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In the present work, a portable and low-cost planar waveguide based resonance light scattering (RLS) scanner (termed as: PW-RLS scanner) has been developed for microarray detection. The PW-RLS scanner employs a 2 × 4 white light emitting diode array (WLEDA) as the excitation light source, a folded optical path with a complementary metal oxide semiconductor (CMOS) as the signal/image acquisition device and stepper motors with gear drives as the mechanical drive system. The biological binding/recognizing events on the microarray can be detected with an evanescent waveguide-directed illumination and light-scattering label (e.g., nanoparticles) while the microarray slide acts as an evanescent waveguide substrate. The performance of the as-developed PW-RLS scanner has been evaluated by analyzing type 2 diabetes mellitus (T2DM) risk genes. Highly selective and sensitive (less than 1% allele frequency at the attomole-level) T2DM risk gene detection is achieved using single-stranded DNA functionalized gold nanoparticles (ssDNA-GNPs) as detection probes. Additionally, the successful simultaneous analysis of 15 T2DM patient genotypes suggests that the device has great potential for the realization of a personalized diagnostic test for a given disease or patient follow-up.
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Luz , Análisis de Secuencia por Matrices de Oligonucleótidos/instrumentación , Dispositivos Ópticos , Dispersión de Radiación , Diseño de Equipo , Metales/química , Óxidos/química , SemiconductoresRESUMEN
Hepatocellular carcinoma (HCC) is among the deadliest malignancies worldwide and still a pressing clinical problem. Icaritin, a natural compound obtained from the Epimedium genus plant, has garnered significant attention as a potential therapeutic drug for HCC therapies. Mitophagy plays a crucial role in mitochondrial quality control through efficiently eliminating damaged mitochondria. However, the specific mechanisms of the interplay between mitophagy and apoptosis in HCC is still unclear. We aimed to explore the cross-talk between icaritin-induced mitophagy and apoptosis in HCC cells and investigate its potential mechanisms. Firstly, we confirmed that icaritin inhibits proliferation and migration while inducing mitochondrial damage and reactive oxygen species (ROS) production in HCC cells. Secondly, based on proteomics analysis, we discovered that icaritin inhibits the growth of tumor cells and disrupts their mitochondrial homeostasis through the regulation of both mitophagy and apoptosis. Thirdly, icaritin causes mitophagy mediated by PINK1-Parkin signaling via regulating feedforward loop. Furthermore, knockdown of PINK1/Parkin leads to inhibition of mitophagy, which promotes cell death induced by icaritin in HCC cells. Finally, autophagy/mitophagy inhibitors remarkably enhance icaritin-induced cell death and anticancer efficacy. Collectively, our findings reveal that icaritin suppresses growth, proliferation and migration of HCC cell through induction of mitophagy and apoptosis, while inhibition of mitophagy significantly increased the anti-cancer and pro-apoptotic effects of icaritin, indicating that targeting autophagy or mitophagy is a novel approach to overcome drug resistance and enhance anticancer therapies.
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Carcinoma Hepatocelular , Flavonoides , Neoplasias Hepáticas , Humanos , Mitofagia , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/patología , Autofagia , Ubiquitina-Proteína Ligasas/metabolismo , Proteínas Quinasas/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
The long non-coding RNA, urothelial cancer-associated 1 (UCA1) is an important regulator in several tumors. However, to the best of our knowledge, the clinical roles of UCA1 in cervical cancer remain unclear. Thus, the present study aimed to investigate the function and mechanism of UCA1 in cervical cancer. Reverse transcription-quantitative PCR analysis was performed to detect UCA1 and microRNA (miR)-299-3p expression in cervical cancer tissues and cell lines. The Cell Counting Kit-8 and Transwell assays were performed to assess cell proliferation and invasion, respectively. Furthermore, the dual-luciferase reporter assay was performed to confirm the association between UCA1 and miR-299-3p. Rescue experiments were performed to determine the mechanism of the UCA1/miR-299-3p axis. The results demonstrated that UCA1 expression was upregulated in cervical cancer tissues and cell lines. Furthermore, overexpression of UCA1 enhanced the proliferation and invasion of cervical cancer cells, the effects of which were reversed following UCA1 knockdown. Notably, UCA1 interacted with miR-299-3p and negatively regulated miR-299-3p expression. In addition, miR-299-3p expression was downregulated in cervical cancer tissues and cell lines. Overexpression of miR-299-3p suppressed the proliferation and invasion of cervical cancer cells, reversing the effects of UCA1 knockdown on cervical cancer cell proliferation. Taken together, the results of the present study suggest that UCA1 promotes cell proliferation and invasion by regulating miR-299-3p expression in cervical cancer.
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BACKGROUND: Ovarian cancer is the most common female gynecological malignancy. SNHG20, as a long non-coding RNA, has been proven to be an important regulator in the occurrence and development of various tumors. However, the potential mechanism of SNHG20 in ovarian cancer is unclear. OBJECTIVE: The present study was aimed to investigate the functions and mechanisms of SNHG20 in ovarian cancer. METHODS: The expression of SNHG20 and miR-217 in ovarian cancer tissues and cell lines was detected by qRT-PCR. CCK-8 assay was used to measure cell proliferation in transfected cells. The transwell assay was used to detect the relative invasion rate of transfected cells. The putative binding sites between SNHG20 and miR-217 were predicted by software LncBase v.2, and the interaction between SNHG20 and miR-217 was confirmed by dual-luciferase reporter assays and RIP assay. The rescue experiments were used to illustrate potential mechanisms. RESULTS: SNHG20 was upregulated in ovarian cancer tissues and cell lines. Overexpression of SNHG20 promoted ovarian cancer cell proliferation and invasion. MiR-217 was downregulated in ovarian cancer tissues and cells, and was negatively regulated by SNHG20. Moreover, miR-217 overexpression inhibited ovarian cancer cell proliferation and invasion. Furthermore, miR-217 mimic reversed the inhibitory effect of SNHG20 overexpression on the biological behavior of ovarian cancer cells. CONCLUSIONS: SNHG20 promoted cell proliferation and invasion by sponging miR-217 in ovarian cancer. These results suggested that SNHG20 and miR-217 might provide new targets for therapeutic application in ovarian cancer.
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Proliferación Celular/genética , MicroARNs/genética , Neoplasias Ováricas/genética , ARN Largo no Codificante/genética , Línea Celular Tumoral , Movimiento Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Neoplasias Ováricas/patología , Unión Proteica/genéticaRESUMEN
To investigate the effects of urea-formaldehyde (UF) resin impregnation combined heat treatment (IMPG-HT) on the pyrolysis behavior of poplar wood, the chemical composition, pyrolysis characteristics, pyrolysis kinetics, and gaseous products released during pyrolysis of untreated (control), IMPG-HT, IMPG and HT woods were analyzed. The results demonstrate that IMPG-HT changes pyrolysis behavior of poplar wood significantly. Unlike the control and HT samples, the thermogravimetric / derivative thermogravimetric (TG/DTG) curves of IMPG wood shift toward lower temperature, and the shoulder on DTG curves weaken or even disappear. The maximum mass loss rate of IMPG-HT samples decreases, and carbon residual yield increases to 23% or more and activation energy (E) increases sharply after conversion rate (α) reaching 0.80. HT improves the thermal stability of IMPG wood, which is represented by the increase of decomposition temperature (Td) and DTG peak temperature (Tpeak) and the higher E value of IMPG-HT wood. For the pyrolysis gaseous products, IMPG-HT wood produces nitrogen-containing gases (HNCO and NH3) due to the presence of UF resin, but the amounts of these gases are less than that produced by IMPG wood because the heat treatment had removed part of N elements.
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Biomasa , Formaldehído/química , Pirólisis/efectos de los fármacos , Urea/química , Madera/química , Calor , Cinética , Populus/química , Temperatura , Madera/efectos de los fármacosRESUMEN
The San Wu Huangqin Decoction (SWHD), a traditional Chinese medicine formula, is used to treat colds caused by exposure to wind-pathogen, hyperpyrexia, infectious diseases and cancer; moreover, it is used for detoxification. The individual herbs of SWHD, such as Sophora flavescens and Scutellaria baicalensis, exhibit a wide spectrum of antiviral, anti-inflammatory, antibacterial, anticancer and other properties. The Chinese compound formula of SWHD is composed of S. flavescens, S. baicalensis and Rehmannia glutinosa. However, the effect of SWHD on the influenza virus (IFV) and its mechanism remain unknown. The aim of this study was to evaluate, for the first time, whether SWHD could be used to treat influenza. Results showed that SWHD could effectively inhibit influenza A/PR/8/34 (H1N1) virus at different stages of viral replication (confirmed through antiviral effect assay, penetration assay, attachment assay and internalization assay) in vitro. It could reduce the infection of the virus in a dose- and time-dependent manner, as confirmed by observing the cell cytopathic effect and calculating the cell viability (p < 0.05). SWHD demonstrated better antiviral activity than oseltamivir in the evaluation of antiviral prophylaxis on influenza (p < 0.05). The antiviral activity of SWHD may be related to its regulation ability on the immune system. Western blot, real-time polymerase chain reaction and indirect immunofluorescence assay showed that the expression of the four target viral proteins of the IFV (namely, haemagglutinin (HA), neuraminidase (NA), nucleoprotein (NP) and matrix-2 (M2)) reduced significantly (p < 0.05). Moreover, SWHD (23.40 and 11.70 g/kg) significantly alleviated the clinical signs, reduced the mortality and increased the survival time of infected mice (p < 0.05). The lung index, virus titres, pathological changes in lung tissues and the expression of key proteins of the IFV in mice also decreased (p < 0.05). In conclusion, SWHD possessed anti-influenza activity. This work provided a new view of complementary therapy and drug discovery for clinical treatment.
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Antivirales/farmacología , Medicamentos Herbarios Chinos/farmacología , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Infecciones por Orthomyxoviridae/prevención & control , Infecciones del Sistema Respiratorio/prevención & control , Transporte Activo de Núcleo Celular/efectos de los fármacos , Animales , Antivirales/química , Núcleo Celular/metabolismo , Efecto Citopatogénico Viral/efectos de los fármacos , Perros , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/química , Genes Virales/genética , Pulmón/patología , Pulmón/virología , Células de Riñón Canino Madin Darby , Ratones , Estructura Molecular , Nucleoproteínas/metabolismo , Infecciones por Orthomyxoviridae/patología , Infecciones por Orthomyxoviridae/virología , Infecciones del Sistema Respiratorio/patología , Infecciones del Sistema Respiratorio/virología , Análisis de Supervivencia , Transcripción Genética/efectos de los fármacos , Carga Viral/efectos de los fármacosRESUMEN
OBJECTIVE: To investigate the antipyretic mechanism of Herba Ephedrae (Eph)-Ramulus Cinnamomi (RC) herb pair on yeast-induced pyrexia in rats. METHODS: Totally 30 qualified male SD rats were randomly assigned to the normal control (NC) group, the pyrexia model (model) group, the Eph, RC and Eph-RC treatment groups by a random digital table, 6 rats in each group. Each rat received a 20% aqueous suspension of yeast (10 mL/kg) except the NC group. The 3 treatment groups were administered 8.1, 5.4 and 13.5 g/kg Eph, RC and Eph-RC respectively at 5 and 12 h after yeast injection, the NC group and the model groups were administered equal volume of distilled water. Rectal temperatures were measured at 0, 6, 8, 10, 12, 15, 18, 24 and 30 h and urine was collected prior to yeast injection and at 6, 10, 18, 24, 30, and 36 h after yeast injection. Then urine metabolomic profiling by gas chromatography tandem mass spectrometry, coupled with multivariate statistical analysis and pattern recognition techniques were used to explore the antipyretic effects of Eph-RC. Partial least squares discriminate analysis was used to analyze the metabolomics dataset including classification and regression in metabolomics plot profiling. RESULTS: Compared with the NC group, rectal temperatures were significantly higher in the model group (P<0.01), while 3 treatment groups decreased significantly compared with the model group (P<0.05 or P<0.01). Rectal temperatures of Eph-RC-treated rats started to go down at 6 h, and markedly decreased at 8, 12, 15, 18 and 24 h (P<0.05 or P<0.01), while those of the Eph and RC groups had decreased firstly at 8 h and were markedly lower at 12 h (P<0.05 or P<0.01). Seventeen potential biomarkers related to pyrexia were confirmed and identified, including pyruvic acid, L-phenylalanine, L-tyrosine, phenylacetic acid, hippuric acid, succinic acid, citrate and so on. Eight potential alterations of metabolic pathways including phenylalanine metabolism, citrate cycle, tryptophan metabolism, biosynthesis of valine, leucine and isoleucine, were identified in relation to the antipyretic effects of Eph-RC using MetPA software. CONCLUSION: The antipyretic effect of Eph-RC herb pair on yeast-induced pyrexia in rats involved correction of perturbed amino acid, fatty acid, and carbohydrate metabolism according to the metabolic pathway analysis with MetPA.
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Antipiréticos/farmacología , Cinnamomum/química , Medicamentos Herbarios Chinos/uso terapéutico , Ephedra sinica/química , Fiebre/tratamiento farmacológico , Animales , Fiebre/metabolismo , Cromatografía de Gases y Espectrometría de Masas , Masculino , Redes y Vías Metabólicas/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
Allergic rhinitis (AR) is one of the most common allergic diseases, which adversely affect patients' quality of life. Mahuang Fuzi Xixin decoction (MFXD) has been widely used to treat AR in clinics in Asian countries. This study investigated the effect and possible therapeutic mechanisms of MFXD in the treatment of AR. A Wistar rat model of ovalbumin- (OVA-) induced AR was established and then treated with three doses of MFXD; AR symptoms, serum total immunoglobulin E, histamine, histopathological features, and release and expression of factors related to type 1 helper T (Th1) and type 2 helper T (Th2) responses were analyzed. Our study demonstrated that MFXD has a good therapeutic effect on OVA-induced allergic inflammation in an AR rat model as manifested in reduced frequencies of sneezing and nasal scratching and in reduced serum levels of total IgE and HIS. In addition, MFXD regulates imbalance in Th1/Th2 cells caused by AR by simultaneously attenuating Th1 and Th2 responses, such as by reducing the serum levels of IFN-γ and IL-4 and mRNA expression levels of IFN-γ, IL-4, GATA-3, and STAT-6. This study provided valuable information on the immunoregulatory effect of MFXD for the treatment of AR in future clinical studies.
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Medicamentos Herbarios Chinos/uso terapéutico , Rinitis Alérgica/tratamiento farmacológico , Rinitis Alérgica/inmunología , Células TH1/efectos de los fármacos , Células Th2/efectos de los fármacos , Animales , Citocinas/efectos de los fármacos , Citocinas/genética , Modelos Animales de Enfermedad , Femenino , Histamina/sangre , Inmunoglobulina E/sangre , Interleucina-4/sangre , Ovalbúmina , Fitoterapia , Ratas , Ratas Wistar , Rinitis Alérgica/inducido químicamente , Rinitis Alérgica/fisiopatología , Balance Th1 - Th2/efectos de los fármacosRESUMEN
Shuang-Huang-Lian injectable powder (SHL)-a classical purified herbal preparation extracted from Scutellaria baicalensis, Lonicera japonica, and Forsythia suspense-has been used against human adenovirus III (HAdV3) for many years. The combination herb and its major bioactive compounds, including chlorogenic acid, baicalin, and forsythia glycosides A, are effective inhibitors of the virus. However, no comprehensive studies are available on the antiviral effects of SHL against HAdV3. Moreover, it remains unclear whether the mixture of chlorogenic acid, baicalin, and forsythia glycosides A (CBF) has enhanced antiviral activity compared with SHL. Therefore, a comparative study was performed to investigate the combination which is promising for further antiviral drug development. To evaluate their antivirus activity in parallel, the combination ratio and dose of CBF were controlled and consistent with SHL. First, the fingerprint and the ratio of CBF in SHL were determined by high performance liquid chromatography. Then, a plaque reduction assay, reverse transcription polymerase chain reaction (PCR), real-time polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay (ELISA) were used to explore its therapeutic effects on viral infection and replication, respectively. The results showed that SHL and CBF inhibited dose- and time-dependently HAdV3-induced plaque formation in A549 and HEp-2 cells. SHL was more effective than CBF when supplemented prior to and after viral inoculation. SHL prevented viral attachment, internalization, and replication at high concentration and decreased viral levels within and out of cells at non-toxic concentrations in both cell types. Moreover, the expression of tumor necrosis factor alpha (TNF)-α, interleukin (IL)-1ß, and IL-6 was lower and the expression of interferon (IFN)-γ was higher in both cell types treated with SHL than with CBF. In conclusion, SHL is much more effective and slightly less toxic than CBF.
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Adenovirus Humanos/efectos de los fármacos , Antivirales/farmacología , Mezclas Complejas/farmacología , Medicamentos Herbarios Chinos/farmacología , Extractos Vegetales/farmacología , Adenovirus Humanos/fisiología , Antivirales/química , Antivirales/aislamiento & purificación , Línea Celular , Cromatografía Líquida de Alta Presión , Mezclas Complejas/química , Mezclas Complejas/aislamiento & purificación , Citocinas/antagonistas & inhibidores , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Ensayo de Inmunoadsorción Enzimática , Forsythia/química , Humanos , Lonicera/química , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Scutellaria baicalensis/química , Carga Viral , Ensayo de Placa Viral , Acoplamiento Viral/efectos de los fármacos , Internalización del Virus/efectos de los fármacos , Replicación Viral/efectos de los fármacosRESUMEN
OBJECTIVE: To investigate the pharmacokinetic characteristics of three phenylpropanoids (cinnamic acid, cinnamic alcohol and coumarin) in Ramulus Cinnamomi (GZ) and Ramulus Cinnamomi-Ephedrae Herba (MH) herb-couple (GZMH). METHODS: Twelve male Sprague-Dawley rats were randomly and equally divided into the GZ and GZMH herb-couple groups. Blood samples were collected at 0, 0.08, 0.25, 0.5, 0.75, 1.5, 3, 4, 6, 8, 12, 24, 36 and 48 h after oral administration. The three phenylpropanoids in rat plasma were quantified using an ultra-performance liquid-chromatography with tandem mass spectrometry (UPLC-MS/MS) method for pharmacokinetic study. RESULTS: In GZMH group, the area under the curve (AUC), mean retention time (MRT) of cinnamic acid and coumarin were increased significantly (P<0.01, respectively), and biological half-life (t1/2z) was obviously shorter (P<0.05) compared with the GZ group. There were no significant differences in the mean retention time from 0 to ∞ (MRT0-∞), the peak concentration (Cmax), the time to peak (Tmax) and t1/2z, except for AUC and MRT0-t (the mean retention time from 0 to t) of cinnamic alcohol in the GZMH group by comparison to the GZ group (P<0.01, respectively). The AUC, MRT (both P<0.01) and t1/2z (P<0.05) of coumarin were increased significantly, while Cmax, and Tmax were decreased slightly by comparison to the GZ group (P>0.05). CONCLUSIONS: There were statistically significant differences in some pharmacokinetic parameters of the three compounds between GZ and GZMH groups, which meant that MH could affect the absorption and elimination of the three compounds.
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OBJECTIVE: To inspect the effect of activated carbon with different dosage and temperature on quality of paclitaxel injection. METHOD: Determinations in WS1-(X-026)-2001Z-paclitaxel injection were refered to compare the effect of different dosage and temperature for activated carbon on the taxol content, related material, clarity and bacterial endotoxin. RESULT: When used with 0.25% and 35 degrees C, activated carbon will ensure the quality of paclitaxel injection. CONCLUSION: 0.25% and 35 degrees C are the best condition when activated carbon is used in paclitaxel injection.
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Antineoplásicos Fitogénicos/administración & dosificación , Carbón Orgánico/administración & dosificación , Paclitaxel/administración & dosificación , Carbón Orgánico/análisis , Composición de Medicamentos/métodos , Inyecciones , Control de Calidad , TemperaturaRESUMEN
OBJECTIVE: Mahuang-Shigao herb-pair is a famous formula composed of Ephedra and Gypsum. The herb-pair is frequently used for treating cold symptoms and bronchial asthma in the clinical practice of Chinese medicine (CM). In the present study, we evaluated evidence for the benefit of combined use of Ephedra and Gypsum by analyzing the antipyretic and anti-asthmatic activities of Ephedra-Gypsum. METHODS: The antipyretic effects of Ephedra-Gypsum were evaluated in yeast-induced hyperthermia test. Thirty male Wistar rats were randomly divided into 5 groups, including control group, standard aspirin group, and 3 Ephedra- Gypsum groups of different doses (6, 12, 24 g/kg). Ephedra-Gypsum extract and asprin were administered orally 6 h after the injection of yeast solution and body temperature was measured every 1 h for 8 h. The antiasthmatic effects of Ephedra-Gypsum were evaluated using an ovalbumin (OVA)-induced asthmatic rat model. Thirty-six male SD rats were randomly divided into 6 groups. Rats were alternately sensitized and OVA+Al(OH) challenged by exposure to mists of ovalbumin. Ephedra-Gypsum extracts (6, 12, 24 g/kg) or dexamethasone were administered 45 min prior to the allergen challenge for 8 days. Latent period and the weight of wet to dry ratio of lung were determined. In addition, the eosinophils in blood and white blood cell (WBC) were counted by an YZ-Hemavet Analyzer. RESULTS: The Ephedra-Gypsum extracts at test dose (6, 12, 24 g/kg) significantly and dose-dependently attenuated yeast-induced fever in rats. The Ephedra-Gypsum extracts also prolonged the latent period, reduced OVA-induced increases in eosinophils and WBC, and decreased the wet and dry weight ratio of the lungs in the anti-asthmatic test. CONCLUSIONS: These findings indicate that the Ephedra-Gypsum extract has antipyretic and anti-asthmatic properties. Hence, the results support additional scientific evidence in prescriptions.
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Antiasmáticos/uso terapéutico , Antipiréticos/uso terapéutico , Sulfato de Calcio/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Ephedra/química , Extractos Vegetales/uso terapéutico , Alcaloides/análisis , Animales , Asma/tratamiento farmacológico , Fiebre/tratamiento farmacológico , Pulmón/efectos de los fármacos , Pulmón/patología , Masculino , Tamaño de los Órganos/efectos de los fármacos , Ovalbúmina , Ratas Sprague-Dawley , Ratas WistarRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The Mahuang-Xingren (MX) herb pair, the combination of Herba Ephedrae (Mahuang in Chinese) and Semen Armeniacae Amarum (Xingren in Chinese), is a core component of traditional Chinese medicine formulations used to treat asthma and bronchitis. Although Xingren is considered to be toxic, MX is widely used in the clinic and has few adverse effects. The mechanism underlying detoxification of Xingren by Mahuang in MX remains unknown and merits investigation. AIM OF THE STUDY: To determine the mechanism underlying detoxification of Xingren by Mahuang in MX. MATERIALS AND METHODS: Acute toxic effects were evaluated in mice after oral administration of Mahuang, Xingren, and MX aqueous extracts. Synergism, additivity, and antagonism were quantified by determining the CI (combination index) and DRI (dose-reduction index), which were calculated by the median effect method. High performance liquid chromatography analysis of bioactive compounds (ephedrine, pseudoephedrine and amygdalin) in aqueous extracts and data from previous pharmacokinetic studies in rats were combined to explore the potential mechanism of toxicity antagonism by the components of MX. Moreover, the cytotoxic effects of amygdalin and amygdalin activated by ß-glucosidase (including different proportions of l-amygdalin and d-amygdalin) were also investigated. RESULTS: Mahuang prevented and antagonized the acute toxicity of Xingren and allowed escalation of the Xingren dose. Pearson correlation analysis indicated that the proportion of d-amygdalin was closely correlated with the antagonism of Xingren toxicity. The antagonism of its acute toxicity was primarily attributed to stereoselective metabolism of amygdalin. Interestingly, the process was facilitated by Mahuang, which led to reduced levels of the d-prunasin in vivo and thus reduced toxicity. Furthermore, the mechanism was also evaluated by testing the cytotoxicity of amygdalin. Metabolism of d-amygdalin was a major cause of cytotoxicity and no stereoselective metabolism occurred in culture medium. CONCLUSIONS: A comprehensive study of Xingren detoxification in the context of the MX combination suggested that stereoselective metabolism of amygdalin facilitated by Mahuang may be the crucial mechanism underlying detoxification of Xingren in the MX combination. Therefore, Mahuang acts to enhance and control the effects of Xingren in the MX combination. These results illustrate the rationale behind the combination of Mahuang and Xingren.
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Amigdalina/metabolismo , Amigdalina/toxicidad , Medicamentos Herbarios Chinos/farmacología , Ephedra sinica , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Combinación de Medicamentos , Medicamentos Herbarios Chinos/metabolismo , Medicamentos Herbarios Chinos/toxicidad , Nitrilos/metabolismo , EstereoisomerismoRESUMEN
The Mahuang-Xingren herb-pair (MX), the combination of Herba Ephedrae (Mahuang in Chinese) and Semen Armeniacae Amarum (Xingren in Chinese), is a classical combination used in traditional Chinese Medicine to treat asthma and bronchitis. A simple and reliable ultra-performance liquid chromatography-tandem mass spectrometry method was developed to simultaneously quantify and compare the pharmacokinetics of 5 ephedra alkaloids and epimers of amygdalin and prunasin in rat plasma after oral administration of Mahuang, Xingren, and MX aqueous extracts. Samples were pretreated by a single-step protein precipitation with acetonitrile, and diphenhydramine hydrochloride and puerarin were used as internal standards. Pharmacokinetic parameters were investigated using DAS 3.2.2 (Mathematical Pharmacology Professional Committee of China, Shanghai, China). The validated method demonstrated adequate sensitivity, selectivity, and process efficiency for the bioanalysis of 8 compounds, including 3 pairs of epimers. MX administration improved the bioavailability of amygdalin and prunasin. Furthermore, MX facilitated intake of lower doses of ephedra alkaloids and increased elimination rates in comparison with Mahuang alone. These results illustrate the rationale behind the preferred use of the combination of Mahuang and Xingren. To our knowledge, this is the first report of stereo-selective metabolism of amygdalin. Further, the metabolic mechanism underlying this phenomenon merits future research attention.
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Asteraceae/química , Medicamentos Herbarios Chinos/análisis , Medicamentos Herbarios Chinos/farmacocinética , Ephedra/química , Amigdalina/análisis , Amigdalina/farmacocinética , Animales , Disponibilidad Biológica , Cromatografía Líquida de Alta Presión , Masculino , Nitrilos/análisis , Nitrilos/farmacocinética , Control de Calidad , Ratas , Ratas Sprague-Dawley , Estándares de Referencia , Reproducibilidad de los Resultados , Estereoisomerismo , Espectrometría de Masas en TándemRESUMEN
The combination of Herba Ephedrae (Mahuang in Chinese) and Radix Aconiti Lateralis (Fuzi in Chinese) is a classical preparation in traditional Chinese medicine and used for treating colds and rheumatic arthralgia. However, herbal medicines containing ephedrines and Aconitum alkaloids are strictly regulated because of the potential for adverse effects on the cardiovascular system and the central nervous system. We aimed to investigate the pharmacokinetics of 11 alkaloids in the Mahuang-Fuzi combination and single-herb extracts after oral administration in rats. The alkaloids were norephedrine, norpseudoephedrine, ephedrine, pseudoephedrine, methylephedrine, aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine and benzoylhypaconine. Simultaneous determination of the alkaloids, including two pairs of diastereomers, was achieved in 14.5 min by a simple, rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry method. The separation was performed on a Zorbax SB-Aq column (100 mm × 2.1 mm, 3.5 µm) at a flow rate of 0.3 mL/min using acetonitrile-0.1% formic acid aqueous solution as the mobile phase. The validated method demonstrated adequate sensitivity, selectivity and process efficiency for the quantitative analysis of complex herbal components. Compared with single-herb extracts, alkaloids in plasma (except methylephedrine, benzoylmesaconine and benzoylhypaconine) showed slower elimination (the mean residence time or half-life was longer), although the maximum plasma concentration and area under the plasma concentration curve values decreased. Accumulation may occur with continuous drug intake. These results suggest that drug monitoring may be essential for the safe use of the Mahuang-Fuzi combination.
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Aconitum/química , Alcaloides/farmacocinética , Medicamentos Herbarios Chinos/farmacocinética , Extractos Vegetales/farmacocinética , Aconitina/análogos & derivados , Aconitina/sangre , Aconitina/farmacocinética , Administración Oral , Alcaloides/sangre , Animales , Cromatografía Liquida , Medicamentos Herbarios Chinos/química , Efedrina/análogos & derivados , Efedrina/sangre , Efedrina/farmacocinética , Semivida , Límite de Detección , Masculino , Fenilpropanolamina/sangre , Fenilpropanolamina/farmacocinética , Extractos Vegetales/química , Seudoefedrina/sangre , Seudoefedrina/farmacocinética , Ratas , Ratas Wistar , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Espectrometría de Masas en TándemRESUMEN
Herb Ephedra (Ma Huang in Chinese) and Ramulus Cinnamomi (Gui Zhi in Chinese) are traditional Chinese herbs, often used together to treat asthma, nose and lung congestion, and fever with anhidrosis. Due to the adverse effects of ephedrine, clinical use of Ma Huang is restricted. However, Gui Zhi extract has been reported to decrease spontaneous activity in rats and exert anti-inflammatory and neuroprotective effects. The present study explored the possible inhibitory effect of Gui Zhi on Ma Huang-induced neurotoxicity in rats when the two herbs were used in combination. All Ma Huang and Ma Huang-Gui Zhi herb pair extracts were prepared using methods of traditional Chinese medicine and were normalized based on the ephedrine content. Two-month-old male Sprague-Dawley rats (n = 6 rats/group) were administered Ma Huang or the Ma Huang-Gui Zhi herb pair extracts for 7 days (ephedrine = 48 mg/kg), and locomotor activity was measured. After 7 days, oxidative damage in the prefrontal cortex was measured. Gui Zhi decreased hyperactivity and sensitization produced by repeated Ma Huang administration and attenuated oxidative stress induced by Ma Huang. The results of this study demonstrate the neuroprotective potential of Gui Zhi in Ma Huang-induced hyperactivity and oxidative damage in the prefrontal cortex of rats when used in combination.
RESUMEN
OBJECTIVE: To develop a method for determining the serum astragaloside in rats fed with Buyanghuanwu dicoction (a preparation of a traditional Chinese medicine). METHODS: A solid-phase extraction column was employed for pretreating the serum samples. The fluorescence characteristics of the extract were measured following chemical derivatization with anisic acid-sulphuric acid. RESULTS: The endogenous interference was removed by solid-phase extraction. The excitation and emission maxima of the reaction product from astragaloside and anisic acid were at 310 nm and 376 nm respectively. The linear range of the calibration curve was 1.0 to 10.0 microg/ml with r=0.999 9. The average recovery rate of the method was 97% with relative standard derivation of 2.59%(n=5). CONCLUSION: This method is rapid and highly sensitive, and useful for monitoring the concentration of astragaloside in rat serum.
Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Saponinas/sangre , Triterpenos/sangre , Animales , Ratas , EspectrofotometríaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Herba Ephedra (Mahuang in Chinese), is derived from dried Ephedra sinica Stapf stems and has been widely used to treat the common cold, coughs, asthma, and edema for thousands of years. The Mahuang-Guizhi herb-pair is a famous formula composed of Mahuang and Ramulus Cinnamomi (Guizhi in Chinese, the dried twig of Cinnamomum cassia Presl.), used to improve pharmacological effects and reduce toxicity. In order to investigate the influence of Mahuang-Guizhi herb-pair ratios on bioavailability, the plasma pharmacokinetics profiles of five ephedrine alkaloids were compared following oral administration of four different ratios to rats. MATERIALS AND METHODS: Sprague-Dawley rats were randomly assigned to four groups and orally administered Mahuang-Guizhi (ratios 3:0; 3:1; 3:2; 3:4, w/w). Assays for five ephedrine alkaloids (ephedrine, pseudoephedrine, methylephedrine, norephedrine, and norpseudoephedrine) were developed and validated using ultra-high-performance liquid chromatography tandem mass spectrometry coupled with liquid-liquid extraction. RESULTS: Key pharmacokinetic parameters of the five ephedrine alkaloids (maximal plasma concentration, mean residence time, and half-life) were significantly different (p<0.05) after oral administration of Mahuang-Guizhi herb-pair ratios, as compared to those of Mahuang. CONCLUSION: Ephedrine alkaloid pharmacokinetic differences in rat plasma could help explain previous findings of pharmacological and toxicity differences between Mahuang and Mahuang-Guizhi herb-pair preparations. These results could facilitate future studies to increase the efficacy and decrease the toxicity of Mahuang and Guizhi.
Asunto(s)
Alcaloides/farmacocinética , Cinnamomum aromaticum/química , Ephedra sinica/química , Administración Oral , Alcaloides/administración & dosificación , Alcaloides/aislamiento & purificación , Animales , Disponibilidad Biológica , Cromatografía Líquida de Alta Presión/métodos , Semivida , Extracción Líquido-Líquido , Ratas , Ratas Sprague-Dawley , Espectrometría de Masas en Tándem/métodosRESUMEN
OBJECTIVE: To isolate and identify the chemical constituents of Shuanghuanglian injection. METHODS: Chromatography and spectral analysis were performed to isolate and identify the chemical constituents respectively. RESULTS AND CONCLUSION: Seven compounds were isolated from Shuanghuanglian injection, including chlorogenic acid (I), caffeic acid (II), chrysophanol (III), physcion (IV), rutin (V), baicalein (VI) and glucose (VII). The compounds III, IV, V and VII were isolated and identified in Shuanghuanglian injection for the first time.