ABSTRACT:Berberine, one of the most commonly used natural products, exhibits a poor plasma concentration-effect relationship whose underlying mechanisms remain largely unclear. This study was designed to test the hypothesis that extensive first-pass elimination and abundant tissue distribution of berberine may be its specific pharmacokinetic properties. For that, four different dosing routes, intragastric, intraduodenal, intraportal, and intravenous, were used to investigate the gastric, intestinal, and hepatic first-pass elimination of berberine. After intragastric dosing, approximately half of berberine ran intact through the gastrointestinal tract and another half was disposed of by the small intestine, leading to an extremely low extent of absolute oral bioavailability in rats (0.36%). Moreover, the major berberine metabolites were identified and quantified in rat enterocyte S9 fractions, portal vein plasma, and intestinal perfusates; plasma concentrations and tissue distribution of berberine and its major metabolites were determined as well. Data indicated that M1, M2 glucuronide, and M3 were the major metabolites generated from the small intestine and that there was a 70-fold increase in the ratio of the area under the concentration-time curve value for berberine (liver versus plasma). We conclude that intestinal first-pass elimination of berberine is the major barrier of its oral bioavailability and that its high extraction and distribution in the liver could be other important factors that lead to its low plasma levels in rats.
Background: Wintersweet (Chimonanthus praecox), an important ornamental plant, has evolved unique fragrant aroma and winter-flowering properties, which are critical for its successful sexual reproduction. However, the molecular mechanisms underlying these traits are largely unknown in this species. In addition, wintersweet is also a typical representative species of the magnoliids, where the phylogenetic position of which relative to eudicots and monocots has not been conclusively resolved. Results: Here, we present a chromosome-level wintersweet genome assembly with a total size of 695.36 Mb and a draft genome assembly of Calycanthus chinensis. Phylogenetic analyses of 17 representative angiosperm genomes suggest that Magnoliids and eudicots are sister to monocots. Whole-genome duplication signatures reveal two major duplication events in the evolutionary history of the wintersweet genome, with an ancient one shared by Laurales, and a more recent one shared by the Calycantaceae. Whole-genome duplication and tandem duplication events have significant impacts on copy numbers of genes related to terpene and benzenoid/phenylpropanoid (the main floral scent volatiles) biosynthesis, which may contribute to the characteristic aroma formation. An integrative analysis combining cytology with genomic and transcriptomic data reveals biological characteristics of wintersweet, such as floral transition in spring, floral organ specification, low temperature-mediated floral bud break, early blooming in winter, and strong cold tolerance. Conclusions: These findings provide insights into the evolutionary history of wintersweet and the relationships among the Magnoliids, monocots, and eudicots; the molecular basis underlying floral scent biosynthesis; and winter flowering, and highlight the utility of multiomics data in deciphering important ornamental traits in wintersweet.
Our work is the first study to explore the national and provincial composite carbon storage variations in terrestrial ecosystems of China caused by the entire flows of land use type conversion (LUTC). Only water body was excluded. The results indicated that terrestrial ecosystems of China lost 219 Tg-C due to LUTC from 1980 to 1995, and the amount was 60 Tg-C during the period 1995-2010. Despite the decrease in the total amount, carbon losses from LUTC intensified, but most of the losses were balanced by the opposite conversions. Our analyses also revealed that LUTCs in China were becoming detrimental to carbon reduction, mainly due to the insufficient increase of forest land to meet the growing demand for carbon absorption, the accelerating disappearance of grassland and the rapid expansion of settlements. More than 50% of the carbon storage variations for a single LUTC flow concentrated in several provinces. To improve China’s LUTC status from the aspect of low-carbon, Heilongjiang, Sichuan, Inner Mongolia, Tibet, Qinghai, Xinjiang and coastal regions, such as Shandong, Jiangsu and Liaoning, should be dealt with first according to their conditions. This study can be helpful to planners, policy makers and scholars concerned about carbon reduction in China.
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