Biotransformation of Timosaponin BII into Seven Characteristic Metabolites by the Gut Microbiota

Timosaponin BII is one of the most abundant Anemarrhena saponins and is in a phase II clinical trial for the treatment of dementia. However, the pharmacological activity of timosaponin BII does not match its low bioavailability. In this study, we aimed to determine the effects of gut microbiota on timosaponin BII metabolism. We found that intestinal flora had a strong metabolic effect on timosaponin BII by HPLC-MS/MS. At the same time, seven potential metabolites (M1–M7) produced by rat intestinal flora were identified using HPLC/MS-Q-TOF. Among them, three structures identified are reported in gut microbiota for the first time. A comparison of rat liver homogenate and a rat liver microsome incubation system revealed that the metabolic behavior of timosaponin BII was unique to the gut microbiota system. Finally, a quantitative method for the three representative metabolites was established by HPLC-MS/MS, and the temporal relationship among the metabolites was initially clarified. In summary, it is suggested that the metabolic characteristics of gut microbiota may be an important indicator of the pharmacological activity of timosaponin BII, which can be applied to guide its application and clinical use in the future.     

Catalytic Enantioselective Assembly of Homoallylic Alcohols from Dienes,Aryldiazonium Salts,and Aldehydes

A highly selective multicomponent carbonyl allylation reaction of 1,3‐butadienes, aryldiazonium tetrafluoroborates, and aldehydes has been established under the combined catalysis of palladium acetate and chiral anion phase transfer to render the favorable assembly of chiral Z‐configured homoallylic alcohols in high yields and with excellent levels of enantioselectivity.     

Catalytic Enantioselective Assembly of Homoallylic Alcohols from Dienes,Aryldiazonium Salts,and Aldehydes

A highly selective multicomponent carbonyl allylation reaction of 1,3‐butadienes, aryldiazonium tetrafluoroborates, and aldehydes has been established under the combined catalysis of palladium acetate and chiral anion phase transfer to render the favorable assembly of chiral Z‐configured homoallylic alcohols in high yields and with excellent levels of enantioselectivity.     

固体电解质Rb4Cu16I7Cl13制备及离子导电性研究

液态固体电解质材料的离子电导率低,安全性问题在一定程度上限制了其发展与应用,而固体电解质材料在室温下具有很好的稳定性和高的离子电导率值,具有较好的应用前景.本文采用机械化学球磨法制备固体电解质Rb₄Cu₁₆I₇Cl₁₃粉末,探索制备工艺和球磨参数,对其晶体结构进行解析、观察粉体微观结构、通过交流阻抗谱及等效电路分析得到了离子电导率与活化能、并详细探讨其离子传导性能与晶体结构的关系以及化学成分稳定性进行研究.实验结果表明,在480 rpm转速下球磨6 h时可得到纯的固体电解质Rb₄Cu₁₆I₇Cl₁₃物相.粉体晶粒尺寸分布均匀,均在20 nm-400 nm之间,室温下固体电解质Rb₄Cu₁₆I₇Cl₁₃离子电导率可达到0.213 S/cm且活化能为0.087(9)eV.在真空干燥条件下存放5天和12天后观察了微观形貌和化学稳定性...     

Significance of Dosimetry in Photodynamic Therapy of Injured Arteries: Classification of Biological Responses

With conflicting results in the literature on the ability of photodynamic therapy (PDT) to inhibit intimal hyperplasia (IH), the present study systematically investigated the effects of drug and light dosimetry on the biologic responses in the artery wall. The rat common carotid artery was balloon-injured and pressurized with benzoporphyrin-derivative monoacid ring (BPD). Then, PDT was performed with an external laser at different fluences and the biologic responses of the artery wall were histologically examined at 24 h and at 2 weeks. Photodynamic therapy effects on injured arteries can be classified into four stages: low-dose PDT using 0.5 microgram/mL BPD at 50 J/cm2 (stage I) resulted in incomplete cell eradication and significant IH at 2 weeks. Irradiation with 100 J/cm2 at the same BPD concentration (stage II) completely eradicated the cells in the artery wall at 24 h but still led to IH at 2 weeks. However, 25 micrograms/mL BPD at 100 J/cm2 (stage III) resulted in total cell eradication at 24 h and inhibition of IH at 2 weeks. In contrast, high-dose PDT with 25 micrograms/mL BPD and 200 J/cm2 (stage IV) led to thrombus development and vascular occlusion at 24 h. These data, demonstrating the different stages of PDT effects on injured arteries, emphasize the critical importance of appropriate PDT dosimetry for the effective inhibition of IH.     

Biotransformation of Liquiritigenin into Characteristic Metabolites by the Gut Microbiota

The bioavailability of flavonoids is generally low after oral administration. The metabolic transformation of flavonoids by the gut microbiota may be one of the main reasons for this, although these metabolites have potential pharmacological activities. Liquiritigenin is an important dihydroflavonoid compound found in Glycyrrhiza uralensis that has a wide range of pharmacological properties, such as antitumor, antiulcer, anti-inflammatory, and anti-AIDS effects, but its mechanism of action remains unclear. This study explored the metabolites of liquiritigenin by examining gut microbiota metabolism and hepatic metabolism in vitro. Using LC-MS/MS and LC/MSⁿ-IT-TOF techniques, three possible metabolites of liquiritigenin metabolized by the gut microbiota were identified: phloretic acid (M3), resorcinol (M4), and M5. M5 is speculated to be davidigenin, which has antitumor activity. By comparing these two metabolic pathways of liquiritigenin (the gut microbiota and liver microsomes), this study revealed that there are three main metabolites of liquiritigenin generated by intestinal bacteria, which provides a theoretical basis for the study of pharmacologically active substances in vivo.