, markedly suppressed MOG-specific T cell proliferation in a dose-dependent manner, dramatically reduced the IL-17, IL-6, IL-23, and RORγt production and induced the Foxp3 expression in both the periphery and the inflamed spinal cord. These findings indicated that β-elemene amelioration EAE was, to a large extent, due to inhibit differentiation and development of Th17 cells depends on down-regulating expression of IL-6, IL-23, RORγt signaling, and promoting expansion in Treg cells. Suggesting it is useful in the control of MS and other Th17 cell-mediated inflammatory diseases.

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Posted: December 11, 2018, 10:37 pm
PMID:  Front Med. 2011 Mar ;5(1):101-5. Epub 2011 Mar 17. PMID: 21681682Abstract Title:  Downregulation effects of beta-elemene on the levels of plasma endotoxin, serum TNF-alpha, and hepatic CD14 expression in rats with liver fibrosis.Abstract:  It has been demonstrated thatβ-elemene could protect against carbon tetrachloride (CCl(4))-induced liver fibrosis in our laboratory work, and the aim of this paper is to reveal the protective mechanisms of β-elemene. The hepatic fibrosis experimental model was induced by the hypodermical injection of CCl(4) in Wistar male rats. β-elemene was intraperitoneally administered into rats for 8 weeks (0.1 mL/100 g bodyweight per day), and plasma endotoxin content was assayed by biochemistry. The serum TNF-α level was detected using radioactive immunity. CD14 expression in rat livers was measured by immunohistochemistry and Western blot. The results showed that β-elemene can downregulate the levels of plasma endotoxins, serum TNF-α, and hepatic CD14 expression in rats with liver fibrosis. β-elemene plays an important role in downregulating the lipopolysaccharide signal transduction pathway, a significant pathway in hepatic fibrosis development.

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Posted: December 11, 2018, 10:33 pm
PMID:  J Neurooncol. 2012 Apr ;107(2):307-14. Epub 2011 Dec 11. PMID: 22160627Abstract Title:  Β-elemene inhibits Hsp90/Raf-1 molecular complex inducing apoptosis of glioblastoma cells.Abstract:  β-Elemene, an active component of herb medicine Curcuma wenyujin, has been shown to antagonize glioblastoma cells by inducing apoptosis. However, how β-elemene induces apoptosis of these cells remains unclear. In this study, we report that β-elemene disrupted the formation of the Hsp90/Raf-1 complex, a key step in maintaining the conformation stability of Raf-1, and caused deactivation of Raf-1 and inhibition of the ERK pathway, thereby leading to apoptosis of glioblastoma cells. Specifically, treatment of glioblastoma cell lines with β-elemene attenuated phosphorylation of multiple members of the kinase families in the Ras/Raf/MEK/ERK cascade, including Raf-1 and ERK as well as downstream signaling targets such as Bcl-2. These results suggest that the Hsp90/Raf-1 complex could be a promising molecular target for new drug development for the treatment of glioblastoma.

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Posted: December 11, 2018, 10:11 pm
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