PMID: 

Food Funct. 2019 Jul 23. Epub 2019 Jul 23. PMID: 31334539

Abstract Title: 

Acute treatment with Mangifera indica L. leaf extract attenuates liver inflammation in rats fed a cafeteria diet.

Abstract: 

This study investigates the acute anti-inflammatory activity of Mangifera indica L. leaf extract and mangiferin in the liver of rats fed a cafeteria diet. This study was a randomized longitudinal experimental study. The animals were divided into three groups – Control: cafeteria diet (CD); Extract: CD + leaf extract (250 mg kg-1); and Mangiferin: CD + mangiferin (40 mg kg-1). Body weight and food intake were measured every week. On day eight, mRNA and protein expression of inflammatory markers were evaluated in the liver. Also, liver weight, SOD activity and malondialdehyde concentration were measured. Treatment for only eight days with mango leaf extract and mangiferin increased SOD activity. Mangiferin intake increased the mRNA expression of PPAR-α and HSP72. The leaf extract treatment enhanced PPAR-α mRNA expression. Mangiferin and leaf extract consumption caused a lower concentration of NFκB (p65) in nuclear extracts, and greater IL-10 mRNA and protein levels. This study highlights the potential of acute treatment with mango leaf extract and mangiferin to prevent liver inflammation caused by fat-rich diets. These results indicate a new use for a product that has low cost, is found in great amounts, and is not routinely used.

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PMID: 

Mol Immunol. 2019 Aug 3 ;114:233-242. Epub 2019 Aug 3. PMID: 31386980

Abstract Title: 

Mangiferin suppresses allergic asthma symptoms by decreased Th9 and Th17 responses and increased Treg response.

Abstract: 

Mangiferin is the major bioactive ingredient in the leaves of Mangifera indica L., Aqueous extract of such leaves have been traditionally used as an indigenous remedy for respiratory diseases including cough and asthma in Traditional Chinese Medicine. Mangiferin was shown to exert its anti-asthmatic effect by modulating Th1/Th2 cytokines imbalance via STAT6 signaling pathway. However, compelling evidence indicated that subtypes of T helpers and regulatory T cells other than Th1/Th2 were also involved in the pathogenesis of asthma. In current study, we investigated the effects of mangiferin on the differentiation and function of Th9, Th17 and Treg cells in a chicken egg ovalbumin (OVA)-induced asthmatic mouse model. Mangiferin significantly attenuated the symptoms of asthma attacks, reduced the total number of leukocytes, EOS and goblet cells infiltration in lung. Simultaneously, treatment with mangiferin remarkably decreased the proportion of Th9 and Th17 cells; reduced the levels of IL-9, IL-17A; inhibited the expression of PU.1 and RORγt in lung. However, the proportion of Treg cells, the expression of IL-10, TGF-β1 and Foxp3 were increased by mangiferin. Our data suggest that mangiferin exerted anti-asthmatic effect through decreasing Th9 and Th17 responses and increasing Treg response in OVA-induced asthmatic mouse model.

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PMID: 

Psychoneuroendocrinology. 2019 Jul 30 ;109:104397. Epub 2019 Jul 30. PMID: 31377557

Abstract Title: 

Elevated hs-CRP level is associated with depression in younger adults: Results from the Korean National Health and Nutrition Examination Survey (KNHANES 2016).

Abstract: 

INTRODUCTION: Reports on the association between the level of circulating high-sensitivity C-reactive protein (hs-CRP) and depression have been inconsistent. The aim of this study was to examine the association between hs-CRP and depression in a large sample.METHODS: This study used data obtained from a representative Korean sample of 5447 people who participated in the first (2016) year of the seventh Korean National Health and Nutrition Examination Survey (KNHNES VII-1). Depression was identified using a cutoff of 5 on the Patient Health Questionnaire-9 (PHQ-9), and high hs-CPR level was defined as≥ 3.0 mg/L.FINDINGS: Participants with a high CRP levels had a significantly higher rate of depression than did those with a low hs-CRP levels (25.1% vs. 19.8%, p = 0.007). Serum hs-CRP was independently associated with the PHQ-9 total score after adjusting for potentially confounding factors (B = 0.014; 95% CI = 0.008-0.020). After controlling for body mass index (BMI), smoking, alcohol use problems, hypertension, diabetes, dyslipidemia, chronic illness related hs-CRP, and metabolic syndrome. Furthermore, elevated hs-CRP level was significantly associated with an increased risk ofdepression (adjusted OR = 1.44; 95% CI = 1.01-2.07) in younger adults, but no significant association was observed among older adults.CONCLUSION: These findings suggest a significant correlation between high hs-CRP levels and depression in younger adults. Further studies are necessary to investigate the age-specific association and the biological mechanism involved.

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PMID: 

J Chem Neuroanat. 2019 Jun 19 ;100:101657. Epub 2019 Jun 19. PMID: 31228532

Abstract Title: 

Investigation of the neuroprotective effects of thymoquinone on rat spinal cord exposed to 900 MHz electromagnetic field.

Abstract: 

Exposure to electromagnetic field in long-term use of cell phones has increased concerns about serious health problems. Our aim was to survey the possible effects of electromagnetic field radiation (60 min/day for 28 days) on the spinal cords of 12 weeks old rats. Further, we investigated whether the administration of thymoquinone (10 mg/kg/day) would protect the spinal cord tissue against the adverse effects of electromagnetic field or not. Twenty-four adult male Wistar albino rats were assigned randomly into four groups: control, electromagnetic field, thymoquinone and electromagnetic field + thymoquinone. The cervical spinal cords of all rats was evaluated using the stereological, biochemical and histological methods. The number of motor neurons were reduced in the electromagnetic field group compared to the control group (p 

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PMID: 

Environ Toxicol. 2019 Jul 12. Epub 2019 Jul 12. PMID: 31298468

Abstract Title: 

Thymoquinone suppresses the proliferation of renal cell carcinoma cells via reactive oxygen species-induced apoptosis and reduces cell stemness.

Abstract: 

Thymoquinone is a phytochemical compound isolated from Nigella sativa and has various biological effects, including anti-inflammation, antioxidation, and anticancer. Here, we further investigated the anticancer effects and associated molecular mechanism of 2-methyl-5-isopropyl-1,4-benzoquinone (thymoquinone) on human renal carcinoma cell lines 786-O and 786-O-SI3 and transitional carcinoma cell line BFTC-909. Results showed that thymoquinone significantly reduced cell viability, inhibited the colony formation of renal cancer cells, and induced cell apoptosis and mitochondrial membrane potential change in both cancer cells. In addition, thymoquinone also triggered the production of reactive oxygen species (ROS) and superoxide and the activation of apoptotic and autophagic cascade. ROS inhibition suppressed the caspase-3 activation and restored the decreased cell viability of 786-O-SI3 in response to thymoquinone. Autophagy inhibition did not restore the cell viability of 786-O-SI3 suppressed by thymoquinone. Moreover, thymoquinone suppressed the cell sphere formation and the expression of aldehyde dehydrogenase, Nanog, Nestin, CD44, and Oct-4 in 786-O-SI3 cells. The tumor-bearing model showed that thymoquinone in vivo inhibited the growth of implanted 786-O-SI3 cell. All these findings indicate that thymoquinone inhibits the proliferation of 786-O-SI3 and BFTC-909 cell possibly due to the induction of ROS/superoxide and the consequent apoptosis, suggesting that thymoquinone may be a potential anticancer supplement for genitourinary cancer.

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PMID: 

Life Sci. 2019 Jul 20:116673. Epub 2019 Jul 20. PMID: 31336121

Abstract Title: 

Thymoquinone upregulates TRAIL/TRAILR2 expression and attenuates hepatocellular carcinoma in vivo model.

Abstract: 

AIMS: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide. Indeed, chemotherapeutic drugs-induced systemic toxicity results in suboptimal cancer treatment. Consequently, there is a need for exploring of a safe and effective therapy for cancer patients. This study aimed to evaluate the hepatoprotective effect of thymoquinone (TQ) against thioacetamide (TAA)-induced HCC. Also, we investigated TQ's ability to sensitize cancer cells toward TRAIL/TRAILR2 apoptotic pathway.MAIN METHODS: Forty male Sprague Dawley rats were divided into 4 groups (n = 10) as follows: control group, CMC group, HCC group and HCC + TQ group. Serum levels of liver function biomarkers and Alpha-Fetoprotein (AFP), as well as hepatic levels of glutathione (GSH) and Alpha-Fetoprotein (MDA) were measured. Transforming growth factor-beta 1 (TGF-β1), TRAILR2, TRAIL, caspase-3, caspase-9, caspase-8 and B cell lymphoma-2 (Bcl-2) mRNA levels were assessed by Quantitative, Real-Time PCR. Fibrosis percentage and necroinflammation were quantified by histopathological examination.KEY FINDINGS: Our results indicated improvement in liver functions, decrease in AFP level and attenuation of HCC progression in TQ treated rats. TQ upregulated TRAIL/TRAILR2 and subsequently enhanced apoptosis as hinted by caspase-3 upregulation and Bcl-2 downregulation. Also, TQ decreased TGF-β1 gene expression level. Moreover, HCC + TQ group showed significant increase in hepatic GSH level and marked decrease in hepatic MDA level.SIGNIFICANCE: This study proved that TQ is able to suppress HCC development via decreasing oxidative stress, suppression of TGF-β1 and induction of TRAIL-mediated apoptosis.

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PMID: 

Drug Chem Toxicol. 2019 May 29:1-6. Epub 2019 May 29. PMID: 31137984

Abstract Title: 

The effect of chronic supplementation ofon splenocytes response in rats following treadmill exercise.

Abstract: 

) was shown to recover fatigue and imbalanced immune system. Therefore, effect of chronic administration ofhydroethanolic extract on splenocytes response in sedentary and exercised animals, was evaluated. Male Wistar rats were randomly divided into non-treated (control sedentary (C), moderately trained (MT; Velocity 20 m/min, 30 min/day 8 weeks), and over-trained (OT; Velocity 25 m/min, 60 min/day 11 weeks)), andtreated animals (Nisa, 200 mg/kg, orally) (control (Nisa-C), moderately trained (Nisa-MT) and over-trained (Nisa-OT)). Finally, cell viability and proliferation, as well as interleukin 4 (IL-4) and interferon-γ (IFN-γ) secretion in non-stimulated and concanavalin A (Con A)-stimulated splenocytes, were evaluated. In the absence of the mitogen, cell viability in Nisa-C and Nisa-OT, cell proliferation in Nisa-C and Nisa-MT, IFN-γ concentration in Nisa-MT and Nisa-OT and IFN-γ/IL-4 ratio in Nisa C, Nisa-MT and Nisa-OT were higher compared to non-treated groups; but, IL-4 level in Nisa-MT was lower than non-treated groups. In the presence of the mitogen, cell viability in Nisa-C and Nisa-OT, IL-4 concentration in Nisa-C and Nisa-OT groups, and IFN-γ concentration and IFN-γ/IL-4 ratio in Nisa-MT were higher, while IFN-γ/IL-4 ratio was lower in Nisa-C group compared to non-treated groups. Moreover, IFN-γ/IL-4ratio in stimulated and non-stimulated splenocytes supernatant was higher in Nisa-MT compared to Nisa-C and Nisa-OT groups.chronic administration may shift Th1/Th2 cytokines profile of splenocytes towards Th1, especially in over-trained and non-stimulated condition. Moderate exercise andsupplementation may improve disorders associated with elevated Th2 such as overtraining syndrome.

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PMID: 

J Food Biochem. 2019 Apr ;43(4):e12793. Epub 2019 Jan 29. PMID: 31353586

Abstract Title: 

Thymoquinone attenuates phosphorylation of AKT to inhibit kidney cancer cell proliferation.

Abstract: 

Thymoquinone (Tq) is an active compound from Nigella sativa which is used in traditional medicine. The effect of Tq on kidney cancer and the pathway of action remain unproven. Herein, we report the anticancer properties of Tq on kidney cancer cells. Tq demonstrated anti-proliferative effects in A498 cells with a GIvalue of 40.07 µM and Caki-1 cells with a GI50 of 51.04 µM by the MTT assay. Tq exhibited nuclear fragmentation and inhibited trans-endothelial migration of A498 and Caki-1 cells in a dose-responsive manner. Time-dependent increase in Annexin V-positive cells and sub-G/Gcell population was observed post-Tq treatment. The compound increased Bax protein levels and reduced Bcl-2 protein levels dose dependently in cells, thereby favoring apoptosis. Tq decreased the phosphorylation of Akt in both kidney cell types. The results suggest effective anticancer activity of Tq on kidney cancer cells which may be mediated by the Akt pathway. PRACTICAL APPLICATIONS: Results from the current investigation will through more light on the mechanistic pathway of Tq activity on the inhibition of kidney cancer cell proliferation. The output of this preclinical in vitro study may be translated into better chemotherapeutics of Tq and its analogs to treat kidney cancer. However, a detailed investigation on in vivo models is recommended.

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PMID: 

Complement Ther Med. 2019 Aug ;45:149-155. Epub 2019 Jun 14. PMID: 31331553

Abstract Title: 

The effect of Nigella sativa L. supplementation on serum C-reactive protein: A systematic review and meta-analysis of randomized controlled trials.

Abstract: 

OBJECTIVE: Evidence on the efficacy ofNigella sativa supplementation is equivocal, thus the aim of this systematic review and meta-analysis of randomized clinical trials (RCTs) was to examine the effect of Nigella sativa (N. sativa) supplementation on plasma C-reactive protein (CRP) concentrations.METHODS: PubMed, Scopus, ISI Web of Science, Cochrane library, and Google Scholar databases were searched (up to April 2019) to identify RCTs investigating the effects of N. sativa seed and seed oil supplementation on CRP. Weighted mean differences (WMD) was pooled using a random-effects model. Standard methods were also used for assessment of heterogeneity, sensitivity analysis, and publication bias.RESULTS: Eventually only five articles which reported data of interest entered for data analysis. The meta-analysis showed a significant reduction in serum CRP (WMD: -0.55 mg/L, 95% CI: -1.02, -0.08, P = 0.02), with significant heterogeneity between selected studies (I = 77.3%). Between-study heterogeneity disappeared following subgroup analysis, stratified by baseline BMI (≥30 kg/m: I = 2.8%). However, the effect of N. sativa seed and seed oil supplementation on CRP was only significant in studies that were conducted on participants with BMI ≥ 30 kg/m(WMD: -0.50 mg/L, 95% CI: -0.85, -0.15).CONCLUSIONS: This meta-analysis suggests thatN. sativa seed and seed oil supplementation can significantly reduce serum CRP level. However, RCTs with a larger sample size and longer follow-up periods should be conducted for future investigations to confirm the veracity of these results.

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PMID: 

Biosci Rep. 2019 Aug 2. Epub 2019 Aug 2. PMID: 31375555

Abstract Title: 

stimulate insulin secretion from isolated rat islets and inhibit the digestion and absorption of (CH2O)n in the gut.

Abstract: 

seeds are traditionally reputed as possessing anti-diabetic properties. As a result, we aim to explore the mechanism of its anti-hyperglycemic activity. This present study uses various experimental designs including gastrointestinal motility, intestinal disaccharidase activity and inhibition of carbohydrate digestion and absorption in the gut.  The animals used as type 2 diabetic models were induced with streptozotocin to make them as such. Oral glucose tolerance test was performed to confirm that the animals were indeed diabetic. The extract reduced postprandial glucose, suggesting it interfered with glucose absorption in the gut.  Italso improved glucose (2.5g/kg/5ml) tolerance in rats.  Furthermore, treatment withproduced a significant improvement in gastrointestinal (GI) motility, while reduced disaccharidase enzyme activity in fasted rats. The extract produced a similar effect within acute oral sucrose (2.5g/kg/5ml) load assay.  Following sucrose administration, a substantial amount of unabsorbed sucrose was found in six different parts of the GI tract. This indicates thathas the potentiality to liberate GI content and reduce or delay glucose absorption. A potential hypoglycemic activity of the extract found in insulin release assay, where the extract significantly improved insulin secretion from isolated rat islets. These concluded present findings give rise to the implication thatseeds are generating postprandial anti-hyperglycemic activity within type 2 diabetic animal models via reducing or delaying carbohydrate digestion and absorption in the gut as well as improving insulin secretion in response to the plasma glucose.

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