RESUMO
Rhizoma Paridis is a traditional Chinese medicine commonly used in the clinical treatment of gynecological diseases. Previous studies have shown that aqueous extracts of Rhizoma Paridis exhibit some hepatotoxicity to hepatocytes. Here, using lipidomics analysis, we investigated the potential hepatotoxicity of Rhizoma Paridis and its possible mechanism. The hepatic damaging of different solvent extracts of Rhizoma Paridis on zebrafish larvae were determined by a combination of mortality dose, biochemical, morphological, and functional tests. We found that ethyl acetate extracts (AcOEtE) were the most toxic fraction. Notably, lipidomic responsible for the pharmacological effects of AcOEtE were investigated by Q-Exactive HF-X mass spectrometer (Thermo Scientific high-resolution) coupled in tandem with a UHPLC system. Approximately 1958 unique spectral features were detected, of which 325 were identified as unique lipid species. Among these lipid species, phosphatidylethanolamine cardiolipin Ceramide (Cer), lysophosphatidylinositol sphingosine (Sph), etc., were significantly upregulated in the treated group. Pathway analysis indicates that Rhizoma Paridis may cause liver damage via interfering with the glycerophospholipid metabolism. Collectively, this study has revealed previously uncharacterized lipid metabolic disorder involving lipid synthesis, metabolism, and transport that functionally determines hepatic fibrosis procession.
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Background: Yiqi Huoxue Decoction (YQHXD) is a traditional Chinese medicine that promotes blood circulation, removes blood stasis, facilitates diuresis, and alleviates edema. It is composed of 10 herbal medicines and has extensive application in treating nephrotic syndrome (NS). However, the active components and the potential mechanism of YQHXD for treating NS remain unclear. Methods: We set up a sensitive and rapid method based on Ultra-High Performance Liquid Chromatograph-Mass (UPLC-MS) to identify the compounds in YQHXD and constituents absorbed into the blood. Disease genes were collected through GeneCards, DisGeNET, and OMIM database. Genes of compounds absorbed into blood were predicted by the TCMSP database. We constructed Disease-Drug-Ingredient-Gene (DDIG) network using Cytoscape, established a Protein-protein interaction (PPI) network using String, Gene biological process (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed using DAVID. Cellular experiments were performed to validate the results of network pharmacology. Result: A total of 233 compounds in YQHXD and 50 constituents absorbed into the blood of rats were identified. The 36 core targets in the PPI network were clustered in the phosphatidylinositol 3 kinase-RAC serine/threonine-protein kinase (PI3K-AKT) and nuclear factor kappa-B (NF-κB) signaling pathways. Luteolin, Wogonin, Formononetin, and Calycosin were top-ranking components as potentially active compounds. Conclusion: The results of our studies show that YQHXD is able to enhance renal function, alleviate podocyte injury, and improve adriamycin nephrotic syndrome.
RESUMO
A new anticancer ligustrazine derivative, 3beta-hydroxyolea-12-en-28-oic acid-3,5,6-trimethylpyrazin-2-methyl ester (T-OA, C38H58O3N2), was previously reported. It was synthesized via conjugating the effective antitumor ingredients of a classic traditional Chinese medicine (TCM) formulation. In the present study, anticancer efficacy of T-OA was evaluated in vivo using a murine sarcoma S180 model. Reduction of the tumor weight and tumor HE staining regions demonstrated that T-OA had promising inhibition effects and a 50% inhibitory rate in S180 mice. Combining the immunohistochemistry, we found T-OA exerted its antitumor activity by preventing the expression of nuclear transcription factor NF-kappaB/p65 and COX-2 in S180 mice. The acute toxic test showed that LD50 value of T-OA exceeded 6.0 g/kg via gavage in mice. In addition, a simple and rapid HPLC-UV method was developed and validated to study the pharmacokinetic characteristics of the compound. After single-dose oral administration, time to reach peak concentration of T-OA (3.97 microg/mL) was 8.33 h; the elimination half-life and area under the concentration-time curve from t = 0 to the last time of T-OA was 4.50 h and 48.01 microg x h/mL, respectively.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Inibidores de Ciclo-Oxigenase 2 , Ciclo-Oxigenase 2/biossíntese , Pirazinas/farmacologia , Fator de Transcrição RelA/antagonistas & inibidores , Administração Oral , Animais , Antineoplásicos Fitogênicos/farmacocinética , Calibragem , Cromatografia Líquida de Alta Pressão , Interpretação Estatística de Dados , Estabilidade de Medicamentos , Feminino , Imuno-Histoquímica , Limite de Detecção , Masculino , Camundongos , Pirazinas/farmacocinética , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sarcoma 180/tratamento farmacológico , Sarcoma 180/patologia , Espectrofotometria UltravioletaRESUMO
To discover new anti-cancer agents with multi-effect and low toxicity, a series of ligustrazine derivatives were synthesized using several effective anti-tumor ingredients of Shiquandabu Wan as starting materials. Our idea was enlightened by the "combination principle" in drug discovery. The ligustrazine derivatives' anti-tumor activities were evaluated on the HCT-8, Bel-7402, BGC-823, A-549 and A2780 human cancer cell lines. In addition the angiogenesis activities were valued by the chick chorioallantoic membrane (CAM) assay. 1,7-bis(4-(3,5,6-Trimethylpyrazin-2-yl)-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (4) and 3 α,12 α-dihydroxy-5ß-dholanic acid-3,5,6-trimethylpyrazin-2-methyl ester (5) not only displayed antiproliferative activities on these cancer cells, but also dramatically suppressed normal angiogenesis in CAM. The LD50 value of the compound 5 exceeded 3.0 g/kg by oral administration in mice.
Assuntos
Inibidores da Angiogênese/síntese química , Antineoplásicos Fitogênicos/síntese química , Membrana Corioalantoide/irrigação sanguínea , Medicamentos de Ervas Chinesas/química , Pirazinas/síntese química , Inibidores da Angiogênese/farmacologia , Animais , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Embrião de Galinha , Membrana Corioalantoide/efeitos dos fármacos , Descoberta de Drogas , Feminino , Humanos , Dose Letal Mediana , Espectroscopia de Ressonância Magnética , Camundongos , Neovascularização Fisiológica/efeitos dos fármacos , Pirazinas/farmacologiaRESUMO
OBJECTIVE: To identify dihydroflavonol glycoside isomers in Smilax glabra. METHOD: The sample was analyzed by HPLC-MS in combination with HPLC-1H-NMR. RESULT: Four dihydroflavonol glycoside isomers were identified as astilbin, neoastilbin, isoastilbin, neoisoastilbin. CONCLUSION: The method is simple and rapid for the identification of dihydroflavonol glycosides in S. glabra.
Assuntos
Flavonóis/análise , Flavonóis/química , Glicosídeos/análise , Glicosídeos/química , Smilax/química , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Isomerismo , Espectroscopia de Ressonância Magnética , Espectrometria de MassasRESUMO
AIM: To establish a comprehensive HPLC analytical method of Huanglianjiedu decoction. METHODS: This study was performed by HPLC-UV/MS to identify the chemical constituents of the whole and individual herbs of the "Huanglianjiedu decoction". Zorbax Extend C18 (150 mm x 4. 6 mm ID, 5 microm) column was used; the mobile phase was composed of acetonitrile (A) and water (B, with 0.5% acetic acid) with gradient elution; the flow rate was 1.0 mL x min(-1) and the column temperature was setup at 25 degrees C. The detection wavelength was 254 nm. RESULTS: The chromatogram of Huanglianjiedu decoction showed 21 main peaks. Peaks 1, 2, 5 and 18 were from Gardenia jasminoides Ellis, Peaks 8, 13, 14, 15, 16, 17, 19 and 21 from Scutellaria baicalensis Georgi. While 10 from Coptis chinensis Franch and 20 from Phellodendron amurense Rupr., Peaks 3, 4, 6, 9, 11 and 12 came from them together. Peak 7 presented in the chromatograms of the herbs except Gardenia jasminoides Ellis. By comparison of the retention time, the on-line UV spectra and MS spectra, 11 peaks were identified as 5 (geniposide), 9 (jatrorrhizine), 10 (coptisine), 11 (palmatine), 12 (berberine), 13 (baicalin), 15 (oroxin A), 17 (wogonoside), 19 (baicalein), 20 (obaculactone), 21 (wogonin), then eight of them were quantified by HPLC-UV. CONCLUSION: The method could represent the characteristics of Huanglianjiedu decoction, and it could be used to evaluate the quality and quantity of Huanglianjiedu decoction. It distinguished between Coptis chinensis Franch and Phellodendron amurense Rupr. by HPLC for the first time.
Assuntos
Coptis/química , Medicamentos de Ervas Chinesas/química , Phellodendron/química , Plantas Medicinais/química , Berberina/análogos & derivados , Berberina/análise , Alcaloides de Berberina/análise , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/isolamento & purificação , Gardenia/química , Espectrometria de Massas/métodos , Controle de Qualidade , Scutellaria baicalensis/química , Espectrofotometria Ultravioleta/métodosRESUMO
To study the safety of Aconitum medicinal herbs in clinic and identify Aconitum alkaloids poisoning in forensic medicine, Aconitum alkaloids and their metabolites were separated and identified in human urine by liquid chromatography-electrospray ionization-multi-stage mass spectrometry (LC-ESI-MS(n)) and chemical pathway of metabolism was investigated. The alkaloids and their metabolites in the urine sample were extracted with solid-phase cartridges and separated by HPLC with acetonitrile-water-formic acid (40:60:0.5) mobile phase. Structures of five metabolites and three parent Aconitum alkaloids were identified with multi-stage mass spectrometry data through comparison with authentic substances as aconitine (M(1)), mesaconitine (M(2)), hypaconitine (M(3)), benzoylaconine (M(4)), benzoylmesaconine (M(5)), benzoylhypaconine (M(6)), 16-O-demethylaconitine (M(7)) and 16-O-demethylhypaconitine (M(8)), respectively. Among them, M(8) was identified and reported for the first time. Metabolic pathways of Aconitum alkaloids in human body were proposed.