Cancer is defined as the abnormal cell growth that can cause life-threatening malignancies with high financial costs for patients as well as the health care system. Natural polyphenols have long been ...used for the prevention and treatment of several disorders due to their antioxidant, anti-inflammatory, cytotoxic, antineoplastic, and immunomodulatory effects discussed in the literature; thus, these phytochemicals are potentially able to act as chemopreventive and chemotherapeutic agents in different types of cancer. One of the problems regarding the use of polyphenolic compounds is their low bioavailability. Different types of formulations have been designed for the improvement of bioavailability of these compounds, nanonization being one of the most notable approaches among them. This study aimed to review current data on the nanoformulations of natural polyphenols as chemopreventive and chemotherapeutic agents and to discuss their molecular anticancer mechanisms of action. Nanoformulations of natural polyphenols as bioactive agents, including resveratrol, curcumin, quercetin, epigallocatechin-3-gallate, chrysin, baicalein, luteolin, honokiol, silibinin, and coumarin derivatives, in a dose-dependent manner, result in better efficacy for the prevention and treatment of cancer. The impact of nanoformulation methods for these natural agents on tumor cells has gained wider attention due to improvement in targeted therapy and bioavailability, as well as enhancement of stability. Today, several nanoformulations are designed for delivery of polyphenolic compounds, including nanosuspensions, solid lipid nanoparticles, liposomes, gold nanoparticles, and polymeric nanoparticles, which have resulted in better antineoplastic activity, higher intracellular concentration of polyphenols, slow and sustained release of the drugs, and improvement of proapoptotic activity against tumor cells. To conclude, natural polyphenols demonstrate remarkable anticancer potential in pharmacotherapy; however, the obstacles in terms of their bioavailability in and toxicity to normal cells, as well as targeted drug delivery to malignant cells, can be overcome using nanoformulation-based technologies, which optimize the bioefficacy of these natural drugs.
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•Shade treatment reduced the contents of most catechins in preharvest tea leaves.•Shade treatment increased the theaflavin contents in preharvest tea leaves.•Shade treatment increased ...polyphenoloxidase (PPO) activity in preharvest tea leaves.•CsPPO3 was highly expressed under shade treatment.•CsPPO3 recombinant protein exhibited PPO function.
Catechins and theaflavins are important metabolites contributing to tea function and quality. Catechins are known to transform into theaflavins during the tea manufacturing process, but the same transformation in preharvest tea leaves is unknown. Herein, we determined that shade treatment (dark), an agronomic practise widely used in tea cultivation, reduced the contents of most catechins, but increased the theaflavin contents, in preharvest tea leaves (cv. Yinghong No.9). This was attributed to the activation of polyphenoloxidase (PPO) activity in darkness. Furthermore, CsPPO3 was highly expressed under darkness, and thus CsPPO3 had been cloned, sequenced, and characterization. The CsPPO3 recombinant protein exhibited PPO function. Furthermore, shade treatment also reduced the catechin contents and increased the theaflavin contents in Yabukita and Hoshinomidori, suggesting that this phenomenon might not be specific to certain tea cultivars. This information will aid in understanding of theaflavin formation and its response to environmental factors at the preharvest tea stage.
Extensive epidemiological and clinical evidence associates diets high in flavanol-containing foods with cardiovascular health benefits in humans. Catechin and epicatechin, the most common flavanols ...in foods, are present in the diet in different enantiomeric forms. This study investigated the influence of the stereochemical configuration of flavanols on their absorption, metabolism, and biological activity. Healthy adult males were asked to consume equal amounts of the stereochemically pure flavanols (−)epicatechin, (−)catechin, (+)catechin, and (+)epicatechin (1.5
mg/kg bw) in a well-defined cocoa-based, dairy-containing drink matrix, and flavanol levels were subsequently determined in plasma and 24-h urine. The results obtained show that the stereochemical configuration of flavanols has a profound influence on their uptake and metabolism in humans. In addition, we assessed the vasodilatory activity of each flavanol stereoisomer in vivo and found (−)-epicatechin to be the single stereoisomer capable of mediating a significant arterial dilation response. Importantly, this effect was independent of the classic antioxidant properties of flavanols. Overall, these results indicate that the proposed beneficial health effects associated with the consumption of flavanol-containing foods will significantly depend on the stereochemical configuration of the flavanols ingested.
Abstract
The global pandemic crisis, coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has claimed the lives of millions of people across ...the world. Development and testing of anti-SARS-CoV-2 drugs or vaccines have not turned to be realistic within the timeframe needed to combat this pandemic. Here, we report a comprehensive computational approach to identify the multi-targeted drug molecules against the SARS-CoV-2 proteins, whichare crucially involved in the viral–host interaction, replication of the virus inside the host, disease progression and transmission of coronavirus infection. Virtual screening of 75 FDA-approved potential antiviral drugs against the target proteins, spike (S) glycoprotein, human angiotensin-converting enzyme 2 (hACE2), 3-chymotrypsin-like cysteine protease (3CLpro), cathepsin L (CTSL), nucleocapsid protein, RNA-dependent RNA polymerase (RdRp) and non-structural protein 6 (NSP6), resulted in the selection of seven drugs which preferentially bind to the target proteins. Further, the molecular interactions determined by molecular dynamics simulation revealed that among the 75 drug molecules, catechin can effectively bind to 3CLpro, CTSL, RBD of S protein, NSP6 and nucleocapsid protein. It is more conveniently involved in key molecular interactions, showing binding free energy (ΔGbind) in the range of −5.09 kcal/mol (CTSL) to −26.09 kcal/mol (NSP6). At the binding pocket, catechin is majorly stabilized by the hydrophobic interactions, displays ΔEvdW values: −7.59 to −37.39 kcal/mol. Thus, the structural insights of better binding affinity and favorable molecular interaction of catechin toward multiple target proteins signify that catechin can be potentially explored as a multi-targeted agent against COVID-19.
Graphical Abstract
Graphical Abstract
The use of Catechin as an antibacterial agent is becoming ever-more common, whereas unstable and easy oxidation, have limited its application. A simple and low-energy-consuming approach to synthesize ...highly stable and dispersive Catechin-Cu nanoparticles(NPs) has been developed, in which the stability and dispersivity of the NPs are varied greatly with the pH value and temperature of the reaction. The results demonstrate that the optimal reaction conditions are pH 11 at room temperature. As-synthesized NPs display excellent antimicrobial activity, the survival rates of bacterial cells exposed to the NPs were evaluated using live/dead Bacterial Viability Kit. The results showed that NPs at the concentration of 10 ppm and 20 ppm provided rapid and effective killing of up to 90% and 85% of S. aureus and E. coli within 3 h, respectively. After treatment with 20 ppm and 40 ppm NPs, the bacteria are killed completely. Furthermore, on the basis of assessing the antibacterial effects by SEM, TEM, and AFM, it was found the cell membrane damage of the bacteria caused by direct contact of the bacteria with the NPs was the effective mechanism in the bacterial inactivation.
The coronavirus disease (COVID-19) pandemic, resulting from human-to-human transmission of a novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), has led to a global health crisis. Given ...that the 3 chymotrypsin-like protease (3CLpro) of SARS-CoV-2 plays an indispensable role in viral polyprotein processing, its successful inhibition halts viral replication and thus constrains virus spread. Therefore, developing an effective SARS-CoV-2 3CLpro inhibitor to treat COVID-19 is imperative. A fluorescence resonance energy transfer (FRET)-based method was used to assess the proteolytic activity of SARS-CoV-2 3CLpro using intramolecularly quenched fluorogenic peptide substrates corresponding to the cleavage sequence of SARS-CoV-2 3CLpro. Molecular modeling with GEMDOCK was used to simulate the molecular interactions between drugs and the binding pocket of SARS-CoV-2 3CLpro. This study revealed that the Vmax of SARS-CoV-2 3CLpro was about 2-fold higher than that of SARS-CoV 3CLpro. Interestingly, the proteolytic activity of SARS-CoV-2 3CLpro is slightly more efficient than that of SARS-CoV 3CLpro. Meanwhile, natural compounds PGG and EGCG showed remarkable inhibitory activity against SARS-CoV-2 3CLpro than against SARS-CoV 3CLpro. In molecular docking, PGG and EGCG strongly interacted with the substrate binding pocket of SARS-CoV-2 3CLpro, forming hydrogen bonds with multiple residues, including the catalytic residues C145 and H41. The activities of PGG and EGCG against SARS-CoV-2 3CLpro demonstrate their inhibition of viral protease activity and highlight their therapeutic potentials for treating SARS-CoV-2 infection.
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•An effective SARS-CoV-2 3CLpro inhibitor is imperative for COVID-19 treatment.•The Vmax of SARS-CoV-2 3CLpro was about 2-fold higher than that of SARS-CoV 3CLpro.•PGG and EGCG show potent inhibitory activity against SARS-CoV-2 3CLpro.•PGG and EGCG strongly interact with the catalytic sites of SARS-CoV-2 3CLpro.•PGG and EGCG possess therapeutic potentials for treating SARS-CoV-2 infection.
Chemotherapy for cancer treatment has been demonstrated to cause some side effects on healthy tissues and multidrug resistance of the tumor cells, which greatly limits therapeutic efficacy. To ...address these limitations and achieve better therapeutic efficacy, combination therapy based on nanoparticle platforms provides a promising approach through delivering different agents simultaneously to the same destination with synergistic effect. In this study, a novel green tea catechin-based polyion complex (PIC) micelle loaded with doxorubicin (DOX) and (-)-Epigallocatechin-3-O-gallate (EGCG) was constructed through electrostatic interaction and phenylboronic acid-catechol interaction between poly(ethylene glycol)-block-poly(lysine-co-lysine-phenylboronic acid) (PEG-PLys/PBA) and EGCG. DOX was co-loaded in the PIC micelles through π-π stacking interaction with EGCG. The phenylboronic acid-catechol interaction endowed the PIC micelles with high stability under physiological condition. Moreover, acid cleavability of phenylboronic acid-catechol interaction in the micelle core has significant benefits for delivering EGCG and DOX to same destination with synergistic effects. In addition, benefiting from the oxygen free radicals scavenging activity of EGCG, combination therapy with EGCG and DOX in the micelle core could protect the cardiomyocytes from DOX-mediated cardiotoxicity according to the histopathologic analysis of hearts. Attributed to modulation of EGCG on P-glycoprotein (P-gp) activity, this kind of PIC micelles could effectively reverse multidrug resistance of cancer cells. These results suggested that EGCG based PIC micelles could effectively overcome DOX induced cardiotoxicity and multidrug resistance.
We have hypothesized that mobilization of endogenous copper ions by plant polyphenols such as EGCG and consequent oxidative degradation of cellular DNA could be an important mechanism of their ...anticancer properties.
The viability, productivity and survival of higher plants under the adverse factors influence are largely determined by the functional activity of the antioxidant system. The aim of our work was to ...investigate changes in formation of high-molecular (superoxide dismutase and peroxidase) and low-molecular (phenolics, including flavanols and proanthocyanidins) antioxidants in callus culture of Camellia sinensis under influence of phenolic precursors (L-phenylalanine—3 mM, trans-cinnamic acid—1 mM, naringenin—0.5 mM). According to the data obtained, the effect of precursors on tea callus cultures did not lead to significant increasing of superoxide dismutase and peroxidase activity in most cases. However, it led to the increased accumulation of the total phenolics content, as well as flavanols and proanthocyanidins contents. For C. sinensis callus cultures, the most promising regulator of phenolic compounds was L-phenylalanine, in the presence of which its content increased almost twice. Thus, the exogenous effect of various precursors is possible to use for the targeted regulation of certain phenolics classes accumulation in plant cells.
Extracts of tea, especially green tea, and tea polyphenols have been shown to inhibit the formation and development of tumours at different organ sites in animal models. There is considerable ...evidence that tea polyphenols, in particular (-)-epigallocatechin-3-gallate, inhibit enzyme activities and signal transduction pathways, resulting in the suppression of cell proliferation and enhancement of apoptosis, as well as the inhibition of cell invasion,angiogenesis and metastasis. Here, we review these biological activities and existing data relating tea consumption to human cancer risk in an attempt to understand the potential use of tea for cancer prevention.
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