A multiple endpoint approach reveals potential in vitro anticancer properties of thymoquinone in human renal carcinoma cells.

PMID: 

Food Chem Toxicol. 2019 Dec 27 ;136:111076. Epub 2019 Dec 27. PMID: 31883990

Abstract Title: 

A multiple endpoint approach reveals potential in vitro anticancer properties of thymoquinone in human renal carcinoma cells.

Abstract: 

Thymoquinone (TQ) is a monoterpene isolated from the oil of Nigella sativa seeds. The aim of this work was to evaluate the cytotoxic effects induced by TQ and its impact on the migration and invasion potential of 786-O human renal cancer cells. These cells were exposed to TQ (1-100 μM) for 24 and 48 h and cell viability assessed using the Crystal Violet and MTS assays. TQ treatment clearly decreased cell viability in a concentration- and time-dependent manner. TQ exposure moderately increased intracellular ROS levels and co-incubation with reduced glutathione markedly increased cell viability. Moreover, the effect of TQ in the cell cycle distribution was evaluated using flow cytometry, and an increase in the sub-G1 population was observed, especially at 30 μM, along with an increase in the % of apoptotic cells. TQ did not show genotoxic effects at a non-cytotoxic concentration (1.0 μM). At this concentration level, TQ significantly decreased the collective migration of 786-O cells, whereas it had no effect in chemotactic migration. TQ also decreased the invasiveness potential of 786-O cells, as evaluated by the transwell invasion assay. Overall, these results suggest that TQ presents an anticancer potential in the context of renal cancer, warranting further investigation.

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The antidiabetic effect of thymoquinone: A systematic review and meta-analysis of animal studies.

PMID: 

Food Res Int. 2020 Jan ;127:108736. Epub 2019 Oct 15. PMID: 31882078

Abstract Title: 

The antidiabetic effect of thymoquinone: A systematic review and meta-analysis of animal studies.

Abstract: 

Thymoquinone (2-isopropyl-5-methylbenzo-1, 4-quinone) (TQ) is a quinone derivative with a yellow crystalline appearance, abundantly found in black cumin, Nigella sativa L. TQ has diverse pharmacological properties. The aim of this systematic review on the antidiabetic effects of TQ is to evaluate the currently available evidence and conduct meta-analysis. A literature search of articles published until 25 January 2019 was done on PubMed, EMBASE, Web of Sciences and Scopus databases, using relevant keywords. The meta-analysis included 18 studies that examined the serum glucose (SG) level or serum insulin level or body weight (BW). In the meta-analysis it was found that with an overall pooled standardized mean difference (SMD) of -9.176 mg/dl (95%CI: -10.759, -7.593; p = 0.000); TQ reduced the SG level (-9.176 mg/dl) significantly in the STZ-induced diabetes model. Moreover, a meta-analysis of the effect of TQ on BW demonstrated that TQ has a statistically significant effect on the BW of diabetic animals with an overall pooled SMD of 4.509 (95%CI: 3.234, 5.784; p = 0.000). In addition, the overall pooled estimate of the level of serum insulin was significant with SMD of 1.681 (95%CI: 0.858, 2.503; p = 0.000). Therefore, the meta-analysis showed that TQ has a significant antidiabetic effect through its actionon the SG, serum insulin level, and BW of the animals.

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The reviewed reports confirmed the strong anti-cancer efficacy of thymoquinone.

PMID: 

Saudi Pharm J. 2019 Dec ;27(8):1113-1126. Epub 2019 Sep 25. PMID: 31885471

Abstract Title: 

Thymoquinone (2-Isoprpyl-5-methyl-1, 4-benzoquinone) as a chemopreventive/anticancer agent: Chemistry and biological effects.

Abstract: 

Cancer remains the topmost disorders of the mankind and number of cases is unceasingly growing at unprecedented rates. Although the synthetic anti-cancer compounds still hold the largest market in the modern treatment of cancer, natural agents have always been tried and tested for potential anti-cancer properties. Thymoquinone (TQ), a monoterpene and main ingredient in the essential oil ofhas got very eminent rankings in the traditional systems of medicine for its anti-cancer pharmacological properties. In this review we summarized the diverse aspects of TQ including its chemistry, biosynthesis, sources and pharmacological properties with a major concern being attributed to its anti-cancer efficacies. The role of TQ in different aspects involved in the pathogenesis of cancer like inflammation, angiogenesis, apoptosis, cell cycle regulation, proliferation, invasion and migration have been described. The mechanism of action of TQ in different cancer types has been briefly accounted. Other safety and toxicological aspects and some combination therapies involving TQ have also been touched. A detailed literature search was carried out using various online search engines like google scholar and pubmed regarding the available research and review accounts on thymoquinone upto may 2019. All the articles reporting significant addition to the activities of thymoquinone were selected. Additional information was acquired from ethno botanical literature focusing on thymoquinone. The compound has been the centre of attention for a long time period and researched regularly in quite considerable numbers for its various physicochemical, medicinal, biological and pharmacological perspectives. Thymoquinone is studied for various chemical and pharmacological activities and demonstrated promising anti-cancer potential. The reviewed reports confirmed the strong anti-cancer efficacy of thymoquinone. Furtherandresearch is strongly warranted regarding the complete exploration of thymoquinone in ethnopharmacological context.

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Nigella sativa seed oil supplements may decrease the liver enzymes and lipid profiles in the patients with NAFLD.

PMID: 

J Diabetes Metab Disord. 2019 Dec ;18(2):453-459. Epub 2019 Sep 11. PMID: 31890671

Abstract Title: 

The effect ofoil on serum levels of inflammatory markers, liver enzymes, lipid profile, insulin and fasting blood sugar in patients with non-alcoholic fatty liver.

Abstract: 

Background: Non-alcoholic fatty liver disease (NAFLD) is one of the metabolic disturbances associated with inflammation.(NS) seed oil has different chemical compounds including Thymoquinone (TQ), unsaturated fatty acids, and flavonoids. NSs are used as anti-inflammatory and antioxidants in medical sciences. This study aimed to investigate the effect of NS oil on several parameters in serum levels of patients with NAFLD.Methods: Forty-four patients diagnosed with NAFLD participated in a randomized, double-blind, placebo-controlled clinical trial. Patients were randomly assigned into two groups; one receiving NS oil and the other receiving placebo (paraffin oil), for 8 weeks. Blood samples were taken from the patients at the beginning and the end of the study. Afterwards, liver enzymes (ALT, AST, and GGT), inflammatory markers (Hs-CRP, TNF-α, and IL-6), insulin, lipid profiles (total cholesterol, triglyceride, VLDL, LDL-C, and HDL-C), FBS, and blood pressure were measured.Results: Consumption of NS seed oil as supplement decreased the FBS level, lipid profiles (TG, TC, LDL, VLDL), liver enzymes (AST and ALT), hs-CRP inflammatory marker, IL-6, TNF-α, while it increased the HDL-C levels, compared to the placebo group ( 

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Nigella sativa supplementation may provide additional benefits for the treatment of asthma.

PMID: 

Am J Emerg Med. 2019 Nov 29. Epub 2019 Nov 29. PMID: 31892440

Abstract Title: 

The influency of Nigella sativa for asthma control: A meta-analysis.

Abstract: 

INTRODUCTION: The efficacy of Nigella sativa supplementation for asthma control remains controversial. We conduct a systematic review and meta-analysis to explore the influence of Nigella sativa supplementation on asthma control.METHODS: We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through June 2019 for randomized controlled trials (RCTs) assessing the efficacy of Nigella sativa supplementation for asthma control. This meta-analysis is performed using the random-effect model.RESULTS: Four RCTs are included in the meta-analysis. Overall, compared with control group for asthma, Nigella sativa supplementation is associated with increased ACT scores (Std. MD = 0.50; 95% CI = 0.11 to 0.88; P = 0.01), FEV1 (Std. MD = 1.84; 95% CI = 0.07 to 3.60; P = 0.04), but demonstrates no obvious impact on PEF (Std. MD = 3.11; 95% CI = -1.30 to 7.52; P = 0.17), IL-4 (Std. MD = -0.31; 95% CI = -1.21 to 0.59; P = 0.50), or IFN-γ (Std. MD = 1.11; 95% CI = -0.44 to 2.67; P = 0.16).CONCLUSIONS: Nigella sativa supplementation may provide additional benefits for the treatment of asthma.

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Tanshinone IIA enhances the inhibitory effect of imatinib on proliferation and motility of acute leukemia cell line TIB‑152.

PMID: 

Oncol Rep. 2019 Dec 31. Epub 2019 Dec 31. PMID: 31894340

Abstract Title: 

Tanshinone IIA enhances the inhibitory effect of imatinib on proliferation and motility of acute leukemia cell line TIB‑152 in vivo and in vitro by inhibiting the PI3K/AKT/mTOR signaling pathway.

Abstract: 

Acute lymphoblastic leukemia (ALL) is a malignant hematological disease. Tanshinone IIA (Tan IIA) has antitumor activity in vitro and in vivo. The aim of the present study was to investigate the effects of Tan IIA in combination with imatinib (IM) on the proliferation, apoptosis, migration and invasion of acute T lymphocytic leukemia TIB‑152 cells in vivo and in vitro, and analyzethe potential underlying mechanism. Tan IIA and IM, alone and in combination, significantly inhibited proliferation, migration and invasion of TIB‑152 cells, and promoted apoptosis; the effect of co‑treatment with Tan IIA plus IM was enhanced. IGF‑1 promoted the proliferation, migration andinvasion of TIB‑152 cells and inhibited apoptosis, while Tan IIA treatment significantly reversed these effects. In vivo experiments demonstrated that treatment with Tan IIA and IM, alone or in combination, significantly inhibited tumor growth in TIB‑152 xenograft mice; the growth inhibitionof Tan IIA plus IM was the strongest observed. Western blot analysis revealed that the combination of Tan IIA and IM resulted in significantly lower levels of p‑PI3K, p‑AKT and p‑mTOR in cells and tissues compared with the IM and Tan alone treatment groups. In addition, the combination of Tan IIA and IM significantly decreased the levels of Ki67, cleaved caspase‑3, VEGF and MMP‑9 in cells and tissues, and the level of caspase‑3 was significantly increased. Taken together, the results revealed that Tan IIA enhanced the inhibitory effect of imatinib on TIB‑152 cell proliferation, migration and invasion, and induced apoptosis, which may be associated with inhibition of the PI3K/AKT/mTOR signaling pathway.

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Nephroprotective effect of herbal extract Eurycoma longifolia on paracetamol-induced nephrotoxicity.

PMID: 

Evid Based Complement Alternat Med. 2019 ;2019:4916519. Epub 2019 May 13. PMID: 31214269

Abstract Title: 

Nephroprotective Effect of Herbal Extracton Paracetamol-Induced Nephrotoxicity in Rats.

Abstract: 

Paracetamol (PCM) is a well-known drug widely used for its analgesic and antipyretic properties. PCM is generally considered as safe but overdose of PCM can cause nephrotoxicity. Traditionally, herbs have been used for the treatment of drug or toxin-induced renal disorders and numerous medicinal plants were tested for nephroprotection effect in PCM-induced nephrotoxicity model. The aim of the present study was to evaluate the protective effect of the herbal extract(EL) against PCM-induced nephrotoxicity rat model. Forty Wistar rats were randomly divided into five groups of eight rats each: control (vehicle 10 ml/kg), PCM alone (200 mg/kg PCM), EL 100 (EL 100 mg/kg+200 mg/kg PCM), EL 200 (EL 200 mg/kg+200 mg/kg PCM), and EL 400 (EL 400 mg/kg+200 mg/kg PCM). All animals from control group received vehicle daily and animals from groups PCM alone, EL 100, EL 200, and EL 400 received repeated dose of PCM and the assigned treatment of EL daily for a period of 14 days. On the 15th day, serum creatinine, blood urea nitrogen, protein, and albumin were measured in blood and creatinine clearance was measured in urine collected over 24 hours. Kidney sections of all experimental groups underwent histopathological analysis. There was a significant (p

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Protective effects of fulvotomentosides on cadmium-induced hepatotoxicity.

PMID: 

Zhongguo Yao Li Xue Bao. 1992 May ;13(3):213-7. PMID: 1442101

Abstract Title: 

Protective effects of fulvotomentosides on cadmium-induced hepatotoxicity.

Abstract: 

Fulvotomentosides (Ful) is the total saponins of Lonicera fulvotomentosa. In the present study, we examined the effects of Ful on cadmium (CdCl2)-induced acute liver injury in mice. Ful pretreatment (150 mg.kg-1, sc x 3 d) remarkably decreased CdCl2 (3.7 mg Cd.kg-1, iv)-induced liver damage as indicated by serum activities of alanine aminotransferase and sorbitol dehydrogenase. Distribution of Cd to 12 organs and hepatic subcellular fractions was determined 2 h after Cd challenge. Ful pretreatment did not produce a marked shift in the distribution of Cd to various organs, but markedly altered the hepatic subcellular distribution of Cd, with more Cd bound to metallothionein (MT) in the cytosol, less in the nuclear, mitochondrial, and microsomal fractions. Ful pretreatment produced a dose-dependent increase in hepatic MT as determined by the Cd.hemoglobin assay. In conclusion, Ful protected against Cd hepatotoxicity by inducing MT, which binds Cd in the cytosol and lowers the amount of Cd available to other critical organelles and proteins.

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Toxic acetaminophen exposure induces distal lung ER stress, proinflammatory signalling, and emphysematous changes in the adult murine lung.

PMID: 

Oxid Med Cell Longev. 2019 ;2019:7595126. Epub 2019 Nov 28. PMID: 31885815

Abstract Title: 

Toxic Acetaminophen Exposure Induces Distal Lung ER Stress, Proinflammatory Signaling, and Emphysematous Changes in the Adult Murine Lung.

Abstract: 

Clinical studies have demonstrated a strong association between both acute toxic exposure and the repetitive, chronic exposure to acetaminophen (APAP) with pulmonary dysfunction. However, the mechanisms underlying this association are unknown. Preclinical reports have demonstrated that significant bronchiolar injury occurs with toxic APAP exposure, but very little information exists on how the distal lung is affected. However, cells in the alveolar space, including the pulmonary epithelium and resident macrophages, express the APAP-metabolizing enzyme CYP2E1 and are a potential source of toxic metabolites and subsequent distal lung injury. Thus, we hypothesized that distal lung injury would occur in a murine model of toxic APAP exposure. Following exposure of APAP (280 mg/kg, IP), adult male mice were found to have significant proximal lung histopathology as well as distal lung inflammation and emphysematous changes. Toxic APAP exposure was associated with increased CYP2E1 expression in the distal lung and accumulation of APAP-protein adducts. This injury was associated with distal lung activation of oxidant stress, endoplasmic reticulum stress, and inflammatory stress response pathways. Our findings confirm that following toxic APAP exposure, distal lung CYP2E1 expression is associated with APAP metabolism, tissue injury, and oxidant, inflammatory, and endoplasmic reticulum signaling. This previously unrecognized injury may help improve our understanding of the relationship between APAP and pulmonary-related morbidity.

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N-acetylcysteine can protect against polystyrene microplastic induced sperm damage.

PMID: 

Ecotoxicol Environ Saf. 2019 Dec 30 ;190:110133. Epub 2019 Dec 30. PMID: 31896473

Abstract Title: 

Exposure to polystyrene microplastics causes reproductive toxicity through oxidative stress and activation of the p38 MAPK signaling pathway.

Abstract: 

Microplastics (MP) are receiving increased attention as a harmful environmental pollutant, however information on the reproduction toxicity of MP in terrestrial animals, especially mammals, is limited. In this experiment, we investigated the impact of polystyrene microplastics (micro-PS) on the reproductive system of male mice. Healthy Balb/c mice were exposed to saline or to different doses of micro-PS for 6 weeks. The results showed that micro-PS exposure resulted in a significant decrease in the number and motility of sperm, and a significant increase in sperm deformity rate. We also detected a decrease in the activity of the sperm metabolism-related enzymes, succinate dehydrogenase (SDH) and lactate dehydrogenase (LDH), and a decrease in the serum testosterone content in the micro-PS exposure group. We found that micro-PS exposure caused oxidative stress and activated JNK and p38 MAPK. In addition, we found that when N-acetylcysteine (NAC) scavenges ROS, and when the p38 MAPK-specific inhibitor SB203580 inhibits p38MAPK, the micro-PS-induced sperm damage is alleviated and testosterone secretion improves. In conclusion, our findings suggest that micro-PS induces reproductive toxicity in mice through oxidative stress and activation of the p38 MAPK signaling pathways.

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