PMID: 

J Surg Res. 2019 Dec 6 ;247:1-7. Epub 2019 Dec 6. PMID: 31816476

Abstract Title: 

Protective Effect of Epigallocatechin Gallate in Ischemia-Reperfusion Injury of Rat Skeletal Muscle.

Abstract: 

BACKGROUND: Reactive oxygen species-induced cell injury has been considered to be one of the main etiologic factors in ischemia-reperfusion injury (IRI). As a potential antioxidant agent, epigallocatechin gallate (EGCG) was examined in skeletal muscle of the rats after IRI with or without treatment.MATERIALS AND METHODS: Tourniquet application applied to the rats' hind limbs was selected as the appropriate IRI method. Animals were randomly distributed to one of the following groups: (1) sham control + SF (saline) (10 mg/kg/i.p.) (SC-SF), (2) IRI (4 + 2 h) + SF (10 mg/kg/i.p.) (IRI-SF), (3) IRI and EGCG (25 mg/kg/i.p.) (IRI-EG25), and (4) IRI and EGCG (50 mg/kg/i.p) (IRI-EG50). In another set of experiments with identical groups, the only difference was that the reperfusion period was 24 h. A number of different parameters relating to the damage seen in the skeletal muscles, lungs, kidneys, and liver and particular cytokines were measured by proper analytical methods.RESULTS: In comparison with the SC-SF group, IRI (4 + 2 h) induced an increase in the total oxidative status of skeletal muscle (10.17 ± 0.61 versus 15.74 ± 1.10) and blood creatine phosphokinase (CPK) (669.88 ± 50.23 versus 7202.38 ± 766.13) and lactate dehydrogenase levels (686.00 ± 67.48 versus 1343.00 ± 113.01). Although 25 mg/kg EGCG could not reverse these parameters to their normal levels, the higher dose of EGCG, that is, 50 mg/kg, was sufficient to prevent the increases seen in total oxidative status (8.55 ± 0.85) and CPK levels (4741.63 ± 339.40). In addition, reduced total antioxidant status of skeletal muscle in the IRI-SF group (0.50 ± 0.06) was elevated by the administration of EGCG (50 mg/kg) (0.85 ± 0.04). Regarding remote organ injury, only alanine transaminase (ALT) and aspartate transaminase (AST) levels were found to be increased, showing a slight damage in liver tissue. However, neither dose of EGCG was able to prevent this deleterious effect. As for cytokines (interleukin-1β, IL-6, IL-8, tumor necrosis factor-α, and monocyte chemotactic protein-1), there were no differences between the study groups. In regard to long-term IRI (i.e., 4 + 24 h), statistically significantlyelevated parameters in the IRI-SF group were as follows: CPK, lactate dehydrogenase, creatinine (Cr), and blood urea nitrogen. On the other hand, none of them were influenced by either dose of EGCG. According to the results, EGCG demonstrates a considerable protective effect toward IRI (4 + 2 h)of skeletal muscle.CONCLUSIONS: Although oxidative stress seems to play a significant role both in the pathogenesis of IRI and in the mechanism of action of EGCG, there is no evidence that inflammatory cytokines are, at least in our model, crucial mediators regarding the former events.

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PMID: 

J Cardiovasc Pharmacol. 2019 Dec 30. Epub 2019 Dec 30. PMID: 31895874

Abstract Title: 

Protective effect of epigallocatechin gallate on endothelial disorders in atherosclerosis.

Abstract: 

Healthy vascular endothelial cells regulate vascular tone and permeability, prevent vessel wall inflammation, enhance thromboresistance, and contribute to general vascular health. Furthermore, they perform important functions including the production of vasoactive substances such as nitric oxide (NO) and endothelium-derived hyperpolarizing factors, as well as the regulation of smooth muscle cell functions. Conversely, vascular endothelial dysfunction leads to atherosclerosis, thereby enhancing the risk of stroke, myocardial infarction, and other cardiovascular diseases (CVDs). Observational studies and randomized trials showed that green tea intake was inversely related to CVD risk. Furthermore, evidence indicates that epigallocatechin gallate (EGCG) found in green tea might exert a preventive effect against CVDs. EGCG acts as an antioxidant, inducing NO release and reducing endothelin-1 production in endothelial cells. EGCG enhances the bioavailability of normal NO by reducing levels of the endogenous NO inhibitor asymmetric dimethylarginine. Furthermore, it inhibits the enhanced expression of adhesion molecules such as vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 and attenuates monocyte adhesion. In addition, EGCG prevents enhanced oxidative stress via the Nrf2/HO-1 pathway. These effects indicate that it might prevent the production of reactive oxygen species, inhibit inflammation, and reduce endothelial cell apoptosis during the initial stages of atherosclerosis. The current review summarizes recent research in this area and discusses novel findings regarding the protective effect of EGCG on endothelial dysfunction and CVDs in general.

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PMID: 

J Cell Physiol. 2020 Jan 14. Epub 2020 Jan 14. PMID: 31943177

Abstract Title: 

EGCG regulates CTR1 expression through its pro-oxidative property in non-small-cell lung cancer cells.

Abstract: 

Copper transporter 1 (CTR1) plays an important role in increasing cisplatin intake. Our previous studies showed that CTR1 expression was upregulated by (-)-epigallocatechin-3-gallate (EGCG), a green tea polyphenol, therefore enhanced cisplatin sensitivity in ovary cancer and non-small-cell lung cancer (NSCLC) cells. In the current study in the non-small-cell lung cancer cells, we uncovered a potential mechanism of EGCG-induced CTR1 through its pro-oxidative property. We found that EGCG increased reactive oxygen species (ROS) generation, while in the presence of ROS scavenger N-acetyl-cysteine (NAC), ROS production waseliminated. Changes of CTR1 expression were consistent with the ROS level. Simultaneously, EGCG downregulated ERK1/2 while upregulated lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) through ROS to induce CTR1 expression. Besides, in a nude mouse xenografts model, EGCG treatment raised ROSlevel, expression of CTR1 and NEAT1 in tumor tissue. Also, ERK1/2 and p-ERK1/2 were suppressed as well. Taken together, these results suggested a novel mechanism that EGCG mediated ROS to regulate CTR1 expression through the ERK1/2/NEAT1 signaling pathway, which provided more possibilities for EGCGas a natural agent in adjuvant therapy of lung cancer.

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PMID: 

Int J Clin Exp Pathol. 2019 ;12(9):3222-3234. Epub 2019 Sep 1. PMID: 31934166

Abstract Title: 

ERα36 is an effective target of epigallocatechin-3-gallate in hepatocellular carcinoma.

Abstract: 

Epigallocatechin-3-gallate (EGCG) is a natural product with potential anti-cancer property whose direct target has not been identified. This study intended to investigate ERα36, a new isoform of estrogen receptor alpha (ERa), as a therapeutic target of EGCG in hepatocellular carcinoma (HCC). In this work, we examined the expression level of ERs in HCC cell lines and a normal human liver cell line, and evaluated inhibition effect of EGCG on these cells, and further on Hep3B. The results showed that ERα36 was the main ER in HCC cells and served as a biomarker of responsiveness to EGCG inhibition, and there was a positive correlation between ERα36 expression level and inhibitory effect of EGCG as indicated by IC.experiments also showed dose-dependent inhibition of EGCG on ERα36 high-expressing Hep3B. EGCG exerted inhibition on Hep3B cells by both anti-proliferation and pro-apoptosis. ERα36-EGFR-Her-2 feedback loop, PI3K/Akt and MAPK/ERK pathways were inhibited, while caspase 3 was activated by EGCG in Hep3B cells, with p-ERK accumulated in cytoplasm. The inhibitory effect of EGCG was significantly attenuated when ERα36 was pre-activated. This is the first evidence that EGCG exerts its anti-cancer effect by inhibiting ERα36, followed with inhibition of the ERα36-EGFR-Her-2 feedback loop and PI3K/Akt, MAPK/ERK pathway, activation of caspase 3, and accumulationof p-ERK in cytoplasm. It suggests that ERα36 might be an efficient target of EGCG in HCC.

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PMID: 

Drug Des Devel Ther. 2019 ;13:4275-4290. Epub 2019 Dec 18. PMID: 31908414

Abstract Title: 

The Protective Role of Tanshinone IIA in Silicosis Rat Model via TGF-β1/Smad Signaling Suppression, NOX4 Inhibition and Nrf2/ARE Signaling Activation.

Abstract: 

Purpose: Silicosis is an occupational disease caused by inhalation of silica and there are no effective drugs to treat this disease. Tanshinone IIA (Tan IIA), a traditional natural component, has been reported to possess anti-inflammatory, antioxidant, and anti-fibrotic properties. The current study's purpose was to examine Tan IIA's protective effects against silica-induced pulmonary fibrosis and to explore the underlying mechanisms.Methods: 48 male SD rats were randomly divided into four groups (n=12): i) Control group; ii) Silicosis group; iii) Tan IIA group; iv) Silicosis +Tan IIA group. Two days after modeling, the rats of Tan IIA group and Silicosis +Tan IIA group were given intraperitoneal administration 25 mg/kg/d Tan IIA for 40 days. Then, the four groups of rats were sacrificed and the lung inflammatory responses were measured by ELISA, lung damage and fibrosis were analyzed by hematoxylin and eosin (H&E) staining and Masson staining, the expression levels of collagen I, fibronectin andα-smooth muscle actin (α-SMA) were measured by immunohistochemistry. The markers of oxidative stress were measured by commercial kits, and the activity of the TGF-β1/Smad and NOX4, Nrf2/ARE signaling pathways were measured by RT-PCR and Western blotting.Results: The silica-induced pulmonary inflammtory responses, structural damage and fibrosis were significantly attenuated by Tan IIA treatment. In addition, treatment with Tan IIA decreased collagen I, fibronectin andα-SMA expression, and inhibited TGF-β1/Smad signaling in the lung tissue. The upregulated levels of oxidative stress markers in silicosis rats were also markedly restored following Tan IIA treatment. Furthermore, treatment with Tan IIA reduced NOX4 expression and enhanced activation of the Nrf2/ARE pathway in the lung tissue of silicosis rats.Conclusion: These findings suggest that Tan IIA may protect lung from silica damage via the suppression of TGF-β1/Smad signaling, inhibition of NOX4 expression and activation of the Nrf2/ARE pathway.

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PMID: 

Ecotoxicol Environ Saf. 2020 Jan 13 ;191:110202. Epub 2020 Jan 13. PMID: 31945511

Abstract Title: 

Potential ameliorative effects of epigallocatechin-3-gallate against cigarette smoke exposure induced renal and hepatic deficits.

Abstract: 

The environmental pollution caused by cigarette smoke (CS) seriously endangers people's health. Epigallocatechin-3-gallate (EGCG) is the most abundant catechin in green tea. In this study, rats were exposed to CS for 90 days. Kidney function was evaluated by detecting the levels of serum creatinine and blood urea nitrogen. Liver function was evaluated by detecting the activities of alanine aminotransferase and aspartate transaminase. The renal and hepatic oxidative stress and inflammation were assessed by detecting the levels of malondialdehyde, reduced glutathione, antioxidant enzymes (superoxide dismutase and glutathione peroxidase) and proinflammatory cytokines. Organ fibrosis was evaluated by observing collagen deposition via masson staining, by examining the hydroxyproline level, by measuring the mRNA levels of fibrosis-associated genes collagen (Col)-1A1 and Col-3A1, as well as by assessing the activity of profibrotic TGF-β1 pathway. Additionally, renal and hepatic epithelial-mesenchymal transition (EMT) were evaluated. It was observed that EGCG ameliorated the renal and hepatic oxidative stress, inflammation, EMT, as well as inhibited the activation of TGF-β1 signaling pathway induced by CS. These results showed that EGCG could attenuate CS-induced renal and hepatic fibrosis.

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PMID: 

Evid Based Complement Alternat Med. 2019 ;2019:7514046. Epub 2019 Dec 13. PMID: 31915451

Abstract Title: 

Therapeutic Effect of Tanshinone IIA on Liver Fibrosis and the Possible Mechanism: A Preclinical Meta-Analysis.

Abstract: 

Background: Liver fibrosis is a serious human health problem, and there is a need for specific antifibrosis drugs in the clinic. Tanshinone IIA has recently been reported to have a role in the treatment of liver fibrosis. However, the evidence supporting its antifibrotic effect is not sufficient, and the underlying mechanism is not clear. We thus performed this meta-analysis of animal research to assess the therapeutic effect of tanshinone IIA on liver fibrosis and analyzed the possible associated mechanism to provide a reference for further clinical drug preparation and clinical research.Methods: We collect related articles from the databases PubMed, Web of Science, Embase, Wanfang, VIP, and CNKI. The quality of the included studies was evaluated according to the SYRCLE risk of bias tool for animal studies. Data were analyzed using RavMan 5.3 and Stata 12.0 software.Results: A total of 404 articles were retrieved from the databases. After screening, 11 articles were included in the analysis. The included studies' methodological quality was generally low, and an obvious publication bias was found. The results showed that tanshinone IIA significantly improved liver function in experimental animals and reduced the level of liver fibrosis by reducing inflammation and inhibiting immunity, antiapoptotic processes, and HSC activation.Conclusion: Tanshinone IIA can effectively improve liver fibrosis and liver function in animal models and is worthy of future higher quality animal studies and clinical drug trials.

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PMID: 

Int J Clin Exp Pathol. 2019 ;12(10):3791-3798. Epub 2019 Oct 1. PMID: 31933767

Abstract Title: 

Tanshinone IIA reduces oxidized low-density lipoprotein-induced inflammatory responses by downregulating microRNA-33 in THP-1 macrophages.

Abstract: 

Atherosclerosis is a leading cause of cardiovascular diseases. Oxidized low-density lipoprotein (ox-LDL) is commonly used to construct atherosclerosis cell models. Macrophages-secreted pro-inflammatory factors play vital roles in the development of atherosclerosis. Tanshinone IIA (Tan) is an effective therapeutic agent for atherosclerotic cardiovascular diseases. However, the molecular mechanisms by which Tan protects against atherogenesis have not been thoroughly elucidated. In the present study, we aimed to search for microRNA targets of Tan in ox-LDL-stimulated macrophages. Interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) levels were determined by matching ELISA commercial kits. RT-qPCR assay was conducted to measure microRNA-33 (miR-33) expression. We found that ox-LDL induced the secretion of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and the expressionof microRNA-33 (miR-33) in THP-1 macrophages. Tan inhibited pro-inflammatory cytokine secretion and miR-33 expression in ox-LDL-stimulated THP-1 macrophages. Also, the depletion of miR-33 suppressed pro-inflammatory cytokine secretion in ox-LDL-stimulated THP-1 macrophages. Moreover, miR-33 upregulation abrogated the inhibitory effect of Tan on pro-inflammatory cytokine secretion in ox-LDL-stimulated THP-1 macrophages. In conclusion, Tan inhibited ox-LDL-induced pro-inflammatory cytokine secretion by downregulating miR-33 in THP-1 macrophages, hinting that Tan might exert its atheroprotectiveeffects by targeting miR-33 and reducing pro-inflammatory responses.

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PMID: 

Mech Ageing Dev. 2020 Jan 14:111209. Epub 2020 Jan 14. PMID: 31953123

Abstract Title: 

Potential of coconut oil and medium chain triglycerides in the prevention and treatment of Alzheimer's disease.

Abstract: 

Alzheimer's disease (AD) is the most common form of dementia. Currently, there is no effective medication for the prevention or treatment of AD. This has led to the search for alternative therapeutic strategies. Coconut oil(CO) has a unique fatty acid composition that is rich in medium chain fatty acids(MCFA), a major portion of which directly reaches the liver via the portal vein, thereby bypassing the lymphatic system. Given that brain glucose hypometabolism is a major early hallmark of AD, detectable well before the onset of symptoms, ketone bodies from MCFA metabolism can potentially serve as an alternative energy source to compensate for lack of glucose utilisation in the brain. Additionally, neuroprotective antioxidant properties of CO have been attributed to its polyphenolic content. This review discusses how the metabolism of CO and MCFA may aid in compensating the glucose hypometabolism observed in the AD brain. Furthermore, we present the current evidence of the neuroprotective properties of CO on cognition, amyloid-β pathogenicity, inflammation and oxidative stress. The current review addresses the influence of CO/MCFA on other chronic disorders that are risk factors for AD, and addresses existing gaps in the literature regarding the use of CO/MCFA as a potential treatment for AD.

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PMID: 

Heliyon. 2019 Oct ;5(10):e02612. Epub 2019 Oct 20. PMID: 31673647

Abstract Title: 

Antibacterial and immunomodulator activities of virgin coconut oil (VCO) against.

Abstract: 

Antibiotics have components to inhibit infections against, but they depend on judicious use to minimize the incidence of resistance forms. Strategies to improve the current situation include research in finding a new antimicrobial from virgin coconut oil (VCO). The saturated fatty acid, lauric acid (LA) (C12) contain in VCO was reported to have antibacterial activities. This study developed antimicrobial of VCO as an antimicrobial and immunomodulatory agent.used in this study had been isolated and identified from the mastitis milk crossbreed Etawa goat from Riau, Indonesia. The susceptibility ofto VCO was tested using the broth dilution method. The inhibition mechanisms ofhad been studied by scanning electron microscopy (SEM) after treatment with VCO, and potential of VCO, which is known in phagocytosis macrophage.test confirmed the inhibitory effect of VCO on the growth ofat the concentration of 200μl (equal to 0.102 % LA). Based on the result of the phagocytosing assay, VCO could increase the ability of the macrophage cells to phagocytesignificantly at a concentration of 200μL (equal to 0.102% LA). This study concluded that the VCO could inhibit the growth ofwith destructive mechanisms of bacterial cell walls and increase the ability of the phagocytic immune cells.

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