PMID: 

Molecules. 2019 Oct 10 ;24(20). Epub 2019 Oct 10. PMID: 31658733

Abstract Title: 

20(S)-Ginsenoside Rg3 Promotes HeLa Cell Apoptosis by Regulating Autophagy.

Abstract: 

20()-Ginsenoside Rg3 (GRg3) has various bioactivities including anti-cancer effects and inhibition of autophagy. However, no reports have investigated the appearance of autophagy or the connection between autophagy and apoptosis in HeLa cells treated with 20()-GRg3. Cell viability was measured by CCK-8 (cell counting kit-8) assays. Apoptosis and the cell cycle were analyzed by Hoechst 33342 staining and flow cytometry. Apoptotic pathways were examined by ROS (reactive oxygen species) determination and rhodamine 123 assays. Western blot analysis was used to determine changes in protein levels. Autophagy induction was monitored by acidic vesicular organelle staining and EGFP-LC3 transfection. 20()-GRg3 inhibited autophagy of cells in a starved state, making it impossible for cells to maintain a steady state through autophagy, and then induced apoptosis. 20()-GRg3 blocked the late stage of autophagy (fusion of lysosomes and degradation of autophagic lysosomes), including a decrease in acidic vesicular organelle fluorescence, increased LC3 I-II conversion, accumulation of EGFP-LC3 fluorescence, GFP-mRFP-LC3 red-green fluorescence ratio, degradation of the substrate p62, and loss of the balance between autophagy and apoptosis, which induced apoptosis. ROS increased, the mitochondrial membrane potential decreased, apoptotic inducer AIF was released from mitochondria, and nuclear transfer occurred, triggering a series of subsequent apoptotic events. Autophagy inducer rapamycin inhibited the apoptosis induced by 20()-GRg3, whereas autophagy inhibitor BA1 promoted apoptosis induced by 20()-GRg3. Therefore, 20()-GRg3 promoted HeLa cell apoptosis by regulating autophagy. In the autophagic state, 20()-GRg3 can be used as a novel autophagy inhibitor in synergy with tumor-blocking therapies such as chemotherapy, which supports its application in the medical field.

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PMID: 

Antioxidants (Basel). 2019 Aug 3 ;8(8). Epub 2019 Aug 3. PMID: 31382635

Abstract Title: 

Nrf2 Plays an Essential Role in Long-Term Brain Damage and Neuroprotection of Korean Red Ginseng in a Permanent Cerebral Ischemia Model.

Abstract: 

Cerebral ischemia is a devastating disease with a high incidence of death and disability; however, effective therapeutics remain limited. The transcriptional factor Nrf2 has been shown to play a pivotal role in the endogenous defense against brain oxidative stress and inflammation, and therefore represents a promising target for stroke intervention. However, the long-term effects of Nrf2 and the standardized Korean red ginseng (ginseng), a potent Nrf2 natural inducer, on permanent cerebral ischemic damage have not yet been reported. Wildtype (WT) and Nrf2adult mice were pretreated with either vehicle or ginseng, and were subjected to permanent distal middle cerebral artery occlusion (pdMCAO). The infarct volume, the reactive astrocytes and microglia, and the water regulatory protein aquaporin 4 (AQP4) were examined at 28 days after stroke. When compared with the WT matched controls, the Nrf2 disruption significantly enlarged the infarct volume (40.4± 10.1%) and exacerbated the progression of reactive gliosis and AQP4 protein levels after pdMCAO. In contrast, ginseng significantly reduced the infarct volume and attenuated the reactive gliosis and AQP4 in the ischemic WT mice (47.3 ± 6.9%), but not in the Nrf2mice (25.5± 5.6%). In conclusion, Nrf2 plays an important role in the long-term recovery of permanent cerebral ischemic damage and the neuroprotection of ginseng.

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PMID: 

Gastroenterology. 2019 Oct 23. Epub 2019 Oct 23. PMID: 31655031

Abstract Title: 

Western Diet Promotes Intestinal Colonization by Collagenolytic Microbes and Promotes Tumor Formation Following Colorectal Surgery.

Abstract: 

BACKGROUND & AIMS: The western diet, which is high in fat, is a modifiable risk factor for colorectal recurrence after curative resection. We investigated the mechanisms by which the western diet promotes tumor recurrence, including changes in the microbiome, in mice that underwent colorectal resections.METHODS: BALB/c male mice were fed either standard chow diet or western-type diet (characterized by high fat, no fiber, and decreased minerals and vitamins) for 4 weeks; some mice were given antibiotics or ABA-PEG20k-Pi20 (Pi-PEG), which inhibits collagenase production by bacteria but not bacterial growth, in drinking water. Colorectal resections and anastomoses were then performed. The first day after surgery, mice were given enemas containing collagenolytic rodent-derived strain of Enterococcus faecalis (strain E2), and the second day they were given mouse colon carcinoma cells (CT26). Twenty-one days later, distal colons were removed and colon contents (feces, distal colon, and tumor) were collected. Colon tissues were analyzed by histology, for the presence of collagenolytic colonies, and by 16S rRNA sequencing. determined the anatomical distribution of E faecalis at the site of the anastomosis and within tumors using in situ hybridization. Mouse imaging analyses were used to identify metastases.RESULTS: Colorectal tumors were found in 88% of mice fed the western diet and given antibiotics, surgery, and E faecalis compared with only 30% of mice fed the standard diet followed by the same procedures. Colon tumor formation correlated with the presence of collagenolytic E faecalis and Proteus mirabilis. Antibiotics eliminated collagenolytic E faecalis and P mirabilis but did not reduce tumor formation. However, antibiotics promoted emergence of Candida parapsilosis, a collagenase-producing microorganism. Administration of a Pi-PEG reduced tumor formation and maintained diversity of the colon microbiome.CONCLUSIONS: We identified a mechanisms by which diet and antibiotic use can promote tumorigenesis by colon cancer cells at the anastomosis following colorectal surgery. Strategies to prevent emergence of these microbe communities or their enzymatic activities might be used to reduce the risk of tumor recurrence in patients undergoing colorectal cancer surgery.

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PMID: 

Plants (Basel). 2018 Jan 26 ;7(1). Epub 2018 Jan 26. PMID: 29373566

Abstract Title: 

Cistus incanus from Strandja Mountain as a Source of Bioactive Antioxidants.

Abstract: 

The purpose of the present study is to survey the extraction conditions and explore the antioxidant potential of the wild herb, which is non-traditional in Bulgarian ethnomedicine and widespread in the Strandja Mountain. The influence of the extraction time (0-500 min) and solvent composition (0-50% ethanol in water) on the polyphenols, flavonoid yields and on the antioxidant capacity of the extracts of leaves, stalks (wood parts) and bud mixture were studied. The antioxidant capacity (AOC) was evaluated by use of scavenging assays of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals. Total polyphenol and flavonoid contents were quantified using UV-vis (ultraviolet-visible) spectrophotometry. The optimal yield of the desired components was obtained with 30% ethanol in water solvent at the 390th min of extraction time. In addition, the influence of seasonality (winter and summer), and of the different aerial parts-hard-coated seeds, buds, and a mixture of leaves and stalks of the wild plant-on the presence of polyphenols, flavonoids, and AOC were investigated. The present work revealed that the high values of polyphenols, flavonoids and the high AOC occurred not only in the summer leaves, but were also found in the winter leaves, hard-coated seeds, buds, and stalks. Based on the obtained results, thefrom Strandja Mountain could be an excellent new source of natural antioxidants in food and for the pharmaceutical industries.

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PMID: 

Cardiol J. 2019 Mar 26. Epub 2019 Mar 26. PMID: 30912576

Abstract Title: 

The effect of Cistus incanus herbal tea supplementation on oxidative stress markers and lipid profile in healthy adults.

Abstract: 

BACKGROUND: Oxidative stress and dyslipidemia play a critical role in the development of cardiovascular disease. Regular intake of polyphenol-rich diets is associated with a reduced risk of cardiovascular diseases.METHODS: The present study was a pilot study with 24 healthy volunteers and was designed to determine if a 12-week administration of Cistus incanus herbal tea, containing phenolic acids and flavonoids, reduces cardiovascular risk factors including oxidative stress and dyslipidemia in healthy adults. Phenolic compounds profile and antibacterial activity of Cistus incanus infusion were also measured.RESULTS: Herbal infusion led to improvement in lipid profile by increase (D4%, p = 0.033) high-density lipoprotein cholesterol concentration and decrease triglyceride (D14%, p = 0.013) concentrations. In addition, the Cistus incanus diet was associated with decreased serum concentrations of malondialdehyde (D16%, p

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PMID: 

J Tradit Complement Med. 2019 Oct ;9(4):383-392. Epub 2018 Oct 9. PMID: 31453135

Abstract Title: 

Antibacterial and antioxidant effects ofL. extract and its fractions.

Abstract: 

The production of reactive species over physiological levels associated to pathogenic bacteria could represent a high risk for many diseases. TheL. is used around the world due its pharmacological proprieties. So, in this study our aim is to test for the first time ifL. extract (eeRo) and its fractions (DCM, EA, ButOH) could have better or similar antioxidant action to standars and among themselvesorin brain, stomach and liver of rats. Moreover, we intend to clarify their possible effects on pathogenic bacteria. The eeRo was obtained from the dried leaves subjected to an alcoholic extraction and fractioned. The quantification of the constituents of eeRo and fractions were done by HPLC. The antioxidant proprieties ofwas analyzed by DPPHradical scavenging, total antioxidant, dichlorofluorescein, lipid peroxidation and sodium nitroprusside -induced lipid peroxidation assays. The Minimum inhibitory concentrations ofL. were tested with standard strains of danger bacteria. The eeRo, DCM, EA had significant total antioxidant and DPPHradical scavenging activities. The DCM and eeRo got significant effects against basal levels of reactive species in liver, stomach and brain. The eeRo and DCM protected the liver and brain against lipid peroxidation. The eeRo, DCM, EA and ButOH had inhibitory effect in the Gram-positive and Gram-negative bacteria. In general way, the DCM and eeRo had the best antioxidant and antibacterial effects among all tested fractions.

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PMID: 

Food Funct. 2019 Oct 25. Epub 2019 Oct 25. PMID: 31650134

Abstract Title: 

Regulation effects of rosemary (Rosmarinus officinalis Linn.) on hepatic lipid metabolism in OA induced NAFLD rats.

Abstract: 

Rosmarinus officinalis Linn. is a kind of medicinal and edible homologous plant, which is popular in the Mediterranean region with a significant effect on mind tranquilization, anti-oxidation, and metabolic improvement. However, the hypolipidemic effects and mechanism of rosemary ethanol extract (RO) and their metabolites are less known. In this study, the hypolipidemic effects of RO and its active compounds were clarified. The results showed that RO, rosmarinic acid (RA) and carnosic acid (CA) significantly reduced the contents of liver triglyceride (TG), total cholesterol (TC), free fatty acids (FFA) and improved cell hypertrophy, vacuolation, and cell necrosis in the liver of orotic acid induced non-alcoholic fatty liver disease (NAFLD) model rats. The mechanism and related pathways of RO and its main metabolites against lipid disorder were related to the up-regulation of the phosphorylation of adenosine 5'-monophosphate(AMP)-activated protein kinase (AMPK) and the inhibition of the sterol regulatory element binding protein-1c (SREBP-1c) cracking into the nucleus, following the down-regulation of fatty acid synthesis. In conclusion, our study demonstrates that RA and CA are active substances of RO, and provides scientific evidence to support functional food product development for improving NAFLD.

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PMID: 

Drug Des Devel Ther. 2019 ;13:2811-2824. Epub 2019 Aug 13. PMID: 31496657

Abstract Title: 

Piceatannol inhibits oxidative stress through modification of Nrf2-signaling pathway in testes and attenuates spermatogenesis and steroidogenesis in rats exposed to cadmium during adulthood.

Abstract: 

Background: Cadmium (Cd) is considered a heavy metal and potential pollutant to the environment.Purpose: The purpose of this study was to evaluate the protective potential of piceatannol (PT; 10 mg/kg body weight/day) against cadmium (Cd; 5 mg/kg body weight/day)-induced testicular dysfunction in Wistar rats.Materials and methods: Rats were randomly divided into four groups: control, PT, Cd, and Cd + PT.Results: Treatment with Cd resulted in a significant decrease in body, testicular, and epididymal weights, sperm quantity and quality, steroidogenic marker-enzyme activities, mRNA- and protein-expression levels of SF1, StAR, and P450 side chain-cleaving enzyme, and serum male sex hormonal levels when compared to controls. Testicular malondialdehyde levels were significantly increased, with a significant reduction in enzymatic and nonenzymatic antioxidants in Cd-treated rats compared to control rats. Testicular histomorphometric results supported the biochemical and molecular alterations observed in the study. In addition, significant downregulation in mRNA- and protein-expression levels of cytosolic Nrf2, HO1,γGCS, GPx, and NQO1, as well as significant upregulation in mRNA- and protein-expression levels of Nrf2 and Keap1 in testicular tissue, were noticed in rats administered Cd. PT treatment inCd-treated rats caused marked alleviation in body and organ weights, sperm analysis, steroidogenesis, serum hormonal levels, histomorphometric changes, and oxidative and antioxidative status in testes when compared to Cd alone-treated rats. Further, treatment of rats with PTl showed a marked improvement in mRNA- and protein-expression levels of Nrf2 and its regulated genes and proteins.Conclusion: The present study provides compelling evidence that PT treatment results in significant protection against Cd-induced testicular dysfunctions, such as spermatogenesis, steroidogenesis, and oxidative stress in rats, possibly through modification of the Nrf2-Keap1 signalling pathway.

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PMID: 

Curr Comput Aided Drug Des. 2019 Oct 25. Epub 2019 Oct 25. PMID: 31654519

Abstract Title: 

Benefit of passion fruit as an anti-ulcerogenic diet: Scientific evidence by in-vitro and in-silico H+/K+ATPase inhibitory activity assessment.

Abstract: 

BACKGROUND: H+/K+ ATPase a well-known protein present in the parietal cells is a better target for the prevention and treatment of the disease. Flavonoids have been reported to elicit beneficial effect by inhibiting the proton pump as well as by antioxidant mechanism.METHODOLOGY: In this study chloroform fraction of hydro-alcoholic extract of passion fruit was screened for proton pump inhibitory assay using goat parietal cell. Report and conclusion: The flavonoid rich fruit possess a good radical scavenging activity against DPPH. 10.41µg/mL is sufficient to inhibit the 50% activity of the ATPase enzyme of goat parietal cell. A synergistic activity was also achieved by the fruit with sub-effective doses of lansoprazole. Fenton's oxidation was also protected by the fruit induced by H2O2. Including the in-silico findings, the beneficial potency of passion fruit in curing ulcer has been evidenced and perhaps the fruit can be a good dietary supplement for the prevention and its associated complications.

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PMID: 

Eur Oral Res. 2019 Sep ;53(3):99-105. Epub 2019 Sep 1. PMID: 31579889

Abstract Title: 

The effects of morus nigra on the alveolar bone loss in experimentally-induced periodontitis.

Abstract: 

Purpose: The aim of this study is to evalute the anti-inflammatory effects of morus migra on experimentally-induced periodontitis in rats.Materials and methods: Twenty-four Wistar-albino rats were randomly divided into three groups: control group (C, n=8), experimental periodontitis (PER, n=8), experimental periodontitis and treated with Morus nigra (MN+PER, n=8) (50 mg/kg per day for 21 days). After 21 days, the rats were sacrificed, and alveolar bones were evaluated histopathologically and histometrically analyzed to obtain level of alveolar bone loss. The detection of RANKL and OPG were immunohistochemically performed. Serum and tissue levels of MMP-8 and MMP-13 were also analyzed.Results: Morus nigra treatment decreased tissue MMP-8 and MMP-13 levels and there were significant differences in the case of tissue levels of MMP-8 and MMP-13 between groups PER and MN+PER (p=0.035, p=0.041). There were no significant differences among all the groups serum levels of MMP-8 and MMP-13 (p=0.067, p=0.082). In the histometric evaluation, alveolar bone loss was greater in the PER group compared to C and MN groups (p=0.035). Immuno-histochemical staining of RANKL activities were found significantly lower (p=0.037) and OPG activities were found significantly higher in MN+PER group when compared to PER group (p=0.021).Conclusion: The present study reveals that systemic administration of Morus nigra significantly inhibited the regional alveolar bone resorption and contributes to periodontal healing in the rat experimental-periodontitis models.

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