Probiotic BSH activity and anti-obesity potential of Lactobacillus plantarum strain TCI378 isolated from Korean Kimchi.
PMID: Prev Nutr Food Sci. 2019 Dec ;24(4):434-441. Epub 2019 Dec 31. PMID: 31915639 Abstract Title: Probiotic BSH Activity and Anti-Obesity Potential ofStrain TCI378 Isolated from Korean Kimchi. Abstract: (.) is a human probiotic beneficial for the prevention and improvement of disease, yet properties of differentstrains are diverse. To obtain astrain that possesses greater potential against gastrointestinal dysfunction, we isolatedTCI378 (TCI378) from naturally fermented Korean kimchi. TCI378 has shown potential as probiotic since it can survive at pH 3.0 and in the presence of 0.3% bile acid. The bile salt hydrolase activity of TCI378 was shown by formation of opaque granular white colonies on solid de Man Rogosa Sharpe (MRS) medium supplemented with taurodeoxycholic acid, and its cholesterol-lowering ability in MRS medium supplemented with cholesterol. The metabolites of TCI378 from liquid culture in MRS medium prevented emulsification of bile salts. Moreover, both the metabolites of TCI378 and the dead bacteria reduced oil droplet accumulation in 3T3-L1, as detected by Oil red O staining. The expressions of adipocyte-specific genesandwere suppressed by the metabolites of TCI378, indicating TCI378 may have anti-obesity effects in adipocytes. Thesedata show the potential of the prophylactic applications of TCI378 and its metabolites for reducing fat and lowering cholesterol.
Probiotic properties and neuroprotective effects of Lactobacillus buchneri KU200793 isolated from Korean fermented foods.
PMID: Int J Mol Sci. 2020 Feb 12 ;21(4). Epub 2020 Feb 12. PMID: 32059401 Abstract Title: Probiotic Properties and Neuroprotective Effects ofKU200793 Isolated from Korean Fermented Foods. Abstract: The purpose of this study was to evaluate the probiotic characteristics and neuroprotective effects of bacteria isolated from Korean fermented foods. Three bacterial strains (KU200060,KU200171, andKU200793) showed potential probiotic properties, such as high tolerance against artificial gastric juice and bile salts, sensitivity to antibiotics, nonproduction of carcinogenic enzymes, and high adhesion to intestinal cells. Heat-killedKU200060 andKU200793 showed higher antioxidant activity than heat-killedKU200171. The conditioned medium (CM) was used to evaluate the reaction between HT-29 cells and each heat-killed strain. All CMs protected SH-SY5Y cells from 1-methyl-4-phenylpyridinium (MPP)-induced toxicity. The expression of brain-derived neurotropic factor (BDNF) mRNA in HT-29 cells treated with CM containing heat-killedKU200793 was the highest. The CM significantly reduced the Bax/Bclratio and increased BDNF mRNA expression in SH-SY5Y cells treated with MPP. These results indicate thatKU200793 can be used as a prophylactic functional food, having probiotic potential and neuroprotective effects.
The effects of combinatorial genistein and sulforaphane in breast tumor inhibition: role in epigenetic regulation.
PMID: Int J Mol Sci. 2018 Jun 13 ;19(6). Epub 2018 Jun 13. PMID: 29899271 Abstract Title: The Effects of Combinatorial Genistein and Sulforaphane in Breast Tumor Inhibition: Role in Epigenetic Regulation. Abstract: Dietary compounds that possess the properties of altering epigenetic processes are gaining popularity as targets for cancer prevention studies. These compounds when administered at optimal concentrations and especially in combination can have enhanced effects in cancer prevention or therapy. It is important to study the interaction of two or more compounds in order to assess their role in enhancing prevention. Genistein (GEN), found in soy, has been extensively studied for its role as an epigenetic modifier especially as a DNA methyltransferase (DNMT) inhibitor and sulforaphane (SFN), found in cruciferous vegetables, is known as a histone deacetylase (HDAC) inhibitor. However, very little is known about the effects of these two compounds in conjunction in breast cancer prevention or therapy. In our current study, we determined that, at certain doses, the compounds have synergistic effects in decreasing cellular viability of breast cancer cell lines. Our results indicate that the combination of GEN and SFN is much more effective than their single doses in increasing the rate of apoptosis and lowering the colony forming potential of these cells. We determined that these compounds inhibit cell cycle progression to G2 phase in MDA-MB-231 and G1 phase in MCF-7 breast cancer cell lines. Additionally, we determined that the combination is effective as an HDAC and histone methyltransferase (HMT) inhibitor. Furthermore, we demonstrated that this combination downregulates the levels of HDAC2 and HDAC3 both at the mRNA and protein levels. We also found that these compounds have the potential to downregulate KLF4 levels, which plays an important role in stem cell formation. The combination of GEN and SFN is also effective in downregulating hTERT levels, which is known to be activated when KLF4 binds to its promoter region. Our hypothesis is further strengthened bystudies, where the combination is administered to transgenic mice in the form of genistein and SFN-enriched broccoli sprouts. We have demonstrated that the combination is more effective in preventing or treating mammary cancer via extending tumor latency and reducing tumor volumes/sizes than either of these dietary components administered alone. These results are consistent with ourstudy suggesting potential preventive and therapeutic effects of this novel dietary combinatorial approach against breast cancer.
PMID: Mol Nutr Food Res. 2018 09 ;62(18):e1800079. Epub 2018 Aug 29. PMID: 30079608 Abstract Title: Cruciferous Vegetables, Isothiocyanates, and Bladder Cancer Prevention. Abstract: Bladder cancer is a significant health burden due to its high prevalence, risk of mortality, morbidity, and high cost of medical care. Epidemiologic evidence suggests that diets rich in cruciferous vegetables, particularly broccoli, are associated with lower bladder cancer risk. Phytochemicals in cruciferous vegetables, such as glucosinolates, which are enzymatically hydrolyzed to bioactive isothiocyanates, are possible mediators of an anticancer effect. In vitro studies have shown inhibition of bladder cancer cell lines, cell cycle arrest, and induction of apoptosis by these isothiocyanates, in particular sulforaphane and erucin. Although not yet completely understood, many mechanisms of anticancer activity at the steps of cancer initiation, promotion, and progression have been attributed to these isothiocyanates. They target multiple pathways including the adaptive stress response, phase I/II enzyme modulation, pro-growth, pro-survival, pro-inflammatory signaling, angiogenesis, and even epigenetic modulation. Multiple in vivo studies have shown the bioavailability of isothiocyanates and their antitumoral effects. Although human studies are limited, they support oral bioavailability with reasonable plasma and urine concentrations achieved. Overall, both cell and animal studies support a potential role for isothiocyanates in bladder cancer prevention and treatment. Future studies are necessary to examine clinically relevant outcomes and define guidelines on ameliorating the bladder cancer burden.
Xanthohumol chalcone acts as a powerful inhibitor of carcinogenesis in drug-resistant human colon carcinoma.
PMID: J BUON. 2019 Nov-Dec;24(6):2442-2447. PMID: 31983118 Abstract Title: Xanthohumol chalcone acts as a powerful inhibitor of carcinogenesis in drug-resistant human colon carcinoma and these effects are mediated via G2/M phase cell cycle arrest, activation of apoptotic pathways Abstract: PURPOSE: Xanthohumol is a prenylated flavonoid of plant origin and has been reported to exhibit a spectrum of pharmacological properties including anticancer effects. However, the anticancer properties of Xanthohumol have not been thoroughly evaluated against drug-resistant colon cancer cells. This study was undertaken to evaluate the anticancer effects of Xanthohumol against the human colon cancer cell line HT-29 and normal CDD-18Co cell line.METHODS: HT-29 cell viability was evaluated by cell counting kit-8 (CCK8) assay. Apoptotic effects were examined by fluorescence microscopy using DAPI staining and flow cytometry using annexin V/propidium iodide (PI) staining. Effects on cell cycle were studied by flow cytometry while western blot analysis was done to study effects on protein expressions.RESULTS: The results showed that Xanthohumol causes a dramatic decrease in the HT-29 cell viability with an IC50 of 10µM. However, an IC50>100µM for Xanthohumol against the normal CDD-18Co cells suggested cancer cell specific activity. DAPI staining revealed nuclear fragmentation, suggesting xanthohumol induces apoptosis in HT-29 cells. Xanthohumol also caused activation of caspase-3 and 9 and increased the Bax/Bcl-2 ratio. Cell cycle analysis showed that this molecule caused arrest of the HT-29 cells at the G2/M phase of the cell cycle. The induction of G2/M cell cycle was also accompanied with depletion of the expression of cyclin B1. The effects of Xanthohumol were also investigated on the Ras/MEK/ERK signalling pathway which revealed that Xanthohumol also blocks the MEK/ERK signalling pathway in colon cancer cells in a concentration-dependent manner.CONCLUSIONS: Xanthohumol may prove an efficient lead molecule for the development of more potent anticancer agents through semi-synthetic approaches.
Prostate and breast cancer cells death induced by xanthohumol investigated with Fourier transform infrared spectroscopy.
PMID: Spectrochim Acta A Mol Biomol Spectrosc. 2020 Jan 25 ;231:118112. Epub 2020 Jan 25. PMID: 32014658 Abstract Title: Prostate and breast cancer cells death induced by xanthohumol investigated with Fourier transform infrared spectroscopy. Abstract: Fourier Transform Infrared spectroscopy was applied to detect in vitro cell death induced in prostate (PC-3) and breast (T47D) cancer cell lines treated with xanthohumol (XN). After incubation of the cancer cells with XN, specific spectral shifts in the infrared spectra arising from selected cellular components were identified that reflected biochemical changes characteristic for apoptosis and necrosis. Detailed analysis of specific absorbance intensity ratios revealed the compositional changes in the secondary structure of proteins and membrane lipids. In this study, for the first time we examined the changes in these molecular components and linked them to deduce the involvement of molecular mechanisms in the XN-induced death of the selected cancer cells. We showed that XN concentration-dependent changes were attributed to phospholipid ester carbonyl groups, especially in the case of T47D cells, suggesting that XN acts as an inhibitor of cell proliferation. Additionally, we observed distinct changes in the region assigned to the absorption of DNA, which were correlated with a specific marker of cell death and dependent on the XN dose and the type of cancer cells. The microscopic observation and flow cytometry analysis revealed that the decrease in cancer cell viability was mainly related to the induction of necrotic cell death. Moreover, the T47D cells were slightly more sensitive to XN than the PC-3 cells. Considering the results obtained, it can be assumed that apoptosis and necrosis induced by XN may contribute to the anti-proliferative and cytotoxic properties of this flavonoid against cancer cell lines PC-3 and T47D.
Combination of xanthohumol and phenethyl isothiocyanate inhibits NF-κB and activates Nrf2 in pancreatic cancer cells.
n/a PMID: Toxicol In Vitro. 2020 Feb 15:104799. Epub 2020 Feb 15. PMID: 32070777 Abstract Title: Combination of xanthohumol and phenethyl isothiocyanate inhibits NF-κB and activates Nrf2 in pancreatic cancer cells. Abstract: Phytochemicals such as phenethyl isothiocyanate (PEITC), indole-3-carbinol (I3C), xanthohumol (XAN), and resveratrol (RES) have been shown to target signaling pathways that are involved in the proliferation and survival of different pancreatic cancer (PC) cell lines. While the activity of these compounds alone was extensively studied, their combinations were never assessed. Thus, the aim of this study was to evaluate and compare the effect of PEITC, I3C, XAN, and RES and their combinations on the expression and activation of NF-κB and Nrf2 in human PC cell line PANC-1. The combination of XAN and PEITC was more efficient than the single compounds in reducing the binding of NF-κB p65 subunits by 47-60% and expression of p65 gene by 28-48%. The combination of XAN and PEITC also enhanced the activation and expression of Nrf2and subsequently the expression of GSTP, NQO1, and SOD genes which are controlled by this transcription factor. Modulation of the activity of NF-κB and Nrf2 by the combination of XAN and PEITC was found to lead to reduced proliferation of PANC-1 cells. These results suggest that the combination ofXAN and PEITC might be considered as a novel strategy for the prophylaxis and/or treatment of PC.
Sulforaphane normalizes intestinal flora and enhances gut barrier in mice with BBN-induced bladder cancer.
PMID: Mol Nutr Food Res. 2018 12 ;62(24):e1800427. Epub 2018 Nov 22. PMID: 30302904 Abstract Title: Sulforaphane Normalizes Intestinal Flora and Enhances Gut Barrier in Mice with BBN-Induced Bladder Cancer. Abstract: SCOPE: Gut microbiota imbalance, inflammation, and gut barrier deficiency play an important role in carcinogenesis. Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, has been proven to be highly effective in inhibiting cancer. The objective of this study is to investigate the potential roles of the gut microbiota in the inhibition of BBN-induced bladder cancer by SFN.METHODS AND RESULTS: N-butyl-N-(4-hydroxybutyl)-nitrosamine is used to induce bladder cancer in male C57BL/6 mice, with or without SFN for 23 weeks. SFN ameliorates the histological changes characteristic of bladder cancer, resulting in fewer submucosal capillaries. SFN normalizes gut microbiota dysbiosis in mice with BBN-induced bladder cancer with a significant increase in Bacteroides fragilis and Clostridium cluster I. SFN also increases butyric acid levels in the mouse colon, and repairs the injury to the mucosal epithelium of the colon and cecum through the upregulation of the expression of tight junction proteins and GLP2. SFN greatly decreases the release of cytokines (IL-6) and secretory immunoglobulin A in the mice with bladder cancer.CONCLUSION: These results suggest that SFN protects against chemical-induced bladder cancer through normalizing the composition of gut microbiota and repairing the physiological destruction of the gut barrier, as well as decreasing inflammation and the immune response.
PMID: Neuroscience. 2020 Feb 4. Epub 2020 Feb 4. PMID: 32032666 Abstract Title: Meditation Increases the Entropy of Brain Oscillatory Activity. Abstract: We address the hypothesis that the entropy of neural dynamics indexes the intensity and quality of conscious content. Previous work established that serotonergic psychedelics can have a dysregulating effect on brain activity, leading to subjective effects that present a considerable overlap with the phenomenology of certain meditative states. Here we propose that the prolonged practice of meditation results in endogenous increased entropy of brain oscillatory activity. We estimated the entropy of band-specific oscillations during the meditative state of traditions classified as 'focused attention' (Himalayan Yoga), 'open monitoring' (Vipassana), and 'open awareness' (Isha Shoonya Yoga). Among all traditions, Vipassana resulted in the highest entropy increases, predominantly in the alpha and low/high gamma bands. In agreement with previous studies, all meditation traditions increased the global coherence in the gamma band, but also stabilized gamma-range dynamics by lowering the metastability. Finally, machine learning classifiers could successfully generalize between certain pairs of meditation traditions based on the scalp distribution of gamma band entropies. Our results extend previous findings on the spectral changes observed during meditation, showing how long-term practice can lead to the capacity for achieving brain states of high entropy. This constitutes an example of an endogenous, self-induced high entropy state.
Yoga is an effective intervention to decrease anxiety and depression in high-risk antepartum women on hospitalized bedrest.
PMID: Complement Ther Clin Pract. 2020 Feb ;38:101079. Epub 2019 Dec 14. PMID: 32056815 Abstract Title: Effects of yoga on anxiety and depression for high risk mothers on hospital bedrest. Abstract: BACKGROUND: and purpose: In recent years, yoga practitioners have joined forces with medical programs to approach patients' well-being holistically. This study is a randomized controlled trial to assess the effects of a specialized adapted yoga program on anxiety and depression for high-risk expectant mothers on bedrest in a hospital setting.MATERIALS AND METHODS: Seventy-nine pregnant subjects on physician ordered hospitalized bedrest were randomized into two groups: receiving biweekly yoga sessions (intervention group) or receiving no yoga (control group). Data collection tool was the Hospital Anxiety and Depression Scale (HADS) to assess outcomes after delivery.RESULTS: Yoga, even as little as three sessions, showed significant impact in reducing anxiety and depression high-risk pregnant women on hospitalized bedrest. Perceived anxiety and depression overall scores were lower in the intervention group than in the control group (p
Effectiveness of yoga as the public health intervention module in the management of diabetes and diabetes associated dementia.
PMID: Neuroepidemiology. 2020 Feb 19:1-17. Epub 2020 Feb 19. PMID: 32074622 Abstract Title: Effectiveness of Yoga as the Public Health Intervention Module in the Management of Diabetes and Diabetes Associated Dementia in South East Asia: A Narrative Review. Abstract: BACKGROUND: Diabetes mellitus (DM) is widely spread in South Asian (ASEAN) and Indian sub-continent. The increasing healthcare costs of DM can be prevented in the developing world by improved public healthcare interventions. Modifiable risk factors of DM like sedentary lifestyle, obesity, and stressful conditions are associated with its progression; however, the epidemiological data collected by Public Institutions are limited.SUMMARY: A review of published literature describing geographic distribution of DM and associated dementia in South Asian region, particularly India, was conducted with the purpose of assessing the feasibility and challenges associated with the Yoga-based risk reduction. PubMed and Google Scholar databases were searched for DM and dementia-related articles by using a combination of keywords: Diabetes, Diabetes related Dementia Southeast Asia, Pre-diabetes, Yoga, lifestyle modification, Dementia and Exercise. The epidemiological data generated from these diseases have not prompted to any major public health policies. Yoga can be a cost-effective intervention for the prevention of Type 2 DM (T2DM) and its associated cognitive decline when detected early. If nationwide intervention of Yoga is brought about by the state, its integration in health care will become more meaningful and acceptable. Key Message: Studies suggest that Yoga and change in lifestyle can modify the health risks associated with T2DM and associated dementia if it is mainstreamed with the public health initiative of Ayushman Bharat scheme.
PMID: Arch Gynecol Obstet. 2020 Jan ;301(1):53-60. Epub 2020 Feb 14. PMID: 32060683 Abstract Title: Polycystic ovary syndrome management: a review of the possible amazing role of berberine. Abstract: PURPOSE: The therapy of polycystic ovary syndrome (PCOS) is based on synthetic hormones associated with lifestyle changes, but these therapies cannot be taken continuously, especially by women who would like to become pregnant. Thus, nutraceutical compounds were investigated as possible agents for treatment of PCOS. Berberine is shown to be effective against insulin resistance and obesity, particularly against visceral adipose tissue (VAT). Because of these properties, researchers theorized that berberine could be effective in PCOS treatment.METHODS: The aim of this narrative review was to assess the state of the art about the use of berberine in PCOS management.RESULTS: This review included 5 eligible studies. Despite the number of studies considered being low, the number of women studied is high (1078) and the results are interesting. Two authors find out that berberine induced a redistribution of adipose tissue, reducing VAT in the absence of weight loss and improved insulin sensitivity, quite like metformin. One author demonstrated that berberine improved the lipid pattern. Moreover, three authors demonstrated that berberine improved insulin resistance in theca cells with an improvement of the ovulation rate per cycle, so berberine is also effective on fertility and live birth rates.CONCLUSIONS: Finally, berberine is safe to use in premenopausal women who want to get pregnant and showed few side effects in all the cited studies. In conclusion, the use of berberine for PCOS is safe and promising, even if more studies are needed to create a consensus about the dosage of berberine useful for long-term therapy.
Berberine promotes XIAP-mediated cells apoptosis by upregulation of miR-24-3p in acute lymphoblastic leukemia.
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.
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.
Berberine encapsulated PEG-coated liposomes attenuate Wnt1/β-catenin signaling in rheumatoid arthritis via miR-23a activation.
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.
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.
Berberine alleviates monosodium glutamate induced postnatal metabolic disorders associated vascular endothelial dysfunction.
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.
Whole mung bean (Vigna radiata L.) supplementation prevents high-fat diet-induced obesity and disorders in a lipid profile.
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.
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.
Depression and dementia from hyponatremia in brain cancer patients exposed to frozen food chemicals.
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.
Isothiocyanates are detected in human synovial fluid following broccoli consumption and can affect the tissues of the knee joint.
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.
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
The chemopreventive isothiocyanate sulforaphane reduces anoikis resistance and anchorage-independent growth in non-small cell human lung cancer cells.
PMID: Toxicol Appl Pharmacol. 2019 01 1 ;362:116-124. Epub 2018 Oct 24. PMID: 30365975 Abstract Title: The chemopreventive isothiocyanate sulforaphane reduces anoikis resistance and anchorage-independent growth in non-small cell human lung cancer cells. Abstract: The capacity of cancer cells to resist detachment-induced apoptosis, i.e. anoikis, as well as anchorage-independent growth are crucial prerequisites for tumor metastasis. Therefore, agents interfering these properties may provide novel anti-metastatic strategies. Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, is known as a potent chemopreventive agent, but its effect on anoikis resistance has not been investigated. In this study, two non-small cell lung cancer (NSCLC) cell lines, A549 and CL1-5 cells, were treated with SFN under either suspension or adhesion conditions. SFN exhibited more potent cytotoxicity against suspending rather than adherent cancer cells. The selective cytotoxicity was due to the induction of anoikis, as evident by chromatin condensation, Annexin V binding, and activation of the mitochondrial apoptotic pathway. SFN also inhibited NSCLC cell to form spherical colonies, suggesting that anchorage-independent growth was prevented by SFN. Consistently, SFN treatment led to inactivation of FAK and Akt, down-regulation ofβ-catenin, and up-regulation of the cyclin-dependent kinase inhibitor p21. Because A549 cells with wild-type p53 are more sensitive to SFN than p53-mutant CL1-5 cells, p53 dependency of SFN responses were determined in p53-knockdown A549 cells. Knockdown of p53 attenuated the ability of SNF to inhibit anoikis resistance and sphere formation in A549 cancer cells, suggesting that the presence of p53 in NSCLC cancer cells is involved in the sensitivity to SFN. These results provide new insight into mechanisms underlying the chemopreventive ability of SFN and suggest a potential benefit of SFN tointerfere with tumor metastasis.
PMID: J Med Food. 2019 Feb ;22(2):121-126. Epub 2018 Oct 27. PMID: 30372361 Abstract Title: Isothiocyanate from Broccoli, Sulforaphane, and Its Properties. Abstract: Sulforaphane is an isothiocyanate occurring in stored form as glucoraphanin in cruciferous vegetables such as cabbage, cauliflower, and kale, and at high levels in broccoli especially in broccoli sprouts. Glucoraphanin requires the plant enzyme myrosinase for converting it into sulforaphane. Sulforaphane is metabolized through mercapturic acid pathway, being conjugated with glutathione and undergoes further biotransformation, yielding metabolites. Sulforaphane is extensively investigated and is in the interest in medicine for its health benefits. It has been shown that sulforaphane may protect against various types of cancer, may also decrease the risk of cardiovascular disease, and help in autism and osteoporosis. Our review offers a short summary of interesting properties of sulforaphane. Both the in vitro and in vivo methods/models and clinical studies are mentioned.
PMID: J Asian Nat Prod Res. 2020 Apr ;22(4):386-396. Epub 2019 Mar 1. PMID: 30821482 Abstract Title: Hepatic protective effects of sulforaphane through the modulation of inflammatory pathways. Abstract: The aim of this study was to investigate the effects of sulforaphane (SFN) on lipopolysaccharide (LPS)-induced liver failure, and to elucidate underlying mechanisms. SFN, a natural isothiocyanate present in cruciferous vegetables such as broccoli and cabbage, is effective in preventing carcinogenesis, diabetes, and inflammatory responses. Mice were treated intravenously with SFN at 12 h after LPS treatment. LPS significantly increased mortality, serum levels of liver damage markers, and inflammatory cytokines, and toll-like receptor 4 (TLR4) protein expression, which were reduced by SFN. Our results suggest that SFN protects against LPS-induced liver damage, indicating its potential to treat liver diseases.
PMID: Biol Reprod. 2019 Jul 1 ;101(1):223-234. PMID: 31004475 Abstract Title: Sulforaphane ameliorates high-fat diet-induced spermatogenic deficiency in mice†. Abstract: Sulforaphane (SFN), a dietary isothiocyanate that is mainly found in cruciferous vegetables, possesses anti-oxidative and anticancer activity and modulates inflammation. However, little is known about the role of SFN in obesity-related male reproductive defects. The present study aimed to investigate the effects of SFN on high-fat diet (HFD)-induced male spermatogenic impairment and further clarify the possible underlying mechanisms. In this study, 8-week-old mice were randomly divided into four groups. Mice were fed a normal diet or an HFD with or without SFN supplementation. Sulforaphane was subcutaneously injected at a dose of 0.5 mg/kg 5 days/week for 4 weeks beginning 8 weeks after initiation of the HFD. The results demonstrated that SFN could protect against HFD-induced reproductive dysfunction in male mice. Moreover, SFN also improved reproductive ability, as demonstrated by an increased pregnancy rate and decreased embryo resorption rate in comparison to the corresponding HFD group. We also observed a decrease in apoptosis and an attenuation of endoplasmic reticulum (ER) stress after SFN treatment. In vitro studies of mouse and human sperm samples also revealed that SFN protects against the palmitic acid-induced reduction in sperm viability and motility by inhibiting ER stress in an AMP-activated protein kinase (AMPK)-dependent manner. AMPK-dependent ER stress attenuation by SFN was further confirmed using AMPK knockout mice. Taken together, these data show that SFN protects against HFD-induced male reproductive dysfunction by inhibiting ER stress and apoptosis. These findings may be helpful for identifying new therapeutic methods to treat male infertility.
These data suggest that consuming raw cruciferous vegetables may be associated with a lower odds of stomach cancer.
PMID: Nutr Cancer. 2020 ;72(1):52-61. Epub 2019 May 16. PMID: 31094219 Abstract Title: Cruciferous Vegetable Consumption and Stomach Cancer: A Case-Control Study. Abstract: To investigate the association between regular cruciferous vegetable intake and stomach cancer.A hospital-based, case-control study was conducted at Roswell Park Comprehensive Cancer Center in Buffalo, NY, which included 292 stomach cancer patients and 1168 cancer-free controls recruited between 1992 and 1998 as part of the Patient Epidemiology Data System (PEDS). Dietary and other epidemiologic and confounding variables were collected by questionnaire. Multivariable logistic regression analyses were utilized to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between usual pre-diagnostic cruciferous vegetable intake and stomach cancer, with adjustment for other stomach cancer risk factors and dietary characteristics.We observed strong inverse associations between stomach cancer and highest versus lowest intakes of total cruciferous vegetables (OR = 0.59, 95% CI: 0.42-0.83), raw cruciferous vegetables (OR = 0.53, 95% CI: 0.38-0.73), raw broccoli (OR = 0.61, 95% CI: 0.43-0.86), raw cauliflower (OR = 0.51, 95% CI: 0.35-0.73), and Brussels sprouts (OR = 0.66, 95% CI = 0.48-0.91).These data suggest that consuming raw cruciferous vegetables may be associated with a lower odds of stomach cancer, even after considering other dietary characteristics.
Dietary supplementation with sulforaphane attenuates liver damage and heme overload in a sickle cell disease murine model.
PMID: Exp Hematol. 2019 09 ;77:51-60.e1. Epub 2019 Aug 9. PMID: 31404577 Abstract Title: Dietary supplementation with sulforaphane attenuates liver damage and heme overload in a sickle cell disease murine model. Abstract: Sickle cell disease (SCD) is a recessively inherited blood disorder caused by abnormalβ-globin production. The β-globin mutation changes erythrocyte morphology into a sickle shape and increases erythrocyte vulnerability to hemolysis. Oxidative stress and concomitant inflammation eventually result in damage to multiple organs. Nrf2 is a master regulator of the oxidative stress response, homeostasis, and metabolism. Keap1 modulates Nrf2 protein levels; Nrf2 inducers alter nuclear Nrf2 levels by interacting with Keap1. Genetic modification of Keap1 helps to reduce inflammation and tissue damage in SCD model mice through Nrf2 induction. Here, we investigated the benefits of a mild and safe Nrf2 agonist, sulforaphane (SFN), in ameliorating SCD pathology in a murine model. SFN is a phytochemical and is found in cruciferous vegetables as its inert precursor, glucoraphanin. We found that dietary SFN administration for 14 days or 2 months increased the expression of Nrf2-dependent cytoprotective genes, but SFN uptake did not have deleterious effects on the food consumption and growth of SCD model mice. SFN ameliorated the liver damage of SCD mice, which could be validated by the rescue of liver function and the significantly reduced liver necrotic area. SFN administrationalso helped to eliminate heme released from lysed sickle cells. These results indicate that dietary supplementation with SFN relieves SCD symptoms by inducing Nrf2 and support our contention that SFN is a potential drug for the long-term treatment of children with SCD.
PMID: J Epidemiol. 2019 Dec 14. Epub 2019 Dec 14. PMID: 31839643 Abstract Title: Intake of vegetables and fruits and the risk of cataract incidence in a Japanese population: the Japan Public Health Center-based Prospective Study. Abstract: BACKGROUND: Although the consumption of vegetables and fruits is reported to influence the risk of cataract, no prospective study of this association from Asia has yet appeared. Here, we investigated the association between vegetable and fruit intake and cataract incidence in a large-scale population-based prospective cohort study in Japan.METHODS: This study included 32,387 men and 39,333 women aged 45-74 years who had no past history of cataract and had completed a dietary questionnaire of the Japan Public Health Center-based Prospective Cohort Study. The incidence of cataract was evaluated after five-year follow-up. We used multiple logistic regression analyses to estimate the sex-specific odds ratios (ORs), with adjustment for confounding factors.RESULTS: We identified 1,836 incident cataracts in 594 men and 1,242 women. In men, OR for cataract was decreased with higher intake of vegetables (OR=0.77; 95% CI, 0.59-1.01; Ptrend across quartile categories=0.03) and cruciferous vegetables (OR=0.74; 95% CI, 0.57-0.96; Ptrend=0.02). In contrast, OR for cataract was increased with higher intake of vegetables among women (OR=1.28; 95% CI, 1.06-1.53; Ptrend=0.01). Green and yellow vegetable and fruit intake were not associated with cataract in either sex.CONCLUSIONS: This study suggests that vegetables may reduce the risk of cataracts in men, but not in women.
Allyl isothiocyanate, a constituent of cruciferous vegetables, inhibits growth of PC-3 human prostate cancer xenografts in vivo.
PMID: Carcinogenesis. 2003 Oct ;24(10):1665-70. Epub 2003 Aug 1. PMID: 12896904 Abstract Title: Allyl isothiocyanate, a constituent of cruciferous vegetables, inhibits growth of PC-3 human prostate cancer xenografts in vivo. Abstract: We have shown previously that allyl isothiocyanate (AITC), a constituent of cruciferous vegetables, significantly inhibits survival of PC-3 and LNCaP human prostate cancer cells in culture, whereas proliferation of a normal prostate epithelial cell line is minimally affected by AITC even at concentrations that are highly cytotoxic to the prostate cancer cells. The present studies were designed to test the hypothesis that AITC administration may retard growth of human prostate cancer xenografts in vivo. Bolus i.p. injection of 10 micromol AITC, three times per week (Monday, Wednesday and Friday) beginning the day of tumor cell implantation, significantly inhibited the growth of PC-3 xenograft (P