GreenMedInfo

Content Was Refreshed: 20 Aug 2018 | 09:35:56

GreenMedInfo

Fluoroquinolone (FQs) antibiotics are very strong and are, in fact, chemotherapeutic agents in their method of action and adverse event profile. Many times safer antibiotics are available. FQ toxicioty (FQAD) is real. Become an informed patient and know the risks involved.

Posted: August 19, 2018, 11:56 pm

This humble, but immensely powerful seed, kills MRSA, heals the chemical weapon poisoned body, stimulates regeneration of the dying beta cells within the diabetic's pancreas, and yet too few even know it exists.

The seeds of the annual flowering plant, Nigella Sativa, have been prized for their healing properties since time immemorial. While frequently referred to among English-speaking cultures as Roman coriander, black sesame, black cumin, black caraway and onion seed, it is known today primarily as black seed, which is at the very least an accurate description of its physical appearance.

Posted: August 19, 2018, 11:29 pm
PMID:  Thorax. 2018 Aug 13. Epub 2018 Aug 13. PMID: 30104262Abstract Title:  Pro-inflammatory effects of e-cigarette vapour condensate on human alveolar macrophages.Abstract:  OBJECTIVE: Vaping may increase the cytotoxic effects of e-cigarette liquid (ECL). We compared the effect of unvaped ECL to e-cigarette vapour condensate (ECVC) on alveolar macrophage (AM) function.METHODS: AMs were treated with ECVC and nicotine-free ECVC (nfECVC). AM viability, apoptosis, necrosis, cytokine, chemokine and protease release, reactive oxygen species (ROS) release and bacterial phagocytosis were assessed.RESULTS: Macrophage culture with ECL or ECVC resulted in a dose-dependent reduction in cell viability. ECVC was cytotoxic at lower concentrations than ECL and resulted in increased apoptosis and necrosis. nfECVC resulted in less cytotoxicity and apoptosis. Exposure of AMs to a sub-lethal 0.5% ECVC/nfECVC increased ROS production approximately 50-fold and significantly inhibited phagocytosis. Pan and class one isoform phosphoinositide 3 kinase inhibitors partially inhibited the effects of ECVC/nfECVC on macrophage viability and apoptosis. Secretion of interleukin 6, tumour necrosis factorα, CXCL-8, monocyte chemoattractant protein 1 and matrix metalloproteinase 9 was significantly increased following ECVC challenge. Treatment with the anti-oxidant N-acetyl-cysteine (NAC) ameliorated the cytotoxic effects of ECVC/nfECVC to levels not significantly different from baseline and restored phagocytic function.CONCLUSIONS: ECVC is significantly more toxic to AMs than non-vaped ECL. Excessive production of ROS, inflammatory cytokines and chemokines induced by e-cigarette vapour may induce an inflammatory state in AMs within the lung that is partly dependent on nicotine. Inhibition of phagocytosis also suggests users may suffer from impaired bacterial clearance. While further research is needed to fully understand the effects of e-cigarette exposure in humans in vivo, we caution against the widely held opinion that e-cigarettes are safe.

read more

Posted: August 18, 2018, 10:12 pm
PMID:  Am J Physiol Lung Cell Mol Physiol. 2018 Aug 9. Epub 2018 Aug 9. PMID: 30091379Abstract Title:  Comparison of the effects of e-cigarette vapor with cigarette smoke on lung function and inflammation in mice.Abstract:  Electronic cigarettes (e-cig) are advertised as a less harmful nicotine delivery system or as a new smoking cessation tool. We aimed to assess the in vivo effects of e-cigarette vapor in the lung and to compare them to those of cigarette smoke (CS). We exposed C57BL/6 mice for either 3 days or 4 weeks to ambient air, CS or e-cig vapor containing: i) propylene glycol/vegetable glycerol (1:1; PG:VG-Sol), ii) PG:VG with nicotine (G:VG-N), or iii) PG:VG with nicotine and flavor (PG:VG- N+F) and determined oxidative stress, inflammation and pulmonary mechanics. E-cig vapors, especially PG:VG- N+F, increased bronchoalveolar lavage fluid (BALF) cellularity, Muc5ac production, as well as BALF and lung oxidative stress markers at least comparably and in many cases more than CS. BALF protein content at both time points studied was only elevated in the PG:VG- N+F group. After 3 days, PG:VG-Sol altered tissue elasticity, static compliance and airway resistance, while after 4 weeks, CS was the only treatment adversely affecting these parameters. Airway hyperresponsiveness in response to methacholine was increased similarly in the CS and PGVG-N+F groups. Our findings suggest that exposure to e-cig vapor can trigger inflammatory responses and adversely affect respiratory system mechanics. In many cases, the added flavor in e-cigs exacerbated the detrimental effects of e-cig vapor. We conclude that both e-cig vaping and conventional cigarette smoking negatively impact lung biology.

read more

Posted: August 18, 2018, 10:04 pm
PMID:  Am J Respir Cell Mol Biol. 2018 03 ;58(3):366-377. PMID: 28960086Abstract Title:  Maternal E-Cigarette Exposure in Mice Alters DNA Methylation and Lung Cytokine Expression in Offspring.Abstract:  E-cigarette usage is increasing, especially among the young, with both the general population and physicians perceiving them as a safe alternative to tobacco smoking. Worryingly, e-cigarettes are commonly used by pregnant women. As nicotine is known to adversely affect children in utero, we hypothesized that nicotine delivered via e-cigarettes would negatively affect lung development. To test this, we developed a mouse model of maternal e-vapor (nicotine and nicotine-free) exposure and investigated the impact on the growth and lung inflammation in both offspring and mothers. Female Balb/c mice were exposed to e-fluid vapor containing nicotine (18 mg/ml nicotine E-cigarette [E-cig18], equivalent to two cigarettes per treatment, twice daily,) or nicotine free (E-cig0 mg/ml) from 6 weeks before mating until pups weaned. Male offspring were studied at Postnatal Day (P) 1, P20, and at 13 weeks. The mothers were studied when the pups weaned. In the mothers' lungs, e-cigarette exposure with and without nicotine increased the proinflammatory cytokines IL-1β, IL-6, and TNF-α. In adult offspring, TNF-α protein levels were increased in both E-cig18 and E-cig0 groups, whereas IL-1β was suppressed. This was accompanied by global changes in DNA methylation. In this study, we found that e-cigarette exposure during pregnancy adversely affected maternal and offspring lung health. As this occurred with both nicotine-free and nicotine-containing e-vapor, the effects are likely due to by-products of vaporization rather than nicotine.

read more

Posted: August 18, 2018, 9:58 pm
PMID:  Int J Mol Med. 2017 Dec ;40(6):1881-1888. Epub 2017 Sep 28. PMID: 29039443Abstract Title:  Grape seed proanthocyanidins inhibit the proliferation, migration and invasion of tongue squamous cell carcinoma cells through suppressing the protein kinase B/nuclear factor-κB signaling pathway.Abstract:  Tongue squamous cell carcinoma (TSCC) is the most common oral squamous cell carcinoma. Despite significant advances in combined therapies, the 5-year survival rate of patients with TSCC has not notably improved; this is due to regional recurrences and lymph node metastasis. Grape seed proanthocyanidins (GSPs) are consumed as dietary supplements worldwide and possess anticancer activity against several different types of cancer. However, their effect on TSCC and the underlying mechanisms by which they function remain unclear. In the present study, it was identified that GSPs significantly inhibited the viability and induced the apoptosis of Tca8113 cells in a dose-dependent manner. This was associated with a significantly increased expression of the pro-apoptosis regulator BAX protein and a significantly decreased expression of the anti-apoptosis regulator Bcl-2 protein at 100 µg/ml GSPs. In addition, at non-toxic concentrations GSPs significantly inhibited the secretion of matrix metalloproteinase-2 (MMP-2) and MMP-9 from Tca8113 cells, as well as their migration and invasion. Furthermore, it was demonstrated that GSPs significantly inhibited the phosphorylation of protein kinase B (Akt) and IκB kinase, as well as the translocation of nuclear factor-κB (NF-κB) into the nucleus of Tca8113 cells. Taken together, these results suggest that GSPs inhibit the proliferation, migration and invasion of Tca8113 cells through suppression of the Akt/NF-κB signaling pathway. This indicates that GSPs may be developed as a novel potential chemopreventive agent against TSCC.

read more

Posted: August 18, 2018, 9:45 pm
PMID:  Mol Med Rep. 2017 Dec ;16(6):9189-9196. Epub 2017 Oct 10. PMID: 29039545Abstract Title:  Grape seed proanthocyanidins protect cardiomyocytes against hypoxia/reoxygenation injury by attenuating endoplasmic reticulum stress through PERK/eIF2α pathway.Abstract:  The aim of the present study was to observe the protective effect of grape seed proanthocyanidins (GSPs) against endoplasmic reticulum (ER) stress‑mediated apoptosis caused by hypoxia/reoxygenation (H/R) injury in H9C2 cardiomyocytes along with its potential mechanisms. H9C2 cardiomyocytes underwent hypoxia for 3 h followed by reoxygenation for 3 h. Different doses of GSPs (50, 100 and 200 µg/ml) were administered 30 min before hypoxia. Cell viability was assessed, as well as lactic dehydrogenase (LDH) activity, cell apoptosis rate, expression levels of glucose‑regulated protein 78 (GRP78), C/EBP‑homologous protein (CHOP), protein kinase RNA‑like ER kinase (PERK), and eukaryotic translation initiation factor‑2 (eIF2α) mRNA and protein. The results revealed that GSPs improved cell viability, reduced LDH activity and reduced the apoptosis rate in cells subjected to H/R, and that the protective effect was most significant when 100 µg/ml in GSPs was administered. GSPs treatment also decreased mRNA and protein expression of GRP78, CHOP, eIF2α and the level of the phosphorylated form of PERK. Furthermore, GSPs displayed a similar protective effect to that of established ER stress inhibitor 4‑phenyl butyric acid. In conclusion, the findings of this study suggest that GSPs may protect H9C2 cardiomyocytes from H/R injury by decreasing ER stress‑mediated apoptosis through the suppression of the PERK/eIF2α signaling pathway.

read more

Posted: August 18, 2018, 9:39 pm
PMID:  Toxics. 2017 Apr 11 ;5(2). Epub 2017 Apr 11. PMID: 29051443Abstract Title:  Vitis vinifera Extract Ameliorate Hepatic and Renal Dysfunction Induced by Dexamethasone in Albino Rats.Abstract:  This study was conducted to evaluate the biochemical effects of grape seed extract against dexamethasone-induced hepatic and renal dysfunction in a female albino rat. Twenty-eight adult female rats were divided randomly into four equal groups: Group 1: animals were injected subcutaneously with saline and consider as normal control one. Group 2: animals were injected subcutaneously with dexamethasone in a dose of 0.1 mg/kg body weight. Group 3: animals were injected subcutaneously with 0.1 mg/kg body weight of dexamethasone, and then treated with a grape seed extract in a dose of 200 mg/kg body weight by oral gavage. Group 4: animals were injected subcutaneously with 0.1 mg/kg body weight of dexamethasone, and then treated with a grape seed extract in a dose of 400 mg/kg body weight by oral gavage. After 4 weeks, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) activities, albumin, uric acid, creatinine, and glucose levels were assayed. Hepatic reduced glutathione (GSH), total protein content, and catalase and glucose-6-phosphate dehydrogenase activities were also assayed. Dexamethasone administration caused elevation of serum levels of glucose, uric acid, creatinine, ALT, AST activities, and a decrease in other parameters such as hepatic glutathione, total protein levels, and catalase enzyme activity. Treatment withL. seed extract showed a significant increase in the body weight of rats in the group treated withL. seed extract orally compared with the dexamethasone control group. An increase in GSH and catalase activity in response to oral treatment withL. seed extract was observed after treatment. Grape seed extract positively affects glucocorticoid-induced hepatic and renal alteration in albino rats.

read more

Posted: August 18, 2018, 9:18 pm
PMID:  Mol Med Rep. 2017 Dec ;16(6):9393-9400. Epub 2017 Oct 19. PMID: 29152654Abstract Title:  Nephrin loss is reduced by grape seed proanthocyanidins in the experimental diabetic nephropathy rat model.Abstract:  Diabetic nephropathy (DN) is one of the major causes of end‑stage renal failure. Grape seed proanthocyanidin extracts (GSPE) are known to act as antioxidants. The current study aimed to determine the effects of GSPE on the streptozotocin (STZ)‑induced diabetic rat model and to explore the underlying mechanism of its action. Wistar rats were induced intoa diabetic state by injection of STZ and were treated with 250 mg·kg‑1·day‑1 GSPE for 24 weeks. Kidney samples were collected for observation of renal pathological changes by light microscope (periodic acid‑Schiff staining) and electron microscopy. Reverse transcription‑polymerase chainreaction, western blotting, and immunohistochemical staining were used to detect the mRNA and protein expression of the receptor for advanced glycation end‑products (RAGE), nephrin and podocin. The results indicated that diabetic rats treated with GSPE had markedly reduced Ccr, urinary albumin excretion, ratio of kidney weight to body weight, AGEs and ECM accumulation (P

read more

Posted: August 18, 2018, 9:05 pm
PMID:  Exp Gerontol. 2018 Jan ;101:101-112. Epub 2017 Nov 22. PMID: 29174497Abstract Title:  Antioxidant action of grape seed polyphenols and aerobic exercise in improving neuronal number in the hippocampus is associated with decrease in lipid peroxidation and hydrogen peroxide in adult and middle-aged rats.Abstract:  The present study explored the effects of swimming training and grape seed proanthocyanidin extract (GSPE) on neuronal survival in the hippocampus (HC) of middle-aged rats along with oxidative stress (OS) parameters. Further, the bioavailability of the GSPE, catechin, epicatechin and gallic acid were measured in the HC and plasma. Male Wistar rats were grouped into: sedentary control, SE-C; swimming trained, SW-T; SE-C, supplemented sedentary, SE-C(PA) and swimming trainees, SW-T(PA). The supplement was a daily dose of 400mg GSPE/kg body weight. Swimming training lasted for 2h/day and for 14weeks. Glutathione level was increased in response to single and combined interventions in the middle-aged rats. Adult trainees showed increased glutathione peroxidase activity unlike middle-aged wherein increase was seen in SE-C(PA) alone. Lowered catalase activity with age in the HC increased in response to the combined interventions although single interventions were also effective. HC from both ages showed decrease in lipid peroxidation and hydrogen peroxide levels in response to the interventions. GSPE constituents were seen in the HC of swimming trained middle-aged and adult rats. The study suggests that combined intervention is effective in decreasing LPO and HOgeneration in the HC. Further, the neuronal numbers and planimetric volumes of CA1 pyramidal layer was significantly reduced in middle-aged rats compared to adults. Interestingly, both interventions enhanced the numbers and volumes in adult and middle-aged rats. Thus, age-associated decrease in CA1 neurons could be restored by both the interventions. The results of the present study will help in developing effective therapies for age-associated degenerative changes and cognitive deficits.

read more

Posted: August 18, 2018, 8:53 pm
PMID:  J Nutr Biochem. 2018 Feb ;52:115-123. Epub 2017 Oct 12. PMID: 29175668Abstract Title:  Grape seed procyanidin extract ameliorates lead-induced liver injury via miRNA153 and AKT/GSK-3β/Fyn-mediated Nrf2 activation.Abstract:  Lead-induced hepatotoxicity is characterized by an extensive oxidative stress. Grape seed procyanidin extract (GSPE) possesses abundant biological activities. Herein, we investigated the protective role of GSPE against lead-induced liver injury and determined the potential molecular mechanisms. In vivo, rats were treated with/without lead acetate (PbAc) (0.05%, w/v) in the presence/absence of GSPE (200 mg/kg). In vitro, hepatocytes were pretreated with/without GSPE (100μg/ml) in the presence/absence of PbAc (100 μM). PbAc administration to rats resulted in anemia, liver dysfunction, lead accumulation in the bone and liver, oxidative stress, DNA damage and apoptosis. GSPE significantly attenuated these adverse effects, except lead accumulation in liver. GSPE alsodecreased the expression of miRNA153 and increased the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and levels of its downstream protein, and protein kinase B (AKT) phosphorylation in PbAc-induced liver injury. In primary hepatocytes treated with PbAc, GSPE increased hepatocyte viability and decreased lactate dehydrogenase release and reactive oxygen species levels. Dietary GSPE attenuated PbAc-induced liver injury in rats via an integrated mechanism associated with the miRNA153 and AKT/glycogen synthase kinase 3 beta/Fyn-mediated Nrf2 activation.

read more

Posted: August 18, 2018, 8:37 pm
PMID:  J Investig Clin Dent. 2018 May ;9(2):e12318. Epub 2018 Jan 18. PMID: 29349878Abstract Title:  Efficacy of grape seed extract gel in the treatment of chronic periodontitis: A randomized clinical study.Abstract:  AIM: The aim of the present study was to assess the effectiveness of applying grape seed extract (GSE) gel in periodontal pockets for the treatment of chronic periodontitis.METHODS: Eighty-six sites with pocket depth (PD)>4 mm were selected from five systemically-healthy patients in whom scaling, and root planing were performed, and oral instructions were given, a week earlier. PD, gingival index (GI), plaque index (PI), and bleeding on probing (BOP) were measured, and sites were then divided into the control group (N = 38) and GSE group (N = 48). Four doses of formulated 2% mucoadhesive GSE gel were applied to GSE group sites at baseline visit (T0), and 3, 6, and 9 days after T0. Similarly, a control gel was applied to the control sites. PD, PI, GI and BOP were re-evaluated after 4 weeks and 6 months offirst gel application.RESULTS: Paired t test for both the control and GSE groups showed a significant reduction for all variables after 6 months of gel application (P 

read more

Posted: August 18, 2018, 8:05 pm
PMID:  Int J Oncol. 2018 Jan ;52(1):127-138. Epub 2017 Nov 1. PMID: 29115601Abstract Title:  Ginsenoside Rg3 targets cancer stem cells and tumor angiogenesis to inhibit colorectal cancer progression in vivo.Abstract:  Anti-angiogenic therapy has been successfully applied to treat colorectal cancer (CRC). Ginsenoside Rg3, derived from the Chinese herb ginseng, has anti-vascularization effects and can inhibit tumor growth and metastasis, and can sensitize cancer cells to chemotherapy. Therefore, in the present study, we investigated whether Rg3 could be appropriate for CRC treatment. Growth of CRC cells was assessed by an MTT (methyl thiazolyl tetrazolium) assay in vitro and using orthotopic xenograft models in vivo. mRNA expression was evaluated using real-time PCR. Protein levels were tested by western blotting, flow cytometry and immunohistochemistry. Migration was determined using a wound-healing assay. Stemness was further confirmed using a plate cloneformation assay. We found that Rg3 repressed the growth and stemness of CRC cells both in vitro and in vivo. Rg3 also impaired the migration of CRC cells in vitro. Rg3 downregulated the expressions of angiogenesis-related genes, and repressed the vascularization of CRC xenografts. In addition, Rg3 strengthened the cytotoxicity of 5-Fluorouracil and oxaliplatin against orthotopic xenografts in vivo. Moreover, Rg3 downregulated the expressions of B7-H1 and B7-H3, high expressions of which were associated with reduced overall survival (OS) of CRC patients. Hence, Rg3 not only repressed the growth and stemness of CRC cells, but could also remodel the tumor microenvironment through repressing angiogenesis and promoting antitumor immunity. Therefore, Rg3 could be a novel therapeutic for the CRC treatment.

read more

Posted: August 18, 2018, 9:04 am
PMID:  Biomed Pharmacother. 2018 Jan ;97:1282-1288. Epub 2017 Dec 14. PMID: 29156516Abstract Title:  Synergistic anticancer activity of 20(S)-Ginsenoside Rg3 and Sorafenib in hepatocellular carcinoma by modulating PTEN/Akt signaling pathway.Abstract:  Sorafenib, a multikinase inhibitor for hepatocellular carcinoma treatment, inhibits the Raf/MAPK/ERK signaling pathway. However, PI3K/Akt signaling pathway is activated by Sorafenib and cross-talks with the Raf/MAPK/ERK signaling pathway, leading to drug resistance. 20(S)-Ginsenoside Rg3 has been reported with significant anticancer effect to numerous carcinomas by inhibition of PI3K-Akt signaling pathway. Hence, we aim to examine the synergistic anticancer activity of 20(S)-Ginsenoside Rg3 and Sorafenib via modulation of PTEN/Akt signaling pathway. Human hepatocellular carcinoma cell lines HepG2 and Huh7 were used. Cell viability, clonogenic assay, apoptosis assay, western blot analysis, xenograft treatment and immunohistochemistry were carried out. The viability of hepatocellular carcinoma cells significantly decreased by the treatment of Sorafenib combined with 20(S)-Ginsenoside Rg3, as well as the enhanced apoptotic rates. The levels of PTEN, Bax and cleaved caspase-3 expression increased, while the levels of phospho-PDK1 and phospho-Akt expression decreased by the treatment of Sorafenib combined with 20(S)-Ginsenoside Rg3. In vivo, the tumor volumes and weight decreased in the Sorafenib combined with 20(S)-Ginsenoside Rg3 group. The results demonstrated the synergistic anticancer activity of 20(S)-Ginsenoside Rg3 and Sorafenib in HCC by modulating PTEN/Akt signaling pathway. These findings suggest a promising strategy for HCC treatment, which could be performed in a sufficiently frequent manner.

read more

Posted: August 18, 2018, 8:00 am
PMID:  Biomed Pharmacother. 2017 Dec ;96:1240-1245. Epub 2017 Nov 21. PMID: 29169725Abstract Title:  Ginsenoside Rg3 inhibits colorectal tumor growth via down-regulation of C/EBPβ/NF-κB signaling.Abstract:  Colorectal cancer (CRC), the third most frequent occurred cancer, is associated with high mortality and extremely poor prognosis. Ginsenoside Rg3 (Rg3), one of the pharmacologically active components of traditional Chinese herbal medicine Panax ginseng, exerts antitumor effects against several types of cancer growth, including colorectal cancer. However, the detailed molecular mechanisms and particularly the signaling pathways that are decisive in this process are not yet fully elucidated. The present study was carried out to determine the antitumor effects of Rg3 using human colorectal cells in vitro and Xenograft tumor model of human colon cancer in vivo. We found that Rg3 effectively suppressed the proliferation of cancer cells in three human colorectal cancer cell lines (HCT116, HT29, SW480). In addition, intraperitoneal injection of Rg3 for 3 weeks significantly inhibited the growth of xenografts in nude mice. Furthermore, we determined the potential underlying mechanisms for these actions. Treatment with Rg3 significantly inhibited the transactivation of C/EBPβ and NF-κB, as well as the association of C/EBPβ with p65-NFκB in nucleus. However, when SW-480 cells were co-transfected with C/EBPβ, or pretreatment with TNFα, Rg3 failed to inhibit tumor growth. Taken together, our results revealed a robust anti-tumor effect of Rg3, which is mediated by inhibition of C/EBPβ/NF-κB signaling.

read more

Posted: August 18, 2018, 7:55 am
PMID:  Cancer Lett. 2018 Feb 28 ;415:73-85. Epub 2017 Dec 2. PMID: 29199005Abstract Title:  Ginsenoside Rg3 sensitizes hypoxic lung cancer cells to cisplatin via blocking of NF-κB mediated epithelial-mesenchymal transition and stemness.Abstract:  Cisplatin is a first line chemotherapy in lung cancer, but decreased susceptibility may limit its application. In solid tumors, hypoxia alters the microenvironment and is associated with proliferation, metastasis, and drug sensitivity. The hypoxia-induced desensitization of cisplatin is not clearly elucidated. 20 (R)-Ginsenoside (Rg3), the traditional Chinese medicine, is extracted from ginseng and has antitumor activities. In this study, we evaluated if Rg3 is effective in improving cisplatin sensitivity by blocking hypoxia. We found that the inhibition of proliferation potential by cisplatin was reduced in cobalt chloride (CoCl)-induced hypoxia in lung cancer cells. Hypoxia caused alterations in epithelial-mesenchymal transition (EMT), which were detected by cellular morphology and EMT protein markers, and in stemness analyzed by spheroid formation and marker molecules. Hypoxia also activated EMT, which was mediated by the nuclear factorκB (NF-κB) pathway, and stemness, and Rg3 inhibited the activation of the NF-κB pathway. Furthermore, Rg3 could increase the sensitivity to cisplatin by inhibiting EMT and stemness in hypoxic lung cancer cells, and this effect was confirmed in vivo. In conclusion, Rg3 may improve the sensitivityof cisplatin in lung cancer therapy.

read more

Posted: August 18, 2018, 7:48 am
PMID:  Cells. 2018 Jul 21 ;7(7). Epub 2018 Jul 21. PMID: 30037060Abstract Title:  The Purified Extract from the Medicinal Plant, Bacopaside II, Inhibits Growth of Colon Cancer Cells In Vitro by Inducing Cell Cycle Arrest and Apoptosis.Abstract:  Aquaporin-1 (AQP1), a transmembrane pore-forming molecule, facilitates the rapid movement of water and small solutes across cell membranes. We have previously shown that bacopaside II, an extract from the medicinal herb, blocks the AQP1 water channel and impairs migration of cells that express AQP1. The aim of this study was to further elucidate the anti-tumour potential of bacopaside II in colon cancer cells. Expression of AQP1 in HT-29, SW480, SW620 and HCT116 was determined by quantitative PCR and western immunoblot. Cells were treated with bacopaside II, and morphology, growth, autophagy, cell cycle and apoptosis assessed by time-lapse microscopy, crystal violet, acridine orange, propidium iodide (PI) and annexin V/PI staining respectively. AQP1 expression was significantly higher in HT-29 than SW480, SW620 and HCT116. Bacopaside II significantly reduced growth at≥20 µM for HT-29 and ≥15 µM for SW480, SW620 and HCT116. Inhibition of HT-29 at 20 µM was primarily mediated by G0/G1 cell cycle arrest, and at 30 µM by G2/M arrest and apoptosis. Inhibition of SW480, SW620 and HCT116 at ≥15 µM was mediated by G2/M arrest and apoptosis. These results arethe first to show that bacopaside II inhibits colon cancer cell growth by inducing cell cycle arrest and apoptosis.

read more

Posted: August 18, 2018, 7:36 am
PMID:  Environ Toxicol. 2018 Jul 2. Epub 2018 Jul 2. PMID: 29964319Abstract Title:  Hepatoprotective effect of ginsenoside Rg1 from Panax ginseng on carbon tetrachloride-induced acute liver injury by activating Nrf2 signaling pathway in mice.Abstract:  Oxidative stress and inflammatory response are well known to be involved in the pathogenesis of acute liver injury. This study was performed to examine the hepatoprotective effect of ginsenoside Rg1 (Rg1) against CCl-induced acute liver injury, and further to elucidate the involvement of Nrf2 signaling pathway in vivo and in vitro. Mice were orally administered Rg1 (15, 30, and 60 mg/kg) or sulforaphane (SFN) once daily for 1 week prior to 750 μL/kg CClinjection. The results showed that Rg1 markedly altered relative liver weights, promoted liver repair, increased the serum level of TP and decreased the serum levels of ALT, AST and ALP. Hepatic oxidative stress was inhibited by Rg1, as evidenced by the decrease in MDA, and increases in GSH, SOD, and CAT in the liver. Further research demonstrated that Rg1 suppressed liver inflammation response through repressing the expression levels of inflammation-related genes including TNF-α, IL-1β, IL-6, COX-2, and iNOS. In addition, Rg1 enhanced antioxidative stress and liver detoxification abilities by up-regulating Nrf2 and its target-genes such as GCLC, GCLM, HO-1, NQO1, Besp, Mrp2, Mrp3, Mrp4, and down-regulating Cyp2e1. However, the changes in Nrf2 target-genes, as well as ameliorative liver histology induced by Rg1 were abrogated by Nrf2 antagonist all-transretinoic acid in vivo and Nrf2 siRNA in vitro. Overall, the findings indicated that Rg1 might be an effective approach for the prevention against acute liver injury by activating Nrf2 signaling pathway.

read more

Posted: August 18, 2018, 7:30 am
PMID:  J Microbiol Biotechnol. 2018 Mar 28 ;28(3):391-396. PMID: 29316736Abstract Title:  Ginsenoside-Rb2 and 20(S)-Ginsenoside-Rg3 from Korean Red Ginseng Prevent Rotavirus Infection in Newborn Mice.Abstract:  It is well known that Korean red ginseng has various biological activities. However, there is little knowledge about the antiviral activity of Korean red ginseng and its ginsenosides. In this study, we addressed whether oral administration of ginsenoside-Rb2 and -Rg3 is able to protect against rotavirus (RV) infection. The protective effect of ginsenosides against RV infection was examined using an in vivo experiment model in which newborn mice (10-day-old) were inoculated perorally (p.o.) with 1.5× 10plaque-forming units/mouse of RV strain SA11. When various dosages of ginsenoside-Rb2 (25-250 mg/kg) were administered 3days, 2 days, or 1 day before virus challenge, treatment with this ginsenoside at the dosage of 75 mg/kg 3days before virus infection most effectively reduced RV-induced diarrhea. In addition, consecutive administration of ginsenoside-Rb2 (75 mg/kg) at 3 days, 2 days, and 1 day before virus infection was more effective than single administration on day -3. The consecutive administration of ginsenoside-Rb2 also reduced virus titers in the bowels of RV-infected mice. In an experiment to compare the protective activity between ginsenoside-Rb2 and its two hydrolytic products (20(S)- and 20(R)-ginsenoside-Rg3), 20(S)-ginsenoside-Rg3, but not 20(R)-ginsenoside-Rg3, prevented RV infection. These results suggest that ginsenoside-Rb2 and its hydrolytic product, 20(S)-ginsenoside-Rg3, are promising candidates as an antiviral agent to protect against RV infection.

read more

Posted: August 18, 2018, 6:45 am
PMID:  Oncol Lett. 2018 Mar ;15(3):2889-2898. Epub 2017 Dec 19. PMID: 29435015Abstract Title:  Phosphoproteomic analysis of the antitumor effects of ginsenoside Rg3 in human breast cancer cells.Abstract:  The incidence of breast cancer has been increasing in China and the age of breast cancer onset is earlier compared with Western countries. Compounds commonly used in Traditional Chinese Medicine (TCM) are an important source of anticancer drugs. Ginseng is one of the most common medicines used in TCM. Ginsenosides, which are saponins found in the ginseng plant, are the major active components responsible for the chemopreventive effects of ginseng in cancer. However, the mechanisms by which ginsenosides exert their anticancer effects remain elusive. The current study combined tandem mass tag (TMT)-based quantification with titanium dioxide-based phosphopeptide enrichment to quantitatively analyze the changes in phosphoproteomes in breast cancer MDA-MB-231 cells that occur following treatment with the ginsenoside Rg3. A total of 5,140 phosphorylation sites on 2,041 phosphoproteins were quantified and it was demonstrated that the phosphorylation status of 13 sites were altered in MDA-MB-231 cells following treatment with Rg3. The perturbed phosphoproteins were: Cleavage and polyadenylation specificity factor subunit 7, elongation factor 2 (EEF2), HIRA-interacting protein 3, melanoma-associated antigen D2, myosin phosphatase Rho-interacting protein, probable E3 ubiquitin-protein ligase MYCBP2, PRKC apoptosis WT1 regulator protein, protein phosphatase 1 regulatory subunit 12A, E3 SUMO-protein ligase RanBP2, Septin-9, thymopoietin, and E3 UFM1-protein ligase 1. Western blotting confirmed that Rg3 increased the phosphorylation of EEF2 on Thr57 but did not alter the protein expression of EEF2 in MDA-MB-231 and HCC1143 cells. These ginsenoside Rg3-regulated proteins are involved in various biological processes, including protein synthesis, cell division and the inhibition of nuclear factor-κB signaling. The results of the present study revealed that Rg3 exerts its anticancer effects via a combination of different signaling pathways.

read more

Posted: August 18, 2018, 6:35 am
PMID:  J Ginseng Res. 2018 Jul ;42(3):352-355. Epub 2017 Apr 24. PMID: 29983617Abstract Title:  Alleviation of diabetic complications by ginsenoside Rg3-enriched red ginseng extract in western diet-fed LDLmice.Abstract:  In this study, we precisely showed how the Rg3-enriched red ginseng extract (Rg3-RGE) lowers glucose, triglyceride, and low-density lipoprotein (LDL) levels in LDLmice. Aspartate aminotransferase/serum glutamic-oxaloacetic transaminase), alanine aminotransferase /serum glutamate-pyruvate transaminase, and steatohepatitis were found to be reduced, and atheroma formation was inhibited by Rg3-enriched red ginseng extract.

read more

Posted: August 18, 2018, 6:27 am
PMID:  Regul Toxicol Pharmacol. 2018 Jul 17 ;98:58-68. Epub 2018 Jul 17. PMID: 30030101Abstract Title:  Ginsenoside Rg1 protects against acetaminophen-induced liver injury via activating Nrf2 signaling pathway in vivo and in vitro.Abstract:  Acetaminophen (APAP) is a worldwide used drug for treating fever and pain. However, APAP overdose is the leading cause of drug-induced liver injury. The purpose of the current study is to evaluate the hepatoprotective effect of ginsenoside Rg1 (Rg1), the main pharmacologically active compounds of Panax ginseng, against APAP-induced acute liver injury, and further to elucidate the involvement of Nrf2 signaling pathway by in vivo and in vitro experiments. Male C57BL/6 mice were treated with Rg1 for 3 days before injection of APAP. Serum and liver tissue samples were collected 6 h later. The results indicated that Rg1 significantly attenuated APAP-induced hepatotoxicity and oxidative stress in a dose-dependent manner. Rg1 effectively enhanced antioxidant and detoxification capacity, which is largely dependent on up-regulating Nrf2 nuclear translocation, reducing Keap1 protein expression and up-regulating Nrf2 target genes including GCLC, GCLM, HO-1, NQO1, Ugt1a1, Ugt1a6, Ugt2b1, Sult2a1, Mrp2, Mrp3 and Mrp4. Furthermore, Rg1 repressed the activities of Cyp2e1, Cyp3a11, Cyp1a2, which are important enzymes in the formation of APAP toxic metabolite N-acetyl-p-benzoquinone imine. However, the changes in transporters and enzymes, as well as ameliorative liver histology induced by Rg1 were abrogated by Nrf2 antagonist all-transretinoic acid in vivo and Nrf2 siRNA in vitro. In conclusion, Rg1 produced hepatoprotective effects against APAP-induced acute liver injuryvia Nrf2 signaling pathway. Rg1 might be an effective approach for the prevention against acute liver injury.

read more

Posted: August 18, 2018, 6:15 am
PMID:  Sci Rep. 2018 Aug 14 ;8(1):12154. Epub 2018 Aug 14. PMID: 30108263Abstract Title:  Gingerol suppresses sepsis-induced acute kidney injury by modulating methylsulfonylmethane and dimethylamine production.Abstract:  Acute kidney injury (AKI) and metabolic dysfunction are critical complications in sepsis syndrome; however, their pathophysiological mechanisms remain poorly understood. Therefore, we evaluated whether the pharmacological properties of 6-gingerol (6G) and 10-gingerol (10G) could modulate AKI and metabolic disruption in a rat model of sepsis (faecal peritonitis). Animals from the sham and AKI groups were intraperitoneally injected with 6G or 10G (25 mg/kg). Septic AKI decreased creatinine clearance and renal antioxidant activity, but enhanced oxidative stress and the renal mRNA levels of tumour necrosis factor-α, interleukin-1β, and transforming growth factor-β. Both phenol compounds repaired kidney function through antioxidant activity related to decreased oxidative/nitrosative stress and proinflammatory cytokines. Metabolomics analysis indicated different metabolic profiles for the sham surgery group, caecal ligation and puncture model alone group, and sepsis groups treated with gingerols.H nuclear magnetic resonance analysis detected important increases in urinary creatine, allantoin, and dimethylglycine levels in septic rats. However, dimethylamine and methylsulfonylmethane metabolites were more frequently detected in septic animals treated with 6G or 10G, and were associated with increased survival of septic animals. Gingerols attenuated septic AKI by decreasing renal disturbances, oxidative stress, and inflammatory response through a mechanism possibly correlated with increased production of dimethylamine and methylsulfonylmethane.

read more

Posted: August 18, 2018, 6:02 am
PMID:  J Biochem Mol Toxicol. 2018 Aug 8:e22206. Epub 2018 Aug 8. PMID: 30091159Abstract Title:  [6]-Gingerol-induced cell cycle arrest, reactive oxygen species generation, and disruption of mitochondrial membrane potential are associated with apoptosis in human gastric cancer (AGS) cells.Abstract:  Ginger (Zingiber officinale Roscoe), a monocotyledonous herb, is widely used as an herbal medicine owing to the phytoconstituents it possesses. In the current study, the quantity of [6]-gingerol, the major phenolic ketone, in the fresh ginger and dried ginger rhizome was found to be 6.11 µg/mg and 0.407 µg/mg. Furthermore, [6]-gingerol was assessed for its antiapoptotic effects in human gastric adenocarcinoma (AGS) cells evidenced by acridine orange/ethidium bromide staining technique and Annexin-V assay. An increase in reactive oxygen species (ROS) generation led to a decrease in mitochondrial membrane potential (MMP) and subsequent induction of apoptosis. Results disclose that perturbations in MMP are associated with deregulation of Bax/Bcl-2 ratio at protein level, which leads to upregulation of cytochrome-c triggering the caspase cascade. These enduringly suggest that [6]-gingerol can be effectively used for targeting the mitochondrial energy metabolism to manage gastric cancer cells.

read more

Posted: August 18, 2018, 5:49 am
PMID:  Sci Rep. 2018 Jan 19 ;8(1):1270. Epub 2018 Jan 19. PMID: 29352129Abstract Title:  Molecular characterization of the grape seeds extract's effect against chemically induced liver cancer: In vivo and in vitro analyses.Abstract:  The purpose of this study was to investigate the anti-cancer property of grape seed extract (GSE) during early stages of developing liver cancer using a two-stage carcinogenic model combining diethylnitrosamine (DEN) and 2-Acetyl Aminofluorene (2-AAF). Administration of GSE at doses 25, 50 and 100 mg/kg per day started at the beginning of promotion periods and continued for 14 weeks. GSE dramatically inhibited pre-neoplastic foci formation as well as significantly decreased the number and the area of placental glutathione-S-transferase in livers of DEN-2AAF-treated rats by approximately 4&10 fold deductions, respectively. GSE's effects were associated with induced apoptosis, reduced cell proliferation, decreased oxidative stress and down regulation of histone deacetylase activity and inflammation makers, such as cyclooxygenase 2, inducible nitric oxide synthase, nuclear factor-kappa B-p65 and p- phosphorylated tumor necrosis factor receptor expressions in liver. GSE treatment also decreased the viability of HepG2 cells and induced early and late apoptosis through activating caspase-3 and Bax. Furthermore, GSE induced G2/M and G1/S cell cycle arrest. The present study provides evidence that the GSE's anticancer effect is mediated through the inhibition of cell proliferation, induction of apoptosis, modulating oxidative damage and suppressing inflammatory response.

read more

Posted: August 18, 2018, 5:31 am
Content Was Refreshed: 20 Aug 2018 | 09:35:57
Last Modified: April 28, 2018