PMID: 

Nutr Cancer. 2019 Oct 11:1-16. Epub 2019 Oct 11. PMID: 31604383

Abstract Title: 

Vanillin extracted from Proso and Barnyard millets induce apoptotic cell death in HT-29 human colon cancer cell line.

Abstract: 

In the present study, we hypothesized that the active compound extracted from Proso and Barnyard millets inhibits cell proliferation and apoptosis induction in colon cancer cell line. The bioactive compounds from these millets were purified by supercritical fluid extraction and their structure was elucidated using spectroscopic methods. Extracted bioactive components from these millets were similar in chemical structure to the phenolic aldehyde-Vanillin [4-Hydroxy-3-methoxybenzaldehyde]. Cell proliferative effect was assessed by MTT assay using HT-29 cell line. Compound 1 significantly inhibited the proliferation of HT-29 cells when treated with concentrations of 250 µg/ml and 1,000 µg/ml for 48 h, while compound 2 moderately inhibited the proliferation of the HT-29 cell line at the same concentration and time period. Cytotoxic activity of extracted compounds by the release of lactate dehydrogenase confirms that these compounds were not toxic to the cells at 250 µg/ml of compounds 1 and 2. In addition, flow cytometry results show a significant cell arrest in the G0/G1 phase and increase in the apoptotic cells in sub G0 phase, in a dose-dependent manner when compared with the control. The conclusion of this study suggests that the anticancer property of these millets is mediated through the presence of vanillin.

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PMID: 

Biochem Biophys Res Commun. 2019 Oct 29 ;519(1):106-112. Epub 2019 Aug 29. PMID: 31472955

Abstract Title: 

Vitexin alleviates non-alcoholic fatty liver disease by activating AMPK in high fat diet fed mice.

Abstract: 

Non-alcoholic fatty liver disease (NAFLD) is a most common liver disorder characterized by accumulation of fat in the liver and currently there is no approved treatment for it. Obesity and diabetes being leading cause of NAFLD, compounds having anti-obesity activity and potential to reduce insulin resistance are considered suitable candidate for NAFLD treatment. In this study, we checked effect of vitexin, a naturally occurring flavonoid, on high fat diet (HFD) induced NAFLD in C57BL/6J mice. In presence of vitexin, significant reduction in body and liver weight, triglyceride and cholesterol content in serum and liver was observed. Serum Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) levels were reduced significantly by vitexin which were elevated in HFD group whereas serum lipase activity remained unchanged. Vitexin suppressed de novo lipogenesis by downregulating expression of Peroxisome proliferator-activated receptorγ (PPARγ), CCAAT/enhancer-binding protein-α (C/EBP-α), sterol regulatory element-binding protein-1c (SREBP-1c), Fatty acid synthase (FAS) and Acetyl-CoA Carboxylase (ACC). Additionally, it also enhanced fatty acid oxidation and lipolysis by upregulating Peroxisome proliferator-activated receptorα (PPAR-α), carnitine palmitoyltransferase-1a (CPT-1a) and Adipose triglyceride lipase (ATGL). Inhibition of lipogenesis and activation of lipolysis and fatty acid oxidation by vitexin was found to be mediated by activation of AMP-activated protein kinase (AMPK). Vitexin also improved insulin signalling by activating insulin receptor substrate-1 (IRS-1) and its downstream target AKT. AMPK activation of vitexin was possibly through binding of vitexin to leptin receptor (LepR) which was confirmed by molecular docking studies and by observed enhanced expression of LepR. Thus, we propose that vitexin alleviates NAFLD by activating AMPK possibly by binding to LepR.

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PMID: 

Drug Dev Res. 2019 Dec ;80(8):1120-1127. Epub 2019 Sep 4. PMID: 31486114

Abstract Title: 

Vitexin ameliorates preeclampsia phenotypes by inhibiting TFPI-2 and HIF-1α/VEGF in a l-NAME induced rat model.

Abstract: 

Preeclampsia (PE) is a leading cause of maternal and perinatal morbidity and mortality with few safe, effective, and minimally invasive therapeutics. Inflammation, oxidative stress, and angiogenic imbalance have been reported to contribute to PE pathogenesis. Vitexin (VI) possesses various pharmacological activities including the potent regulation of the above biological processes in different conditions. This study aims to investigate whether VI has therapeutic potential to PE and the underlying mechanisms. Sprague-Dawley pregnant rats pretreated with or without VI were fed with l-NAME-containing water to induce experimental PE. Results showed that VI decreased high systolic blood pressure and urinary protein in PE rats time- and dose-dependently. Meanwhile, VI of higher dosage (45, 60 mg/kg) corrected abnormal pregnancy outcomes, including low pup weight and low pups/placenta ratio. In addition, VI of high dosage (60 mg/kg) decreased sFlt-1, increased PlGF and alleviated oxidative stress both in blood and placental samples compared with nontreated PE group. Furthermore, VI alleviated placental TFPI-2, HIF 1α, and VEGF in PE rats. In short, the present study suggests that the inhibition of placental TFPI-2 and HIF-1α/VEGF might be one of the potential mechanisms underlying the protective effects of VI to experimental PE induced by l-NAME.

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PMID: 

Clin Transl Oncol. 2019 Nov 1. Epub 2019 Nov 1. PMID: 31677055

Abstract Title: 

Vitexin, an inhibitor of hypoxia-inducible factor-1α, enhances the radiotherapy sensitization of hyperbaric oxygen on glioma.

Abstract: 

PURPOSE: Vitexin, an inhibitor of hypoxia-inducible factor (HIF)-1α, has anti-tumor effect. However, whether it can enhance the radiotherapy sensitization of hyperbaric oxygen (HBO) on glioma is unclear. This study aimed to investigate the effect of vitexin.METHODS: The nude mice with paw-transplanted glioma were divided into four groups: control group, HBO + radiation group, HBO + vitexin group, and HBO + vitexin + radiation group. The mice of last two groups were daily given vitexin 75 mg/kg by intraperitoneal injection. 30 min after administration of vitexin, the HBO-treated mice were daily placed in HBO chamber for 60 min. The radiation-treated mice were given local tumor irradiation once every week during the HBO treatment, and the dose of irradiation was 10 Gy/time. The experimental treatment lasted for 21 days.RESULTS: Compared with the HBO + radiation group, the tumor volume, tumor weight, and tumor weight coefficient in the HBO + vitexin + radiation group were lower (p 

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PMID: 

Biomed Pharmacother. 2020 Jan ;121:109683. Epub 2019 Nov 24. PMID: 31810123

Abstract Title: 

Effect of vitexin on alleviating liver inflammation in a dextran sulfate sodium (DSS)-induced colitis model.

Abstract: 

As one of commonly used herbs with dual-purpose of drug and food, it has been reported that vitexin has hepatoprotective effects. However, the protective effects of vitexin on colitis-induced liver injury as well as the underlying molecular mechanisms remain unclear. The purpose of the current study was to investigate the effects and mechanisms of vitexin on liver injury induced by acute ulcerative colitis in mice. In this study, the mice model of acute ulcerative colitis was induced by 4 % dextran sodium sulphate (DSS). And then, the degree of liver injury in colitis mice was evaluated, the hepatic ALT, AST, TC and TG levels were measured by specific determination kits, the levels of TNF-α, IL-6 and IL-1β were examined by ELISA, the expressions of TLR4/NF-κB pathway related protein were detected by western blot analysis. The results indicated that hepatic histopathological changes induced by DSS were normalized by vitexin treatment, administration of vitexin decreased the liver levels of ALT and TC in mice with liver injury and reduced the release amounts of DSS-induced pro-inflammatory cytokines TNF-α, IL-6 and IL-1β. Furthermore, we found that vitexin inhibited the activation of TLR4/NF-κB signaling pathway induced by DSS. In conclusion, vitexin possess hepatoprotective activities against colitis-induced liver injury, it has potential application prospects in the treatment of liver injury induced by ulcerative colitis.

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PMID: 

Mol Biol Rep. 2019 Dec ;46(6):6361-6370. Epub 2019 Oct 3. PMID: 31583572

Abstract Title: 

In vitro and in silico anticancer activity of amygdalin on the SK-BR-3 human breast cancer cell line.

Abstract: 

In spite of several studies that have shown the cytotoxic effects of amygdalin on the different cancer cell lines, however, the chemopreventive potential of amygdalin on the breast cancer cell line is not completely understood. We investigated the effect of amygdalin on the cell death and the level of pro-apoptotic Bax protein and anti-apoptotic Bcl-2 protein in SK-BR-3 human breast cancer cell line. The cell viability of SK-BR-3 cells was evaluated by MTT assay in different concentration of amygdalin. The level of Bax and Bcl-2 in SK-BR-3 cells were measured by western blot analysis. For statistical analysis, One-way ANOVA was used for the comparison of Bax and Bcl-2 protein level and percent of cell viability between groups. The molecular docking studies of amygdalin within the Bcl-2 (PDB ID: 4LVT) and HER2 (PDB ID: 3RCD) active site, were performed using AutoDock 4.2.5. Amygdalin induced a significant reduction of cell viability in SK-BR-3 after 24-h treatment in a dose-dependent manner. Also, amygdalin causes an increase in pro-apoptotic Bax protein and a decrease in anti-apoptotic Bcl-2 protein expression in the SK-BR-3 cells. Molecular docking studies showed that amygdalin interacts with the active site amino acids of Bcl-2 and HER2 through hydrogen bonding and some hydrophobic interactions. Amygdalin can induce apoptotic death in SK-BR-3 cells by increasing pro-apoptotic Bax protein and decreasing anti-apoptotic Bcl-2 protein expression. The results suggest that amygdalin may be a valuable candidate for the treatment of breast cancer, especially in HER2 positive cells.

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PMID: 

J Ethnopharmacol. 2019 Nov 23:112418. Epub 2019 Nov 23. PMID: 31770567

Abstract Title: 

Anti-inflammatory and anti-arthritic activity in extract from the leaves of Eriobotrya japonica.

Abstract: 

ETHNOPHARMACOLOGICAL RELEVANCE: The Eriobotrya japonica (EJ) is a Chinese medicinal plant that is currently grown in Brazil. E. japonica leaves infusion is traditionally used in the treatment of inflammation; however, there are few scientific studies showing the effects of these properties on joint articular and persistent experimental inflammation.AIM OF THE STUDY: The present research had objective investigation of the effect of infusion obtained from leaves of E. japonica (EJLE) on acute and persistent experimental articular inflammation.MATERIALS AND METHODS: The Swiss mice were treated orally with EJLE and analyzed for acute pleural inflammation (30, 100, and 300 mg/kg), paw edema induced by carrageenan (100 mg/kg), acute knee inflammation induced by zymosan (100 mg/kg), and persistent inflammation induced by Complete Freund's Adjuvant (CFA) (30 and 100 mg/kg). Mechanical hyperalgesia, cold and edema were analyzed.RESULTS: The chromatographic analysis of EJLE revealed the presence of corosolic acid, oleanolic acid, and ursolic acid. EJLE presented anti-inflammatory activity in the pleurisy model, inhibiting leukocyte migration, protein extravasation and nitric oxide production. In the articular inflammation model, EJLE reduced the number of leukocytes in the joint cavity, paw edema and hyperalgesia (4 h after induction). In the persistent inflammation model induced by CFA, the extract reduced paw edema after 11 days of mechanical and cold hyperalgesia on day 6.CONCLUSIONS: The EJLE has anti-inflammatory and antihyperalgesic potential in models of acute and persistent experimental articular inflammation, making this infusion a new possibility for complementary treating acute or chronic articular inflammatory diseases.

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PMID: 

J Ginseng Res. 2019 Oct ;43(4):676-683. Epub 2019 May 21. PMID: 31695571

Abstract Title: 

Safety and antifatigue effect of Korean Red Ginseng: a randomized, double-blind, and placebo-controlled clinical trial.

Abstract: 

Background: Korean Red Ginseng (KRG) is widely used for strengthening the immune system and fighting fatigue, especially in people with deficiency syndrome. However, there is concern that the long-term application or a high dose of KRG can cause"fireness"( in Chinese) because of its"dryness"( in Chinese). The aim of this study was to assess the safety and efficacy of a 4-week treatment with KRG in participants with deficiency syndrome.Methods: This was a 4-week, randomized, double-blind, placebo-controlled clinical trial. A total of 180 Chinese participants were randomly allocated to three groups: placebo control group, participants were given a placebo, 3.6 g/d; KRG 1.8 g and 3.6 g groups. The primary outcomes were the changes in fireness and safety evaluation (adverse events, laboratory tests, and electrocardiogram). The secondary outcomes were the efficacy of KRG on fatigue, which include the following: traditional Chinese medicine (TCM) symptom scale and fatigue self-assessment scale.Results: Of the 180 patients, 174 completed the full study. After 4 weeks of KRG treatment, the Fire-heat symptoms score including Excess fire-heat score and Deficient fire-heat score showed no significant change as compared with placebo treatment, and no clinically significant changes in any safety parameter were observed. Based on the TCM syndrome score and fatigue self-assessment score, TCM symptoms and fatigue were greatly improved after treatment with KRG, which showed a dose- and time-dependent effect. The total effective rate was also significantly increased in the KRG groups.Conclusion: Our study revealed that KRG has a potent antifatigue effect without significant adverse effects in people with deficiency syndrome. Although a larger sample size and longer treatment may be required for a more definite conclusion, this clinical trial is the first to disprove the common conception of"fireness"related to KRG.

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PMID: 

J Ginseng Res. 2019 Oct ;43(4):625-634. Epub 2019 Feb 28. PMID: 31700260

Abstract Title: 

Ginsenoside Rg3 and Korean Red Ginseng extract epigenetically regulate the tumor-related long noncoding RNAs RFX3-AS1 and STXBP5-AS1.

Abstract: 

Background: Ginsenoside Rg3, a derivative of steroidal saponins abundant in ginseng, has a range of effects on cancer cells, including anti-cell proliferation and anti-inflammation activity. Here, we investigate two long noncoding RNAs (lncRNAs), STXBP5-AS1 and RFX3-AS1, which are hypomethylated and hypermethylated in the promoter region by Rg3 in MCF-7 cancer cells.Methods: The lncRNAs epigenetically regulated by Rg3 were mined using methylation array analysis. The effect of the lncRNAs on the apoptosis and proliferation of MCF-7 cells was monitored in the presence of Rg3 or Korean Red Ginseng (KRG) extract after deregulating the lncRNAs. The expression of the lncRNAs and their target genes was examined using qPCR and Western blot analysis. The association between the expression of the target genes and the survival rate of breast cancer patients was analyzed using the Kaplan-Meier Plotter platform.Results: STXBP5-AS1 and RFX3-AS1 exhibited anti- and pro-proliferation effects, respectively, in the cancer cells, and the effects of Rg3 and KRG extract on apoptosis and cell proliferation were weakened after deregulating the lncRNAs. Of the genes located close to STXBP5-AS1 and RFX3-AS1 on the chromosome, STXBP5, GRM1, RFX3, and SLC1A1 were regulated by the lncRNAs on the RNA and protein level. Breast cancer patients that exhibited a higher expression of the target genes of the lncRNAs had a higher metastasis-free survival rate.Conclusion: The current study is the first to identify lncRNAs that are regulated by the presence of Rg3 and KRG extract and that subsequently contribute to inhibiting the proliferation of cancer cells.

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PMID: 

Neural Regen Res. 2020 May ;15(5):887-893. PMID: 31719254

Abstract Title: 

Korean red ginseng promotes hippocampal neurogenesis in mice.

Abstract: 

Neurogenesis in the adult hippocampus plays a major role in cognitive ability of animals including learning and memory. Korean red ginseng (KRG) has long been known as a medicinal herb with the potential to improve learning and memory; however, the mechanisms are still elusive. Therefore, we evaluated whether KRG can promote cognitive function and enhance neurogenesis in the hippocampus. Eight-week-old male C57BL/6 mice received 50 mg/kg of 5-bromo-2'-deoxyuridine (BrdU) intraperitoneally and 100 mg/kg of KRG or vehicle orally once a day for 14 days. Pole, Rotarod and Morris water maze tests were performed and the brains were collected after the last behavioral test. Changes in the numbers of BrdU- and BrdU/doublecortin (DCX; a marker for neuronal precursor cells and immature neurons)-positive cells in the dentate gyrus and the gene expression of proliferating cell nuclear antigen (a marker for cell differentiation), cerebral dopamine neurotrophic factor and ciliary neurotrophic factor in the hippocampus were then investigated. KRG-treated mice came down the pole significantly faster and stood on the rotarod longer than vehicle-treated mice. The Morris water maze test showed that KRG administration enhanced the learning and memory abilities significantly. KRG also significantly increased BrdU- and BrdU/DCX-positive cells in the dentate gyrus as well as the proliferating cell nuclear antigen, cerebral dopamine neurotrophic factor and ciliary neurotrophic factor mRNA expression levels in the hippocampus compared to vehicle. Administration of KRG promotes learning and memory abilities, possibly by enhancing hippocampal neurogenesis. This study was approved by the Pusan National University Institutional Animal Care and Use Committee (approval No. PNU-2016-1071) on January 19, 2016.

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