[Comparative study on excretion of Shuganning Injection and Scutellariae Radix extract in bile, urine, and feces of rats].

Scutellariae Radix extract is one of the important components in Shuganning Injection. In this study, an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method was established for simultaneously determining five components in Shuganning Injection and Scutellariae Radix extract in bile, urine, and feces of rats, so as to reveal the difference in the excretion process of Shuganning Injection and Scutellariae Radix extract in rats and explore the law of the excretion process of the five components in vivo before and after the compatibility of Scutellariae Radix. Rats were injected with Shuganning Injection and Scutellariae Radix extract(4.2 mL·kg~(-1)), respectively, and the excretion of baicalin, baicalein, oroxylin A, oroxylin A-7-O-ß-D-glucuronide, and scutellarin in bile, urine, and feces of rats in 24 h was observed. The results showed that except for baicalin, the other four index components were excreted as prototype components in a high proportion after intravenous injection of Shuganning Injection and Scutellariae Radix extract in rats, respectively. The excretion of each component was relatively high in urine and less in feces and bile. After the compatibility of Scutellariae Radix extract, the accumulative excretion of five index components in rats all decreased. Among them, the cumulative excretion of baicalein in bile, urine, and feces significantly decreased by 26.67%, 48.11%, and 31.01%. The cumulative excretion of baicalin in bile, urine, and feces decreased significantly by 70.69%, 19.43%, and 31.22%. The result showed that the five index components in Scutellariae Radix extract were mainly excreted by the kidneys, and other components in Shuganning Injection delayed the excretion process and prolonged the residence time. This study is of great significance for elucidating the compatibility rationality of Shuganning Injection.

Urinary Tract Infections Caused by Uropathogenic Escherichia coli: Mechanisms of Infection and Treatment Options.

Urinary tract infections (UTIs) are common bacterial infections that represent a severe public health problem. They are often caused by Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumonia), Proteus mirabilis (P. mirabilis), Enterococcus faecalis (E. faecalis), and Staphylococcus saprophyticus (S. saprophyticus). Among these, uropathogenic E. coli (UPEC) are the most common causative agent in both uncomplicated and complicated UTIs. The adaptive evolution of UPEC has been observed in several ways, including changes in colonization, attachment, invasion, and intracellular replication to invade the urothelium and survive intracellularly. While antibiotic therapy has historically been very successful in controlling UTIs, high recurrence rates and increasing antimicrobial resistance among uropathogens threaten to greatly reduce the efficacy of these treatments. Furthermore, the gradual global emergence of multidrug-resistant UPEC has highlighted the need to further explore its pathogenesis and seek alternative therapeutic and preventative strategies. Therefore, a thorough understanding of the clinical status and pathogenesis of UTIs and the advantages and disadvantages of antibiotics as a conventional treatment option could spark a surge in the search for alternative treatment options, especially vaccines and medicinal plants. Such options targeting multiple pathogenic mechanisms of UPEC are expected to be a focus of UTI management in the future to help combat antibiotic resistance.

Metabolites-Based Network Pharmacology to Preliminarily Verify In Vitro Anti-Inflammatory Effect of Ardisiacrispin B.

Ardisiae Crenatae Radix is an ethnic medicinal herb with good anti-inflammatory activity. Ardisiacrispin B is one of the main components in Ardisiae Crenatae Radix extract, with a content of up to 16.27%, and it may be one of the pharmacological components through which Ardisiae Crenatae Radix exerts anti-inflammatory activity. At present, reports on ardisiacrispin B mainly focus on anti-tumor effects, and there have been no reports on anti-inflammatory activities. As a triterpenoid saponin, due to its large molecular weight and complex structure, the composition of substances that function in the body may include other forms after metabolism, in addition to compounds with original structures. Exploring the anti-inflammatory effects on the prototypes and metabolites of the compound may provide a more comprehensive response to the characteristics of ardisiacrispin B's anti-inflammatory action. In this study, ardisiacrispin B was analyzed for metabolites to explore its metabolic processes in vivo. Subsequently, the anti-inflammatory effects of the prototypes and metabolites were further analyzed through network pharmacology, with the expectation of discovering the signaling metabolic pathways through which they may act. Finally, the anti-inflammatory effects of ardisiacrispin B in vitro and the effects on key signaling pathways at the protein level were explored. The results of this study showed that the isolated compounds were confirmed to be ardisiacrispin B. After the metabolite analysis, a total of 26 metabolites were analyzed, and the metabolism process in rats mainly involves oxidation, dehydration, glucuronide conjugation, and others. Speculation as to the anti-inflammatory molecular mechanisms of the prototypes and metabolites of ardisiacrispin B revealed that it may exert its anti-inflammatory effects mainly by affecting the PI3K-AKT pathway. Further anti-inflammatory mechanisms demonstrated that ardisiacrispin B had a good anti-inflammatory effect on LPS-induced RAW264.7 cells and a strong inhibitory effect on NO, TNF-α, and IL-1ß release in cells. Furthermore, it had significant inhibitory effects on the expression of PI3K, P-PI3K, AKT, and P-AKT. This study supplements the gaps in the knowledge on the in vivo metabolic process of ardisiacrispin B and explores its anti-inflammatory mechanism, providing an experimental basis for the development and utilization of pentacyclic triterpenoids.

Anti-Rheumatoid Arthritis Pharmacodynamic Substances Screening of Periploca forrestii Schltr.: Component Analyses In Vitro and In Vivo Combined with Multi-Technical Metabolomics.

The purpose of this study was to elucidate the metabolic action patterns of P. forrestii against rheumatoid arthritis (RA) using metabolomics, and to obtain its potential effective substances for treating RA. First, the therapeutic effects of P. forrestii against RA were confirmed; second, the chemical composition of P. forrestii was analyzed, and 17 prototypes were absorbed into blood; subsequently, plasma metabolomics studies using UPLC-Triple-TOF-MS/MS and GC-MS were performed to disclose the metabolomics alterations in groups, which revealed 38 altered metabolites after drug intervention. These metabolites were all associated with the arthritis pathophysiology process (-log(p) > 1.6). Among them, sorted by variable important in projection (VIP), the metabolites affected (VIP ≥ 1.72) belonged to lipid metabolites. Finally, Pearson's analysis between endogenous metabolites and exogenous compounds was conducted to obtain potential pharmacological substances for the P. forrestii treatment of RA, which showed a high correlation between five blood-absorbed components and P. forrestii-regulated metabolites. This information provides a basis for the selection of metabolic action modes for P. forrestii clinical application dosage, and potential pharmacological substances that exerted anti-RA effects of P. forrestii were discovered. The study provided an experimental basis for further research on pharmacoequivalence, molecular mechanism validation, and even the development of new dosage forms in the future.

[Simultaneous determination of eleven volatile components in Cinnamomi Oleum by GC-MS].

A gas chromatography-triple quadrupole mass spectrometry(GC-MS) method was established for the simultaneous determination of eleven volatile components in Cinnamomi Oleum and the chemical pattern recognition was utilized to evaluate the quality of essential oil obtained from Cinnamomi Fructus medicinal materials in various habitats. The Cinnamomi Fructus medicinal materials were treated by water distillation, analyzed using GC-MS, and detected by selective ion monitoring(SIM), and the internal standards were used for quantification. The content results of Cinnamomi Oleum from various batches were analyzed by hierarchical clustering analysis(HCA), principal component analysis(PCA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) for the statistic analysis. Eleven components showed good linear relationships within their respective concentration ranges(R~2>0.999 7), with average recoveries of 92.41%-102.1% and RSD of 1.2%-3.2%(n=6). The samples were classified into three categories by HCA and PCA, and 2-nonanone was screened as a marker of variability between batches in combination with OPLS-DA. This method is specific, sensitive, simple, and accurate, and the screened components can be utilized as a basis for the quality control of Cinnamomi Oleum.

[Determination of plasma protein binding rate of Shuganning Injection using equilibrium dialysis and UPLC-MS/MS].

Traditional Chinese medicine(TCM) compound preparations have complex compositions. As a widely used TCM injection, Shuganning Injection, its in vivo processes are not yet fully understood. Determining the plasma protein binding rate is of great significance for pharmacokinetic and pharmacodynamic studies. In this experiment, the equilibrium dialysis method combined with UPLC-MS/MS technology was used to determine the plasma protein binding rates of 10 components, including p-hydroxyacetophenone, caffeic acid, baicalein, oroxylin A, geniposide, baicalin, cynaroside, oroxylin A-7-O-ß-D-glucuronide, scutellarin, and hyperoside, in Shuganning Injection in rat and human plasma to provide a theoretical basis for further elucidating the in vivo processes of Shuganning Injection and guiding clinical medication. The results showed that, except for baicalein and geniposide, the plasma protein binding rates of the other eight components were higher in human plasma than in rat plasma, and there were interspecies differences. In human plasma, except for geniposide, caffeic acid, and baicalin, the plasma protein binding rates of the remaining seven components were above 80%, with baicalein and oroxylin A exceeding 90%. All components exhibit a high level of binding to plasma proteins, with the exception of geniposide.

[Content determination of seven active components of Eucommiae Cortex in aortic vascular endothelial cells of spontaneously hypertensive rats by UPLC-MS/MS].

In the present study, the contents of seven active components [genipinic acid(GA), protocatechuic acid(PCA), neochlorogenic acid(NCA), chlorogenic acid(CA), cryptochlorogenic acid(CCA),(+)-pinoresinol di-O-ß-D-glucopyranosid(PDG), and(+)-pinoresinol 4'-O-ß-D-glucopyranoside(PG)] of Eucommiae Cortex in aortic vascular endothelial cells of spontaneously hypertensive rats(SHR) were simultaneously determined by ultra-high liquid chromatography-triple quadrupole mass spectrometry(UPLC-MS/MS). The qualified SHR models were selected. The primary aortic endothelial cells(VECs) of rats were separated and cultured by ligation and adherence, followed by subculture. After successful identification, an UPLC-MS/MS method for simultaneously determining the contents of GA, PCA, NCA, CA, CCA, PDG, PG in seven components of Eucommiae Cortex in VECs was established, including specificity, linearity, matrix effect, recovery, accuracy, precision and stability. The established method had the lo-west limit of quantification of 0.97-4.95 µg·L~(-1), accuracy of 87.26%-109.6%, extraction recovery of 89.23%-105.3%, matrix effect of 85.86%-106.2%, and stability of 86.00%-112.5%. Therefore, the established accurate UPLC-MS/MS method could rapidly and simultaneously determine the contents of the seven active components of Eucommiae Cortex in VECs of SHRs, which provided a refe-rence for the study of cellular pharmacokinetics of active components of Eucommiae Cortex extract.

Comparative pharmacokinetics of 11 components from the active part of Gerberae Piloselloidis Herba after oral administration in control and asthmatic mice.

Gerberae Piloselloidis Herba, a traditional Chinese medicine, is often employed to treat such lung-related diseases as coughs, asthma, and pulmonary carbuncles in southwest China. Our previous study demonstrated that its active fraction, prepared from Gerberae Piloselloidis Herba, exerts an obvious beneficial effect on asthma. However, the pharmacokinetics of its major constituents remain unclear. Therefore, an ultra-performance mass spectrometry-electrospray ionization-tandem mass spectrometry method was successfully established to simultaneously perform the pharmacokinetics of the main 11 components of the active fraction between normal and ovalbumin-induced asthmatic mice. Compared to the normal group, in asthmatic mice the peak concentration of arbutin, marmesin, caffeoylquinic acids, and flavonoid glycosides clearly increased, while for luteolin it significantly declined; the area under the curve for arbutin and luteolin showed an increase, but the values of marmesin, caffeoylquinic acids, and flavonoid glycosides revealed a decline; the peak time for arbutin, caffeoylquinic acids and flavonoid glycosides decreased, while for marmesin and luteolin it significantly augmented; apart from marmesin, the half-life for all compounds shortened significantly. It is indicated that the pathology of asthma could lead to an alteration in the pharmacokinetic profiles of the 11 components in plasma, providing a reference for further exploration of the pharmacodynamic basis of the anti-bronchial effect of Gerberae Piloselloidis Herba.

Chemical profiling and quantification of multiple components in Jin-Gu-Lian capsule using a multivariate data processing approach based on UHPLC-Orbitrap Exploris 240 MS and UHPLC-MS/MS.

The Jin-Gu-Lian capsule, a Chinese Miao herbal compound, is widely used to treat rheumatoid arthritis. In this study, a rapid, selective, and sensitive UHPLC-Orbitrap Exploris 240 MS method was developed to analyze the chemical composition of Jin-Gu-Lian capsules. A total of 88 compounds were identified, including 23 flavonoids, 23 organic acids, 14 phenylpropanoids, 12 phenols, eight alkaloids, four terpenes, three quinones, and one ketone. Among these, 21 compounds were clearly detected based on a comparison with reference standards and selected as quality control markers. Thereafter, these compounds were simultaneously determined in the Jin-Gu-Lian capsules. The established method was successfully validated and applied for the simultaneous determination of 21 biologically active compounds in Jin-Gu-Lian capsules of 27 sample batches. Quantitative data of the analytes were analyzed using multivariate statistical analysis to determine the quality of the Jin-Gu-Lian capsules. Four compounds (JGLC6 [salidroside], JGLC8 [chlorogenic acid], JGLC12 [liriodendrin], JGLC19 [quercetin]) were identified as chemical markers for quality control of Jin-Gu-Lian capsules. Altogether, the established method was validated as a novel and efficient tool, that can be used for rapid analysis of Jin-Gu-Lian capsules. Accordingly, this study serves as a reference for scientific research on traditional Chinese and ethnic medicine.

Towards Better Sinomenine-Type Drugs to Treat Rheumatoid Arthritis: Molecular Mechanisms and Structural Modification.

Sinomenine is the main component of the vine Sinomenium acutum. It was first isolated in the early 1920s and has since attracted special interest as a potential anti-rheumatoid arthritis (RA) agent, owing to its successful application in traditional Chinese medicine for the treatment of neuralgia and rheumatoid diseases. In the past few decades, significant advances have broadened our understanding of the molecular mechanisms through which sinomenine treats RA, as well as the structural modifications necessary for improved pharmacological activity. In this review, we summarize up-to-date reports on the pharmacological properties of sinomenine in RA treatment, document their underlying mechanisms, and provide an overview of promising sinomenine derivatives as potential RA drug therapies.

Pharmacokinetics Study of Jin-Gu-Lian Prescription and Its Core Drug Pair (Sargentodoxa cuneata (Oliv.) Rehd. et W and Alangium chinense (Lour.) Harms) by UPLC-MS/MS.

Jin-Gu-Lian (JGL) is traditionally used by Miao for the treatment of rheumatism arthralgia. At the same time, the combination of Sargentodoxa cuneata (Oliv.) Rehd. et W (SC) and Alangium chinense (Lour.) Harms (AC), the core drug pair (CDP) in the formula of JGL, is used at high frequencies in many Miao medicine prescriptions for rheumatic diseases. However, previous research lacks the pharmacokinetic study of JGL, and study on the compatibility of its CDP with other medicinal herbs in the formula is needed. This study aims to establish a simple, rapid, and sensitive Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS) method for the simultaneous determination of four main bioactive components of JGL in rat plasma, including Salidroside (Sal), Anabasine (Ana), Chlorogenic Acid (CA), and Protocatechuic Acid (PCA), and compare the pharmacokinetic properties of two groups of rats after being orally administrated with JGL and its CDP extracts, respectively. The results showed that area under the plasma concentration-time curve (AUC), mean retention time (MRT), and clearance rate (CL), of Sal, Ana, CA and PCA in the two groups of rats were changed in different degrees. The CDP combined with other drugs could significantly increase the absorption of Sal and Ana, prolong its retention time in vivo, and may accelerate the absorption rate of CA and PCA. This indicated that the combination of CDP and other herbs may affect the pharmacokinetics process of active components in vivo, increase the exposure and bioavailability of compounds in the JGL group, and prolong the retention time, which may be the reason why JGL has a better inhibitory effect on inflammatory cytokines, providing a viable orientation for the compatibility investigation of herb medicines.

Quality Control of Oleum Cinnamomi Assisted by Network Pharmacology Strategy.

Oleum Cinnamomi is a traditional medicine used by the Hmong, the essential oil obtained from Fructus Cinnamomi, for the treatment of coronary heart disease. Information regarding the efficient quality control markers of it is lacking, which has become a bottleneck restricting its development and utilization. Here, an integrated qualitative analysis approach based on a GC-MS and network pharmacology strategy was applied to explore quality control markers for the assessment of Oleum Cinnamomi. Firstly, the compounds of Oleum Cinnamomi were detected by GC-MS. In total, 57 chemical components were identified, mainly monoterpenes and sesquiterpenes, accounting for 83.05% of total essential oil components. Secondly, network pharmacology was adopted to explore the compounds linked to target genes of coronary heart disease. Fifty-two compounds were found, indicating the effectiveness of Oleum Cinnamomi in the treatment of coronary heart disease. Among them, 10 compounds, including eucalyptol, were chosen as potential effective compounds in Oleum Cinnamomi. Thirdly, an established GC-MS SIM method was validated and applied for the simultaneous determination of the contents of these 10 compounds using 20 sample batches of Oleum Cinnamomi. It was preliminarily found that the contents of these 10 compounds differed in Oleum Cinnamomi from different origins. Finally, quantitative analyte data were analyzed using multivariate statistical analysis to determine Oleum Cinnamomi quality. Four compounds (eucalyptol, p-cymene, sabinene, ß-pinene) were identified as chemical markers for quality control. Accordingly, this study provides new strategies to explore the quality control markers and develops a novel method for the quality assessment of Oleum Cinnamomi.

Identification of Protosappanoside D from Caesalpinia decapetala and Evaluation of Its Pharmacokinetic, Metabolism and Pharmacological Activity.

Protosappanoside D (PTD) is a new component isolated from the extract of Caesalpinia decapetala for the first time. Its structure was identified as protosappanin B-3-O-ß-D-glucoside by 1H-NMR, 13C-NMR, 2D-NMR and MS techniques. To date, the pharmacological activities, metabolism or pharmacokinetics of PTD has not been reported. Therefore, this research to study the anti-inflammatory activity of PTD was investigated via the LPS-induced RAW264.7 cells model. At the same time, we also used the UHPLC/Q Exactive Plus MS and UPLC-MS/MS methods to study the metabolites and pharmacokinetics of PTD, to calculate its bioavailability for the first time. The results showed that PTD could downregulate secretion of the pro-inflammatory cytokines. In the metabolic study, four metabolites were identified, and the primary degradative pathways in vivo involved the desaturation, oxidation, methylation, alkylation, dehydration, degradation and desugarization. In the pharmacokinetic study, PTD and its main metabolite protosappanin B (PTB) were measured after oral and intravenous administration. After oral administration of PTD, its Tmax was 0.49 h, t1/2z and MRT(0-t) were 3.47 ± 0.78 h and 3.06 ± 0.63 h, respectively. It shows that PTD was quickly absorbed into plasma and it may be eliminated quickly in the body, and its bioavailability is about 0.65%.

[Simultaneous determination of content of eight components in Caesalpinia decapetala by UPLC-MS/MS].

The present study established the ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method for simultaneous determination of the content of eight major active components in Caesalpinia decapetala and performed the quality evaluation of C. decapetala from different habitats with the chemical pattern recognition. The analysis was carried out on a Waters BEH C_(18) column(2.1 mm×100 mm, 1.7 µm) at 40 ℃, with the mobile phase of water containing 0.1% formic acid(A) and acetonitrile containing 0.1% formic acid under gradient elution, the flow rate of 0.3 mL·min~(-1), and the injection volume of 1 µL. The electrospray ionization(ESI) source in the negative mode and multiple reaction monitoring(MRM) were used for MS quantitative analysis. The content results were analyzed by the hierarchical cluster analysis(HCA) and principal component analysis(PCA) for the evaluation of the quality difference. Eight components showed good linear relationships within their respective concentration ranges(r>0.999), with the average recoveries of 96.85%-103.4% and RSD of 0.52%-2.8%. The analysis results showed that the quality of samples from different batches was different. The samples were classified into three clusters by HCA and PCA. The method is simple, sensitive, accurate, and efficient, and can be used for the quality evaluation of C. decapetala.

[Pharmacokinetics and tissue distribution of four components from root bark of Caesalpinia decapetala in rats by UPLC-MS/MS].

To identify the pharmacodynamic material basis of root bark of Caesalpinia decapetala extract and clarify the dynamic changes and distribution characteristics of the compounds in vivo.UPLC-MS/MS was used for simultaneous determination of 3-deoxysappanchalcone, isoliquiritigenin, protosappanin B, and protosappanin B-10-O-ß-D-glucoside in plasma, heart, liver, spleen, lung, kidney, stomach and duodenum of rats, to further study the pharmacokinetics and tissue distribution of root bark of C.decapetala extract in rats.Statistical analysis of obtained data demonstrated that the established analytical methods of the four components in biological matrix met the requirements of biological sample determination.The pharmacokinetic parameters showed that the t_(1/2 z), T_(max), C_(max), AUC_(0-t), MRT_(0-t), and CL_(z/F) of each component were 4.57-13.47 h, 0.22-0.51 h, 27.60-6 418.38 µg·L~(-1), 112.45-11 824.25 h·µg·L~(-1), 3.89-9.01 h, and 9.85-96.87 L·h~(-1)·kg~(-1), respectively.The results of tissue distribution revealed that at different time points, the components were widely but unevenly distributed in the body.Specifically, they were more distributed in the stomach and duodenum, followed by liver, spleen, lung, and kidney, and the least distribution was observed in the heart.

[Establishment of PK-PD model in anti-inflammatory active components in Inula cappa extract based on lipopolysaccharide-induced in vitro inflammation model].

In the present study, a pharmacokinetics(PK)-pharmacodynamics(PD) model in the anti-inflammatory active components in Inula cappa extract was established based on the lipopolysaccharide(LPS)-induced in vitro inflammation model in order to clarify the relationship between the dynamic changes of anti-inflammatory active components in inflammatory cells and their efficacy. Firstly, the inflammation model in vitro was induced by 1 µg·mL~(-1) LPS in RAW264.7 cells for 24 h. After treatment with 400 µg·mL~(-1) I. cappa extract, the pharmacokinetics(PK) of five anti-inflammatory active components, including luteolin(LUT), chlorogenic acid(CA), cryptochlorogenic acid(CCA), 3,4-dicaffeoylquinic acid(3,4-DCQA), and 4,5-dicaffeoylquinic acid(4,5-DCQA), in normal cells and inflammatory cells was compared. Meanwhile, the PD study was carried out by measuring the inflammatory factors NO and TNF-α in the cell supernatant at each time point, which was fitted with PK by the Phoenix Model in the WinNonlin 8.2 to establish the PK-PD model for five components including LUT, CA, CCA, 3,4-DCQA, and 4,5-DCQA. The results showed that compared with normal cells, the model cells showed increased or decreased uptake of five components, advanced T_(max), faster absorption, prolonged MRT and t_(1/2), and increasing or decreasing trend of CL_(z/F) and V_(z/F). When NO was used as the efficacy index, the PK-PD model after the integration of the multi-effect components in I. cappa was E=7.45×\[1-Ce~(5.74)/(78.24~(5.74)+Ce~(5.74))\], while with TNF-α as the efficacy index, the PK-PD model after the integration of the multi-effect components in I. cappa was E=79.28×[1-Ce~(6.45)/(85.10~(6.45)+Ce~(6.45))]. The results of the study suggested that the inflammatory state could change the cellular PK of I. cappa. The anti-inflammatory effect of active components in I. cappa might be related to the down-regulation of the secretion of NO and TNF-α in inflammatory cells, and NO and TNF-α might serve as the anti-inflammatory targets of active components of I. cappa.

[Pharmacokinetics of three index components of Periploca forrestii in rats by microdialysis combined with UPLC-MS/MS].

The present study established a UPLC-MS/MS method for the content determination of Periploca forrestii microdialysis samples and investigated the pharmacokinetics of three index components of P. forrestii in rats. The effects of flow rate and concentration of perfusate on the recovery rate were investigated by the concentration difference method(increment method and decrement method). The microdialysis samples at different time points were collected, and the concentrations of three index components were determined by UPLC-MS/MS. The actual drug concentrations were corrected with the in vivo recovery rate, and the pharmacokinetic parameters were calculated by WinNonlin 8.2. In the in vitro recovery test, the recovery rate measured by the increment method and the decrement method was inversely proportional to the flow rate and independent of the concentration. The pharmacokinetic parameter AUC_(0-t) values of 3-O-caffeoyl quinic acid, 4-O-caffeoyl quinic acid, and 5-O-caffeoyl quinic acid were(23 911.23±5 679.67),(16 688.43±3 448.45), and(9 677.02±1 606.74) min·µg·L~(-1), respectively. C_(max) values were(170.66±58.02),(121.61±48.14), and(69.69±18.23) µg·L~(-1), respectively. The UPLC-MS/MS method has the advantages of specificity, rapidity, high sensitivity, and accurate quantification. It can simultaneously determine the concentration of 3-O-caffeoyl quinic acid and other two index components in microdialysis samples and is suitable for the pharmacokinetics study of the three index components of P. forrestii in normal rats.

[Differences in intestinal absorption characteristics of Cynanchum auriculatum extract based on in situ intestinal circulation perfusion model in two states].

The present study aimed to investigate the intestinal absorption characteristics of six components(syringic acid, scopoletin, baishouwu benzophenone, caudatin, qingyangshengenin, and deacylmetaplexigenin) in Cynanchum auriculatum extract. In situ intestinal circulation perfusion model was employed to investigate the differences in intestinal absorption characteristics of C. auriculatum extract under the influence of different intestinal segments, different drug concentrations, and bile in the normal and functional dyspepsia(FD) states. The results showed that the absorption of baishouwu benzophenone decreased with the increase in the concentration of C. auriculatum extract(P<0.01), while the absorption of syringic acid and other components increased in a dose-independent manner, suggesting that baishouwu benzophenone might follow active absorption, while other components might not be on a single absorption pattern. The main absorption sites of each component in the normal state were different from those in the FD state. The cumulative absorption conversion rates in the FD state were generally lower than those in the normal state, and bile inhibited the absorption of other components except for scopoletin in both states(P<0.05). As revealed, the small intestine showed selectivity to the absorption of drugs, and the pathological state(such as FD) and bile both affected the absorption of the main components, which provides a theoretical basis for the development of new drugs and further development of C. auriculatum.

[Excretion of Cynanchum auriculatum extract in urine and feces of normal and functional dyspepsia rats].

In the present study, the excretion of four active components(qingyangshengenin, deacylmetaplexigenin, baishouwu benzophenone, and scopoletin) in Cynanchum auriculatum extract in the urine and feces of normal and functional dyspepsia(FD) rats was investigated. Rats were divided into a normal group and an FD model group. The FD model was induced by oral administration of ice hydrochloric acid combined with irregular feeding. The C. auriculatum extract was administered orally at a dose of 1 g·kg~(-1). The rat urine and feces were collected at 4, 8, 12, 24, 36, 48, 60, 72, and 84 h for UPLC-ESI-MS/MS analysis. The differences in excretion of the four components were compared between normal and FD rats. The results showed that except for the baishouwu benzophenone in the feces, the components such as qingyangshengenin in the urine and feces did not reach the plateau value within 84 h. Qingyangshengenin was mainly excreted through defecation, and the cumulative excretion rates in the normal state and FD were 0.32% and 0.66%, respectively. Deacylmetaplexigenin was mainly excreted through urination, and the cumulative excretion rates in the normal state and FD were 6.70% and 7.56%, respectively. Baishouwu benzophenone was mainly excreted through defecation in the normal state, but mainly excreted through urination in the FD state, with cumulative excretion rates of 0.41% and 0.52%, respectively. Scopoletin was mainly excreted through urination, with cumulative excretion rates of 0.83% and 2.13% in the normal state and FD, respectively. In general, the components were mainly excreted in the urine in the FD state. Compared with the normal group, the FD group showed decreased cumulative excretion rates of qingyangshengenin, baishouwu benzophenone, and scopoletin in the urine(P<0.05). Therefore, FD had a certain influence on the excretion of the main components of C. auriculatum extract, and the excretion of each component through urination and defecation was low, suggesting that there might be a wide range of metabolic pathways after oral administration and components were mainly excreted in the form of metabolites. This experiment provides a reference for the new drug development and clinical application of C. auriculatum.

[Uptake and transport of Laportea bulbifera extract in Caco-2 cell model].

Laportea bulbifera extract is effective in resisting inflammation and shows a good therapeutic effect on rheumatoid arthritis in rats. However, the absorption characteristics of active components in L. bulbifera extract in Caco-2 cells are still unclear, which limits the in-depth development of L. bulbifera resources. The purpose of this study was to investigate the absorption and transport mechanism of the active components of L. bulbifera extract in the Caco-2 cell model and explore the effects of different factors(concentration, time, pH value, temperature, and efflux transporter inhibitor) on its uptake and transport. The results showed that L. bulbifera extract at the concentration of 2.0-8.0 mg·mL~(-1) showed no toxicity to Caco-2 cells. The uptake and transport of L. bulbifera extract in the Caco-2 cell model were concentration-dependent and time-dependent. The main absorption mechanism was passive diffusion, and acidic condition(pH 5.0-6.0) and 37 ℃ were more favorable for drug absorption. P_(app)>1.0×10~(-6 )cm·s~(-1) of each component indicated that L. bulbifera was a moderately absorbed drug. P-gp, MRP2, and BCRP were not involved in its uptake and transport.