Coffee or tea: Anti-inflammatory properties in the context of atherosclerotic cardiovascular disease prevention.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of premature death worldwide. Inflammation and its biomarkers, like C-reactive protein (CRP), among the risk factors, such as hypertension, lipid disorders, and diabetes, may be also responsible for the residual cardiovascular disease (CVD) risk. Modern lipid-lowering treatment with statins, ezetimibe, PCSK9 inhibitors, or bempedoic acid does not fully protect against inflammation. The recommendations of the International Lipid Expert Panel (ILEP) indicate selected nutraceuticals with anti-inflammatory properties. Diet may have a significant impact on inflammation. Especially interesting in the context of inflammation is the consumption of coffee and tea. These drinks in many observational studies significantly reduced cardiovascular risk and mortality. The question is whether the anti-inflammatory effects of these drinks contribute significantly to the observed clinical effects. Thus, in this narrative review, we primarily discuss the anti-inflammatory properties of consuming tea and coffee. Based on a comprehensive analysis of the studies and their meta-analyses, inconsistent results were obtained, which makes it impossible to conclusively state how clinically significant the potential anti-inflammatory properties of black and green tea and coffee are. A number of confounding factors can cause the inconsistency of the available results. Consumption of tea and coffee appears to increase adiponectin concentrations, decrease reactive oxygen species, decrease low density lipoprotein (LDL) cholesterol concentrations (effect of green tea, etc.). Despite the still uncertain anti-inflammatory effect of tea and coffee, we recommend their consumption as a part of the healthy diet.

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.

Gut microbiota, a new frontier to understand traditional Chinese medicines.

As an important component of complementary and alternative medicines, traditional Chinese medicines (TCM) are gaining more and more attentions around the world because of the powerful therapeutic effects and less side effects. However, there are still some doubts about TCM because of the questionable TCM theories and unclear biological active compounds. In recent years, gut microbiota has emerged as an important frontier to understand the development and progress of diseases. Together with this trend, an increasing number of studies have indicated that drug molecules can interact with gut microbiota after oral administration. In this context, more and more studies pertaining to TCM have paid attention to gut microbiota and have yield rich information for understanding TCM. After oral administration, TCM can interact with gut microbiota: (1) TCM can modulate the composition of gut microbiota; (2) TCM can modulate the metabolism of gut microbiota; (3) gut microbiota can transform TCM compounds. During the interactions, two types of metabolites can be produced: gut microbiota metabolites (of food and host origin) and gut microbiota transformed TCM compounds. In this review, we summarized the interactions between TCM and gut microbiota, and the pharmacological effects and features of metabolites produced during interactions between TCM and gut microbiota. Then, focusing on gut microbiota and metabolites, we summarized the aspects in which gut microbiota has facilitated our understanding of TCM. At the end of this review, the outlooks for further research of TCM and gut microbiota were also discussed.

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.

Targeting activator protein 1 signaling pathway by bioactive natural agents: Possible therapeutic strategy for cancer prevention and intervention.

Activator protein 1 (AP-1) is a key transcription factor in the control of several cellular processes responsible for cell survival proliferation and differentiation. Dysfunctional AP-1 expression and activity are involved in several severe diseases, especially inflammatory disorders and cancer. Therefore, targeting AP-1 has recently emerged as an attractive therapeutic strategy for cancer prevention and therapy. This review summarizes our current understanding of AP-1 biology and function as well as explores and discusses several natural bioactive compounds modulating AP-1-associated signaling pathways for cancer prevention and intervention. Current limitations, challenges, and future directions of research are also critically discussed.

Targeting oncogenic transcription factors by polyphenols: A novel approach for cancer therapy.

Inflammation is one of the major causative factor of cancer and chronic inflammation is involved in all the major steps of cancer initiation, progression metastasis and drug resistance. The molecular mechanism of inflammation driven cancer is the complex interplay between oncogenic and tumor suppressive transcription factors which include FOXM1, NF-kB, STAT3, Wnt/ß- Catenin, HIF-1α, NRF2, androgen and estrogen receptors. Several products derived from natural sources modulate the expression and activity of multiple transcription factors in various tumor models as evident from studies conducted in cell lines, pre-clinical models and clinical samples. Further combination of these natural products along with currently approved cancer therapies added an additional advantage and they considered as promising targets for prevention and treatment of inflammation and cancer. In this review we discuss the application of multi-targeting natural products by analyzing the literature and future directions for their plausible applications in drug discovery.

Characteristics of oleuropeinolytic strains of Lactobacillus plantarum group and influence on phenolic compounds in table olives elaborated under reduced salt conditions.

The technological characteristics of five oleuropeinolytic strains of the Lactobacillus plantarum group selected within 135 isolates from table olives were investigated. The metabolism of phenolic compounds during elaboration of green (cv. Chalkidikis) and black (cv. Kalamata) olives under reduced salt conditions was evaluated. Olives of both cultivars were fermented in two different kinds of brine (Brine A containing 2.3% NaCl, 32.3 mM Ca-acetate and 33.9 mM Ca-lactate and Brine B containing 4% NaCl, pH 5.0 in both brines) by five selected strains of L. plantarum group. After 60 days of fermentation, the analysis of phenolic compounds was performed by HPLC and nine compounds were identified and quantified: oleuropein, hydroxytyrosol, tyrosol and vanillin and the phenolic acids protocatechuic, caffeic, p-hydroxybenzoic, vanillic and p-coumaric acid. The study can lead to the development of starter culture potentially active in biological debittering of olives during fermentation in order to unify the debittering and fermentation process during elaboration of table olives.

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.

The profiles of free, esterified and insoluble-bound phenolics in peach juice after high pressure homogenization and evaluation of their antioxidant capacities, cytoprotective effect, and inhibitory effects on α-glucosidase and dipeptidyl peptidase-â £.

The phenolic profiles, antioxidant capacities, cytoprotective effect, and α-glucosidase and DPP-IV inhibitory capacity of free (FP), esterified (EP) and insoluble-bound (IBP) phenolic fractions in 'Lijiang snow' peach juice after high pressure homogenization (HPH) were investigated, and the molecular docking was used to explore the enzyme inhibition mechanism. HPH increased total phenolic and total flavonoid contents in three fractions without changing compositions. The IC50 of radicals scavenged by three fractions were all reduced by HPH. The best inhibition on intracellular ROS production were found for phenolic fractions after HPH at 300 MPa, with ROS levels ranged within 95.26-119.16 %. HPH at 300 MPa reduced the apoptosis rates of FP and EP by 16.52 % and 9.33 %, respectively. All phenolic fractions showed effective inhibition on α-glucosidase and DPP-IV by formation of hydrogen bonding and van der Waals forces. This study explored the feasibility of HPH to enhance the phenolics and bioactivity of peach juice.

Removal of polyphenols from anthocyanin-rich extracts using 4-vinylpyridine crosslinked copolymers.

In this work, new sorbents for the purification of anthocyanin-rich extracts were evaluated. Copolymers of 4-vinylpyridine crosslinked with trimethylolpropane trimethacrylate (poly(4VP-co-TRIM)) or 1,4-dimethacryloyloxybenzene (poly(4VP-co-14DMB)) were tested for their potential to capture polyphenols. Copolymers were obtained by seed swelling polymerization in the form of microspheres with permanent porous structure - attractive features of sorbents used for sample purification by dispersive solid phase extraction. The microspheres were characterized by AFM, elemental analysis, SEM, and nitrogen adsorption-desorption method. Their capacity to remove polyphenols was evaluated using spectrophotometry, HPLC-DAD, and LC-MS/MS. For proof-of-concept, the aqueous extracts of berries classified into three different groups regarding their anthocyanin composition (strawberries, raspberries, blackcurrants) were selected. It was found that studied microspheres adsorbed flavonoids more effectively compared to primary secondary amine and graphitized carbon black. Copolymers of 4-vinylpyridine also capture anthocyanins and might be used for the purification of extracts of fruits before LC-MS/MS analysis to reduce the matrix effect.

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.

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.

Membrane permeabilizers enhance biofortification of Brassica microgreens by interspecific transfer of metabolites from tea (Camellia sinensis).

Interspecific metabolite transfer (ISMT) is a novel approach for plants biofortification. In this study, the effect of tea (Camellia sinensis; Cs), with or without membrane permeabilizers EDTA and Tween, as a donor plant on broccoli, cauliflower and kale sprouts was investigated. As a result, caffeine- and catechin-enriched broccoli, cauliflower and kale microgreens were produced. Kale sprouts were most permeable for catechins from Cs, while cauliflower was most permeable for caffeine. Cs + EDTA significantly increased vitamin C in broccoli and kale. Among the tested enzymes activity, pancreatic lipase was the most affected by the treatment with broccoli and cauliflower biofortified with Cs or Cs combined with permeabilizers. Broccoli sprouts biofortified with Cs most significantly inhibited α-amylase, while those biofortified with Cs combined with permeabilizers most significantly inhibited α-glucosidase. Results point to ISMT combined with membrane permeabilizers as a promising and eco-friendly biofortification strategy to improve the biopotential of Brassica microgreens.

Effect of ultra-high pressure pretreatment on the phenolic profiles, antioxidative activity and cytoprotective capacity of different phenolic fractions from Que Zui tea.

This study aims to explore whether ultra-high pressure (UHP) pre-treatment strengthened the bioaccessibility and bioactivities of the free (QF), esterified (QE) and insoluble-bound phenolics (QIB) from Que Zui tea (QT). The results revealed that the extraction yields, the total phenolic (TPC) and total flavonoid contents (TFC) of three phenolic fractions from QT were markedly increased after ultra-high pressure (UHP) processing (p < 0.05). A total of 19 and 20 compounds were characterized and quantified in non- and UHP-treated QT, respectively, including the content of 6'-O-caffeoylarbutin (11775.68 and 13248.87 µg/g of dry extract) was highest in QF, the content of caffeic acid was highest in QE (2131.58 and 7362.99 µg/g of dry extract) and QIB (9151.89 and 10930.82 µg/g of dry extract). QF, QE and QIB from QT after UHP processing had better antioxidant, ROS scavenging, and anti-apoptosis effects. The possible mechanism of cytoprotective effect was related to Keap1-Nrf2 pathway.

Boosting the antioxidant potential of pasta by a premature stop mutation in wheat keto-acythiolase-2.

Phenolics are a class of chemical compounds possessing antioxidant activity, which are mainly located in the wheat (Triticum aestivum) bran. Different approaches have been used in food industry to increase the availability of phenolics. Compared to these methods, however, genetic improvement of the wheat antioxidant potential, is a cost-effective, easier and safer approach. Here, we showed a single premature stop mutation in the keto-acythiolase-2 (kat-2b) gene, which significantly improved the antioxidant potential of pasta by a 60 ± 16% increase in its antioxidant potential by increasing the accumulation of ferulic acid. These changes are likely determined by the increased transcription (46% higher) and activity (120% higher) of the phenylalanine lyase genes observed in the mutated line compared to the control. Even if more studies will need to be done, overall, this study suggested that the kat-2b mutant could represent an excellent genetic resource to improve wheat's antioxidant and health-promoting potential.

Major anthocyanins in elderberry effectively trap methylglyoxal and reduce cytotoxicity of methylglyoxal in HepG2 cell line.

The accumulation of advanced glycation end-products (AGEs) in the body is implicated in numerous diseases, being methylglyoxal (MGO) one of the main precursors. One of the strategies to reduce AGEs accumulation might be acting in an early stage of glycation by trapping MGO. Thus, this work aimed to evaluate, for the first time, the potential of elderberries polyphenols to trap MGO, access the formation of MGO adducts, and evaluate the cytoprotection effect in HepG2 and Caco-2 cells. The results demonstrated that monoglycosylated anthocyanins (cyanidin-3-glucoside and cyanidin-3-sambubioside) are very efficient in trapping MGO, forming mono- and di-adducts. Quercetin-3-glucoside and quercetin-3-rutinoside reacted slowly, while diglycosylated anthocyanins did not react. The trapping of MGO by elderberry monoglycosylated anthocyanins significantly decreased the MGO cytotoxicity in HepG2 cells (∼70 % of cell viability), while the effect in Caco-2 cells was lower (∼50 %). Thus, elderberry phenolics present antiglycation potential by trapping MGO.

Comparative effectiveness of phlegm-heat clearing Chinese medicine injections for AECOPD: A systematic review and network meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Qingkailing (QKL), Reduning (RDN), Xiyanping (XYP), Tanreqing (TRQ) and Yuxingcao (YXC) injections are all phlegm-heat clearing Chinese medicine (CM) injections composed of the extract from traditional CM materials. Evidence from clinical studies and animal experiments indicates that the above CM injections are effective supplementary therapy for acute exacerbation chronic obstructive pulmonary disease (AECOPD), and clinicians are faced with a difficult choice on the optimal phlegm-heat clearing CM injection for AECOPD. AIM OF THE STUDY: This systematic review and Bayesian network meta-analysis aimed to evaluate the comparative effectiveness of five commonly used phlegm-heat clearing CM injections for COPD. MATERIALS AND METHODS: A pairwise and network meta-analyses were performed to assess the effectiveness of QKL, RDN, TRQ, XYP and YXC on AECOPD. Randomized controlled trials (RCTs) were identified by searching English and Chinese databases. The primary outcome was lung function (forced expiration volume [FEV1] and forced vital capacity [FVC]), blood gas analysis index was secondary outcome measure. Winbugs and Stata 15.0 software were used for data analysis. RESULTS: A total of 57 RCTs were included. The pairwise analyses showed that each of the injections combined with routine treatment were superior to routine treatment alone [FEV1: QKL, MD 0.20, 95% CI (0.06, 0.35); RDN, MD 0.24, 95% CI (0.08, 0.40); TRQ, MD 0.24, 95% CI (0.19, 0.29); XYP, MD 0.26, 95% CI (0.20, 0.32); YXC MD 0.73, 95% CI (0.06, 1.41)]. The network meta-analysis provided the following rank of lung function improvement: FEV1: YXC > TRQ > XYP > RDN > QKL; FVC: YXC > TRQ > QKL > RDN > XYP. RDN and YXC ranked highest in blood gas analysis index. RDN was the highest ranked injection for effectiveness, followed by QKL, TRQ, XYP, then YXC. Most of the injections appeared safe, with severe adverse events rarely reported. CONCLUSION: This study suggests that YXC and TRQ are the most effective therapies in treating AECOPD patients. RDN and YXC are more effective in the alleviation of clinical symptoms. Given that the safety of YXC is controversial, TRQ and RDN may be preferable as phlegm-heat clearing CM injections in the adjuvant treatment of AECOPD.

Functionalization of sweet potato leaf polyphenols by nanostructured composite ß-lactoglobulin particles from molecular level complexations: A review.

Sweet potato leaf polyphenols (SPLPs) have shown potential health benefits in the food and pharmaceutical industries. Nowadays, consumption of SPLPs from animal feeds to foodstuff is becoming a trend worldwide. However, the application of SPLPs is limited by their low bioavailability and stability. ß-lactoglobulin (ßlg), a highly regarded whey protein, can interact with SPLPs at the molecular level to form reversible or irreversible nanocomplexes (NCs). Consequently, the functional properties and final quality of SPLPs are directly modified. In this review, the composition and structure of SPLPs and ßlg, as well as methods of molecular complexation and mechanisms of formation of SPLPsßlgNCs, are revisited. The modified functionalities of SPLPsßlgNCs, especially protein conformational structures, antioxidant activity, solubility, thermal stability, emulsifying, and gelling properties including allergenic potential, digestibility, and practical applications are discussed for SPLPs future development.

Inhibition of the SARS-CoV-2 3CLpro main protease by plant polyphenols.

The abundance of polyphenols in edible plants makes them an important component of human nutrition. Considering the ongoing COVID-19 pandemic, a number of studies have investigated polyphenols as bioactive constituents. We applied in-silico molecular docking as well as molecular dynamics supported by in-vitro assays to determine the inhibitory potential of various plant polyphenols against an important SARS-CoV-2 therapeutic target, the protease 3CLpro. Of the polyphenols in initial in-vitro screening, quercetin, ellagic acid, curcumin, epigallocatechin gallate and resveratrol showed IC50 values of 11.8 µM to 23.4 µM. In-silico molecular dynamics simulations indicated stable interactions with the 3CLpro active site over 100 ns production runs. Moreover, surface plasmon resonance spectroscopy was used to measure the binding of polyphenols to 3CLpro in real time. Therefore, we provide evidence for inhibition of SARS-CoV-2 3CLpro by natural plant polyphenols, and suggest further research into the development of these novel 3CLpro inhibitors or biochemical probes.

Phoenix dactylifera L. date tree pollen fertility effects on female rats in relation to its UPLC-MS profile via a biochemometric approach.

Date palm (Phoenix dactylifera L.) is among the most ancient cultivated crops, of special value owing to its fruits high nutritive and economic benefits. Asides, date palm pollen is a high energy material that has been used traditionally used for fertility enhancement. In this study, effects of date palm pollen crude extract and its fractions viz., petroleum ether, methylene chloride, ethyl acetate and n-butanol on the female reproductive system were evaluated for the first time in relation to its metabolite fingerprint. Fertility activity was evaluated in immature female rats by assessing their FSH-, LH- and estrogen- activities. To pinpoint active hormonal agents in crude pollen extract and fractions, UPLC- MS analysis was employed for metabolites profiling, and in correlation to extract/fraction bioassays using multivariate OPLS analysis. Results revealed that both polar n-butanol and non-polar petroleum ether fractions exhibited the strongest activities; with a significant increase in FSH (25.7 mIU/ml in n-butanol group), estradiol (414.7 pg/ml in petroleum ether group) and progesterone levels (122.4 pg/ml in n-butanol group). Correlation between UPLC-MS and fraction bioassays was attempted using multivariate OPLS analysis to reveal for bioactive hits in these fractions. This study provides the first report on the fertility effect of date palm pollen in female rats and in relation to its metabolite fingerprint.