PMID: 

Aging (Albany NY). 2020 Feb 13 ;12. Epub 2020 Feb 13. PMID: 32062612

Abstract Title: 

Berberine promotes XIAP-mediated cells apoptosis by upregulation of miR-24-3p in acute lymphoblastic leukemia.

Abstract: 

BACKGROUND: Berberine (BBR) has gained considerable attention because of its anti-tumor activity. BBR can induce apoptosis of acute lymphoblastic leukemia (ALL) cells through the MDM2/p53 pathway. However, the effects of BBR on those ALL patients with p53 deficiency remain unclear.RESULTS: We found that BBR reduced ALL cell viability and induced apoptosis in p53-null EU-4 and p53-mutant EU-6 cells by downregulating X-linked inhibitor of apoptosis protein (XIAP), which is increased in ALL tissues and cells. BBR-induced cell apoptosis was attenuated by inhibition of XIAP that was controlled by PIM-2. Mechanistic studies showed that BBR treatment induced an enhancement of miR-24-3p. PIM-2 is a direct target of miR-24-3p. Blockade of PIM-2 or miR-24-3p reversed BBR-induced cell apoptosis.studies, BBR remarkably alleviated leukemia conditions in a EU4 xenograft mouse model, whereas inhibition of miR-24-3p significantly reversed the effects of BBR in the leukemia condition.CONCLUSIONS: miR-24-3p/PIM-2/XIAP signaling contributes to BBR-mediated leukemia mitigation in p53-defect ALL, which should be further developed as a treatment strategy in ALL patients with p53 deficiency.METHODS: Cell viability and apoptosis were determined using CCK-8 and TUNEL assays, respectively. The dual-luciferase reporter gene system was used to determine the interaction between miR-24-3p and 3'-untranslated regions (UTRs) of PIM-2.

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PMID: 

Front Pharmacol. 2019 ;10:1658. Epub 2020 Jan 29. PMID: 32063859

Abstract Title: 

Berberine Maintains the Neutrophil N1 Phenotype to Reverse Cancer Cell Resistance to Doxorubicin.

Abstract: 

This study explores the contributions of neutrophils to chemotherapeutic resistance and berberine-regulated cancer cell sensitivity to doxorubicin (DOX).experiments, continuous DOX treatment led to the shift of HL-60 cells to N2 neutrophils and thus induced chemotherapeutic resistance. The combination treatment with DOX and 2µM berberine resulted in the differentiation of HL-60 cells toward N1 and therefore stimulated HL-60 cell immune clearance. Berberine increased reactive oxygen species (ROS) and decreased autophagy and therefore induced apoptosis in HL-60-N2 cells with morphological changes, but had no effect on cell viability in HL-60-N1 cells. The neutrophil-regulating efficacy of berberine was confirmed in the urethane-induced lung carcinogenic model and H22 liver cancer allograft model. Furthermore, we found that DOX-derived neutrophils had high levels of CD133 and CD309 surface expression, which prevented both chemotherapeutic sensitivity and immune rejection by self-expression of PD-L1 and surface expression of PD-1 receptor on T cells, whereas berberine could downregulate CD133 and CD309 surface expression. Finally, berberine-relevant targets and pathways were evaluated. This study first suggestsan important role of berberine in regulating neutrophil phenotypes to maintain cancer cell sensitivity to DOX.

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PMID: 

Eur J Pharm Biopharm. 2020 Feb 14. Epub 2020 Feb 14. PMID: 32068029

Abstract Title: 

Berberine encapsulated PEG-coated liposomes attenuate Wnt1/β-catenin signaling in rheumatoid arthritis via miR-23a activation.

Abstract: 

Bone erosion is a debilitating pathological process of osteopathic disorder like rheumatoid arthritis (RA). Current treatment strategies render low disease activity but with disease recurrence. To find an alternative, we designed this study with an aim to explore the underlying therapeutic effect of PEGylated liposomal BBR (PEG-BBR) against Wnt1/β-catenin mediated bone erosion in adjuvant-induced arthritic (AA) rat model and fibroblast-like synoviocytes (FLS) with reference to microRNA-23a (miR-23a) activity. Our initial studies using confocal microscopy and Near-Infrared Imaging (NIR) showed successful internalization of PEG-BBR and PEG-miR-23a in vitro and in vivo respectively and was retained till 48 h. The preferential internalization of PEG-BBR into the inflamed joint region significantly reduced the gene and protein level expression of major Wnt1 signaling mediators and reduced bone erosion in rats. Moreover, PEG-BBR treatmentin FLS cells attenuated the gene and protein expression levels of FZD4, LRP5, β-catenin, and Dvl-1 through the induction of CYLD. Furthermore, inhibition of these factors resulted in reduced bone loss and increased calcium retainability by altering the RANKL/OPG axis. PEG-BBR treatment markedly inhibited the expression of LRP5 protein on par with the DKK-1 (LRP5 inhibitor/Wnt signaling inhibitor) and suppressed the transcriptional activation of β-catenin inside the cells. We further witnessed that miR-23a altered the expression levels of LRP5 through RNA interference. Overall, our findings endorsed that miR-23a possesses a multifaceted therapeutic efficiency like berberine in RA pathogenesis and can be considered as a potential candidate for the therapeutic targeting of Wnt1/β-catenin in RA disease condition.

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PMID: 

Vascul Pharmacol. 2020 Feb 15:106660. Epub 2020 Feb 15. PMID: 32070767

Abstract Title: 

Berberine protects Kawasaki disease-induced human coronary artery endothelial cells dysfunction by inhibiting of oxidative and endoplasmic reticulum stress.

Abstract: 

Kawasaki disease (KD) is an acute febrile illness characterized by systemic vasculitis especially in coronary arteries. Berberine (BBR) shows several beneficial effects on cardiovascular system. The present study is to investigate whether BBR exerts protective effect against KD-induced damage of human coronary artery endothelial cell (HCAECs) and the underlying mechanisms. HCAECs exposed to medium with 15% serum from KD patients or healthy volunteers for 24 h. Stimulated HCAECs were treated with vehicle (without BBR) and BBR (20 μM) for 24 h, the cell apoptosis, cell cycle, induction of intracellular reactive oxygen species (ROS) and protein expression were examined by flow cytometry and western blot. The KD-induced differentially expressed proteins in HCAECs were determined by quantitative proteomics. BBR inhibited HCAECs from apoptosis and arrested cell cycle at G0/G1 stage. BBR protected HCAECs from injury by inhibiting expression of THBD, vWF and EDN1. Bioinformatics analysis suggested that the oxidative and ER stress were involved inKD-induced damage in HCAECs. ROS production and the protein expression of ATF4, p-EIF2α, p-PERK, XBP1, p-IRE1, HSP90B1, HSPG2, DNAJC3, P4HB and VCP were increased by serum from KD patients and decreased by BBR treatment. BBR exerts its protective effects on KD-induced damage of HCAECs through itsinhibitory effects on oxidative and ER stress indicating BBR as a therapeutic candidate for KD.

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PMID: 

Arch Physiol Biochem. 2020 Feb 19:1-12. Epub 2020 Feb 19. PMID: 32072839

Abstract Title: 

Berberine alleviates monosodium glutamate induced postnatal metabolic disorders associated vascular endothelial dysfunction in newborn rats: possible role of matrix metalloproteinase-1.

Abstract: 

Excessive food additives Monosodium glutamate (MSG) results in metabolic disorders with increased Cardiovascular diseases CVD. We aimed to emphasise berberine (BBR) effect on MSG induced metabolic syndrome (MetS) and its associated endothelial dysfunction. Newborn rats were divided into control group, MSG group (4mg/g) each other day for the first 14days of life and MSG + BBR group that was given MSG then BBR in dose 150mg/kg/day for 6weeks. Body weight, food intake, systolic blood pressure, biochemical metabolic and oxidative stress markers were evaluated. Aortic tissue homogenate Endothelin -1 (ET-1) and matrix metalloproteinase -1 (MMP-1) assessment, in addition to histological and EM examination were done. Newborn rats MSG exposure results in typical adult life MetS and oxidative stress with significant increase in ET-1 and MMP-1with aortic vasculopathy. BBR significantly improved all the disturbed parameters; suppress increased body weight (BW), food intake (FI) and partly improved the aortic vasculopathy lesions, holding a promise for BBR as a defending agent against MSG metabolic and vascular disorders.HIGH LIGHT MSGMSG is frequently consumed as a flavour enhancer especially between children and adolescentExcessive utilisation MSG is associated MS with vascular endothelial dysfunctionMMP-1 may be involved in atherosclerotic plaque formationBBR has beneficial outcome for metabolic disorders induced by MSG among newly born ratsBBR has a role in management vascular inflammation and remodelling.

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PMID: 

Eur J Nutr. 2020 Feb 11. Epub 2020 Feb 11. PMID: 32048004

Abstract Title: 

Whole mung bean (Vigna radiata L.) supplementation prevents high-fat diet-induced obesity and disorders in a lipid profile and modulates gut microbiota in mice.

Abstract: 

PURPOSE: Obesity, a strong risk factor for metabolic disorder, has become a major impediment for public health globally. The objective of this study was to assess the anti-obesity effect of mung bean, and the relationship between the gut microbiota modulatory effects of mung bean and the prevention of obesity.METHODS: Thirty-two four-week-old male C57BL/6 J mice were divided into four groups: normal chow diet (NCD), high-fat diet (HFD), a high-fat diet supplemented with 30% whole mung bean flour (HFD-WMB), and a high-fat diet supplemented with 30% decorticated mung bean flour (HFD-DMB). The ability of a mung bean-based diet to combat obesity-related metabolic disorder was determined by assessing the changes in physiological, histological, biochemical parameters, and gut microbiota composition of mice with HFD-induced obesity at 12 weeks.RESULTS: Both of WMB and DMB supplementation can effectively alleviate HFD-induced lipid metabolic disorders, which was accompanied by a reduction in hepatic steatosis. However, the only supplementation with WMB significantly reduced HFD-induced body weight gain, fat accumulation, and adipocyte size, and ameliorated the glucose tolerance and insulin resistance by sensitizing insulin action. Furthermore, high-throughput pyrosequencing of 16S rRNA revealed that WMB and DMB supplementation could normalize HFD-induced gut microbiota dysbiosis. Especially, WMB and DMB supplementation significantly promoted the relative abundance of Akkermansia and Bifidobacterium, respectively, and both of them significantly restored the relative abundance of several HFD-dependent taxa back to normal status in this study. Spearman's correlation analysis revealed that those genera are closely correlated with obesity-related indices.CONCLUSIONS: Although WMB showed better beneficial effects on HFD-induced obesity in comparison with DMB, DMB still retained some health benefits. Moreover, the alleviation of HFD-induced changes by mung bean supplementation was, at least, partially conciliated by structural modulation of gut microbiota.

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PMID: 

J Invest Dermatol. 2020 Feb 5. Epub 2020 Feb 5. PMID: 32057839

Abstract Title: 

Short-term exposure to a Western diet induces psoriasiform dermatitis by promoting accumulation of IL-17A-producingγδ T cells.

Abstract: 

A Western diet (WD)-characterized by its high fat and simple sugar content-is thought to predispose individuals to inflammatory skin diseases such as psoriasis, through the development of obesity. This scenario, however, is being challenged by emerging data suggesting that dietary components, rather than obesity itself, may exacerbate psoriasis. We herein show that short-term feeding with a diet analogous to the WD in mice leads to Th1/Th17-biased skin inflammation before significant body weight gain. Feeding for as little as 4 weeks with WD promoted mild dermatitis and accumulation of IL-17A-producingγδ T cells in the skin. Strikingly, γδ T cells from WD-fed mice exhibited enriched IL-23 receptor expression and increased potential to produce IL-17A after IL-23 stimulation. In contrast to wild-type mice, WD-fed TCRδ-deficient and CCR6-deficient mice had reduced skin inflammation and IL-17A expression. Supplementation with a bile acid sequestrant, cholestyramine, prevented WD-induced skin inflammation along with a reduction in the infiltration of γδ T cells and the expression of proinflammatory mediators. In summary, our data revealed dietary influences in inflammatory signaling in the skin. The dysregulation of IL-23 pathways and BA pathways may be key to the development of WD-associated psoriasiform dermatitis.

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PMID: 

Pak J Pharm Sci. 2019 Nov ;32(6(Supplementary)):2859-2864. PMID: 32024625

Abstract Title: 

Depression and dementia from hyponatremia in brain cancer patients exposed to frozen food chemicals.

Abstract: 

Frozen food chemicals contain neurotoxins which disturb electrolyte levels. Altered electrolyte levels can induce mental illnesses. This study was focused on finding the prevalence of depression, dementia, intake of antidepressants and electrolytic alterations in brain cancer (BC) patients and in control group (CG) who were taking frozen and canned food. The levels of electrolytes were compared in both groups through Mann-Whitney U test. The Odds Ratio (OR) and Relative Risks (RR) were calculated of having a specific occurrence or condition of brain cancer patients vs. controls. Majority (41.42%) patients were from the age group 33-57 years. There were 52% male and 47% female patients. There was more occurrence of dementia (41%) and depression (6%) in patients as compared to CG. 94% patients were found with dementia. 32% patients were having low levels of sodium and 43% were having low levels of potassium. High levels of potassium (26%) were found in CG. 76% patients and 73% controls were taking canned food in moderation. 69% patients and 50% controls were taking frozen food in moderation. The potassium levels (p value: 0.00001) and sodium levels (p value: 0.01468) were found at significant difference in brain cancer patients and control group. Statistically significantly higher odds of outcome (OR>1) and increased relative risks (RR) were reported in dementia, depression and intake of anti-depressants for BC vs. CG. This epidemiological study reports hyponatremia as a significantly different parameter between brain cancer patients and controls. Food's chemicals induce hyponatremia, which can disturb mental states to develop different neurological conditions.

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PMID: 

Sci Rep. 2017 06 13 ;7(1):3398. Epub 2017 Jun 13. PMID: 28611391

Abstract Title: 

Isothiocyanates are detected in human synovial fluid following broccoli consumption and can affect the tissues of the knee joint.

Abstract: 

Osteoarthritis is a major cause of disability and there is no current pharmaceutical treatment which can prevent the disease or slow its progression. Dietary advice or supplementation is clearly an attractive option since it has low toxicity and ease of implementation on a population level. We have previously demonstrated that sulforaphane, a dietary isothiocyanate derived from its glucosinolate precursor which is found in broccoli, can prevent cartilage destruction in cells, in in vitro and in vivo models of osteoarthritis. As the next phase of this research, we enrolled 40 patients with knee osteoarthritis undergoing total knee replacement into a proof-of-principle trial. Patients were randomised to either a low or high glucosinolate diet for 14 days prior to surgery. We detected ITCs in the synovial fluid of the high glucosinolate group, but not the low glucosinolate group. This was mirrored by an increase in ITCs and specifically sulforaphane in the plasma. Proteomic analysis of synovial fluid showed significantly distinct profiles between groups with 125 differentially expressed proteins. The functional consequence of this diet will now be tested in a clinical trial.

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PMID: 

J Nutr Biochem. 2019 01 ;63:27-34. Epub 2018 Sep 21. PMID: 30317146

Abstract Title: 

Broccoli consumption affects the human gastrointestinal microbiota.

Abstract: 

The human gastrointestinal microbiota is increasingly linked to health outcomes; however, our understanding of how specific foods alter the microbiota is limited. Cruciferous vegetables such as broccoli are a good source of dietary fiber and phytonutrients, including glucosinolates, which can be metabolized by gastrointestinal microbes. This study aimed to determine the impact of broccoli consumption on the gastrointestinal microbiota of healthy adults. A controlled feeding, randomized, crossover study consisting of two 18-day treatment periods separated by a 24-day washout was conducted in healthy adults (n=18). Participants were fed at weight maintenance with the intervention period diet including 200 g of cooked broccoli and 20 g of raw daikon radish per day. Fecal samples were collected at baseline and at the end of each treatment period for microbial analysis. Beta diversity analysis indicated that bacterial communities were impacted by treatment (P=.03). Broccoli consumption decreased the relative abundance of Firmicutes by 9% compared to control (P=.05), increased the relative abundance of Bacteroidetes by 10% compared to control (P=.03) and increased Bacteroides by 8% relative to control (P=.02). Furthermore, the effects were strongest among participants with body mass index

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