Reductive Metabolism of Ellagitannins in the Young Leaves of Castanopsis sieboldii

The leaves of Castanopsis sieboldii (Fagaceae) contain characteristic hexahydroxydiphenoyl (HHDP) esters of 28-O-glucosyl 2α,3β,23,24-tetrahydroxyolean- and urs-12-en-28-oic acids. In this study, uncharacterized substances were detected in the young leaves, which are not observed in the mature leaves. Preliminary HPLC analyses indicated that the substances had dehydro-HHDP (DHHDP) ester groups; however, the esters were unstable and decomposed during extraction. Therefore, the compounds were isolated as their stable phenazine derivatives by extracting the young leaves with acidic aqueous EtOH containing o-phenylenediamine. The structures of the phenazine derivatives indicated that the unstable metabolites of the young leaves were 3,24-DHHDP esters of the abovementioned triterpenes. Extraction of the young leaves with 80% acetonitrile containing reducing agents, ascorbic acid or dithiothreitol afforded the corresponding HHDP esters. Furthermore, heating of the young leaves in 80% acetonitrile also yielded the same HHDP esters as the reduction products. The results suggested that the HHDP esters are reductively produced from DHHDP esters in the young leaves. In addition, the structures of five previously reported triterpene HHDP esters were revised

A descriptive analysis of spontaneous reports of antipsychotic‐induced tardive dyskinesia and other extrapyramidal symptoms in the Japanese Adverse Drug Event Report database

Abstract AimThe aim of this study is to summarize the spontaneous reports of tardive dyskinesia (TD) and extrapyramidal symptoms (EPSs) that occurred in Japan over the past decade. MethodsThe study analyzed TD and EPS cases reported in the Japanese Adverse Drug Event Report database between April 2011 and March 2021. The cases were stratified by the diagnoses of schizophrenia, bipolar disorders, and depressive disorders. ResultsIn total, 800 patients including a total of 171 TD cases and 682 EPS cases were reported in the JADER database across psychiatric diagnosis. The cases were caused by first‐generation antipsychotics (FGA, TD: n = 105, EPS: n = 245) and second‐generation antipsychotics (SGA, TD: n = 144, EPS: n = 598). The SGA were categorized based on Neuroscience‐based Nomenclature (NbN) regarding pharmacological domain and mode of action, which were reported evenly as the offending agents. Among reported treatment and outcome in TD cases (n = 67, 37.6%) and EPS cases (n = 405, 59.3%), the relatively limited number of TD cases were reported as recovered/improved was also limited (n = 32, 47.8%) compared to those of EPS cases (n = 266, 65.7%). Some cases still had residual symptoms or did not recover fully (TD: n = 21, 31.3%, EPS: n = 77, 19.0%). Conclusion Tardive dyskinesia and EPS have been widely reported in Japan over the past decade across psychiatric diagnoses and antipsychotic classes. Limitations It is important to acknowledge the presence of reporting bias and the lack of comparators to accurately assess risks. Owing to the nature of spontaneous reporting, the estimation of prevalence is not feasible

Reductive Metabolism of Ellagitannins in the Young Leaves of Castanopsis sieboldii

The leaves of Castanopsis sieboldii (Fagaceae) contain characteristic hexahydroxydiphenoyl (HHDP) esters of 28-O-glucosyl 2α,3β,23,24-tetrahydroxyolean- and urs-12-en-28-oic acids. In this study, uncharacterized substances were detected in the young leaves, which are not observed in the mature leaves. Preliminary HPLC analyses indicated that the substances had dehydro-HHDP (DHHDP) ester groups; however, the esters were unstable and decomposed during extraction. Therefore, the compounds were isolated as their stable phenazine derivatives by extracting the young leaves with acidic aqueous EtOH containing o-phenylenediamine. The structures of the phenazine derivatives indicated that the unstable metabolites of the young leaves were 3,24-DHHDP esters of the abovementioned triterpenes. Extraction of the young leaves with 80% acetonitrile containing reducing agents, ascorbic acid or dithiothreitol afforded the corresponding HHDP esters. Furthermore, heating of the young leaves in 80% acetonitrile also yielded the same HHDP esters as the reduction products. The results suggested that the HHDP esters are reductively produced from DHHDP esters in the young leaves. In addition, the structures of five previously reported triterpene HHDP esters were revised

Reinvestigation of the Stereochemistry of the <i>C</i>‑Glycosidic Ellagitannins, Vescalagin and Castalagin

The stereochemistry of the <i>C</i>-glycosidic ellagitannins, vescalagin and castalagin, has been reinvestigated using computational methods. DFT calculations of their ¹H and ¹³C NMR spectra, as well as TDDFT calculations of the ECD spectra of their des-hexahydroxydiphenoyl analogues, revealed that the structure of the triphenoyl moiety of vescalagin and castalagin should be revised

Acute effects of air pollutants on pulmonary function among students: a panel study in an isolated island

Abstract Background Many epidemiological studies on the health effects of air pollutants have been carried out in regions with major sources such as factories and automobiles. However, the health effects of air pollutants in regions without major sources remain unclear. This study investigated the acute effects of ambient air pollution on pulmonary function among healthy students in an isolated island without major artificial sources of air pollutants. Methods A panel study was conducted of 43 healthy subjects who attended a school in an isolated island in the Seto Inland Sea, Japan. We measured the forced expiratory volume in 1 s (FEV1) and peak expiratory flow (PEF) every morning for about 1 month in May 2014. Ambient concentrations of particulate matter ≤ 2.5 μm in diameter (PM2.5), particulate matter between 2.5 and 10 μm in diameter (PM10-2.5), black carbon (BC), ozone (O3), and nitrogen dioxide (NO2) were measured. The associations between the concentrations of air pollutants and pulmonary function were analyzed using mixed-effects models. Results A decrease in FEV1 was significantly associated with BC concentrations (−27.28 mL [95%confidence interval (CI):−54.10,−0.46] for an interquartile range (IQR) increase of 0.23 μg/m3). The decrease in PEF was significantly associated with indoor O3 concentrations (−8.03 L/min [95% CI:−13.02,−3.03] for an IQR increase of 11 ppb). Among subjects with a history of allergy, an increase in PM2.5 concentrations was significantly associated with low FEV1. In subjects with a history of asthma, an inverse association between the indoor O3 concentration and pulmonary function was observed. Conclusions Our results demonstrate that increases in BC and O3 concentrations have acute effects on the pulmonary function among students in an isolated island without major artificial sources of air pollutants