Evaluation of Gemcitabine and Epigallocatechin-3-Gallate Loaded Solid Lipid Nanoparticles on Benzopyrene Induced Lung Cancer Model Via Intranasal Route: Improved Pharmacokinetics and Safety Profile.

The objective of this study was to create a new treatment for lung cancer using solid lipid nanoparticles (SLNs) loaded with gemcitabine (GEM) and epigallocatechin-3-gallate (EGCG) that can be administered through the nose. We analyzed the formulation for its effectiveness in terms of micromeritics, drug release, and anti-cancer activity in the benzopyrene-induced Swiss albino mice lung cancer model. We also assessed the pharmacokinetics, biodistribution, biocompatibility, and hemocompatibility of GEM-EGCG SLNs. The GEM-EGCG SLNs had an average particle size of 93.54 ± 11.02 nm, a polydispersity index of 0.146 ± 0.05, and a zeta potential of -34.7 ± 0.4 mV. The entrapment efficiency of GEM and EGCG was 93.39 ± 4.2% and 89.49 ± 5.1%, respectively, with a sustained release profile for both drugs. GEM-EGCG SLNs had better pharmacokinetics than other treatments, and a high drug targeting index value of 17.605 for GEM and 2.118 for EGCG, indicating their effectiveness in targeting the lungs. Blank SLNs showed no pathological lesions in the liver, kidney, and nasal region validating the safety of SLNs. GEM-EGCG SLNs also showed fewer pathological lesions than other treatments and a lower hemolysis rate of 1.62 ± 0.10%. These results suggest that GEM-EGCG SLNs could effectively treat lung cancer.

Photodynamic effect of vascular-targeted polyphenol nanoparticles on Endothelial cells.

BACKGROUND: Port wine stains (PWS) are vascular malformations, and photodynamic therapy (PDT) is a promising treatment. Emerging drug delivery methods employ nanoparticles (NPs) to enhance drug permeability and retention in diseased blood vessels and improve drug bioavailability. (-) -epigallocatechin-3-gallate glycine (EGCG) has anti-angiogenetic effects and boosts photodynamic therapy. Chlorin e6 (Ce6) is capable of efficiently producing singlet oxygen, rendering it a very promising photosensitizer for utilization in nanomedicine. MATERIAL AND METHODS: EGCG-Ce6-NPs were synthesized and characterized using various techniques. The photodynamic effects of EGCG-Ce6-NPs on endothelial cells were evaluated. The compatibility and toxicity of the nanoparticle was tested using the CCK-8 assay. The intracellular uptake of the nanoparticle was observed using an inverted fluorescence microscope, and the intracellular fluorescence intensity was detected using flow cytometry. The ROS generation and apoptosis induced by EGCG-Ce6-NPs was observed using confocal laser scanning microscopy and flow cytometry respectively. RESULTS: EGCG-Ce6-NPs exhibited stability, spherical shape of uniform size while reducing the particle diameter, low polydisperse profile and retaining the ability to effectively generate singlet oxygen. These characteristics suggest promising potential for enhancing drug permeability and retention. Additionally, EGCG-Ce6-NPs demonstrated good compatibility with endothelial cells and enhanced intracellular uptake of Ce6. Furthermore, EGCG-Ce6-NPs increased activation efficiency, induced significant toxicity, more reactive oxygen species, and a higher rate of late apoptosis after laser irradiation. CONCLUSION: This in vitro study showed the potentials EGCG-Ce6-NPs for the destruction of endothelial cells in vasculature.

Simultaneous determination of five constituents of areca nut extract in rat plasma using UPLC-MS/MS and its application in a pharmacokinetic study.

Areca nuts have been used as a traditional Chinese medicine (TCM) for thousands of years. Recent studies have shown that it exhibits good pharmacological activity and toxicity. In this study, the pharmacokinetics of five major components of areca nut extract in rats were investigated using a highly sensitive ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-MS/MS) method. Arecoline, arecaidine, guvacoline, guvacine, and catechin were separated and quantified accurately using gradient elution with mobile phases of (A) water containing 0.1 % formic acid-10 mM ammonium formate, and (B) methanol. The constituents were detected under a timing switch between the positive and negative ion modes using multiple reaction monitoring (MRM). Each calibration curve had a high R2 value of >0.99. The method accuracies ranged -7.09-11.05 % and precision values were less than 14.36 %. The recovery, matrix effect, selectivity, stability, and carry-over of the method were in accordance with the relevant requirements. It was successfully applied for the investigation of the pharmacokinetics of these five constituents after oral administration of areca nut extract. Pharmacokinetic results indirectly indicated a metabolic relationship between the four areca nut alkaloids in rats. For further clarification of its pharmacodynamic basis, this study provided a theoretical reference.

Enhanced in vitro bioavailability of resveratrol-loaded emulsion stabilized by ß-lactoglobulin-catechin with excellent antioxidant activity.

The study aimed to fabricate ß-Lactoglobulin-catechin (ß-La-Ca) conjugates as a natural designed antioxidant emulsifier to improve the physicochemical stability of resveratrol emulsion delivery system. Fourier transform infrared (FT-IR) and fluorescence spectroscopy analysis confirmed the formation of conjugates using free radical grafting. The antioxidant ability of emulsion was evaluated by DPPH scavenging activities and ORAC experiments. The emulsion stabilized by ß-La-Ca conjugates exhibited strong antioxidant activity with ORAC value of 2541.39 ± 29.58 µmol TE/g, which was significantly higher than that by ß-Lactoglobulin alone with 387.96 ± 23.45 µmol TE/g or their mixture with 948.23 ± 32.77 µmol TE/g. During the whole simulated gastrointestinal digestion, emulsion stabilized by ß-La-Ca conjugates exhibited excellent oxidative stability that the lipid was mainly digested in the small intestine. This behavior attributed to the greater stability of resveratrol to chemical transformation leading to a higher overall bioavailability in vivo. These results suggested that the ß-La-Ca conjugates could be used to fabricate the emulsion-based delivery system to improve the oxidative stability and bioavailability of chemically labile hydrophobic bioactive compounds.

The intestinal-level metabolic benefits of green tea catechins: Mechanistic insights from pre-clinical and clinical studies.

BACKGROUND: The intestinal-level host-microbiota interaction has been implicated in the pathogenesis of chronic diseases. The current review is intended to provide a comprehensive insight into deciphering whether intestinal-level bioactivities mediate the overall metabolic health benefits of green tea catechins. PURPOSE: We have comprehensively discussed pre-clinical and clinical evidences of intestinal-level changes in metabolism, microbiota, and metabolome due to catechin-rich green tea treatments, ultimately limiting metabolic diseases. Exclusive emphasis has been given to purified catechins and green tea, and discussions on extraintestinal mechanisms of metabolic health benefits were avoided. METHODS: A literature search for relevant pre-clinical and clinical studies was performed in various online databases (e.g., PubMed) using specific keywords (e.g., catechin, intestine, microbiota). Out of all the referred literature, ∼15% belonged to 2021-2023, ∼51% were from 2011-2020, and ∼32% from 2000-2010. RESULT: The metabolic health benefits of green tea catechins are indeed influenced by the intestinal-level bioactivities, including reduction of mucosal inflammation and oxidative stress, attenuation of gut barrier dysfunction, decrease in intestinal lipid absorption and metabolism, favorable modulation of mucosal nuclear receptor signaling, alterations of the luminal global metabolome, and mitigation of the gut dysbiosis. The results from the recent clinical studies support the pre-clinical evidences. The challenges and pitfalls of the currently available knowledge on catechin bioactivities have been discussed, and constructive directions to harness the translational benefits of green tea through future interventions have been provided. CONCLUSION: The metabolism, metabolome, and microbiota at the intestinal epithelia play critical roles in catechin metabolism, pharmacokinetics, bioavailability, and bioactivities. Especially the reciprocal interaction between the catechins and the gut microbiota dictates the metabolic benefits of catechins.

Exposure of Fexofenadine, but Not Pseudoephedrine, Is Markedly Decreased by Green Tea Extract in Healthy Volunteers.

Green tea (GT) alters the disposition of a number of drugs, such as nadolol and lisinopril. However, it is unknown whether GT affects disposition of hydrophilic anti-allergic drugs. The purpose of this study was to investigate whether pharmacokinetics of fexofenadine and pseudoephedrine are affected by catechins, major GT components. A randomized, open, 2-phase crossover study was conducted in 10 healthy Japanese volunteers. After overnight fasting, subjects were simultaneously administered fexofenadine (60 mg) and pseudoephedrine (120 mg) with an aqueous solution of green tea extract (GTE) containing (-)-epigallocatechin gallate (EGCG) of ~ 300 mg or water (control). In vitro transport assays were performed using HEK293 cells stably expressing organic anion transporting polypeptide (OATP)1A2 to evaluate the inhibitory effect of EGCG on OATP1A2-mediated fexofenadine transport. In the GTE phase, the area under the plasma concentration-time curve and the amount excreted unchanged into urine for 24 hours of fexofenadine were significantly decreased by 70% (P < 0.001) and 67% (P < 0.001), respectively, compared with control. There were no differences in time to maximum plasma concentration and the elimination half-life of fexofenadine between phases. Fexofenadine was confirmed to be a substrate of OATP1A2, and EGCG (100 and 1,000 µM) and GTE (0.1 and 1 mg/mL) inhibited OATP1A2-mediated uptake of fexofenadine. On the contrary, the concomitant administration of GTE did not influence the pharmacokinetics of pseudoephedrine. These results suggest that intake of GT may result in a markedly reduced exposure of fexofenadine, but not of pseudoephedrine, putatively by inhibiting OATP1A2-mediated intestinal absorption.

Ergogenic Effects of Green Tea Combined with Isolated Soy Protein on Increasing Muscle Mass and Exercise Performance in Resistance-Trained Mice.

It is well known that supplementation with high protein after exercise can effectively promote muscle synthesis and repair, while green tea is rich in catechins that have antioxidant effects. We aimed to explore the effects of green tea combined with isolated soy protein on increase muscle mass in resistance-trained mice. A total of 32 male ICR mice (8-weeks old) were divided into four groups (n = 8/group), sedentary control group (SC), isolated soy protein with green tea group (ISPG), resistance training group (RT), isolated soy protein and green tea combine with resistance training group (ISPG + RT). All mice received control or ISPG by oral gavage for four consecutive weeks. Forelimb grip and exhaustive swimming time were used for exercise performance evaluation. In biochemical profile, we analyzed lactate, ammonia, blood urea nitrogen (BUN), and glucose and muscle damage index creatine kinase (CK) after exercise as biochemical parameters of exercise fatigue. The grip strength, muscular endurance, and exhaustive swimming time of the ISPG + RT group were significantly increased than other groups (p < 0.05), and also significantly decreased in serum lactate and ammonia levels (p < 0.05, respectively). The ISP + RT group was not only increased in quadriceps weight, (p < 0.05) but also decreased EFP (p < 0.05). We recommend using a 4-week supplementation with ISPG, combined with RT, to increase muscle mass, exercise performance, glycogen storage, and reduce fatigue biochemical parameters after exercise. The benefits of long-term supplementation or application to human supplementation can be further explored in the future.

Simultaneous determination of selected catechins and pyrogallol in deer intoxications by HPLC-MS/MS.

A selective and sensitive analytical method for the determination of selected catechins (catechin, epicatechin, gallocatechin, epigallocatechin) and pyrogallol in biological matrices by HPLC-MS/MS was developed. The utilized sample preparation technique was a two-stage liquid-liquid extraction using ethyl acetate. The HPLC-system was equipped with a Phenomenex Luna Pentafluorophenyl Column (150 × 2 mm, 5 µm) and operated with an acetonitrile-water gradient as a mobile phase system. Detection was performed with a 3200 Q Trap mass spectrometer. For analysis the mass spectrometer was used in the MRM-mode with negative ionization. The method validation was performed with serum as matrix. The selectivity of the method as well as the linearity of calibration was successfully proven for all analytes. The limits of quantification were between 5.3 and 11.2 ng/mL and the recovery rates were above 50 % for all analytes. Results from the samples of three deer poisoning cases demonstrated that the developed HPLC-MS/MS method is applicable to real biological samples.

Study on mechanism of low bioavailability of black tea theaflavins by using Caco-2 cell monolayer.

This study aimed to clarify the bioavailability mechanism of theaflavins by using the Caco-2 monolayer in vitro model. Prior to the transport of theaflavin (TF), theaflavin-3-gallate (TF3G), theaflavin-3'-gallate (TF3'G), and theaflavin-3, 3'-digallate (TFDG), we found the cytotoxicity of theaflavins was in the order of TF3'G > TFDG > TF3G > TF, suggesting the galloyl moiety enhances the cytotoxicity of theaflavins. Meantime, the galloyl moiety made theaflavins unstable, with the stability in the order of TF > TFDG > TF3G/TF3'G. Four theaflavins showed poor bioavailability with the Papp values ranging from 0.44 × 10-7 to 3.64 × 10-7 cm/s in the absorptive transport. All the theaflavins showed an efflux ratio of over 1.24. And it is further confirmed that P-glycoprotein (P-gp), multidrug resistance associated proteins (MRPs) and breast cancer resistance protein (BCRP) were all shown to contribute to the efflux transport of four theaflavins, with P-gp playing the most important role, followed by MRPs and BCRP. Moreover, theaflavins increased the expression of P-gp, MRP1, MPR3, and BCRP while decreased the expression of MRP2 at the transcription and translation levels. Additionally, the gallated theaflavins were degraded into simple theaflavins and gallic acids when transported through Caco-2 monolayers. Overall, the structural instability, efflux transporters, and cell metabolism were all responsible for the low bioavailability of four theaflavins in Caco-2 monolayers.

Effect of catechin and commercial preparation of green tea essence on the pharmacokinetics of l-dopa in rabbits.

The aim of this study was to investigate drug interactions of L-dopa/carbidopa with catechin and green tea essence in rabbits following the simultaneous administration via an intramuscular injection of catechin or via an intragastric route for green tea essence with L-dopa/carbidopa. The results indicated that catechin at doses of 10, 20 and 50 mg/kg increased the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-t ) of L-dopa by about 69, 78 and 42%, respectively. The metabolic ratios of the AUC0-t for 3-O-methyldopa (3-OMD)/L-dopa significantly decreased by about 56, 68 and 76% (P < 0.05), respectively. In addition, a single dose of 5/1.25 mg/kg L-dopa/carbidopa was co-administrated with 150 mg/kg green tea essence via an intragastric route with an oral-gastric tube. Comparing the related pharmacokinetic parameters of L-dopa, the clearance and metabolic ratio of L-dopa decreased by 20 and 19% (P < 0.05), respectively. In conclusion, catechin and green tea essence can significantly affect the metabolism of L-dopa by the catechol-O-methyltransferase (COMT) metabolic pathway. Catechin can enhance L-dopa bioavailability, and both catechin and green tea essence decreased 3-OMD formation. Therefore, catechin and green tea essence may increase L-dopa efficacy for Parkinson's disease treatment.

Reinforcing the Combinational Immuno-Oncotherapy of Switching "Cold" Tumor to "Hot" by Responsive Penetrating Nanogels.

Although immuno-oncotherapy in clinic has gained great success, the immunosuppressive tumor microenvironment (TME) existing in the "cold" tumor with insufficient and exhausted lymphocytes may result in a lower-than-expected therapeutic efficiency. Therefore, a properly designed synergistic strategy that can effectively turn the "cold" tumor to "hot" should be considered to improve the therapeutic effects of immuno-oncotherapy. Herein, TME-responsive penetrating nanogels (NGs) were developed, which can improve the delivery and penetration of the co-loaded resiquimod (R848) and green tea catechin (EGCG) in tumors by a nano-sized controlled releasing system of the soluble cyclodextrin-drug inclusion complex. Consequently, the NGs effectively promoted the maturation of dendritic cells, stimulated the cytotoxic T lymphocytes (CTLs), and decreased the PD-L1 expression in tumors. The combination of NGs with the OX40 agonist (αOX40) further synergistically enhanced the activation and infiltration of CTLs into the deep tumor and inhibited the suppression effects from the regulatory T cells (Tregs). As a result, an increased ratio of active CTLs to Tregs in tumors (20.66-fold) was achieved with a 91.56% tumor suppression effect, indicating a successful switch of "cold" tumors to "hot" for an immunologically beneficial TME with significantly improved anti-tumor immune therapeutics. This strategy could be tailored to other immuno-oncotherapeutic approaches to solve the urgent efficiency concerns of the checkpoint-based treatment in clinic.

Epicatechin gallate and epigallocatechin gallate are potent inhibitors of human arylacetamide deacetylase.

Recently, in addition to carboxylesterases (CESs), we found that arylacetamide deacetylase (AADAC) plays an important role in the metabolism of some clinical drugs. In this study, we screened for food-related natural compounds that could specifically inhibit human AADAC, CES1, or CES2. AADAC, CES1, and CES2 activities in human liver microsomes were measured using phenacetin, fenofibrate, and procaine as specific substrates, respectively. In total, 43 natural compounds were screened for their inhibitory effects on each of these enzymes. Curcumin and quercetin showed strong inhibitory effects against all three enzymes, whereas epicatechin, epicatechin gallate (ECg), and epigallocatechin gallate (EGCg) specifically inhibited AADAC. In particular, ECg and EGCg showed strong inhibitory effects on AADAC (IC50 values: 3.0 ± 0.5 and 2.2 ± 0.2 µM, respectively). ECg and EGCg also strongly inhibited AADAC-mediated rifampicin hydrolase activity in human liver microsomes with IC50 values of 2.2 ± 1.4 and 1.7 ± 0.4 µM, respectively, whereas it weakly inhibited p-nitrophenyl acetate hydrolase activity, which is catalyzed by AADAC, CES1, and CES2. Our results indicate that ECg and EGCg are potent inhibitors of AADAC.

Associations between caseinophosphopeptides and theaflavin-3,3'-digallate and their impact on cellular antioxidant activity.

Caseinophosphopeptides (CPPs) are a group of bioactive polypeptides hydrolyzed from caseins. Theaflavin-3,3'-digallate (TF-3) is a characteristic biofunctional polyphenol in black tea. In the present study, the interactions between CPPs and TF-3 were systematically investigated with fluorescence quenching, quartz crystal microbalance with dissipation monitoring (QCM-D), circular dichroism (CD), and small-angle X-ray scattering (SAXS). Both fluorescence quenching and QCM-D studies demonstrated that TF-3 interacted with CPPs primarily through hydrogen bonding. Other forces were also involved. The addition of TF-3 did not change the secondary structures and the radius of gyration of CPPs, but it induced the aggregation of CPPs. The size of the aggregates increased with the concentration of TF-3. The impact of the association between TF-3 and CPPs on the antioxidant activity of TF-3 was studied by the cellular antioxidant activity (CAA) assay, which revealed that the cellular antioxidant activity of TF-3 was enhanced after binding to CPPs.

Sustained release of epigallocatechin-3-gallate from chitosan-based scaffolds to promote osteogenesis of mesenchymal stem cell.

Epigallocatechin-3-gallate (EGCG) is a kind of flavonoids and has the ability to promote differentiation of mesenchymal stem cells (MSCs) into osteoblasts. However, the EGCG is easily metabolized by cells during cell culture, which reduces its bioavailability. Therefore, in this paper, EGCG-loaded chitosan nanoparticles (ECN) were fabricated and entrapped into chitosan/alginate (CS/Alg) scaffolds to form CS/Alg-ECN scaffolds for improving the bioavailability of EGCG. The human umbilical cord mesenchymal stem cells (HUMSCs) were cultured on CS/Alg-ECN scaffolds to induce osteogenic differentiation. The results indicated that the CS/Alg-ECN scaffolds continuously released EGCG for up to 16 days. Besides, these results suggested that CS/Alg-ECN scaffolds promoted osteoblast differentiation through activating Wnt/ß-catenin signaling pathway. Collectively, this study demonstrated that the entrapment ECN into CS/Alg scaffolds was a promising strategy for promoting osteogenesis of MSCs.

Impact of Green Tea Catechin Ingestion on the Pharmacokinetics of Lisinopril in Healthy Volunteers.

Lisinopril, a highly hydrophilic long-acting angiotensin-converting enzyme inhibitor, is frequently prescribed for the treatment of hypertension and congestive heart failure. Green tea consumption may reduce the risk of cardiovascular outcomes and total mortality, whereas green tea or its catechin components has been reported to decrease plasma concentrations of a hydrophilic ß blocker, nadolol, in humans. The aim of this study was to evaluate possible effects of green tea extract (GTE) on the lisinopril pharmacokinetics. In an open-label, randomized, single-center, 2-phase crossover study, 10 healthy subjects ingested 200 mL of an aqueous solution of GTE containing ~ 300 mg of (-)-epigallocatechin gallate, a major catechin component in green tea, or water (control) when receiving 10 mg of lisinopril after overnight fasting. The geometric mean ratio (GTE/control) for maximum plasma concentration and the area under the plasma concentration-time curve of lisinopril were 0.289 (90% confidence interval (CI) 0.226-0.352) and 0.337 (90% CI 0.269-0.405), respectively. In contrast, there were no significant differences in time to reach maximum lisinopril concentration (6 hours in both phases) and renal clearance of lisinopril (57.7 mL/minute in control vs. 56.9 mL/minute in GTE). These results suggest that the extent of intestinal absorption of lisinopril was significantly impaired in the presence of GTE, whereas it had no major effect on the absorption rate and renal excretion of lisinopril. Concomitant use of lisinopril and green tea may decrease oral exposure to lisinopril, and therefore result in reduced therapeutic efficacy.

Non-ionic surfactant vesicles as a carrier system for dermal delivery of (+)-Catechin and their antioxidant effects.

Numerous skin disorders and diseases are related to oxidative stress. The application of an antioxidant, serving as a strong defense agent against oxidation, is of great interest in dermatology yet remains challenging for delivery. This paper aimed to develop a niosome carrier system to deliver the antioxidant (+) Catechin into the skin. (+) Catechin-loaded niosomes were prepared using film hydration technique and the physicochemical properties of drug-loaded niosomes were characterised and investigated by a series of in vitro and ex vivo studies. The optimised formulation displayed an acceptable size in nanoscale (204 nm), high drug entrapment efficiency (49%) and amorphous state of drug in niosomes. It was found that (+) Catechin-loaded niosomes could effectively prolong the drug release. Drug deposition in the viable layers of human skin was significantly enhanced when niosomal carriers were applied (p < 0.05). Compared to the pure drug, the niosomal formulation had a greater protective effect on the human skin fibroblasts (Fbs). This is consistent with the observation of internalisation of niosomes by Fbs which was concentration-, time- and temperature-dependent, via an energy-dependent process of endocytosis. The research highlighted that niosomes are potential topical carriers for dermal delivery of antioxidants in skin-care and pharmaceutical products.

Effects of (-)-epicatechin on mitochondria.

Mitochondrial dysfunction is observed in a broad range of human diseases, including rare genetic disorders and complex acquired pathologies. For this reason, there is increasing interest in identifying safe and effective strategies to mitigate mitochondrial impairments. Natural compounds are widely used for multiple indications, and their broad healing properties suggest that several may improve mitochondrial function. This review focuses on (-)-epicatechin, a monomeric flavanol, and its effects on mitochondria. The review summarizes the available data on the effects of acute and chronic (-)-epicatechin supplementation on mitochondrial function, outlines the potential mechanisms involved in mitochondrial biogenesis induced by (-)-epicatechin supplementation and discusses some future therapeutic applications.

Tissue distribution and molecular docking research on the active components of Bidens bipinnata L. against hyperlipidemia.

Bidens bipinnata L. is a folk medicinal plant in China that shows significant antihyperlipidemia effectiveness. However, studies of the underlying mechanism study are lacking. In order to explore the potential action sites and the underlying mechanism of treating hyperlipidemic, this work undertook tissue distribution and molecular docking research on the markers of B. bipinnata L., which were obtained through serum pharmacochemistry and network database retrieval. The results showed that seven compounds (gallic acid, protocatechuic acid, rutin, hyperoside, bipinnate polyacetylenicloside, luteolin and quercetin) were screened out as markers. Owing to the diversity of chemical structures, they exhibited an inconsistent trend in tissue distribution. However, all of them had high levels in the liver and no specific distribution in other tissues. More interestingly, seven proteins-HMGCR (1HWK), NR3C1 (4P6W), CYP1A2 (2HI4), RXRA (4PP3), CES1 (1MX1), HSD11B1 (2RBE) and CYP1A1 (4I8V)-showed significant binding affinity with three or more markers, suggesting that they may be the target proteins of B. bipinnata L. This study preliminarily sheds light on the tissue distribution and targets of B. bipinnata L., providing some useful information on the underlying mechanisms of the antihyperlipidemia effect.

Black Tea Theaflavin Detoxifies Metabolic Toxins in the Intestinal Tract of Mice.

SCOPE: This study is to determine the in vivo efficacy of black tea theaflavin (TF) to detoxify two metabolic toxins, ammonia and methylglyoxal (MGO), in mice METHODS AND RESULTS: Under in vitro conditions, TF is able to react with ammonia, MGO, and hydrogen peroxide to produce its aminated, MGO conjugated, and oxidized products, respectively. In TF-treated mice, the aminated TF, the MGO conjugates of TF and aminated TF, and the oxidized TF are searched using LC-MS/MS. The results provide the first in vivo evidence that the unabsorbed TF is able to trap ammonia to form the aminated TF; furthermore, both TF and the aminated TF have the capacity to trap MGO to generate the corresponding mono-MGO conjugates. Moreover, TF is oxidized to dehydrotheaflavin, which underwent further amination in the gut. By exposing TF to germ-free (GF) mice and conventionalized mice (GF mice colonized with specific-pathogen-free microbiota), the gut microbiota is demonstrated to facilitate the amination and MGO conjugation of TF. CONCLUSION: TF has the capacity to remove the endogenous metabolic toxins through oxidation, amination, and MGO conjugation in the intestinal tract, which can potentially explain why TF still generates in vivo efficacy while showing a poor systematic bioavailability.

The pharmacological activity of epigallocatechin-3-gallate (EGCG) on Alzheimer's disease animal model: A systematic review.

BACKGROUND: Alzheimer's disease (AD) is currently incurable and there is an urgent need to develop new AD drugs. Many studies have revealed the potential neuroprotective effect of Epigallocatechin-3-O-gallate (EGCG), the main antioxidant in green tea, on animal models of AD. However, a systematic review of these reports is lacking. PURPOSE: To assess the effectiveness of EGCG for AD treatment using systematic review and meta-analysis of pre-clinical trials. METHODS: We conducted a systematic search of all available randomized controlled trials (RCTs) performed up to November 2019 in the following electronic databases: ScienceDirect, Web of Science, and PubMed. 17 preclinical studies assessing the effect of EGCG on animal AD models have been identified. Meta-analysis and subgroup analysis was performed to evaluate cognition improvement of various types of AD models. The study quality was assessed using the CAMARADES checklist and the criteria of published studies. RESULTS: Our analysis shows that the methodological quality ranges from 3 to 5, with a median score of 4. According to meta-analysis of random-effects method, EGCG showed a positive effect in AD with shorter escape latency (SMD= -9.24, 95%CI= -12.05 to -6.42) and decreased Aß42 level (SD= -25.74,95%CI= -42.36 to -9.11). Regulation of α-, ß-, γ-secretase activity, inhibition of tau phosphorylation, anti-oxidation, anti-inflammation, anti-apoptosis, and inhibition of AchE activity are reported as the main neuroprotective mechanisms. Though more than 100 clinical trials have been registered on the ClinicalTrials.gov, only one clinical trial has been conducted to test the therapeutic effects of EGCG on the AD progression and cognitive performance. CONCLUSION: Here, we conducted this review to systematically describe the therapeutic potential of EGCG in animal models of AD and hope to provide a more comprehensive assessment of the effects in order to design future clinical trials. Besides, the safety, blood-brain barrier (BBB) penetration and bioavailability issues in conducting clinical trials were also discussed.