Fragile Treg cells: Traitors in immune homeostasis?

Regulatory T (Treg) cells play a key role in maintaining immune tolerance and tissue homeostasis. However, in some disease microenvironments, Treg cells exhibit fragility, which manifests as preserved FoxP3 expression accompanied by inflammation and loss of immunosuppression. Fragile Treg cells are formatively, phenotypically and functionally diverse in various diseases, further complicating the role of Treg cells in the immunotherapeutic response and offering novel targets for disease treatment by modulating specific Treg subsets. In this review, we summarize findings on fragile Treg cells to provide a framework for characterizing the formation and role of fragile Treg cells in different diseases, and we discuss how this information may guide the development of more specific Treg-targeted immunotherapies.

Treating cancer through modulating exosomal protein loading and function: The prospects of natural products and traditional Chinese medicine.

Exosomes, small yet vital extracellular vesicles, play an integral role in intercellular communication. They transport critical components, such as proteins, lipid bilayers, DNA, RNA, and glycans, to target cells. These vesicles are crucial in modulating the extracellular matrix and orchestrating signal transduction processes. In oncology, exosomes are pivotal in tumor growth, metastasis, drug resistance, and immune modulation within the tumor microenvironment. Exosomal proteins, noted for their stability and specificity, have garnered widespread attention. This review delves into the mechanisms of exosomal protein loading and their impact on tumor development, with a focus on the regulatory effects of natural products and traditional Chinese medicine on exosomal protein loading and function. These insights not only offer new strategies and methodologies for cancer treatment but also provide scientific bases and directions for future clinical applications.

Mulberry leaf (Morus alba L.): A review of its potential influences in mechanisms of action on metabolic diseases.

The leaves of Morus alba L. (called Sangye in Chinese, ML), which belong to the genus Morus., are highly valuable edible plants in nutrients and nutraceuticals. In Asian countries including China, Japan and Korea, ML are widely used as functional foods including beverages, noodles and herbal tea because of its biological and nutritional value. Meanwhile, ML-derived products in the form of powders, extracts and capsules are widely consumed as dietary supplements for controlling blood glucose and sugar. Clinical studies showed that ML play an important role in the treatment of metabolic diseases including the diabetes, dyslipidemia, obesity, atherosclerosis and hypertension. People broadly use ML due to their nutritiousness, deliciousness, safety, and abundant active benefits. However, the systematic pharmacological mechanisms of ML on metabolic diseases have not been fully revealed. Therefore, in order to fully utilize and scale relevant products about ML, this review summarizes the up-to-date information about the ML and its constituents effecting on metabolic disease.

Genus Suaeda: Advances in phytology, chemistry, pharmacology and clinical application (1895 - 2021).

More than 100 species of annual herb genus Suaeda widely distribute (Asia, North America, northern Africa and Europe), are rich in resources (about hundreds of millions of tons/Y) and have a long historical application. Most of them are mainly used for traditional food, feed and medicine. Recently, they have been employed to repair saline-alkali land and beautify the environment. So far, only 27 species have been reported on the bioactivity diversity, broad spectrum and effectiveness in clinical practice. Therefore, the in-depth and extensive research of Suaeda has become a research hotspot around the world. However, only one review summarized the nutritional, chemical and biological values of Suaeda. By searching the international authoritative databases (ACS Publications, ScienceDirect, PubMed, Springer, web of Science and Bing International etc.) and collecting 103 literatures closely related to Suaeda (1895-2021), herewith a comprehensive and systematic review was conducted on the phytology, chemistry, pharmacology and clinical application, enveloping the classification evolution between Amaranthaceae and Chenopodiaceae, distribution and common botanical characteristics; involving 9 chemical categories of 163 derivatives covering 14 new and 6 first-isolated ones, and appraising the content determination of 6 categories of components; mainly including the pharmacology of 13 species in vivo and vitro; estimating the clinical application of 16 species cured the related diseases of eight human physiological system except for the motor system. It is expected that this paper will provide forward-looking scientific ideas and literature support for the further modern research, development and utilization of the genus.

Nano-based drug delivery systems used as vehicles to enhance polyphenols therapeutic effect for diabetes mellitus treatment.

Diabetes mellitus is one of the biggest health emergencies of the 21st century worldwide, characterized by deficiency in insulin secretion and/or action, leading to hyperglycemia. Despite the currently available antidiabetic therapeutic options, 4.2 million people died in 2019 due to diabetes. Thus, new effective interventions are required. Polyphenols are plant secondary metabolites and have been recognized for their vast number of biological activities, including potential antidiabetic effects. However, the poor bioavailability and high metabolization of polyphenols restrict their biological effects in vivo. Nanotechnology is a promising area of research to improve the therapeutic effect of several compounds. Therefore, this review provides an overview of the literature about the utility of nano-based drug delivery systems as vehicles of polyphenols in diabetes treatment. It was possible to conclude that, in general, nano-based drug delivery systems can potentiate the beneficial antidiabetic properties of polyphenols, when compared with the free compounds, opening a new field of research in diabetology.

Ethanol extracts of Danlou tablet attenuate atherosclerosis via inhibiting inflammation and promoting lipid effluent.

As a chronic inflammatory disease, atherosclerosis is characterized by accumulation of lipid-rich macrophages on the inner walls of arteries. Deposited macrophages promote atherosclerotic lesion progression; therefore they are viewed as the main targets in order to alleviate atherosclerosis. Danlou tablet, a patented Chinese Medicine, has long been used to treat cardiovascular diseases. In the present study, we used Apolipoprotein E-deficient (ApoE-/-) mice model and in vitro cell line of RAW264.7 to explore the mechanisms of ethanol extracts of Danlou tablet (EEDT) in treating atherosclerosis. The potential targets that EEDT works to treat atherosclerosis were predicted by "Network pharmacology analysis", based on which we designed mRNA array of 93 genes. Then mRNA array and oil red O staining were performed in aortic extracted from the cohorts of Control (C57BL/6 mice, chow fed), Model (ApoE-/- C57BL/6 mice, 20 weeks of high-fat diet) and EEDT intervening (ApoE-/- mice, 20 weeks of high-fat diet with 12 weeks of EEDT treatment) group. Furthermore, mRNA array, inflammation cytokines and lipid content were examined in RAW264.7 cell line. It was showed that EEDT decreased the expressions of inflammation cytokines by down regulating NF-κB singling pathway and accelerated cholesterol effluent through activating PPARα/ABCA1 signaling pathway. On the other hand, activation of NF-κB pathway or suppression of PPARα/ABCA1 signaling pathway both abolished the therapeutic effect of EEDT. In conclusion, EEDT played a key role in anti-inflammation and preventing lipid deposition in macrophages of atherosclerosis via suppressing NF-κB signaling and triggering PPARα/ABCA1 signaling pathway.

Natural medicines for the treatment of fatigue: Bioactive components, pharmacology, and mechanisms.

It is a common phenomenon that people are in a sub-health condition and facing "unexplained fatigue", which seriously affects their health, work efficiency and quality of life. Meanwhile, fatigue is also a common symptom of many serious diseases such as HIV/AIDS, cancer, and schizophrenia. However, there are still no official recommendations for the treatment of various forms of fatigue. Some traditional natural medicines are often used as health care products, such as ginseng, Cordyceps militaris (L.ex Fr.Link) and Rhodiola rosea L., and these have been reported to have specific anti-fatigue effects with small toxic and side effects and rich pharmacological activities. It may be promising treatment strategy for sub-health. In this review, we first outline the generation of fatigue. Furthermore, we put emphasis on the anti-fatigue mechanism, bioactive components, and clinic trials of natural medicines, which will contribute to the development of potential anti-fatigue agents and open up novel treatments for sub-health.

Gut microbiota in phytopharmacology: A comprehensive overview of concepts, reciprocal interactions, biotransformations and mode of actions.

The dynamic and delicate interactions amongst intestinal microbiota, metabolome and metabolism dictates human health and disease. In recent years, our understanding of gut microbial regulation of intestinal immunometabolic and redox homeostasis have evolved mainly out of in vivo studies associated with high-fat feeding induced metabolic diseases. Techniques utilizing fecal transplantation and germ-free mice have been instrumental in reproducibly demonstrating how the gut microbiota affects disease pathogenesis. However, the pillars of modern drug discovery i.e. evidence-based pharmacological studies critically lack focus on intestinal microflora. This is primarily due to targeted in vitro molecular-approaches at cellular-level that largely overlook the etiology of disease pathogenesis from the physiological perspective. Thus, this review aims to provide a comprehensive understanding of the key notions of intestinal microbiota and dysbiosis, and highlight the microbiota-phytochemical bidirectional interactions that affects bioavailability and bioactivity of parent phytochemicals and their metabolites. Potentially by focusing on the three major aspects of gut microbiota i.e. microbial abundance, diversity, and functions, I will discuss phytochemical-microbiota reciprocal interactions, biotransformation of phytochemicals and plant-derived drugs, and pre-clinical and clinical efficacies of herbal medicine on dysbiosis. Additionally, in relation to phytochemical pharmacology, I will briefly discuss the role of dietary-patterns associated with changes in microbial profiles and review pharmacological study models considering possible microbial effects. This review therefore, emphasize on the timely and critically needed evidence-based phytochemical studies focusing on gut microbiota and will provide newer insights for future pre-clinical and clinical phytopharmacological interventions.

Galloyl derivatives from Caesalpinia coriaria exhibit in vitro ovicidal activity against cattle gastrointestinal parasitic nematodes.

Gastrointestinal nematodes (GIN) are responsible for enormous economic losses worldwide. The use of anthelmintic drugs reduces the parasitic burden in ruminants. However, the excessive use of these drugs triggers anthelmintic resistance in these parasites, which leads to a worrisome inefficacy of most of the commercially available antiparasitic drugs. Caesalpinia coriaria is an arboreal legume possessing medical properties, although the antiparasitic potential of this plant against animal parasitic nematodes has not yet been studied. The aim of this study was to assess the in vitro ovicidal activity of a hydro-alcoholic extract (HA-E) from C. coriaria fruits against GIN and to identify the compounds responsible for this activity through an egg hatch inhibition (EHI) assay. GIN eggs obtained from cattle faeces were used in bio-guided assays. The HA-E was subjected to a liquid-liquid extraction using water and ethyl acetate to obtain two fractions, an organic fraction (EtOAc-F, 27% yield) and an aqueous (Aq-F, 73% yield) fraction. The chromatographic fractionation of the EtOAc-F (2 gr) was performed on a glass column packed with silica gel and eluted with dichloromethane/methanol with 10% ascending polarity. The bioactive compounds were analysed using high-performance liquid chromatography (HPLC) with UV detection, nuclear magnetic resonance (NMR) spectroscopy and mass spectroscopy (MS). The HA-E extract and the EtOAc-F showed ovicidal activity at a LC50 of 0.92 and 0.16 mg/mL, respectively. A concentration-dependant effect was observed in both treatments. Chromatographic fractionation of the EtOAc-F, allowed for the isolation and characterisation of three important compounds: methyl gallate (1), gallic acid (2) and an unidentified compound (UC). The bioactive molecules (2 and UC) displayed an ovicidal activity close to 100% at 1 mg/mL concentration. The results of this work show that gallic acid (2) isolated from C. coriaria fruits is responsible for its ovicidal activity. The use of Caesalpinia coriaria could be explored in future studies as an environmentally-friendly alternative for the control of GIN in ruminants.

Anthocyanins in cardioprotection: A path through mitochondria.

Constantly growing experimental data from in vitro, in vivo and epidemiological studies show the great potential of anthocyanin-containing fruit and berry extracts or pure individual anthocyanins as cardioprotective food components or pharmacological compounds. In general it is regarded that the cardioprotective activity of anthocyanins is related to their antioxidant properties. However there are recent reports that certain anthocyanins may protect the heart against ischemia/reperfusion-induced injury by activating signal transduction pathways and sustaining mitochondrial functions instead of acting solely as antioxidants. In this review, we summarize the proposed mechanisms of direct or indirect actions of anthocyanins within cardiac cells with the special emphasis on recently discovered their pharmacological effects on mitochondria in cardioprotection: reduction of cytosolic cytochrome c preventing apoptosis and sustainment of electron transfer between NADH dehydrogenase and cytochrome c supporting oxidative phosphorylation in ischemia-damaged mitochondria.

Effects of post-fermentation addition of green tea extract for sulfur dioxide replacement on Sauvignon Blanc wine phenolic composition, antioxidant capacity, colour, and mouthfeel attributes.

This study examines the feasibility of replacing SO2 in a New Zealand Sauvignon Blanc wine with a green tea extract. The treatments included the control with no preservatives (C), the addition of green tea extract at 0.1 and 0.2 g/L (T1 and T2), and an SO2 treatment at 50 mg/L (T3). Five monomeric phenolic compounds were detected in the green tea extract used for the experiment, and their concentrations ranged in the order (-)-epigallocatechin gallate > (-)-epigallocatechin > (-)-epicatechin > (-)-epicatechin gallate > gallic acid. At the studied addition rates, these green tea-derived phenolic compounds contributed to ∼70% of the antioxidant capacity (ABTS), ∼71% of the total phenolic index (TPI), and âˆ¼ 84% of tannin concentration (MCPT) of the extract dissolved in a model wine solution. Among wine treatments, T1 and T2 significantly increased the wine's colour absorbance at 420 nm, MCPT, gallic acid and total monomeric phenolic content. TPI and ABTS were significantly higher in wines with preservatives (i.e., T2 > T1 â‰… T3 > C, p < 0.05). These variations were observed both two weeks after the treatments and again after five months of wine aging. Additionally, an accelerated browning test and a quantitative sensory analysis of wine colour and mouthfeel attributes were performed after 5 months of wine aging. When exposed to excessive oxygen and high temperature (50 °C), T1 and T2 exhibited ∼29% and 24% higher browning capacity than the control, whereas T3 reduced the wine's browning capacity by ∼20%. Nonetheless, the results from sensory analysis did not show significant variations between the treatments. Thus, using green tea extract to replace SO2 at wine bottling appears to be a viable option, without inducing a negative impact on the perceptible colour and mouthfeel attributes of Sauvignon Blanc wine.

Metabolomics analysis based on UHPLC-QqQ-MS/MS to discriminate grapes and wines from different geographical origins and climatological characteristics.

With the proliferation of the consumer's awareness of wine provenance, wines with unique origin characteristics are increasingly in demand. This study aimed to investigate the influence of geographical origins and climatological characteristics on grapes and wines. A total of 94 anthocyanins and 78 non-anthocyanin phenolic compounds in grapes and wines from five Chinese viticultural vineyards (CJ, WH, QTX, WW, and XY) were identified by UHPLC-QqQ-MS/MS. Chemometric methods PCA and OPLS-DA were established to select candidate differential metabolites, including flavonols, stilbenes, hydroxycinnamic acids, peonidin derivatives, and malvidin derivatives. CCA showed that malvidin-3-O-glucoside had a positive correlation with mean temperature, and quercetin-3-O-glucoside had a negative correlation with precipitation. In addition, enrichment analysis elucidated that the metabolic diversity in different origins mainly occurred in flavonoid biosynthesis. This study would provide some new insights to understand the effect of geographical origins and climatological characteristics on phenolic compounds in grapes and wines.

Integration of non-targeted/targeted metabolomics and electronic sensor technology reveals the chemical and sensor variation in 12 representative yellow teas.

Yellow tea is a lightly fermented tea with unique sensory qualities and health benefits. However, chemical composition and sensory quality of yellow tea products have rarely been studied. 12 representative yellow teas, which were basically covered the main products of yellow tea, were chosen in this study. Combined analysis of non-targeted/targeted metabolomics and electronic sensor technologies (E-eye, E-nose, E-tongue) revealed the chemical and sensor variation. The results showed that yellow big tea differed greatly from yellow bud teas and yellow little teas, but yellow bud teas could not be effectively distinguished from yellow little teas based on chemical constituents and electronic sensory characteristics. Sensor variation of yellow teas might be attributed to some compounds related to bitterness and aftertaste-bitterness (4'-dehydroxylated gallocatechin-3-O-gallate, dehydrotheasinensin C, myricitin 3-O-galactoside, phloroglucinol), aftertaste-astringency (methyl gallate, 1,5-digalloylglucose, 2,6-digalloylglucose), and sweetness (maltotriose). This study provided a comprehensive understanding of yellow tea on chemical composition and sensory quality.

Phytochemical investigation and antioxidant properties of unripe tomato cultivars (Solanum lycopersicum L.).

Unripe tomatoes are among the main waste produced during tomato cultivation and processing. In this study, unripe tomatoes from seven different Italian cultivars have been investigated to evaluate their nutraceutical potential. Phytochemical investigation allowed shedding light on the identification of seventy-five bioactive compounds. The highest amount of polyphenolic and glycoalkaloids along with the high level of antioxidant activities was found in the Datterini tomatoes variety. The peculiarity of this variety is the high chlorogenic acid content, being ten times higher compared to the other cultivars examined. Moreover, the total α-tomatine amount has been found substantially higher (34.699 ± 1.101 mg/g dry weight) with respect to the other tomato varieties analyzed. Furthermore, the cultivars metabolomic profiles were investigated with the PCA approach. Based on Datterini cultivar's metabolomic profile, its waste-recovery could represent a good option for further added value products in pharmaceutical and nutraceutical areas with a high α-tomatine content.

Unraveling the effects of low protein-phenol binding affinity on the structural properties of beta-lactoglobulin.

Non-covalent interactions of phenolics with proteins cannot always be readily identified, often leading to contradictory results described in the literature. This results in uncertainties as to what extent phenolics can be added to protein solutions (for example for bioactivity studies) without affecting the protein structure. Here, we clarify which tea phenolics (epigallocatechin gallate (EGCG), epicatechin and gallic acid) interact with the whey protein ß-lactoglobulin by combining various state-of-the-art-methods. STD-NMR revealed that all rings of EGCG can interact with native ß-lactoglobulin, indicating multidentate binding, as confirmed by the small angle X-ray scattering experiments. For epicatechin, unspecific interactions were found only at higher protein:epicatechin molar ratios and only with 1H NMR shift perturbation and FTIR. For gallic acid, none of the methods found evidence for an interaction with ß-lactoglobulin. Thus, gallic acid and epicatechin can be added to native BLG, for example as antioxidants without causing modification within wide concentration ranges.

Presence of free gallic acid and gallate moieties reduces auto-oxidative browning of epicatechin (EC) and epicatechin gallate (ECg).

Auto-oxidation of flavan-3-ols leads to browning and consequently loss of product quality during storage of ready-to-drink (RTD) green tea. The mechanisms and products of auto-oxidation of galloylated catechins, the major flavan-3-ols in green tea, are still largely unknown. Therefore, we investigated auto-oxidation of epicatechin gallate (ECg) in aqueous model systems. Oxidation products tentatively identified based on MS included δ- or γ-type dehydrodicatechins (DhC2s) as the main contributors to browning. Additionally, various colourless products were detected, including epicatechin (EC) and gallic acid (GA) from degalloylation, ether-linked ε-type DhC2s, and 6 new coupling products of ECg and GA possessing a lactone interflavanic linkage. Supported by density function theory (DFT) calculations, we provide a mechanistic explanation on how presence of gallate moieties (D-ring) and GA affect the reaction pathway. Overall, presence of gallate moieties and GA resulted in a different product profile and less intense auto-oxidative browning of ECg compared to EC.

Enzymatic browning: The role of substrates in polyphenol oxidase mediated browning.

Enzymatic browning is a biological process that can have significant consequences for fresh produce, such as quality reduction in fruit and vegetables. It is primarily initiated by polyphenol oxidase (PPO) (EC 1.14.18.1 and EC 1.10.3.1) which catalyses the oxidation of phenolic compounds. It is thought that subsequent non-enzymatic reactions result in these compounds polymerising into dark pigments called melanins. Most work to date has investigated the kinetics of PPO with anti-browning techniques focussed on inhibition of the enzyme. However, there is substantially less knowledge on how the subsequent non-enzymatic reactions contribute to enzymatic browning. This review considers the current knowledge and recent advances in non-enzymatic reactions occurring after phenolic oxidation, in particular the role of non-PPO substrates. Enzymatic browning reaction models are compared, and a generalised redox cycling mechanism is proposed. The review identifies future areas for mechanistic research which may inform the development of new anti-browning processes.

Effects of different maceration techniques on the colour, polyphenols and antioxidant capacity of grape juice.

This study investigated the effects of different maceration techniques on the colour parameters, phenolic content and antioxidant activity of grape juice. Maceration techniques influenced colour parameters, and a* and Hue ranged from -0.77 to 0.55 and 60.90 to 104.40, respectively. The microwave and microwave and sonication combination increased the total monomeric anthocyanin, phenolic and flavonoid contents. Malvidin 3-O-glucoside increased more than twofold, and delphinidin 3-O-glucoside and cyanidin 3-O-glucoside increased one fold according to the enzymatic method in the microwave treatments. The microwave technique was the most effective technique for antioxidant capacity, but sonication, cold and thermosonication results were lower than enzymatic treatment. The microwave and microwave and sonication enhanced the polyphenols with strong antioxidant power, such as catechin from 0.87 to 37.40 and trans-resveratrol from 0.09 to 0.23 mg/100 g, by comparison with the enzymatic technique. The findings suggested these two techniques were the most effective techniques for maceration.

Insights into the effects of extractable phenolic compounds and Maillard reaction products on the antioxidant activity of roasted wheat flours with different maturities.

Experiments were performed to determine the effect of roasting whole wheat flours at 80 °C, 100 °C and 120 °C for 30 min on four forms of phenolics, Maillard reaction products (MRPs), and the DPPH scavenging activity (DSA) at 15, 30 and 45 days after flowering (15-DAF, 30-DAF, and 45-DAF). Roasting increased the phenolic content and antioxidant activity of the wheat flours, which were the dominant contributions to the formation of Maillard reaction products. The highest total phenolic content (TPC) and total phenolic DSA (TDSA) were determined in the DAF-15 flours at 120 °C/30 min. The DAF-15 flours exhibited the highest browning index and fluorescence of free intermediate compounds and advanced MRPs, suggesting that a substantial quantity of MRPs were formed. Four forms of phenolic compounds were detected with significantly different DSAs in the roasted wheat flours. The insoluble-bound phenolic compounds exhibited the highest DSA, followed by the glycosylated phenolic compounds.

Combined use of vacuum impregnation and encapsulation technologies for phenolic enrichment of strawberries.

Plant-based phenolic extracts have gained significant attention in the food industry due to their antimicrobial and health-promoting effects. However, their usage is limited because of poor water solubility and instability during processing. Therefore, encapsulation of phenolics with a suitable carrier system is essential for overcoming these problems and increasing their application in food products. In this study, encapsulated phenolic extracts were used for the first time in vacuum impregnation (VI). For this purpose, different phenolic extracts (cinnamon, turmeric, pomegranate peel) were obtained from the plant source. PPE was selected because it has the highest total phenolic content, antioxidant capacity, and antimicrobial activity against Botrytis cinerea. Then, PPE was encapsulated with different emulsifiers (T80, GMO, IN, WPI, and LEC). After the characterization and stability studies were performed, PPE encapsulated with T80 was used to produce a functional strawberry snack by VI technology. The results showed that the diffusion rate of EPPE was significantly increased compared to the control and PPE-VI group. EPPE-enriched strawberries were the preferred snack with high-quality characteristics.