Numerous studies revealed that spinal inflammation and immune response play an important role in neuropathic pain. In this study, we investigated the effects of intrathecal injection of a Toll-like ...receptor (TLR4) inhibitor epigallocatechin gallate (EGCG) on neuropathic pain induced by chronic constriction injury of the sciatic nerve (CCI). A total of 120 rats were randomly assigned into 4 groups: sham-operated group, CCI group, CCI plus normal saline group and CCI plus EGCG group. CCI and sham surgeries were performed and both thermal hyperalgesia and mechanical allodynia were tested. Lumbar spinal cord was sampled and the mRNA and protein expressions of TLR4 and High Mobility Group 1 protein (HMGB1) were detected, the contents of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-10 (IL-10) were measured by ELISA, and immunohistochemistry for nuclear factor kappa B (NF-κB) was also carried out. When compared with the sham group, both mechanical and heat pain thresholds were significantly decreased, and the mRNA and protein expressions of TLR4 and HMGB1, the contents of TNF-α, IL-1β and IL-10 in the spinal cords and NF-κB expression in the spinal dorsal horn were markedly increased in CCI rats (
P
<
0.05). After intrathecal injection of EGCG (1
mg/kg) once daily from 1
day before to 3
days after CCI surgery, the expressions of TLR4, NF-κB, HMGB1, TNF-α and IL-1β were markedly decreased while the content of IL-10 in the spinal cord increased significantly accompanied by dramatical improvement of pain behaviors in CCI rats (
P<
0.05). These results show that the TLR4 signaling pathway plays an important role in the occurrence and development of neuropathic pain, and the therapy targeting TLR4 might be a novel strategy in the treatment of neuropathic pain.
Catechin is a flavonoid naturally present in numerous dietary products and fruits (e.g., apples, berries, grape seeds, kiwis, green tea, red wine, etc.) and has previously been shown to be an ...antioxidant and beneficial for the gut microbiome. To further enhance the health benefits, bioavailability, and stability of catechin, we synthesized and characterized catechin pentaacetate and catechin pentabutanoate as two new ester derivatives of catechin. Catechin and its derivatives were assessed in vivo via intra-amniotic administration (Gallus gallus), with the following treatment groups: (1) non-injected (control); (2) deionized H2O (control); (3) Tween (0.004 mg/mL dose); (4) inulin (50 mg/mL dose); (5) Catechin (6.2 mg/mL dose); (6) Catechin pentaacetate (10 mg/mL dose); and (7) Catechin pentabutanoate (12.8 mg/mL dose). The effects on physiological markers associated with brush border membrane morphology, intestinal bacterial populations, and duodenal gene expression of key proteins were investigated. Compared to the controls, our results demonstrated a significant (p < 0.05) decrease in Clostridium genera and E. coli species density with catechin and its synthetic derivative exposure. Furthermore, catechin and its derivatives decreased iron and zinc transporter (Ferroportin and ZnT1, respectively) gene expression in the duodenum compared to the controls. In conclusion, catechin and its synthetic derivatives have the potential to improve intestinal morphology and functionality and positively modulate the microbiome.
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•WPI was complexed with caffeic acid(CA) or epigallocatechin gallate (EGCG)•Complexation with CA led to largerchanges in WPI conformation than with EGCG.•Complexation with WPI ...protected CA and EGCG during in vitro digestion.•Protein digestion pattern was dependent on the pH of complexes preparation.
Whey protein isolate (WPI) interactions with (-)-epigallocatechin gallate (EGCG) and caffeic acid (CA) at pH 3.5 and 7.0 were investigated concerning complex formation and antioxidant capacity, before and after simulated digestion. Complex formation was evidenced by protein structural changes when WPI was associated with CA or EGCG. Reducing capacity and FRAP values increased as the phenolic compound concentration increased while ORAC values remained unchanged. In general, compared to the isolated compounds, complexation suppressed the antioxidant capacity possibly due to hydrophobic interaction and H-bonding between these compounds. Protein:phenolic complexation in 1:0.5 M ratio did not affect the digestibility compared to WPI (83%), except for WPI:CA at pH 7.0 (73%). The hydrophilicity profile of the digested samples suggested that pH of complexation and type of phenolic affected the protein cleavage pattern. Furthermore, the phenolic compounds were more stable when associated with the protein since they were protected from the simulated gastrointestinal environment.
Different concentrations of catechin (0, 10, 50, 100 and 200μmol/g protein) were added to pork myofibrillar protein (MP) suspensions, and the related changes in protein conformational and gel ...properties were investigated. The results showed that catechin at 200μmol/g protein led to the greatest increase in the surface hydrophobicity of MP. A significant loss of thiols (SH) content was observed in MP in the presence of catechin. The low concentration of catechin of 10μmol/g led to slight changes in the MP gel strength and water-holding capacity. However, catechin at higher concentrations (50, 100 and 200μmol/g protein) caused severe deterioration of MP gelation. The microstructure and dynamic rheological properties confirmed the unfavorable effect of catechin on the MP gel properties. The results indicate that catechin caused changes in MP conformational and gel properties, which may be due to the catechin–MP covalent interactions and the exposure of hydrophobic domains caused by catechin.
•Catechin addition changed the structure and gel properties of MP.•Catechin increased the surface hydrophobicity and decreased the SH content of MP.•Decrease of gel strength and WHC by catechin was concentration-dependency.•SEM and rheological properties confirmed the unfavorable effect of catechin on gel.
Increasing interest in the health benefits of tea has led to the inclusion of tea extracts in dietary supplements and functional foods. However, epidemiologic evidence regarding the effects of tea ...consumption on cancer and cardiovascular disease risk is conflicting. While tea contains a number of bioactive chemicals, it is particularly rich in catechins, of which epigallocatechin gallate (EGCG) is the most abundant. Catechins and their derivatives are thought to contribute to the beneficial effects ascribed to tea. Tea catechins and polyphenols are effective scavengers of reactive oxygen species in vitro and may also function indirectly as antioxidants through their effects on transcription factors and enzyme activities. The fact that catechins are rapidly and extensively metabolized emphasizes the importance of demonstrating their antioxidant activity in vivo. In humans, modest transient increases in plasma antioxidant capacity have been demonstrated following the consumption of tea and green tea catechins. The effects of tea and green tea catechins on biomarkers of oxidative stress, especially oxidative DNA damage, appear very promising in animal models, but data on biomarkers of in vivo oxidative stress in humans are limited. Larger human studies examining the effects of tea and tea catechin intake on biomarkers of oxidative damage to lipids, proteins, and DNA are needed.
Referee: Dr. Jeffrey Blumberg, USDA HNRC on Aging, Tufts University, Antioxidants Research Lab, 711 Washington Street, Boston, MA 02111-1524
Dietary flavonoids may improve endothelial function and ultimately lead to beneficial cardiovascular effects.
The objective was to assess whether pure dietary flavonoids can modulate nitric oxide and ...endothelin-1 production and thereby improve endothelial function.
A randomized, placebo-controlled, crossover trial in 12 healthy men was conducted to compare the acute effects of the oral administration of 200 mg quercetin, (-)-epicatechin, or epigallocatechin gallate on nitric oxide, endothelin-1, and oxidative stress after nitric oxide production was assessed via the measurement of plasma S-nitrosothiols and plasma and urinary nitrite and nitrate concentrations. The effects on oxidative stress were assessed by measuring plasma and urinary F(2)-isoprostanes. Plasma and urinary concentrations of quercetin, (-)-epicatechin, and epigallocatechin gallate were measured to establish the absorption of these flavonoids.
Relative to water (control), quercetin and (-)-epicatechin resulted in a significant increase in plasma S-nitrosothiols, plasma nitrite, and urinary nitrate concentrations (P < 0.05), but not in plasma nitrate or urinary nitrite. Epigallocatechin gallate did not alter any of the measures of nitric oxide production. Quercetin and (-)-epicatechin resulted in a significant reduction in plasma endothelin-1 concentration (P < 0.05), but only quercetin significantly decreased the urinary endothelin-1 concentration. None of the 3 treatments significantly changed plasma or urinary F(2)-isoprostane concentrations. Significant increases in the circulating concentrations of the 3 flavonoids were observed (P < 0.05) after the corresponding treatment.
Dietary flavonoids, such as quercetin and (-)-epicatechin, can augment nitric oxide status and reduce endothelin-1 concentrations and may thereby improve endothelial function.
Suit[3]ane Chen, Xiao-Yang; Shen, Dengke; Cai, Kang ...
Journal of the American Chemical Society,
11/2020, Volume:
142, Issue:
47
Journal Article
Peer reviewed
Suitanes are a class of mechanically interlocked molecules (MIMs) that consist of two components: a body with limbs protruding outward and a suit that fits appropriately around it, so that there is ...no easy way for the suit to be removed from the body. Herein, we report the synthesis and characterization of a suit3ane, which contains a benzotrithiophene derivative (THBTT) with three protruding hexyl chains as the body and a 3-fold symmetric, extended pyridinium-based cage, namely, HexaCage 6+, as the suit. Central to its realization is effective templation, provided by THBTT during cage formation, an observation that has been supported by the strong binding constant between benzotrithiophene (BTT) and the empty cage. The solid-state structure of the suit3ane reveals that the body is confined within the suit’s cavity with its alkyl chains protruding outward through the orifices in the cage. Notably, such a seemingly unstable molecule, having three flexible alkyl chains as its only protruding limbs, does not dissociate after prolonged heating in CD3CN at 100 °C under pressure for 7 days. No evidence for guest exchange with the host was observed at this temperature in a 2:1 mixture of THBTT and HexaCage 6+ in CD3CN. The results indicate that flexible protruding limbs are sufficient for a suit3ane to remain mechanically stable even at high temperatures in solution.
The role of catechins in the epigenetic regulation of gene expression has been widely studied; however, if and how this phenomenon relates to the redox properties of these polyphenols remains ...unknown. Our earlier study demonstrated that exposure of the human colon adenocarcinoma HT29 cell line to these antioxidants affects the expression of redox-related genes. In particular, treatment with (−)-epigallocatechin (EGC) downregulated transcription of gene encoding sulfiredoxin-1 (SRXN1), the peroxidase involved in the protection of cells against hydrogen peroxide-induced oxidative stress. The aim of this study was to investigate whether the observed SRXN1 downregulation was accompanied by changes in the DNA methylation level of its promoter and, if so, whether it was correlated with the redox properties of catechins. The impact on DNA methylation profile in HT29 cells treated with different concentrations of five catechins, varying in chemical structures and standard reduction potentials as well as susceptibility to oxidation, was monitored by a methylation-sensitive high-resolution melting technique employing the SRXN1 promoter region as a model target. We demonstrated that catechins, indeed, are able to modulate DNA methylation of the SRXN1 gene in a redox-related manner. The nonlinear method in the statistical analysis made it possible to fish out two parameters (charge transfer in oxidation process Qox and time of electron transfer t), whose strong interactions correlated with observed modulation of DNA methylation by catechins. Based on these findings, we present a proof-of-concept that DNA methylation, which limits SRXN1 expression and thus restricts the multidirectional antioxidant action of SRXN1, may represent a mechanism protecting cells against reductive stress caused by particularly fast-reacting reductants such as EGC and (−)-epicatechin gallate (ECG) in our study.
This study evaluated the relationship between the neuroprotective effects of procyanidins and their structural characteristics. In vitro, a rat pheochromocytoma cell line (PC12) was exposed to the ...grape seed-derived procyanidin monomers: catechin (C), epicatechin (EC), and epicatechin gallate (ECG); the procyanidin dimers: procyanidin B1 (B1), procyanidin B2 (B2), procyanidin B3 (B3), procyanidin B4 (B4), procyanidin B1-3-
-gallate (B1-G), and procyanidin B2-3-
-gallate (B2-G); and the procyanidin trimers: procyanidin C1 (C1) and
-acetyl-l-cysteine (NAC) for 24 h. Cells were then incubated with 200 μM H
O
for 24 h. In vivo, zebrafish larvae (AB strain) 3 days post-fertilization were incubated with NAC or procyanidins (C, EC, ECG, B1, B2, B3, B4, B1-G, B2-G, C1) in 300 µM H
O
for 4 days. Different grape seed procyanidins increased the survival of PC12 cells challenged with H
O
, improved the movement behavior disorder of zebrafish caused by H
O
, inhibited the increase of ROS and MDA and the decrease of GSH-Px, CAT, and SOD activities, and up-regulated the Nrf2/ARE pathway. The neuroprotective effects of the procyanidin trimer C1 treatment group were greater than the other treatment groups. These results suggest that the neuroprotective effect of procyanidins is positively correlated with their degree of polymerization.
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![Suit[3]ane](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0002-7863/small "Suit[3]ane")
