Integrated chemical characterization, metabolite profiling, and pharmacokinetics analysis of Zhijun Tangshen Decoction by UPLC-Q/TOF-MS.

Diabetic nephropathy (DN) is the main cause of end-stage renal disease worldwide and a major public issue affecting the health of people. Therefore, it is essential to explore effective drugs for the treatment of DN. In this study, the traditional Chinese medicine (TCM) formula, Zhijun Tangshen Decoction (ZJTSD), a prescription modified from the classical formula Didang Decoction, has been used in the clinical treatment of DN. However, the chemical basis underlying the therapeutic effects of ZJTSD in treating DN remains unknown. In this study, compounds of ZJTSD and serum after oral administration in rats were identified and analyzed using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS). Meanwhile, a semi-quantitative approach was used to analyze the dynamic changes in the compounds of ZJTSD in vivo. UPLC-Q/TOF-MS analysis identified 190 compounds from ZJTSD, including flavonoids, anthraquinones, terpenoids, phenylpropanoids, alkaloids, and other categories. A total of 156 xenobiotics and metabolites, i.e., 51 prototype compounds and 105 metabolites, were identified from the compounds absorbed into the blood of rats treated with ZJTSD. The results further showed that 23 substances with high relative content, long retention time, and favorable pharmacokinetic characteristics in vivo deserved further investigations and validations of bioactivities. In conclusion, this study revealed the chemical basis underlying the complexity of ZJTSD and investigated the metabolite profiling and pharmacokinetics of ZJTSD-related xenobiotics in rats, thus providing a foundation for further investigation into the pharmacodynamic substance basis and metabolic regulations of ZJTSD.

Screening of metabolic markers present in Oxytropis by UHPLC-Q-TOF/MS and preliminary pharmacophylogenetic investigation.

Plants belonging to the Oxytropis genus, family Leguminosae, are found throughout the world, with about 80 species mainly distributed in northwest and northeast China. The plants have medicinal properties and many plants have been used as folk medicine for the treatment of colds, inflammation of carbuncle swelling, pain, and different types of bleeding. In recent years, due to the reduced availability of wild resources and increased clinical demand, additional Oxytropis species have been used in Mongolian medicine. This study explored the medicinal potential of four Oxytropis species, investigating their phylogeny, chemical components, and pharmacological activities. Oxytropis myriophylla (Pall) DC., Oxytropis hirta Bunge, and Oxytropis bicolor Bge. were found to be closely related at the taxonomic level. While previous investigations on the bioactive constituents of Oxytropis have been limited and have concentrated largely on flavonoids and saponins, the present study established a novel UHPLC-Q-TOF/MS based on metabolite profiling to comprehensively analyze the chemical composition of the four Oxytropis species and to identify marker compounds. A total of 75 compounds were identified from the four species, with 23 identified as characteristic marker components. Twenty-six marker compounds were identified in O. myriophylla from different geographical regions. Analysis of pharmacological activity showed that extracts of O. myriophylla and O. hirta had stronger anti-inflammatory activity than the extracts from the other species. The relationships between the chemical components, traditional curative uses, and pharmacological activities were analyzed to provide a preliminary documentation of the pharmacophylogenetic characteristics of the Oxytropis family as a whole. Several marker compounds, including licoricesaponin G2, licoricesaponin J2, and glycyrrhizic acid found in O. hirta were found to have effective anti-inflammatory activity, consistent with the traditional application of reducing swelling and healing wounds. This preliminary investigation into the pharmacophylogeny of the genus Oxytropis will contribute to the conservation and exploitation of the medicinal resources of this genus.

Establishment of fingerprint and mechanism of anti-myocardial ischemic effect of Syringa pinnatifolia.

This study established the fingerprint of Syringa pinnatifolia Hemsl. (SP), analyzed the SP ingredients absorbed into the rats blood, and evaluated its anti-myocardial ischemic effect to provide a scientific basis for the follow-up development and research of SP and lay a foundation for its clinical application using ultra-performance liquid chromatography-Q Exactive-mass spectrometry and GC-MS. Myocardial infarction was induced in rat by ligating the left anterior descending branch of the rat coronary artery, and SP alcohol extract was administered to evaluate its anti-myocardial ischemic effect. We analyzed the SP ingredients absorbed into the rats blood, screened the active compounds, established a database of SP anti-myocardial ischemic targets, and explored the possible mechanism of SP in treating myocardial infarction using bioinformatics. The rats were examined using echocardiography, serum biomarkers were determined, and pathological changes were observed by histopathological examination. TUNEL staining was performed to detect the apoptotic level of cells, and Western blot and quantitative real-time polymerase chain reaction were performed to detect the expression levels of Bcl-2, Bax, and Caspase-3 in heart tissues. In the fingerprint of SP, 24 common peaks were established, and the similarity evaluation results of 10 batches of SP were all >0.9. Ultra-performance liquid chromatography-Q Exactive-mass spectrometry and GC-MS detected 17 active ingredients in the drug-containing serum, including terpenoids, flavonoids, phenols, phenylpropanoids, and phenolic acids, the most abundant of which was resveratrol. Enrichment analysis of SP targets against myocardial ischemia revealed that key candidate targets of SP were significantly enriched in multiple pathways associated with apoptosis. Resveratrol was administered to the successfully modeled rats, and the results showed that the resveratrol group significantly decreased left ventricular end-diastolic diameter and left ventricular end-systolic diameter and significantly increased ejection fraction and fractional shortening in all groups compared with the model group. Resveratrol significantly decreased the levels of creatine kinase isoenzyme and lactate dehydrogenase in serum compared to the model group (P < 0.001). Hematoxylin-eosin staining of rat myocardial tissue showed that all lesions were reduced under microscopic observation in the resveratrol group compared with the model group. Real-time polymerase chain reaction and Western blot results showed that the resveratrol group downregulated the expression of the proapoptotic factor Bax, upregulated the expression of the antiapoptotic factor Bcl-2, and decreased the expression of Caspase-3. The established fingerprints are accurate, reliable, and reproducible and can be used as an effective method for quality control of the herbs. The anti-myocardial ischemia effect of SP is that resveratrol improves cardiac function and inhibits cardiomyocyte apoptosis to protect cardiomyocytes. The present study provides ample evidence for the clinical use of SP, suggesting that this drug has great potential in the treatment of ischemic heart disease.

Negotiating Lay and Clinical Issues: Implementing a Lay Navigation Program in Cancer Care.

PURPOSE: Patients with cancer face daunting coordination problems at a vulnerable time. Lay navigation programs offer 1 approach to address these problems, but how to best implement these programs presents challenges. We sought to describe those implementation challenges at 1 academic cancer center to inform future efforts. METHODS: We performed a mixed methods study using standard implementation outcomes 1 year after program initiation. Quantitative data from the electronic medical record and qualitative data from in-depth interviews, focus groups, and ethnographic observations were included in analyses. The study took place at a National Cancer Institute-designated comprehensive cancer center across 12 tumor-specific clinics. RESULTS: Supportive care concerns, scheduling, and clinical-related issues were the most frequent issues navigators encountered. Effective navigation required continuous, time-consuming, invisible work, including building and maintaining a broad knowledge base of resources and health system processes, as well as cultivating relationships with diverse and changing clinical teams. The acceptability and appropriateness of lay navigator activities were mixed among clinic and social work staff, related to negotiating lines between clinical and nonclinical care. CONCLUSION: After 1 year of implementation, lay navigators still found it difficult to interpret and prioritize complex patient needs in a way that all clinical staff found appropriate. Negotiating these issues has made it difficult to develop the strong relationships with clinical teams that are needed for an integrated approach to patient care. To successfully coordinate patient care, it seems that lay navigation programs should be integrated with clinical teams to provide more seamless patient care.

[Macroscopic and microscopic identification of Mongolian medicine Potentilla glabra].

OBJECTIVE: To provide the identification basis for Mongolian medicine Potentilla glabra. METHODS: Macroscopic and microscopic identification were applied to observe macroscopic, histological, superficial, and powder characteristics of its stems and leaves. RESULTS: The following characteristics were observed: The cork layer sandwiched with sclerenchyma ring which was main composed of fibers, accompanied by stone cells and large cell layer; Catheter with fiber existed in xylem; Beaded thickened anticlinal wall in leaf epidermal cell; Stomatal infinitive; Small clusters of calcium oxalate crystal and different type of leaf transverse section. CONCLUSION: These characteristics can provide evidences for the identification and quality control of Potentilla glabra.