PMID: 

Anticancer Agents Med Chem. 2019 Jul 29. Epub 2019 Jul 29. PMID: 31362681

Abstract Title: 

Quercetin Promotes Cell Cycle Arrest and Apoptosis and Attenuates the Proliferation of Human Chronic Myeloid Leukemia Cell Line-K562 Through Interaction with HSPs (70 and 90), MAT2A and FOXM1.

Abstract: 

BACKGROUND: Chronic Myeloid Leukaemia (CML) starts in certain blood-forming cells of the bone marrow when cells acquire Philadelphia chromosome. Nowadays, scientists attempt to find novel and safe therapeutic agents and approaches for CML therapy as using of the Tyrosine Kinase Inhibitors (TKIs), CML conventional treatment agents, has some restrictions and also adverse effects. Recently, it has been proposed that phytochemicals, such as flavonoids due to their low side effects and notable safety have the potential to use for CML therapy.MATERIALS AND METHODS: K-562 cells were exposed with three concentrations of the querectin (10, 40 and 80µM) for 12, 24 and 48 hours. After that, these cells apoptosis rate was estimated using Annexin-V/PI staining and flowcytometry analysis, and their proliferation rate was evaluated using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT). Finally, expression of the 70 and 90 kilodalton heat shock proteins (HSP70 and 90), methionine adenosyltransferase 2A (MAT2A), Forkhead box protein M1 (FOXM1), caspase-3 and -8, Bcl-X(L) and Bax involved in leukemic cells survival and proliferation was assessed using Real-Time PCR within 12, 24 and 48 hours after exposure with quercetin 40 and 80µM.RESULTS: Considering consequences, querecetin induced apoptosis in K-562 cells, and also abrogated these cells proliferation. On the other hand, RT-PCR results showed a reduction in some of the candidate genes expression, especially HSP70, Bcl-X(L) and FOXM1, when cells were treated with quercetin 40 and 80µM. Also, Bax, caspase-3 and caspase-8 expression was significantly improved in K-562 cells upon quercetin exposure.CONCLUSION: We concluded that CML therapy by querecetin due to its anti-proliferative and anti-survival potentials could lead to the promising therapeutic outcome through targeting major survival and proliferation involved genes expression.

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PMID: 

Biosci Rep. 2019 Aug 30 ;39(8). Epub 2019 Aug 13. PMID: 31366565

Abstract Title: 

Quercetin modulates signaling pathways and induces apoptosis in cervical cancer cells.

Abstract: 

Cancer cells have the unique ability to overcome natural defense mechanisms, undergo unchecked proliferation and evade apoptosis. While chemotherapeutic drugs address this, they are plagued by a long list of side effects and have a poor success rate. This has spurred researchers to identify safer bioactive compounds that possess chemopreventive and therapeutic properties. A wide range of experimental as well as epidemiological data encourage the use of dietary agents to impede or delay different stages of cancer. In the present study, we have examined the anti-ancer property of ubiquitous phytochemical quercetin by using cell viability assay, flow cytometry, nuclear morphology, colony formation, scratch wound assay, DNA fragmentation and comet assay. Further, qPCR analysis of various genes involved in apoptosis, cell cycle regulation, metastasis and different signal transduction pathways was performed. Proteome profiler was used to quantitate the expression of several of these proteins. We find that quercetin decreases cell viability, reduces colony formation, promotes G-M cell cycle arrest, induces DNA damage and encourages apoptosis. Quercetin induces apoptosis via activating both apoptotic pathways with a stronger effect of the extrinsic pathway relying on the combined power of TRAIL, FASL and TNF with up-regulation of caspases and pro-apoptotic genes. Quercetin could inhibit anti-apoptotic proteins by docking studies. Further, quercetin blocks PI3K, MAPK and WNT pathways. Anticancer effect of quercetin observed in cell-based assays were corroborated by molecular biology studies and yielded valuable mechanistic information. Quercetin appears to be a promising candidate with chemopreventive and chemotherapeutic potential and warrants further research.

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PMID: 

Med Sci Monit. 2019 Aug 4 ;25:5795-5800. Epub 2019 Aug 4. PMID: 31377749

Abstract Title: 

Quercetin Exerted Protective Effects in a Rat Model of Sepsis via Inhibition of Reactive Oxygen Species (ROS) and Downregulation of High Mobility Group Box 1 (HMGB1) Protein Expression.

Abstract: 

BACKGROUND Sepsis is a severe medical condition. Approximately 0.75 million people are diagnosed with sepsis in the USA annually. Several of anti-inflammatory drugs are used to manage sepsis, but with a very low success rate. This study examined the possible protective effects of a naturally occurring flavanone, quercetin, in a rat model of sepsis. MATERIAL AND METHODS The study was carried out using Wistar albino rats. Sepsis was induced by cecal ligation and puncture methods. Histological analysis was performed by hematoxylin and eosin (HE) staining. Reactive oxygen species (ROS) levels were determined by flow cytometery. Superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX) activities were determined by standard assays. Protein expression was determined by Western blot analysis. RESULTS The results showed that quercetin reduced the tissue edema, congestion, and hemorrhage, increased the alveolar volume, and helped to maintain the lung anatomy of septic rats. Admistration of quercetin at the dosage of 15 and 20 mg/kg to septic rats caused significant reduction in the ROS levels. The activities and the expression of SOD, CAT, and APX were significantly decreased upon administration of quercetin in the septic rats at the dosage of 15 and 20 mg/kg. The effects of quercetin were also examined on the expression of the High mobility group box 1 (HMGB1) protein in septic rats. The results showed that quercetin caused a significant decrease in HMGB1 protein levels. CONCLUSIONS The findings of this study suggest that quercetin has therapeutic potential in the treatment of sepsis.

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PMID: 

Can J Physiol Pharmacol. 2019 Jul 31:1-5. Epub 2019 Jul 31. PMID: 31365282

Abstract Title: 

Blueberry extract attenuates doxorubicin-induced damage in H9c2 cardiac cells.

Abstract: 

The objective of this study was to analyze the cardioprotective roles of 3 wild blueberry genotypes and one commercial blueberry genotype by measuring markers of oxidative stress and cell death in H9c2 cardiac cells exposed to doxorubicin. Ripe berries of the 3 wild blueberry genotypes were collected from a 10-year-old clearcut forest near Nipigon, Ontario, Canada (49°1'39″N, 87°52'21″W), whereas the commercial blueberries were purchased from a local grocery store. H9c2 cardiac cells were incubated with 15 μg gallic acid equivalent/mL blueberry extract for 4 h followed by 5 μM doxorubicin for 4 h, and oxidative stress and active caspase 3/7 were analyzed. The surface area as well as total phenolic content was significantly higher in all 3 wild blueberry genotypes compared with the commercial species. Increase in oxidative stress due to doxorubicin exposure was attenuated by pre-treatment with all 3 types of wild blueberries but not by commercial berries. Furthermore, increase in caspase 3/7 activity was also attenuated by all 3 wild genotypes as well. These data demonstrate that wild blueberry extracts can attenuate doxorubicin-induced damage to H9c2 cardiomyocytes through reduction in oxidative stress and apoptosis, whereas the commercial blueberry had little effect.

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PMID: 

J Cardiovasc Pharmacol. 2019 Jul ;74(1):30-37. PMID: 31274840

Abstract Title: 

Cinnamaldehyde Ameliorates High-Glucose-Induced Oxidative Stress and Cardiomyocyte Injury Through Transient Receptor Potential Ankyrin 1.

Abstract: 

Oxidative stress plays a critical role in diabetic cardiomyopathy. Transient receptor potential ankyrin subtype 1 (TRPA1) has antioxidative property. In this study, we tested whether activation of TRPA1 with cinnamaldehyde protects against high-glucose-induced cardiomyocyte injury. Cinnamaldehyde remarkably decreased high-glucose-induced mitochondrial superoxide overproduction, upregulation of nitrotyrosine, P22, and P47, and apoptosis in cultured H9C2 cardiomyocytes (P

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PMID: 

Exp Cell Res. 2019 Jul 12:111500. Epub 2019 Jul 12. PMID: 31306656

Abstract Title: 

Cinnamaldehyde enhances apoptotic effect of oxaliplatin and reverses epithelial-mesenchymal transition and stemnness in hypoxic colorectal cancer cells.

Abstract: 

Oxaliplatin has been widely applied in clinical tumor chemotherapy, the treatment failure of which mainly blames on low susceptibility resulted from intrinsic or acquired drug resistance in tumor cells. Microenvironmental hypoxia is one of the important pathological features of solid tumors, which is closely related to the radiochemotherapy tolerance and poor prognosis. Cinnamaldehyde is extracted from Cinnamomum cassia with inhibiting effect against kinds of tumors. In this study, we demonstrated that hypoxia reduced the sensitivity to oxaliplatin in colorectal cancer (CRC) cells via inducing EMT and stemness. Nonetheless, cinnamaldehyde increased the curative effect of oxaliplatin by promoting apoptosis both in vitro and in vivo. Mechanistically, cinnamaldehyde and oxaliplatin synergistically reversed hypoxia-induced EMT and stemness of CRC cells and suppressed hypoxia-activated Wnt/β-catenin pathway synergistically. These consequences uncovered the potential therapeutic value of cinnamaldehyde and provided novel ideas on improving the sensitivity of oxaliplatin in CRC therapy.

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PMID: 

Environ Sci Pollut Res Int. 2019 Jan ;26(1):240-249. Epub 2018 Nov 3. PMID: 30392171

Abstract Title: 

Protective effect of cinnamon against acetaminophen-mediated cellular damage and apoptosis in renal tissue.

Abstract: 

Acetaminophen, APAP, is a common over-the-counter drug with antipyretic-analgesic action. When APAP is used in large doses, it causes hepatotoxicity and nephrotoxicity but safe at therapeutic doses. Cinnamon (Cinnamomum zeylanicum) is extensively used in folk medicine due to its high content of natural antioxidants. The current investigation was planned to study the possible ameliorative effect of cinnamon toward induced APAP-apoptosis and cellular damage in renal cells. Four groups (nine rats each) were used; negative control group administrated distilled water for 15 days; positive control APAP group administrated a single dose of APAP (1 g/kg) orally on the last day; APAP+Cin L (200 mg/kg) and APAP+Cin H (400 mg/kg) aqueous extract of cinnamon orally once a day for 15 days. An hour after the last dose of cinnamon, all rats in the third and fourth group were administrated a single dose of APAP (1 g/kg) orally. GC/MS analysis was performed to identify the plant used in the study. APAP markedly increased serum levels of creatinine, BUN, and glucose and decreased levels of albumin and total protein. In addition, APAP could also exert severe alterationin the kidney histopathology along with upregulation of caspase-3 and PCNA. However, pre-treatment with cinnamon ameliorated the APAP-induced cellular alterations and apoptosis, possibly through its high content of antioxidants.

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PMID: 

PLoS One. 2019 ;14(8):e0220720. Epub 2019 Aug 14. PMID: 31412065

Abstract Title: 

Cortical tau burden and behavioural dysfunctions in mice exposed to monosodium glutamate in early life.

Abstract: 

Although monosodium glutamate (MSG)-induced neurotoxicity has been recognized for decades, the potential similarities of the MSG model to Alzheimer's disease (AD)-type neuropathology have only recently been investigated. MSG-treated mice were examined behaviourally and histologically in relation to some features of AD. Four-week old mice received 5 subcutaneous MSG (2 g/kg) injections on alternate days, or saline. At age 10-12 weeks, they were given a battery of behavioural tests for species-typical behaviours and working memory. The mice were killed at 12 weeks and the brains excised. Accumulation of hyperphosphorylated tau protein was assessed in cortical and hippocampal neurons by immunohistochemistry, and in cerebral cortical homogenates. A 78% increase in cortical concentrations of phosphorylated tau protein was observed in the MSG mice. Intracellular hyperphosphorylated tau immunostaining was observed diffusely in the cortex and hippocampus, together with cortical atrophic neurons, extensive vacuolation and dysmorphic neuropil suggestive of spongiform neurodegeneration. Nest-building was significantly impaired, and spontaneous T-maze alternation was reduced, suggesting defective short-term working memory. Subcutaneous MSG treatment also induced a 56% reduction in exploratory head dips in a holeboard (P = 0.009), and a non-significant tendency for decreased burrowing behaviour (P = 0.085). These effects occurred in the absence of MSG-induced obesity or gross locomotor deficits. The findings point to subcutaneous MSG administration in early life as a cause of tau pathology and compromised species-typical behaviour in rodents. Determining whether MSG can be useful in modelling AD requires further studies of longer duration and full behavioural characterization.

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PMID: 

J Complement Integr Med. 2019 Aug 21. Epub 2019 Aug 21. PMID: 31433781

Abstract Title: 

The combined effect of vitamin C and omega-3 polyunsaturated fatty acids on fatigue following coronary artery bypass graft surgery: a triple-blind clinical trial.

Abstract: 

Background Fatigue is a common compliant among patients who undergo coronary artery bypass graft (CABG) surgery. This may affect patients' function in all aspects. A few studies have already assessed the influence of complementary therapies on minimizing fatigue. This study aimed to investigate the combined effect of vitamin C and omega-3 polyunsaturated fatty acids (n-3 PUFA) on fatigue following CABG surgery. Methods In this randomized, triple-blind placebo-controlled trial, 160 patients who already underwent CABG surgery were randomly assigned into an experimental or a control groups. Each group consisted of 80 patients. The experimental group was given both n-3 PUFA and vitamin C the day before surgery. They also received the same supplements in the first 5 days of operation. The control group received only placebo. Subjects in both groups responded to Multidimensional Fatigue Inventory (MFI-20) scale in the beginning, and at the end of the intervention as well as on the fifth day of the operation. Chi-square test and independent t-test were used for data analysis. Results The mean fatigue score in experimental and control groups came up to 62.01 ± 4.06 and 67.92 ± 4.95 (p

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PMID: 

Int J Reprod Biomed (Yazd). 2019 Apr ;17(4). Epub 2019 May 28. PMID: 31435603

Abstract Title: 

Effects of monosodium glutamate on apoptosis of germ cells in testicular tissue of adult rat: An experimental study.

Abstract: 

Background: Monosodium glutamate (MSG) is used as a flavoring and food seasoning. Some studies have reported the oxidative effects of using this substance on various tissues.Objective: This study has investigated the effects of MSG and the protective effect of vitamin C (vit C) on apoptosis of testicular germ cells and biochemical factors.Materials and Methods: In this experimental study, 24 adult male Wistar rats were randomly divided into four groups: control (received distilled water), vit C group (150 mg/kg), experimental group 1 (MSG 3 gr/kg), experimental group 2 (MSG 3 gr/kg + vit C 150 mg/kg). The rats were gavaged for 30 days, and then were sacrificed, the right testis was isolated for biochemical examinations for the glutathione, malondialdehyde, and left testis used in histological experiments. Tunnel staining was used to determine the number of apoptotic cells.Results: The results showed that apoptotic cells in the MSG group had a significant increase compared to the control group (P = 0.001), but the number of these cells in the MSG co-administered with vit C and vit C groups were significantly lower than the MSG group. Germinal epithelial thickness also decreased in MSG group compared to the control group.Conclusion: MSG can lead to increase apoptotic changes in the germinal epithelial of the testicle, and vit C as an antioxidant can modify the pathological and biochemical changes induced by MSG.

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