Microbial-Transferred Metabolites and Improvement of Biological Activities of Green Tea Catechins by Human Gut Microbiota.

Green tea catechins (GTCs) are dietary polyphenols with broad bioactivities that undergo extensive microbial metabolism in the human gut. However, microbial-transferred metabolites and their health benefits are not fully understood. Herein, the microbial metabolism of GTCs by human fecal microbiota and dynamic alteration of the microbiota were integrally investigated via in vitro anaerobic fermentation. The results showed that the human gut microbiota exhibited a strong metabolic effect on GTCs via UHPLC-MS/MS analysis. A total of 35 microbial-transferred metabolites were identified, far more than were identified in previous studies. Among them, five metabolites, namely EGCG quinone, EGC quinone, ECG quinone, EC quinone, and mono-oxygenated EGCG, were identified for the first time in fermented GTCs with the human gut microbiota. Consequently, corresponding metabolic pathways were proposed. Notably, the antioxidant, α-amylase, and α-glucosidase inhibitory activities of the GTCs sample increased after fermentation compared to those of the initial unfermented sample. The results of the 16S rRNA gene sequence analysis showed that the GTCs significantly altered gut microbial diversity and enriched the abundancy of Eubacterium, Flavonifractor, etc., which may be further involved in the metabolisms of GTCs. Thus, these findings contribute to a better understanding of the interactions between GTCs and gut microbiota, as well as the health benefits of green tea consumption.

Microbial-Transferred Metabolites of Black Tea Theaflavins by Human Gut Microbiota and Their Impact on Antioxidant Capacity.

Theaflavins (TFs), the primary bioactive components in black tea, are poorly absorbed in the small intestine. However, the biological activity of TFs does not match their low bioavailability, which suggests that the gut microbiota plays a crucial role in their biotransformation and activities. In this study, we aimed to investigate the biotransferred metabolites of TFs produced by the human gut microbiota and these metabolites' function. We profiled the microbial metabolites of TFs by in vitro anaerobic human gut microbiota fermentation using liquid chromatography tandem mass spectrometry (LC-MS/MS) methods. A total of 17 microbial metabolites were identified, and their corresponding metabolic pathways were proposed. Moreover, full-length 16S rRNA gene sequence analysis revealed that the TFs altered the gut microbiota diversity and increased the relative abundance of specific members of the microbiota involved in the catabolism of the TFs, including Flavonifractor_plautii, Bacteroides_uniformis, Eubacterium_ramulus, etc. Notably, the antioxidant capacity of the TF sample increased after fermentation compared to the initial sample. In conclusion, the results contribute to a more comprehensive understanding of the microbial metabolites and antioxidant capacity of TFs.

The active compounds derived from Psoralea corylifolia for photochemotherapy against psoriasis-like lesions: The relationship between structure and percutaneous absorption.

8­Methoxypsoralen (8-MOP) in combination with ultraviolet A (PUVA) is a photochemotherapy for management of psoriasis. 8-MOP is a natural compound from Psoralea corylifolia. The present work was undertaken to evaluate the percutaneous absorption of five compounds derived from P. corylifolia, and to further explore the inhibitory effect on psoriasis-like lesions generated by imiquimod stimulation in a mouse model. 8-MOP, psoralen, isopsoralen, psoralidin, and bakuchiol were comparatively tested for in vitro skin permeation, keratinocyte apoptosis, and in vivo antipsoriatic potency. The pig ear skin deposition of 8-MOP, isopsoralen, and bakuchiol at an equimolar dose was 0.47, 0.58, and 0.50 nmol/mg, respectively, which was comparable and higher than that of psoralen (0.25 nmol/mg) and psoralidin (0.14 nmol/mg). Psoralidin and bakuchiol were absorbed into the skin without further penetration across the skin. Besides experimental data of physicochemical properties, the hydrogen bond number, total polarity surface, and stratum corneum lipid docking calculated could explain the correlation of the penetrant structure with the skin permeability. The antiproliferative activity against keratinocytes was stronger for 8-MOP and isopsoralen than the others. Topical application of PUVA by using 8-MOP and isopsoralen on imiquimod-induced plaque significantly reduced transepidermal water loss from 55 to 33 and 38 g/m2/h, respectively. The epidermal thickening elicited by imiquimod (117 µm) was decreased to 62 and 26 µm by 8-MOP and isopsoralen application. IL-6 expression in psoriasiform skin was downregulated by isopsoralen but not 8-MOP. Isopsoralen may be a potential candidate for PUVA therapy.

Intravenous anti-MRSA phosphatiosomes mediate enhanced affinity to pulmonary surfactants for effective treatment of infectious pneumonia.

The aim of this study was to develop PEGylated phosphatidylcholine (PC)-rich nanovesicles (phosphatiosomes) carrying ciprofloxacin (CIPX) for lung targeting to eradicate extracellular and intracellular methicillin-resistant Staphylococcus aureus (MRSA). Soyaethyl morphonium ethosulfate (SME) was intercalated in the nanovesicle surface with the dual goals of achieving strengthened bactericidal activity of CIPX-loaded phosphatiosomes and delivery to the lungs. The isothermal titration calorimetry (ITC) results proved the strong association of SME phosphatiosomes with pulmonary surfactant. We demonstrated a superior anti-MRSA activity of SME phosphatiosomes compared to plain phosphatiosomes and to free CIPX. A synergistic effect of CIPX and SME nanocarriers was found in the biofilm eradication. SME phosphatiosomes were readily engulfed by the macrophages, restricting the intracellular MRSA count by 1-2 log units. SME phosphatiosomes efficiently accumulated in the lungs after intravenous injection. In a rat model of lung infection, the MRSA burden in the lungs could be decreased by 8-fold after SME nanosystem application.

Passive targeting of thermosensitive diblock copolymer micelles to the lungs: synthesis and characterization of poly(N-isopropylacrylamide)-block-poly(ε-caprolactone).

BACKGROUND: Amphiphilic poly(N-isopropylacrylamide)-block-poly(ε-caprolactone) (PNiPAAm-b-PCL) copolymers were synthesized by ring-opening polymerization to form thermosensitive micelles as nanocarriers for bioimaging and carboplatin delivery. RESULTS: The critical micelle concentration increased from 1.8 to 3.5 mg/l following the decrease of the PNiPAAm chain length. The copolymers revealed a lower critical solution temperature (LCST) between 33 and 40°C. The copolymers self-assembled to form spherical particles of 146-199 nm in diameter. Carboplatin in micelles exhibited a slower release at 37°C relative to that at 25°C due to the gel layer formation on the micellar shell above the LCST. The micelles containing dye or carboplatin were intravenously injected into the rats for in vivo bioimaging and drug biodistribution. The bioimaging profiles showed a significant accumulation of micelles in the lungs. The micelles could minimize the reticuloendothelial system (RES) recognition of the dye. In vivo biodistribution demonstrated an improved pulmonary accumulation of carboplatin from 2.5 to 3.4 µg/mg by the micelles as compared to the control solution. Carboplatin accumulation in the heart and kidneys was reduced after encapsulation by the micelles. CONCLUSION: This study supports the potential of PNiPAAm-b-PCL micelles to passively target the lungs and attenuate RES uptake and possible side effects.