Alpinetin alleviates osteoporosis by promoting osteogenic differentiation in BMSCs by triggering autophagy via PKA/mTOR/ULK1 signaling.

Osteoporosis, a systemic bone disease that is characterized by a reduction in bone mass and destruction of bone microstructure, is becoming a serious problem worldwide. Bone marrow mesenchymal stem cells (BMSCs) can differentiate into bone-forming osteoblasts, and play an important role in maintaining homeostasis of bone metabolism, thus being a potential therapeutic target for osteoporosis. Although the phytochemical alpinetin (APT) has been reported to possess a variety of pharmacological activities, it is still unclear whether APT can influence the osteogenic differentiation of on BMSCs and if it can improve osteoporosis. In this study, we found that APT treatment was able to enhance osteogenic differentiation levels of human BMSCs in vitro and mouse ones in vivo as revealed by multiple osteogenic markers including increased alkaline phosphatase activity and osteocalcin expression. Mechanistically, the protein kinase A (PKA)/mTOR/ULK1 signaling was involved in the action of APT to enhance the osteogenic differentiation of BMSCs. In addition, oral administration of APT significantly mitigated the bone loss in a dexamethasone-induced mouse model of osteoporosis through strengthening PKA signaling and autophagy. Altogether, these data demonstrate that APT promotes osteogenic differentiation in BMSCs by augmenting the PKA/mTOR/ULK1 autophagy signaling, highlighting its potential therapeutic application for treating osteoporotic diseases.

Influence of tea polyphenol and bovine serum albumin on tea cream formation by multiple spectroscopy methods and molecular docking.

The sensory qualities and shelf life of tea beverage strongly affected by tea cream that forms by the interaction of polyphenols and protein. The study aimed to investigate the effects of the interactions between tea polyphenols (TPs) and bovine serum albumin (BSA) on tea cream formation at different concentrations. The tea cream formation increased with TPs and BSA concentration increased. The optimal concentration (TPs: 800 mg/L, BSA: 40 mg/L), for high clarities and contents of phytochemicals, was selected by the technique for order preference by similarity to ideal solution (C = 0.7572). The interaction mechanism of TPs-BSA was investigated by fluorescence spectroscopy, UV-visible absorption spectroscopy, synchronous fluorescence spectroscopy, and molecular docking. TPs interacted with BSA via static quenching process, affecting tryptophan and tyrosine residue microenvironment of BSA. Ester catechins had more binding affinity than non-ester catechins. Hydrogen bonds were the main interaction forces of TPs-BSA.

Camellia sinensis and Litsea coreana Ameliorate Intestinal Inflammation and Modulate Gut Microbiota in Dextran Sulfate Sodium-Induced Colitis Mice.

SCOPE: Polyphenol-enriched herbal extracts have been proved as alternative therapeutic strategies for experimentally induced colitis. The in vivo and in vitro anti-inflammatory effects of Camellia sinensis (green, white, yellow, oolong, black, and dark tea) and Litsea coreana (hawk tea) are comparatively explored. METHODS AND RESULTS: HPLC analysis confirms dissimilarities among phytochemical compositions of these teas. The tea extracts (TEs) significantly decrease the production of pro-inflammatory cytokines (IL-6, IL-12, and tumor necrosis factor-α) and increase the anti-inflammatory cytokines (IL-10) in LPS-stimulated RAW 264.7 macrophages and a dextran sodium sulfate (DSS)-induced colitis mouse model. The treatment of TEs in colitis mice can ameliorate colon inflammation, pro-oxidative enzyme activity, colon integrity, and suppress the activation of nuclear factor-κB. Of note, green TE significantly attenuates the DSS-induced decrease in richness and diversity of gut microbiota. Moreover, TEs are capable of exerting a prebiotic effect on gut microbiota by increasing the abundance of potentially beneficial bacteria (e.g., Faecalibaculum, and Bifidobacterium), and decreasing the abundance of potentially harmful bacteria (e.g., Bacteroids, and Mucispirillum). TEs restore the decreased production of SCFAs in the feces of colitic mice. CONCLUSION: The treatment of seven types of tea can alleviate DSS-induced colitis in mice, and modulate the dysbiosis of gut microbiota in colitis mice.

Discovery of Biased Mu-Opioid Receptor Agonists for the Treatment of Pain.

G protein-biased mu-opioid receptor (MOR) agonists have been developed as promising new potent analgesic drugs with fewer adverse side effects than standard MOR agonists. PZM21 represents a unique chemotype unrelated to known opioids, which makes it a desirable lead for modification to find analgesics with new chemical entities. In the present study, we synthesized and tested novel PZM21 derivatives as potent biased MOR agonists by introducing a benzodioxolane group to replace the hydroxybenzene of PZM21. The new compounds displayed more potent analgesic activities in vivo and greater bias toward G protein signaling in vitro than did PZM21. These results suggest that the benzodioxolane group is essential for the maintenance of bias. Compounds 7 i ((S)-1-(3-(benzo[d][1,3]dioxol-4-yl)-2-(dimethylamino)propyl)-3-phenethylurea) and 7 j ((S)-1-(3-(benzo[d][1,3]dioxol-4-yl)-2-(dimethylamino)propyl)-3-benzylurea) could serve as new leads for further modifications to find novel biased MOR agonists with greater G protein signaling potency and less ß-arrestin-2 recruitment.

Characterization of Volatile Compounds and Sensory Analysis of Jasmine Scented Black Tea Produced by Different Scenting Processes.

Jasmine scented black tea is widely popular in China and the scenting process is the most crucial issue affecting its aroma quality. This study aimed to analyze the influence of different processes on aroma quality and the specific contribution of volatiles to aroma quality. To achieve it, the headspace solid-phase microextraction method combined with gas-chromatography mass-spectrometry was used to identify and quantify the volatile compounds, and further collected the characteristics according to odor activity values or contents. The quantitative descriptive analysis (QDA) and traditional sensory analysis (TSA) were used to evaluate its aroma quality and the correlation analysis between QDA and characteristic aroma compounds was carry out to analyze the specific contribution of characteristics to sensory quality. The GC/MS results showed that 130 aroma components and 20 characteristics were identified in 6 tea samples and more new volatile components appeared and less original volatile components disappeared in traditional scenting process (TSP) compared with continuous scenting process (CSP). The QDA and TSA results showed that TSP samples had better "overall" and "jasmine" than CSP samples. The correlation analysis between QDA and characteristics showed that nerolidol and methylbenzoate were related to "overall," linalool and methyl anthranilate to "jasmine," and decanal and benzeneacetaldehyde to "sweet floral," "roasted," and "fermented." This study suggested that TSP is a favorable scenting process for black tea, and QDA is an objective and digital sensory evaluation method for jasmine scented black tea. PRACTICAL APPLICATION: Compare the effect of scenting technology on the aroma quality of jasmine scented black tea based on sensory analysis and chemical analysis, and suggested a favorable scenting process for processing jasmine scented black tea with better qualities. Explore the correlation between aroma composition and specific aroma properties to provide some useful information about guiding the scenting process to acquire a product with target aroma qualities. And the application of QDA for evaluation of jasmine scented black tea was better for consumers to understand the quality attributes of product.