scholarly journals Qihuzha Granule Alleviated Cyclophosphamide-induced Immune Deficiency in Mice via IL-6 Related Signaling Pathways

2021 ◽  
Author(s):  
Ting Zhong ◽  
Min Feng ◽  
Minzhi Su ◽  
Hongshan Wu ◽  
Qing Li ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Signaling Pathway ◽  
Immune Regulation ◽  
Structural Integrity ◽  
Mrna Level ◽  
Deficiency Syndrome ◽  
Protective Effects ◽  
Protein Levels ◽  
Mapk Pathways ◽  
Ifn Γ

Abstract BackgroundQihuzha granule (QHZG) is a Chinese patent medicine, composed of 11 kinds of edible medicinal plants, which is used to treat dyspepsia and anorexia in children caused by spleen and stomach deficiency syndrome. However, its role and mechanism in immunosuppression induced by cyclophosphamide remained unclear. The purpose of this study is to investigate the effect of QHZG on immunosuppression induced by cyclophosphamide in mice and its possible mechanism.MethodsThe immunosuppression injury model was induced by intraperitoneal injection of cyclophosphamide (100 mg/kg); the mRNA level of cytokines (IL-2/4/6, IFN-γ) and critical targets of signaling pathways related to immune regulation (JNK, ERK, P38, JAK2, SRC and STAT3) were tested by QPCR; related protein levels were detected by western blotting; hematoxylin-eosin (HE) staining was employed to observe the histological alterations; macrophages and neutrophils in the mouse spleen were examined by immunofluorescence analysis. ResultsQHZG significantly increased the spleen index and thymus index of mice with immunodeficiency induced by cyclophosphamide and up-regulated the mRNA expression of cytokines (IL-2/4/6, IFN-γ) and critical targets of signaling pathways related to immune regulation (JNK, ERK, P38, JAK2, SRC and STAT3), which were decreased by cyclophosphamide treatment. The results of immunofluorescence staining and histological analysis showed that QHZG could also protect mice from immunosuppressive injury caused by cyclophosphamide via keeping structural integrity of spleen, and partially restoring the production levels of macrophages and monocytes in the spleen. Further studies indicated that QHZG could significantly counter the decline of phosphorylated protein levels of JAK2/SRC-STAT3 axes (P-JAK2, P-SRC and P-STAT3), and MAPK pathways (P-JNK, P-ERK and P-P38) induced by cyclophosphamide, suggesting that the protective effects of QHZG on immunosuppressive injury triggered by cyclophosphamide were involved in JAK2/SRC-STAT3 axes, and MAPK pathways. Meanwhile, we also found that QHZG could partially restore the vital phosphorylated proteins of PI3K/Akt/mTOR signaling pathway (P-Akt, P-mTOR), which were reduced by cyclophosphamide. The data implied that PI3K signaling pathway was also responsible for the protection of QHZG against the immunosuppression induced by cyclophosphamide in mice. ConclusionsOur study demonstrated that QHZG protected mice from cyclophosphamide-triggered immunosuppressive injury via IL-6 and its downstream signaling pathways including PI3K/Akt/mTOR signal pathway and JAK2-SRC/MAPK/STAT3 axes. These results suggested that QHZG might serve as a new drug for the treatment of the immunosuppression caused by cyclophosphamide therapy.

scholarly journals Protective Effects of 6,7,4′-Trihydroxyflavanone on Hypoxia-Induced Neurotoxicity by Enhancement of HO-1 through Nrf2 Signaling Pathway

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 341 ◽  
Author(s):  
Hyun-Su Lee ◽  
Gil-Saeng Jeong
Keyword(s):  
Signaling Pathway ◽  
Neurodegenerative Disorders ◽  
Nuclear Translocation ◽  
Protoporphyrin Ix ◽  
Protective Role ◽  
Osteoclast Formation ◽  
Protective Effects ◽  
Protein Levels ◽  
Nrf2 Signaling Pathway ◽  
Pre Treatment

Since hypoxia-induced neurotoxicity is one of the major causes of neurodegenerative disorders, including the Alzheimer’s disease, continuous efforts to find a novel antioxidant from natural products are required for public health. 6,7,4′-trihydroxyflavanone (THF), isolated from Dalbergia odorifera, has been shown to inhibit osteoclast formation and have an antibacterial activity. However, no evidence has reported whether THF has a protective role against hypoxia-induced neurotoxicity. In this study, we found that THF is not cytotoxic, but pre-treatment with THF has a cytoprotective effect on CoCl2-induced hypoxia by restoring the expression of anti-apoptotic proteins in SH-SY5y cells. In addition, pre-treatment with THF suppressed CoCl2-induced hypoxia-related genes including HIF1α, p53, VEGF, and GLUT1 at the mRNA and protein levels. Pre-treatment with THF also attenuated the oxidative stress occurred by CoCl2-induced hypoxia by preserving antioxidant proteins, including SOD and CAT. We revealed that treatment with THF promotes HO-1 expression through Nrf2 nuclear translocation. An inhibitor assay using tin protoporphyrin IX (SnPP) confirmed that the enhancement of HO-1 by pre-treatment with THF protects SH-SY5y cells from CoCl2-induced neurotoxicity under hypoxic conditions. Our results demonstrate the advantageous effects of THF against hypoxia-induced neurotoxicity through the HO-1/Nrf2 signaling pathway and provide a therapeutic insight for neurodegenerative disorders.

Discussion On The Mechanism of Que In The Treatment of Breast Neoplasms And Immune Prevention And Treatment

2021 ◽  
Author(s):  
Dan Qiu ◽  
Xianxin Yan ◽  
Xinqin Xiao ◽  
Guijuan Zhang ◽  
Yanqiu Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
T Cell ◽  
Breast Neoplasms ◽  
Signaling Pathway ◽  
Immune Regulation ◽  
Γδ T Cells ◽  
Protein Levels ◽  
Stat1 Signaling ◽  
Mcf 7

Abstract Background: The precancerous disease of breast cancer is an inevitable stage in the emergence and development of breast neoplasms. Breast cancer (BC) is a common malignant tumor in female worldwide. A large number of literatures have proved that, as antitumor drugs, flavonoid compounds can promote proliferation and immune regulation of T cell. Many researchers believe that Quercetin (Que) has great potential in the field of anti-breast cancer. Besides that, γδ T cells are a class of non-traditional T cells, which have long attracted attention due to their potential in immunotherapy. Above all, JAK/STAT1 signaling pathway is closely related to the immunity.MethodsIn the experiment designed in this paper, we first used Que, one of the flavonoids, to screen the target gene. Then, MCF-10A, MCF-10AT, MCF-7 and MDA-MB231 BC cells were co-cultured with Que for 24h and 48h, apoptosis was found in some the cells. We then cultured Que with γδ T cells and found that Que can promote the proliferation of Vδ2 T cell subsets of γδ T cells, thus enhancing the killing effect of γδ T cells. Western blot was use to showed the change of JAK/STAT1 signaling pathway related proteins after the Que was co-cultured with MCF-10AT and MCF-7 for 48h.ResultsNetwork pharmacology has shown that Que related pathways include the JAK/STAT1 signaling pathway and are associated with precancerous breast cancers. Que induced apoptosis of MCF-10AT, MCF-7 and MDA-MB-231 in a time and concentration-dependent manner. Most importantly, Que can promote the differentiation of γδ T cells into the Vδ2 T cell subpopulation, this means that Que and γδ T cells may play a synergistic role in killing tumor cells and cellular immune regulation. In addition, our results showed that Que can increase in protein levels of IFNγ-R, p-JAK2 and p-STAT1, while the concomitant decrease protein levels of PD-L1.ConclusionsIn conclusion, Que plays a synergistic role in killing BC cells and promoting apoptosis by regulating the expression of IFNγ-R, p-JAK2, p-STAT1, and PD-L1 in the JAK/STAT1 signaling pathway and promoting the regulation of γδ T cells. Que may be a potential drug for the prevention of precancerous breast cancer and adjuvant treatment of BC.

scholarly journals Arginine Deiminase and Biotin Metabolism Signaling Pathways Play an Important Role in Human-Derived Serotype V, ST1 Streptococcus agalactiae Virulent Strain upon Infected Tilapia

Animals ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 849
Author(s):  
Yu Liu ◽  
Liping Li ◽  
Zhiping Luo ◽  
Rui Wang ◽  
Ting Huang ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Signaling Pathway ◽  
Streptococcus Agalactiae ◽  
Functional Annotation ◽  
Virulent Strain ◽  
Comprehensive Analysis ◽  
Arginine Deiminase ◽  
Differentially Expressed ◽  
Comprehensive Understanding ◽  
Protein Levels

Our previous study showed that human-derived Streptococcus agalactiae (serotype V) could infect tilapia, but the mechanism underlying the cross-species infection remains unrecognized. In this study, a multi-omics analysis was performed on human-derived S.agalactiae strain NNA048 (virulent to tilapia, serotype V, ST1) and human-derived S.agalactiae strain NNA038 (non-virulent to tilapia, serotype V, ST1). The results showed that 907 genes (504 up/403 down) and 89 proteins (51 up/38 down) were differentially expressed (p < 0.05) between NNA038 and NNA048. Among them, 56 genes (proteins) were altered with similar trends at both mRNA and protein levels. Functional annotation of them showed that the main differences were enriched in the arginine deiminase system signaling pathway and biotin metabolism signaling pathway: gdhA, glnA, ASL, ADI, OTC, arcC, FabF, FabG, FabZ, BioB and BirA genes may have been important factors leading to the pathogenicity differences between NNA038 and NNA048. We aimed to provide a comprehensive analysis of the human-derived serotype V ST1 S.agalactiae strains, which were virulent and non-virulent to tilapia, and provide a more comprehensive understanding of the virulence mechanism.

scholarly journals Luteolin Alleviates AflatoxinB1-Induced Apoptosis and Oxidative Stress in the Liver of Mice through Activation of Nrf2 Signaling Pathway

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1268
Author(s):  
Shahid Ali Rajput ◽  
Aftab Shaukat ◽  
Kuntan Wu ◽  
Imran Rashid Rajput ◽  
Dost Muhammad Baloch ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Signaling Pathway ◽  
Aflatoxin B1 ◽  
Physiological Saline ◽  
Protective Effects ◽  
Biochemical Alterations ◽  
Protein Levels ◽  
Nrf2 Signaling Pathway ◽  
Induced Apoptosis

Aflatoxin B1 (AFB1), a threatening mycotoxin, usually provokes oxidative stress and causes hepatotoxicity in animals and humans. Luteolin (LUTN), well-known as an active phytochemical agent, acts as a strong antioxidant. This research was designed to investigate whether LUTN exerts protective effects against AFB1-induced hepatotoxicity and explore the possible molecular mechanism in mice. A total of forty-eight mice were randomly allocated following four treatment groups (n = 12): Group 1, physiological saline (CON). Group 2, treated with 0.75 mg/kg BW aflatoxin B1 (AFB1). Group 3, treated with 50 mg/kg BW luteolin (LUTN), and Group 4, treated with 0.75 mg/kg BW aflatoxin B1 + 50 mg/kg BW luteolin (AFB1 + LUTN). Our findings revealed that LUTN treatment significantly alleviated growth retardation and rescued liver injury by relieving the pathological and serum biochemical alterations (ALT, AST, ALP, and GGT) under AFB1 exposure. LUTN ameliorated AFB1-induced oxidative stress by scavenging ROS and MDA accumulation and boosting the capacity of the antioxidant enzyme (CAT, T-SOD, GSH-Px and T-AOC). Moreover, LUTN treatment considerably attenuates the AFB1-induced apoptosis in mouse liver, as demonstrated by declined apoptotic cells percentage, decreased Bax, Cyt-c, caspase-3 and caspase-9 transcription and protein with increased Bcl-2 expression. Notably, administration of LUTN up-regulated the Nrf2 and its associated downstream molecules (HO-1, NQO1, GCLC, SOD1) at mRNA and protein levels under AFB1 exposure. Our results indicated that LUTN effectively alleviated AFB1-induced liver injury, and the underlying mechanisms were associated with the activation of the Nrf2 signaling pathway. Taken together, LUTN may serve as a potential mitigator against AFB1-induced liver injury and could be helpful for the development of novel treatment to combat liver diseases in humans and/or animals.

scholarly journals Pilose Antler Peptide-3.2KD Ameliorates Adriamycin-Induced Myocardial Injury Through TGF-β/SMAD Signaling Pathway

2021 ◽  
Vol 8 ◽  
Author(s):  
Yan Xu ◽  
Xiaobo Qu ◽  
Jia Zhou ◽  
Guangfu Lv ◽  
Dong Han ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Myocardial Fibrosis ◽  
Myocardial Injury ◽  
Pathological Examination ◽  
Protective Mechanism ◽  
Protective Effects ◽  
Expression Levels ◽  
Smad Signaling ◽  
Protein Levels ◽  
Smad Signaling Pathway

Adriamycin (ADR)-based combination chemotherapy is the standard treatment for some patients with tumors in clinical, however, long-term application can cause dose-dependent cardiotoxicity. Pilose Antler, as a traditional Chinese medicine, first appeared in the Han Dynasty and has been used to treat heart disease for nearly a thousand years. Previous data revealed pilose antler polypeptide (PAP, 3.2KD) was one of its main active components with multiple biological activities for cardiomyopathy. PAP-3.2KD exerts protective effects againt myocardial fibrosis. The present study demonstrated the protective mechanism of PAP-3.2KD against Adriamycin (ADR)-induced myocardial injury through using animal model with ADR-induced myocardial injury. PAP-3.2KD markedly improved the weight increase and decreased the HW/BW index, heart rate, and ST height in ADR-induced groups. Additionally, PAP-3.2KD reversed histopathological changes (such as disordered muscle bundles, myocardial fibrosis and diffuse myocardial cellular edema) and scores of the heart tissue, ameliorated the myocardial fibrosis and collagen volume fraction through pathological examination, significantly increased the protein level of Bcl-2, and decreased the expression levels of Bax and caspase-3 in myocardial tissue by ELISA, compared to those in ADR-induced group. Furthermore, ADR stimulation induced the increased protein levels of TGF-β1 and SMAD2/3/4, the increased phosphorylation levels of SMAD2/3 and the reduced protein levels of SMAD7. The expression levels of protein above in ADR-induced group were remarkably reversed in PAP-3.2KD-treated groups. PAP-3.2KD ameliorated ADR-induced myocardial injury by regulating the TGF-β/SMAD signaling pathway. Thus, these results provide a strong rationale for the protective effects of PAP against ADR-induced myocardial injury, when ADR is used to treat cancer.

scholarly journals Antioxidant and anti-inflammatory effect of ligustilide on sepsis-induced acute kidney injury via TLR4/NF-κB and Nrf2/HO-1 signaling

2021 ◽  
Vol 20 (1) ◽  
pp. 83-87
Author(s):  
Xiumin Yang ◽  
Chencai Qiao ◽  
Chao Zheng ◽  
Qingjun Deng
Keyword(s):  
Acute Kidney Injury ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Serum Levels ◽  
Heme Oxygenase 1 ◽  
Protein Levels ◽  
Anti Inflammatory ◽  
Commercial Kits

Purpose: To investigate the protective effect of ligustilide on sepsis-induced acute kidney injury (AKI) and the signaling pathways involved.Methods: Sepsis-induced AKI was established by cecal ligation and puncture (CLP) in mice. Histopathological renal damage was examined using hematoxylin and eosin (H & E) staining while creatinine and cytokines were measured using commercial kits. Protein levels were determined by Western blotting.Results: Vacuoles, dilations, degeneration, and necrosis were observed in CLP mouse kidneys, but these alterations were countered by 20 mg/kg of ligustilide. Serum creatinine, blood urea nitrogen (BUN), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were significantly increased in CLP mice compared with control. Furthermore, the serum levels of these indicators in serum were lowered by ligustilide (p < 0.01). The expression levels of Toll-like receptor 4 (TLR4) TLR4 and phosphorylated nuclear factor (NF)-κB in CLP mice were also downregulated by ligustilide. Malondialdehyde (MDA) and myeloperoxidase (MPO) levels increased in CLP mice, but were attenuated by ligustilide (p < 0.01). Superoxide dismutase (SOD) and glutathione (GSH) levels decreased in CLP mice but were increased by ligustilide (p < 0.01). Increased expression of Nrf2 and heme oxygenase-1 (HO-1) were observed in CLP mice, and were further enhancced by ligustilide.Conclusion: Ligustilide exerts antioxidant and anti-inflammatory effects on sepsis-induced AKI via TLR4/NF-κB and Nrf2/HO-1 signaling pathways. Keywords: Ligustilide, Sepsis, Acute kidney injury, TLR4/NF-κB signaling pathway, Nrf2/HO-1 signaling pathway

scholarly journals Proanthocyanidins Protect Against Cadmium-Induced Diabetic Nephropathy Through p38 MAPK and Keap1/Nrf2 Signaling Pathways

2022 ◽  
Vol 12 ◽  
Author(s):  
Pin Gong ◽  
Peipei Wang ◽  
Sihui Pi ◽  
Yuxi Guo ◽  
Shuya Pei ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Protective Mechanism ◽  
Protective Effects ◽  
Antioxidative Status

Diabetic nephropathy (DN) is one of the most devastating complications of diabetes mellitus. Although cadmium (Cd) exposure might be involved in the pathogenesis of DN, the underlying mechanism is still unclear. In this study, we explored the protective effects and possible mechanism of proanthocyanidins (OPC) from grape seed using a mouse model of Cd-induced DN. The successful establishment of this model was verified by analyzing the physiological and biochemical indices of mice, including their body weight and tissue ratio; levels of blood glucose, creatinine, microalbumin, total cholesterol, triglycerides, high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol; and was based on histopathological examination. Oxidative-antioxidative status, elemental analysis, and key signaling pathway analysis were performed to explore the possible protective mechanism of OPC. The protective effects of OPC and its possible mechanism in preventing the progression of DN were investigated using a multidimensional approach, including its ability in regulating oxidative-antioxidative status (lipid peroxidation, protein carbonyl, superoxide dismutase, and glutathione GST, GSH-Px), metal-binding ability (Cd levels in the kidneys and urine and MT content) and mediation of essential elements (Zn, Ca, Cu, and Fe levels in the kidneys), and activation of the p38 MAPK and Keap1/Nrf2 signaling pathways. OPC exhibited a significant renoprotective effect, attributed to the metal-chelating ability, anti-oxidative effect, and mediation of oxidative stress-related signaling pathway. These results highlight the potential of OPC in preventing or treating DN in humans and suggest the dietary intake of grapes, which are rich in polyphenols, for the prevention of type 2 diabetes mellitus and its complications.

Tangeretin Inhibits Oxidative Stress and Inflammation via Upregulating Nrf-2 Signaling Pathway in Collagen-Induced Arthritic Rats

Pharmacology ◽  
2019 ◽  
Vol 104 (3-4) ◽  
pp. 187-195 ◽  
Author(s):  
Xing Li ◽  
Peigen Xie ◽  
Yu Hou ◽  
Shudong Chen ◽  
Peiheng He ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Chinese Herb ◽  
Biological Properties ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Ifn Γ ◽  
Anti Inflammatory

Background/Aims: Tangeretin (TAN), a major phytochemical in tangerine peels and an important Chinese herb, has multiple biological properties, especially antioxidative and anti-inflammatory effects. However, the mechanisms remain unclear. Based on these findings, the aim of the present study was to assess the antioxidant and anti-inflammatory properties of TAN in bovine type II collagen-induced arthritis rats. Methods: TAN (50 mg/kg) was given orally once daily for 14 days. The effects of treatment were evaluated by biochemical assay (articular elastase, myeloperoxidase, end products of lipid peroxidation [MDA], antioxidant enzyme, such as superoxide dismutase, catalase, glutathione), nitric oxide, and inflammatory cytokines (interleukin-1β [IL-1β], ­IL-10, tumor necrosis factor-alpha [TNF-α], interferon-γ [IFN-γ], and prostaglandin E2 [PGE2]). The protective effects of TAN against rheumatoid arthritis (RA) were evident from the decrease in arthritis scoring. Furthermore, the Nrf-2 signaling pathway was assessed to illustrate the molecular mechanism. Results: TAN had therapeutic effects on RA by decreasing the oxidative stress damage and regulating inflammatory cytokine expression, including suppression of the accumulation of MDA products, decreasing the IL-1β, TNF-α, IFN-γ, and PGE2 levels, enhancing the IL-10 and the activity of antioxidant enzymes, which was through upregulating Nrf-2 signaling pathway. Conclusion: TAN might have potential as a therapeutic agent for the treatment of RA.

scholarly journals Effects of Dexmedetomidine Postconditioning on Myocardial Ischemia/Reperfusion Injury in Diabetic Rats: Role of the PI3K/Akt-Dependent Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Xiangyang Cheng ◽  
Jing Hu ◽  
Ya Wang ◽  
Hongwei Ye ◽  
Xiaohong Li ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Signaling Pathway ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Mrna Level ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Protective Effects ◽  
Sod Activity ◽  
Group I

Objective. The present study was designed to determine whether dexmedetomidine (DEX) exerts cardioprotection against myocardial I/R injury in diabetic hearts and the mechanisms involved. Methods. A total of 30 diabetic rats induced by high-glucose-fat diet and streptozotocin (STZ) were randomly assigned to five groups: diabetic sham-operated group (DM-S), diabetic I/R group (DM-I/R), diabetic DEX group (DM-D), diabetic DEX + Wort group (DM-DW), and diabetic Wort group (DM-W). Another 12 age-matched male normal SD rats were randomly divided into two groups: sham-operated group (S) and I/R group (I/R). All rats were subjected to 30 min myocardial ischemia followed by 120 min reperfusion except sham groups. Plasmas were collected to measure the malondialdehyde (MDA), creatine kinase isoenzymes (CK-MB), and lactate dehydrogenase (LDH) levels and superoxide dismutase (SOD) activity at the end of reperfusion. Pathologic changes in myocardial tissues were observed by H-E staining. The total and phosphorylated form of Akt and GSK-3β protein expressions were measured by western blot. The ratio of Bcl-2/Bax at mRNA level was detected by reverse transcription-polymerase chain reaction (RT-PCR). Results. DEX significantly reduced plasma CK-MB, MDA concentration, and LDH level and increased SOD activity caused by I/R. The phosphorylation of Akt and GSK-3β was increased, Bcl-2 mRNA and the Bcl-2/Bax ratio was increased, and Bax mRNA was decreased in the DEX group as compared to the I/R group, while posttreatment with Wort attenuated the effects induced by DEX. Conclusion. The results of this study suggest that DEX postconditioning may increase the phosphorylation of GSK-3β by activating the PI3K/Akt signaling pathway and may inhibit apoptosis and oxidative stress of the myocardium, thus exerting protective effects in diabetic rat hearts suffering from I/R injury.

scholarly journals Systematic Bioinformatic Analyses of Nutrigenomic Modifications by Polyphenols Associated with Cardiometabolic Health in Humans—Evidence from Targeted Nutrigenomic Studies

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2326
Author(s):  
Tatjana Ruskovska ◽  
Irena Budić-Leto ◽  
Karla Fabiola Corral-Jara ◽  
Vladimir Ajdžanović ◽  
Anna Arola-Arnal ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Mrna Level ◽  
Bioinformatic Analysis ◽  
Mapk Signaling ◽  
Cardiometabolic Health ◽  
Protective Effects ◽  
Dietary Polyphenols ◽  
Cardiometabolic Disorders

Cardiometabolic disorders are among the leading causes of mortality in the human population. Dietary polyphenols exert beneficial effects on cardiometabolic health in humans. Molecular mechanisms, however, are not completely understood. Aiming to conduct in-depth integrative bioinformatic analyses to elucidate molecular mechanisms underlying the protective effects of polyphenols on cardiometabolic health, we first conducted a systematic literature search to identify human intervention studies with polyphenols that demonstrate improvement of cardiometabolic risk factors in parallel with significant nutrigenomic effects. Applying the predefined inclusion criteria, we identified 58 differentially expressed genes at mRNA level and 5 miRNAs, analyzed in peripheral blood cells with RT-PCR methods. Subsequent integrative bioinformatic analyses demonstrated that polyphenols modulate genes that are mainly involved in the processes such as inflammation, lipid metabolism, and endothelial function. We also identified 37 transcription factors that are involved in the regulation of polyphenol modulated genes, including RELA/NFKB1, STAT1, JUN, or SIRT1. Integrative bioinformatic analysis of mRNA and miRNA-target pathways demonstrated several common enriched pathways that include MAPK signaling pathway, TNF signaling pathway, PI3K-Akt signaling pathway, focal adhesion, or PPAR signaling pathway. These bioinformatic analyses represent a valuable source of information for the identification of molecular mechanisms underlying the beneficial health effects of polyphenols and potential target genes for future nutrigenetic studies.

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