Although progress has been achieved in the pharmacological activity and toxicity of Radix Polygoni Multiflori (RPM), the chemical basis of its toxicity is still unclear. Here, we performed a multicompound pharmacokinetic analysis and investigated the tissue distribution and excretion characteristics of RPM components after oral administration in rats. The findings demonstrated that the active ingredients of the RPM extract were quickly absorbed after oral administration, with high exposure levels of emodin, 2,3,5,4′-teterahydroxystilbene-2-O-β-D-glucoside (TSG), citreorosein, torachrysone-8-O-glucoside (TG), emodin-8-O-β-D-glucoside (EG), and physcion-8-O-β-D-glucoside (PG). The tissue distributions of emodin, TSG, TG, EG, and PG were high in the liver and kidney. These components were the key contributors to the effectiveness and toxicity of RPM on the liver and kidney. Most of the active ingredients were mainly excreted through feces and bile, while a few were converted into other products in the body and excreted through urine and feces.
Resistance and tolerance of biofilms to antibiotics is the greatest challenge in the treatment of bacterial infections. Therefore, developing an effective strategy against biofilms is a top priority. Liposomes are widely used as antibiotic drug carriers; however, common liposomes lack affinity for biofilms. Herein, biofilm-targeted antibiotic liposomes are created by simply adjusting their cholesterol content. The tailored liposomes exhibit significantly enhanced bacterial inhibition and biofilm eradication effects that are positively correlated with the cholesterol content of liposomes. The experiments further demonstrate that this enhanced effect can be ascribed to the effective drug release through the pores, which are formed by the combination of cholesterol microdomains in liposomal lipid bilayers with membrane-damaged toxins in biofilms. Consequently, liposome encapsulation with a high cholesterol concentration improves noticeably the pharmacodynamics and biocompatibility of antibiotics after pulmonary administration. This work may provide a new direction for the development of antibiofilm formulations that can be widely used for the treatment of infections caused by bacterial biofilms.
Astragalus Membranaceus (AM) is widely applied in Chinese herbal compound formulas for treating various kinds of diseases. However, relative pharmacokinetics data on AM in nonrodents is still lacking. Here, an UPLC-MS/MS method for determining the six main compounds of AM was developed. The chromatographic separation was carried out by a Waters Acquity UPLC HSS T3 column (100 Â 2.1 mm, 1.8 μm) with gradient elution of water-formic acid (99.98:0.02, v/v) and acetonitrile-formic acid (99.98:0.02, v/v) at a flow rate of 0.3 ml/min within 11 min. Analyses of all compounds were conducted in multiple reaction monitoring mode with a positive/negative ion-switching mode of an electrospray ionization source in a single run. The analytical method was validated in terms of specificity, linearity, accuracy, precision, stability, etc. The method showed excellent linearity (r > 0.999) over certain concentration ranges. The intra-day and inter-day precisions were evaluated, and the RSD values were <12.4%. Furthermore, the validated method was successfully applied to determine the six components in plasma after oral administration of AM aqueous extract to beagle dogs and the pharmacokinetic parameters were obtained. Together, this study provides a reference for medication in the clinical practice of AM.
Herb medicine has a long history of application and is still used worldwide. With the development of complementary and alternative medicine, the interaction between herb and drugs has attracted more and more attention. Herb-drug interactions (HDI) could cause decreased efficiency, increased toxicity, and affect the drug absorption and disposition processes due to the interference of their pharmacological or pharmacokinetic effects. Hence, the mechanisms and results of herb-pharmacokinetic interactions should be comprehensively summarized. Here, we have summarized the mechanisms of HDI and pharmacokinetic interactions in the last ten years based on searching on PubMed, Science Direct, and Web of Science with different keywords. Besides, the pharmacokinetic interactions were related to nine commonly used herbs and drugs, including Ginseng, Salvia miltiorrhiza, Ginkgo biloba, Garlic, Coptis chinensis, St. John's wort, Ginger, Licorice, Silythistle and Fructus Schisandrae. This review provides an overview of HDI to provide a reference for the rational and safe clinical use of herbs and drugs.
Idiopathic pulmonary fibrosis (IPF) is a kind of lifethreatening interstitial lung disease characterized by progressive dyspnea with accurate pathogenesis unknown. At present, heat shock protein inhibitors are gradually used to treat IPF. Silybin, a heat shock protein C-terminal inhibitor, has high safety and good application prospects. In this work, we have developed a silybin powder able to be used for inhalation administration for the treatment of IPF. Silybin powder was prepared by the spray drying method and identified using cascade impactometry, particle size, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared (FT-IR) spectroscopy. A rat model of bleomycininduced IPF was used to assess the effect of inhaled silybin spray-dried powder. Lung hydroxyproline content, wet weight, histology, inflammatory factor expression, and gene expression were examined. The results showed that inhaled silybin spray-dried powder alleviated inflammation and fibrosis, limited hydroxyproline accumulation in the lungs, modulated gene expression in the development of IPF, and improved postoperative survival. The results of this study suggest that silybin spray-dried powder is an attractive candidate for the treatment of IPF.
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