PMID: 

Mayo Clin Proc. 2019 03 ;94(3):432-446. Epub 2019 Feb 18. PMID: 30792067

Abstract Title: 

Yoga as Antihypertensive Lifestyle Therapy: A Systematic Review and Meta-analysis.

Abstract: 

OBJECTIVE: To investigate the efficacy of yoga as antihypertensive lifestyle therapy and identify moderators that account for variability in the blood pressure (BP) response to yoga.METHODS: We systematically searched 6 electronic databases from inception through June 4, 2018, for articles published in English language journals on trials of yoga interventions that involved adult participants, reported preintervention and postintervention BP, and had a nonexercise/nondiet control group. Our search yielded 49 qualifying controlled trials (56 interventions). We (1) evaluated the risk of bias and methodological study quality, (2) performed meta-regression analysis following random-effects assumptions, and (3) generated additive models that represented the largest possible clinically relevant BP reductions.RESULTS: On average, the 3517 trial participants were middle-aged (49.2±19.5 years), overweight (27.9±3.6 kg/m) adults with high BP (systolic BP, 129.3±13.3 mm Hg; diastolic BP, 80.7±8.4 mm Hg). Yoga was practiced 4.8±3.4 sessions per week for 59.2±25.0 minutes per session for 13.2±7.5 weeks. On average, yoga elicited moderate reductions in systolic BP (weighted mean effect size, -0.47; 95% CI, -0.62-0.32, -5.0 mm Hg) and diastolic BP (weighted mean effect size, -0.47; 95% CI, -0.61 to -0.32; -3.9 mm Hg) compared with controls (P

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PMID: 

Pharmacol Res. 2019 Sep ;147:104347. Epub 2019 Jul 14. PMID: 31315066

Abstract Title: 

Citrus aurantium L. var. amara Engl. inhibited lipid accumulation in 3T3-L1 cells and Caenorhabditis elegans and prevented obesity in high-fat diet-fed mice.

Abstract: 

Natural products with anti-obesity effects and few side effects have attracted great attention recently. Citrus aurantium L. var. amara Engl. (CAVA) is popularly consumed as an edible and medicinal resource in China. However, its anti-obesity effects were poorly understood. The anti-obesity effects of CAVA extracts were systematically evaluated using 3T3-L1 cells, Caenorhabditis elegans (C. elegans) and high fat diet (HFD)-fed mice. Flavonoid-rich (EA) extracts with neohesperidin, hesperidin and naringin comprising 32.15%, were isolated from CAVA. EA extracts treatment significantly inhibited differentiation of 3T3-L1 preadipocytes by modulating lipid metabolism-related mediators. EA extracts supplementation also inhibited antioxidant responses in C. elegans by decreasing reactive oxygen species generation and malonaldehyde value, and increasing superoxide dismutase content. EA extracts feeding markedly decreased triglyceride (TG) content, and affected expression of genes involved in lipid and glucose metabolism in wild type C. elegans. TG content in mdt-15 (XA7702) mutants was not decreased by EA extracts administration, suggesting that EA extracts treatment might inhibit lipid accumulation in C. elegans dependent on mdt-15. EA extracts intervention further reduced body weight gain and modulated plasma biochemical parameters in HFD-fed mice. EA extracts treatment prevented HFD-induced epididymal adipose hypertrophy, liver oxidative injuries and steatosis. EA extracts administration also strongly prevented HFD-induced reduction of gut microbial diversity, decreased the Firmicutes-to-Bacteroidetes ratio and the Erysipelotrichaceae abundance, and enhanced the Bifidobacteriace abundance in HFD-fed mice. EA extracts from blossoms of CAVA were excellent antiobesogenic candidates that acted through multiple mechanisms that acted simultaneously.

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PMID: 

Asian Spine J. 2019 Oct 4. Epub 2019 Oct 4. PMID: 31575107

Abstract Title: 

Evaluation of Anti-inflammatory and Regenerative Efficiency of Naringin and Naringenin in Degenerated Human Nucleus Pulposus Cells: Biological and Molecular Modeling Studies.

Abstract: 

Study Design: Development of an in vitro model for assessing the anti-inflammatory efficacies of naringin (Nar) and naringenin (NG).Purpose: To evaluate the efficacy of natural flavonoids as therapeutic drugs against anti-inflammatory processes in the nucleus pulposus (NP) cells using in-vitro and in-silico methods.Overview of Literature: Intervertebral disc (IVD) disease is a common cause of low back pain. Chronic inflammation and degeneration play a significant role in its etiopathology. Thus, a better understanding of anti-inflammatory agents and their role in IVD degeneration and pro-inflammatory cytokines expression is necessary for pain management and regeneration in IVD.Methods: We performed primary cell culture of NP cells; immunocytochemistry; gene expression studies of cytokines, metalloproteases, extracellular proteins, and apoptotic markers using quantitative polymerase chain reaction and reverse transcription-polymerase chain reaction (RT-PCR); cytotoxicity assay (MTT); and molecular docking studies using AutoDock 4.2 software (Molecular Graphics Laboratory, La Jolla, CA, USA) to confirm the binding mode of proteins and synthesized complexes. We calculated the mean±standard deviation values and performed analysis of variance and t-test using SPSS ver. 17.0 (SPSS, Inc., Chicago, IL, USA).Results: Molecular docking showed that both Nar and NG bind to the selected genes of interest. Semi-quantitative RT-PCR analysis reveals differential gene expression of collagen (COL)9A1, COL9A2, COL9A3, COL11A2, COMT (catechol-O-methyltransferase), and THBS2 (thrombospondin 2); up regulation of ACAN (aggrecan), COL1A1, COL11A1, interleukin (IL)6, IL10, IL18R1, IL18RAP, metalloprotease (MMP)2, MMP3, MMP9, ADAMTS5 (a disintegrin and metalloproteinase with thrombospondin motifs 5), IGF1R (insulin-like growth factor type 1 receptor), SPARC (secreted protein acidic and cysteine rich), PARK2 (parkin), VDR (vitamin D receptor), and BCL2 (B-cell lymphoma 2); down regulation of IL1A, CASP3 (caspase 3), and nine genes with predetermined concentrations of Nar and NG.Conclusions: The present study evaluated the anti-inflammatory and regenerative efficiencies of Nar and NG in degenerated human NP cells. Altered gene expressions of cytokines, metalloproteases, extracellular proteins, apoptotic genes were dose responsive. The molecular docking (in silico) studies showed effective binding of these native ligands (Nar and NG) with genes identified as potent inhibitors of inflammation. Thus, these natural flavonoids could serve as anti-inflammatory agents in the treatment of low back pain and sciatica.

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PMID: 

Nutr Diabetes. 2019 Oct 7 ;9(1):28. Epub 2019 Oct 7. PMID: 31591391

Abstract Title: 

Naringenin improves insulin sensitivity in gestational diabetes mellitus mice through AMPK.

Abstract: 

BACKGROUND: Gestational diabetes mellitus (GDM) is a temporary form of diabetes during pregnancy, which influences the health of maternal-child in clinical practice. It is still urgent to develop new effective treatment for GDM. Naringenin is a bioactive ingredient with multiple activities including anti-diabetic. In current study, the effects of naringenin on GDM symptoms, insulin tolerance, inflammation, and productive outcomes were evaluated and the underlying mechanisms were explored.METHODS: We administrated naringenin to GDM mice and monitored the GDM symptoms, glucose and insulin tolerance, inflammation and productive outcomes. We established tumor necrosis factor alpha (TNF-α)-induced insulin resistance skeletal muscle cell model and evaluated the effects of naringenin on reactive oxygen species (ROS) production, glucose uptake and glucose transporter type 4 (GLUT4) membrane translocation.RESULTS: We found that naringenin ameliorated GDM symptoms, improved glucose and insulin tolerance, inhibited inflammation, and improved productive outcomes. It was further found that naringenin inhibited TNF-α-induced ROS production, enhanced GLUT4 membrane translocation, and glucose uptake, which were abolished by inhibition of AMP-activated protein kinase (AMPK).CONCLUSION: Naringenin improves insulin sensitivity in gestational diabetes mellitus mice in an AMPK-dependent manner.

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PMID: 

J Environ Pathol Toxicol Oncol. 2018 ;37(2):139-150. PMID: 30055549

Abstract Title: 

Melatonin Improves Behavioral and Biochemical Outcomes in a Rotenone-Induced Rat Model of Parkinson's Disease.

Abstract: 

Parkinson's disease (PD) is the second most common neurodegenerative disease followed only by Alzheimer's disease and affects millions of people worldwide. Despite the plethora of preclinical and clinical studies, there is currently a paucity of therapeutic agents for PD that can promote neuroprotection. In addition, the therapeutic agents currently available only help with improvement of PD symptoms. Therefore, it is imperative to find new therapeutic avenues for PD patients to minimize the economic and social burden on the concerned families. Rotenone is a frequently used neurotoxin in developing a PD model to aid in understanding the mechanisms of neuronal death. In addition, several studies have investigated the effects of melatonin, a neurohormone that is neuroprotective in various neurological diseases due to its anti-apoptotic, anti-inflammatory, and anti-oxidative properties. Our study investigated the role of melatonin-induced tyrosine hydroxylase (TH) and sensory motor function in a rotenone rat model to determine whether melatonin had any positive effects. Our results revealed that melatonin improves motor function by upregulation of TH in striatum of the brain. In addition, melatonin inhibits the striatal degeneration as shown by histopathological analysis. Therefore, results from the current study provide evidence for melatonin as a promising candidate for effective future therapeutic strategies for PD.

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PMID: 

Front Pharmacol. 2019 ;10:937. Epub 2019 Aug 29. PMID: 31555129

Abstract Title: 

Arctigenin Attenuates Tumor Metastasis Through Inhibiting Epithelial-Mesenchymal Transition in Hepatocellular CarcinomaSuppressing GSK3β-Dependent Wnt/β-Catenin Signaling Pathwayand.

Abstract: 

Arctigenin (ARG) has been reported to be a bioactive lignan fromexerting various activities including anti-cancer and immune-regulation. The present study aimed to investigate the anti-metastasis activity and mechanism of ARG against hepatocellular carcinomaand. The results showed that ARG exhibited a significant cytotoxicity on Hep G2 and SMMC 7721 cells (but not on normal liver cells LO2). In addition, the migration and invasion of Hep G2 and SMMC 7721 cells were also remarkably repressed. Furthermore, ARG attenuated Wnt/β-catenin signaling activation, resulting in the down-regulation of β-catenin target genes including c-Myc, cyclin D1, MMP-9, and ZO-1. Noticeably, ARG attenuated the activation of Wnt/β-catenin through a GSK3β-dependent pathway. Besides, we also found that ARG potentially inhibited epithelial-mesenchymal transition by up-regulating the epithelial and down-regulating the mesenchymal marker proteins., intraperitoneal injection of ARG not only significantly inhibited the growth of subcutaneous transplanted tumor but also dramatically alleviated the tumor metastasis in liver. Our data demonstrated that ARG exerted anti-epithelial-mesenchymal transition and anti-metastasis activities against hepatocellular carcinoma, which might make it a candidate as a preventive agent for cancer metastasis.

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PMID: 

Biochem Biophys Res Commun. 2019 Sep 26. Epub 2019 Sep 26. PMID: 31564411

Abstract Title: 

Arctigenin enhances the sensitivity of cisplatin resistant colorectal cancer cell by activating autophagy.

Abstract: 

Arctigenin is the active content of arctium lappa that present anti-cancer abilities in various carcinomas. However, its role and underlying mechanism in drug-resistant colorectal cancer cells has not been addressed. The present study used SW480 and SW620 to established cisplatin-resistant colorectal cancer cell lines, and explored the impact of arctigenin on these cells. Arctigenin at 100 μM significantly inhibited cell proliferation of cisplatin treated R-SW480 and R-SW620 cells as compared with cells treated with cisplatin alone. Arctigenin elevates cell apoptosis, up-regulated pro-apoptotic protein cleaved-caspase-3 and caspase-9 expression level in cisplatin treated R-SW480and R-SW620 cells. Additionally, arctigenin triggered autophagy and promoted LC3-Ⅱ and p65 expression, while inhibited LC3-Ⅰexpression. Arctigenin impeded the ICof not only cisplatin but also oxaliplatin, doxorubicin and Paclitaxel of R-SW480 and R-SW620 cells. More importantly, the mRNA expression of multi drug resistance 1 (MDR1) and protein expression of pgp were significantly inhibited by arctigenin administration. Taken together, arctigenin has the potential in sensitize colorectal cancer cells by activating autophagy, which induced cell apoptosis and inhibited cell growth. Our study revealed that arctigenin has the potential for colorectal cancer treatment and may be useful in adjuvant chemotherapy.

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PMID: 

J Pak Med Assoc. 2019 Aug ;69(Suppl 3)(8):S103-S107. PMID: 31603888

Abstract Title: 

Gingko Biloba protects cardiomyocytes against acute doxorubicin induced cardiotoxicity by suppressing oxidative stress.

Abstract: 

Objective: To evaluate the cardio-protective effect of Ginkgo Biloba (GB) on doxorubicin induced-cardiotoxicity.Methods: The experimental study was conducted at the College of Medicine, Mustansiriya University, Baghdad, Iraq, from January to March, 2016, and comprised thirty Wistar Sprague male rats aged 3-4 months and weighing 200-400 g. The rats were divided into three equal groups (n=10); GroupІ (control): rats were treated with distilled water, Group ІІ (doxorubicin): rats were treated with distilled water and doxorubicin 20 mg/kg, and Group ІІІ (GB): rats were treated with GB and doxorubicin 20mg/kg. Serum malondialdehyde (MDA), glutathione reductase (GSH), lipid peroxidise (LPO),tumour necrosis factor-alpha (TNF-α), cardiac troponin (cTnI), brain natriuretic peptide (BNP) and caspase-3 (Cas-3) were measured using enzyme-linked immunosorbent assay kits. SPSS 20 was used to compare the effect GB with doxorubicin on the biomarkers of doxorubicin induced-cardiotoxicity.Results: Doxorubicin led to cardiotoxicity through elevation of cTnI, BNP, Cas-3 and LPO compared with controls (p

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PMID: 

Adv Pharm Bull. 2019 Aug ;9(3):490-496. Epub 2019 Aug 1. PMID: 31592099

Abstract Title: 

The Effects of Thymoquinone on Viability, and Anti-apoptotic Factors (BCL-XL, BCL-2, MCL-1) in Prostate Cancer (PC3) Cells: An In Vitro and Computer-Simulated Environment Study.

Abstract: 

Since active plant ingredients can induce apoptosis in many tumors, in this study we evaluate the apoptotic effects of thymoquinone (TQ) on PC3 cells. Also, we predicted the interaction of TQ with BCL-XL, BCL-2, and MCL-1anti-apoptotic factors by computer-simulated environment.PC3 cells were treated with different concentrations of TQ (0- 80µM) and ICwas determined using 3-(4, 5-dimethylthiaztol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Apoptotic and cytotoxicity effects of TQ were analyzed using flowcytometry and comet assay, respectively. Changes in energy and the molecular interactions of TQ with BCL-XL, BCL-2 and MCL-1 anti-apoptotic factors were investigated using simulation.ICvalue was 40µM. TQ led to the destruction of the genome of PC3 cells and inducing apoptosis. Molecular dynamics (MD) revealed that the root mean-square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), and the number of hydrogen and hydrophobic bonds between TQ and residues of BCL-2, BCL-XL and MCL-1were significantly (

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PMID: 

Curr Med Chem. 2019 Oct 11. Epub 2019 Oct 11. PMID: 31604405

Abstract Title: 

Targeting inflammatory mediators: An anticancer mechanism of thymoquinone action.

Abstract: 

BACKGROUND: Thymoquinone is a promising anticancer molecule of which chemopreventive role is well-known at least in vitro and in animal model. In this review article, we have focused on the anti-inflammatory activities of thymoquionone in cancer cells.METHOD: Research data on inflammation, cancer and thymoquinone was acquired from pubmed, scopus, web of science and google scholar. We have reviewed paper from the middle of last century, but mostly cited papers from last ten years.RESULTS: In addition to chemopreventive role, studies indicated that thymoquinone also have potential immunotherapeutic role, as thymoquinone can target and modulate inflammatory modulators, like nuclear factor kappa B (NF-κβ), interleukins, tumor necrosis factor-α (TNF-α), and certain growth factors. As chronic inflammation plays role in cancer development, controlling inflammatory pathways is an important mechanism of immunotherapeutic action of anticancer molecule.CONCLUSION: This article reviewed the role of inflammation on cancer development, and the action of thymoquinone on inflammatory molecules, which have been proved in vitro and in vivo. Much more attention is required for studying the immunotherapeutic role of thymoquinone and developing this molecule as future immunotherapeutic drug.

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