PMID: 

Environ Sci Pollut Res Int. 2020 Feb 17. Epub 2020 Feb 17. PMID: 32064580

Abstract Title: 

Protective effects of quercetin against oxidative stress induced by bisphenol-A in rat cardiac mitochondria.

Abstract: 

Research has shown a relationship between the exposures to a chemical agent called bisphenol-A (BPA), which is extensively used in the production of polycarbonate plastics and the incidence of cardiovascular diseases. This association is most likely caused by the BPA's ability to disrupt multiple cardiac mechanisms, including mitochondrial functions. Therefore, this study aimed to explore the ability of quercetin (QUER) to limit the cardiotoxic effect of BPA in the rat's cardiac mitochondria. The experiment was carried out on 32 male Wistar rats, which were randomly assigned to four groups. The negative control group received olive oil; the positive control group received olive oil plus BPA (250 mg/kg); the third group received olive oil, BPA, and QUER (75 mg/kg); and the fourth group received olive oil and QUER, all orally for 14 days. The rats were slaughtered 24 h after the last treatment. The measured parameters included creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) asthe biomarkers of cardiotoxicity, triglyceride (TG), total cholesterol (TC), and low-density and high-density lipoprotein cholesterol (LDL-C and HDL-C) as the measures of dyslipidemia, glutathione (GSH) content, catalase activity (CAT), reactive oxygen species (ROS), lipid peroxidation (LPO), and the level of damage to the mitochondrial membranes as the indicators of the impact of QUER on the BPA cardiotoxic effect. Finally, the rats treated with QUER showed better results in terms of serum CK-MB, serum LDH, serum lipid profile, GSH level, CAT activity, mitochondrial membrane potential (ΔΨm), LPO, and ROS. According to the results, QUER could be used as a protective agent against BPA-induced mitochondrial toxicity.

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PMID: 

Int J Environ Res Public Health. 2020 Feb 13 ;17(4). Epub 2020 Feb 13. PMID: 32069886

Abstract Title: 

Association of Urinary Levels of Bisphenols A, F, and S with Endometriosis Risk: Preliminary Results of the EndEA Study.

Abstract: 

The aim of this study was to explore associations of urinary concentrations of bisphenols A (BPA), S (BPS), and F (BPF) and of thiobarbituric acid reactive substances (TBARS) with the risk of endometriosis in women of childbearing age.: This case-control study enrolled 124 women between January 2018 and July 2019: 35 women with endometriosis (cases) and 89 women without endometriosis undergoing abdominal surgery for other reasons (controls). Endometriosis was diagnosed (cases) or ruled out (controls) by laparoscopic inspection of the pelvis and the biopsy of suspected lesions (histological diagnosis). Fasting urine samples were collected before surgery to determine concentrations of BPA, BPS, BPF, and TBARS. Associations of bisphenol and TBARS concentrations with endometriosis risk were explored with multivariate logistic and linear regression analyses.After adjustment for urinary creatinine, age, BMI, parity, and residence, endometriosis risk was increased with each 1 log unit of BPA [OR 1.5; 95%CI 1.0-2.3] andΣbisphenols [OR 1.5; 95%CI 0.9-2.3] but was not associated with the presence of BPS and BPF. Classification of the women by tertiles of exposure revealed statistically significant associations between endometriosis risk and the second tertile of exposure to BPA [OR 3.7; 95%CI 1.3-10.3] and Σbisphenols [OR 5.4; 95%CI 1.9-15.6]. In addition, TBARS concentrations showed a close-to-significant relationship with increased endometriosis risk [OR 1.6; 95%CI 1.0-2.8], and classification by TBARS concentration tertile revealed that the association between endometriosis risk and concentrations of BPA[OR 2.0; 95%CI 1.0-4.1] and Σbisphenols [OR 2.2; 95%CI 1.0-4.6] was only statistically significant for women in the highest TBARS tertile (>4.23μM).: Exposure to bisphenols may increase the risk of endometriosis, and oxidative stress may play a crucial role in this association. Further studies are warranted to verify these findings.

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PMID: 

Proc Natl Acad Sci U S A. 2020 Feb 18. Epub 2020 Feb 18. PMID: 32071231

Abstract Title: 

Bisphenol A and bisphenol S disruptions of the mouse placenta and potential effects on the placenta-brain axis.

Abstract: 

Placental trophoblast cells are potentially at risk from circulating endocrine-disrupting chemicals, such as bisphenol A (BPA). To understand how BPA and the reputedly more inert bisphenol S (BPS) affect the placenta, C57BL6J mouse dams were fed 200μg/kg body weight BPA or BPS daily for 2 wk and then bred. They continued to receive these chemicals until embryonic day 12.5, whereupon placental samples were collected and compared with unexposed controls. BPA and BPS altered the expression of an identical set of 13 genes. Both exposures led to adecrease in the area occupied by spongiotrophoblast relative to trophoblast giant cells (GCs) within the junctional zone, markedly reduced placental serotonin (5-HT) concentrations, and lowered 5-HT GC immunoreactivity. Concentrations of dopamine and 5-hydroxyindoleacetic acid, the main metaboliteof serotonin, were increased. GC dopamine immunoreactivity was increased in BPA- and BPS-exposed placentas. A strong positive correlation between 5-HTGCs and reductions in spongiotrophoblast to GC area suggests that this neurotransmitter is essential for maintaining cells within the junctional zone. In contrast, a negative correlation existed between dopamineGCs and reductions in spongiotrophoblast to GC area ratio. These outcomes lead to the following conclusions. First, BPS exposure causes almost identical placental effects as BPA. Second, a major target of BPA/BPS is either spongiotrophoblast or GCs within the junctional zone. Third, imbalances in neurotransmitter-positive GCs and an observed decrease in docosahexaenoic acid and estradiol, also occurring in response to BPA/BPS exposure, likely affect the placental-brain axis of the developing mouse fetus.

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PMID: 

Nutrients. 2020 Feb 20 ;12(2). Epub 2020 Feb 20. PMID: 32093297

Abstract Title: 

Possible Involvement of Vitamin C in Periodontal Disease-Diabetes Mellitus Association.

Abstract: 

Ascorbic acid (vitamin C) is an important water-soluble vitamin found in many fruits and vegetables. It has well-documented beneficial effects on the human body and is used as a supplement, alone or in combination with other vitamins and minerals. Over recent years, research has focused on possible new therapeutic actions in chronic conditions including periodontal disease (PD). We conducted a systematic review on clinical trials from four databases (PubMed, Clinical Trials, Cochrane, Web of Science) which measured plasmatic/salivary levels of ascorbic acid in PD-diabetes mellitus (DM) association. Six studies were included in our review, three of them analyzing patients with different grades of PD and DM who received vitamin C as a treatment (500 mg vitamin C/day for 2 months and 450 mg/day for 2 weeks) or as part of their alimentation (guava fruits), in combination with standard therapies and procedures. Decreased levels of vitamin C were observed in PD patients with DM but data about efficacy of vitamin C administration are inconclusive. Given the important bidirectional relationship between PD and DM, there is a strong need for more research to assess the positive effects of ascorbic acid supplementation in individuals suffering from both diseases and also its proper regimen for these patients.

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PMID: 

Oncol Lett. 2019 Mar ;17(3):3503-3510. Epub 2019 Jan 18. PMID: 30867790

Abstract Title: 

Hydroxyl safflower yellow A regulates the tumor immune microenvironment to produce an anticancer effect in a mouse model of hepatocellular carcinoma.

Abstract: 

Hepatocellular carcinoma (HCC) is a serious threat to human health. Chemotherapy drugs such as cisplatin are widely used in cancer treatment, but can cause severe side effects. Hydroxyl safflower yellow A (HSYA) is a water-soluble chalcone glycoside substance extracted from safflowers (Carthamus tinctorius L.) that has been reported to inhibit tumor growth with few side effects. The tumor immune microenvironment is crucial for the proliferation and invasiveness of tumor cells, and it is mediated by forkhead box P3-positive (FOXP3+) regulatory T cells (Tregs) and retinoic acid receptor-related orphan receptor-γ (RORγ)-expressing Th17 cells. FOXP3+ Tregs inhibit immunoreaction and FOXP3 is a key indicator of Tregs. RORγ isoform 2, also known as RORγt, is an important transcription factor in Th17 cells that may promote cancer progression. In the present study, the antitumor effect of HSYA on HCC was investigated, as well as its impact on the tumor immune microenvironment. Following the establishment of a mouse model for HCC, hematoxylin and eosin staining were performed to observe histological changes in liver tumors, and the spleen and thymus were weighed to calculate the spleen and thymus indexes. The proportion of FOXP3+ Tregs in the spleen was determined by flow cytometry, and expression levels of Foxp3 and Rorγt were examined by reverse transcription-quantitative polymerase chain reaction and western blot analysis. The results of the present study showed that cisplatin inhibited tumorgrowth, caused weight loss and reduced the immunoreactivity of the mice. HSYA inhibited tumor growth without causing significant weight loss. The proportion of FOXP3-expressing Tregs in the spleen and the expression of Foxp3 and Rorγt mRNA decreased following treatment with certain doses of HSYA.In conclusion, HSYA inhibited tumor growth without detrimental effects on the weight of the mice, indicating that HSYA may be suitable as a novel therapy for HCC patients.

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PMID: 

Pak J Biol Sci. 2019 Jan ;22(8):383-392. PMID: 31930826

Abstract Title: 

In vitroAnticancer Activity of Quinoa and Safflower Seeds and Their Preventive Effects on Non-alcoholic Fatty Liver.

Abstract: 

BACKGROUND AND OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is not only the most common cause of liver diseases in humans but also it may complicate and become a risk factor for liver cancer. The present work aimed to evaluate the anticancer activity (in vitro) of quinoa and safflower seeds powder and their beneficial effects against NAFLD (in vivo).MATERIALS AND METHODS: Proximate analysis, fatty acids profile, total phenolic and phytic acid of quinoa and safflower seeds were assessed. Also their anticancer activities (in vitro) against liver cancer were evaluated. The preventive effect of both seeds on NAFLD was evaluated using twenty four male rats. NAFLD was induced in rats by high fructose diet (HFD) for 4 weeks. The effects of HFD and HFD supplemented with 20% quinoa or safflower powder on plasma and liver lipids, lipid peroxidation, total protein, albumin as well as liver and kidney functions were determined.RESULTS: Quinoa seeds powder was promising in cytotoxicity against hepatocarcinoma cell line HEPG2 (IC50 was 14.6μg). Feeding rats on HFD produced dyslipidemia and significant increase in liver functions and lipid peroxidation with significant elevation in liver triglycerides and total cholesterol. Quinoa and safflower seeds powder produced improvement in the biochemical parameters with different degrees.CONCLUSION: Quinoa and safflower seeds powder possessed cytotoxicity against hepatocarcinoma cell line HEPG2 and afford hepato-protection against NAFLD.

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PMID: 

Neurochem Res. 2020 Feb 21. Epub 2020 Feb 21. PMID: 32080784

Abstract Title: 

Synergic Effects of Berberine and Curcumin on Improving Cognitive Function in an Alzheimer's Disease Mouse Model.

Abstract: 

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, and no effective therapies have been found to prevent or cure AD to date. Berberine and curcumin are extracts from traditional Chinese herbs that have a long history of clinical benefits for AD. Here, using a transgenic AD mouse model, we found that the combined berberine and curcumin treatment had a much better effect on improving the cognitive function of mice than the single-drug treatment, suggesting synergic effects of the combined berberine and curcumin treatment. In addition, we found that the combined berberine and curcumin treatment had significant synergic effects on reducing soluble amyloid-β-peptideproduction. Furthermore, the combination treatment also had remarkable synergic effects on decreasing inflammatory responses and oxidative stress in both the cortex and hippocampus of AD mice. We also found that the combination treatment performed much better than the single drugs in reducing the APP and BACE1 levels and increasing AMPKα phosphorylation and cell autophagy, which might be the underlying mechanism of the synergic effects. Taken together, the result of this study reveal the synergic effects and potential underlying mechanisms of the combined berberine and curcumin treatment in improving the symptoms of AD in mice. This study sheds light on a new strategy for exploring new phytotherapies for AD and also emphasizes that more research should focus on the synergic effects of herbal drugs in the future.

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PMID: 

Life Sci. 2020 Feb 22:117456. Epub 2020 Feb 22. PMID: 32097666

Abstract Title: 

Mechanism of berberine in treating Helicobacter pylori induced chronic atrophic gastritis through IRF8-IFN-γ signaling axis suppressing.

Abstract: 

AIMS: In this study, we will investigate the therapeutic effects of berberine (BBR) in Helicobacter pylori (H. pylori) induced chronic atrophic gastritis (CAG). Furthermore, potential mechanisms of BBR in regulating IRF8-IFN-γ signaling axis will also be investigated.MATERIALS AND METHODS: H. pylori were utilized to establish CAG model of rats. Therapeutic effects of BBR on serum supernatant indices, and histopathology of stomach were analyzed in vivo. Moreover, GES-1 cells were infected by H. pylori, and intervened with BBR in vitro. Cell viability, morphology, proliferation, and quantitative analysis were detected by high-content screening (HCS) imaging assay. To further investigate the potential mechanisms of BBR, relative mRNA, immunohistochemistry and protein expression in IRF8-IFN-γ signaling axis were measured.KEY FINDINGS: Results showed serum supernatant indices including IL-17, CXCL1, and CXCL9 were downregulated by BBR intervention, while, G-17 increased significantly. Histological injuries of gastric mucosa induced by H. pylori also were alleviated. Moreover, cell viability and morphology changes of GES-1 cells were improved by BBR intervention. In addition, proinflammatory genes and IRF8-IFN-γ signaling axis related genes, including Ifit3, Upp1, USP18, Nlrc5, were suppressed by BBR administration in vitro and in vivo. The proteins expression related to IRF8-IFN-γ signaling axis, including Ifit3, IRF1 and Ifit1 were downregulated by BBR intervention.

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PMID: 

Cancer Manag Res. 2020 ;12:695-702. Epub 2020 Jan 30. PMID: 32099466

Abstract Title: 

The Anti-Cancer Mechanisms of Berberine: A Review.

Abstract: 

Berberine (BBR) has been extensively studied in vivo and vitro experiments. BBR inhibits cell proliferation by regulating cell cycle and cell autophagy, and promoting cell apoptosis. BBR also inhibits cell invasion and metastasis by suppressing EMT and down-regulating the expression of metastasis-related proteins and signaling pathways. In addition, BBR inhibits cell proliferation by interacting with microRNAs and suppressing telomerase activity. BBR exerts its anti-inflammation and antioxidant properties, and also regulates tumor microenvironment. This review emphasized that BBR as a potential anti-inflammation and antioxidant agent, also as an effective immunomodulator, is expected to be widely used in clinic for cancer therapy.

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PMID: 

Clin Cancer Res. 2020 Feb 25. Epub 2020 Feb 25. PMID: 32098768

Abstract Title: 

Discovery of berberine that targetedly induce autophagic degradation of both BCR-ABL and BCR-ABL T315I through recruiting LRSAM1 for overcoming imatinib-resistance.

Abstract: 

PURPOSE: Imatinib, the breakpoint cluster region protein (BCR)/Abelson murine leukemia viral oncogene homolog (ABL) inhibitor, is widely used to treat chronic myeloid leukemia (CML). However, imatinib resistance develops in many patients. Therefore, new drugs with improved therapeutic effects are urgently needed. Berberine (BBR) is a potent BCR-ABL inhibitor for imatinib-sensitive and -resistant CML.EXPERIMENTAL DESIGN: Protein structure analysis and virtual screening were used to identify BBR targets in CML. Molecular docking analysis, surface plasmon resonance imaging (SPRi), nuclear magnetic resonance (NMR) assays, and thermoshift assays were performed to confirm the BBR target. The change in BCR-ABL protein expression after BBR treatment was assessed by western blotting. The effects of BBR were assessed in vitro in cell lines, in vivo in mice, and in human CML bone marrow cells as a potential strategy to overcome imatinib resistance.RESULTS: We discovered that BBR bound to the protein tyrosine kinase (PTK) domain of BCR-ABL. BBR inhibited the activity of BCR-ABL and BCR-ABL with the T315I mutation, and it also degraded these proteins via the autophagic lysosome pathway by recruiting E3 ubiquitin-protein ligase LRSAM1. BBR inhibited the cell viability and colony formation of CML cells and prolonged survival in CML mouse models with imatinib sensitivity and resistance.CONCLUSIONS: The results show that BBR directly binds to and degrades BCR-ABL and BCR-ABL T315I via the autophagic lysosome pathway by recruiting LRSAM1. The use of BBR is a new strategy to improve the treatment of CML patients with imatinib sensitivity or resistance.

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