RESUMO
Compound Shenhua Tablet, a medicine comprising seven herbs, is employed in treating IgA nephropathy. This study aimed to meticulously analyze its chemical composition. Based on a list of candidate compounds, identified through extensive literature review pertinent to the tablet's herbal components, the composition analysis entailed the systematic identification, characterization, and quantification of the constituents. The analyte-capacity of LC/ESI-MS-based and GC/EI-MS-based assays was evaluated. The identified and characterized constituents were quantified to determine their content levels and were ranked based on the constituents' daily doses. A total of 283 constituents, classified into 12 distinct categories, were identified and characterized in the Compound Shenhua Tablet. These constituents exhibited content levels of 1-10 982 µg·g-1, with daily doses of 0.01-395 µmol·d-1. The predominant constituents, with daily doses of ≥ 10 µmol·d-1, include nine organic acids (citric acid, quinic acid, chlorogenic acid, cryptochlorogenic acid, gallic acid, neochlorogenic acid, isochlorogenic acid C, isochlorogenic acid B, and linoleic acid), five iridoids (specnuezhenide, nuezhenoside G13, nuezhenidic acid, secoxyloganin, and secologanoside), two monoterpene glycosides (paeoniflorin and albiflorin), a sesquiterpenoid (curzerenone), a triterpenoid (oleanolic acid), and a phenylethanoid (salidroside). Additionally, there were 83, 126, and 55 constituents detected in the medicine with daily doses of 1-10, 0.1-1, and 0.01-0.1 µmol·d-1, respectively. The combination of the LC/ESI-MS-based and GC/EI-MS-based assays demonstrated a complementary relationship in their analyte-capacity for detecting the constituents present in the medicine. This comprehensive composition analysis establishes a solid foundation for further pharmacological research on Compound Shenhua Tablet and facilitates the quality evaluation of this complex herbal medicine.
Assuntos
Medicamentos de Ervas Chinesas , Glomerulonefrite por IGA , Humanos , Medicina Tradicional Chinesa , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas em Tandem , Glomerulonefrite por IGA/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , ComprimidosRESUMO
Fennel, commonly used in traditional Chinese medicine, is known as Foeniculum vulgare Mill. And its clinical application has been shown to target many biological systems including gastroenterology, endocrinology, gynecology and respiratory. The main constituent of the fennel essential oil is transanethole, which has been described to have antiinflammatory and antibacterial activities. The aim of the present study was to define the antiinflammatory influence in acute lung injury (ALI)bearing mice. For 3 days, ALIbearing mice were induced by lipopolysaccharide (LPS) suspension in normal saline (24 mg/kg). On the fourth day, the transanethole was administrated (36.4, 72.8 or 145.6 mg/kg) as well as dexamethasone (5 mg/kg) once per day for 7 consecutive days in mice. Following the completion of drug administration mice were sacrificed. Hematoxylin and eosin staining was performed in the lung paraffin section, for comparisons between monocyte and eosinophil cells in bronchoalveolar lavage fluid. The relative gene expression of interleukin (IL)10 and IL17 was determined by reverse transcriptionquantitative polymerase chain reaction. These two cytokines and the proportion of T helper 17 (Th17) cells and T regulatory (Treg) cells were determined by flow cytometry. The main constituent of fennel, transanethole, eliminated LPSinduced histopathological changes, decreased the number of inflammatory cells and resulted in a notable reduction in IL17 mRNA expression. In addition, transanethole increased IL10 mRNA expression in isolated lung tissues and resulted in a marked elevation in Treg cells and reduction in Th17 cells in spleen tissues. The results of the present study indicated that the main constituent of fennel, transanethole may be an antiinflammation component, which influenced the regulation of Th17/Treg responses. Therefore, this medicinal herb may support a healing effect on diseases of inflammatory.
Assuntos
Lesão Pulmonar Aguda , Anisóis/farmacologia , Foeniculum/química , Lipopolissacarídeos/toxicidade , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/patologia , Derivados de Alilbenzenos , Animais , Anisóis/química , Interleucina-10/imunologia , Interleucina-17/imunologia , Masculino , Camundongos , Linfócitos T Reguladores/patologia , Células Th17/patologiaRESUMO
BACKGROUND: Radix Wikstroemia indica (RWI), named "Liao Ge Wang" in Chinese, is a kind of toxic Chinese herbal medicine (CHM) commonly used in Miao nationality of South China. "Sweat soaking method" processed RWI could effectively decrease its toxicity and preserve therapeutic effect. However, the underlying mechanism of processing is still not clear, and the Q-markers database for processed RWI has not been established. PURPOSE: Our study is to investigate and establish the quality evaluation system and potential Q-markers based on "effect-toxicity-chemicals" relationship of RWI for quality/safety assessment of "sweat soaking method" processing. METHODS: The variation of RWI in efficacy and toxicity before and after processing was investigated by pharmacological and toxicological studies. Cytotoxicity test was used to screen the cytotoxicity of components in RWI. The material basis in ethanol extract of raw and processed RWI was studied by UPLC-Q-TOF/MS. And the potential Q-markers were analyzed and predicted according to "effect-toxicity-chemical" relationship. RESULTS: RWI was processed by "sweat soaking method", which could preserve efficacy and reduce toxicity. Raw RWI and processed RWI did not show significant difference on the antinociceptive and anti-inflammatory effect, however, the injury of liver and kidney by processed RWI was much weaker than that by raw RWI. The 20 compounds were identified from the ethanol extract of raw product and processed product of RWI using UPLC-Q-TOF/MS, including daphnoretin, emodin, triumbelletin, dibutyl phthalate, Methyl Paraben, YH-10â¯+â¯OH and matairesinol, arctigenin, kaempferol and physcion. Furthermore, 3 diterpenoids (YH-10, YH-12 and YH-15) were proved to possess the high toxicity and decreased by 48%, 44% and 65%, respectively, which could be regarded as the potential Q-markers for quality/safety assessment of "sweat soaking method" processed RWI. CONCLUSION: A Q-marker database of processed RWI by "sweat soaking method" was established according to the results and relationship of "effect-toxicity-chemicals", which provided a scientific evidence for processing methods, mechanism and the clinical application of RWI, also provided experimental results to explore the application of Q-marker in CHM.
Assuntos
Biomarcadores Farmacológicos/análise , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Wikstroemia/química , Analgésicos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , China/etnologia , Cromatografia Líquida/métodos , Cumarínicos/análise , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/análise , Emodina/análogos & derivados , Emodina/análise , Furanos/análise , Humanos , Lignanas/análise , Espectrometria de Massas/métodos , Camundongos , Extratos Vegetais/análise , Extratos Vegetais/farmacologiaRESUMO
Psoralen and isopsoralen are secondary plant metabolites found in many fruits, vegetables, and medicinal herbs. Psoralen-containing plants (Psoralea corylifolia L.) have been reported to cause hepatotoxicity. Herein, we found that psoralen and isopsoralen were oxidized by CYP450s to reactive furanoepoxide or γ-ketoenal intermediates, causing a mechanism-based inhibition of CYP3A4. Furthermore, in GSH-depleted mice, the hepatotoxicity of these reactive metabolites has been demonstrated by pre-treatment with a well-known GSH synthesis inhibitor, L-buthionine-S, Rsulfoxinine (BSO). Moreover, a molecular docking simulation of the present study was undertaken to understand the coordination reaction that plays a significant role in the combination of unstable intermediates and CYP3A4. These results suggested that psoralen and isopsoralen are modest hepatotoxic agents, as their reactive metabolites could be deactivated by H2O and GSH in the liver, which partly contributes to the ingestion of psoralen-containing fruits and vegetables being safe.
RESUMO
1. Rutaecarpine, a quinolone alkaloid isolated from the unripe fruit of Evodia rutaecarpa, is one of the main active components used in a variety of clinical applications, including the treatment of hypertension and arrhythmia. However, its hepatotoxicity has also been reported in recent years. 2. Reactive metabolites (RMs) play a vital role in drug-induced liver injury. Rutaecarpine has a secondary amine structure that may be activated to RMs. The aim of the study was to investigate the inhibition of rutaecarpine on CYPs and explore the possible relationship between RMs and potential hepatotoxicity. 3. A cell counting kit-8 cytotoxicity assay indicated that rutaecarpine can decrease the primary rat hepatocyte viability, increase lactate dehydrogenase and reactive oxygen species, reduce JC-1, and cause cell stress and membrane damage. The indexes were significantly restored by adding ABT, an inhibitor of CYPs. A cocktail assay showed that CYP1A2, CYP2C9, CYP2C19, CYP2E1 and CYP3A4 can be inhibited by rutaecarpine in human liver microsomes. The IC50 values of CYP1A2 with and without NADPH were 2.2 and 7.4 µM, respectively, which presented a 3.3 shift. The results from a metabolic assay indicated that three mono-hydroxylated metabolites and two di-hydroxylated metabolites were identified and two GSH conjugates were also trapped. 4. Rutaecarpine can inhibit the activities of CYPs and exhibit a potential mechanism-based inhibition on CYP1A2. RMs may cause herb-drug interactions, providing important information for predicting drug-induced hepatotoxicity.