Metabolomics analysis delineates the therapeutic effects of Yinlan Tiaozhi capsule on triton WR-1339 -induced hyperlipidemia in mice.

Hyperlipidemia is a disorder of lipid metabolism resulting from abnormal blood lipid metabolism and is one of the most frequent metabolic diseases that endanger people's health. Yinlan Tiaozhi capsule (YL) is a formulated TCM widely used to treat hyperlipidemia. The purpose of this study was to discover biomarkers utilizing untargeted metabolomics techniques, as well as to analyze the mechanisms underlying the changes in metabolic pathways linked to lipid-lowering, anti-inflammation, and regulation of angiogenesis in hyperlipidemia mice. To assess the efficacy of YL, serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) levels were measured. Biochemical examinations showed that YL significantly reduced the levels of TC, TG, LDL-c, Il6, Tnf-α, and Vegfa in hyperlipidemia mice (p < 0.01). YL also significantly increased the levels of HDL-c and Alb (p < 0.01). Twenty-seven potential serum biomarkers associated with hyperlipidemia were determined. These differential metabolites were related to the reduction of serum lipid levels in hyperlipidemia mice, probably through metabolic pathways such as linoleic acid metabolism, glycerophospholipid metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and D-glutamine and D-glutamate metabolism. Further correlation analysis showed that the serum lipid reduction through YL was related to the metabolites (amino acid metabolites, phospholipids metabolites, and fatty acids metabolites). The present study reveals that YL has a profound effect on alleviating triton WR-1339-induced hyperlipidemia, inflammation, and angiogenesis and that the positive effects of YL were primarily associated with the correction of metabolic abnormalities and the maintenance of metabolite dynamic balance.

[Prediction and analysis of Q-markers of Elephantopus scaber based on its UPLC fingerprint, content determination of components, and in vitro a nti-tumor activity].

This study aimed to provide scientific evidence for predicting quality markers(Q-markers) of Elephantopus scaber by establishing UPLC fingerprint of E. scaber from different geographical origins and determining the content of 13 major components, as well as conducting in vitro anti-cancer activity investigation of the main components. The chromatographic column used was Waters CORTECS UPLC C_(18)(2.1 mm×150 mm, 1.6 µm), and the mobile phase consisted of acetonitrile and 0.1% formic acid solution(gradient elution). The column temperature was set at 30 ℃, and the flow rate was 0.2 mL·min~(-1). The injection volume was 1 µL, and the detection wavelength was 240 nm. The UPLC fingerprint of E. scaber was fitted using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 edition) to determine common peaks, evaluate similarity, identify and determine the content of major components. The CCK-8 assay was used to explore the inhibitory effect of the main components on the proliferation of lung cancer cells. The results showed that in the established UPLC fingerprint of E. scaber, 35 common peaks were identified. Thirteen major components, including neochlorogenic acid(peak 1), chlorogenic acid(peak 2), cryptochlorogenic acid(peak 3), caffeic acid(peak 4), schaftoside(peak 6), galuteolin(peak 9), isochlorogenic acid B(peak 10), isochlorogenic acid A(peak 12), isochlorogenic acid C(peak 18), deoxyelephantopin(peak 28), isodeoxyelephantopin(peak 29), isoscabertopin(peak 31), and scabertopin(peak 32) were identified and quantified, and a quantitative analysis method was established. The results of the in vitro anti-cancer activity study showed that deoxyelephantopin, isodeoxyelephantopin, isoscabertopin, and scabertopin in E. scaber exhibited inhibition rates of lung cancer cell proliferation exceeding 80% at a concentration of 10 µmol·L~(-1), higher than the positive drug paclitaxel. These results indicate that the fingerprint of E. scaber is highly characteristic, and the quantitative analysis method is accurate and stable, providing references for the research on quality standards of E. scaber. Four sesquiterpene lactones in E. scaber show significant anti-cancer activity and can serve as Q-markers for E. scaber.

Deciphering the mechanisms of Yinlan Tiaozhi capsule in treating hyperlipidemia by combining network pharmacology, molecular docking and experimental verification.

Yinlan Tiaozhi capsule (YLTZC) has been widely used to treat hyperlipidemia (HLP). However, its material basis and underlying pharmacological effects remain unclean. The current study aimed to explore the mechanisms involved in the treatment of YLTZC on HLP based on network pharmacology, molecular docking, and experimental verification. Firstly, UPLC-Q-TOF-MS/MS was used to comprehensively analyze and identify the chemical constituents in YLTZC. A total of 66 compounds, mainly including flavonoids, saponins, coumarins, lactones, organic acids, and limonin were characterized and classified. Simultaneously, the mass fragmentation pattern of different types of representative compounds was further explored. By network pharmacology analysis, naringenin and ferulic acid may be the core constituents. The 52 potential targets of YLTZC, including ALB, IL-6, TNF, and VEGFA, were considered potential therapeutic targets. Molecular docking results showed that the core active constituents of YLTZC (naringenin and ferulic acid) have a strong affinity with the core targets of HLP. Lastly, animal experiments confirmed that naringenin and ferulic acid significantly upregulated the mRNA expression of ALB and downregulated the mRNA expression of IL-6, TNF, and VEGFA. In sum, the constituents of YLTZC, such as naringenin and ferulic acid, might treat HLP by regulating the mechanism of angiogenesis and inhibiting inflammatory responses. Furthermore, our data fills the gap in the material basis of YLTZC.

Network pharmacology analysis and experimental validation to explore the mechanism of Bushao Tiaozhi capsule (BSTZC) on hyperlipidemia.

Bushao Tiaozhi Capsule (BSTZC) is a novel drug in China that is used in clinical practice and has significant therapeutic effects on hyperlipidemia (HLP). In our previous study, BSTZC has a good regulatory effect on lipid metabolism of HLP rats. However, its bioactive compounds, potential targets, and underlying mechanism remain largely unclear. We extracted the active ingredients and targets in BSTZC from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and literature mining. Subsequently, core ingredients, potential targets, and signaling pathways were determined through bioinformatics analysis, including constructed Drug-Ingredient-Gene symbols-Disease (D-I-G-D), protein-protein interaction (PPI), the Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, the reliability of the core targets was evaluated using in vivo studies. A total of 36 bioactive ingredients and 209 gene targets were identified in BSTZC. The network analysis revealed that quercetin, kaempferol, wogonin, isorhamnetin, baicalein and luteolin may be the core ingredients. The 26 core targets of BSTZC, including IL-6, TNF, VEGFA, and CASP3, were considered potential therapeutic targets. Furthermore, GO and KEGG analyses indicated that the treatment of HLP by BSTZC might be related to lipopolysaccharide, oxidative stress, inflammatory response and cell proliferation, differentiation and apoptosis. The pathway analysis showed enrichment for different pathways like MAPK signaling pathway, AGE-RAGE signaling pathway in diabetic, IL-17 signaling pathway and TNF signaling pathway. In this study, network pharmacology analysis, and experiment verification were combined, and revealed that BSTZC may regulate key inflammatory markers and apoptosis for ameliorating HLP.

Network Pharmacology and Molecular Docking-Based Prediction of the Mechanism of Qianghuo Shengshi Decoction against Rheumatoid Arthritis.

Qianghuo Shengshi decoction (QHSSD) is a classical Chinese medicine formula, which is used in clinical practice for the treatment of rheumatoid arthritis (RA) in China. However, the pharmacological mechanism of QHSSD on RA has remained unclear by now. We collected and screened active compounds and its potential targets by the pharmacology platform of Chinese herbal medicines. In addition, the therapeutic targets of RA were obtained and selected from databases. Network construction analyzed that 128 active compounds may act on 87 candidate targets and identified a total of 18 hub targets. GO annotation and KEGG enrichment investigated that the action mechanism underlying the treatment of RA by QHSSD might be involved in cell proliferation, angiogenesis, anti-inflammation, and antioxidation. Finally, molecular docking verification showed that TP53, VEGFA, TNF, EGFR, and NOS3 may be related to the RA treatment and molecular dynamics simulation showed the stability of protein-ligand interactions. In this work, QHSSD might exert therapeutic effect through a multicomponent, multitarget, and multipathway in RA from a holistic aspect, which provides basis for its mechanism of action and subsequent experiments.

Corrigendum to "Selection of quality markers of Jasminum amplexicaule based on its anti-diarrheal and anti-inflammatory activities: Effect-target affiliation-traceability-pharmacokinetics strategy" [Chinese Herbal Medicines 11 (2019) 379-386].

[This corrects the article DOI: 10.1016/j.chmed.2019.08.002.].

Tanshinol A Ameliorates Triton-1339W-Induced Hyperlipidemia and Liver Injury in C57BL/6J Mice by Regulating mRNA Expression of Lipemic-Oxidative Injury Genes.

Tanshinol A, which is derived from a traditional Chinese herbal Radix Salviae Miltiorrhizae is indicative of a hypolipidemic candidate. Therefore, we aim to validate its hypolipidemic activity of tanshinol A and explore its mechanism in triton-1339W-induced hyperlipidemic mice model, which possess multiply pathogenesis for endogenous lipid metabolism disorder. Experimental hyperlipidemia mice are treated with or without tanshinol A (i.g. 40, 20, 10 mg/kg), and blood and liver tissue were collected for validating its hypolipidemic and hepatic protective effect, and hepatic mRNA expression profile, which was associated with lipid metabolism dysfunction and liver injury, was detected by RT-qPCR. As results show, triton-1339W-induced abnormal of serum TC, TAG, HDL-C, LDL-C, SOD, MDA, GOT, and GPT is remarkably attenuated by tanshinol A. In pathological experiment, triton-1339W-induced hepatocellular ballooning degeneration, irregular central vein congestion, and inflammation infiltration are alleviated by tanshinol A. Correspondingly, hepatic mRNA expression of Atf4, Fgf21, Vldlr, Nqo1, Pdk4, and Angptl4, which are genes regulating lipemic-oxidative injury, are significantly increased by tanshinol A by 2~6 fold. Abcg5, Cd36, and Apob, which are responsible for cholesterol metabolism, are mildly upregulated. Noticeably, triton-1339W-suppressed expressions of Ptgs2/Il10, which are genes responsible for acute inflammation resolution in liver injury, are remarkably increased by tanshinol A. Conclusively, tanshinol A exerted hypolipidemic effect and hepatoprotective effect through restoring triton-1339W-suppressed mRNA expression, which may be involved in Atf4/Fgf21/Vldlr and Ptgs2/Il-10 signaling pathways.

Selection and evaluation of quality markers from Yinlan capsule and its LXRα-mediated therapy for hyperlipidemia.

BACKGROUND: The selection of active compounds for the quality evaluation of traditional Chinese medicine (TCM), specifically complex formulas, remains a challenge for researchers, as components selected as indexes usually have no clear relation with the therapeutic effects of interest. As a suggested resolution, quality control markers (Q-markers) showed good perspective for discriminating numerous compounds found for specific efficacies. In the presented study, the components of the Yinlan (YL) capsule, a TCM patent formula comprising four ingredients, were evaluated and selected for their lipid regulatory effects using principles for Q-marker selection. PURPOSE: The mechanism of TCM therapeutic effects involves several pathways and targets that combine to become an integrated action in the body. Therefore, it is assumed that specific compounds in YL should have good affinity for related targets and obvious effects (both up- and downregulating). Thus, a series of experiments, including cytobiology, animal-based pharmacodynamics, computer-assisted drug design, conventional content determination and pharmacokinetics, would be helpful for the selection and final confirmation of Q-markers. METHODS: The capsule was first administered to Wistar mice fed a high-fat diet and tested for their triglycerides (TG) and total cholesterol (TC) values to evaluate the effectiveness of YL. Then, liver tissue was extracted for gene expression. According to the results, the compounds in YL with good affiliation were selected and determined using UHPLC-MS-MS, and those with adequate results in the capsule were chosen as Q-marker candidates. Finally, pharmacokinetics research was performed; the candidates with desirable metabolite and bioavailability parameters were confirmed as Q-markers of YL. RESULTS: YL capsule was capable of lowering TG and TC levels. For target selection, the expression of LXR mRNA increased significantly at all three tested dosages. Downstream genes, such as LCAT, CYP7A1, and ABCA1, and intestinal FXR mRNA also showed significant increases in expression. For screening of the Q-marker candidates, 5 compounds were selected according to abovementioned results. The pharmacokinetics research demonstrated that the rats exploited lupeol and ginsenoside Rb3 in a desirable pattern with adequate bioavailability, which confirmed their roles as lipid regulatory Q-markers. CONCLUSION: The YL capsule was demonstrated to have obvious lipid regulatory effects, which are mainly exerted by targeting LXR and its related pathway. Lupeol and ginsenoside Rb3 were validated as Q-markers that represent the anti-hyperlipidemia activity of the capsule.

[Chemical Constituents from Jasminum elongatum].

Objective: To investigate the chemical constituents of Jasminum elongatum. Methods: The chemical constituents were isolated and purified by various column chromatographic methods and preparative HPLC. Their structures were identified by physicochemical properties and spectral analysis. Results: Nine compounds were isolated from the methanol extract of Jasminum elongatum and identified as protocatechuic acid( 1),caffeic acid( 2),salicylic acid( 3),isovanillic acid( 4),ferulic acid( 5),methyl caffeate( 6),caffein( 7),3,6-diisopropylpiperazin-2,5-dione( 8),scopoletin( 9). Conclusion: All the compounds are isolated from the this plants for the first time.

[Rapid Identification of Chemical Components in Polygonum multiflorum Formula Granules by UPLC/Q-TOF MS].

OBJECTIVE: To establish a simple and reliable method for rapid separation and identification of chemical components in Polygonum multiflorum Formula Granules. METHODS: An ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometric method( UPLC/Q-TOF MS) was used. The separation was performed on an Agilent Eclipse Plus C18 RRHD(100 mm x 2.1 mm, 1.8 µm) column with a mobile phase of water and acetonitrile in a gradient elution mode. The flow rate was 0.4 mL/min and the column temperature was maintained at 25 degrees C. TOF MS was applied for qualitative analysis under positive ion mode. RESULTS: Five compounds were identified by the time of flight mass spectrometry and literature data. CONCLUSION: This method is accurate, rapid and sensitive, it can provide reference for the quality control of Polygonum multiflorum Formula Granules.

Peniphenones A-D from the mangrove fungus Penicillium dipodomyicola HN4-3A as inhibitors of Mycobacterium tuberculosis phosphatase MptpB.

A pair of unusual benzannulated 6,6-spiroketal enantiomers [(-)-1 and (+)-1] and three new biogenetically related compounds (2-4), together with two known related analogues (5 and 6), have been isolated from a mangrove fungus, Penicillium dipodomyicola HN4-3A. Their structures were elucidated on the basis of spectroscopic analysis (1D and 2D NMR data) and X-ray crystallography. The absolute configurations of enantiomers (-)-1 and (+)-1 were determined using quantum chemical calculations of the electronic circular dichroic (ECD) spectra. Compounds 2 and 3 exhibited strong inhibitory activity against Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB) with IC50 values of 0.16±0.02 and 1.37±0.05 µM, respectively.

Cytotoxic norsesquiterpene peroxides from the endophytic fungus Talaromyces flavus isolated from the mangrove plant Sonneratia apetala.

Four new norsesquiterpene peroxides, named talaperoxides A-D (1-4), as well as one known analogue, steperoxide B (5, or merulin A), have been isolated from a mangrove endophytic fungus, Talaromyces flavus. Their structures were elucidated mainly by 1D and 2D NMR. Structures of 1, 2, and 5 were further confirmed by single-crystal X-ray diffraction, and their absolute configurations were also determined using copper radiation. Cytotoxic activities of compounds 1-5 were evaluated in vitro against human cancer cell lines MCF-7, MDA-MB-435, HepG2, HeLa, and PC-3. Compounds 2 and 4 showed cytotoxicity against the five human cancer cell lines with IC50 values between 0.70 and 2.78 µg/mL.