PMID: 

Arch Pharm Res. 2020 Jan 27. Epub 2020 Jan 27. PMID: 31989480

Abstract Title: 

Mangiferin ameliorates placental oxidative stress and activates PI3K/Akt/mTOR pathway in mouse model of preeclampsia.

Abstract: 

Preeclampsia is an inflammatory disease which can induce oxidative stress in placenta. Oxidative stress in preeclampsia is regulated by the phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway. Mangiferin, an anti-oxidative molecule, is reported to ameliorate oxidative stress in the kidney and brain through activating the PI3K/Akt/mTOR pathway. We aimed to investigate the effects of mangiferin in a mouse model of preeclampsia, which was induced by phosphatidylserine/dioleoyl-phosphatidycholine (PS/PC) from day 5 to 17 of pregnancy. The female pregnant mice were divided into five groups according to drug treatment. Animals received mangiferin orally at doses of 10, 20, 40 mg/kg/day from day 0.5 to 17. In preeclampsia mouse model, elevated systolic blood pressure and proteinuria were ameliorated by mangiferin treatment. Mangiferin attenuated fms-like tyrosine kinase-1 and placental growth factor expression and oxidative stress in both blood and placenta of preeclampsia mice. The suppressed PI3K/Akt/mTOR pathway in placenta was activated by mangiferin treatment. This study demonstrates that mangiferin ameliorates placental oxidative stress and activates PI3K/Akt/mTOR pathway in a mouse model of preeclampsia.

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PMID: 

Bioorg Med Chem. 2020 Feb 15 ;28(4):115304. Epub 2020 Jan 7. PMID: 31956052

Abstract Title: 

Mangiferin: A promising natural xanthone from Mangifera indica for the control of acyclovir – resistant herpes simplex virus 1 infection.

Abstract: 

Mangiferin is found in many plant species as the mango tree (Mangifera indica) with ethnopharmacological applications and scientific evidence. The emergence of resistant herpes simplex virus (HSV) strains to Acyclovir (ACV) has encouraged the search for new drugs. We investigated the in vitro and in vivo activity of mangiferin obtained from M. indica against ACV-resistant HSV-1 (AR-29) and sensitive (KOS) strains. The in vitro activity was performed under varying treatment protocols. The substance showed a CC > 500 μg/mL and ICof 2.9 μg/mL and 3.5 μg/mL, respectively, for the AR-29 and KOS strains. The in vivo activity was performed in Balb/c mice treated with 0.7% topical mangiferin formulation. This formulation inhibited most effectively the AR-29 strain, attenuated the lesions, postponed their appearance or enhanced healing, in comparison to control group. We demonstrated the potentiality of mangiferin from M. indica to control HSV replication with emphasis to ACV-resistant infection.

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PMID: 

J Nutr Biochem. 2019 Dec 20 ;78:108324. Epub 2019 Dec 20. PMID: 32004926

Abstract Title: 

Green tea polyphenols decrease weight gain, ameliorate alteration of gut microbiota, and mitigate intestinal inflammation in canines with high-fat-diet-induced obesity.

Abstract: 

Green tea polyphenols (GTPs) exhibit beneficial effects towards obesity and intestinal inflammation; however, the mechanisms and association with gut microbiota are unclear. We examined the role of the gut microbiota of GTPs treatment for obesity and inflammation. Canines were fed either a normal diet or high-fat diet with low (0.48% g/kg), medium (0.96% g/kg), or high (1.92% g/kg), doses of GTPs for 18 weeks. GTPs decreased the relative abundance of Bacteroidetes and Fusobacteria and increased the relative abundance of Firmicutes as revealed by 16S rRNA gene sequencing analysis. The relative proportion of Acidaminococcus, Anaerobiospirillum, Anaerovibrio, Bacteroides, Blautia, Catenibactetium, Citrobacter, Clostridium, Collinsella, and Escherichia were significantly associated with GTPs-induced weight loss. GTPs significantly (P

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PMID: 

J Agric Food Chem. 2018 Jun 27 ;66(25):6317-6325. Epub 2018 Jun 14. PMID: 29871486

Abstract Title: 

Attenuation of tert-Butyl Hydroperoxide ( t-BHP)-Induced Oxidative Damage in HepG2 Cells by Tangeretin: Relevance of the Nrf2-ARE and MAPK Signaling Pathways.

Abstract: 

The current study evaluates the protective effects of tangeretin, a representative polymethoxyflavone (PMF) mainly isolated from the peels of citrus fruits, against tert-butyl hydroperoxide ( t-BHP)-induced oxidative damage in HepG2 cells and the potential mechanisms of this protection. Tangeretin suppressed t-BHP-induced oxidative damage, as evaluated by cell viability, reactive-oxygen-species (ROS) levels, lactate dehydrogenase (LDH) leakage and glutathione (GSH) levels. Further mechanistic studies showed that tangeretin up-regulated the expression of heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). Moreover, tangeretin induced antioxidant-responsive-element (ARE)-dependent luciferase activation, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) nuclear translocation, and mitogen-activated-protein-kinase (MAPK) phosphorylation. Results in the study indicate that the protective effects of tangeretin may be at least partly due to its capacity to up-regulate the antioxidant enzymes NQO1 and HO-1 via the MAPK-Nrf2-ARE signaling pathway. Tangeretin may play an effective protective role in liver injury.

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PMID: 

Cureus. 2019 Dec 22 ;11(12):e6443. Epub 2019 Dec 22. PMID: 31998571

Abstract Title: 

The Beneficiary Role of Selenium in Type II Diabetes: A Longitudinal Study.

Abstract: 

Introduction Selenium (Se) is an antioxidotic element that is able to protect the pancreatic islets from oxidative stress, improve their functionality, and suspend atherosclerosis. The current paper is an attempt to demonstrate the beneficiary impact of administrating Se to patients with diabetes type 2 who are being treated with oral hypoglycemic agents, based on their glycemic and lipidemic profile. Methods The study involves 94 individuals, 72 male and 22 female patients aged 48 to 64 years old with diabetes mellitus type 2. They did not present any diabetic complications or significant comorbidities. They were following a Mediterranean diet and were monitored in order to maintain a steady body mass index (BMI). They were administered with Se 200μg, taken once daily on an empty stomach. The laboratory testing included fasting blood glucose, hemoglobin A1c (HbA1c), total cholesterol, triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL). The tests were performed before, three months after, and six months after theadministration of selenium. Results The study resulted in a statistically significant reduction in the blood levels of glucose, HbA1c, cholesterol, and LDL in both three months and six months after the beginning of the treatment. HDL did not present any change during the first three months but didpresent a statistically significant increase in six months. Triglycerides did not present a significant reduction in both three and six months. Conclusion It appears that the administration of Se to type-2 diabetic patients can improve their glycemic and lipidemic profile, while larger definite trials are needed to provide further evidence.

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PMID: 

Biol Trace Elem Res. 2020 Jan 30. Epub 2020 Jan 30. PMID: 32002792

Abstract Title: 

Nobiletin Regulates ROS/ADMA/DDAHII/eNOS/NO Pathway and Alleviates Vascular Endothelium Injury by Iron Overload.

Abstract: 

Iron overload is harmful to health and associates with intracellular excessive reactive oxygen species (ROS) generation. Nobiletin (Nob) is known to be antioxidant and anti-inflammatory. However, whether Nob can protect endothelial cells against iron overload has not been studied, and the specific mechanism has not yet been elucidated. In this study, we have identified the protective effects of Nob, and its underlying molecular mechanism in human umbilical vein endothelial cells (HUVECs) suffered from iron overload via ROS/ADMA/DDAHII/eNOS/NO pathway. We found that compared with 50 μM iron dextran treatment, co-treatment with 20 μM Nob increased cell viability and decreased lactate dehydrogenase activity. Besides, Nob could upregulate DDAHII expression and activity, promote eNOS phosphorylation to produce more NO, reduce ADMA content, and therefore increase superoxide dismutase, catalase, and glutathione peroxidase activities, and decrease malondialdehyde level and ROS generation. Nob also inhibited mitochondrial permeability transition pore (mPTP) openness and cleaved caspase-3 expression, and decreased apoptosis induced by iron overload. These results were consistent when Nob was replaced by the positive control reagents L-arginine (a competitive substrate of ADMA), cyclosporin A (an mPTP closing agent), or edaravone (a free radical scavenger). The addition of pAD/DDAHII-shRNA adenovirus reversed the above effects of Nob. These data suggested that the protective mechanism of Nob was to inhibit ROS burst, upregulate DDAHII expression and activity, promote eNOS phosphorylation, produce NO, reduce ADMA content, and ultimately alleviate iron overload damage in vascular endothelium.

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PMID: 

Neurosci Lett. 2019 07 13 ;705:112-117. Epub 2019 Apr 27. PMID: 31039425

Abstract Title: 

Role of tangeritin against cognitive impairments in transgenic Drosophila model of Parkinson's disease.

Abstract: 

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. As there is no permanent cure for the disease, the use of herbal compounds with antioxidant potential will be an effective approach for controlling the progression of disease. In this context the effect of tangeritin (a polymethoxy flavone concentrated in the peels of citrus fruits) was studied at final doses of 5, 10 and 20 μM on PD model flies. The doses were established in diet and the PD flies were allowed to feed on it for 24 days. The effect was studied on cognitive impairments. Immunostaining of brain sections for tyrosine hydroxylase was also performed. The docking studies were also carried out to give a plausible binding site of tangeritin on alpha synuclein molecule. The results of the study showed that tangeritin is effective in improving the cognitive impairments.

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PMID: 

J Agric Food Chem. 2015 Nov 4 ;63(43):9520-7. Epub 2015 Oct 26. PMID: 26468759

Abstract Title: 

Tangeretin from Citrus reticulate Inhibits Respiratory Syncytial Virus Replication and Associated Inflammation in Vivo.

Abstract: 

Human respiratory syncytial virus (RSV) is a common pathogen that causes pneumonia and bronchiolitis in infants and young children. Our previous study showed that tangeretin from Citrus reticulate possessed potent in vitro anti-RSV effects comparable to that of ribavirin. Therefore, in this study, we investigated the in vivo anti-RSV activity of tangeretin in 3-week-old male BALB/c mice. A plaque reduction assay and fluorescence quantitative polymerase chain reaction (FQ-PCR) showed that tangeretin inhibited RSV replication in the lung of mice. Moreover, a luminex assay indicated tangeretin relieved RSV-induced lung inflammation by attenuating interleukin (IL)-1β secretion. Possible anti-inflammatory mechanisms of tangeretin were preliminarily explored using a RSV-infected macrophage model. A FQ-PCR, enzyme-linked immunosorbent assay (ELISA), and luciferase assay revealed that tangeretin inhibited RSV-induced inflammation by suppressing nuclear factor-κB(NF-κB) activation. This study demonstrates that tangeretin inhibited RSV replication and RSV-induced lung inflammation in vivo and may be useful in preventing and treating RSV infections and inflammation.

PMID: 

Int J Mol Med. 2014 Jul ;34(1):183-90. Epub 2014 Apr 22. PMID: 24756136

Abstract Title: 

Antiviral activity of ginseng extract against respiratory syncytial virus infection.

Abstract: 

Panax ginseng has been known to have a number of immuno-modulatory effects. In this study, we investigated whether Panax Korean red ginseng extract (KRGE) has in vitro and in vivo antiviral effects on respiratory syncytial virus (RSV) infection. KRGE improved the survival of human lung epithelial cells against RSV infection and inhibited RSV replication. In addition, KRGE treatment suppressed the expression of RSV-induced inflammatory cytokine genes (IL-6 and IL-8) and the formation of reactive oxygen species in epithelial cell cultures. Oral administration of mice with KRGE resulted in lowering lung viral loads after RSV infection. Additionally, the in vivo effects of KRGE showed an enhanced level of interferon-γ (IFN-γ) producing dendritic cells subsequent to RSV infection. Taken together, these results suggested that KRGE has antiviral activity against RSV infection.

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PMID: 

J Virol. 2014 Apr ;88(8):4229-36. Epub 2014 Jan 29. PMID: 24478430

Abstract Title: 

Resveratrol inhibits the TRIF-dependent pathway by upregulating sterile alpha and armadillo motif protein, contributing to anti-inflammatory effects after respiratory syncytial virus infection.

Abstract: 

UNLABELLED: Respiratory syncytial virus (RSV) is the most important cause of lower respiratory tract infection in young children and the leading cause of infant hospitalization worldwide. Uncontrolled response to RSV is mediated by a toll-like receptor (TLR)-mediated immune response. Resveratrol possesses anti-RSV activity and is an inhibitor of the TRIF/TBK1/IRF-3 complex. We hypothesize that resveratrol inhibits the TRIF-dependent pathway through upregulation of SARM post-RSV infection. BALB/c mice were infected with RSV and were injected with resveratrol 1 h postinoculation. SARM short interfering RNA was administered to RSV-infected and resveratrol-treated mice. Lung function was measured by whole-body plethysmography, lung histopathology was examined, and lymphocytes in bronchoalveolar lavage fluid were quantified. SARM and TRIF protein expression were detected in the lung by Western blot analyses. The expression of gamma interferon in bronchoalveolar lavage fluid (BALF) was evaluated by enzyme-linked immunosorbent assay (ELISA). SARM expression was reduced and TRIF expression was increased after infection with RSV. Resveratrol increased SARM expression and decreased TRIF expression after RSV infection. SARM knockdown in resveratrol-treated mice enhanced gamma interferon production, RSV-induced airway inflammation, and airway hyperresponsiveness (AHR). Resveratrol decreased TRIF expression and prevented the RSV-mediated reduction of SARM expression. Resveratrol-mediated inhibition of the TRIF-dependent pathway may be dependent on SARM expression.IMPORTANCE: Our study provides insights into the regulation of innate immunity in response to RSV infection. The results suggest that resveratrol-mediated alterations in SARM have therapeutic potential against RSV immunopathology caused by deregulation of the TLR-mediated immune response. Ultimately, improved insight into the complex interplay between TLR adaptor proteins and the occurrence of severe RSV infection might lead to novel therapeutic treatment strategies, such as TLR adjuvants.

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