Urolithin A promotes atherosclerotic plaque stability by limiting inflammation and hypercholesteremia in Apolipoprotein E-deficient mice.

Urolithin A (UroA), a dietary phytochemical, is produced by gut bacteria from fruits rich in natural polyphenols ellagitannins (ETs). The efficiency of ETs metabolism to UroA in humans depends on gut microbiota. UroA has shown a variety of pharmacological activities. In this study we investigated the effects of UroA on atherosclerotic lesion development and stability. Apolipoprotein E-deficient (ApoE-/-) mice were fed a high-fat and high-cholesterol diet for 3 months to establish atherosclerosis model. Meanwhile the mice were administered UroA (50 mg·kg-1·d-1, i.g.). We showed that UroA administration significantly decreased diet-induced atherosclerotic lesions in brachiocephalic arteries, macrophage content in plaques, expression of endothelial adhesion molecules, intraplaque hemorrhage and size of necrotic core, while increased the expression of smooth muscle actin and the thickness of fibrous cap, implying features of plaque stabilization. The underlying mechanisms were elucidated using TNF-α-stimulated human endothelial cells. Pretreatment with UroA (10, 25, 50 µM) dose-dependently inhibited TNF-α-induced endothelial cell activation and monocyte adhesion. However, the anti-inflammatory effects of UroA in TNF-α-stimulated human umbilical vein endothelial cells (HUVECs) were independent of NF-κB p65 pathway. We conducted RNA-sequencing profiling analysis to identify the differential expression of genes (DEGs) associated with vascular function, inflammatory responses, cell adhesion and thrombosis in UroA-pretreated HUVECs. Human disease enrichment analysis revealed that the DEGs were significantly correlated with cardiovascular diseases. We demonstrated that UroA pretreatment mitigated endothelial inflammation by promoting NO production and decreasing YAP/TAZ protein expression and TEAD transcriptional activity in TNF-α-stimulated HUVECs. On the other hand, we found that UroA administration modulated the transcription and cleavage of lipogenic transcription factors SREBP1/2 in the liver to ameliorate cholesterol metabolism in ApoE-/- mice. This study provides an experimental basis for new dietary therapeutic option to prevent atherosclerosis.

Ficus virens proanthocyanidins induced apoptosis in breast cancer cells concomitantly ameliorated 5-fluorouracil induced intestinal mucositis in rats.

5-Fluorouracil (5-FU) is a commonly used chemotherapeutic agent for breast cancer. However, its use often leads to drug resistance and mucositis. This study aimed to investigate whether proanthocyanidins from Ficus virens possessed anti-breast cancer and anti-mucositis activities. The results showed that the cytotoxic effects of the proanthocyanidins against MDA-MB-231 and MCF-7 breast cancer cells were in the order of stem barks proanthocyanidins (SPAs) > leaves proanthocyanidins > fruits proanthocyanidins. Moreover, SPAs induced apoptosis in both cell lines which were accompanied with an increase in loss of mitochondrial membrane potential, production of reactive oxygen species, Bax to Bcl-2 protein expression ratio, and activated caspase 3. Furthermore, intraperitoneal injection of 5-FU (150 mg/kg body weight) resulted in body weight loss and jejunal injury in the rats while administration of SPAs (100 mg/kg body weight) counteracted these changes. Collectively, our study demonstrated that SPAs induced apoptosis cell death in breast cancer cells while ameliorating the symptoms of intestinal mucositis in rats.Therefore, SPAs merits further exploration as a potential therapeutic agent for breast cancer and chemotherapy-induced mucositis.

Proanthocyanidins from Uncaria rhynchophylla induced apoptosis in MDA-MB-231 breast cancer cells while enhancing cytotoxic effects of 5-fluorouracil.

Breast cancer is the most frequently diagnosed cancer and cause of cancer death in women worldwide. Current treatments often result in systematic toxicity and drug resistance. Combinational use of non-toxic phytochemicals with chemotherapeutic agents to enhance the efficacy and reduce toxicity would be one promising approach. In this study, bioactive proanthocyanidins from Uncaria rhynchophylla (UPAs) were isolated and their anti-breast cancer effects alone and in combination with 5- fluorouracil (5-FU) were investigated in MDA-MB-231 breast cancer cells. The results showed that UPAs significantly inhibited cell viability and migration ability in a dose-dependent manner. Moreover, UPAs induced apoptosis in a dose-dependent manner which was associated with increased cellular reactive oxygen species production, loss of mitochondrial membrane potential, increases of Bax/Bcl-2 ratio and levels of cleaved caspase 3. Treatments of the cells with UPAs resulted in an increase in G2/M cell cycle arrest. Cytotoxic effects of 5-FU against MDA-MB-231 cells were enhanced by UPAs. The combination treatment of UPAs and 5-FU for 48 h elicited a synergistic cytotoxic effect on MDA-MB-231 cells. Altogether, these data suggest that UPAs are potential therapeutic agents for breast cancer.

A review on the structure-function relationship aspect of polysaccharides from tea materials.

Tea (Camellia sinensis) has a long history of medicinal use in the world. The chemical components of tea mainly consist of polyphenols (TPP), proteins, polysaccharides (TPS), chlorophyll, alkaloids, and so on. Great advances have been made in chemical and bioactive studies of catechins and TPP from tea in recent decades. However, the TPS from tea materials have received much less consideration than that of TPP. The number of relevant publications on the TPS from tea leaves and flowers has increased rapidly in recent years. This mini-review summarizes the structure-function relationship of TPS from tea leaves and flowers. The application of purified TPS from tea material as functional or nutritional foods was still little. It will help to develop the function foods with tea TPS and better understand the structure-bioactivity relationship of tea TPS.

Noncovalent interaction of dietary polyphenols with bovine hemoglobin in vitro: molecular structure/property-affinity relationship aspects.

The relationship between the structural properties of selected dietary polyphenols and their affinities for bovine hemoglobin (bHB) was investigated by fluorescence analysis. The presence of an additional methoxy group on flavonoids weakened the affinities for bHB by 1.15-13.80 times. Hydroxylation on rings A, B, and C also significantly affected the affinity for bHB. The glycosylation of flavonoids decreased the affinities for bHB by 1 order of magnitude depending on the conjugation site and the class of sugar moiety. Hydrogenation of the C2═C3 double bond also decreased the binding affinity. The galloylated catechins exhibited higher binding affinities for bHB than nongalloylated. The glycosylation of resveratrol increased its affinity for bHB. The binding process with bHB was strongly influenced by the structural differences of dietary polyphenols. The affinities for bHB increased with increasing partition coefficients and decreased with increasing hydrogen bond donor and acceptor numbers of polyphenols, which suggested that the binding interaction was mainly caused by the hydrophobic force.

Which model based on fluorescence quenching is suitable to study the interaction between trans-resveratrol and BSA?

There are several models by means of quenching fluorescence of BSA to determine the binding parameters. The binding parameters obtained from different models are quite different from each other. Which model is suitable to study the interaction between trans-resveratrol and BSA? Herein, twelve models based fluorescence quenching of BSA were compared. The number of binding sites increasing with increased binding constant for similar compounds binding to BSA maybe one approach to resolve this question. For example, here eleven flavonoids were tested to illustrate that the double logarithm regression curve is suitable to study binding polyphenols to BSA.

Supercritical fluid CO2 extraction of essential oil from Marchantia convoluta: global yields and extract chemical composition

The essential oil of Marchantia convoluta was obtained by supercritical (carbon dioxide) extraction using methanol as a modifier. Global yields were determined according to the orthogonal design. The effects of different parameters, such as pressure, temperature, modifier volume and extraction time, on the supercritical fluid extraction (SFE) of essential oil from M. convoluta were investigated. Maximum global yields were obtained using the following conditions: extraction temperature, 35°C; dynamic time, 35 min; pressure, 15 Mpa and modifier volume, 40 mL. The essential oil extract was analyzed by capillary gas chromatography with mass spectrometric detector (GC-MS). The compounds were identified according to their retention indices and mass spectra (EI, 70 eV). The results from GC-MS and literature were compared.

Induction of apoptosis and transient increase of phosphorylated MAPKs by diallyl disulfide treatment in human nasopharyngeal carcinoma CNE2 cells.

This study was undertaken to elucidate the effect of diallyl disulfide (DADS), an oil-soluble organosulfur compound found in garlic, in suppressing human nasopharyngeal carcinoma cells. A potent increase (of at least 9-fold) in apoptotic cells has accompanied 1) a decrease in cell viability, 2) a increase of the fraction of S-phase cells by up to 63.8%, and 3) a transient increase of the phospho-p38 and phospho-p42/44 (phosphorylated p38 MAPK and phosphorylated p42/44 MAPK) in a time- and concentration-dependent manner. These results indicate that DADS can induce apoptosis in human nasopharyngeal carcinoma cells via, at least partly, S-phase block of the cell cycle, related to a rise in MAPK phosphorylation.