Pharmacokinetics and tissue distribution of five bioactive components in the Corydalis yanhusuo total alkaloids transdermal patch following Shenque acupoint application in rats assessed by ultra-performance liquid chromatography-tandem mass spectrometry.

The purpose of this study was to evaluate the pharmacokinetics and tissue distribution of the Corydalis yanhusuo total alkaloids transdermal patch (CTTP) following Shenque acupoint application in rats. The concentrations of corydaline, tetrahydropalmatine, tetrahydrocolumbamine, protopine, and dehydrocorydaline in rat plasma and various tissues were simultaneously detected by ultra-performance liquid chromatography-tandem mass spectrometry after Shenque acupoint administration of CTTP. Plasma, heart, liver, spleen, lung, and kidney tissue samples were collected at specific times and separated by gradient elution on an ACQUITY UPLC HSS T3 column (1.8 µm, 100 mm × 2.1 mm) with a mobile phase of 0.01% formic acid aqueous solution and acetonitrile-0.01% formic acid. The methodological results showed that the selectivity, linear range, accuracy, precision, stability, matrix effect, and extraction recovery of the established method met the requirements of biological sample analysis. The results indicated that CTTP following Shenque acupoint administration rapidly delivered adequate drug into rat blood and maintained an effective plasma level for a significantly longer time than non-acupoint administration. Furthermore, CTTP effectively reached the liver through Shenque acupoint administration and showed tissue selectivity. The data obtained could provide a prospect for the treatment of chronic pain with CTTP following Shenque acupoint application.

An integrated fecal microbiome and metabolome in rats reveal variations in gut microbiota and fecal metabolic phenotype of Semen Euphorbiae and Semen Euphorbiae Pulveratum.

Semen Euphorbiae (SE) is a toxic traditional Chinese medicine made from the dry or mature seed of Euphorbia lathyris L. Research demonstrates that the toxic side-effects from eating SE are associated with intestinal disturbance. By processing to produce Semen Euphorbiae Pulveratum (SEP), the toxicity is reduced, and diarrhea is attenuated. However, there are minimal studies on the differential effects between SE and SEP on microbiota and fecal metabolites. In this study, 16S rDNA sequencing and UPLC-Q-TOF/MS were interpreted with PCA and OPLS-DA multivariate analysis to understand the effect of SE and SEP on the gut microbiota and fecal metabolic phenotype in rats. Compared to the blank control group, the results showed that both SE and SEP were associated with increased microbes from the phylum Firmicutes and decreased Bacteroidetes, but the change was not as strong in the SEP administration group. Meanwhile, the fecal metabolism of rats also changed significantly, since 17 additional metabolites were detected in both groups, including amino acid metabolites, bacterial metabolites, and lipid metabolites. Our results indicate that the SEP administration group may reduce toxicity by differentially influencing intestinal metabolites and flora.

Construction of magnetic drug delivery system and its potential application in tumor theranostics.

Magnetic nanoparticles(NPs) are characterized by a rich variety of properties. Because of their excellent physical and chemical properties, they have come to the fore in biomedicine and other fields. The magnetic NPs were extensively studied in magnetic separation of cells, targeted drug delivery, tumor hyperthermia, chemo-photothermal therapy, magnetic resonance imaging (MRI) and other biomedical fields. Magnetic NPs are increasingly used in magnetic resonance imaging (MRI) based on their inherent magnetic targeting, superparamagnetic enzyme-like catalytic properties and nanoscale size. Poly(lactic-co-glycolic acid) (PLGA) is a promising biodegradable material approved by FDA and EU for drug delivery. Currently, PLGA-based magnetic nano-drug delivery systems have attracted the attention of researchers. Herein, we achieved the effective encapsulation of sized-controlled polyethylene glycol-3,4-dihydroxy benzyl-amine-coated superparamagnetic iron oxide nanoparticles (SPIO NPs) and euphorbiasteroid into PLGA nanospheres via a modified multiple emulsion solvent evaporation method (W1/O2/W2). NPs with narrow size distribution and acceptable magnetic properties were developed that are very useful for applications involving cancer therapy and MRI. Furthermore, SPIO-PLGA NPs enhanced the MRI T2 relaxation properties of tumor sites.The prepared SPIO NPs and magnetic PLGA nanospheres can be promising magnetic drug delivery systems for tumor theranostics. This study has successfully constructed a tumor-targeting and magnetic-targeting smart nanocarrier with enhanced permeability and retention, multimodal anti-cancer therapeutics and biodegradability, which could be a hopeful candidate for anti-tumor therapy in the future.

Characterization of diterpene metabolism in rats with ingestion of seed products from Euphorbia lathyris L. (Semen Euphorbiae and Semen Euphorbiae Pulveratum) using UHPLC-Q-Exactive MS.

Previous pharmacological studies have indicated that diterpenoids are the primary effective chemical cluster in the seeds of Euphorbia lathyris L. The seed products are used in traditional Chinese medicine in the forms of Semen Euphorbiae (SE) and Semen Euphorbiae Pulveratum (SEP). However, the metabolism of the plant's diterpenoids has not been well elucidated, which means that the in vivo metabolite products have not been identified. The current study screened the physiological metabolites of six diterpenes [Euphorbia factor L1 (L1), L2 (L2), L3 (L3), L7a (L7a), L7b (L7b), and L8 (L8)] in feces and urine of rats after oral administration of SE and SEP using UHPLC-Q-Exactive MS. A total of 22 metabolites were detected in feces and 8 in urine, indicating that the major elimination route of diterpenoids is via the colon. Hydrolysis, methylation, and glucuronidation served as the primary metabolic pathways of these diterpenoids. In sum, this study contributed to the elucidation of new metabolites and metabolic pathways of SE and SEP, and the new chemical identities can be used to guide further pharmacokinetic studies.

Metabonomics analysis of semen euphorbiae and semen Euphorbiae Pulveratum using UPLC-Q-TOF/MS.

Semen Euphorbiae (SE), the dry and mature seed of Euphorbia lathyris L., a common traditional Chinese medicine, has significant pharmacological activity. However, its toxicity limits its clinical application, and less toxic Semen Euphorbiae Pulveratum (SEP) is often used clinically. To explore the possible mechanism of SE frost-making and attenuation, this study used ultrahigh-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry to perform a comprehensive metabolomics analysis of serum and urine samples from rats treated with SE and SEP, and performed histopathological evaluation of liver, kidney and colon tissues. Meanwhile, the different metabolites were visualized through multivariate statistical analysis and the HMDB and KEGG databases were used to distinguish the differential metabolites of SE and SEP to reveal related metabolic pathways and their significance. In total, 32 potential biomarkers, 14 in serum and 18 in urine, were identified. The metabolic pathway analysis revealed that arachidonic acid metabolism, sphingolipid metabolism, tyrosine and tryptophan biosynthesis, the tricarboxylic acid cycle and seven other metabolic pathways were significantly altered. Importantly, compared with SE, SEP reduced the metabolic disorder related to endogenous components. The mechanism may be related to the regulation of lipid metabolism, intestinal flora metabolites, amino acid metabolism and energy metabolism. This study provided new insights into the possible mechanism of SE freezing and attenuation.

Comparison of Pharmacokinetics and Tissue Distribution Characteristics of Three Diterpenoid Esters in Crude and Prepared Semen Euphorbiae.

BACKGROUND: Semen Euphorbiae (SE) and Semen Euphorbiae Pulveratum (SEP) have a long history of medicinal use. SEP is the processed product of SE; both ancient and modern studies have shown that SEP has a lower toxicity compared to SE. To clarify the influence of processing on the pharmacological properties of SE and SEP, a study was carried out to compare the pharmacokinetics and distribution characteristics of three active compounds after oral administration of SE and SEP extracts. METHODS: A UPLC-MS/MS method was established to simultaneously determine the contents of Euphorbia factors L1, L2, and L3 in rat plasma and mouse tissues after an oral administration of crude and processed SE with approximately the same dosage. Plasma and heart, liver, spleen, lung, kidney, and colon tissue samples were treated with ethyl acetate and separated by gradient elution on a C18 column with a mobile phase of 0.1% formic acid and methanol. RESULTS: The established method had good selectivity, linear range, accuracy, precision, stability, matrix effect, and extraction recovery. The area under the concentration time curve, time to maximum concentration, maximum concentration, half-life of elimination, and mean retention time of plasma samples in SEP-treated group decreased, and the clearance in SEP-treated group increased. Moreover, the active component concentrations in colon, liver, and kidney tissues were more followed by those in the heart, lungs, and spleen. CONCLUSION: These results indicate that the processing could influence the pharmacokinetics and tissue distribution of Euphorbia factors L1, L2, and L3 after oral administration of crude and processed SE. The data obtained may lay a foundation for the clinical use of SE and for further study on the processing mechanism of SE.