ArticleLiterature Review

Molecular understanding of Epigallocatechin gallate (EGCG) in cardiovascular and metabolic diseases

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Abstract

Ethnopharmacological relevance: The compound epigallocatechin-3-gallate (EGCG), the major polyphenolic compound present in green tea [Camellia sinensis L. (Theaceae], has shown numerous cardiovascular health promoting activity through modulating various pathways. However, molecular understanding of the cardiovascular protective role of EGCG has not been reported. Aim of the review: This review aims to compile the preclinical and clinical studies that had been done on EGCG to investigate its protective effect on cardiovascular and metabolic diseases in order to provide a systematic guidance for future research. Materials and methods: Research papers related to EGCG were obtained from the major scientific databases, for example, Science direct, PubMed, NCBI, Springer and Google scholar, from 1995 to 2017. Results: EGCG was found to exhibit a wide range of therapeutic properties including anti-atherosclerosis, anti-cardiac hypertrophy, anti-myocardial infarction, anti-diabetes, anti-inflammatory and antioxidant. These therapeutic effects are mainly associated with the inhibition of LDL cholesterol (anti-atherosclerosis), inhibition of NF-κB (anti-cardiac hypertrophy), inhibition of MPO activity (anti-myocardial infarction), reduction in plasma glucose and glycated hemoglobin level (anti-diabetes), reduction of inflammatory markers (anti-inflammatory) and the inhibition of ROS generation (antioxidant). Conclusion: EGCG shows different biological activities and in this review, a compilation of how this bioactive molecule plays its role in treating cardiovascular and metabolic diseases was discussed.

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... Due to the unavailability of tissue from the cTnI-D127Y patient, we measured the Ca 2+ -sensitivity in guinea pig skinned fibers after exchanging about 60% of the endogenous cardiac troponin by cTnI-D127Y or cTnI-WT ( Figure S3.2). We found that the pCa 50 value was shifted to the left by about 0.5 pCa units (Table 1, Figure 2A). In contrast to cTnC-G34S, maximal force obtained with cTnI-D127Y was slightly, but not significantly, reduced compared to controls (Table 1, Figure S3.2). ± 0.14. ...
... We found that the pCa50 value was shifted to the left by about 0.5 pCa units (Table 1, Figure 2A). In contrast to cTnC-G34S, maximal force obtained with cTnI-D127Y was slightly, but not significantly, reduced compared to controls (Table 1, Figure S3.2). 50 In addition, we analyzed the Ca 2+ -sensitivity in vitro using reconstituted thin filaments. In a first approach, we investigated whether the formation of thin filaments was affected by the two mutants using co-sedimentation. ...
... (C) Representative data for the Ca 2+ dependent increase in fluorescence intensity of thin filaments (TF) reconstituted with troponin complexes (Tn-WT, Tn-G34S, or Tn-D127Y), Tm-PM, cMyBPC, and myosin-S1. Data points are represented as mean of normalized fluorescence ± SEM vs. pCa and fitted to the Hill equation to obtain pCa 50 and nHill values (n = 6-9). Table 2. Summary of y min , y max , and Amp values of the actomyosin-S1-ATPase activity. ...
Article
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Rare pediatric non-compaction and restrictive cardiomyopathy are usually associated with a rapid and severe disease progression. While the non-compaction phenotype is characterized by structural defects and is correlated with systolic dysfunction, the restrictive phenotype exhibits diastolic dysfunction. The molecular mechanisms are poorly understood. Target genes encode among others, the cardiac troponin subunits forming the main regulatory protein complex of the thin filament for muscle contraction. Here, we compare the molecular effects of two infantile de novo point mutations in TNNC1 (p.cTnC-G34S) and TNNI3 (p.cTnI-D127Y) leading to severe non-compaction and restrictive phenotypes, respectively. We used skinned cardiomyocytes, skinned fibers, and reconstituted thin filaments to measure the impact of the mutations on contractile function. We investigated the interaction of these troponin variants with actin and their inter-subunit interactions, as well as the structural integrity of reconstituted thin filaments. Both mutations exhibited similar functional and structural impairments, though the patients developed different phenotypes. Furthermore, the protein quality control system was affected, as shown for TnC-G34S using patient’s myocardial tissue samples. The two troponin targeting agents levosimendan and green tea extract (-)-epigallocatechin-3-gallate (EGCg) stabilized the structural integrity of reconstituted thin filaments and ameliorated contractile function in vitro in some, but not all, aspects to a similar degree for both mutations.
... EGCG with abundant phenolic hydroxyl groups was endowed between PEI-Tpl and nanogels to establish a sandwiched LBL coating and improve the overall performance of the multifunctional coating (35). In addition, EGCG also had protective effects on the endothelial cell function and inhibited SMC proliferation (30,36). HA, a typical component of glycocalyx, not only induces the adhesion and proliferation of endothelial cells but also promotes the conversion of SMCs to a contractile phenotype with low proliferation (37), instead of the synthetic phenotype, which causes restenosis at cardiovascular implantable devices. ...
... Combined with the results of the DPPH assay, it can be concluded that, in all experimental results, R@NG/EGCG/Tpl performed the best anti-inflammatory activity among the three groups due to the antioxidant and anti-inflammatory EGCG. As an anti-inflammatory agent, EGCG was proven to inhibit the TNF- expression and up-regulate the IL-10 expression, thereby suppressing the activation of inflammatory cells (36). On the basis of the above, it was substantiated that the R@NG/ EGCG/Tpl coating inhibited the inflammation of macrophages differentiated from monocytes by suppressing free radical production and regulating the expression of inflammation-related proteins. ...
... As shown in Fig. 4G, the mean radius ratio of R@NG/EGCG/Tpl was significantly lower than that of the control group after both 24 and 72 hours, which suggested that the cell morphology of HUASMCs on the surface of R@NG/EGCG/Tpl was rounder than that of the control group. EGCG generally protects endothelial cell function and inhibits SMC proliferation (30,36). HA had been demonstrated to induce the adhesion and proliferation of endothelial cells by binding to CD44 and the receptor for HA-mediated motility (46). ...
Article
Interrelated coagulation and inflammation are impediments to endothelialization, a prerequisite for the long-term function of cardiovascular materials. Here, we proposed a self-regulating anticoagulant coating strategy combined with anti-inflammatory capacity, which consisted of thrombin-responsive nanogels with anticoagulant and anti-inflammatory components. As an anticoagulant, rivaroxaban was encapsulated in nanogels cross-linked by thrombin-cleavable peptide and released upon the trigger of environmental thrombin, blocking the further coagulation cascade. The superoxide dismutase mimetic Tempol imparted the antioxidant property. Polyphenol epigallocatechin gallate (EGCG), in addition to its anti-inflammatory function in synergy with Tempol, also acted as a weak cross-linker to stabilize the coating. The effectiveness and versatility of this coating were validated using two typical cardiovascular devices as models, biological valves and vascular stents. It was demonstrated that the coating worked as a precise strategy to resist coagulation and inflammation, escorted reendothelialization on the cardiovascular devices, and provided a new perspective for designing endothelium-like functional coatings.
... EGcG is the primary polyphenolic compound in green tea and exhibits cardiovascular health-promoting activity by regulating various pathways (56,57). Because EGcG is extracted from green tea, it has almost no side effects (56,58,59), and this compound exhibits cardioprotection, neuroprotection, renal protection, osteoprotection and anticancer properties, as well as the ability to manage obesity, metabolic syndrome and type 2 diabetes (60), thus making it an ideal safe and effective drug for the treatment of myocardial remodeling (61). ...
... EGcG is the primary polyphenolic compound in green tea and exhibits cardiovascular health-promoting activity by regulating various pathways (56,57). Because EGcG is extracted from green tea, it has almost no side effects (56,58,59), and this compound exhibits cardioprotection, neuroprotection, renal protection, osteoprotection and anticancer properties, as well as the ability to manage obesity, metabolic syndrome and type 2 diabetes (60), thus making it an ideal safe and effective drug for the treatment of myocardial remodeling (61). In certain epidemiological studies, drinking green tea has been shown to decrease the risk of cardiovascular disease (62,63). ...
Article
Myocardial remodeling is a complex pathological process and its mechanism is unclear. The present study investigated whether epigallocatechin gallate (EGCG) prevents myocardial remodeling by regulating histone acetylation and explored the mechanisms underlying this effect in the heart of a mouse model of transverse aortic constriction (TAC). A TAC mouse model was created by partial thoracic aortic banding (TAB). Subsequently, TAC mice were injected with EGCG at a dose of 50 mg/kg/day for 12 weeks. The hearts of mice were collected for analysis 4, 8 and 12 weeks after TAC. Histopathological changes in the heart were observed by hematoxylin and eosin, Masson trichrome and wheat germ agglutinin staining. Protein expression levels were investigated using western blotting. Cardiac function of mice was detected by echocardiography. The level of histone acetylated lysine 27 on histone H3 (H3K27ac) first increased and then decreased in the hearts of mice at 4, 8 and 12 weeks after TAC. The expression levels of two genes associated with pathological myocardial remodeling, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), also increased initially but then decreased. The expression levels of histone deacetylase 5 (HDAC5) gradually increased in the hearts of mice at 4, 8 and 12 weeks after TAC. Furthermore, EGCG increased acetylation of H3K27ac by inhibiting HDAC5 in the heart of TAC mice treated with EGCG for 12 weeks. EGCG normalized the transcriptional activity of heart nuclear transcription factor myocyte enhancer factor 2A in TAC mice treated for 12 weeks. The low expression levels of myocardial remodeling‑associated genes (ANP and BNP) were reversed by EGCG treatment for 12 weeks in TAC mice. In addition, EGCG reversed cardiac enlargement and improved cardiac function and survival in TAC mice when treated with EGCG for 12 weeks. Modification of the HDAC5‑mediated imbalance in histone H3K27ac served a key role in pathological myocardial remodeling. The present results show that EGCG prevented and delayed myocardial remodeling in TAC mice by inhibiting HDAC5.
... Caffeine was found effective against obesity via raising AMP-activated protein kinase phosphorylation in visceral adipose tissues (Pang et al. 2008). The recent findings suggested the ability of polyphenols to regulate obesity by activating adenosine 5′monophosphate-activated protein kinase (Eng et al. 2018). Moreover, the in-vitro study of complex polyphenols (tannins) showed effects on 3 T3-1 pre-adipocyte cells and revealed the antiobesity activity of tannins (Sung et al. 2015). ...
... Hypertension refers to an increased rate of blood pressure that is now a global health problem. Hypertension is also a metabolic syndrome that results in various health effects such as diabetes, cardiovascular diseases (Eng et al. 2018). Catechins reported for the decrease in systolic blood pressure without any adverse effect to hypertensive patients (Nagao et al. 2007). ...
... Caffeine was found effective against obesity via raising AMP-activated protein kinase phosphorylation in visceral adipose tissues (Pang et al. 2008). The recent findings suggested the ability of polyphenols to regulate obesity by activating adenosine 5′monophosphate-activated protein kinase (Eng et al. 2018). Moreover, the in-vitro study of complex polyphenols (tannins) showed effects on 3 T3-1 pre-adipocyte cells and revealed the antiobesity activity of tannins (Sung et al. 2015). ...
... Hypertension refers to an increased rate of blood pressure that is now a global health problem. Hypertension is also a metabolic syndrome that results in various health effects such as diabetes, cardiovascular diseases (Eng et al. 2018). Catechins reported for the decrease in systolic blood pressure without any adverse effect to hypertensive patients (Nagao et al. 2007). ...
Chapter
The food industry is generating huge amounts of by-products, about 1,890,000 tons, which should be better recycled into pharmaceuticals, cosmetics and functional foods, for instance, in order to save costs and avoid pollution. Here we review food by-products and methods of extraction. We present bioactive compounds from fruits, vegetable, tea, coffee, egg, nuts, meat and dairy products. Extracting methods include soxhlet, maceration, microwave, ultrasound, pressure.
... (− )-Epigallocatechin-3-gallate (EGCG, Fig. 1A), an active polyphenol compound derived from green tea, possesses multiple biological activities, such as antitumor, antibacterial, antiinflammatory, antiarteriosclerosis, and cytoprotective activities and is involved in the maintenance of mitochondrial function through multiple targets and mechanisms by changing the expression of some proteins (Nrf-2, ET-1, HO1, NADPH and Bcl-2) and cytokines and regulating ROS/ERK/JNK-p53, ADMA/DDAH/NOS/NO and PI-3K/AKT/NF-κB pathway [24,25]. EGCG has strong antioxidant activity and chelates divalent metal ions, such as iron, owing to its special stereochemical structure [26,27]. ...
... We believe that EGCG is a candidate phytochemical. A large number of studies have demonstrated that EGCG could affect the expression of specific proteins and signal pathways, such as AMPK and related pathways [28,30,[60][61][62], and intervene in a variety of RCD forms, such as autophagy, apoptosis, and ferroptosis [34][35][36][63][64][65], all of which confirm its pharmacological characteristics, multiple targets, and underlying mechanisms [24,25]. Our results revealed that in DIC, EGCG pretreatment effectively decreased iron accumulation, inhibited excess ROS generation and oxidative stress, and rectified abnormal lipid metabolism in vitro and in vivo, which was similar to the intervention effects of the ferroptosis inhibitor Fer-1 [19,20], iron chelator Dxz [52,58], and mitochondrial free radical scavenger MitoTEMPO [18,19]. ...
Article
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Reports indicate that the mechanism of doxorubicin (Dox)-induced cardiotoxicity is very complex, involving multiple regulatory cell death forms. Furthermore, the clinical intervention effect is not ideal. Iron dependence, abnormal lipid metabolism, and excess reactive oxygen species generation, three characteristics of ferroptosis, are potential therapeutic intervention targets. Here, we confirmed in vitro and in vivo that at least autophagy, apoptosis, and ferroptosis are involved in Dox cardiotoxicity-induced damage. When the neonatal rat cardiomyocytes and H9C2 cells or C57BL/6 mice were subjected to Dox-induced cardiotoxicity, epigallocatechin-3-gallate pretreatment could effectively decrease iron accumulation, inhibit oxidative stress and abnormal lipid metabolism, and thereby alleviate Dox cardiotoxicity-induced ferroptosis and protect the myocardium according to multiple functional, enzymatic, and morphological indices. The underlying mechanism was verified to involve the upregulation and activation of AMP-activated protein kinase α2, which promoted adaptive autophagy, increased energy supply, and maintained mitochondrial function. We believe that epigallocatechin-3-gallate is a candidate phytochemical against Dox-induced cardiotoxicity.
... Mounting epidemiological studies have revealed that tea drinking reduces the incidence of acute cardiovascular events (Eng, Thanikachalam, and Ramamurthy 2018). Epigallocatechin-3-gallate (EGCG), is the most abundant bioactive polyphenol from green tea (Eng, Thanikachalam, and Ramamurthy 2018). ...
... Mounting epidemiological studies have revealed that tea drinking reduces the incidence of acute cardiovascular events (Eng, Thanikachalam, and Ramamurthy 2018). Epigallocatechin-3-gallate (EGCG), is the most abundant bioactive polyphenol from green tea (Eng, Thanikachalam, and Ramamurthy 2018). Apart from green tea, it is also present in white, oolong, bleack teas, strawberries, cranberries, kiwis, blackberries, Brazil nut, pecans, cherries, peaches, pears, apples, avocados, pistachios and hazelnuts (Arts, Van De Putte, and Hollman 2000;Bhagwat, Haytowitz, and Holden 2014). ...
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Vascular diseases arise due to vascular endothelium dysfunction in response to several pro-inflammatory stimuli and invading pathogens. Thickening of the vessel wall, formation of atherosclerotic plaques consisting of proliferating smooth muscle cells, macrophages and lymphocytes are the major consequences of impaired endothelium resulting in atherosclerosis, hypercholesterolemia, hypertension, type 2 diabetes mellitus, chronic renal failure and many others. Decreased nitric oxide (NO) bioavailability was found to be associated with anomalous endothelial function because of either its reduced production level by endothelial NO synthase (eNOS) which synthesize this potent endogenous vasodilator from L-arginine or its enhanced breakdown due to severe oxidative stress and eNOS uncoupling. Polyphenols are a group of bioactive compounds having more than 7000 chemical entities present in different cereals, fruits and vegetables. These natural compounds possess many OH groups which are largely responsible for their strong antioxidative, anti-inflammatory antithrombotic and anti-hypersensitive properties. Several flavonoid-derived polyphenols like flavones, isoflavones, flavanones, flavonols and anthocyanidins and non-flavonoid polyphenols like tannins, curcumins and resveratrol have attracted scientific interest for their beneficial effects in preventing endothelial dysfunction. This article will focus on in vitro as well as in vivo and clinical studies evidences of the polyphenols with eNOS modulating activity against vascular disease condition while their molecular mechanism will also be discussed.
... Quercetin has several anti-inflammatory properties (20), also inhibits obesity (21),type-2 diabetes (21) and inflammation (20), (21). 4) Epigallocatechin is a polyphenol (22),has therapeutic effects against cardiovascular diseases (23) and metabolic diseases (23), has immense anti cancer properties (24),It also regulates cancer stem cells (24),also interacts with metalloproteinase (24) and has significant regulation and modulation in signalling pathways (24), (25). Epigallocatechin inhibits Plpro(Papain like Protease) which is a crucial for viral polyprotein processing and cleavage (27), (28), (29). ...
... Quercetin has several anti-inflammatory properties (20), also inhibits obesity (21),type-2 diabetes (21) and inflammation (20), (21). 4) Epigallocatechin is a polyphenol (22),has therapeutic effects against cardiovascular diseases (23) and metabolic diseases (23), has immense anti cancer properties (24),It also regulates cancer stem cells (24),also interacts with metalloproteinase (24) and has significant regulation and modulation in signalling pathways (24), (25). Epigallocatechin inhibits Plpro(Papain like Protease) which is a crucial for viral polyprotein processing and cleavage (27), (28), (29). ...
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SARS-Cov-2 or COVID-19 has caused a global disaster and catastrophe which has consequently led to a pandemic for the last two decades, the world has faced coronaviruses similar to SARS-Cov-2 such as SARS-Cov and Mers-Cov. In this study, a wide range of proteins such as Plpro (Papain like Protease), Rdrp (RNA-Dependent-RNA-Polymerase), Mpro or 3cl Protease and Spike Protein. The selected proteins were listed retrieved from RCSB PDB(https://www.rcsb.org/) And Zhang lab (https://www.zhanglab.ccmb.med.umich.edu/COVID-19/) with their corresponding and respective PDB-ID. The 3d Structures or 2D Structures of these molecules were selected on the sole basis of resolved resolution (in Å)of the structures during the X-ray crystallography and Electron Microscopy. Structures were retrieved in .pdb format. The three dimensional ligand molecules were retrieved from PubChem chemical structure In Spatial Data Base (.SDF) format. The respective ligand molecules are; Hesperidin, Kaempferol, Quercetin, Epigallocatechin. This molecular docking shows significant data of polyphenols, flavonoids and bioflavonoids inhibiting SARS-Cov-2 proteins which could lead to conclusive data for treatment of polyphenols, flavonoids and bioflavonoids against SARS-Cov-2.
... The mechanism of this phenomenon is still unclear, but in general, lack of sleep increases oxidative stress in the hippocampus and other areas of the brain (Singh et al., 2008). EGCG is the major and most active constituent of tea catechins (Eng et al., 2018). There is growing evidence that EGCG has a variety of health benefits, largely related to its antioxidant properties. ...
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Tea polyphenols (TP) are one of the most functional and bioactive substances in tea. The interactions between TP and intestinal microbiota suggest that probiotics intervention is a useful method to ameliorate neurological diseases. Now, numerous researches have suggested that TP plays a significant role in modulating intestinal bacteria, especially in the area of sustaining a stable state of intestinal microbial function and abundance. Furthermore, homeostatic intestinal bacteria can enhance the immunity of the host. The close reciprocity between intestinal microbiota and the central nervous system provides a new chance for TP to modulate neural-related diseases depending on intestinal microbiota. Therefore, based on the bidirectional relationship between the brain and the intestines, this review provides a new clue to solve insomnia symptoms and related neurological diseases that will enable us to better study the bidirectional effects of TP and intestinal microbiota on the improvement of host health. Practical applications This review provides a new clue to solve insomnia symptoms and related neurological diseases that will enable us to better study bidirectional effects of TP and intestinal microbiota on the improvement of host health.
... We excluded 14systematic reviews for the following reasons: one was a conference abstract [35], one was a non-English publication [44], one publication included only extracts or capsules [39], one study combined tea and wine with tea in the analyses [37], three were not systematic reviews [41,42,45], one publication did not assess tea intake [43], one publication was a systematic review of in vitro studies [36], one publication included CVD markers only as a secondary outcome [38], one publication was a protocol manuscript [51], two publications did not contain data [47,48], and one publication search predated 2010 [40]. Twenty-three publications [2,3,11,[18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34]46] remained after dual full-text screening and searching the reference lists of included systematic reviews. ...
Article
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Brewed tea (Camellia sinensis) is a major dietary source of flavonoids, in particular flavan-3-ols. Tea consumption has been suggested to be inversely associated with a decreased risk of cardiovascular disease (CVD). Several biological mechanisms support the inverse relationship between tea flavonoid intake and CVD risk. Given the recent accumulating evidence from various systematic reviews regarding the role of tea as a beverage in reducing CVD risk and severity, we conducted an umbrella review to describe and critically evaluate the totality of evidence to date. We searched the PubMed, Web of Science, Cochrane Database of Systematic Reviews, and BIOSIS databases for systematic reviews published between January 1, 2010 and February 22, 2020 reporting relationships between tea (C. sinensis) consumption and CVD mortality, CVD diagnosis or incidence, CVD events, stroke events, blood pressure, endothelial function, blood lipids and triglycerides, and inflammatory markers. Herein, we describe results from 23 included systematic reviews. Consistently consuming 2 cups of unsweet tea per day offers the right levels of flavonoids to potentially decrease CVD risk and its progression. This is supported by the consistency between a recent high-quality systematic review and dose-response meta-analyses of population-based studies demonstrating beneficial effects of consumption on CVD mortality, CVD events and stroke events and medium- to high-quality systematic reviews of intervention studies that further elucidate potential benefits on both validated (i.e., SBP, DBP, total cholesterol, and LDL-cholesterol) and emerging risk biomarkers of CVD (TNF-ɑ and IL-6). On the basis of this umbrella review, the consumption of tea as a beverage did not seem to be harmful to health; therefore, the benefits of moderate consumption likely outweigh risk. Future large, clinical intervention studies will provide better mechanistic insight with the ability to confirm the outcome effects shown across observational studies. The review protocol was registered on PROSPERO (https://www.crd.york.ac.uk/PROSPERO/) as CRD42020218159. • KEY MESSAGES • It is reasonable to judge that 2 cups of unsweet tea per day has the potential to decrease CVD risk and progression due to its flavonoid content. • The primary side effects of tea documented in human studies are hepatotoxicity and gastrointestinal disturbances (i.e., vomiting and diarrhea) after high-dose supplemental intake. • Additional clinical research is needed to fully elucidate the effects of tea flavonoids on markers of CVD, as many studies were under-powered to detect changes.
... EGCG interferes with many disease-related signaling mechanisms, specifically by inhibiting a small number of targets, at biologically relevant concentrations delivered by dietary consumption [46]. Its beneficial effects in CVDs have been extensively tested experimentally and in prospective cohort studies [30,47]. Our present findings reveal molecular details of the mechanism of EGCG-mediated inhibition of NF-κB. ...
Article
Tea contains antioxidant catechins thought to exert health-promoting protective effects against conditions involving chronic inflammation, such as cardiovascular diseases. The most abundant catechin in tea is Epigallocatechin Gallate (EGCG), thought to be a key contributor to tea’s health-promoting actions. EGCG exerts protective cardiovascular effects via its antioxidant, antiinflammatory, hypolipidemic, anti-thrombogenic, and anti-hypertensive actions. Because EGCG inhibits the strong proinflammatory gene-inducing transcription factor NF-κB, we analyzed the chemical and molecular details of the mechanism by which EGCG mediates NF-κB inhibition. We quantified and mapped key parameters of its chemical reactivity including its electrophilic Fukui ƒ+ function, in silico covalent binding, and identified its frontier Molecular Orbitals (MOs) and nucleophilic susceptibility. These physical and chemical reactivity parameters revealed that the bond-forming MOs are distributed on the B ring of the EGCG oxidized state with nucleophilic susceptibility, and that this B ring has properties that favor participating in a Cys-alkylating 1,4-addition reaction. Molecular modeling and docking analysis further revealed that EGCG bonds covalently with Cys-38 of NF-κB-p65, and thereby inhibits its DNA binding ability. We also generated a model pharmacophore based on the EGCG-NF-κB complex. We conclude that EGCG covalently binds to NF-κB-p65 and inhibits it by abolishing its DNA binding, by chemical mechanisms that may inform design of EGCG derivatives as novel anti-inflammatory agents.
... Epigallocatechin gallate (EGCG) is the major component of green tea catechins, which has been extensively investigated and is well known for its prominent biological activities against obesity, atherosclerosis, and diabetes (8)(9)(10). Many studies revealed that EGCG could prevent or alleviate obesity-related pathologies by manipulating the microbial ecology of the gut (11)(12)(13). ...
Article
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This study aimed to investigate the regulatory effect of epigallocatechin gallate (EGCG) on the composition of the gut microbiome, the transcriptomic profiling of ileum, and their interplay in high fat diet (HFD) induced obese mice. Intragastric administration of EGCG to C57BL/6J mice for 14 consecutive weeks remarkably decreased HFD induced excessive fat deposition ( p < 0.001), and the increment of serum TG, TC, HDL-C ( p < 0.05), as well as improved glucose tolerance ( p < 0.001). EGCG shifted the gut microbiota mainly by elevating the relative abundance of Parasutterrlla, Bacteroides , and Akkermansia ( p < 0.01), decreasing that of norank_f_Erysipelotrichaceae, unclassified_f_Ruminococcaceae, Anaerotruncus, Roseburia, norank_Lachnospiraceae , and Lachnospiraceae_UCG_006 ( p < 0.01) at the genus level. In addition, EGCG affected the transcriptomic profiling of ileum, and the differentially expressed (DE) genes after HFD or/and EGCG treatment were mostly enriched in the immune reaction of ileum, such as the GO term of “immune effector process” and “phagocytosis, recognition.” Furthermore, the KEGG category of “immune diseases,” “immune system,” and “infection diseases: bacterial” were commonly enriched by the DE genes of the two treatments. Among those DE genes, 16 immunoglobulins heavy chain variable region encoded genes ( Ighvs ) and other immunity-related genes, such as complement component 2 ( C2 ), interferon-induced transmembrane protein 1 ( Iftm1 ), polymeric immunoglobulin receptor ( pigR ), and alanyl aminopeptidase ( Anpep ), were highly correlated with the shifted microbes in the gut ( p < 0.05, absolute r > 0.5). Overall, the results suggested that EGCG ameliorated the HFD induced metabolic disorder mainly by regulating gut microbiome profiling and the immunoglobulin production of ileum, while the genes expressed in the ileum, especially Ighvs, C2, Iftm1, pigR , and Anpep , might play important roles in coordinating the immunity of mice regarding the gut microbes and the host interactions.
... Epigallocatechin-3-gallate (EGCG) is a powerful natural antioxidant with both hypolipidemic activity and antihypertensive effects. Several studies support the view that EGCG has many benefits in the treatment of cardiovascular diseases [82][83][84]. However, the low bioavailability and instability of EGCG limit its effectiveness in the prevention and treatment of human cardiovascular diseases. ...
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Natural products have antitumor, anti-inflammatory, antioxidant, and other pharmacological activities and are an important source of drugs for prevention and treatment of various diseases. However, the inherent defects of natural products in physiological media such as poor solubility and stability and short biological half-life limit their clinical application. In recent years, more and more attention has been paid to the science of drug delivery by nanoscale materials. A large number of in vitro and in vivo studies have further confirmed the efficacy and safety of nanomedicine based on natural products in preclinical models of various diseases. In this review, we summarized the achievements of nanomaterials in improving the efficacy of natural products, introduced the research progress in several key fields of natural product-based nanomedicine in medical application, and discussed the challenges and prospects of clinical transformation of nanomedicine.
... Resveratrol was found to stimulate endothelial production of nitric oxide, reduce oxidative stress, inhibit vascular inflammation, and prevent platelet aggregation [10]. Recent studies have found that some natural polyphenols have antiosteoarthritic effects such as epigallocatechin gallate, resveratrol, piceatannol, pterostilbene, and honokiol [11][12][13][14][15]. eir structures are shown in Figure 2. e specific mechanism of anti-OA is described in Section 3. ...
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Background: Osteoarthritis (OA) is a clinical joint degenerative disease, the pathogenic factors of which include age, obesity, and mechanical injury. Its main pathological features include cartilage loss, narrowing of joint space, and osteophyte formation. At present, there are a variety of treatment methods for OA. Natural products, which are gradually being applied in the treatment of OA, are advantageous as they present with low toxicity and low costs and act on multiple targets. Methods: The terms "natural products," "osteoarthritis," and "chondrocytes" were searched in PubMed to screen the related literature in the recent 10 years. Results: We comprehensively introduced 62 published papers on 48 natural products involving 6, 3, 5, 12, 4, and 5 kinds of terpenoids, polysaccharides, polyphenols, flavonoids, alkaloids, and saponins, respectively (and others). Conclusion: The mechanisms of their anti-OA action mainly involve reducing the production of inflammatory factors, reducing oxidative stress, regulating the metabolism of chondrocytes, promoting the proliferation of chondrocytes, or inhibiting chondrocyte apoptosis. This article summarizes the anti-OA activity of natural products in the last 10 years and provides candidate monomers for further study for use in OA treatment.
... Lots of literatures reported that EGCG exhibited beneficial activity in treating coronary artery disorder [11,12]. More importantly, EGCG was discovered to had protective activity on I/R-resulted damage in many tissues, such as kidney [13], brain [14], skeletal muscle [15] and heart [16]. ...
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Myocardial ischemia/reperfusion (I/R) injury is a serious issue during the therapy of myocardial infarction. Herein, we explored the beneficial influence of Epigallocatechin-3-gallate (EGCG) on hypoxia/reoxygenation (H/R)-stimulated cardiomyocyte H9c2 cells damage, along with possible internal molecular mechanism related autophagy related 4C (ATG4C). H9c2 cells were subjected to H/R stimulation and/or EGCG treatment. ATG4C mRNA expression was measured via q-PCR assay. ATG4C overexpression plasmid (OE-ATG4C) was transfected to arise ATG4C level. Cell viability, apoptosis, reactive oxygen species (ROS) production, ATP level were tested via CCK-8 assay, Annexin V-FITC/PI staining, DCFH-DA staining and ATP Assay Kit, respectively. Western blotting was performed to test Cleaved-caspase 3, Cleaved-caspase 9, cytochrome C and LC3B protein levels. H/R stimulation resulted in H9c2 cell viability loss, promoted cell apoptosis and ROS overproduction, as well as lowered ATP level in cells. EGCG treatment alleviated H/R-resulted H9c2 cell viability loss, cell apoptosis, ROS overproduction and reduction of ATP level. Moreover, H/R stimulation reduced the ATG4C expression in H9c2 cells, while EGCG raised the ATG4C expression. Overexpression of ATG4C strengthened the beneficial influence of EGCG on H/R-stimulated H9c2 cell viability, apoptosis and ROS production. Besides, ATG4C overexpression weakened the H/R-stimulated H9c2 cell autophagy via reducing LC3B II/I expression. EGCG exerted beneficial influence on H/R-stimulated cardiomyocytes, which protected cardiomyocytes from H/R-stimulated viability loss, apoptosis and ROS overproduction via enhancing ATG4C expression.
... Epigallocatechin-3-gallate (EGCG), which is an ester that forms through the reaction of epigallocatechin and gallic acid, is the major catechin in tea [140]. Substantial evidence suggests that EGCG elicit a wide range of properties, including antioxidant and anti-lipid deposition and anti-inflammation [141][142][143]. ...
Article
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Cardiovascular diseases are the leading causes of the death around the world. An elevation of the low-density lipoprotein cholesterol (LDL-C) level is one of the most important risk factors for cardiovascular diseases. To achieve optimal plasma LDL-C levels, clinal therapies were investigated which targeted different metabolism pathways. However, some therapies also caused various adverse effects. Thus, there is a need for new treatment options and/or combination therapies to inhibit the LDL-C level. Dietary polyphenols have received much attention in the prevention of cardiovascular diseases due to their potential LDL-C lowering effects. However, the effectiveness and potential mechanisms of polyphenols in lowering LDL-C is not comprehensively summarized. This review focused on dietary polyphenols that could reduce LDL-C and their mechanisms of action. This review also discussed the limitations and suggestions regarding previous studies.
... In 2017, Marunaka and team reviewed quercetin's anti-hypertensive action and the potential underlying mechanisms involved [22]. Eng and colleagues compiled preclinical and clinical studies on epigallocatechin gallate's function in cardiovascular and metabolic diseases later in 2018 [23]. Choy and colleagues also studied the possible impact of flavonoids in minimising inflammation associated with cardiovascular disease by modulating NFкB signalling [24]. ...
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Clinically, timely reperfusion strategies to re-establish oxygenated blood flow in ischemic heart diseases seem to salvage viable myocardium effectively. Despite the remarkable improvement in cardiac function, reperfusion therapy could paradoxically trigger hypoxic cellular injury and dysfunction. Experimental laboratory models have been developed over the years to explain better the pathophysiology of cardiac ischemia–reperfusion injury, including the in vitro hypoxia-reoxygenation cardiac injury model. Furthermore, the use of nutritional myocardial conditioning techniques have been successful. The cardioprotective potential of flavonoids have been greatly linked to its anti-oxidant, anti-apoptotic and anti-inflammatory properties. While several studies have reviewed the cardioprotective properties of flavonoids, there is a scarce evidence of their function in the hypoxia-reoxygenation injury cell culture model. Hence, the aim of this review was to lay out and summarize our current understanding of flavonoids’ function in mitigating hypoxia-reoxygenation cardiac injury based on evidence from the last five years. We also discussed the possible mechanisms of flavonoids in modulating the cardioprotective effects as such information would provide invaluable insight on future therapeutic application of flavonoids.
... Epigallocatechin-3-gallate (EGCG) is a green tea polyphenol belonging to sub-class flavonoids [49] ( Figure 1B). EGCG is known to have beneficial effects against cardiovascular diseases [50] and cancer [51,52] and plays a protective role in protein misfolding. EGCG functions in neuroprotection by acting as an anti-oxidant and iron chelator [53]. ...
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Background: Alzheimer's disease is a type of dementia denoted by progressive neuronal death due to the accumulation of proteinaceous aggregates of Tau. Post-translational modifications like hyperphosphorylation, truncation, glycation, etc. play a pivotal role in Tau pathogenesis. Glycation of Tau aids in paired helical filament formation and abates its microtubule-binding function. The chemical modulators of Tau PTMs, such as kinase inhibitors and antibody-based therapeutics, have been developed, but natural compounds, as modulators of Tau PTMs are not much explored. Materials and methods: We applied biophysical and biochemical techniques like fluorescence kinetics, oligomerization analysis and transmission electron microscopy to investigate the impact of EGCG on Tau glycation in vitro. The effect of glycation on cytoskeleton instability and its EGCG-mediated rescue were studied by immunofluorescence microscopy in neuroblastoma cells. Results: EGCG inhibited methyl glyoxal (MG)-induced Tau glycation in vitro. EGCG potently inhibited MG-induced advanced glycation endproducts formation in neuroblastoma cells as well modulated the localization of AT100 phosphorylated Tau in the cells. In addition to preventing the glycation, EGCG enhanced actin-rich neuritic extensions and rescued actin and tubulin cytoskeleton severely disrupted by MG. EGCG maintained the integrity of the Microtubule Organizing Center (MTOC) stabilized microtubules by Microtubule-associated protein RP/EB family member 1 (EB1). Conclusions: We report EGCG, a green tea polyphenol, as a modulator of in vitro methylglyoxal-induced Tau glycation and its impact on reducing advanced glycation end products in neuroblastoma cells. We unravel unprecedented function of EGCG in remodeling neuronal cytoskeletal integrity.
... Therefore, it is possible that the pharmacological modulation of GSK3b or other desmin-modifying enzymes could result in decreased desmin aggregation. We also showed that the green tea polyphenol epigallocatechin gallate (EGCG) can effectively 'de-aggregate' desmin fibrils in vitro [35], providing yet another rationale for the beneficial effects of EGCG in the protection from heart disease [106]. Proteinopathies have gained considerable attention in recent years, and pharmacological approaches that aim to stabilize unstable protein conformations or limit fibrillization are either being tested or approved for clinical use [30]. ...
Article
Desmin is the primary intermediate filament (IF) protein of cardiac, skeletal and smooth muscle. By linking the contractile myofibrils to the sarcolemma and cellular organelles, desmin IF contribute to muscle structural and cellular integrity, force transmission, and mitochondrial homeostasis. Mutations in desmin cause myofibril misalignment, mitochondrial dysfunction, and impaired mechanical integrity leading to cardiac and skeletal myopathies in humans, often characterized by the accumulation of protein aggregates. Recent evidence indicates that desmin filaments also regulate proteostasis and cell size. In skeletal muscle, changes in desmin filament dynamics can facilitate catabolic events as an adaptive response to a changing environment. In addition, post‐translational modifications of desmin and its misfolding in the heart have emerged as key determinants of homeostasis and disease. In this review, we provide an overview of the structural and cellular roles of desmin, and propose new models for its novel functions in preserving the homeostasis of striated muscles.
... Epigallocatechin gallate (EGCG), an important component of green tea, is a nutraceutical with strong antioxidant, anticarcinogenic, anti-inflammatory, and cardioprotective bioactivities [10][11][12][13]. Importantly, EGCG has promising effects on nutrient metabolism [14]. ...
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Epigallocatechin gallate (EGCG) and L-theanine (LTA) are important bioactive components in tea that have shown promising effects on nutrient metabolism. However, whether EGCG alone or combined with LTA can regulate the glucose, lipid, and protein metabolism of healthy rats remains unclear. Therefore, we treated healthy rats with EGCG or the combination of EGCG and LTA (EGCG+LTA) to investigate the effects of EGCG on nutrient metabolism and the role of LTA in the metabolism-regulatory effects of EGCG. The results showed that compared with the control group, EGCG activated insulin and AMP-activated protein kinase (AMPK) signals, thus regulating glucose, lipid, and protein metabolism. Compared with EGCG, EGCG+LTA enhanced hepatic and muscle glycogen levels and suppressed phosphorylation of AMPK, glycogen synthase 2, mammalian target of rapamycin, and ribosomal protein S6 kinase. In addition, EGCG+LTA inhibited the expression of liver kinase B1, insulin receptor and insulin receptor substrate, and promoted the phosphorylation level of acetyl-CoA carboxylase. Furthermore, both EGCG and EGCG+LTA were harmless for young rats. In conclusion, EGCG activated AMPK and insulin pathways, thereby promoting glycolysis, glycogen, and protein synthesis and inhibiting fatty acid (FA) and cholesterol synthesis. However, LTA cooperated with EGCG to promote glycogen metabolism and suppressed the effect EGCG on FA and protein synthesis via AMPK signals.
... In addition, various type of antioxidants, such as polyphenols, vitamin E and C, flavonoids, ferulic, tempol, statins, probucol and its derivatives, immunosuppressants and glucocorticoid play a crucial role in the prevention and treatment of AS through different mechanisms [37][38][39][40][41][42][43][44][45][46]. However, systemic exposure, off-target effects and poor bioavailability remain concerns for drug therapy [47,48]. ...
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Atherosclerosis (AS), a chronic arterial disease, is the leading cause of death in western developed countries. Considering its long-term asymptomatic progression and serious complications, the early prevention and effective treatment of AS are particularly important. The unique characteristics of nanoparticles (NPs) make them attractive in novel therapeutic and diagnostic applications, providing new options for the treatment of AS. With the assistance of reactive oxygen species (ROS)-based NPs, drugs can reach specific lesion areas, prolong the therapeutic effect, achieve targeted controlled release and reduce adverse side effects. In this article, we reviewed the mechanism of AS and the generation and removal strategy of ROS. We further discussed ROS-based NPs, and summarized their biomedical applications in scavenger and drug delivery. Furthermore, we highlighted the recent advances, challenges and future perspectives of ROS-based NPs for treating AS.
... Currently, it is acknowledged that various cell lines have been used to investigate the potential modulatory effects of EGCG against metabolic diseases. For example, in various preclinical models of metabolic syndrome, it was evident that EGCG exposure exhibits a broad range of therapeutic properties, mostly affecting insulin signaling mechanisms such as the phosphorylation of insulin receptor substrate-1 via activating AMP-activated protein kinase (AMPK) pathway, to improve metabolic function (Eng, Thanikachalam, and Ramamurthy 2018). Also, affirming the anti-diabetic activity of EGCG, others have showed that EGCG could enhance glycogen synthesis to inhibit lipogenesis in cultured liver (HepG2) or endothelial cells (Kim et al. 2013;Zhang, Zhang, and Liang 2016). ...
Article
Epigallocatechin gallate (EGCG) is one of the most abundant and powerful flavonoids contained in green tea. Because of the global increase in green tea consumption, there has been a general interest in understanding its health benefits, including its bioactive compounds like EGCG. Indeed, preclinical evidence already indicates that EGCG demonstrated a strong antioxidant and anti-inflammatory properties that could be essential in protecting against metabolic syndrome. The current review explores clinical evidence reporting on the beneficial effects of EGCG supplementation in obese subjects or patients with diverse metabolic complications that include type 2 diabetes and cardiovascular disease. The discussion incorporates the impact of different formulations of EGCG, as well as the effective doses and treatment duration. Importantly, besides highlighting the potential use of EGCG as a nutraceutical, the current review also discusses crucial evidence related to its pharmaceutical development as an agent to hinder metabolic diseases, including its bioavailability and metabolism profile, as well as its well-known biological properties.
... Green tea consumption is correlated with a low incidence of chronic CVDs [27]. EGCG plays a major role in cardiovascular health-promoting activities, including anti-atherosclerosis, anti-cardiac hypertrophy, anti-myocardial infarction, anti-inflammatory, and antioxidant activities [212]. EGCG consumption reduces oxidative stress and enhances the restoration of cardiac function against cardiomyopathy [213]. ...
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Cardiovascular diseases (CVDs) are the most common cause of morbidity and mortality worldwide. The potential benefits of natural antioxidants derived from supplemental nutrients against CVDs are well known. Remarkably, natural antioxidants exert cardioprotective effects by reducing oxidative stress, increasing vasodilation, and normalizing endothelial dysfunction. Recently, considerable evidence has highlighted an important role played by the synergistic interaction between endothelial nitric oxide synthase (eNOS) and sirtuin 1 (SIRT1) in the maintenance of endothelial function. To provide a new perspective on the role of natural antioxidants against CVDs, we focused on microRNAs (miRNAs), which are important posttranscriptional modulators in human diseases. Several miRNAs are regulated via the consumption of natural antioxidants and are related to the regulation of oxidative stress by targeting eNOS and/or SIRT1. In this review, we have discussed the specific molecular regulation of eNOS/SIRT1-related endothelial dysfunction and its contribution to CVD pathologies; furthermore, we selected nine different miRNAs that target the expression of eNOS and SIRT1 in CVDs. Additionally, we have summarized the alteration of miRNA expression and regulation of activities of miRNA through natural antioxidant consumption.
... Diosmin is used as pharmaceutical (Dafron®) for chronic venous disease to provide soothing relief of leg ulcers, ankle swelling, varicose veins, complications of diabetes, venous insufficiency, hemorrhoids, and other conditions of the lower extremities (Murray, 2007). Epigallocatechin gallate (EGCG) has been investigated for Parkinson's disease (Zhou et al., 2018), fatty liver disease (Chen et al., 2018), diabetes (Feng et al., 2018), cardiovascular and metabolic disorders (Eng et al., 2018), and various cancers (Enkhbat et al., 2018;Negri et al., 2018;Zhu etal., 2019). Hidrosmin has also been investigated for chronic venous insufficiency (Honorato and Arcas, 1990;Dominguez et al., 1992), and chronic lymphedema (Jimenez et al., 1991). ...
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Inhibition of the main protease 3CLpro of SARS-CoV and SARS-CoV-2 is being targeted in the search for antivirals to shorten patient recovery times from Covid-19 disease. We investigated 72 flavonoids for their potential to bind with the active catalytic site of 3CLpro for SARS-CoV and SARS-CoV-2. In silico molecular dynamics docking was performed using energy-minimized states of the flavonoids. Three variants of the active catalytic site of the protease 3CLpro were used: one based on x-ray crystallography for SARS-CoV, the second based on x-ray crystallography for SARS-CoV-2, and the third based on a 3D-modeled form of an amino acid sequence alignment of SARS-CoV-2 3CLpro from 8 humans. Docking involved characterization of the best putative pose in the “pocket” of the active site based on altering rotatable bonds in each molecule. The binding energy (kcal/mol) and number of hydrogen bonds were assessed during each pose. Mean binding energy across the 3 variants of 3CLpro was sorted in ascending order to rank each flavonoid, since more negative values indicate stronger binding. The top 10 flavonoids identified were amentoflavone, gallocatechin gallate, diosmin, epigallocatechin gallate, hidrosmin, catechin gallate, elsamitrucin, pectolinaren, quercetin, and isoquercetin. Other flavonoids investigated with significant binding energies were hesperidin, rutin, rhoifolin, and peurarin. Many of the flavonoids identified have been reported in studies of in vitro laboratory-based inhibition of 3CLpro as well as in silico docking studies. Altogether, 14 flavonoids have now been identified in multiple studies: amentoflavone, daidzein, diosmin, epigallocatechin gallate, gallocatechin gallate, herbacetin, hesperidin, luteolin, naringin, peurarin, pectolinarin, quercetin, rhoifolin, and rutin. In vivo animal research is now needed for evaluating whether these flavonoids can minimize early infection and alleviate symptoms and shorten recovery times for late-stage Covid-19 disease. Human prevention trials for minimizing early infection and combination therapy trials with antivirals for shortening recovery times in late-stage Covid-19 disease could also be pursued. Many of these flavonoids are already available as prescription-free supplements, so they are widely available.
... Green tea catechin has been reported to have various healthpromoting properties. Recent research indicates anti-cardiac hypertrophy, anti-atherosclerosis, anti-myocardial infarction, antidiabetic (Eng et al., 2018), antiarthritic (Karatas et al., 2020), antimicrobial (Reygaert, 2018), antidiabetic , cholesterol-lowering, hypouricemic (Purnaningtyas, 2020) (Xu et al., 2017) and COVID-19 (Zhang, Zhang, et al., 2021), respectively, as well as the viruses infecting other animals (e.g. hemorrhagic septicemia virus, ...
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Epigallocatechin gallate (EGCG), a green tea catechin, has gained the attention of current study due to its excellent health‐promoting effects. It possesses anti‐obesity, antimicrobial, anticancer, anti‐inflammatory activities, and is under extensive investigation in functional foods for improvement. It is susceptible to lower stability, lesser bioavailability, and lower absorption rate due to various environmental, processing, formulations, and gastrointestinal conditions of the human body. Therefore, it is the foremost concern for the researchers to enhance its bioactivity and make it the most suitable therapeutic compound for its clinical applications. In the current review, factors affecting the bioavailability of EGCG and the possible strategies to overcome these issues are reviewed and discussed. This review summarizes structural modifications and delivery through nanoparticle‐based approaches including nano‐emulsions, encapsulations, and silica‐based nanoparticles for effective use of EGCG in functional foods. Moreover, recent advances to enhance EGCG therapeutic efficacy by specifically targeting its molecules to increase its bioavailability and stability are also described. Practical applications The main green tea constituent EGCG possesses several health‐promoting effects making EGCG a potential therapeutic compound to cure ailments. However, its low stability and bioavailability render its uses in many disorders. Synthesizing EGCG prodrugs by structural modifications helps against its low bioavailability and stability by overcoming premature degradation and lower absorption rate. This review paper summarizes various strategies that benefit EGCG under different physiological conditions. The esterification, nanoparticle approaches, silica‐based EGCG‐NPs, and EGCG formulations serve as ideal EGCG modification strategies to deliver superior concentrations with lesser toxicity for its efficient penetration and absorption across cells both in vitro and in vivo. As a result of EGCG modifications, its bioactivities would be highly improved at lower doses. The protected or modified EGCG molecule would have enhanced potential effects and stability that would contribute to the clinical applications and expand its use in various food and cosmetic industries.
... In recent time, several review articles have comprehensively highlighted the promising biological activities of EGCG (Chakrawarti et al. 2016;Gan et al. 2018; Khan and Mukhtar 2018;Legeay et al. 2015;Nagle, Ferreira, and Zhou 2006;Riegsecker et al. 2013;Singh, Shankar, and Srivastava 2011;Steinmann et al. 2013;Wang, Li, et al. 2021;Zhang et al. 2021). EGCG exhibits a broad range of therapeutic properties like anti-oxidant (Hung, Hsiao, and Hsieh 2021;Vishnoi, Bodla, and Kant 2018), anti-cancer (Bimonte et al. 2020;Fujiki et al. 2018), anti-inflammatory , anti-viral (Wang, Li, et al. 2021), cardio protective (Eng, Thanikachalam, and Ramamurthy 2018), and neuro protective (Wei et al. 2019) activities ( Figure 1). The strong anti-cancer activity exerted by EGCG could be attributed to its capability to modulate several molecular targets associated with various cancer hallmarks (Aggarwal et al. 2022;Alam et al. 2022;Hayakawa et al. 2016;Rajagopal et al. 2018;Slika et al. 2022). ...
Article
Natural products have been a bedrock for drug discovery for decades. (−)-Epigallocatechin-3-gallate (EGCG) is one of the widely studied natural polyphenolic compounds derived from green tea. It is the key component believed to be responsible for the medicinal value of green tea. Significant studies implemented in in vitro, in cellulo, and in vivo models have suggested its anti-oxidant, anti-cancer, anti-diabetic, anti-inflammatory, anti-microbial, neuroprotective activities etc. Despite having such a wide array of therapeutic potential and promising results in preclinical studies, its applicability to humans has encountered with rather limited success largely due to the poor bioavailability, poor membrane permeability, rapid metabolic clearance and lack of stability of EGCG. Therefore, novel techniques are warranted to address those limitations so that EGCG or its modified analogs can be used in the clinical setup. This review comprehensively covers different strategies such as structural modifications, nano-carriers as efficient drug delivery systems, synergistic studies with other bioactivities to improve the chemico-biological aspects (e.g., stability, bioavailability, permeability, etc.) of EGCG for its enhanced pharmacokinetics and pharmacological properties, eventually enhancing its therapeutic potentials. We think this review article will serve as a strong platform with comprehensive literature on the development of novel techniques to improve the bioavailability of EGCG so that it can be translated to the clinical applications.
... Green tea leaves contain (−)-epigallocatechin-3-gallate (EGCG) (50-60%), (−)-epigallocatechin (EGC) (15-20%), (−)-epicatechin-3-gallate (ECG) (10-15%) and (−)-epicatechin (EC) (5-10%) [13,14]. EGCG, which is reportedly to be more abundant in green tea leaves (7.1 g per 100 g) than in oolong tea (3.4 g per 100 g) and black tea leaves (1.1 g per 100 g) [15], has a potent antioxidant property due to the Chen Chen and Bo Li have contributed equally to this work. eight hydroxyl groups and two triphenolic groups in its basic structure [16,17]. ...
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We aimed to explore the protective effects and potential treatment mechanism of Epigallocatechin-3-gallate (EGCG) in an animal model of chronic exposure in a natural high-altitude hypoxia (HAH) environment. Behavioral alterations were assessed with the Morris water maze test. Iron accumulation in the hippocampus was detected by using DAB enhanced Perls’ staining, MRI, qPCR and colorimetry, respectively. Oxidative stress (malondialdehyde, MDA), apoptosis (Caspase-3), and neural regeneration (brain-derived neurotrophic factor, BDNF) were detected by using ELISA and western blotting. Neural ultrastructural changes were evaluated by transmission electron microscopy (TEM). The results showed that learning and memory performance of rats decreased when exposure to HAH environment. It was followed by iron accumulation, dysfunctional iron metabolism, reduced BDNF and the upregulation of MDA and Caspase-3. TEM confirmed the ultrastructural changes in neurons and mitochondria. EGCG reduced HAH-induced cognitive impairment, iron deposition, oxidative stress, and apoptosis and promoted neuronal regeneration against chronic HAH-mediated neural injury.
Article
Background: Green tea, obtained from the plant Camellis sinensis, is one of the oldest drinks in the world and contains numerous bioactive compounds. Studies have demonstrated the efficacy of green tea in preventing obesity and cardiovascular diseases that may be related to the reduction of lipid levels. Aim: This study aimed to evidence, through a systematic review, the therapeutic potential of green tea on the lipid profile in preclinical studies in obese animals and clinical studies in obese individuals. Methods: This systematic review follows the recommendations of the preferred report items for systematic reviews and meta-analyses. The electronic databases, PubMed (Medline), Science Direct, Scopus, and Web of Science were consulted. Articles from January 2009 to December 2019 were selected. Results: This search resulted in twenty-nine articles were included cirtically reviewed. In experimental studies, green tea administration has been shown to reduce total cholesterol, triglycerides and low-density lipoprotein cholesterol in animals exposed to obesity-inducing diet. In humans’ studies green tea was not shown to be effective for obese lipid control. Because supplementation with green tea extract reduced total cholesterol, triglycerides, low-density lipoprotein for three months at a specific dose. Conclusion: Therefore, green tea appears to act as a protective agent for dyslipidemia in obesity-induced animals. In human studies, green tea has not been shown to be effective in controlling obese lipids.
Article
Plant-based polyphenols are known to exert mitigating effects on the harmful consequences of advanced glycation. In this study, the antioxidant and antiglycation properties of purified black chokeberry polyphenol and its dominant monomers were studied. The phenolics of black chokeberry had a significant inhibitory effect on glycation products at all stages. The highest inhibition of fructosamine (72.27%) was achieved by chlorogenic acid (CA). Epigallocatechin gallate (EGCG) showed an 84.47% inhibition of α-dicarbonyl and 54.44% inhibition of AGEs (advanced glycation end-products). However, the inhibition of α-dicarbonyl was impacted by the presence of Cu²⁺. In addition, an EGCG-induced increase in the protein α-helical structure to 21.43% was observed. Overall, EGCG was the main component inhibited protein glycosylation in the simulated glycation system. Furthermore, the mechanism of inhibition was a combination of scavenging free radicals, capturing metal ions, and alleviating changes in the secondary structure of proteins.
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Colon cancer is a life-threatening disease all over the world and is linked to constant oxidative stress and inflammation. Epigallocatechin gallate (EGCG), is a naturally occurring flavone possessing health benefiting pharmacological properties including antioxidant, anti-inflammatory and free radical scavenging properties. Our study investigates the role of EGCG on N,N′-dimethylhydrazine (DMH), a toxic environmental pollutant, induced colon toxicity. To investigate the effect of EGCG, Wistar rats were given EGCG for 7 days at the two doses of 10 and 20 mg/kg body weight and DMH was injected on the seventh day in all the group rats except the control. Our results indicate that DMH administration increased the oxidative stress (MDA) and depleted the glutathione and antioxidant enzyme activities (SOD, CAT, GR, GST and GPx) which was significantly ameliorated by EGCG treatment. Additionally DMH treatment upregulated inflammatory markers expression (NF-κB, COX-2 and IL-6) and enhanced mucosal damage in the colon. EGCG treatment significantly reduced inflammation and restored the normal histoarchitecture of the colon. We can conclude from the present study findings that EGCG protects the colon from DMH toxicity through its antioxidant and anti-inflammatory potential.
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Objectives: Epigallocatechin-3-gallate (EGCG) has a good therapeutic effect on type 2 diabetes mellitus (T2DM). This work was designed to explore EGCG's effectiveness in insulin resistance (IR) and pancreas islet β-cell function in a rat model of T2DM. Materials and methods: Eight-week-old male Sprague Dawley rats were randomly divided into 6 groups, including the Control (normal diet), Diabetes (high-sucrose high-fat [HSHF] diet combined with tail vein injection of streptozotocin [STZ] for T2DM induction) and Treatment Diabetic rats which were treated with metformin [500 mg/kg/d] or EGCG [25, 50 or 100 mg/kg/d] intragastric administration for 10 weeks. With the exception of control animals, the other groups were fed the HSHF diet. EGCG's effects on IR and insulin secretion were assessed by measuring body weights, and fasting blood glucose (FBG), postprandial blood glucose (PBG) and insulin levels. The morphological and molecular changes of pancreas islet β-cells were examined by hematoxylin-eosin (H&E) staining, transmission electron microscopy (TEM) and immunofluorescence. Results: Rats fed the HSHF diet combined with STZ treatment had increased body weights and blood glucose amounts, accompanied by IR and impaired β-cell function, induced T2DM, and EGCG dose-dependently restored the above indicators. Additionally, EGCG upregulated the pancreatic transcription factors pancreatic duodenal homeobox protein-1 (PDX-1) and musculoaponeurotic fibrosarcoma oncogene homolog A (MafA). Conclusion: These results suggest that EGCG reduces blood glucose amounts, and improve IR and islet β-cell disorder in T2DM.
Article
Epigallocatechin-3-gallate (EGCG) possesses anti-fibrotic potential in diverse tissues; however, the molecular mechanisms underlying the impacts of EGCG on diabetes-induced myocardial fibrosis remain unclear. This present study aimed to unravel the anti-fibrotic effects of EGCG on the heart in type 2 diabetic rats and investigate its molecular mechanisms. Rats were randomly assigned to the following four groups: Normal (NOR), diabetic cardiomyopathy (DCM), DCM + 40 mg/kg EGCG, and DCM + 80 mg/kg EGCG groups. After 8 weeks of EGCG treatment, fasting blood glucose, left ventricular hemodynamic indices, heart index, and myocardial injury-related parameters were measured. Hematoxylin and eosin staining and Sirius Red staining were used to evaluate myocardial pathological alterations and collagen accumulation. The contents of myocardial hydroxyproline, collagen-I, collagen-III, transforming growth factor (TGF)-β1, matrix metalloprotease (MMP)-2, and MMP-9 were measured. The gene expression levels of myocardial TGF-β1, MMP-2, and MMP-9 were detected. Autophagic regulators, including adenosine 5’-monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR), and autophagic markers, including microtubule-associated protein-1 light chain 3 and Beclin1 were estimated. The results indicated that diabetes significantly decreased cardiac contractile function and aggravated myocardial hypertrophy and injury. Furthermore, diabetes repressed the activation of autophagy in myocardial tissue and promoted cardiac fibrosis. Following ingestion with different doses of EGCG, myocardial contractile dysfunction, hypertrophy and injury were ameliorated; myocardial autophagy was activated, and myocardial fibrosis was alleviated in the EGCG treatment groups. In conclusion, these findings suggested that EGCG could attenuate cardiac fibrosis in type 2 diabetic rats, and its underlying mechanisms associated with activation of autophagy via modulation of the AMPK/mTOR pathway and then repression of the TGF-β/MMPs pathway.
Article
The increase in incidence and prevalence of metabolic diseases such as diabetes, obesity and metabolic syndrome, is a health problem worldwide. Nutritional strategies that can impact on mitochondrial activity represent a novel and effective option to modulate energy expenditure and energetic metabolism in cells and tissues and could be used as adjuvant treatments for metabolic-associated disorders. Dietary bioactive compounds also known as “food bioactives” have proven to exert multiple health benefits and counteract metabolic alterations. In the last years, it has been consistently reported that the modulation of mitochondrial function represents one of the mechanisms behind the bioactive compounds-dependent health improvements. In this review, we focus on gathering, summarizing and discussing the evidence that supports the effect of dietary bioactive compounds on mitochondrial activity and the relation of these effects in the pathological context. Despite the evidence presented here on in vivo and in vitro effects, more studies are needed to determine their effectiveness in humans.
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Epigallocatechin-3-gallate (EGCG), an essential polyphenolic constituent found in tea leaves, possesses various potent biological activities. This research was undertaken to investigate the impact of EGCG against endoplasmic reticulum (ER) stress-mediated inflammation and to clarify the underlying molecular mechanism in type 2 diabetic kidneys. The male rats were randomized into four groups: normal, diabetic, low-dose EGCG, and high-dose EGCG. In type 2 diabetic rats, hyperglycemia and hyperlipidemia noticeably caused renal structural damage and dysfunction and aggravated ER stress. Meanwhile, sustained ER stress activated the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and then upregulated the contents of inflammatory cytokines in the diabetic kidney. Following supplementation with 40 mg/kg and 80 mg/kg EGCG, hyperglycemia, hyperlipidemia, and renal histopathological alterations and dysfunction were noticeably ameliorated; renal ER stress, NLRP3 inflammasome, and inflammatory response were markedly repressed in the EGCG treatment groups. In summary, the current study highlighted the renoprotective effects of EGCG in type 2 diabetes and its mechanisms are mainly associated with the repression of ER stress-mediated NLRP3 inflammasome overactivation.
Article
(-)-Epigallocatechin-3-O-gallate (EGCG), the most bioactive catechin in green tea, has drawn significant interest as a potent antioxidant and anti-inflammatory compound. However, the application of EGCG has been limited by its rapid autoxidation at physiological pH, which generates cytotoxic levels of reactive oxygen species (ROS). Herein, we report the synthesis of poly(acrylic acid)-EGCG conjugates with tunable degrees of substitution and their spontaneous self-assembly into micellar nanoparticles with enhanced resistance against autoxidation. These nanoparticles not only exhibited superior oxidative stability and cytocompatibility over native EGCG, but also showed excellent ROS-scavenging and anti-inflammatory effects. This work presents a potential strategy to overcome the stability and cytotoxicity issues of EGCG, making it one step closer toward its widespread application.
Article
BACKGROUND The contribution of bacteria to fermented tea is not clear, and the associated research is relatively limited. To reveal the role of microorganisms in the fermented tea processing, the microbial community and metabolites of Fuzhuan brick tea (FBT), a Chinese traditional fermented tea, were revealed with high throughput sequencing and the Liquid Chromatography-Mass Spectrometry in the current study. RESULTS In the FBT, bacterial communities had a higher abundance and diversity, Lactococcus and Bacillus were the main bacteria, and the Eurotium was the predominant fungus. The predictive metabolic function indicated the pathways of cellular growth, environmental information, genetics, and material metabolism of bacterial communities, while the fungal communities' predictive metabolic function was almost saprotroph. Using the LC–MS, 1143 and 536 metabolites were defined in positive and negative ion mode, respectively. There were essential correlations between bacterial populations and metabolites, e.g., Bacillus was correlated significantly with 44 metabolites (p < 0.05), and Enterococcus was significantly associated with 15 metabolites (p < 0.05). Some of the main active components were significantly correlated with the bacteria, such as Enterococcus, Lactococcus, and Carnobacterium. CONCLUSION Not only the Eurotium, but the bacteria were involved in the changes of metabolomics profile in fermented FBT. The current study assisted in providing new insight into metabolomics profile generating in fermented tea. The present research laid a foundation for controlling the FBT fermentation by artificial inoculation to improve the quality. This article is protected by copyright. All rights reserved.
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Olive (Olea europaea L.) leaves, a raw material for health functional foods and cosmetics have abundant polyphenols including oleuropein (major bioactive compound) with various biological activities: antioxidant, antibacterial, antiviral, anticancer activity, and inhibit platelet activation. Oleuropein has been reported as skin protectant, antioxidant, anti-ageing, anti-cancer, anti-inflammation, anti-atherogenic, anti-viral, and anti-microbial activity. Despite oleuropein is the important compound in olive leaves, there is still no quantitative approach to reveal oleuropein content in commercial products. Therefore, a validated method of analysis has to develop for oleuropein. In this study, the components and oleuropein content in 10 types of products were analyzed using a developed method with ultra-performance liquid chromatography to quadrupole time-of-flight mass spectrometry, charge of aerosol detector, and photodiode array. The total of 18 compounds including iridoids (1, 3, 4, 14, and 16-18), coumarin (2), phenylethanoids (5, 9, and 11), flavonoids (6-8, 10, 12, and 13), lignan (15), were tentatively identified in the leaves extract based high resolution mass spectrometry data, and the content of oleuropein in each product was almost identical between two detection methods. The oleuropein in three commercial product (A, G, H) was contained more over the suggested content, and it of five products (B, E, H, I, J) were analyzed within 5-10% error range. However, the two products (C, D) were found far lower than suggested contents. This study provides that analytical results of oleuropein could be a potential information for the quality control of leaf extract for a manufactured functional food.
Article
Development of functional bioinspired hydrogels that have good releases control character is necessary for the application of these materials in biomedical engineering. Herein, we report a composite hydrogel prepared from several biocompatible carboxymethyl konjac glucomannan (CKGM)/gelatin (G)/tannic acid (TA) functional nano-hydroxyapatite ([email protected]), which has good biodegradability and pH sensitivity. The mechanism of interaction between hydrogels was confirmed by Fourier transform infrared spectroscopy, X-ray diffraction, Scanning electron microscopy and Thermogravimetric analysis. The physico-chemical properties of CKGM/G hydrogels have been significantly improved through the incorporation of [email protected] within the matrix. Studies in the sustained release of epigallocatechin gallate (EGCG) demonstrated that the [email protected]/CKGM/G hydrogels exhibit not only better pH sensitive properties, but also enhanced biocompatibility and encapsulation in comparison to the matrix devoid of [email protected] Consequently, [email protected]/CKGM/G hydrogels using EGCG as a drug release model show the potential for drug delivery.
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In the past decades, phytoconstituents have appeared as critical mediators for immune regulations among various diseases, both in eukaryotes and prokaryotes. These bioactive molecules, showing a broad range of biological functions, would hold tremendous promise for developing new therapeutics. The discovery of phytoconstituents’ capability of functionally regulating immune cells and associating cytokines, suppressing systemic inflammation, and remodeling immunity have rapidly promoted the idea of their employment as anti-inflammatory agents. In this review, we discuss various roles of phyto-derived medicines in the field of inflammatory diseases, including chronic inflammation, autoimmune diseases, and acute inflammatory disease such as COVID-19. Nevertheless, traditional phyto-derived medicines often concurred with their clinical administration limitations, such as their lack of cell specificity, inefficient cytoplasmic delivery, and rapid clearance by the immune system. As alternatives, phyto-derived nano-approaches may provide significant benefits. Both unmodified and engineered nanocarriers present the potential to serve as phytoconstituent delivery systems to improve therapeutic physio-chemical properties and pharmacokinetic profiles. Thus, the development of phytoconstituents’ nano-delivery designs, their new and perspective approaches for therapeutical applications are elaborated herein.
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Background Cancers, cardiovascular and cerebrovascular diseases, and neurodegenerative diseases (NDs) are top-ranked diseases worldwide and for the elderly, they are the top three. In the past decade, dietary flavonoids have become one the of research topics of attention due to their definite protective and to some extent therapeutic effects on cancers, cardiovascular and cerebrovascular diseases, and NDs. In addition, to maximize bioactivities and the utilization of dietary flavonoids, recently great efforts have been devoted to the bioavailability enhancement of dietary flavonoids. Scope and approach Various dietary flavonoid extracts and pure dietary flavonoid molecules that display protective and/or therapeutic effects on cancers, cardiovascular and cerebrovascular diseases, or NDs are demonstrated. Only in vivo bioactive reports and findings with solid evidences (both human and animal-based ones) are compiled in this paper to exemplify the practical use of dietary flavonoids as complementary therapies for cancers, cardiovascular and cerebrovascular diseases, or NDs. Furthermore, the strategies for improving the bioavailability of dietary flavonoids are discussed. Key findings and conclusions: Both dietary flavonoid extracts and pure dietary flavonoid molecules can reduce the risk of cancers, cardiovascular and cerebrovascular diseases, or NDs. Many types of nano-systems like drug nanocrystals, polymer nanoparticles, solid lipid nanoparticles, and nanoliposomes can evidently increase the bioavailability and thereby the therapeutic index for dietary flavonoids. All these findings suggest the potential utility of dietary flavonoids as dietary supplements in the adjuvant therapy of cancers, cardiovascular and cerebrovascular diseases, and NDs.
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Many diseases are accompanied by changes in the redox environment, such as the reducing environment of the tumor cytoplasmic matrix and oxidative stress and the pathological microenvironment of coronary heart disease. The surface modification of interventional devices often ignores these environmental changes. A redox-sensitive coating can better adapt to the changes of pathological environment and achieve more accurate treatment of diseases. In response to these environmental changes, we constructed a sensitive coating to modify the surface of interventional devices. Two kinds of functional molecules, epigallocatechin gallate (EGCG) and cystamine, were chosen to construct the redox-sensitive coating. The phenolic hydroxyl group of EGCG could chelate metal ions and enable it to bind to a metal substrate, while cystamine molecules containing disulfide bonds (-S-S-) can react with EGCG through Michael addition and Schiff base reactions to form EGCG-Cys crosslinked coatings. The disulfide bond in the coating could respond to the redox environment, which could be reduced to -SH by glutathione (GSH) or oxidized to -SO3H by reactive oxygen species (ROS). The sensitivity and response capability of the coating were determined via X-ray photoelectron spectroscopy (XPS) and quartz crystal microbalance (QCM-D) analysis. Furthermore, the safety and cytocompatibility of the coating were evaluated using an in vitro co-culture of vascular endothelial cells (ECs) and smooth muscle cell (SMCs). The histocompatibility of the coating in vivo was confirmed via subcutaneous implantation in rats. Overall, we found that the redox-sensitive coating has potential applications for the surface modification of interventional devices.
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Background Epigallocatechin gallate (EGCG) has attracted increasing attention due to its beneficial effect on cardiovascular health. The aim of this study was to investigate the underlying mechanism by which EGCG protects against myocardial ischaemia/reperfusion injury (I/RI). Methods Murine myocardial I/RI and H2O2-induced cardiomyocyte injury models were established to evaluate the therapeutic effects of EGCG. In the myocardial I/RI mouse model, the echocardiographic parameters of ejection fraction (EF) and fraction shortening (FS) levels, infarct size, histological evaluation and transmission electron microscopy (TEM) were used to evaluate cardiac tissue damage and autophagy. MTT assays, TUNEL staining, flow cytometry and immunofluorescence (IF) were used to monitor cell viability, apoptosis and autophagy in vitro. qRT-PCR and western blotting were used to determine the mRNA and protein levels of key molecules, respectively. The epigenetic regulation of DUSP5 was assessed via RNA immunoprecipitation (RIP), RNA pull-down and chromatin immunoprecipitation (ChIP) assays. Results EGCG significantly improved cardiac function, reduced infarct size, enhanced cell viability and inhibited autophagic activity in both myocardial I/RI mouse models and H2O2-induced cardiomyocyte injury models. Moreover, EGCG suppressed H2O2- or myocardial I/R-increased Gm4419 expression, and Gm4419 overexpression dramatically abolished EGCG-mediated protective effects against myocardial I/RI. Mechanistically, Gm4419 epigenetically suppressed DUSP5 by recruiting EZH2, thus activating ERK1/2 pathway-mediated autophagy. Furthermore, the in vivo experiments further verified that the Gm4419-mediated disruptive effects of EGCG on myocardial I/RI were potentiated by DUSP5 knockdown but attenuated by DUSP5 overexpression. Conclusions In conclusion, our findings demonstrated that EGCG protected against myocardial I/RI by modulating Gm4419/DUSP5/ERK1/2-mediated autophagy.
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Background Septic cardiomyopathy (SC) is a common complication of sepsis that leads to an increase in mortality. The pathogenesis of septic cardiomyopathy is unclear, and there is currently no effective treatment. EGCG (epigallocatechin gallate) is a polyphenol that has anti-inflammatory, antiapoptotic, and antioxidative stress effects. However, the role of EGCG in septic cardiomyopathy is unknown. Methods Network pharmacology was used to predict the potential targets and molecular mechanisms of EGCG in the treatment of septic cardiomyopathy, including the construction and analysis of protein-protein interaction (PPI) network, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and molecular docking. The mouse model of septic cardiomyopathy was established after intraperitoneal injection of LPS (lipopolysaccharide). The myocardial protective effect of EGCG on septic mice is observed by cardiac ultrasound and HE staining. RT-PCR is used to verify the expression level of the EGCG target in the septic cardiomyopathy mouse model. Results A total of 128 anti-SC potential targets of EGCGareselected for analysis. The GO enrichment analysis and KEGG pathway analysis results indicated that the anti-SC targets of EGCG mainly participate in inflammatory and apoptosis processes. Molecular docking results suggest that EGCG has a high affinity for the crystal structure of six targets (IL-6 (interleukin-6), TNF (tumor necrosis factor), Caspase3, MAPK3 (Mitogen-activated protein kinase 3), AKT1, and VEGFA (vascular endothelial growth factor)), and the experimental verification result showed levated expression of these 6 hub targets in the LPS group, but there is an obvious decrease in expression in the LPS + EGCG group. The functional and morphological changes found by echocardiography and HE staining show that EGCG can effectively improve the cardiac function that is reduced by LPS. Conclusion Our results reveal that EGCG may be a potentially effective drug to improve septic cardiomyopathy. The potential mechanism by which EGCG improves myocardial injury in septic cardiomyopathy is through anti-inflammatory and anti-apoptotic effects. The anti-inflammatory and anti-apoptotic effects of EGCG occur not only through direct binding to six target proteins (IL-6,TNF-α, Caspase3, MAPK3, AKT1, and VEGFA) but also by reducing their expression.
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Pre-eclampsia (PE), a pregnancy complication, affects 3-5% of all pregnancies worldwide and is the main cause of maternal and perinatal morbidity. However, there is no drug which can clearly slow this disease progression. Epigallocatechin gallate (EGCG), a natural compound extracted from green tea, has been found to enhance the treatment efficacy of oral nifedipine against pregnancy-induced severe PE. This study aims to clarify the potential targets and pharmacological mechanisms of EGCG in treatment of PE. We used Traditional Chinese Medicine Systems Pharmacology database and Gene Cards database to obtain 179 putative target proteins of EGCG, 550 PE-related hub genes and 39 intersecting targets between EGCG and PE. By using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses, we got the gene entries and enrichment pathways closely related to the intersecting targets. The top 10 enrichment pathways were pathway in cancer, proteoglycans in cancer, HIF-1 signaling pathway, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, bladder cancer, hepatitis B, IL-17 signaling pathway, toxoplasmosis, PI3K-Akt signaling pathway. Furthermore, compound-target-pathway (CTP) and protein-protein interaction (PPI) network analysis were employed to explore the interaction of the top twelve targets for EGCG in treating PE. Molecular docking analysis showed combinations between these targets and EGCG, and the interaction between EGCG and the targets IL-6 and EGFR was confirmed by using molecular dynamic simulation. In conclusion, these findings hint the underlying mechanism of EGCG in the treatment of PE and point out directions in further studies on PE.
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Quercetin and EGCG exhibit anti-diabetic and anti-obesity activities, however, their interactive effects in anti-diabetic/anti-obesity actions and underlying mechanisms remain unclear. This study aimed to fill these knowledge gaps. Quercetin, EGCG or their combination attenuated insulin resistance and decreased hepatic gluconeogenesis in high-fat-high-fructose diet (HFFD)-fed C57BL/6 mice and in palmitic acid (PA)-treated HepG2 cells. In mice, supplementation with quercetin (0.05%w/w), EGCG (0.05%w/w) and their combination (quercetin 0.05%+EGCG 0.05%w/w) reduced weight gain and fasting blood glucose and improved serum biochemical parameters. Compare with quercetin/EGCG alone, the quercetin-EGCG combination reduced gluconeogenesis to a greater extent via IRS-1/Akt/FOXO1-mediated down-regulation of downstream PEPCK and G-6-pase. In HepG2 cells, the quercetin (5 μM)-EGCG (5 μM) co-treatment exerted greater suppression on PA-induced changes in glucose and glycogen contents and hexokinase and G-6-pase activities than quercetin/EGCG alone (each 10 μM). The quercetin-EGCG co-treatment reduced glucose production through targeting FOXO1 and inhibiting the transcription of gluconeogenic enzymes. MiR-27a-3p and miR-96–5p regulated directly FOXO1 expression and function, and co-inhibition of miR-27a-3p and miR-96–5p weakened greatly the protective effect of quercetin-EGCG combination. This is the first report on the contributions of miR-27a-3p and miR-96–5p to the synergistic and protective effect of the quercetin-EGCG co-treatment against PA-induced insulin resistance through inhibiting FOXO1 expression.
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Although epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, has been shown to have many benefits, the effect of EGCG exposure in utero on adult uterine development is unclear. In this study, pregnant C57BL/6 mice were exposed to 1 mg/kg body weight (bw) EGCG dissolved in drinking water from gestational days 0.5–16.5. A significant decrease in uterine weight was observed in the adult female mice, accompanied by uterine atrophy, inflammation, and fibrosis in the endometrium. Uterine atrophy was attributed to the thinning of the endometrial stromal layer and a significant reduction in endometrial cell proliferation. The expression levels of related proteins in the NF-κB and RAF/MEK/ERK signaling pathways were significantly increased, which might be responsible for the occurrence of inflammation. Activation of the transforming growth factor beta (TGF-β1)/Smad signaling pathway might be involved in the development of endometrial fibrosis. The changes in the expression of estrogen receptor α, β (ERα, ERβ), progesterone receptor (PGR), and androgen receptor (AR) might lead to changes in the aforementioned signaling pathways. The promoter region methylation level of Esr2 was increased, and the expression of DNMT3A was evaluated. Our study indicates a risk of EGCG intake during pregnancy affecting uterine development in offspring.
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The world's high-value crop is tea, its aspect plays a powerful role in its marketability. Tea is the utmost extensively absorb aromatic beverage with the legion of health benefit and respond as a remedy for various disease like neurological disorder and cardiovascular. The emerging, spectroscopic and classified approaches for safety and quality assessment determination like electrochemical method, microbial of tea are very effective. These approaches improve the accuracy and sensitivity of the standard and direct technique and increase the speed of the detection process. Also, the approaches are non-destructive, cost-effective, and rapid that provides real-time detection. Application of these approaches in the tea industry from picking, fermentation, sensor evaluation, developing portable devices for real-time safety assessment benefits the tea production mechanism. Recently, colorimetric and chromatography techniques have been reported in several stages of tea processing that are expensive, laborious and inaccurate, and time-consuming. Here, computer vision and deep learning can be explored to overcome inconsistency and inaccuracy. This paper presents an overview of the processing of tea, type of tea, the microbiology of tea, safety & quality evaluation, standard & emerging techniques, and electrochemical detection using separation method, bio electrochemical sensor, and health benefits of tea with distinct tea contaminates. This paper also includes the analytical comparison of distinct approaches proposed by the different researchers for quality analysis of tea and its products. This potential review may guide for evaluation and detection of tea products which further promotes the development of the food industry.
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The potential protective effect of epigallocatechin-3-gallate (EGCG) on type 2 diabetes-induced heart injury was investigated. A rat model of diabetes was achieved by injection of nicotinamide (100 mg/kg, i.p), 20 min before the administration of streptozotocin (55 mg/kg, i.p.). After confirmation of diabetes, EGCG (2 mg/kg, p.o.) was administrated on alternate days for one month. Treatment of diabetic rats with EGCG showed a remarkable reduction in glucose, glycosylated hemoglobin, HOMA-IR and lipid profile levels with an elevation in insulin levels, indicating its antihyperglycemic and antidyslipidemic actions. EGCG treatment also suppressed the increase in the levels of superoxide, 4-hydroxynonenal and protein carbonyl, whereas it increased the content of glutathione and the activities of superoxide dismutase and catalase in heart of diabetic rats, indicating its antioxidant capacity. In addition, EGCG improved heart function of diabetic rats as evidenced by a remarkable reduction in troponin T level and creatine kinase-MB, lactate dehydrogenase and aspartate aminotransferase activities in the serum. Oral administration of EGCG for one month after diabetes induction significantly protected the increase in serum levels of pro-inflammatory cytokines (IL-1 β, IL-6 and TNF-α) and adhesion molecules (ICAM-1 and VCAM-1), suggesting its anti-inflammatory potential. Furthermore, EGCG hampered the mitochondrial apoptotic pathway through increasing Bcl-2 level and decreasing p53, Bax, cytochrome c and caspase-3 and 9 levels in hearts of diabetic rats, indicating its anti-apoptotic action. Diabetic rats treated with EGCG also exhibited decreased level of DNA damage in the myocardium. The histological examinations indicated the cardioprotective effect of EGCG against harmful impact of diabetes. Therefore, these findings suggest that EGCG has a protective effect on the heart affected by type 2 diabetes and recommend it as a complementary supplement for diabetic patients.
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Cardiac diastolic dysfunction (CDD) is the most common form of cardiovascular disorders, especially in elderly people. Cardiac troponin I (cTnI) plays a critical role in the regulation of cardiac function, especially diastolic function. Our previous studies showed that cTnI-low expression induced by histone acetylation modification might be one of the causes that result in diastolic dysfunction in ageing hearts. This study was designed to investigate whether epigallocatechin-3-gallate (EGCG) would modify histone acetylation events to regulate cTnI expression and then improve cardiac functions in ageing mice. Our study shows that EGCG improved cardiac diastolic function of aged mice after 8-week treatment. Low expression of cTnI in the ageing hearts was reversed through EGCG treatment. EGCG inhibited the expression of histone deacetylase 1 (HDAC1) and HDAC3, and the binding levels of HDAC1 in the proximal promoter of cTnI. Acetylated lysine 9 on histone H3 (AcH3K9) levels of cTnI's promoter were increased through EGCG treatment. Additionally, EGCG resulted in an ascent of the binding levels of transcription factors GATA4 and Mef2c with cTnI's promoter. Together, our data indicate that EGCG may improve cardiac diastolic function of ageing mice through up-regulating cTnI by histone acetylation modification. These findings provide new insights into histone acetylation mechanisms of EGCG treatment that may contribute to the prevention of CDD in ageing populations.
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Background/aims: Exposure to arsenic in individuals has been found to be associated with various health-related problems including skin lesions, cancer, and cardiovascular and immunological disorders. (-)-Epigallocatechin-3-gallate (EGCG), the main and active polyphenolic catechin present in green tea, has shown potent antioxidant, anti-apoptotic and anti-inflammatory activity in vivo and in vitro. Thus, the present study was conducted to investigate the protective effects of EGCG against arsenic-induced inflammation and immunotoxicity in mice. Methods: Serum IL-1?, IL-6 and TNF-? were determined by ELISA, tissue catalase (CAT), malonyldialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), nitric oxide and caspase 3 by commercial kits, mitochondrial membrane potential with Rh 123, mitochondrial ROS with 2',7'-dichlorofluorescin diacetate (DCFH-DA), apoptotic and necrotic cells and T-cell phenotyping with Flow cytometry analysis. Results: The results showed that arsenic treatment significantly increased oxidative stress levels (as indicated by catalase, malonyldialdehyde, superoxide dismutase, glutathione and reactive oxygen species), increased levels of inflammatory cytokines and promoted apoptosis. Arsenic exposure increased the relative frequency of the CD8+(Tc) cell subpopulation (from 2.8 to 18.9%) and decreased the frequency of CD4+(Th) cells (from 5.2 to 2.7%). Arsenic exposure also significantly decreased the frequency of T(CD3) (from 32.5% to 19.2%) and B(CD19) cells (from 55.1 to 32.5%). All of these effects induced by NaAsO2 were attenuated by EGCG. Conclusions: The present in vitro findings indicate that EGCG attenuates not only NaAsO2-induced immunosuppression but also inflammation and apoptosis.
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Inflammation plays important roles at different stages of diabetes mellitus, tumorigenesis, and cardiovascular diseases. (−)-Epigallocatechin gallate (EGCG) can attenuate inflammatory responses effectively. However, the immediate early mechanism of EGCG in inflammation remains unclear. Here, we showed that EGCG attenuated the inflammatory response in the immediate early stage of EGCG treatment by shutting off Notch signaling and that the effect did not involve the 67-kDa laminin receptor, the common receptor for EGCG. EGCG eliminated mature Notch from the cell membrane and the nuclear Notch intercellular domain, the active form of Notch, within 2 min by rapid degradation via the proteasome pathway. Transcription of the Notch target gene was downregulated simultaneously. Knockdown of Notch 1/2 expression by RNA interference impaired the downregulation of the inflammatory response elicited by EGCG. Further study showed that EGCG inhibited lipopolysaccharide-induced inflammation and turned off Notch signaling in human primary macrophages. Taken together, our results show that EGCG targets Notch to regulate the inflammatory response in the immediate early stage.
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Toll-like receptor 4 (TLR4) plays an essential role in innate immunity through inflammatory cytokine induction. Recent studies demonstrated that the abnormal activation of TLR4 has a pivotal role in obesity-induced inflammation, which is associated with several diseases, including hyperinsulinemia, hypertriglyceridemia, and cardiovascular disease. Here we demonstrate that (-)-epigallocatechin-3-O-gallate, a natural agonist of the 67-kDa laminin receptor (67LR), suppressed TLR4 expression through E3 ubiquitin-protein ring finger protein 216 (RNF216) upregulation. Our data indicate cyclic GMP mediates 67LR agonist-dependent RNF216 upregulation. Moreover, we show that the highly absorbent 67LR agonist (-)-epigallocatechin-3-O-(3-O-methyl) gallate (EGCG3″Me) significantly attenuated TLR4 expression in the adipose tissue. EGCG3″Me completely inhibited the high-fat/high-sucrose (HF/HS)-induced upregulation of tumor necrosis factor α in adipose tissue and serum monocyte chemoattractant protein-1 increase. Furthermore, this agonist intake prevented HF/HS-induced hyperinsulinemia and hypertriglyceridemia. Taken together, 67LR presents an attractive target for the relief of obesity-induced inflammation.
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Matrix metalloproteinases (MMPs) play a crucial role in developing different types of lung diseases, e.g., pulmonary arterial hypertension (PAH). Green tea polyphenolic catechins such as EGCG and ECG have been shown to ameliorate various types of diseases including PAH. Our present study revealed that among the four green tea catechins (EGCG, ECG, EC, and EGC), EGCG and ECG inhibit pro-/active MMP-2 activities in pulmonary artery smooth muscle cell (PASMC) culture supernatant. Based on the above, we investigated the interactions of pro-/active MMP-2 with the green tea catechins by computational methods. In silico analysis revealed a strong interaction of pro-/active MMP-2 with EGCG/ECG, and galloyl group has been observed to be responsible for this interaction. The in silico analysis corroborated our experimental observation that EGCG and ECG are active in preventing both the proMMP-2 and MMP-2 activities. Importantly, these two catechins appeared to be better inhibitors for proMMP-2 in comparison to MMP-2 as revealed by gelatin zymogram and also by molecular docking studies. In many type of cells, activation of proMMP-2 occurs via an increase in the level of MT1-MMP (MMP-14). We, therefore, determined the interactions of MT1-MMP with the green tea catechins by molecular docking analysis. The study revealed a strong interaction of MT1-MMP with EGCG/ECG, and galloyl group has been observed to be responsible for the interaction.
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Osteopontin (OPN) promotes hepatic fibrosis, and developing therapies targeting OPN expression in settings of hepatic injury holds promise. The polyphenol epigallocatechin-3-gallate (EGCG), found in high concentrations in green tea, downregulates OPN expression through OPN mRNA degradation, but the mechanism is unknown. Previous work has shown that microRNAs can decrease OPN mRNA levels, and other studies have shown that EGCG modulates the expression of multiple microRNAs. In our study, we first demonstrated that OPN induces hepatic stellate cells to transform into an activated state. We then identified three microRNAs which target OPN mRNA: miR-181a, miR-10b, and miR-221. In vitro results show that EGCG upregulates all three microRNAs, and all three microRNAs are capable of down regulating OPN mRNA when administered alone. Interestingly, only miR-221 is necessary for EGCG-mediated OPN mRNA degradation and miR-221 inhibition reduces the effects of EGCG on cell function. In vivo experiments show that thioacetamide (TAA)-induced cell cytotoxicity upregulates OPN expression; treatment with EGCG blocks the effects of TAA. Furthermore, chronic treatment of EGCG in vivo upregulates all three microRNAs equally, suggesting that in more chronic treatment all three microRNAs are involved in modulating OPN expression. We conclude that in in vitro and in vivo models of TAA-induced hepatic fibrosis, EGCG inhibits OPN-dependent injury and fibrosis. EGCG works primarily by upregulating miR-221 to accelerate OPN degradation. EGCG may therefore have utility as a protective agent in settings of liver injury.
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Background: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac muscle disease with left ventricular hypertrophy, interstitial fibrosis and diastolic dysfunction. Increased myofilament Ca²⁺ sensitivity could be the underlying cause of diastolic dysfunction. Epigallocatechin-3-gallate (EGCg), a catechin found in green tea, has been reported to decrease myofilament Ca²⁺ sensitivity in HCM models with troponin mutations. However, whether this is also the case for HCM-associated thick filament mutations is not known. Therefore, we evaluated whether EGCg affects the behavior of cardiomyocytes and myofilaments of an HCM mouse model carrying a gene mutation in cardiac myosin-binding protein C and exhibiting both increased myofilament Ca²⁺ sensitivity and diastolic dysfunction. Methods and Results: Acute effects of EGCg were tested on fractional sarcomere shortening and Ca²⁺ transients in intact ventricular myocytes and on force-Ca²⁺ relationship of skinned ventricular muscle strips isolated from Mybpc3-targeted knock-in (KI) and wild-type (WT) mice. Fractional sarcomere shortening and Ca²⁺ transients were analyzed at 37°C under 1-Hz pacing in the absence or presence of EGCg (1.8 μM). At baseline and in the absence of Fura-2, KI cardiomyocytes displayed lower diastolic sarcomere length, higher fractional sarcomere shortening, longer time to peak shortening and time to 50% relengthening than WT cardiomyocytes. In WT and KI neither diastolic sarcomere length nor fractional sarcomere shortening were influenced by EGCg treatment, but relaxation time was reduced, to a greater extent in KI cells. EGCg shortened time to peak Ca²⁺ and Ca²⁺ transient decay in Fura-2-loaded WT and KI cardiomyocytes. EGCg did not influence phosphorylation of phospholamban. In skinned cardiac muscle strips, EGCg (30 μM) decreased Ca²⁺ sensitivity in both groups. Conclusion: EGCg hastened relaxation and Ca²⁺ transient decay to a larger extent in KI than in WT cardiomyocytes. This effect could be partially explained by myofilament Ca²⁺ desensitization.
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This study evaluated effect of oxalate on epithelial mesenchymal transition (EMT) and potential anti-fibrotic property of epigallocatechin-3-gallate (EGCG). MDCK renal tubular cells were incubated with 0.5 mM sodium oxalate for 24-h with/without 1-h pretreatment with 25 μM EGCG. Microscopic examination, immunoblotting and immunofluorescence staining revealed that oxalate-treated cells gained mesenchymal phenotypes by fibroblast-like morphological change and increasing expression of vimentin and fibronectin, while levels of epithelial markers (E-cadherin, occludin, cytokeratin and ZO-1) were decreased. EGCG pretreatment could prevent all these changes and molecular mechanisms underlying the prevention by EGCG were most likely due to reduced production of intracellular ROS through activation of Nrf2 signaling and increased catalase anti-oxidant enzyme. Knockdown of Nrf2 by small interfering RNA (siRNA) abrogated all the effects of EGCG, confirming that the EGCG protection against oxalate-induced EMT was mediated via Nrf2. Taken together, our data indicate that oxalate turned on EMT of renal tubular cells that could be prevented by EGCG via Nrf2 pathway. These findings also shed light onto development of novel therapeutics or preventive strategies of renal fibrosis in the future.
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Green tea extracts exhibit anti-oxidative and anti-inflammatory actions in different disease conditions. We hypothesized that green tea extract and its catechin constituents ameliorate sodium iodate-induced retinal degeneration in rats by counteracting oxidative stress. In this study, adult Sprague-Dawley rats were intravenously injected with a single dose of sodium iodate. Green tea extract (GTE; Theaphenon-E) or combinations of its catechin constituents, including (-)-epigallocatechin gallate (EGCG), were administered intra-gastrically before injection. Live imaging analysis using confocal scanning laser ophthalmoscopy and spectral-domain optical coherence tomography showed a progressive increase of degenerating profile across the retinal surface and decrease in thickness of outer nuclear layer (ONL) at Day-14 of post-injection. These lesions were significantly ameliorated by Theaphenon-E and catechin combinations with EGCG. Catechins with exclusion of EGCG did not show obvious protective effect. Histological analyses confirmed that Theaphenon-E and catechins containing EGCG protect the retina by reducing ONL disruption. Retinal protective effects were associated with reduced expression of superoxide dismutase, glutathione peroxidase and caspase-3, and suppression of 8-iso-Prostaglandin F2α generation in the retina. In summary, GTE and its catechin constituents are potent anti-oxidants that offer neuroprotection to the outer retinal degeneration after sodium iodate insult, among which EGCG is the most active constituent.
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Epigallocatechin-3-O-gallate (EGCG), derived from green tea, has been studied extensively because of its diverse physiological and pharmacological properties. This study evaluates the protective effect of EGCG on angiotensin II (Ang II)-induced endoglin expression in vitro and in vivo. Cardiac fibroblasts (CFs) from the thoracic aorta of adult Wistar rats were cultured and induced with Ang II. Western blotting, Northern blotting, real-time PCR and promoter activity assay were performed. Ang II increased endoglin expression significantly as compared with control cells. The specific extracellular signal-regulated kinase inhibitor SP600125 (JNK inhibitor), EGCG (100 μM) and c-Jun N-terminal kinase (JNK) siRNA attenuated endoglin proteins following Ang II induction. In addition, pre-treated Ang II-induced endoglin with EGCG diminished the binding activity of AP-1 by electrophoretic mobility shift assay. Moreover, the luciferase assay results revealed that EGCG suppressed the endoglin promoter activity in Ang II-induced CFs by AP-1 binding. Finally, EGCG and the JNK inhibitor (SP600125) were found to have attenuated endoglin expression significantly in Ang II-induced CFs, as determined through confocal microscopy. Following in vivo acute myocardial infarction (AMI)-related myocardial fibrosis study, as well as immunohistochemical and confocal analyses, after treatment with endoglin siRNA and EGCG (50 mg/kg), the area of myocardial fibrosis reduced by 53.4% and 64.5% and attenuated the left ventricular end-diastolic and systolic dimensions, and friction shortening in hemodynamic monitor. In conclusion, epigallocatechin-3-O-gallate (EGCG) attenuated the endoglin expression and myocardial fibrosis by anti-inflammatory effect in vitro and in vivo, the novel suppressive effect was mediated through JNK/AP-1 pathway.
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The relative humidity (RH) and drying shrinkage (DS) of CA mortar and the relationship between them were investigated. Results indicate that RH is high in early age, decreasing with increasing in the age, and slowing down after 90 d; CA mortar shrinks after an initial expansion, the highest expansion value appear at about 7 d, and shrinkage decreases down after 120 d;the parameters of mix proportion, such as water-cement ratio (mW/mC), asphalt-cement ratio (mW/mC), has no significant influence on RH and DS of CA mortar; under sealed curing, RH of CA mortar is higher and slightly reduces in late stage, and DS of CA mortar is lower and slightly increases, even has a slight expansion in long-term. Under open condition, CA mortar undergoes a high shrinkage at late stage, DS and RH show significant linear relation, which can provide guidance for reducing the crack between slab corner and CA mortar layer in CRTS I track. © 2017, Editorial Department of Journal of Building Materials. All right reserved.