Two Omics Methods Expose Anti-Depression Mechanism of Raw and Vinegar-Baked Bupleurum Scorzonerifolium Willd.

Bupleurum scorzonerifolium willd. (BS) and its vinegar-baked product (VBS) has been frequently utilized for depression management in clinical Chinese medicine. This paper aims to elucidate the antidepressant mechanism of BS and VBS from the perspectives of metabonomics and gut microbiota. A rat model of depression was established by CUMS combined with feeding alone to evaluate the antidepressant effects of BS and VBS. UPLC-Q-TOF-MS/MS-based metabolomics and 16S rRNA sequencing of rat feces were applied and the correlation of differential metabolic markers and intestinal floras was analyzed. The result revealed that BS and VBS significantly improved depression-like behaviors and the levels of monoamine neurotransmitters in CUMS rats. There were 27 differential endogenous metabolites between CUMS and normal rats, which were involved in 8 metabolic pathways. Whereas, BS and VBS could regulate 18 and 20 metabolites respectively, wherein fifteen of them were shared metabolites. On the genus level, BS and VBS could regulate twenty-five kinds of intestinal floras in CUMS rats, that is, they increased the abundance of beneficial bacteria and decreased the abundance of harmful bacteria. In conclusion, both BS and VBS exert excellent antidepressant effects by regulating various metabolic pathways and ameliorating intestinal microflora dysfunction.

Optimum Reaction Conditions for the Synthesis of Selenized Ornithogalum caudatum Ait. (Liliaceae) Polysaccharides and Measurement of Their Antioxidant Activity In Vivo.

This study determined the optimum reaction conditions for synthesizing selenium-containing polysaccharides. Polysaccharide IIA (with the highest yield) from Ornithogalum caudatum Ait. (Liliaceae) (OCAPIIA) was extracted and purified. Then, three parameters were selected to optimize the synthesis of selenized OCAPIIA (Se-OCAPIIA) using the Box-Behnken design (BBD) and response surface methodology (RSM). The morphology of Se-OCAPIIA was analyzed by scanning electron microscopy (SEM). The characteristic peaks and the monosaccharide composition of Se-OCAPIIA were evaluated by Fourier-transform infrared spectroscopy and gas chromatography. A D-galactose-induced aging mouse model was established, and the in vivo antioxidant activity of Se-OCAPIIA was measured. The optimal conditions for the synthesis of Se-OCAPIIA were as follows: reaction temperature, 72.38 °C; Na2SeO3 to OCAPIIA mass ratio, 0.93 g/g; and reaction time, 8.05 h. The selenium content of Se-OCAPIIA obtained using the optimized process was 3.131 ± 0.090 mg/g, close to the maximum predicted value (3.152 mg/g). Se-OCAPIIA contained D-mannose, D-glucose, and D-galactose at a molar ratio of 1.00:0.34:0.88. SEM showed that Se-OCAPIIA was spherical and flocculated. Compared with OCAPIIA, Se-OCAPIIA exhibited two characteristic peaks at 833 and 610 cm-1 in the infrared spectrum. Se-OCAPIIA increased catalase, glutathione peroxidase, and superoxide dismutase activities and decreased MDA concentrations in the mouse liver. Moreover, Se-OCAPIIA treatment improved liver morphology, decreased the levels of IL-1ß and IL-6, and increased IL-10 concentration. In conclusion, the synthesis of Se-OCAPIIA is effective, simple, and feasible. Se-OCAPIIA demonstrated high antioxidant activity in vivo and is a promising antioxidant and therapeutic agent.

Screening of Q-markers for the wine-steamed Schisandra chinensis decoction pieces in improving allergic asthma.

BACKGROUND: Traditional Chinese medicine (TCM) posits that Chinese medicinal materials can only be clinically used after being processed and prepared into decoction pieces. Schisandra Chinensis Fructus (derived from the dried and mature fruits of Schisandra chinensis (Turcz.) Baill.) has been used as a traditional antiasthmatic, kidney strengthening, and hepatoprotective agent for 2000 years. The results of previous research show that decoction pieces of wine-steamed Schisandra chinensis (WSC) are more effective than raw decoction pieces of Schisandra chinensis (RSC) for treating cough and asthma. Steaming with wine was demonstrated to promote the dissolution of ingredients. However, the relationship between the changes in the components of the decoction pieces of WSC and the therapeutic effect remains unclear. METHODS: The efficacies of decoctions of RSC and WSC were compared using allergic asthma rats. The potential bioactive components in the serum of the WSC treatment group and the changes in the chemical composition of the RSC decoction pieces before and after wine steaming were determined by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) and ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC H-CLASS XEVO TQD) to speculate quality markers (Q-markers) related to the efficacy of WSC, which were subsequently verified based on a zebrafish inflammation model. RESULTS: Steaming RSC decoction pieces with wine was found to promote improvement of allergic asthma. Reverse tracing of 22 components detected in the serum of the high dose group of WSC (WSC-H) resulted in 12 ingredients being finally designated as potential effective components. Among these ingredients, 5 components, Schisandrin, Schisandrol B, Schisandrin A, Schisandrin B, and Gomisin D, had higher dissolution rates than RSC after steaming with wine. Validation by an inflammatory zebrafish model showed that these 5 ingredients had a dose-dependent effect and were therefore Q-markers for WSC in the treatment of allergic asthma. CONCLUSION: In this study, changes in the components of decoction pieces of RSC and WSC and Q-markers related to WSC efficacy were identified, providing valuable information for expanding the application of WSC and establishing a specific quality standard for WSC.

Bupleurum scorzonerifolium: Systematic research through pharmacodynamics and serum pharmacochemistry on screening antidepressant Q-markers for quality control.

Bupleurum scorzonerifolium (BS) is one of the sources of Bupleuri Radix, which was first recorded in Shennong's classic of materia medica. It has a medicinal history of 2000 years and is now widely used for the treatment of depression clinically. However, the material basis of antidepressant effects is unclear, and the quality evaluation method is lacking. The paper aims to investigate the antidepressant quality markers (Q-markers) of BS by electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF-MS). Firstly, the rat depression model was established by using chronic unpredictable mild stress (CUMS) combined with the solitary confinement method to evaluate the pharmacodynamics of BS. After verification of the antidepressant effect of BS, UPLC-ESI-Q-TOF-MS was used to analyze BS and the blood components of BS. A total of 34 components were identified in BS, in which 8 components, including saikosaponin a (SSa), saikosaponin c (SSc), saikosaponin d (SSd), saikosaponin b1 (SSb1), saikosaponin b2 (SSb2), glycyrrhetinic acid, nootkatone and valerenic acid, were detected in serum. SSa, SSc, SSd, SSb1 and SSb2 were found as metabolites, and glycyrrhetinic acid, nootkatone and valerenic Acid were identified as the prototypes in the blood. The depression model of zebrafish was established with reserpine to verify the antidepressant effect of the potential eight active components. The results showed that all these components could markedly improve the depressive behavior of zebrafish, increase the content of 5-HT and reduce the cortisol content. Finally, according to the principles of effectiveness, accessibility and measurability for Q-markers, SSa, SSc, and SSd were confirmed as Q-markers of BS, and the contents of 3 Q-markers in 10 batches of BS from different origins were determined to be 0.0728-1.465%. In addition, the total contents of 3 Q-markers in BS produced in Lindian, Heilongjiang Province, were higher than those in other origins. This paper provided a reliable method for the quality evaluation of BS for depression treatment.

[Mechanism of Bupleurum scorzonerifolium and Paeonia lactiflora herbal pair against liver cancer: an exploration based on UPLC-Q-TOF-MS combined with network pharmacology].

This study aimed to decipher the pharmacodynamic material basis and mechanism of herbal pair Bupleurum scorzonerifolium-Paeonia lactiflora(BS-PL) against liver cancer based on UPLC-Q-TOF-MS and network pharmacology. MTT assay and human hepatocellular carcinoma HepG2 cells were used to screen the effective part of BS-PL, the active components of which were further analyzed and identified by UPLC-Q-TOF-MS. Next, we applied Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) to screen the active ingredients with OB≥30%. Then TCMSP and SwissTargetPrediction were used to collect and predict component targets, followed by the search of liver cancer-related targets with GeneCards and DisGeNET. The intersection targets were obtained using Venny 2.1.0. Protein-protein interaction(PPI) network was constructed using STRING to uncover the core targets, which were subjected to Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis based on DAVID. Finally, the effects of active ingredients on the expression of main proteins enriched in the key pathways of HepG2 cells were verified by Western blot. The results indicated that compared with 30%, 50%, and 70% ethanol extracts of BS-PL, the n-butanol extraction part(CSYZ) from 95% ethanol extract of BS-PL exhibited the best anti-tumor effect. UPLC-Q-TOF-MS revealed 31 ingredients, 14 of which showed OB≥30%. A total of 220 intersection targets were obtained, from which 35 were selected as the key targets under the condition of two times the median of degree. Among the 215 items with P<0.05 obtained through GO enrichment analysis, 154 were classified into biological processes, 22 into cell components and 39 into molecular functions. KEGG enrichment analysis revealed 95 significantly affected signaling pathways, and the ones(sorted in a descending order by P value) closely related to the anti-liver cancer effect of herbal pair were PI3 K-AKT signaling pathway, TNF signaling pathway, MAPK signaling pathway, HIF-1 signaling pathway, and ErbB signaling pathway. Finally, the PI3 K/AKT signaling pathway involving the largest number of targets was extrapolated, and it was found that this pathway contained 15 core targets and 8 active components. Experimental verification showed that the effective components of BS-PL significantly inhibited the expression of p-PI3 K and p-AKT, consistent with the prediction results of network pharmacology. In conclusion, the main pharmacodynamic substances of BS-PL against liver cancer are 14 components like saikosaponin a, saikosaponin d, and paeoniflorin, which exert the anti-liver cancer effect by regulating PI3 K/AKT pathway.

Two new phenolic acids from the fruits of Forsythia suspense.

Two new phenolic acids forsythiayanoside C (1) and forsythiayanoside D (2), were isolated from the fruits of Forsythia suspense (Thunb.) Vahl. Their structures were elucidated on the basis of chemical and spectral analysis, including 1D, 2D NMR analyses, HRESIMS and CD spectrometry. The cytotoxic and antioxidant activities testing showed that compound 2 exhibited free radical scavenging activity.

[Study on hydrolysable tannin constituents of seed of Juglans regia II].

OBJECTIVE: To study hydrolysable tannin constituents of the seed of Juglans regia. METHOD: The chemical constituents were isolated by Diaion HP-20, Toyopaerl HW-40 and MCI gel CHP-20P column chromatogramphy and identified by physicochemical identification and spectral data. RESULT: Six compounds obtained from the 70% ethanol extract were identified as 1, 2, 3, 4, 6-penta-O-galloyl-3-D-glucose (1), rugosin C (2), 1, 2, 3, 6-tetra-O-galloyl-3-D-glugose (3), tellimagrandin II (4), casuarictin (5), 1-degalloylrugosin F (6). CONCLUSION: All compouds were isolated from the seeds of J. regia for the first time.

[Studies on hydrolysable tannin constituents in seed of Juglans regia(I)].

OBJECTIVE: To study hydrolysable tannin constituents of the seeds of Juglans regia. METHOD: The chemical constituents were isolated by Diaion HP-20 and Toyopaerl HW-40 MCI gel CHP-20P column chromatogramphy and identified by physicochemical identification and spectral data. RESULT: The compounds obtained from the 70% acetone extract were identified as gemin D (1), casuariin (2), pedunculagin (3), tellimagrandin I (4), rugosin F (5), heterophylliin D (6). CONCLUSION: All other compounds which were isolated from the seeds of J. regia for the first time.