PMID: 

Lasers Med Sci. 2020 Feb 7. Epub 2020 Feb 7. PMID: 32030556

Abstract Title: 

Photobiomodulation of inflammatory-cytokine-related effects in a 3-D culture model with gingival fibroblasts.

Abstract: 

The aim of this study was to assess the effects of IL-6 and IL-8 cytokines on human gingival fibroblasts (HGF) cultured in a 3-D model and the possible photobiomodulation (PBM) of such effects by low-level laser therapy. In complete culture medium (DMEM), HGF from a healthy patient were seeded in a type I collagen matrix inserted into 24-well plates. After 5 days of incubation, the cytokines were added or not to serum-free DMEM, which was applied to the cell-enriched matrices. Then, PBM was performed: three consecutive irradiations using LaserTable diode device (780 nm, 0.025 W) at 0.5 J/cmwere delivered or not to the cells. Twenty-four hours after the last irradiation, cell viability and morphology, gene expression, and synthesis of inflammatory cytokines and growth factors were assessed. The histological evaluation demonstrated that, for all groups, matrices presented homogeneous distribution of cells with elongated morphology. However, numerous cytokine-exposed cells were rounded. IL-6 and IL-8 decreased cell viability, synthesis of VEGF, and gene expression of collagen type I. PBM enhanced cell density in the matrices and stimulated VEGF expression, even after IL-6 challenge. Reduced TNF-α synthesis occurred in those cells subjected to PBM. In conclusion, PBM can penetrate collagen matrix and stimulate HGF, highlighting the relevance of this research model for further phototherapy studies and in vitro biomodulation of the healing process.

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PMID: 

J Family Med Prim Care. 2020 Jan ;9(1):69-71. Epub 2020 Jan 28. PMID: 32110567

Abstract Title: 

Effect of artificial sweeteners on insulin resistance among type-2 diabetes mellitus patients.

Abstract: 

Introduction: Incidence of diabetes mellitus has increased over the past few years, mainly due to our eating habits and physical inactivity. This also includes the use of artificial sweetening agents which have broadly replaced other forms of sugars and have shown a paradoxical, negative effect on blood glucose. Ingestion of these artificial sweeteners (AS) results in the release of insulin from pancreas which is mistaken for glucose (due to their sweet taste). This increases the levels of insulin in blood eventually leading to decreased receptor activity due to insulin resistance.Methodology: It is a crosssectional study that was conducted on patients diagnosed with type-2 diabetes mellitus of a tertiary care hospital in Central India. All the diabetics that presented in the OPD were divided into 2 groups based on whether they use AS (group A) or not (group B). Insulin resistance was calculated for each group using HOMA-IR and graphs were plotted.Results: The HOMAIR values for Group A and B ranged from 0.9-24.33 and 0.12-10.83 with mean values 7.39 and 2.6, respectively, showing that the ones who used AS had a higher insulin resistance. The study also showed that the duration of use of artificial sweeteners had a direct impact on insulin resistance.

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PMID: 

J Med Food. 2020 Mar 3. Epub 2020 Mar 3. PMID: 32125927

Abstract Title: 

Naringenin Ameliorate Carbon Tetrachloride-Induced Hepatic Damage Through Inhibition of Endoplasmic Reticulum Stress and Autophagy in Rats.

Abstract: 

Hepatic fibrosis emerges upon exposure of liver to various chemicals and if not treated, it develops various diseases such as cirrhosis and cancer. Carbon tetrachloride (CCl) is a widely used toxin in animal models to develop hepatic fibrosis. Accumulation of unfolded proteins in cells causes stress in the endoplasmic reticulum (ER) and various mechanisms are involved in the cell to reduce the damage caused by these unfolding proteins. The most well known of these is the unfolded protein response. Further, autophagy works to remove these proteins if the damage cannot be repaired and is permanent. In our study, we investigated the effects of naringenin (NRG), a flavanon abundant in citrus fruits, on ER stress and autophagy in CCl-injured rat liver. The animals were given 0.2 mL/kg of CClfor 10 days and treatment group was administered 100 mg/kg of NRG for 14 days. Histopathological examination was performed to show liver damage and to determine the therapeutic properties of the active substance. Transmission electron microscopy (TEM) analysis was carried out to establish cell level damage and effect of treatment. In addition, levels of ER stress and autophagy markers of liver were measured. According to our findings, TEM demonstrated positive effect of NRG and histological examinations reported ameliorative effects. In addition, NRG reduced levels of ER stress markers and inhibited autophagy significantly compared to CCl-treated group. As a result, NRG significantly reduced damage in hepatocytes and provided a significant amelioration.

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PMID: 

Basic Clin Pharmacol Toxicol. 2020 Mar 16. Epub 2020 Mar 16. PMID: 32180335

Abstract Title: 

Citrus fruit-derived flavonoid naringenin and the expression of hepatic organic cation transporter 1 protein in diabetic rats treated with metformin.

Abstract: 

Naringenin possesses many pharmacological effects and may modulate metformin disposition. The purpose of this study was to evaluate the role of naringenin on hepatic expression of organic cation transporter 1 (OCT 1) protein and its associated effects on metformin-associated hyperlactataemia in diabetes. Forty-nine male Sprague Dawley rats randomly assigned to 7 groups (n =7), were orally treated daily with 3.0 ml/kg body weight (BW) of distilled water (group 1) or 60 mg/kg BW of naringenin (groups 2 and 5) or 250 mg/kg BW of metformin (groups 3 and 6), respectively, dissolved in distilled water. Similarly, group 7 was given metformin and naringenin. Groups 4, 5, 6 and 7 were administered intraperitoneally with streptozotocin at a single dose of 60 mg/kg BW to induce diabetes. Glucose tolerance tests were performed. The animals were killed after 8 weeks of treatment, blood was collected and livers excised for further biochemical analysis. Lowered body weight, increased polydipsia and reduced hepatic glycogen concentrations were observed in diabetic rats compared to controls. Naringenin only significantly decreased plasma lactate levels while metformin only or with naringenin significantly increased plasma lactate levels in diabetic compared to non-treated diabetic animals. Metformin only but not naringenin significantly increased plasma lactate levels in non-diabetic compared to control rats. Furthermore, naringenin with or without metformin but not metformin only significantly increased hepatic OCT1 expression in diabetic compared to non-treated diabetic rats. Contrastingly, metformin only but not naringenin significantly increased hepatic OCT 1 expression in non-diabetic rats compared to controls. Diabetic rats treated with metformin exhibited significantly increased plasma metformin concentrations compared to non-diabetic but naringenin significantly dropped this parameter. Conversely, hepatic metformin concentrations were significantly lower in diabetic rats treated with metformin compared to non-diabetic rats but significantly increased when naringenin was added. These results suggest that naringenin ameliorated hyperglycaemia-induced reduction in hepatic OCT 1 expression leading to metformin accumulation and increased lactic acid production.

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PMID: 

Front Mol Biosci. 2020 ;7:25. Epub 2020 Feb 28. PMID: 32181260

Abstract Title: 

Naringenin Inhibition of theQuorum Sensing Response Is Based on Its Time-Dependent Competition With-(3-Oxo-dodecanoyl)-L-homoserine Lactone for LasR Binding.

Abstract: 

Bacterial quorum sensing (QS) is a cell-to-cell communication system that governs the expression of a large set of genes involved in bacterial-host interactions, including the production of virulence factors. Conversely, the hosts can produce anti-QS compounds to impair virulence of bacterial pathogens. One of these inhibitors is the plant flavonoid naringenin, which impairs the production of QS-regulatedvirulence factors. In the present work, we analyze the molecular basis for such inhibition. Our data indicate that naringenin produces its effect by directly binding the QS regulator LasR, hence competing with its physiological activator,-(3-oxo-dodecanoyl)-L-homoserine lactone (3OC12-HSL). Theanalysis of LasR binding to its cognate target DNA showed that the capacity of naringenin to outcompete 3OC12-HSL, when the latter is previously bound to LasR, is low. By using anLasR-based biosensor strain, which does not produce 3OC12-HSL, we determined that the inhibition of LasR is more efficient when naringenin binds to nascent LasR than when this regulator is already activated through 3OC12-HSL binding. According to these findings, at early exponential growth phase, when the amount of 3OC12-HSL is low, naringenin should proficiently inhibit theQS response, whereas at later stages of growth, once 3OC12-HSL concentration reaches a threshold enough for binding LasR, naringenin would not efficiently inhibit the QS response. To test this hypothesis, we analyze the potential effect of naringenin over the QS response by adding naringenin tocultures at either time zero (early inhibition) or at stationary growth phase (late inhibition). In early inhibitory conditions, naringenin inhibited the expression of QS-regulated genes, as well as the production of the QS-regulated virulence factors, pyocyanin and elastase. Nevertheless, in late inhibitory conditions, theQS response was not inhibited by naringenin. Therefore, this time-dependent inhibition may compromise the efficiency of this flavonoid, which will be effective just when used against bacterial populations presenting low cellular densities, and highlight the importance of searching for QS inhibitors whose mechanism of action does not depend on the QS status of the population.

PMID: 

Biosci Rep. 2020 Mar 27 ;40(3). PMID: 32091090

Abstract Title: 

Naringin protects endothelial cells from apoptosis and inflammation by regulating the Hippo-YAP Pathway.

Abstract: 

Atherosclerosis is the primary cause of several cardiovascular diseases. Oxidized low-density lipoprotein (ox-LDL)-induced apoptosis, endothelial-mesenchymal transition (EndMT), and inflammation are crucial for the progression of cardiovascular diseases, including atherosclerosis. Naringin, a major compound from tomatoes, grapefruits, and related citrus, reportedly exhibits potential protective effects during atherosclerosis development; however, its effect on ox-LDL-induced human umbilical vein endothelial cell (HUVEC) damage remains unknown. In the present study, we investigated the anti-apoptotic and anti-inflammatory activities of naringin against ox-LDL-induced endothelial cells, and the underlying mechanism. Naringin pretreatment significantly and concentration-dependently inhibited ox-LDL-induced cell injury and apoptosis. Additionally, naringin restored endothelial barrier integrity by preventing VE-cadherin disassembly and F-actin remodeling, and down-regulated pro-inflammatory factors like IL-1β, IL-6, and IL-18, in the HUVECs. We also demonstrated that naringin treatment restored ox-LDL-induced YAP (yes-associated protein) down-regulation, given the YAP-shRNA attenuated cytoprotective effect of naringin on ox-LDL-induced endothelial cell injury and apoptosis. Collectively, our data indicate that naringin reversed ox-LDL-triggered HUVEC apoptosis, EndMT, and inflammation by inhibiting the YAP pathway. Therefore, naringin may have a therapeutic effect on endothelial injury-related disorders.

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I thought this hype is going to end again, but it has increased so much, and we finally have to start taking a closer look

I thought this hype is going to end again, but it has increased so much, and we finally have to start taking a closer look

PMID: 

Behav Brain Funct. 2020 Feb 27 ;16(1):4. Epub 2020 Feb 27. PMID: 32103758

Abstract Title: 

Naringin provides neuroprotection in CCL2-induced cognition impairment by attenuating neuronal apoptosis in the hippocampus.

Abstract: 

BACKGROUND: Chemokine C-C motif ligand 2 (CCL2) is one of the most widely recognised proinflammatory chemokines in cognitive disorders. Currently, CCL2-targeting drugs are extremely limited. Thus, this study aimed to explore the neuroprotection afforded by naringin in CCL2-induced cognitive impairment in rats.METHODS: Before the CCL2 intra-hippocampal injection, rats were treated with naringin for 3 consecutive days via intraperitoneal injection. Two days post-surgery, the Morris water maze (MWM) and novel object recognition (NORT) tests were performed to detect spatial learning and memory and object cognition, respectively. Nissl staining and dUTP nick-end labelling (TUNEL) staining were performed to assess histopathological changes in the hippocampus. Commercial kits were used to measure the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and the content of malondialdehyde (MDA). Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to examine the relative mRNA expression of interleukin 1β, (IL-1β), interleukin 6 (IL-6), glutamate/aspartate transporter (GLAST), glutamate transporter-1 (GLT-1), phosphate-activated glutaminase (PAG), cysteine aspartic acid-specific protease 8 (caspase-8), cysteine aspartic acid-specific protease 3 (caspase-3), cell lymphoma/leukaemia-2 (Bcl-2), andBcl-2 associated X protein (Bax).RESULTS: In the MWM, the average escape latency and average swimming distance were significantly reduced and the crossing times were increased in the naringin-treated groups, compared with the CCL2 group. The NORT results revealed that, compared with the CCL2 rats, the discrimination index in the naringin-treated rats increased significantly. Nissl and TUNEL staining revealed that naringin protected the structure and survival of the neurons in the CA1 zone of the hippocampus. In the naringin-treated groups, the SOD and GSH-Px activities were increased, whereas the MDA levels were decreased. Furthermore, in the naringin-treated groups, the relative mRNA expression of IL-1β and IL-6 was significantly decreased; GLAST and GLT-1 mRNA expression levels were increased, whereas PAG was decreased. In the naringin-treated groups, the relative mRNA expression levels of caspase-8, caspase-3, and Bax were decreased, whereas that of Bcl-2 was increased.CONCLUSION: Collectively, these data indicated that naringin alleviated the CCL2-induced cognitive impairment. The underlying mechanisms could be associated with the inhibition of neuroinflammation, oxidative stress, apoptosis, and the regulation of glutamate metabolism.

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PMID: 

Drug Des Devel Ther. 2020 ;14:677-696. Epub 2020 Feb 19. PMID: 32109993

Abstract Title: 

Colon Targeting of Naringin for Enhanced Cytoprotection Against Indomethacin-Induced Colitis in Rabbits.

Abstract: 

Background: Naringin is a promising anti-inflammatory drug against various disorders including ulcerative colitis. However, its oral bioavailability is low (8%) possibly due to cleavage at the upper gut. Consequently, colon targeting would be necessary for drug protection at the upper gut, enhanced oral bioavailability and potentiated cytoprotection against colitis.Methodology: This study involved the formulation of compression-coated tablets of naringin employing mixtures of pH-sensitive Eudragit L100-55 (EUD-L100-55) and different time-dependent polymers including ethyl cellulose (EC), sodium alginate (ALG) and sodium carboxymethyl cellulose (SCMC). Drug-polymer interaction during release was assessed using Fourier transform-infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). Tablets were evaluated in vitro. Surface morphology of the optimized tablets either before or after exposure to the different release media was examined employing scanning electron microscopy (SEM). Cytoprotection potential of the optimized tablets against indomethacin-induced colitis in rabbits was screened and compared to core tablets through a histopathological examination of colon, measurement of serum perinuclear antineutrophil cytoplasmic antibodies (pANCA) and immunohistochemical localization of tumor necrosis factor-alpha (TNF-α).Results: FT-IR and DSC results may indicate drug-polymers interaction during release. Release retardation could be related to polymer swelling that was in the order of SCMC>ALG>EC. SEM examination indicated more porous coats at the buffers relative to the acidic medium. Colon targeting was expected in case of coats of 5% ALG, 5% SCMC and 10% EC (w/w) in combination with EUD-L100-55; thus, they were selected for in vivo evaluation. Effective cytoprotection of selected tablets against indomethacin-induced colitis was indicated by a significant (

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