Administration Of Epigallocatechin-3-gallate Research Articles

Maternal EGCG intervention mitigates chronic hypertension during pregnancy in spontaneously hypertensive rats without adverse effects on pregnancy outcomes

Background: Chronic hypertension during pregnancy is a significant concern, associated with increased risks of maternal-fetal morbidity and mortality. Epigallocatechin gallate (EGCG), a compound known for its cardioprotective properties, has gained attention as a potential health supplement due to its favorable safety profile. Objective: This study aims to investigate the effects of maternal EGCG supplementation on elevated blood pressure and pregnancy outcomes in a rodent model of chronic hypertension, specifically using spontaneously hypertensive rats (SHR). Furthermore, the study explores the influence of maternal EGCG supplementation on the blood pressure of SHR offspring during early postnatal development. Methods: SHR dams received oral EGCG at 30 mg/kg body weight. Systolic blood pressure (SBP) monitored weekly throughout gestation period and until postpartum day 21. Pregnancy outcomes - litter size, pup viability, and birth weights - were recorded. SBP in weaned SHR offspring was monitored from 5 to 13 weeks of age to assess long-term effects of maternal EGCG treatment. Daily cage-side observations evaluated general health, behavior, and signs of toxicity. Plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, and creatinine were analyzed to evaluate liver and kidney function. Results: EGCG treatment in SHR dams progressively reduced maternal SBP throughout gestation and the postpartum period. However, EGCG administration did not affect pregnancy outcomes (gestation duration, litter size, and birth weights). Markers of liver and kidney function (ALT, AST, urea, and creatinine) showed no signs of organ injury in EGCG-treated groups. Contrary to expectations, SBP in SHR offspring exposed to perinatal EGCG did not decrease compared to control groups, indicating maternal EGCG did not alter the offspring's hypertension predisposition. Conclusion: Maternal EGCG supplementation effectively lowered blood pressure in hypertensive dams without compromising pregnancy outcomes or causing liver and kidney damage. These findings suggest that EGCG may be a safe cardioprotective supplement during pregnancy. However, perinatal EGCG exposure did not alter the inherent genetic predisposition to hypertension in SHR offspring. Keywords: Theaceae; Camellia sinensis; green tea; catechins, EGCG; hypertension, pregnancy outcomes, perinatal, spontaneously hypertensive rats, chronic hypertension during pregnancy

Epigallocatechin-3-gallate (EGCG) reduced expression of Signal peptide-CUB-EGF domain-containing protein 3 (SCUBE3) and Transforming Growth Factor-β1 (TGF-β1) in visceral pleural tissue cultures of patients with empyema

Abstract* Background Increased expression of signal peptide-CUB-EGF domain-containing protein 3 (SCUBE3) and Transforming Growth Factor-β1 (TGF-β1) has been thought to influence the fibrosis process in many tissues. However, increased expression of these two factors has never been assessed in pleural fibrosis. Pleural fibrosis is a disease that usually results from various infectious processes, such as empyema. Fibrosis formation is recently known to be prevented by Epigallocatechin-3-gallate (EGCG), which is the most potent active substance found in Gambir (Uncaria gambir Roxb) leaves. Thus, further research is needed to determine the potential of EGCG to inhibit the process of pleural fibrosis caused by empyema. Methods An in vitro experimental study with post test-only controlled group was conducted on the pleural tissue of all patients who underwent decortication surgery due to empyema at Dr. M. Djamil Hospital, Padang, Indonesia between March 1st and April 30, 2024. Case samples were obtained by consecutive sampling, and three patients who met the inclusion criteria were obtained. Pleural tissue in each patient was then divided into several groups based on the treatment, namely the control group, 50 μg EGCG administration group, and 100 μg EGCG administration group. We used to determine SCUBE3 and TGF-β1 genes expression. Data were tested using ANOVA and Least Significant Difference (LSD) tests. Results There were significant differences in the SCUBE3 and TGF-β1 genes expression of 50 μg and 100 μg EGCG administration groups and the control groups in the 2 × 2 cm sample preparation (p=0.002) (p=0.014, respectively). Significant differences in TGF-β1 expression were also found between the groups treated with EGCG 50 μg and 100 μg and the control group in the 1 × 1 cm preparation (p=0.019). Conclusion EGCG can potentially decrease SCUBE3 and TGF-β1 expression in patients with pleural empyema.

Protective Effect of Epigallocatechin-3-gallate against Hepatic Oxidative Stress Induced by tert-Butyl Hhydroperoxide in Yellow-Feathered Broilers.

Recent studies have shown that epigallocatechin-3-gallate (EGCG), as an effective antioxidant, could attenuate the oxidative damage, inflammation and necrosis in the liver in response to oxidative stress. The present study investigated whether oral administration of EGCG could effectively alleviate the hepatic histopathological changes and oxidative damage in yellow-feathered broilers induced by tert-butyl hydroperoxide (t-BHP). Broilers were exposed to 600 μmol t-BHP/kg body weight (BW) to induce oxidative stress by intraperitoneal injection every five days, followed by oral administration of different doses of EGCG (0, 20, 40 and 60 mg/kg BW) and 20 mg vitamin E (VE)/kg BW every day during 5-21 days of age. The results showed that t-BHP injection decreased (p < 0.05) body weight and the relative weight of the spleen; the enzyme activities of total antioxidant capacity (T-AOC), catalase (CAT) and total superoxide dismutase (SOD); and gene mRNA expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), CAT, SOD1, SOD2 and acetyl-CoA carboxylase (ACACA); as well as increased (p < 0.05) necrosis formation, malondialdehyde (MDA) content, reactive oxygen species (ROS)accumulation, and peroxisome proliferator activates receptor-α (PPARα) mRNA expression in the liver of yellow-feathered female broilers at 21 days of age. Treatment with 60 mg EGCG/kg BW orally could enhance antioxidant enzyme activities and reverse the hepatic damage induced by t-BHP injection by reducing the accumulation of ROS and MDA in the liver and activating the Nrf2 and PPARα pathways related to the induction of antioxidant gene expression (p < 0.05). In conclusion, intraperitoneal injection of t-BHP impaired body growth and induced hepatic ROS accumulation, which destroyed the antioxidant system and led to oxidative damage in the liver of yellow-feathered broilers from 5 to 21 days of age. It is suggested that EGCG may play an antioxidant role through the Nrf2 and PPARα signaling pathways to effectively protect against t-BHP-induced hepatic oxidative damage in broilers, and the appropriate dose was 60 mg EGCG/kg BW by oral administration.

EGCG alleviates Ochratoxin A-induced pyroptosis in rat's kidney by inhibiting NLRP3/Caspase-1/GSDMD signaling pathway

Ochratoxin A (OTA) exposure is inevitable due to its contamination in foods, and there is no treatment for the OTA induced organ toxicity. We evaluate the effect of epigallocatechin gallate (EGCG) on the nephrotoxicity caused by OTA, and to reveal the relationship of this effect with the NLRP3/Caspase-1/GSDMD pathway dependent pyroptosis. 40 male Wistar albino rats divided into 5 groups (n = 8, per group) 0.5 mg/kg/day OTA were administered to the rats and 50 mg/kg and 100 mg/kg EGCG were administered to the groups by gavage orally for 14 days. Serum urea and creatinine levels increased significantly with OTA exposure. Similarly, it was determined that significant changes in oxidative stress parameters with OTA exposure in kidney tissue. Also, there was a significant increase in kidney tissue TGF-β, NF-κB, IL-1β, IL-18, NLRP3, Caspase-1 and GSDMD mRNA expressions with OTA exposure. EGCG administration augmented a dose-dependent decrease in the aforementioned parameters. NLRP3/Caspase-1/GSDMD pathway is induced in the kidneys due to OTA exposure were shown with this study. Potent antioxidant EGCG could alleviate the pathways specified with this study in OTA nephrotoxicity and its supplementation may be effective strategies for the protection.

Epigallocatechin-3-gallate (EGCG) reduced expression of Signal peptide-CUB-EGF domain-containing protein 3 (SCUBE3) and Transforming Growth Factor-β1 (TGF-β1) in visceral pleural tissue cultures of patients with empyema

Abstract* Background Increased expression of signal peptide-CUB-EGF domain-containing protein 3 (SCUBE3) and Transforming Growth Factor-β1 (TGF-β1) has been thought to influence the fibrosis process in many tissues. However, increased expression of these two factors has never been assessed in pleural fibrosis. Pleural fibrosis is a disease that usually results from various infectious processes, such as empyema. Fibrosis formation is recently known to be prevented by Epigallocatechin-3-gallate (EGCG), which is the most potent active substance found in Gambir (Uncaria gambir Roxb) leaves. Thus, further research is needed to determine the potential of EGCG to inhibit the process of pleural fibrosis caused by empyema. Methods An in vitro experimental study with post test-only controlled group was conducted on the pleural tissue of all patients who underwent decortication surgery due to empyema at Dr. M. Djamil Hospital, Padang, Indonesia between March 1st and April 30, 2024. Case samples were obtained by consecutive sampling, and three patients who met the inclusion criteria were obtained. Pleural tissue in each patient was then divided into several groups based on the treatment, namely the control group, 50 μg EGCG administration group, and 100 μg EGCG administration group. We used to determine SCUBE3 and TGF-β1 genes expression. Data were tested using ANOVA and Least Significant Difference (LSD) tests. Results There were significant differences in the SCUBE3 and TGF-β1 genes expression of 50 μg and 100 μg EGCG administration groups and the control groups in the 2 × 2 cm sample preparation (p=0.002) (p=0.014, respectively). Significant differences in TGF-β1 expression were also found between the groups treated with EGCG 50 μg and 100 μg and the control group in the 1 × 1 cm preparation (p=0.019). Conclusion EGCG can potentially decrease SCUBE3 and TGF-β1 expression in patients with pleural empyema.

Up-regulation of BMAL1 by epigallocatechin-3-gallate improves neurological damage in SBI rats

Brain Muscle ARNT-Like Protein 1 (BMAL1) suppresses oxidative stress in brain injury during surgery. Epigallocatechin-3-gallate (EGCG), a monomer in green tea, has been identified as an antioxidant and a potential agonist for BMAL1. In this work, the mechanism by which BMAL1 is regulated was investigated, as well as the therapeutic effect of EGCG on surgically injured rats. The pathological environment after brain injury during surgery was simulated by excising the right frontal lobe of rats. Rats received an intraperitoneal injection of EGCG immediately after surgery. Neurological scores and cerebral edema were recorded after surgery. Fluoro-Jade C staining, TUNEL staining, western blot, and lipid peroxidation analyses were conducted 3 days later. Here we show that the endogenous BMAL1 level decreased after brain injury. Postoperative administration of EGCG up-regulated the content of BMAL1 around the cerebral cortex, reduced the oxidative stress level, reduced neuronal apoptosis and the number of degenerated neurons, alleviated cerebral edema, and improved neurological scores in rats. This suggests that BMAL1 is an effective target for treating surgical brain injury, as well as that EGCG may be a promising agent for alleviating postoperative brain injury.

Epigallocatechin gallate alleviates non-alcoholic fatty liver disease through the inhibition of the expression and activity of Dipeptide kinase 4

BackgroundNon-alcoholic fatty liver disease (NAFLD) has emerged as the most prevalent glocal cause of chronic hepatic disease, with incidence rates that continue to rise steadily. Treatment options for affected patients are currently limited to dietary changes and exercise interventions, with no drugs having been licensed for the treatment of this disease. There is thus a pressing need for the development of novel therapeutic strategies. Work from our group suggests that the primary bioactive ingredient in green tea, epigallocatechin gallate (EGCG), may help reduce liver fat content and protect against hepatic injury through the inhibition of dipeptidyl peptidase 4 (DPP4) expression and activity. The study investigated the potential pathways by which EGCG may improve NAFLD, identified the sites of interaction between EGCG and DPP4, and proposed novel clinical treatment strategies. MethodsA clinical randomized controlled trial was conducted to investigate the potential efficacy of EGCG in NAFLD patients. The study compared relevant indices before and after EGCG administration. Animal models of NAFLD were constructed using male C57BL/6J mice fed a high-fat diet to observe the ameliorative effects of EGCG on the livers of the model mice and to investigate the potential pathways by which EGCG alleviates NAFLD. The interaction mechanism between EGCG and DPP4 was investigated using oleic acid and palmitic acid-treated HepG2 cell lines. Plasmids in which different sites had been disrupted were used to identify the effective interaction sites. ResultsECGC was found to suppress the accumulation of lipids, inhibit inflammation, remediate dysregulated lipid metabolism, and improve the pathogenesis of NAFLD via the inhibition of the expression and activity of DPP4. ConclusionsThe study results indicate that EGCG has a positive impact on improving NAFLD. These results highlight promising new opportunities to safely and effectively treat NAFLD in the clinic. Study id numberChiCTR2300076741; https://www.chictr.org.cn/

The effect of long-term administration of green tea catechins on aging-related cardiac diastolic dysfunction and decline of troponin I

Aging is an independent risk factor for cardiovascular diseases. Cardiac diastolic dysfunction (CDD), ultimately leading to heart failure with preserved ejection fraction, is prevalent among older individuals. Although therapeutics have made great progress, preventive strategies remain unmet medical needs. Green tea catechins have been shown to be effective in improving aging-related cardiovascular and cerebral disorders in animal models and patients. However, little attention has been paid to whether long-term administration of epigallocatechin gallate (EGCG), the major bioactive ingredient of green tea catechins, could prevent the onset and progression of CDD. In this study, 12-month-old female mice were orally administered 50, 100, and 200 mg EGCG mixed with drinking water for 6 months. Aged mice (18 months old) exhibited the major features of heart failure with preserved ejection fraction, including CDD with preserved ejection fraction, cardiac fibrosis, increased cardiomyocyte apoptosis, and mitochondrial damages, as well as elevated A/B-type natriuretic peptide. Cardiac troponin I (cTnI) expression was also reduced. Long-term administration of 100 or 200 mg EGCG prevented aging-related CDD and exercise capacity decline, along with alleviating myocardial apoptosis and mitochondria damage. The transcription and protein expression of cTnI were increased, which might be achieved by inhibiting the expression and activity of histone deacetylase 1 and reducing its binding level near cTnI's promoter, thereby elevating acetylated histone 3 and acetylated lysine 9 on histone H3 in the aged mice. We provide a novel insight that long-term administration of EGCG is a potentially effective strategy in preventing aging-related CDD and cTnI expression decline.

Evaluation of the antibacterial effect of Epigallocatechin gallate on the major pathogens of canine periodontal disease and therapeutic effects on periodontal disease mice.

Periodontal disease (PD) is a prevalent oral affliction in canines, with limited therapeutic options available. The potential transmission of oral bacteria from canines to humans through inter-species contact poses a risk of zoonotic infection. Epigallocatechin gallate (EGCG), the principal catechin in green tea polyphenols, exhibits antibacterial properties effective against human PD. Given the clinical parallels between canine and human PD, this study explores the feasibility of employing EGCG as a therapeutic agent for canine PD. Initially, a survey and statistical analysis of bacterial infection data related to canine PD in China were conducted. Subsequently, the primary pathogenic bacteria of canine PD were isolated and cultivated, and the in vitro antibacterial efficacy of EGCG was assessed. Furthermore, verify the therapeutic effect of EGCG on a mouse PD model in vivo. The high-throughput 16S rRNA gene sequencing identified Porphyromonas, Fusobacterium, Treponema, Moraxella, and Capnocytophaga as the genera that distinguishing PD from healthy canines' gingival crevicular fluid (GCF) samples in China. The anaerobic culture and drug susceptibility testing isolated a total of 92 clinical strains, representing 22 species, from 72 canine GCF samples, including Porphyromonas gulae, Prevotella intermedia, Porphyromonas macacae, etc. The minimum inhibitory concentration (MIC) ranging of EGCG was from 0.019 to 1.25 mg/mL. Following a 7 days oral mucosal administration of medium-dose EGCG (0.625 mg/mL), the abundance of periodontal microorganisms in PD mice significantly decreased. This intervention ameliorated alveolar bone loss, reducing the average cementoenamel junction to the alveolar bone crest (CEJ-ABC) distance from 0.306 mm ± 0.050 mm to 0.161 mm ± 0.026 mm. Additionally, EGCG (0.3125 mg/mL) markedly down-regulated the expression of inflammatory factor IL-6 in the serum of PD mice. Our research demonstrates the significant antibacterial effects of EGCG against the prevalent bacterium P. gulae in canine PD. Moreover, EGCG exhibits anti-inflammatory properties and proves effective in addressing bone loss in a PD mouse model. These findings collectively suggest the therapeutic potential of EGCG in the treatment of canine PD. The outcomes of this study contribute valuable data, laying the foundation for further exploration and screening of alternative antibiotic drugs to advance the management of canine PD.

Epigallocatechin-3-gallate promotes wound healing response in diabetic mice by activating keratinocytes and promoting re-epithelialization.

Type 2 diabetes (T2D) is a metabolic disorder that causes numerous complications including impaired wound healing and poses a significant challenge for the management of diabetic patients. Epigallocatechin-3-gallate (EGCG) is a natural polyphenol that exhibits anti-inflammatory and anti-oxidative benefits in skin wounds, however, the direct effect of EGCG on epidermal keratinocytes, the primary cells required for re-epithelialization in wound healing remains unknown. Our study aims to examine the underlying mechanisms of EGCG's ability to promote re-epithelialization and wound healing in T2D-induced wounds. Murine models of wound healing in T2D were established via feeding high-fat high-fructose diet (HFFD) and the creation of full-thickness wounds. Mice were administered daily with EGCG or vehicle to examine the wound healing response and underlying molecular mechanisms of EGCG's protective effects. Systemic administration of EGCG in T2D mice robustly accelerated the wound healing response following injury. EGCG induced nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2) and promoted cytokeratin 16 (K16) expression to activate epidermal keratinocytes and robustly promoted re-epithelialization of wounds in diabetic mice. Further, EGCG demonstrated high binding affinity with Kelch-like ECH-associated protein 1 (KEAP1), thereby inhibiting KEAP1-mediated degradation of NRF2. Our findings provide important evidence that EGCG accelerates the wound healing response in diabetic mice by activating epidermal keratinocytes, thereby promoting re-epithelialization of wounds via K16/NRF2/KEAP1 signaling axis. These mechanistic insights into the protective effects of EGCG further suggest its therapeutic potential as a promising drug for treating chronic wounds in T2D.

EPIGALLOCATECHIN-3-GALLATE ALLEVIATES METABOLIC DISORDERS IN RATS SIMULTANEOUSLY EXPOSED TO ROUND-THE-CLOCK LIGHTING AND KEPT ON HIGH-CALORIE CARBOHYDRATE-LIPID DIET

The aim of the study is to investigate the effect of epigallocatechin-3-gallate (EGCG) on the parameters of carbohydrate and lipid metabolism in the blood serum of rats exposed to round-the-clock lighting (RCL) and kept on high-calorie carbohydrate-lipid diet (HCCLD). The experiments were performed on 21 white Wistar rats weighing 210-250 g, divided into 3 groups. Animals in the first group (control) received a standard diet (energy value 2720 kcal/kg) and were exposed to an equally altered light and darkness periods. The rats of the second and third groups were under the constant round-the-clock light exposure and received HCCLD (4477 kcal/kg). In addition to the conditions in the second group, the test animals of the third group were administered EGCG daily through intragastric gavage in a dose of 40 mg/kg. An enzyme-linked immunosorbent assay kit for rat serum was used to assess insulin concentration. The concentration of serum glucose, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and triacylglycerols (TAG) was determined by enzymatic methods using photometric equipment. Insulin resistance was assessed by the HOMA-IR (Homeostatic Model Assessment) index. With the administration of EGCG, the concentration of glucose and insulin in the blood serum decreased by 34.7% and 59.1%, respectively, compared to group 2, and the HOMA-IR was 61.5% lower than in the comparison group. The HDL content increased with the administration of EGCG in the experiment and was 91.3% higher compared to the findings in the group 2. Under these circumstances, the concentrations of VLDL and TAG in the blood serum were significantly lower by 37.5 and 37.1% than the respective values in the group 2. It can be suggested that the administration of the bioflavonoid epigallocatechin-3-gallate significantly alleviates metabolic disorders in rats simultaneously exposed to RCL and kept on HCCLD.

Lipid Profile in Multiple Sclerosis: Functional Capacity and Therapeutic Potential of Its Regulation after Intervention with Epigallocatechin Gallate and Coconut Oil.

Multiple sclerosis (MS) patients present dyslipidemia and functional disability. Epigallocatechin gallate (EGCG) and coconut oil have been shown to be effective against dyslipidemia. To analyze the relationship between lipid profiles, fat consumption, and functional disability in patients with MS after administering EGCG and coconut oil. A four-month pilot study was conducted on 45 MS patients, divided into an intervention group (IG) and a control group (CG). The IG received 800 mg of EGCG and 60 mL of coconut oil. Lipid profiles were measured before and after the intervention, along with other data such as dietary habits, inflammatory markers, and functional capacity. Dyslipidemia did not correlate with the patients' fat consumption. After the intervention, triglycerides (TG) levels were lower in IG compared to CG. This decrease was positively correlated with an improvement in functional disability (determined by the Expanded Disability Status Scale (EDSS)) and negatively with high-density cholesterol (HDL) and apolipoprotein A1. Significant and positive correlations were observed between EDSS and C-reactive protein (CRP) in the IG. These changes in the IG could be related to body fat decrease, whose percentage shows a positive correlation with CRP and TG levels, and a negative correlation with HDL levels. Patients with MS present a certain type of dyslipemia not associated with their nutritional habits. The administration of EGCG and coconut oil seems to decrease blood TG levels, which could explain the functional improvements.

Combination of epigallocatechin 3 gallate and curcumin improves d-galactose and normal-aging associated memory impairment in mice

Previously, we observed curcumin improves aging-associated memory impairment in d-galactose (D-gal) and normal-aged (NA) mice. Evidence showed that multiple agents can be used in managing aging-induced memory dysfunction, drawn by the contribution of several pathways. Curcumin and Epigallocatechin 3 gallate (EGCG) combination substantially reduced the oxidative stress that commonly mediates aging. This study examined the combined effect of EGCG and curcumin on memory improvement in two recognized models, D-gal and normal-aged (NA) mice. The co-administration of EGCG and curcumin significantly (p < 0.05) increased retention time detected by passive avoidance (PA) and freezing response determined in contextual fear conditioning (CFC) compared to the discrete administration of EGCG or curcumin. Biochemical studies revealed that the combination of EGCG and curcumin remarkably ameliorated the levels (p < 0.05) of glutathione, superoxide dismutase, catalase, advanced oxidation protein products, nitric oxide, and lipid peroxidation compared to the monotherapy of EGCG or curcumin in mice hippocampi. The behavioral and biochemical studies revealed that the combination of EGCG and curcumin showed better improvement in rescuing aging-associated memory disorders in mice. EGCG and curcumin combination could serve as a better choice in managing aging-related memory disorders.

Protective effects of epigallocatechin gallate in the mice induced by chronic scrotal hyperthermia

One of the most common complications of chronic scrotal hyperthermia (SHT) is a serious disorder in the male reproductive system. The most important factor in the occurrence of these disorders is oxidative stress. Currently, we investigated the effects of epigallocatechin gallate (EGCG), as a highly potent antioxidant, against cells and tissue disorders in mice affected by chronic SHT. Fifty-six male adult NMRI mice were allocated into seven equal groups. Except the non-treated (Control) group, six other groups were exposed to heat stress. Two treated groups including Preventive and Curative received oral administration of EGCG (50 mg/kg/day) starting immediately before heat exposure and fifteen consecutive days after the end of the heat exposure, respectively. For each treated group, two subgroups including positive control (Pre/Cur + PC groups) and vehicle (Pre/Cur + vehicle groups) were considered. At the end of the study, sperm characteristics, testosterone levels, stereological parameters, apoptosis, oxidant state, and molecular assessments were performed. We found that the sperm parameters, testosterone levels, the numerical density of spermatogonia, primary spermatocytes, spermatids, sertoli, leydig cells, and seminiferous tubules, biochemical factors (except MDA), and expression of c-kit gene were significantly higher in the Preventive and Curative groups, especially in Preventive ones, compared to other groups (P < 0.05). This is while expression of HSP72 and NF-κβ genes, MDA levels, as well as density of apoptotic cells considerably decreased in both EGCG-treated groups compared to other groups and it was more pronounced in Preventive ones (P < 0.05). Generally, EGCG attenuated cellular and molecular disorders induced by heat stress in the testis and it was more pronounced in Preventive status.

Changes in hippocalcin expression in cortical neurons and glial cells by epigallocatechin gallate administration in an animal model of stroke

Changes in hippocalcin expression in cortical neurons and glial cells by epigallocatechin gallate administration in an animal model of stroke

P-631 Alleviating effects of EGCG on ovarian hyperstimulation syndrome and the potential modulating mechanism through the VEGF pathway

Abstract Study question What are the underlying mechanisms of EGCG to alleviate Ovary hyperstimulation syndrome (OHSS)? Summary answer EGCG inhibited VEGF via TGF-β1 classical-SMAD pathway and 67LR-mediated CREB pathway and could reduce the ovarian inflammatory effect and attenuated OHSS progress in rat model. What is known already Ovarian hyperstimulation syndrome (OHSS) is one of the most severe complications of COH during IVF treatment. The pathophysiology of OHSS is characterized by increased capillary permeability, VEGF is an important mediator in OHSS, and serum VEGF levels have been shown to correlate with OHSS severity. (-)-epigallocatechin-3-gallate (EGCG) is the most abundant and biologically active polyphenolic catechin in green tea and has been reported to have multiple effects in humans. Many research indicated that in many pathological processes, EGCG could inhibit VEGF and its receptor expression and have an angiogenesis effect. Herein, EGCG might have a therapeutic effect on OHSS. Study design, size, duration We investigated the role of EGCG in OHSS in vitro and in vivo. The primary human granulosa-lutein(hGL) cells and human granulosa-like tumor (KGN) cell line were cultured and treated with different concentrations of EGCG for 24 hours. Animal OHSS model was established in SD rats by injection of pregnant mare serum gonadotropin (PMSG), and randomly assigned to receive vehicle only or EGCG for 3 days. All experiments were performed 3-8 times for comparisons. Participants/materials, setting, methods The effect of EGCG on KGN and hGL cells was determined by MTT assay. The body weight of rats was measured every day, and the ovary size was measured after removal, the permeability was determined by Evans-blue. The serum estrogen and VEGF level in rats were detected by ELISA. RNA and protein expressions of VEGF, VEGFR-2, TGF-β, and TβR II were detected by qPCR and Western-blotting and immunostaining in vitro and in vivo experiments. Main results and the role of chance Our study demonstrated that administration of EGCG attenuated the development of OHSS in rats, as shown by histological examination and ovarian weight and morphology. The ovary weight was significantly decreased in the EGCG treatment group compared with the OHSS group (147.9 vs 206.5 mg). Additionally, compared to OHSS rats, EGCG treated rats exhibit downregulated ovarian VEGF expression determined by IHC and RT-qPCR. VEGF and E2 protein levels significantly decrease in the serum of the EGCG treatment group. EGCG exerted inhibitory effects on cell growth only in high dose (50uM) and longtime (48h) treatment in KGN and hGL cells. In KGN cells and hGL cells, EGCG significantly reduces the expression of VEGF and TGF-β at the RNA and protein levels. Furthermore, EGCG inhibits TGF-β1-induced VEGF production and secretion in KGN cells by suppressing TGF-β expression and its traditional Smad signaling pathway. EGCG also downregulates VEGF expression through the 67-kDa laminin receptor-mediated PKA-CREB pathway. Limitations, reasons for caution EGCG has been reported to employ a wide range of biological effects. Therefore, its suppressive effects on VEGF and TGF-β signaling pathway might be part of the pharmacological mechanisms to alleviate Ovary hyperstimulation syndrome. Further studies are also needed to explore the therapeutic mechanisms of melatonin from other perspectives. Wider implications of the findings Our findings add mechanistic insight in support of using EGCG as an adjuvant therapy in the management of OHSS. EGCG shows the potential to act as a novel alternative therapeutic drug to treat OHSS. Daily intake of green tea might be beneficial for women under COH to prevent OHSS. Trial registration number Not applicable

Suppression of the excitability of rat nociceptive secondary sensory neurons following local administration of the Phytochemical, (-)-Epigallocatechin-3-gallate

The phytochemical, polyphenolic compound, (-)-epigallocatechin-3-gallate (EGCG), is the main catechin found in green tea. Although a modulatory effect of EGCG on voltage-gated sodium and potassium channels has been reported in excitable tissues, the in vivo effect of EGCG on the excitability of nociceptive sensory neurons remains to be determined. Our aim was to investigate whether local administration of EGCG to rats attenuates the excitability of nociceptive spinal trigeminal nucleus caudalis (SpVc) neurons in response to mechanical stimulation in vivo. Extracellular single unit recordings were made from SpVc neurons in response to orofacial mechanical stimulation of anesthetized rats. The mean firing frequency of SpVc wide-dynamic range neurons following both non-noxious and noxious mechanical stimuli was significantly inhibited by EGCG in a dose-dependent and reversible manner. The mean magnitude of inhibition by EGCG on SpVc neuronal discharge frequency was similar to that of the local anesthetic, 1% lidocaine. Local injection of half-dose of lidocaine replaced the half-dose of EGCG. These results suggest that local injection of EGCG suppresses the excitability of nociceptive SpVc neurons, possibly via the inhibition of voltage-gated sodium channels and opening of voltage-gated potassium channels in the trigeminal ganglion. Therefore, administration of EGCG as a local anesthetic may provide relief from trigeminal nociceptive pain without side effects.

Epigallocatechin gallate effect on Interleukin-1 and MMP-9 expression as Pseudomonas aeruginosa keratitis adjuvant therapy

Link of Video Abstract: https://youtu.be/Ja9klXNlw5A Background: Keratitis Pseudomonas aeruginosa is the most frequently occurring eye infection. It is a rapidly developing condition that can lead to ocular infections (endophthalmitis) and corneal perforation resulting in vision loss. Although prompt administration of antibiotics can effectively kill the bacteria, the corneal damage caused by toxins persists. The following inflammatory process results in corneal thinning, fibrosis, and eventual perforation. Methods: This study is a literature review to support future experimental studies which will be conducted to examine the expression of IL-1b and MMP-9 on pseudomonas keratitis after administration of EGCG. Results: Interleukin-1ß is a proinflammatory cytokine secreted by various immune cells in response to acute and chronic inflammation. At the same time, matrix metalloproteinase (MMP) is a group of proteolytic enzymes involved in the pathophysiology of various ocular surface diseases. Epigallocatechin gallate (EGCG) is the major polyphenol compound in green tea, produced from the Camellia sinensis plant. Recent studies suggest that EGCG has anti-inflammatory and antioxidant effects on various cell types, including the cornea. EGCG inhibits IL-1β, which induces the activation of the NF-kB signaling pathway, which may explain the decrease in uPA expression and the reduction of collagen degradation by corneal fibroblasts. EGCG inhibits the activation of pro-MMP 9 produced by corneal fibroblasts in response to IL-1β stimulation, and this effect is mediated by the inhibition of uPA upregulation without a significant impact on pro-MMP 9 expressions. Conclusion: Epigallocatechin gallate (EGCG) in Camellia sinensis extract has the potential as an alternative adjuvant therapy for bacterial keratitis because it has antibacterial, anti-inflammatory and antioxidant effects.

Epigallocatechin-3-Gallate Alleviates Liver Oxidative Damage Caused by Iron Overload in Mice through Inhibiting Ferroptosis.

Ferroptosis, a form of regulated cell death, has been widely explored as a novel target for the treatment of diseases. The failure of the antioxidant system can induce ferroptosis. Epigallocatechin-3-Gallate (EGCG) is a natural antioxidant in tea; however, whether EGCG can regulate ferroptosis in the treatment of liver oxidative damage, as well as the exact molecular mechanism, is unknown. Here, we discovered that iron overload disturbed iron homeostasis in mice, leading to oxidative stress and damage in the liver by activating ferroptosis. However, EGCG supplementation alleviated the liver oxidative damage caused by iron overload by inhibiting ferroptosis. EGCG addition increased NRF2 and GPX4 expression and elevated antioxidant capacity in iron overload mice. EGCG administration attenuates iron metabolism disorders by upregulating FTH/L expression. Through these two mechanisms, EGCG can effectively inhibit iron overload-induced ferroptosis. Taken together, these findings suggest that EGCG is a potential ferroptosis suppressor, and may be a promising therapeutic agent for iron overload-induced liver disease.

Inhibition of macrophages inflammasome activation via autophagic degradation of HMGB1 by EGCG ameliorates HBV-induced liver injury and fibrosis.

Liver fibrosis is a reversible wound-healing response that can lead to end-stage liver diseases without effective treatment, in which HBV infection is a major cause. However, the underlying mechanisms for the development of HBV-induced fibrosis remains elusive, and efficacious therapies for this disease are still lacking. In present investigation, we investigated the effect and mechanism of green tea polyphenol epigallocatechin-3-gallate (EGCG) on HBV-induced liver injury and fibrosis. The effect of EGCG on liver fibrosis was examined in a recombinant cccDNA (rcccDNA) chronic HBV mouse model by immunohistochemical staining, Sirius red and Masson's trichrome staining. The functional relevance between high mobility group box 1 (HMGB1) and inflammasome activation and the role of EGCG in it were analyzed by Western blotting. The effect of EGCG on autophagic flux was determined by Western blotting and flow cytometric analysis. EGCG treatment efficiently was found to alleviate HBV-induced liver injury and fibrosis in a recombinant cccDNA (rcccDNA) chronic HBV mouse model, a proven suitable research platform for HBV-induced fibrosis. Mechanistically, EGCG was revealed to repress the activation of macrophage NLRP3 inflammasome, a critical trigger of HBV-induced liver fibrosis. Further study revealed that EGCG suppressed macrophage inflammasome through downregulating the level of extracellular HMGB1. Furthermore, our data demonstrated that EGCG treatment downregulated the levels of extracellular HMGB1 through activating autophagic degradation of cytoplasmic HMGB1 in hepatocytes. Accordingly, autophagy blockade was revealed to significantly reverse EGCG-mediated inhibition on extracellular HMGB1-activated macrophage inflammasome and thus suppress the therapeutic effect of EGCG on HBV-induced liver injury and fibrosis. EGCG ameliorates HBV-induced liver injury and fibrosis via autophagic degradation of cytoplasmic HMGB1 and the subsequent suppression of macrophage inflammasome activation. These data provided a new pathogenic mechanism for HBV-induced liver fibrosis involving the extracellular HMGB1-mediated macrophage inflammasome activation, and also suggested EGCG administration as a promising therapeutic strategy for this disease.