RESUMEN
INTRODUCTION: Kamebakaurin is an active constituent of both Rabdosia japonica and Rabdosia excisa, which are utilized in Chinese traditional medicine for improving symptoms in patients with allergies. We investigated the molecular mechanisms of the anti-allergic effects of kamebakaurin using BMMCs. METHODS: The degranulation ratio, histamine release, and the interleukin (IL)-4, leukotriene B4 (LTB4), and cysteinyl leukotriene productions on antigen-triggered BMMC were investigated. Additionally, the effects of kamebakaurin on signal transduction proteins were examined by Western blot and binding to the Syk and Lyn kinase domain was calculated. The effects of kamebakaurin on antigen-induced hyperpermeability were investigated using mouse model. RESULTS: At 10 µ
Asunto(s)
Degranulación de la Célula , Mastocitos , Receptores de IgE , Transducción de Señal , Quinasa Syk , Animales , Mastocitos/inmunología , Mastocitos/metabolismo , Mastocitos/efectos de los fármacos , Receptores de IgE/metabolismo , Transducción de Señal/efectos de los fármacos , Ratones , Degranulación de la Célula/efectos de los fármacos , Degranulación de la Célula/inmunología , Quinasa Syk/metabolismo , Quinasa Syk/antagonistas & inhibidores , Interleucina-4/metabolismo , Liberación de Histamina/efectos de los fármacos , Antígenos/inmunología , Antialérgicos/farmacología , Ratones Endogámicos BALB C , Fosforilación/efectos de los fármacos , Hipersensibilidad/inmunología , Hipersensibilidad/metabolismo , Hipersensibilidad/tratamiento farmacológicoRESUMEN
A series of 1-O-acyl- and 1-oxo-kamebanin analogues were prepared from kamebanin, isolated from Rabdosia excisa and their cytotoxicity was assayed on HL60 promyelocytic leukemia cells and HCT116 human colon cancer cells. The structure-activity relationship study showed that the presence of 1-O-acyl groups of a C3-C5 carbon chain increased the cytotoxic activity.
Asunto(s)
Antineoplásicos , Isodon , Humanos , Antineoplásicos/farmacología , Relación Estructura-Actividad , Células HL-60 , Células HCT116RESUMEN
The present study aimed to investigate the protective effects of kamebakaurin (KA) and 1O, 20O-diacetyl kamebakaurin (Ac2KA) on acetaminophen (APAP)-induced hepatotoxicity and compare the hepatoprotective mechanisms of the two chemicals. Seven-week-old male C57BL/6J mice were orally administered KA, Ac2KA, or an ethanol/olive oil emulsion once per day for 7-days. Twenty-four hours after the final administration, the mice were fasted and then intraperitoneally injected with 450 mg/kg APAP or saline. At 16 h after injection, the mice were euthanized and blood samples were collected for plasma analysis. Pretreatment with KA and Ac2KA significantly attenuated APAP-induced hepatic injury. The protective effect of Ac2KA was stronger than that of KA. These two chemicals attenuated oxidative stress, inflammatory cytokine production, c-jun N-terminal kinase activation, and receptor-interacting protein (RIP)-3 activation. Ac2KA also decreased APAP-induced RIP-1 activation and nuclear factor kappa B (NF-κB) p65 translocation. Moreover, Ac2KA repressed mRNA expression of Cyp1a2/2e1 in the liver. Our results showed that KA and Ac2KA exerted protective effects against APAP-induced hepatotoxicity. The responsible mechanisms may be related to the chemicals' antioxidant activity and the inhibition of c-jun N-terminal kinase activation and RIP-3 activation. The effects of Ac2KA included those of KA, as well as RIP-1 inactivation, NF-κB inhibition, and Cyp inhibition.
Asunto(s)
Acetaminofén/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Diterpenos/farmacología , Sustancias Protectoras/farmacología , Animales , Antioxidantes/química , Antioxidantes/farmacología , Biomarcadores , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Citocinas/metabolismo , Modelos Animales de Enfermedad , Diterpenos/química , Glutatión/metabolismo , Mediadores de Inflamación/metabolismo , Pruebas de Función Hepática , Masculino , Malondialdehído/metabolismo , Ratones , Estructura Molecular , Estrés Oxidativo/efectos de los fármacos , Sustancias Protectoras/química , Transporte de Proteínas , Especies Reactivas de Oxígeno/metabolismoRESUMEN
BACKGROUND: Kamebakaurin (KA) is an ent-kaurane diterpenoid known to have anti-inflammatory potential. In the current study, we investigated whether pretreatment with KA could ameliorate acetaminophen (APAP)-induced hepatotoxicity by inhibiting the anti-inflammatory response in mice. METHODS: Seven-week-old C57BL/6J mice were orally administered KA or olive oil emulsion for seven days. Twenty-four hours after the last KA or olive oil administration, the mice were intraperitoneally injected with 400mg/kg APAP or saline under feed deprived condition. The mice from each group were euthanized and bled for plasma analysis 24h after the injection. RESULT: APAP increased plasma levels of hepatic injury markers (i.e., alanine aminotransferase and aspartate aminotransferase), lipid peroxidation, and pro-inflammatory cytokines. Pretreatment with KA reduced the magnitude of APAP-induced increases in plasma levels of hepatic injury markers, lipid peroxidation, and inflammatory response. In addition, KA exhibited antioxidant capacity in a dose-dependent manner, with slight reactive oxygen species scavenging activity. CONCLUSION: Our results indicate that KA has the ability to protect the liver from APAP-induced hepatotoxicity, presumably by both inhibiting the inflammatory response and oxidative stress.
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Acetaminofén/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Diterpenos/farmacología , Inflamación/inducido químicamente , Peroxidación de Lípido/efectos de los fármacos , Analgésicos no Narcóticos , Animales , Antioxidantes/farmacología , Diterpenos/administración & dosificación , Femenino , Inflamación/tratamiento farmacológico , Ratones , Ratones Endogámicos C57BLRESUMEN
A series of rabdokunmin C analogues were prepared and their inhibitory effect on NF-κB activation was assayed. One of them, 18-acetyl-12-deoxy-11,12-dehydrorabdokunmin C (16) was found to be a promising candidate for an anti-inflammatory agent.
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Diterpenos/síntesis química , Diterpenos/farmacología , FN-kappa B/metabolismo , Animales , Diterpenos de Tipo Kaurano/síntesis química , Diterpenos de Tipo Kaurano/farmacología , Células Hep G2 , Humanos , Leucemia P388/tratamiento farmacológico , Macrófagos/efectos de los fármacos , Ratones , FN-kappa B/genética , Relación Estructura-ActividadRESUMEN
Three new dammarane-type triterpene ginsenosides, together with six known ginsenosides, were isolated from the leaves of Panax ginseng C.A. Meyer. The new saponins were named as ginsenoside Rh11, ginsenoside Rh12, and ginsenoside Rh13. Their structures were elucidated as (20S)-3ß,6α,12ß,20-tetrahydroxydammara-25-ene-24-one 20-O-ß-d-glucopyranoside (1), (20S)-3ß,12ß,20,24,25-pentahydroxydammarane 20-O-ß-d-glucopyranoside (2), and (20S,23E)-3ß,12ß,20,25-tetrahydroxydammara-23-ene 20-O-ß-d-glucopyranoside (3) on the basis of 1D and 2D NMR experiments and mass spectra. The known ginsenosides were identified as ginsenoside M(7cd), ginsenoside Rg6, ginsenoside Rb3, gypenoside XVII, gypenoside IX, and 20-(E)-ginsenoside F4.
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Medicamentos Herbarios Chinos/aislamiento & purificación , Ginsenósidos/aislamiento & purificación , Panax/química , Saponinas/aislamiento & purificación , Triterpenos/aislamiento & purificación , Medicamentos Herbarios Chinos/química , Ginsenósidos/química , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Hojas de la Planta/química , Saponinas/química , Estereoisomerismo , Triterpenos/química , DamaranosRESUMEN
OBJECTIVE: To determine actinoside C in the leaves of Actinidia kolomikta with different growth periods. METHOD: The separation was performed at 25 degrees C on ZORBAX Extend C18 column (4.6 mm x 250 mm, 5 microm), using amixture of methanol and water (51:49) as a mobile phase. The flow rate was 1.2 mL x min(-1), and the wavelength for measurement was 267 nm. RESULT: The results showed that the contents of actinoside C in the leaves of A. kolomikta were variety in different growth periods. Actinoside C could reach its highest content in the middle ten days of June, then the content would decrease in the middle ten days of July slightly, it could reach their lowest content in the middle ten days of August. CONCLUSION: The optimal collective date for A. kolomikta are in the middle ten days of June.
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Actinidia/química , Cromatografía Líquida de Alta Presión/métodos , Flavonas/análisis , Glicósidos/análisis , Hojas de la Planta/química , Actinidia/crecimiento & desarrollo , Flavonas/química , Glicósidos/química , Estructura Molecular , Hojas de la Planta/crecimiento & desarrollo , Plantas Medicinales/química , Plantas Medicinales/crecimiento & desarrollo , Estaciones del AñoRESUMEN
1-O-Monoacyl, 12-O-monoacyl, 1-,12-O-diacyl, and 11,12-dehydrated excisanin A 7,14-acetonides were synthesized from excisanin A isolated from Rabdosia excisa. The structure and cytotoxic activity relationships (SAR) of the natural parent ent-kaurene diterpenes and these semisynthetic analogues were studied by using P388 murine leukemia cells.
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Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Diterpenos/síntesis química , Diterpenos/farmacología , Animales , Antineoplásicos/química , Antineoplásicos/toxicidad , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Diterpenos/química , Diterpenos/toxicidad , Ratones , Estructura Molecular , Relación Estructura-ActividadRESUMEN
OBJECTIVE: To determine 20(S)-ginsengnoside Rh2 in the hydrolysis product of saponins from leaves of Panax qinquefolium. METHOD: The separation was performed on ZORBAX EXEND C18 column (4.6 mm x 250 mm, 5 microm), eluted with methanol and water (85:15) as mobile phase with the rate of 1.2 mL x min(-1) at 25 degrees C, the wavelength for measurement was 203 nm. RESULT: The calibration curve was linear in the range of 0.5-25 microg for 20(S)-ginsengnoside Rh2(r = 0.9999, n = 7). The average recovery was 99.7% (RSD= 1.0%). CONCLUSION: This method is simple, accurate, reliable and reproducible. The result shows that the transform ratio of 20(S)-ginsengnoside Rh2 is high by this hydrolysis method.
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Ginsenósidos/química , Panax/química , Plantas Medicinales/química , Cromatografía Líquida de Alta Presión/métodos , Ginsenósidos/análisis , Ginsenósidos/aislamiento & purificación , Hidrólisis , Hojas de la Planta/química , Tallos de la Planta/químicaRESUMEN
A novel 14,20-epoxy-ent-kaurene diterpenoid, excisanin H (1), and three new ent-kaurene diterpenoids, 2-4, were isolated from aerial parts of Rabdosia excisa along with eight known ent-kaurene diterpenoids, 5-12. The structural elucidations were made using spectral (HREIMS, IR, (1)H, (13)C, and 2D NMR) methods. The absolute configuration of 1 was determined by demonstrating that oxidation of kamebakaurin (8) produced excisanin H (1). These ent-kaurene diterpenoids all showed significant cytotoxic activity against P388 murine leukemia cells.