Integrated metabolism, network pharmacology, and pharmacokinetics to explore the exposure differences of the pharmacodynamic material basis in vivo caused by different extraction methods for Saussurea involucrata.

ETHNOPHARMACOLOGICAL RELEVANCE: Saussurea involucrata Kar.et Kir. (S.I.) has long been used as a precious national medicine and clinically proven to be an effective treatment for rheumatoid arthritis (RA) and cardiovascular diseases. In clinical practice, two extraction methods of S.I., including water decoction and alcohol extraction, are prescribed to treat the same conditions. Nevertheless, no study has been performed on the exposure differences of the pharmacodynamic material basis in vivo caused by different extraction methods. AIM OF THE STUDY: Based on the integrated strategy of metabolism, network pharmacology, and pharmacokinetics, we aimed to reveal exposure differences in pharmacodynamic substances caused by different extraction methods. MATERIALS AND METHODS: Ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS) was employed to identify the chemical constituents of S.I. extracts and the metabolites in vivo after administration. Based on the analysis of prototype components in vivo, the major exposure active constituents, potential therapeutic targets and possible pharmacological mechanisms in RA treatment were investigated using network pharmacological analysis. Seven critical active components, including quercetin, hispidulin, apigenin, chlorogenic acid, arctigenin, syringin, and umbelliferone, were quantitatively compared between the alcohol, and aqueous extraction methods, which had been confirmed by the reference substance. RESULTS: The chemical comparison demonstrated that the types of chemicals in the two extracts were identical, mainly flavonoids, phenylpropanoids, coumarins, lignins, sesquiterpene lactones, and others, but the contents of the primary constituents in the aqueous extract were lower than those of the alcohol extract. A total of 30 prototype components and 174 metabolites were analyzed and identified in rat plasma, urine, fecal, and bile samples. Twenty-three prototype components were analyzed by network pharmacology, and seven critical active components were selected as representative markers for the pharmacokinetic study. Pharmacokinetic studies had shown that the Tmax values of apigenin, hispidulin, chlorogenic acid, arctigenin, and syringin after the oral administration of the alcohol extract were lower than those after the oral administration of the aqueous extract, and the above components in the alcohol extract could increase the absorption. Compared with the aqueous extract group, the Tmax and T1/2 of quercetin and umbelliferone were longer; it was suggested that alcohol extraction might have a slow-release and long-term effect on these two components. The relative bioavailability of apigenin, hispidulin, quercetin, chlorogenic acid, and umbelliferone in the alcohol extract group were higher than those in the aqueous extract group, which was consistent with the traditional clinical experience that alcohol extract could improve the efficacy of S.I. CONCLUSIONS: The major exposure active constituents in vivo were screened. The representative components that could be used in pharmacokinetics were determined by integrating network pharmacology and metabolism studies. The critical active compounds were quantitatively compared between the alcohol and aqueous extraction methods. This study clarified that flavonoids, coumarin, and phenylpropanoids might be the primary material basis that caused the exposure differences between aqueous and alcoholic extracts from S.I.. This research aimed to provide the basis of metabolism in vivo for further studying these pharmacodynamic differences.

Multi-intervention integrated deworming strategy for sustained control of soil-transmitted helminths infections: a case study in Jiangsu Province, China.

BACKGROUND: Soil-transmitted helminths (STH) infections still present a global health problem. Mass drug administration (MDA) is a widely applied strategy to reduce morbidity and mortality caused by STH. Yet, this approach has some shortcomings. In this study, we analyzed the impact of a multi-intervention integrated deworming approach including MDA, health education (HE), and environmental sanitation improvements (ESI) for sustained STH control in Jiangsu Province of China that was applied from 1989 to 2019. METHODS: Data, including infection rate of STH, medications used, coverage of the medication, non-hazardous lavatory rate, and household piped-water access rate in rural areas, and actions related to HE and ESI were collected (from archives) and analyzed in this retrospective descriptive study. Pearson's correlation analysis was applied to test correlations. RESULTS: There was a dramatic decline in the infection rate of STH from 1989 (59.32%) to 2019 (0.12%). From 1995 to 1999, MDA and HE were recommended in rural areas. A negative correlation was observed between infection rate and medication from 1994 to 1998 (r = - 0.882, P = 0.048). From 2000 to 2005, targeted MDA was given to high-risk populations with HE continuously promoting good sanitation behaviors. From 2006 to 2014, targeted MDA + HE and ESI were used to consolidate the control effect. ESI was strengthened from 2006, and a negative correlation was observed between the coverage rate of the non-hazardous lavatory and the infection rate from 2006 to 2019 (r = - 0.95, P < 0.001). The targeted MDA was interrupted in 2015, while continuous efforts like HE and ESI contributed in sustaining STH control. CONCLUSIONS: Multi-intervention integrated deworming strategy contributes to the reduction of STH infections. This approach is a valuable example of how different interventions can be integrated to promote durable STH control.

Synthesis of CdSe Nanoplatelets without Short-Chain Ligands: Implication for Their Growth Mechanisms.

We present a novel route for the synthesis of zinc blende CdSe nanoplatelets (NPLs) that exclude the use of short-chain alkyl carboxylates. CdSe NPLs obtained without acetates are shown to be extremely asymmetric and rectangular. The effects of several experimental parameters such as the nature of cadmium carboxylates, selenium precursors, and precursor concentration ratios are studied. Our experiments, together with complementary small-/wide-angle X-ray scattering results, show that the formation of NPLs is not related to soft templating. We discuss our findings in regard to several other formation mechanisms of NPLs, which have appeared recently in the literature, and propose that the steric hindrance caused by ligand packing exerts an influence on the growth and geometry of two-dimensional NPLs.