ABSTRACT
Tea drinking impacts aging and aging-related diseases. However, knowledge of anti-aging molecules other than the major catechins in complex tea extracts remains limited. Here we used Caenorhabditis elegans to analyze the longevity effects of tea extracts and constituents comprehensively. We found that the hot water extract of green tea prolonged lifespan and heathspan. Further, the MeOH fraction prolonged lifespan significantly longer than other fractions. Correlation analysis between mass spectroscopic data and anti-aging activity suggests that ester-type catechins (ETCs) are the major anti-aging components, including 4 common ETCs, 6 phenylpropanoid-substituted ester-type catechins (PSECs), 5 cinnamoylated catechins (CCs), 7 ester-type flavoalkaloids (ETFs), and 4 cinnamoylated flavoalkaloids (CFs). CFs (200 µM) are the strongest anti-aging ETCs (with the longest 73% lifespan extension). Green tea hot water extracts and ETCs improved healthspan by enhancing stress resistance and reducing ROS accumulation. The mechanistic study suggests that they work by multiple pathways. Moreover, ETCs modulated gut microbial homeostasis, increased the content of short-chain fatty acids, and reduced fat content. Altogether, our study provides new evidence for the anti-aging benefits of green tea and insights into a deep understanding of the chemical truth and multi-target mechanism.
ABSTRACT
Chemotherapy, the most common class of anticancer drugs, is considerably limited owing to its adverse side effects. In this study, we aimed to evaluate the protective effect and mechanism of action of large-leaf yellow tea polysaccharides (ULYTP-1, 1.29 × 104 Da) against chemotherapeutic 5-fluorouracil (5-Fu). Structural characterisation revealed that ULYTP-1 was a ß-galactopyranouronic acid. Furthermore, ULYTP-1 promoted autolysosome formation, activating autophagy and reducing the oxidative stress and inflammation caused by 5-Fu. Our in vivo study of 4 T1 tumour-bearing mice revealed that ULYTP-1 also attenuated 5-Fu toxicity through modulation of the gut microbiota. Moreover, ULYTP-1 effectively protected immune organs and the liver from 5-Fu toxicity, while promoting its tumour-inhibitory properties. The current findings provide a new strategy for optimising chemotherapy regimens in the clinic.
Subject(s)
Fluorouracil , Polysaccharides , Animals , Mice , Cell Line, Tumor , Fluorouracil/therapeutic use , Polysaccharides/pharmacology , Polysaccharides/therapeutic use , Autophagy , TeaABSTRACT
Novel N-ethy-2-pyrrolidinone-substituted flavonols, myricetin alkaloids A-C (1-3), quercetin alkaloids A-C (4a, 4b, and 5), and kaempferol alkaloids A and B (6 and 7), were prepared from thermal reaction products of myricetin, quercetin, kaempferolâl-theanine, respectively. We used HPLC-ESI-HRMS/MS to detect 1-7 in 14 cultivars of green tea and found that they were all present in "Shuchazao," "Longjing 43", "Fudingdabai", and "Zhongcha 108" green teas. The structures of 1-4 and 6 were determined by extensive 1D and 2D NMR spectroscopies. These flavonol alkaloids along with their skeletal flavonols were assessed for anti-Alzheimer's disease effect based on molecular docking, acetylcholinesterase inhibition, and the transgenic Caenorhabditis elegans CL4176 model. Compound 7 strongly binds to the protein amyloid ß (Aß1-42) through hydrogen bonds (BE: -9.5 kcal/mol, Ki: 114.3 nM). Compound 3 (100 µM) is the strongest one in significantly extending the mean lifespan (13.4 ± 0.5 d, 43.0% promotion), delaying the Aß1-42-induced paralysis (PT50: 40.7 ± 1.9 h, 17.1% promotion), enhancing the locomotion (140.0% promotion at 48 h), and alleviating glutamic acid (Glu)-induced neurotoxicity (153.5% promotion at 48 h) of CL4176 worms (p < 0.0001).
Subject(s)
Alkaloids , Alzheimer Disease , Animals , Tea/chemistry , Amyloid beta-Peptides/genetics , Amyloid beta-Peptides/pharmacology , Caenorhabditis elegans/genetics , Quercetin/pharmacology , Acetylcholinesterase , Molecular Docking Simulation , Alkaloids/pharmacology , Alkaloids/chemistry , Alzheimer Disease/drug therapy , Alzheimer Disease/genetics , Flavonols/pharmacologyABSTRACT
Three new cyclic peptides, meristosporins A, B, and C (1-3), one of which features an unusual amino acid, were isolated from the opportunistic pathogen Basidiobolus meristosporus and identified by 1D, 2D NMR, MS/MS, and Marfey's analysis. The biosynthetic pathway of the hexapeptide meristosporin A (1) was deduced based on nonribosomal peptide synthetase gene clusters analysis. Compounds 1 and 2 showed cytotoxicity to RAW264.7 and 293T cells, respectively. These compounds may be involved in the fungal injury caused to human cells.
Subject(s)
Peptides, Cyclic , Tandem Mass Spectrometry , Humans , Peptides, Cyclic/chemistry , Amino Acids , Magnetic Resonance Spectroscopy , Molecular StructureABSTRACT
Epigallocatechin-3-O-(4-O-methyl)gallate (EGCG4â³Me) in Camellia sinensis possesses numerous beneficial biological activities. However, the germplasm rich in EGCG4â³Me and the O-methyltransferase responsible for EGCG4â³Me biosynthesis are poorly understood. Herein, the content of EGCG3â³Me and EGCG4â³Me in the shoots of 13 cultivars was analyzed to demonstrate that EGCG4â³Me is characteristically accumulated in the "GZMe4" cultivar but not in the other 12 cultivars. A novel O-methyltransferase (CsOMTL1) was identified from "GZMe4" using RNA-Seq and correlation analysis. Using the recombinant enzyme, EGCG4â³Me was synthesized in vitro. Overexpression of CsOMTL1 via Agrobacterium-mediated genetic transformation caused constitutive accumulation of EGCG4â³Me in C. sinensis callus. Moreover, the transcription factor CsMADSL1 localized in the nucleus activated the transcription of CsOMTL1 and specifically interacted with its promoter. Hence, our study identified a novel O-methyltransferase that characteristically catalyzes the synthesis of EGCG4â³Me and a positive regulator of EGCG4â³Me synthesis in "GZMe4", which might provide a strategy for the breeding of a tea cultivar rich in EGCG4â³Me.
Subject(s)
Camellia sinensis , Catechin , Camellia sinensis/metabolism , Methyltransferases/genetics , Methyltransferases/metabolism , Plant Breeding , Promoter Regions, Genetic , Transcription Factors/geneticsABSTRACT
Basidiobolus meristosporus is an opportunistic pathogen of mammals with unique habitats, but its metabolites have not been extensively studied. Through semi-preparative HPLC, nine undescribed cyclic pentapeptides were isolated from mycelia of B. meristosporus RCEF4516. The structure of the compounds 1-9 were identified with MS/MS and NMR data and designated as basidiosin D-L respectively. The absolute configurations were determined according to the advanced Marfey's method after compound hydrolysis. Bioactivity testing showed that compounds 1, 2, 3, 4 and 8 decreased NO production in LPS-activated RAW264.7 cells in a concentration-dependent manner. The nine compounds showed cytotoxicity against RAW264.7, 293 T and HepG2 cells. All the compounds except compound 7 showed stronger inhibitory effects on α-glucosidase than acarbose.
Subject(s)
Antineoplastic Agents , alpha-Glucosidases , Animals , Tandem Mass Spectrometry , Acarbose , Anti-Inflammatory Agents/pharmacology , MammalsABSTRACT
Methylation is a common structural modification of catechins in tea, which can improve the bioavailability of catechins. Flavoalkaloids are catechin derivatives with a nitrogen containing five-membered ring at the C-6 or C-8 position. Here we isolated three new methylated flavoalkaloids from Echa 1 green tea (Camellia sinensis cv. Echa 1) and synthesized another four new methylated flavoalkaloids. The structures of the new ester-type methylated catechins (etmc)-pyrrolidinone A-G (1-7) were elucidated by various spectroscopic techniques, including nuclear magnetic resonance (NMR), optical rotation, infrared, UV-vis, experimental and calculated circular dichroism (CD) spectra, and high-resolution mass. Among them, 6 and 7 showed the strongest α-glucosidase inhibitory activity and significantly lowered lipid content of Caenorhabditis elegans with 73.50 and 67.39% inhibition rate, respectively. Meanwhile, 6 and 7 also exhibited strong antioxidant activity in vitro and stress resistance to heat, oxidative stress, and UV irradiation in nematodes.
Subject(s)
Camellia sinensis , Catechin , Animals , Tea/chemistry , Caenorhabditis elegans , Camellia sinensis/chemistry , AntioxidantsABSTRACT
Cordyceps militaris (C. militaris) has been approved and widely used in healthy food. The present study aimed to improve the flavor of summer Keemun black tea (KBT) using C. militaris solid-state fermentation. Combined with sensory evaluation, the volatile and non-volatile components of solid-state fermentation of KBT (SSF-KBT) and KBT were analyzed. The results showed that after the solid-state fermentation, the contents of total polyphenol, total flavonoid, and total free amino acids were significantly reduced. Further non-targeted metabolomics analysis revealed that the contents of non-galloylated catechins and d-mannitol increased, while the galloylated catechins and flavonoid glycosides decreased as did the bitterness and astringency of KBT. Dihydro-ß-ionone and ß-ionone (OAV = 59321.97 and 8154.17) were the aroma-active compounds imparting woody and floral odors in SSF-KBT, respectively. Current study provides a new avenue to develop summer-autumn KBT.
Subject(s)
Camellia sinensis , Catechin , Cordyceps , Tea/chemistry , Fermentation , Camellia sinensis/chemistry , Flavonoids , Catechin/analysis , MetabolomicsABSTRACT
SARS-CoV-2 Mpro (Mpro) is the critical cysteine protease in coronavirus viral replication. Tea polyphenols are effective Mpro inhibitors. Therefore, we aim to isolate and synthesize more novel tea polyphenols from Zhenghedabai (ZHDB) white tea methanol-water (MW) extracts that might inhibit COVID-19. Through molecular networking, 33 compounds were identified and divided into 5 clusters. Further, natural products molecular network (MN) analysis showed that MN1 has new phenylpropanoid-substituted ester-catechin (PSEC), and MN5 has the important basic compound type hydroxycinnamoylcatechins (HCCs). Thus, a new PSEC (1, PSEC636) was isolated, which can be further detected in 14 green tea samples. A series of HCCs were synthesized (2-6), including three new acetylated HCCs (3-5). Then we used surface plasmon resonance (SPR) to analyze the equilibrium dissociation constants (KD) for the interaction of 12 catechins and Mpro. The KD values of PSEC636 (1), EGC-C (2), and EC-CDA (3) were 2.25, 2.81, and 2.44 µM, respectively. Moreover, compounds 1, 2, and 3 showed the potential Mpro inhibition with IC50 5.95 ± 0.17, 9.09 ± 0.22, and 23.10 ± 0.69 µM, respectively. Further, we used induced fit docking (IFD), binding pose metadynamics (BPMD), and molecular dynamics (MD) to explore the stable binding pose of Mpro-1, showing that 1 could tightly bond with the amino acid residues THR26, HIS41, CYS44, TYR54, GLU166, and ASP187. The computer modeling studies reveal that the ester, acetyl, and pyrogallol groups could improve inhibitory activity. Our research suggests that these catechins are effective Mpro inhibitors, and might be developed as therapeutics against COVID-19.
Subject(s)
COVID-19 Drug Treatment , Catechin , Humans , SARS-CoV-2 , Catechin/pharmacology , Tea , Polyphenols , EstersABSTRACT
Green tea polyphenols show positive effects on human health and longevity. However, knowledge of the antiaging properties of green tea is limited to the major catechin epigallocatechin gallate (EGCG). The search for new ingredients in tea with strong antiaging activity deserves further study. Here we isolated and identified two new catechins from Zijuan green tea, named zijuanin E (1) and zijuanin F (2). Their structures were identified by extensive high-resolution mass spectroscopy (HR-MS), nuclear magnetic resonance (NMR), ultraviolet-vis (UV), infrared (IR) and circular dichroism (CD) spectroscopic analyses, and their 13C NMR and CD data were calculated. We used the nematode Caenorhabditis elegans (C. elegans) to analyze the health benefits and longevity effects of 1 and 2. Compounds 1 and 2 (100 µM) remarkably prolonged the lifespan of C. elegans by 67.2% and 56.0%, respectively, delaying the age-related decline of phenotypes, enhancing stress resistance, and reducing ROS and lipid accumulation. Furthermore, 1 and 2 did not affect the lifespan of daf-16, daf-2, sir-2.1, and skn-1 mutant worms, suggesting that they might work via the insulin/IGF and SKN-1/Nrf2 signaling pathways. Meanwhile, 1 and 2 also exhibited strong antioxidant activity in vitro. Surface plasmon resonance (SPR) evidence suggests that zijuanins E and F have strong human serum albumin (HSA) binding ability. Together, zijuanins E and F represent a new valuable class of tea components that promote healthspan and could be developed as potential dietary therapies against aging.
Subject(s)
Caenorhabditis elegans Proteins , Catechin , Animals , Antioxidants/pharmacology , Caenorhabditis elegans , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Catechin/chemistry , Insulin/metabolism , Lipids/pharmacology , Longevity , NF-E2-Related Factor 2/metabolism , Oxidative Stress , Reactive Oxygen Species/metabolism , Serum Albumin, Human/metabolism , Signal Transduction , Tea/chemistryABSTRACT
High-resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR) analysis revealed that there are 20 main components in spores and mycelia extract of Cordyceps fumosorosea strain RCEF 6672 including mannitol (1), uridine (2), adenine (3). N6-(2-hydroxyethyl)-adenosine (4). N6-(2-hydroxyethylacetate)-adenosine (5), fumosoroseanoside A (6) and B (7), ovalicin-4α-alcohol (8), 1-linoleoyl-sn-glycero-3-phosphocholine (9) and its isomer (10), fumosoroseain A (11) and its isomer (12), 5 non-ribosomal peptides (13 to 17) and 3 fatty acids (18 to 20). The compounds 5, 6, 7, 9 and 11 were prepared with preparative and semi-preparative HPLC and identified with 1D and 2D NMR. Compounds 4 and 5 were the first time identified from C. fumosorosea. Compounds 6, 7 and 11 are novel compounds. Compounds 6 and 7 showed antibacterial and antifungal activities, and 11 showed antiaging activity. All the secondary metabolites (4 to 8 and 11 to 17) have strong bioactivities indicating that the metabolites have pharmaceutical development potentiality.
ABSTRACT
Current studies have shown that plasma trimethylamine N-oxide (TMAO) level is closely related to the risk of acute myocardial infarction (AMI), that is, the possibility of AMI occurrence is positively correlated with TMAO level. The production of TMAO is mainly due to the transformation of trimethylamine (TMA) through the hepatic flavin-containing monooxygenase. Hence, inhibition of TMA production is essential. Flavonoids are considered to be mainly responsible for the health-promoting effects, and tea is rich in a variety of flavonoids. However, it is not clear that flavonoids from Lu'an GuaPian tea regulate gut microflora by inhibiting TMA-lyase activity to prevent AMI. Sixteen flavonoids from Lu'an GuaPian tea for the treatment of AMI based on the inhibition of TMA-lyase were summarized and screened. Docking results showed kaempferol 3-O-rutinoside had the highest Vina score, which means that it is the most active and can be used as lead compounds for structural modification. PRACTICAL APPLICATIONS: TMAO can be used as a marker of CHD and thus as a potential research object. Lu'an GuaPian tea is one of the top 10 famous teas in China and has the aroma of chestnuts and orchids. The flavonoids in Lu'an GuaPian tea are mainly composed of flavonoid aglycones and flavonoid glycosides. Since flavonoids have cardiovascular protection and can regulate gut microbiota, and gut microbiota is directly related to TMAO, reduction of TMAO level is to inhibit the transformation from TMA to TMAO. Kaempferol 3-O-rutinoside, quercetin 3-O-rhamnosylgalactoside, kaempferol 3-O-rhamnosylgalactoside, and myricetin 3-O-galactoside in Lu'an GuaPian tea have good binding affinities with TMA-lyase.
Subject(s)
Lyases , Myocardial Infarction , Flavonoids , Humans , Kaempferols , Methylamines , Myocardial Infarction/drug therapy , TeaABSTRACT
INTRODUCTION: Widespread use of antibiotics has led to an increase in bacterial multiple drug resistance, thereby searching for natural antimicrobial agents from plants becomes an effective and alternative approach. In the present study, we selected six foodborne bacteria to evaluate the antibacterial activities of 12 medicinal plants ethyl acetate (EA) extracts. OBJECTIVE: This study aims to search for natural antibiotic substitutes from plant extracts. The antibacterial components were further discussed through chemometric and mass spectroscopic analyses. METHODOLOGY: Agar well diffusion and the microdilution methods were used to test the antibacterial activity. Total phenolic content (TPC) and total flavonoid content (TFC) were used to judge the active phytochemicals. To further characterise the potential antibacterial components, an ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS) coupled with Pearson correlation and feature-based molecular network (FBMN) were proposed. RESULTS: Most of the plant extracts possessed antibacterial activity against Bacillus subtilis and Salmonella typhi. Toona sinensis shoots and Firmiana simplex barks showed high inhibitory activities against Staphylococcus aureus, Shigella dysenteriae, and Escherichia coli strains with minimum inhibitory concentrations (MICs) of 1.56, 0.78, and 0.39 mg/mL, respectively. Salmonella typhi was highly sensitive to Firmiana simplex barks with an inhibitory diameter up to 21.67 ± 0.95 mm, and MIC at 0.78 mg/mL. Moreover, Toona sinensis shoots and Firmiana simplex barks had the highest TPCs. CONCLUSION: Our results indicated that Toona sinensis shoots, Koelreuteria paniculate seeds, and Firmiana simplex barks could be supplied as potential sources of antimicrobial agents. Furthermore, 36 potential bioactive compounds were identified mainly as polyphenols, glycosides, and terpenoids.
Subject(s)
Plants, Medicinal , Acetates , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Chromatography, Liquid , Microbial Sensitivity Tests , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plants, Medicinal/chemistry , Tandem Mass SpectrometryABSTRACT
Vascular endothelial cell injury induced by high glucose (HG) plays an important role in the occurrence and development of diabetic vascular complications. Yellow tea has a protective effect on vascular endothelial cells. However, the molecular mechanisms underlying this effect are unclear. In this study, the effects of the n-butanol fraction of Huoshan large-leaf yellow tea extract (HLYTBE) on vascular endothelial injury were investigated using human umbilical vein endothelial cells (HUVECs) and diabetic mice. In HUVECs, HLYTBE significantly reduced the production of reactive oxygen species, increased the activity of anti-oxidases (superoxide dismutase and glutathione peroxidase), enhanced the production of reduced glutathione, and decreased the level of oxidized glutathione, thereby improving cell viability. HLYTBE also promoted autophagosome formation, increased the LC3-II/LC3-I ratio, increased the expressions of Beclin1 and Atg 5, and decreased the expression of p62. HLYTBE up-regulated p-AMPK and down regulated p-mTOR, and these effects were reversed by compound C, an AMPK inhibitor. HLYTBE reduced apoptosis and cytochrome C expression, and these effects were attenuated by the autophagy inhibitor 3-methyladenine. In vivo studies showed that HLYTBE improved the impaired pyruvate tolerance, glucose tolerance, and insulin resistance; reduced the concentrations of blood glucose, glycated serum protein, lipids, and 8-isomeric prostaglandin 2α; increased the anti-oxidase activity in serum; and alleviated pathological damage in the thoracic aorta of diabetic mice induced by high sucrose-high fat diet along with streptozotocin. The results suggest that HLYTBE protects the vascular endothelium by up-regulating autophagy via the AMPK/mTOR pathway and inhibiting oxidative stress.
Subject(s)
Autophagy/drug effects , Endothelium, Vascular , Glucose/adverse effects , Oxidative Stress/drug effects , Tea , Animals , Cells, Cultured , Down-Regulation/drug effects , Endothelium, Vascular/drug effects , Endothelium, Vascular/pathology , Human Umbilical Vein Endothelial Cells/cytology , Humans , Mice , Plant Preparations/chemistry , Plant Preparations/pharmacology , Up-Regulation/drug effectsABSTRACT
Flavoalkaloids are a unique class of compounds in tea, most of which have an N-ethyl-2-pyrrolidinone moiety substituted at the A ring of a catechin skeleton. 1-Ethyl-5-hydroxy-pyrrolidone, a decomposed product of theanine, was supposed to be the key intermediate to form tea flavoalkaloids. However, we have also detected another possible theanine intermediate, 1-ethyl-5-oxopyrrolidine-2-carboxylic acid, and speculated if there are related conjugated catechins. Herein, four novel spiro-flavoalkaloids with a spiro-γ-lactone structural moiety were isolated from Yingde green tea (Camellia sinensis var. assamica) in our continuing exploration of new chemical constituents from tea. The structures of the new compounds, spiro-flavoalkaloids A-D (1-4), were further elucidated by extensive nuclear magnetic resonance (NMR) spectroscopy together with the calculated 13C NMR, IR, UV-vis, high-resolution mass, optical rotation, experimental, and calculated circular dichroism spectra. We also provided an alternative pathway to produce these novel spiro-flavoalkaloids. Additionally, their α-glucosidase inhibitory activities were determined with IC50 values of 3.34 (1), 5.47 (2), 22.50 (3), and 15.38 (4) µM. Docking results revealed that compounds 1 and 2 mainly interacted with residues ASP-215, ARG-442, ASP-352, GLU-411, HIS-280, ARG-315, and ASN-415 of α-glucosidase through hydrogen bonds. The fluorescence intensity of α-glucosidase could be quenched by compounds 1 and 2 in a static style.
Subject(s)
Alkaloids/pharmacology , Camellia sinensis , Glycoside Hydrolase Inhibitors/pharmacology , Tea/chemistry , Camellia sinensis/chemistry , Catechin , alpha-GlucosidasesABSTRACT
BACKGROUND AND PURPOSE: Previous studies suggest that major Camellia sinensis (tea) catechins can inhibit 3-chymotrypsin-like cysteine protease (3CLpro), inspiring us to study 3CLpro inhibition of the recently discovered catechins from tea by our group. METHODS: Autodock was used to dock 3CLpro and 16 tea catechins. Further, a 3CLpro activity detection system was used to test their intra and extra cellular 3CLpro inhibitory activity. Surface plasmon resonance (SPR) was used to analyze the dissociation constant (KD) between the catechins and 3CLpro. RESULTS: Docking data suggested that 3CLpro interacted with the selected 16 catechins with low binding energy through the key amino acid residues Thr24, Thr26, Asn142, Gly143, His163, and Gln189. The selected catechins other than zijuanin D (3) and (-)-8-(5''R)-N-ethyl-2-pyrrolidinone-3-O-cinnamoylepicatechin (11) can inhibit 3CLpro intracellularly. The extracellular 3CLpro IC50 values of (-)-epicatechin 3-O-caffeoate (EC-C, 1), zijuanin C (2), etc-pyrrolidinone C and D (6), etc-pyrrolidinone A (9), (+)-gallocatechin gallate (GCG), and (-)-epicatechin gallate (ECG) are 1.58 ± 0.21, 41.2 ± 3.56, 0.90 ± 0.03, 46.71 ± 10.50, 3.38 ± 0.48, and 71.78 ± 8.36 µM, respectively. The KD values of 1, 6, and GCG are 4.29, 3.46, and 3.36 µM, respectively. CONCLUSION: Together, EC-C (1), etc-pyrrolidinone C and D (6), and GCG are strong 3CLpro inhibitors. Our results suggest that structural modification of catechins could be conducted by esterificating the 3-OH as well as changing the configuration of C-3, C-3''' or C-5''' to discover strong SARS-CoV-2 inhibitors.
Subject(s)
COVID-19 , Camellia sinensis , Catechin , Catechin/analysis , Catechin/pharmacology , Humans , Molecular Docking Simulation , Protease Inhibitors/pharmacology , SARS-CoV-2 , TeaABSTRACT
Formation of catechins-human serum albumin (HSA) complex contributes to stably transporting catechins and regulating their bioavailability. Recently, a new class of catechins namely flavoalkaloids have been reported from tea. The unique structural modification with an N-ethyl-2-pyrrolidinone ring at catechins from these flavoalkaloids has raised our interest in their HSA binding affinity. Thus, we investigated the interaction between HSA and flavoalkaloids by molecular docking, UV-Vis spectroscopy (UV), fluorescence quenching approaches, and surface plasmon resonance (SPR). Thermodynamic parameters suggest that electrostatic forces contribute greatly to the interaction. The binding ability is affected by different ester group (galloyl or cinnamoyl) at 3-OH, N-ethyl-2-pyrrolidinone substituted position (C-6 or C-8), C-2, C-3 and C-5''' configurations, and hydroxyl group numbers at B ring, among which the 3-O-cinnamoyl substitution and 5'''-R configuration present the strongest contributions. UV showed slight changes in the conformation and microenvironment of HSA during the binding process. The quenching and binding constants suggest that the quenching is a static type. The small KD values (1-20 µM) detected by SPR confirmed the strong binding affinities between HSA and flavoalkaloids. Present study will help us to understand the interaction mechanism between flavoalkaloids and HSA, shedding light on structural modification of common catechins to enhance the stability, bioavailability and bioactivities.
Subject(s)
Catechin/chemistry , Pyrrolidinones , Serum Albumin, Human , Tea/chemistry , Alkaloids/chemistry , Binding Sites , Circular Dichroism , Flavanones/chemistry , Humans , Molecular Docking Simulation , Protein Binding , Spectrometry, Fluorescence , ThermodynamicsABSTRACT
Previous study found a high content of kaempferol-3-O-rutinoside (KR) in Lu'an GuaPian tea, however, the rat plasma protein binding and mechanism of KR for cardiovascular protection are unclear. Thus, we studied plasma protein binding using ultrafiltration followed by UPLC, and screened its inhibition against LPS-induced inflammation injury in vitro as well as the underlying mechanism by molecular docking and western blot. KR showed over 74% plasma protein binding ratio. Furthermore, KR may act on the toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88). In vitro experiments showed that KR decreases the overexpression of TLR4, MyD88, and nuclear factor-κB (NF-κB), which further validates the molecular docking results, suggesting that KR could block TLR4/MyD88/NF-κB signaling. These results indicate that KR could be a potential active agent in the protection of myocardial injury. PRACTICAL APPLICATIONS: Health benefits of tea are largely dependent on the intake of flavonoids. Flavonoids are a group of compounds beneficial to cardiovascular disease and an important part of "functional foods." Lu'an GuaPian tea is mainly produced in Lu'an City, Anhui Province and is one of the top 10 famous teas in China. Kaempferol-3-O-rutinoside in Lu'an GuaPian has good hypoglycemic effect, mainly manifested in a strong inhibition of α-glucosidase and α-amylase activities. Present study showed that kaempferol-3-O-rutinoside could block TLR4/MyD88/NF-κB signaling, suggesting that it could be a potential active agent in the protection of myocardial injury.
Subject(s)
Anti-Inflammatory Agents , Tea , Animals , Anti-Inflammatory Agents/pharmacology , China , Kaempferols , Molecular Docking Simulation , Protein Binding , RatsABSTRACT
Tea, a worldwide popular beverage rich in polyphenols, contributes to the prevention of many diseases and thus is beneficial to human health. Tea is a product through processing the fresh leaves picked from the plant Camellia sinensis (C. sinensis, genus Camellia section Thea). To date, systematic studies have been conducted on the phytochemicals from more than 20 tea varieties and related tea products, resulting in the structural determination of over 400 constituents viz. different types of polyphenols, purines, and their derivatives, mono to tetra-terpenoids, and minor other phytomolecules. These various tea phytochemicals contribute to the anti-oxidative effects, anti-diabetes, anti-inflammation, anti-cancer, blood lipid reduction, neuroprotection, anti-Alzheimer's disease, hepatoprotection, and anti-microbial activities, etc. Staphylococcus aureus (S. aureus), the significant human pathogens, could cause nosocomial and community-acquired infections, which is also responsible for various infectious diseases from mild to severe life-threatening conditions, such as bacteremia (bloodstream infection), endocarditis (heart valves infection), pneumonia, and meningitis (brain infection), leading to 2% clinical disease in of all patient admissions. The multidrug resistance (MDR) and antibiotics losing efficacy, esp. in methicillin resistance Staphylococcus aureus (MRSA) urge for novel antimicrobial agents. The MRSA strains are resistant to the entire class of ß-lactam antibiotics and limit effective treatment, leading to still spread of staphylococcal infections. MRSA also exhibits resistance to cephalosporins, macrolides, fluoroquinolones, aminoglycosides, and glycopeptides (teicoplanine and vancomycin), leading to resistant strains-glycopeptide resistant strain (GRSA) and glycopeptide intermediate (GISA) S. aureus. In this review, chemical constituents responsible for the anti-MRSA activity of tea are explored.
Subject(s)
Camellia sinensis/chemistry , Catechin/chemistry , Catechin/pharmacology , Methicillin-Resistant Staphylococcus aureus/drug effects , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Tea/chemistry , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Humans , Phytochemicals/chemistry , Phytochemicals/pharmacology , PolyphenolsABSTRACT
Tea is an important beverage source of dietary polyphenols and well known for containing phenolic structure diversity. A series of phenylpropanoid-substituted catechins, flavonols, flavan-3-hexoside, and proanthocyanidin are present in different herbs with various biological activities, inspiring our exploration of phenylpropanoid-substituted ester type of catechins (PSECs) due to the enrichment of galloylated catechins in tea. In this study, we used a guiding-screening-location-isolation integrated route including creating a hypothesized PSEC dataset, MS/MS data acquiring, construction of molecular networks, and traditional column chromatography and preliminarily identified 14 PSECs by MS/MS spectrum. Two of these PSECs were further purified and elucidated by NMR and CD spectra. Further MS detection in tea products and fresh leaves suggests that the production of the two new compounds was enhanced during tea processing. The synthesis mechanism was proposed to obtain these types of components for further investigation on their roles in human health protection. This study provides an example for the exploration of new functional ingredients from food sources guided by MS/MS data-based networking, and also new insights into the reaction mechanism to form new catechin conjugates among polyphenols in green tea.