Screening and evaluation of quality markers of Radix Cudramiae for liver disease based on an integrated strategy of in vivo pharmacokinetics and in vitro HPLC fingerprint.

Radix Cudramiae, the dried root of Cudrania cochinchinensis (Lour.) Kudo et Masam., is a valuable ethnomedicine with outstanding antihepatitis activity. However, the lack of reports on quality markers (Q-markers) hindered its quality evaluation and standardization, as a result restricted its clinical application. This paper aimed to discover the Q-markers of Radix Cudramiae with a comprehensive strategy based on in vivo pharmacokinetics and in vitro HPLC fingerprint. A rapid and sensitive ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS/MS) analytical method was firstly developed and validated for simultaneous determination of six potential active ingredients (eriodictyol, dihydrokaempferol, dihydromorin, kaempferol, naringenin and morin) of Radix Cudramiae in rat plasma and tissues, which was successfully applied to the holistic comparison of pharmacokinetics and tissue distribution between normal and acute liver injury rats. On the other hand, a representative HPLC fingerprint of Radix Cudramiae was also established to elucidate the chemical profile for overall quality evaluation. Dihydrokaempferol-7-O-ß-D-glucoside (the naturally existed chemical formation of dihydrokaempferol) and kaempferol screened out with high exposure levels in vivo and high resolution in HPLC fingerprint were finally selected as Q-markers of Radix Cudramiae. To the best of our knowledge, it was the first time for people to discover in vivo properties and pharmacokinetic parameters of components in Radix Cudramiae, as well as the first report on its representative HPLC fingerprint. Also, the integrated strategy could offer an effective way for TCMs Q-markers screening.

Insight gained via ultra-performance liquid chromatography tandem mass spectrometry-based metabolomics: Protective effect of Artemisia argyi H.Lév. & Vaniot essential oil on lipopolysaccharide-induced liver injury mice.

Artemisia argyi H.Lév. & Vaniot essential oil (AAEO) has shown pharmacological effects such as anti-inflammation, antioxidant, and anti-tumor properties. However, the protective effect of AAEO on lipopolysaccharide (LPS)-induced liver injury and its potential protective mechanism are still unclear. In this study, we used ultra-performance liquid chromatography tandem mass spectrometry metabolomics techniques to investigate the changes in liver tissue metabolites in mice exposed to LPS with or without AAEO treatment for 14 days. The biochemical results showed that compared with the control group, AAEO significantly reduced the levels of liver functional enzymes, suggesting a significant improvement in liver injury. In addition, the 18 differential metabolites identified by metabolomics were mainly involved in the reprogramming of arachidonic acid metabolism, tryptophan metabolism, and purine metabolism. AAEO could significantly inhibit the expression of COX-2, IDO1, and NF-κB; enhance the body's anti-inflammatory ability; and alleviate liver injury. In summary, our study identified the protective mechanism of AAEO on LPS-induced liver injury at the level of small molecular metabolites, providing a potential liver protective agent for the treatment of LPS-induced liver injury.

Clinical Value of Serum miR-124 and miR-200C Combined with Ultrasound NT in Screening Down Syndrome in Elderly Puerperae in the Second Trimester.

Objective: To evaluate the clinical value of serum miR-124 and miR-200C combined with ultrasound NT in screening Down syndrome (DS) in elderly puerperae during the second trimester. Methods: 84 elderly pregnant women at high risk of DS were included (DS group: 58, non-DS group: 26). Serum markers (uE3, ß-hCG, AFP, miR-124, and miR-200C) were measured. Differences in markers between groups were analyzed, and a prediction model was used for DS evaluation. Results: The DS group showed higher smoking, drinking, and radiation exposure rates (P < .05). MOM values of ß-hCG and AFP were higher, while MOM value of uE3 was lower in the DS group (P < .05). MiR-124 and miR-200C were up-regulated in the DS group (P < .05). The prediction model and ROC curve analysis indicated the diagnostic value of the markers for DS (AUC = 0.779, 0.817, 0.780, 0.884, 0.887, P < .05). MiR-124 had the highest diagnostic specificity. Conclusion: MiR-124 and miR-200C can serve as auxiliary serum markers for early screening of DS in elderly puerperae during the second trimester.

Cineole inhibits the biosynthesis of leukotrienes and prostaglandins to alleviate allergic rhinitis: Insights from metabolomics.

Allergic rhinitis (AR) is a common allergic disease characterized by nasal congestion, rhinorrhoea, and sneezing. Cineole, a monoterpenoid compound widely present in various volatile oils, has a wide range of pharmacological activities and is of interest in allergic airway diseases for its anti-inflammatory and anti-mucus production abilities. However, the protective effects of cineole in mice with allergic rhinitis and its mechanisms have not been well investigated. In this study, the protective effect of cineole against ovalbumin-induced (OVA-induced) allergic rhinitis and its molecular mechanism is investigated by metabolomic analysis based on ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). OVA combined with aluminum hydroxide adjuvant is used to sensitize and establish the allergic rhinitis (AR) mouse model. The mice are randomly divided into groups of control, AR, cineole (30 mg/kg), and budesonide (38.83 µg/kg). The pharmacodynamic results show that cineole significantly reduces the levels of Th2-type cytokines and OVA-specific IgE (OVA-sIgE) in AR mice, improves nasal mucosal tissue damage and alleviates nasal symptoms compared to the untreated AR group. Metabolomic results show that arachidonic acid (AA) metabolism and tryptophan (Trp) metabolism are reprogrammed on the basis of 27 significantly altered metabolites. Further studies show that cineole inhibits the biosynthesis of pro-inflammatory lipid mediators leukotrienes (LTs) and prostaglandins (PGs) in mice by inhibiting the activity of 5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) in the arachidonic acid metabolic (AA metabolic) pathway. It also inhibits the production of Th2 cytokines and inflammatory cell infiltration, thereby alleviating symptoms such as nasal congestion and nasal leakage. These results reveal the action and molecular mechanism of cineole in alleviating AR and provide a theoretical basis for the clinical application of cineole in treating AR.

Chemical profiling and identification of Radix Cudramiae and their metabolites in rats using an ultra-high-performance liquid chromatography method coupled with time-of-flight tandem mass spectrometry.

Radix Cudramiae, known as "Chuan-Po-Shi" in China, is a herbal medicine widely used in the southwest of the country, especially applied by the Miao and Zhuang nationalities for the treatment of liver diseases, such as acute liver injury and liver fibrosis. As a kind of ethnomedicine, the report on its chemical analysis was still blank, which restricted its clinical application. Therefore, this paper aimed to illustrate the chemical characteristics of Radix Cudramiae. A rapid analytical strategy based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry was developed to profile the natural small-molecular compounds in Radix Cudramiae, as well as the related prototypes and their metabolites in rats after drug administration. As a result, a total of 74 compounds were detected in the aqueous exact of Radix Cudramiae. In vivo, 45 chemicals including 16 prototypes and 29 metabolites in rat serum, along with 35 chemicals including 17 prototypes and 18 metabolites in rat liver, were screened out and identified. For the first time, the chemical constituents of Radix Cudramiae and their metabolic characteristics were discovered. It was hoped that this work would be beneficial for the safe and effective application of Radix Cudramiae in a clinic.