PMID: 

Asia Pac J Clin Nutr. 2019 ;28(4):783-792. PMID: 31826376

Abstract Title: 

Citrus fruit intake and the risk of nasopharyngeal carcinoma.

Abstract: 

BACKGROUND AND OBJECTIVES: Citrus fruit are suggested to be associated with reduced risk of nasopharyngeal carcinoma (NPC), but findings from epidemiologic studies have been inconsistent. We aimed to synthesize the association by conducting a meta-analysis of existing evidence.METHODS AND STUDY DESIGN: Databases including Medline, EMBASE, Web of science, and the Cochrane Library were searched for eligible studies up to March 2019 using a series comprehensive searching terms. The adjusted odds ratios (ORs) of citrus fruit intake with NPC risk from each study were extracted to calculate a pooled association estimate with its 95% confidence interval (CI).RESULTS: Nine studies totaling 3304 cases and 3850 controls were included in this analysis. Citrus fruit intake was significantly associated with reduced risk of NPC (OR: 0.72, 95% CI 0.58-0.91, p=0.005). In addition, this association tended to be stronger in Chinese (OR: 0.67, 95% CI 0.54-0.84, p

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PMID: 

Food Funct. 2019 Dec 18. Epub 2019 Dec 18. PMID: 31850465

Abstract Title: 

Potential roles of dietary flavonoids from Citrus aurantium L. var. amara Engl. in atherosclerosis development.

Abstract: 

Dietary consumption of flavonoids correlated positively with lower risk of cardiovascular disease. However, the precise roles of flavonoids from the blossoms of Citrus aurantium Linn variant amara Engl (CAVA) in atherosclerosis (AS) are still poorly understood. This study aimed to find novel flavonoid-type skeletons with protection against AS. Total flavonoids (CAVAF), homoeriodictyol (HE) and hesperetin-7-O-β-d-glucopyranoside (HG) were isolated from the blossoms of Citrus aurantium Linn variant amara Engl. by chromatography. Their suppressive effects on lipopolysaccharide (LPS)-induced inflammatory responses and ox-LDL-induced foam cell formation were systematically and comparatively investigated using macrophage RAW264.7 cells. HE was more powerful than HG in inhibiting LPS-induced production of nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β) and gene expression in RAW264.7 cells. HE and HG showed different responses to extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases (JNK), P38, P65, IκBα, IκKα/β phosphorylation, and nuclear factor-kappa B (NF-κB) nuclear translocation. HE and HG also differentially decreased oxidized low-density lipoprotein (ox-LDL)-induced foam cell formation by regulating peroxisome proliferator-activated receptor-gamma (PPARγ), phospholipid ATP-binding cassette transporter A1 (ABCA1), phospholipid ATP-binding cassette transporter G1 (ABCG1), scavenger receptor class B type I (SRB1), scavenger receptor class A type I (SRA1) and cluster of differentiation 36 (CD36) expression atgene and protein levels in RAW264.7 cells. HG showed weaker potential than HE in preventing AS development. Their chemical differences might partially explain the discrepancy in their bioactivity. In conclusion, HE and HG might be developed into novel therapeutic agents against inflammation and AS-associated diseases.

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PMID: 

J Agric Food Chem. 2019 Dec 18. Epub 2019 Dec 18. PMID: 31850758

Abstract Title: 

Protective Effect of Naringin on in vitro Gut-Vascular Barrier Disruption of Intestinal Microvascular Endothelial Cells Induced by TNF-α.

Abstract: 

Naringin is a polymethoxylated flavonoid commonly found in citrus species, and has the therapeutic potential in intestinal disorder. However, the effect and mechanism of naringin on gut-vascular barrier disruption has not yet been reported. This study aimed to investigate the distinguishingly and selectively protective effects of naringin on TNF-α-induced gut-vascular barrier disruption and elucidate the potential mechanism. In the present study, an in vitro gut-vascular barrier model composed of rat intestinal microvascular endothelial cells (RIMVECs) was conducted. Evans blue-albumin efflux assay showed that naringin (50 μM) evidently protected the intergrity of RIMVECs monolayer barriers against TNF-α-induced disruption. Naringin maintained the expression and distribution of tight junction proteins including zona occludin-1, occludin, claudin-1 and claudin-2. Additionally, naringin protected RIMVECs from TNF-α-induced apoptosisand cell migration suppression (41.1 ± 2.2% vs 51.1 ± 3.5%; 61.0 ± 5.1% vs 72.2 ± 6.2%). Our results indicate that naringin effectively ameliorates gut-vascular barrier disruption.

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PMID: 

Planta Med. 2019 Dec 11. Epub 2019 Dec 11. PMID: 31860116

Abstract Title: 

Protective Effects of Bergamot (Citrus bergamia Risso&Poiteau) Juice in Rats Fed with High-Fat Diet.

Abstract: 

The bergamot (Risso&Poiteau), a small tree cultivated along the Ionian coast of the Calabria region in Southern Italy, is an ancient plant used for the production of essential oil from fruit peel, but recently evaluated also for the high content of phenolics in the fruit pulp. Indeed, the juice is rich in glycosylated flavone and flavanones, showing a wide range of pharmacological activities. Noteworthy preclinical and clinical studies reported that bergamot juice is effective in reducing plasma lipids. The aim of this study was to evaluate the beneficial effects of ajuice using an experimental animal model of metabolic syndrome and cardiovascular risk. A significant reduction of both triglyceride levels and cardiovascular risk was observed in animals fed with a high-fat diet and bergamot juice. Daily oral treatment with bergamot juice significantly limits a high-fat-induced increase in body, visceral adipose tissue, liver, and heart weight. In addition,juice showed protective effects on hepatic steatosis, probably due to the reduction of oxidative stress and inflammation. Chemical constituents of administered bergamot juice, investigated by means of liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) analyses were represented by a wide range of flavonoids, with neohesperidin, neoeriocitrin, and naringin being the most abundant flavonoids according to previous studies. Furthermore, a considerable amount of brutieridin, a flavanone-glycoside having a 3-hydroxy-3-methyl-glutaryl residue, was observed.

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Despite a 100% vaccination rate, a Texas school closes early for winter break due to a whooping cough outbreak. Clearly the vaccine is failing to work as advertised. 

If ever there was convincing proof that vaccination does not equate to bona fide immunity, it is at St. Theresa Catcholic School in Texas… 

Reported by FoxNews.com on Dec. 19th, the school experienced an outbreak of whooping cough, causing them to close their doors and start their winter break early. 

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PMID: 

Antiviral Res. 2018 10 ;158:8-12. Epub 2018 Aug 1. PMID: 30076863

Abstract Title: 

Antiviral activity of silymarin against Mayaro virus and protective effect in virus-induced oxidative stress.

Abstract: 

Mayaro virus (MAYV) is a neglected arbovirus belonging to the family Togaviridae. Its infection leads to Mayaro fever, with clinical manifestations such as fever, myalgia, headache, rash, arthralgia, vomiting, and diarrhea. The most prominent complaint from infected person is the long-lasting arthritis/arthralgia. The treatment for Mayaro fever is mainly symptom-based and there are no vaccines or antiviral drugs currently available, thus, natural products with anti-MAYV activity may provide a potential alternative. Recent evidences suggest that oxidative stress plays an important role in MAYV infection and compounds capable of modulating oxidative stress could represent a novel therapeutic approach in modulating MAYV-associated oxidative cellular damage. Silymarin is a complex extracted of Silybum marianum, or milk thistle, and its major active compound is silybin, which has a remarkable biological effect. Its antioxidant and antiviral effects, including its antiviral activity against the Chikungunya virus (CHIKV), prompted us to think whether silymarin could also reduce the replication of the MAYV and restore the pro-oxidant/antioxidant balance in the context of MAYV infection, leading to reduced cellular oxidative stress. We assessed the antiviral activity and protective effect of silymarin against oxidative stress in MAYV-infected HepG2 cells. Cytopathic effect inhibition, viral replication, and plaque reduction assays were used to determine the anti-MAYV activity of silymarin. Additionally, we determined whether silymarin could reduce MAYV-induced oxidative cell damage. Briefly, silymarin exhibited potent antiviral activity against MAYV and reduced MAYV-induced ROS formation and levels of malondialdehyde (MDA) and carbonyl protein, which are biomarkers of oxidative stress. In conclusion, the ability of silymarin to inhibit MAYV replication and attenuate MAYV-induce oxidative stress warrants further investigation of this compound as a novel therapeutic approach to Mayaro fever disease.

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PMID: 

Biochem Biophys Rep. 2018 Jul ;14:20-25. Epub 2018 Mar 31. PMID: 29872730

Abstract Title: 

Inhibitory effect of silibinin on hepatitis B virus entry.

Abstract: 

Hepatitis B virus (HBV) infection is a worldwide health problem because of its potential to cause liver cirrhosis and hepatocellular carcinoma. Silibinin is a constituent of an extract of milk thistle, which is empirically used as a herbal medicine for the protection of liver, but its detailed effects on HBV are unknown. Because a previous study reported that silibinin hinders clathlin-mediated endocytosis (CME), we aimed to test whether silibinin inhibits the entry of HBV into hepatocytes. Using HepG2-NTCP-C4 cells, which overexpress sodium taurocholate cotransporting polypeptide (NTCP), it was shown that silibinin inhibited HBV infection dose-dependently. Similar effects were observed using human primary hepatocytes (PXB-cells). Additionally, a combination of silibinin and entecavir reduced HBV DNA in the culture supernatant more than either mono-treatment alone in HepG2-NTCP-C4 cells that had already been infected with HBV. Silibinin decreased transferrin uptake but did not affect the interaction between the HBV envelope and NTCP, suggesting that silibinin might inhibit HBV infection by hindering CME. In conclusion, this study showed that silibinin inhibits HBV entry in vitro.

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PMID: 

J Cell Physiol. 2019 Apr ;234(4):4327-4341. Epub 2018 Aug 25. PMID: 30144397

Abstract Title: 

Silibinin-induced endoplasmic reticulum stress and mitochondrial dysfunction suppress growth of endometriotic lesions.

Abstract: 

Silibinin is a flavonolignan extracted from milk thistle, which has been used for treating liver disorders, various cancers, and gynecological diseases. However, attempts for treating endometriosis with silibinin are lacking. In this study, we observed that silibinin exerts antiproliferative and apoptotic effects on human endometriotic cell lines VK2/E6E7 and End1/E6E7. We also identified that silibinin-induced oxidative stress and lipid peroxidation in human endometriotic cells. Moreover, we observed upregulation of calcium concentration in the cytosol and mitochondrial matrix, which resulted in mitochondrial dysfunction. Furthermore, induction of endoplasmic reticulum stress signals with rapid mitogen-activated protein kinase (MAPK) pathway signaling resulted in apoptosis of both cells. Using an animal model mimicking the retrograde menstruation hypothesis, we verified the effects of silibinin on reducing endometriotic lesions by inhibiting the expression of inflammatory cytokines in mice. Silibinin might be used as a novel therapeutic agent or supplement for inhibiting progression of endometriosis in vitro and in vivo.

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PMID: 

Biomed Res Int. 2018 ;2018:6056948. Epub 2018 Oct 2. PMID: 30370304

Abstract Title: 

Protective Effects of Silymarin and Silibinin against DNA Damage in Human Blood Cells.

Abstract: 

Silymarin (SM), a standardized extract derived from(L.) Gaertn, is primarily composed of flavonolignans, with silibinin (SB) as its major active constituent. The present study aimed to evaluate the antigenotoxic activities of SM and SB using the alkaline comet assay in whole blood cells and to assess their effects on the expression of genes associated with carcinogenesis and chemopreventive processes. Different concentrations of SM or SB (1.0, 2.5, 5.0, and 7.5 mg/ml) were used in combination with the DNA damage-inducing agent methyl methanesulfonate (MMS, 800M) to evaluate their genoprotective potential. To investigate the role of SM and SB in modulating gene expression, we performed quantitative real-time PCR (qRT-PCR) analysis of five genes that are known to be involved in DNA damage, carcinogenesis, and/or chemopreventive mechanisms. Treatment with SM or SB was found to significantly reduce the genotoxicity of MMS, upregulate the expression ofand, and downregulate the expression ofand. We observed no significant changes inexpression levels following treatment with SM or SB. In conclusion, both SM and SB exerted antigenotoxic activities and modulated the expression of genes related to cell protection against DNA damage.

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PMID: 

Life Sci. 2019 Jan 15 ;217:70-80. Epub 2018 Nov 16. PMID: 30452972

Abstract Title: 

Silibinin inhibits endometrial carcinoma via blocking pathways of STAT3 activation and SREBP1-mediated lipid accumulation.

Abstract: 

AIMS: To seek new conservative treatments for young women with early-stage endometrial carcinoma (EC) who desire to retain fertility, we investigated the effects and the underlying mechanism of silibinin in EC, which exhibits promising anti-cancer and tumour-suppressing properties in many malignant tumours.MAIN METHODS: Through relevant experiments such as MTT assay, cell colony formation assay and subcutaneous xenograft experiment, we showed that silibinin inhibited the proliferation of EC cells and tumours. Silibinin significantly induced cell cycle arrest and promoted apoptosis in vitro. In vivo TUNEL assay confirmed the apoptotic effect caused by silibinin. STAT3 is activated in the development of tumours. Silibinin notably inhibited the expression of STAT3 phosphorylation and regulated the expression of downstream genes involved in cell cycle and apoptosis at protein and mRNA levels in EC cells. Furthermore, silibinin decreased the expression of intranuclear SREBP1, which is a key regulator of lipid metabolism in the nucleus, and reduced the lipid accumulation in EC cells. Downregulation of the expression levels of SREBP1 and its downstream genes associated with lipid metabolism was also observed in silibinin-treated EC cells.KEY FINDINGS: The results revealed that a novel anticancer drug, silibinin, markedly suppressed cell proliferation, cell cycle progression, apoptosis inhibition and lipid accumulation by blocking STAT3 and SERBP1 signalling pathways in EC cells.SIGNIFICANCE: Silibinin has anti-tumour characteristics and inhibits abnormal lipid metabolism in EC. This compound is expected to contribute to the conservative and adjuvant treatment of EC and should therefore be investigated further.

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