PMID: 

Inflammation. 2012 Aug ;35(4):1392-401. PMID: 22391746

Abstract Title: 

Resveratrol Inhibits respiratory syncytial virus-induced IL-6 production, decreases viral replication, and downregulates TRIF expression in airway epithelial cells.

Abstract: 

Respiratory syncytial virus (RSV) is the most common pathogen responsible for lower respiratory diseases in children. So far, there is no effective treatment or preventative vaccine available for RSV infection, although ribavirin and dexamethasone are commonly prescribed. Resveratrol has been shown to inhibit the replication of several other viruses, thus the effect of resveratrol on RSV-induced inflammatory mediators in 9HTEo cell cultures was evaluated, and possible mechanisms of action were explored and compared with dexamethasone and ribavirin. Incubation with resveratrol resulted in decreased IL-6 production and partial inhibition of RSV replication. Resveratrol treatment also inhibited virus-induced TIR-domain-containing adapter-inducing interferon-β (TRIF) and TANK binding kinase 1 (TBK1) protein expression. These data demonstrate the ability of resveratrol to inhibit cytokine production by RSV in airway epithelial cells, indicating that it might be a therapeutic agent with both anti-inflammatory and antiviral potential for the treatment ofRSV infection.

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Biosci Biotechnol Biochem. 2020 Jan 21:1-12. Epub 2020 Jan 21. PMID: 31960754

Abstract Title: 

Neuroprotective effect of-derived polysaccharides in neuronal HT22 cell damage induced by hydrogen peroxide.

Abstract: 

Crude extracts and phytochemical compounds derived fromleaves have been demonstrated to exert neuroprotective effects. However, the neuroprotective effects ofleaves-derived polysaccharide extracts (ALPs) have not been investigated. ALP treatment was shown to induce concentration-dependent antioxidant activity in HT22 cells, and to increase cell viability in HO-treated HT22 cells. These effects were correlated with a decrease in major components of oxidation, including: Ca, ROS, and malondialdehyde (MDA). Mediators of the intracellular response to oxidation, including Bax, cytochrome, and cleaved caspases-3, -8, -9, MAPKs, and NF-κB, were positively influenced by ALP treatment under conditions of HO-mediated oxidative stress. In addition, ALP restored the expression of superoxide dismutase (SOD) and associated signaling pathways (PARP, PI3K/AKT and Nrf2-mediated HO-1/NQO-1) following HOtreatment. These results provide new pharmacological evidence that ALP facilitates neuroprotection via prevention of neuronal oxidative stress and promotion of cell survival signaling pathways.ABTS: 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonicacid); AD: Alzheimer's disease; ALP: polysaccharide extracts isolated fromleaves; ARE: antioxidant response element; DPPH: 1,1-diphenyl-picrylhydrazyl; DCFH-DA: 2',7'-dichlorofluorescin diacetate; ECL: electrochemiluminescence; ERK: extracellular regulated kinase; FBS: Fetal bovine serum; FITC: fluorescein isothiocyanate; FRAP: ferric reducing antioxidant power; HO-1: Heme oxygenase-1; JNK: c-jun N-terminal kinase; MAPKs: mitogen-activated protein kinases; MDA: malondialdehyde; MMP: mitochondrial membrane potential; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide; NQO1: NAD(P)H:quinine oxidoreductase 1, Nrf2: nuclear factor-E2-related factor 2; PD: parkinson's disease; PI3K: phosphatidylinositol-3kinase; PVDF: polyvinylidene difluoride; ROS: reactive oxygen species; SOD: Superoxidedismutase; TPTZ: tripydyltriazine.

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PMID: 

Environ Res. 2019 Dec 6 ;182:109013. Epub 2019 Dec 6. PMID: 31918310

Abstract Title: 

Genetic susceptibility may modify the association between cell phone use and thyroid cancer: A population-based case-control study in Connecticut.

Abstract: 

Emerging studies have provided evidence on the carcinogenicity of radiofrequency radiation (RFR) from cell phones. This study aims to test the genetic susceptibility on the association between cell phone use and thyroid cancer. Population-based case-control study was conducted in Connecticut between 2010 and 2011 including 440 thyroid cancer cases and 465 population-based controls with genotyping information for 823 single nucleotide polymorphisms (SNPs) in 176 DNA genes. We used multivariate unconditional logistic regression models to estimate the genotype-environment interaction between each SNP and cell phone use and to estimate the association with cell phone use in populations according to SNP variants. Ten SNPs had P 

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PMID: 

J Nerv Ment Dis. 2020 Jan 7. Epub 2020 Jan 7. PMID: 31913957

Abstract Title: 

Safety and Efficacy of Saffron (Crocus sativus L.) for Treating Mild to Moderate Depression: A Systematic Review and Meta-analysis.

Abstract: 

BACKGROUND: Herbal remedies are becoming increasingly popular for the treatment of depression. Recently, accumulating evidences reveal a positive effect of saffron (Crocus sativus L.) in relieving depressive symptoms. The objective of this meta-analysis was to assess the safety and efficacy of saffron in treating mild to moderate depression by synthesizing all available data.MATERIALS AND METHODS: Relevant studies were retrieved from electronic databases and cross-checking of reference lists. Eligible trials were carefully reviewed, and necessary data were extracted. The Hamilton Rating Scale for Depression or Beck Depression Inventory scores, response rate, remission rate, and adverse effects were compared between saffron and placebo or saffron and antidepressants to assess the efficacy of saffron for depression.RESULTS: Twelve studies were included in the meta-analysis. Overall results showed that saffron possessed better efficacy in the improvement of depressive symptoms when compared with placebo, whereas saffron was as effective as synthetic antidepressants. No significant difference was detected in the incidence of adverse effects between saffron and placebo or between saffron and antidepressants.CONCLUSIONS: Saffron could be considered as an alternative to synthetic antidepressants in the treatment of mild to moderate depression. However, multicenter trials with larger sample size, longer treatment duration, and different ethnic groups are required to verify our results.

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PMID: 

Prev Nutr Food Sci. 2019 Dec ;24(4):363-372. Epub 2019 Dec 31. PMID: 31915630

Abstract Title: 

A Review of Potential Efficacy of Saffron (L.) in Cognitive Dysfunction and Seizures.

Abstract: 

(saffron) is traditionally used to relieve several ailments. Experimental researches have also investigated applications of saffron and its active constituents for the treatment of a wide spectrum of disorders. This review discusses pharmacological/therapeutic properties of saffron and its main components on memory function, learning ability and seizures, to highlight their merit for alleviating these disorders. An extensive literature review was carried out using various databases including ISI Web of Knowledge, Medline/PubMed, Science Direct, Scopus, Google Scholar, Embase, Biological Abstracts, and Chemical Abstracts. The growing body of evidence showed the value of saffron and its' components, alone, or in combination with the other pharmaceuticals, for improving learning and memory abilities and controlling seizures. These findings may provide pharmacological basis for the use of saffron in cognitive disturbance and epilepsy. However, further preclinical and clinical studies are necessary.

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PMID: 

Int J Reprod Biomed (Yazd). 2019 Dec ;17(11):807-818. Epub 2019 Dec 26. PMID: 31911963

Abstract Title: 

Ameliorative effects of crocin on paraquat-induced oxidative stress in testis of adult mice: An experimental study.

Abstract: 

Background: Paraquat (PQ), as a pyridine compound, is widely used worldwide to control annual weeds. The oxidative stress caused by PQ can cause deleterious changes in the testicular tissue.Objective: An investigation on the protective effects of Crocin (CCN) against PQ-induced oxidative damages and apoptotic indices in testicular tissue.Materials and Methods: Twenty-eight adult male albino mice (20-25 gr) were divided into four groups (n = 7/each). The control group received 0.1 ml/day of normal saline by intraperitoneal injection (IP); sham-control group received PQ 5 mg/kg/day, IP, and the experimental groups received PQ (CCN+PQ) and CCN-sole (200 mg/kg/day, IP), respectively, for 35 continuous days. At the end of the treatment period, the testes were dissected out and used for biochemical, molecular, and histological analyses. The expressions of tumor suppressor, B-cell lymphoma 2 (), andwere considered as hallmark factors of mitochondria-dependent apoptosis. Moreover, the testicular superoxide dismutase (SOD) and malondialdehyde (MDA) were evaluated as key biomarkers for oxidative stress.Results: The PQ significantly (p0.02, p0.01) diminished the spermatogenesis indices and SOD, increased MDA levels, and enhanced the apoptosis-related gene expression. However, the co-administration of CCN and PQ significantly (p0.01, p0.01, p0.02) ameliorated the spermatogenesis ratio, upregulated the SOD level as well asexpression, and reduced the MDA content and apoptosis vs the PQ-sole group.Conclusion: This study showed that the antioxidant properties of CCN enable to ameliorate the PQ-induced destructive effects by upregulating the testicular structure, antioxidant and apoptotic status.

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PMID: 

Inflamm Res. 2020 Jan 10. Epub 2020 Jan 10. PMID: 31925528

Abstract Title: 

Crocin alleviates lipopolysaccharide-induced acute respiratory distress syndrome by protecting against glycocalyx damage and suppressing inflammatory signaling pathways.

Abstract: 

OBJECTIVE: To explore the mechanisms of crocin against glycocalyx damage and inflammatory injury in lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) mice and LPS-stimulated human umbilical vein endothelial cells (HUVECs).METHODS: Mice were randomly divided into control, LPS, and crocin + LPS (15, 30, and 60 mg/kg) groups. HUVECs were separated into eight groups: control, crocin, matrix metalloproteinase 9 inhibitor (MMP-9 inhib), cathepsin L inhibitor (CTL inhib), LPS, MMP-9 inhib + LPS, CTL inhib + LPS, and crocin + LPS. The potential cytotoxic effect of crocinon HUVECs was mainly evaluated through methylthiazolyldiphenyl-tetrazolium bromide assay. Histological changes were assessed via hemotoxylin and eosin staining. Lung capillary permeability was detected on the basis of wet-dry ratio and through fluorescein isothiocyanate-albumin assay. Then, proteinlevels were detected through Western blot analysis, immunohistochemical staining, and immunofluorescence.RESULTS: This study showed that crocin can improve the pulmonary vascular permeability in mice with LPS-induced ARDS and inhibit the inflammatory signaling pathways of high mobility group box, nuclear factorκB, and mitogen-activated protein kinase in vivo and in vitro. Crocin also protected against the degradation of endothelial glycocalyx heparan sulfate and syndecan-4 by inhibiting the expressions of CTL, heparanase, and MMP-9 in vivo and in vitro. Overall, this study revealed the protective effectsof crocin on LPS-induced ARDS and elaborated their underlying mechanism.CONCLUSION: Crocin alleviated LPS-induced ARDS by protecting against glycocalyx damage and suppressing inflammatory signaling pathways.

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PMID: 

Pharmacol Rep. 2020 Jan 29. Epub 2020 Jan 29. PMID: 31997260

Abstract Title: 

Crocin: a protective natural antioxidant against pulmonary fibrosis induced by bleomycin.

Abstract: 

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic and fibrotic lung disease of unknown causes. Given the crucial role of oxidative stress in the progression of IPF, antioxidant therapy may be speculated to be an efficient therapeutic approach. Therefore, the present study aimed to evaluate the protective effects of Crocin as a potent, natural antioxidant against Bleomycin-induced PF in male Wistar rats.METHODS: Forty male Wistar rats were randomly divided into four groups. Group 1 received intratracheal saline on day 7 and oral gavage of saline for 28 days. Group 2 received a single dose of Bleomycin on day 7 and oral gavage of saline for 28 days. Groups 3 received a single dose of Bleomycin on day 7, accompanied with oral administration of Crocin for 28 days. Group 4 orally received Crocin for 28 days. Finally, the lungs were removed for measuring the biochemical and histopathological markers.RESULTS: The results showed that Crocin therapy remarkably decreased TNF-α, MDA and NO levels in the lungs of Bleomycin-exposed rats. Furthermore, a significant increase was seen in lung GSH content, catalase, and GPx activities in the Crocin/Bleomycin-treated group as compared with Bleomycin-treated group. However, Crocin could not markedly change the lung index and SOD activity. Histopathological changes, fibrosis and hydroxyproline content of lungs also significantly decreased by Crocin therapy in the Crocin/Bleomycin-treated group.CONCLUSION: In sum, Crocin therapy could modulate biochemical and histological changes induced by Bleomycin; therefore, it might be considered as an effective therapeutic approach against IPF.

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PMID: 

Nutrients. 2020 Jan 9 ;12(1). Epub 2020 Jan 9. PMID: 31936441

Abstract Title: 

Estimation of the Minimum Effective Dose of Dietary Supplement Crocetin for Prevention of Myopia Progression in Mice.

Abstract: 

The natural carotenoid crocetin has been reported to suppress phenotypes of an experimental myopia model in mice. We investigated the minimum effective dose to prevent myopia progression in a murine model. Three-week-old male mice (C57B6/J) were equipped with a -30 diopter (D) lens to induce myopia, and fed with normal chow, 0.0003%, or 0.001% of crocetin-containing chow. Changes in refractive errors and axial lengths (AL) were evaluated after three weeks. Pharmacokinetics of crocetin in the plasma and the eyeballs of mice was evaluated with specific high sensitivity quantitative analysis using liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine the minimum effective dosage. A concentration of 0.001% of crocetin-containing chow showed a significant (

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PMID: 

Int J Mol Sci. 2020 Jan 9 ;21(2). Epub 2020 Jan 9. PMID: 31936544

Abstract Title: 

Crocetin Extracted from Saffron Shows Antitumor Effects in Models of Human Glioblastoma.

Abstract: 

Over recent years, many authors discussed the effects of different natural compounds on glioblastoma (GBM). Due to its capacity to impair survival and progression of different cancer types, saffron extract (SE), named crocetin (CCT), is particularly noteworthy. In this work, we elucidated the antitumor properties of crocetin in glioma in vivo and in vitro models for the first time. The in vitro results showed that the four tumor cell lines observed in this study (U251, U87, U138, and U373), which were treated with increasing doses of crocetin, showed antiproliferative and pro-differentiative effects as demonstrated by a significant reduction in the number of viable cells, deep changes in cell morphology, and the modulation of mesenchymal and neuronal markers. Indeed, crocetin decreased the expression of Cluster of Differentiation CD44, CD90, CXCR4, and OCT3/4 mesenchymal markers, but increased the expression ofβIII-Tubulin and neurofilaments (NFH) neuronal linage-related markers. Epigenetic mechanisms may modulate these changes, since Histone Deacetylase, HDAC1 and HDAC3 were downmodulated in U251 and U87 cells, whereas HDAC1 expression was downmodulated in U138 and U373 cells. Western blotting analysesof Fatty Acid Synthase, FASN, and CD44 resulted in effective inhibition of these markers after CCT treatment, which was associated with important activation of the apoptosis program and reduced glioma cell movement and wound repair. The in vivo studies aligned with the results obtained in vitro. Indeed, crocetin was demonstrated to inhibit the growth of U251 and U87 cells that were subcutaneously injected into animal models. In particular, the Tumor To Progression or TTP values and Kaplan-Meier curves indicated that crocetin had more major effects than radiotherapy alone, but similar effects to temozolomide (TMZ). An intra-brain cell inoculation of a small number of luciferase-transfected U251 cells provided a model that was able to recapitulate recurrence after surgical tumor removal. The results obtained from the orthotopic intra-brain model indicated that CCT treatment increased the disease-free survival (DFS) and overall survival (OS) rates, inducing a delay in appearance of a detectable bioluminescent lesion. CCT showed greater efficacy than Radio Therapy (RT) but comparable efficacy to temozolomide in xenograft models. Therefore, we aimed to continue the study of crocetin's effects in glioma disease, focusing our attention on the radiosensitizing properties of the natural compound and highlighting the ways in which this was realized.

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