Potent Inhibition of Human Cytochrome P450 3A4 by Biflavone Components from Ginkgo Biloba and Selaginella Tamariscina.

CYP3A4-mediated Phase I biotransformation is the rate-limiting step of elimination for many commonly used clinically agents. The modulatory effects of herbal medicines on CYP3A4 activity are one of the risk factors affecting the safe use of drug and herbal medicine. In the present study, the inhibitory effects of nearly hundred kinds of herbal medicines against CYP3A4 were evaluated based on a visual high-throughput screening method. Furthermore, biflavone components including bilobetin (7-demethylginkgetin, DGK), ginkgetin (GK), isoginkgetin (IGK), and amentoflavone (AMF) were identified as the main inhibitory components of Ginkgo biloba L. (GB) and Selaginella tamariscina (P. Beauv.) Spring (ST), which displayed very strong inhibitory effects toward CYP3A4. The inhibitory effects of these biflavones on clinical drugs that mainly undergo CYP3A4-dependent metabolism were evaluated. The IC 50 of GK toward tamoxifen, gefitinib and ticagrelor were found to be of 0.478 ± 0.003, 0.869 ± 0.001, and 1.61 ± 0.039 µM, respectively. These results suggest the potential pharmacokinetic interactions between the identified biflavones and clinical drugs undergoing CYP3A4-mediated biotransformation. The obtained information is important for guiding the rational use of herbal medicine in combination with synthetic pharmaceuticals.

Ecosystem health of the Beiyun River basin (Beijing, China) as evaluated by the method of combination of AHP and PCA.

Ecosystem services provided by river ecosystems rely on healthy ecosystem structure and ecological processes. The Beijing-Tianjin-Hebei urban is a typical water-deficient area. As an important part of the urban-rural integration construction, evaluating the health status of the Beiyun River Basin and discovering the weak links in the water environment are the basis for improving the health of the basin. In this study, analytic hierarchy process (AHP) was used to establish an evaluation index system for the Beiyun River Basin from 5 aspects including water quality, biology, ecology, hydrology, and social functions, and the principal component analysis (PCA) was then used to assign weights to the index layer. The evaluation results showed that the health evaluation results of the Beiyun River Basin in 2019 are "sub-healthy," and the overall health status is getting worse from northwest to southeast. In the middle reaches of the region, the evaluation result is "healthy," followed by the upstream, and the downstream is the worst. The results showed that areas with less human interference or orderly intervention are in better health. High eutrophication level, low bio-diversity, and low vegetation coverage are the main indicators that leads to poor ecosystem health in the Beiyun River Basin. For the comprehensive management of the Beiyun River, the improvement of water quality and habitat ecological restoration are key actions to the health of the upstream ecosystem. The improvement of the health status of the downstream should focus on equal emphasis on water quality and quantity, restoration of biodiversity, and improvement of the quality of the riparian ecological environment.

Cloning and Functional Identification of Phosphoethanolamine Methyltransferase in Soybean (Glycine max).

Phosphoethanolamine methyltransferase (PEAMT), a kind of S-adenosylmethionine-dependent methyltransferases, plays an essential role in many biological processes of plants, such as cell metabolism, stress response, and signal transduction. It is the key rate-limiting enzyme that catalyzes the three-step methylation of ethanolamine-phosphate (P-EA) to phosphocholine (P-Cho). To understand the unique function of PEAMT in soybean (Glycine max) lipid synthesis, we cloned two phosphoethanolamine methyltransferase genes GmPEAMT1 and GmPEAMT2, and performed functional identification. Both GmPEAMT1 and GmPEAMT2 contain two methyltransferase domains. GmPEAMT1 has the closest relationship with MtPEAMT2, and GmPEAMT2 has the closest relationship with CcPEAMT. GmPEAMT1 and GmPEAMT2 are located in the nucleus and endoplasmic reticulum. There are many light response elements and plant hormone response elements in the promoters of GmPEAMT1 and GmPEAMT2, indicating that they may be involved in plant stress response. The yeast cho2 opi3 mutant, co-expressing Arabidopsis thaliana phospholipid methyltransferase (PLMT) and GmPEAMT1 or GmPEAMT2, can restore normal growth, indicating that GmPEAMTs can catalyze the methylation of phosphoethanolamine to phosphate monomethylethanolamine. The heterologous expression of GmPEAMT1 and GmPEAMT2 can partially restore the short root phenotype of the Arabidopsis thaliana peamt1 mutant, suggesting GmPEAMTs have similar but different functions to AtPEAMT1.

Protective effects of dioscin against isoproterenol-induced cardiac hypertrophy via adjusting PKCε/ERK-mediated oxidative stress.

Cardiac hypertrophy (CH) plays a central role in cardiac remodeling and is an independent risk factor for cardiac events. It is imperative to find drugs with protective effect on CH. Dioscin, one natural product, shows various pharmacological activities, and PKCepsilon (PKCε) plays an important role in the physiological hypertrophic responses. Thus, we aimed to investigate the possible protective effect of dioscin on CH through PKCε. In the present study, the isoproterenol (ISO)-induced H9C2 cells and primary cardiomyocytes models, and the ISO-induced rat model were established, and the pharmacodynamics and mechanism of dioscin were investigated. In vitro results prompted that, dioscin significantly improved ISO-induced cardiomyocyte hypertrophy, decreased the levels of cell size, protein content of single cell, reactive oxygen species, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), beta-myosin heavy chain (ß-MHC). Moreover, in vivo, changes in histopathological of the animals caused by ISO are improved by dioscin. And dioscin decreased the index of CH and the levels of CK, MDA, LDH, and increased the levels of GSH, SOD and GSH-Px. Mechanism research showed that dioscin inhibited the expression levels of PKCε, and affected the expression levels of p-MEK, p-ERK, Nrf2, Keap1 and HO-1 to inhibit oxidative stress. In addition, the results of ISO-induced CH in PKCε siRNA transfected H9C2 cells and C57BL/6 mice further showed that the protective effect of dioscin on CH, which was mediated by inhibition of PKCε/ERK signal pathway. In summary, dioscin can effectively inhibit CH by regulating PKCε-mediated oxidative stress, which should be considered as one potent candidate for new drug research and development to treat CH in the future.

Evaluating surface water quality using water quality index in Beiyun River, China.

The Beijing-Tianjin-Hebei urban agglomeration is one of the most water-scarce regions in China, because of the frequent human activities. Water scarcity and pollution have weakened the service functions of water ecosystems and hindered the regional economic development. As the "lifeline" of the economic development of Beijing-Tianjin-Hebei region, the water quality of Beiyun River has been widely concerned. River water quality assessment is one of the most important aspects to enhance water resources management plans. Water quality index (WQI), as one of the most frequently used evaluation tools, was used to comprehensively analyze the water quality in the Beiyun River. Between January 2017 and October 2018, we collected samples from 16 typical sampling sites along the main rivers of the watershed, covering four seasons. Seventeen water quality parameters, including temperature, pH, conductivity, dissolved oxygen (DO), chemical oxygen demand (COD), biochemical oxygen demand (BOD5), ammonia nitrogen (NH3-N), total phosphorus (TP), oil, volatile phenol (VP), fluoride, sulfide, surfactant, lead (Pb), copper (Cu), zinc (Zn), and arsenic (As), were used to calculate WQI. The average WQI values of Beiyun River in winter, spring, summer, and autumn were 88.15, 71.70, 78.92, and 90.12, respectively, explaining the water quality was "good" generally. There were significant differences in the spatial distribution of WQI values from Beiyun River, and water quality of upstream and downstream was better than that of midstream. In addition, correlation analysis was applied to explore the correlation between land use types and water quality. Water quality was significant negatively correlated with agriculture land and rural residential land, and a positive relationship between urban land and water quality. Generally, we believe that people's related activities on different land use are major elements impacting the water quality. Water environment improvement ought to increase the wastewater collection rate and sewage treatment capacity in rural areas, especially in the midstream of the Beiyun River. Graphical abstract.