Screening of Key Components for Melanogenesis Inhibition of Polygonum cuspidatum Extract Based on the Spectrum-Effect Relationship and Molecular Docking.

Polygonum cuspidatum (PC) extract has been listed in the "Catalog of Used Cosmetic Ingredients (2021 Edition)", which can inhibit melanogenesis, thus exerting a whitening effect, and has been widely used in cosmetics. However, there are currently no quality standards for PC extract used in cosmetics, and the bioactive components associated with anti-melanogenesis remain unclear. In view of this, the present study was the first to investigate the spectrum-effect relationship between fingerprints of PC extract and melanogenesis inhibition. Ten batches of PC extract fingerprints were established by HPLC. Pearson's correlation analysis, gray correlation analysis (GRA) and orthogonal partial least squares regression analysis (OPLSR) were used to screen out resveratrol, emodin and physcion as the main whitening active ingredients using the inhibition of tyrosinase in B16F10 cells as the pharmacological index. Then, the melanogenesis inhibitory effects of the above three components were verified by tyrosinase inhibition and a melanin content assay in B16F10 cells. The interaction between small molecules and proteins was investigated by the molecular docking method, and it was confirmed by quantitative real-time PCR (qRT-PCR) that resveratrol, emodin and physcion significantly down-regulated the transcript levels of melanogenesis-related factors. In conclusion, this study established a general model combining HPLC fingerprinting and melanogenesis inhibition and also analyzed the spectrum-effect relationship of PC extract, which provided theoretical support for the quality control of PC extract in whitening cosmetics.

Chemotherapy-induced phlebitis via the GBP5/NLRP3 inflammasome axis and the therapeutic effect of aescin.

BACKGROUND AND PURPOSE: Intravenous infusion of chemotherapy drugs can cause severe chemotherapy-induced phlebitis (CIP) in patients. However, the underlying mechanism of CIP development remains unclear. EXPERIMENTAL APPROACH: RNA-sequencing analysis was used to identify potential disease targets in CIP. Guanylate binding protein-5 (GBP5) genetic deletion approaches also were used to investigate the role of GBP5 in NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in lipopolysaccharide (LPS) primed murine bone-marrow-derived macrophages (BMDMs) induced by vinorelbine (VIN) in vitro and in mouse models of VIN-induced CIP in vivo. The anti-CIP effect of aescin was evaluated, both in vivo and in vivo. KEY RESULTS: Here, we show that the expression of GBP5 was upregulated in human peripheral blood mononuclear cells from CIP patients. Genetic ablation of GBP5 in murine macrophages significantly alleviated VIN-induced CIP in the experimental mouse model. Mechanistically, GBP5 contributed to the inflammatory responses through activating NLRP3 inflammasome and driving the production of the inflammatory cytokine IL-1ß. Moreover, aescin, a mixture of triterpene saponins extracted from horse chestnut seed, can alleviate CIP by inhibiting the GBP5/NLRP3 axis. CONCLUSION AND IMPLICATIONS: These findings suggest that GBP5 is an important regulator of NLRP3 inflammasome in CIP mouse model. Our work further reveals that aescin may serve as a promising candidate in the clinical treatment of CIP.

The Chromosome-level genome of Aesculus wilsonii provides new insights into terpenoid biosynthesis and Aesculus evolution.

Aesculus L. (buckeye and horse chestnut) are woody plant species with important horticultural and medicinal values. Aesculus seeds are widely used as biomedicine and cosmetic ingredients due to their saponins. We report a chromosomal-scale genome of Aesculus wilsonii. Sequences amounting to a total of 579.01 Mb were assembled into 20 chromosomes. More than half of the genome (54.46%) were annotated as repetitive sequences, and 46,914 protein-coding genes were predicted. In addition to the widespread gamma event with core eudicots, a unique whole-genome duplication (WGD) event (17.69 Mya) occurred in Aesculus after buckeye differentiated from longan. Due to WGD events and tandem duplications, the related synthetic genes of triterpene saponins unique to Aesculus increased significantly. Combined with transcriptome characterization, the study preliminarily resolved the biosynthetic pathway of triterpenoid saponins like aescin in A. wilsonii genome. Analyses of the resequencing of 104 buckeye accessions revealed clear relationship between the geographic distribution and genetic differentiation of buckeye trees in China. We found that the buckeye species found in southern Shaanxi is A. wilsonii rather than A. chinensis. Population dynamics analysis further suggests that the population size and evolution of existing buckeye species have been influenced by climate fluctuations during the Pleistocene and recent domestication events. The genome of A. wilsonii and population genomics of Aesculus provide a resource for future research on Hippocastanaceae. These findings will contribute to the utilization and diversity protection of Aesculus.

Sodium aescinate and its bioactive components induce degranulation via oxidative stress in RBL-2H3 mast cells.

Sodium aescinate (SA) is a vital salt of sodium escin from Aesculus wilsonii Rehd seeds. SA injection (SAI) has received great success in treating cerebral edema, venous reflux disease and other inflammatory conditions. Recently, high incidences of immediate hypersensitivity reactions were reported after SA infusion, which raised questions on safety and risk associated with its clinical application. This study was designed to check whether SAI and its four components induce degranulation using RBL-2H3 mast cells. For this purpose, we evaluated different treatment levels of SAI (20, 40, 60, 80 and 100 µg ml-1) and its four characteristic components, SA-A, SA-B, SA-C and SA-D, at 60 µg ml-1 in different tests including cell viability test, ß-hexosaminidase and histamine assays, oxidative stress indices, apoptosis analysis and intracellular calcium ions in RBL-2H3 cells. Our results demonstrated that SAI at 80 µg ml-1 and 100 µg ml-1, and its two components (SA-B and SA-D) at 60 µg ml-1 were responsible for disturbing cell morphology and cell viability, elevated levels of ß-hexosaminidase, histamine, modulation of oxidative stress indices, induced apoptosis and increase in intracellular calcium ions in RBL-2H3 cells, when compared with the control. Our results demonstrated for the first time that SAI was more likely to induce immediate hypersensitivity reactions attributable to degranulation via oxidative stress caused by SA-B and SA-D components. These results would not only be useful for the safety of end user but also for the industry to improve the quality of SA infusion.