Skp1-CUL1-ROC1-F-box E3 ubiquitin ligases' main component S-phase kinase-associated protein 2 (Skp2) is responsible for specifically recognizing ubiquitination-modified substrates to be degraded such as p27 and p21 in the case of binding with adaptor protein Cks1. Pharmacological inhibition of Skp2 has exhibited promising antitumor activity. Herein, we present the design and optimization of a series of [1,2,4]triazolo[1,5-]pyrimidine-based small molecules targeting Skp2.
View Article and Find Full Text PDFInt J Environ Res Public Health
October 2022
Anthropogenic activities have altered ecosystem service functions in the karst mountainous areas. The implementation of ecological restoration projects by the government, the behavior, attitude, and willingness of farmers to participate in their implementation, the application of pesticides and fertilizers, in addition to other socio-economic activities, have had a significant impact on the ecosystem services (ESS) of the region. Taking Guangnan County, a typical karst mountainous area in Yunnan Province, as an example, this study analyzes the evolutionary characteristics of six types of ESS and the driving mechanism of the change in ESS from the anthropogenic macro and micro perspective using questionnaire surveys and the multivariate logistic model.
View Article and Find Full Text PDFEndothelial dysfunction initiates and exacerbates hypertension, atherosclerosis and other cardiovascular complications in diabetic mellitus. FGF21 is a hormone that mediates a number of beneficial effects relevant to metabolic disorders and their associated complications. Nevertheless, it remains unclear as to whether FGF21 ameliorates endothelial dysfunction.
View Article and Find Full Text PDFZhongguo Zhong Yao Za Zhi
September 2016
To predict the mechanism of liver injury induced by Genkwa Flos, we investigated the effect of chloroform extract on UGTs and UGT1A1 activities of the liver microsomes in rat and human. In the present study, 4-nitrophenol(4-NP) and β-estradiol were elected as substrates to determine activities of UGTs and UGT1A1 by UV and HPLC. The results showed that there were 1.
View Article and Find Full Text PDFEur J Drug Metab Pharmacokinet
April 2017
Background And Objectives: In our previous studies, it was found that there existed pharmacokinetic interactions between magnoflorine and the rest of the ingredients in Coptidis Rhizoma. In this study, the pharmacokinetic interaction mechanism of magnoflorine with the rest of the components in Coptidis Rhizoma was researched based on the intestinal absorption and metabolism characteristics.
Methods: The absorption characteristics of magnoflorine in each rat intestinal segments were evaluated by non-everted intestinal sac model.
Zhongguo Zhong Yao Za Zhi
February 2016
To predit the mechanism of metabolic drug-drug interactions of hydroxygenkwanin with other drugs, we investigated the inhibition inhibitory effect of hydroxygenkwanin on UGTs and UGT1A1 activities of different liver microsomes. In the present study, 4-nitrophenol (4-NP) and β-estradiol were elected as substrates to determine activities of UGTs and UGT1A1 by UV and HPLC, respectively. The results showed that, hydroxygenkwanin significantly inhibited UGTs activity in rat, mouse and human liver microsomes.
View Article and Find Full Text PDFContext Previous studies have shown that Scutellariae Radix, the dried root of Scutellaria baicalensis Georgi (Labiatae), has a certain inhibitory effect on P-glycoprotein (P-gp), but the effects of its main active constituents on P-gp are still ambiguous. Objectives In vitro studies were performed to investigate the effects of its main active constituents (baicalin and its aglycone, baicalein) on the activity and expression of P-gp in intestine using Caco-2 cells and rat gut sacs. Materials and methods In Caco-2 cell experiments, the effects of baicalin and baicalein on P-gp activity were investigated using a P-gp substrate, rhodamine 123 and non-substrate fluorescein Na, by determining their intracellular fluorescence accumulation, and their effects on P-gp expression were determined using flow cytometry.
View Article and Find Full Text PDFIn the present study, the effects of six Coptidis alkaloids (berberine, epiberberine, coptisine, jatrorrhizine, palmatine and magnoflorine) on liver microsomes UGTs and UGT1A1 activities in rats and mice were investigated in vitro and in vivo to study the mechanism of metabolic drug-drug interactions of Coptidis Rhizoma with other drugs. In vitro rat and mice liver microsomal incubation systems combined with UDPGA were applied, as well as mice liver microsomes after administration of six Coptidis alkaloids. 4-Nitrophenol and β-estradiol were selected as substrates to determine activities of UGTs and UGT1A1 by UV and HPLC, respectively.
View Article and Find Full Text PDFEthnopharmacological Relevance: Scutellariae radix (Scutellaria baicalensis Georgi) and Coptidis rhizoma (Coptis chinensis Franch), known as traditional Chinese medicine (TCM), have been widely used with the effects of suppressing fever, dispelling dampness, purging fire and removing toxicosis. Owing to their unimaginable complexity, it is difficult to understand their pharmacokinetic properties in detail. The aim of this study was to develop an optimal proteomics approach to analyze the protein profiling related with ADME/Tox in rat liver treated with S.
View Article and Find Full Text PDFCoptisine (COP), a protoberberine alkaloid (PBA) from Chinese medicinal plants (such as family Berberidaceae), may be useful for improving central nervous system disorders. However, its pharmacokinetics, disposition and metabolism are not well defined. In the present study, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established for the analysis of COP in biological samples.
View Article and Find Full Text PDFTo figure out the stability and intestinal bacteria metabolites of rats in vitro of astragaloside IV ( AST), this research was done to explore the stability of AST in the artificial gastric juice. artificial intestinal juice and rat liver homogenate and the metabolism in rat intestinal in vitro. HPLC was used to calculate the remaining rate of AST in biological samples by measuring the content of AST, while metabolites were determined by combining the methods of TLC, HPLC and LC-MS/MS.
View Article and Find Full Text PDFEpiberberine, one of the most important isoquinoline alkaloid in Coptidis Rhizoma, possesses extensive pharmacological activities. In this paper, the liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to study phase I and phase II metabolites. A Thermo HPLC system (including Surveyor AS, Surveyor LC Pump, Surveyor PDA.
View Article and Find Full Text PDFMagnoflorine, an important aporphine alkaloid in Coptidis Rhizoma, is increasingly attracting research attention because of its pharmacological activities. The in vivo and in vitro metabolism of magnoflorine was investigated by LC LTQ-Orbitrap MS. In vivo samples including rat urine, feces, plasma and bile were collected separately after both oral (50 mg kg(-1) ) and intravenous administration (10 mg kg(-1) ) of magnoflorine, along with in vitro samples prepared by incubating magnoflorine with rat intestinal flora and liver microsome.
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