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Currently, available medicine does not satisfy the clinical unmet needs of periodontal disease. Therefore, novel drugs with improved efficacy profiles are needed. We previously demonstrated that YH14642, water extracts of Notoginseng Radix and Rehmanniae Radix Preparata, improved probing depths in double-blind phase II clinical trial. However, it still has hurdles for commercialization due to the low efficiency of active compound extraction. To resolve this issue, we developed YH23537 through process optimization to extract active compounds efficiently while still achieving the chemical profile of YH14642. In this study, we investigated the therapeutic effects of YH23537 compared with YH14642 using a canine model of ligature-induced periodontitis. Human gingival fibroblast (hGF) cells were treated with various concentrations of YH23537 or YH14642 with lipopolysaccharide (LPS) for 24 hr. IL-6 and IL-8 levels in the conditioned media were determined using Luminex. Sixteen 3-year-old male beagle dogs had their teeth scaled and polished using a piezo-type ultrasonic scaler under general anesthesia and brushed once daily for the following 2 weeks. Two weeks after the scaling procedure, the left upper second premolar (PM2), third premolar (PM3), and fourth premolar (PM4) as well as the left lower PM3, PM4, and first molar (M1) were ligated with silk-wire twisted ligatures. The dogs were fed with soft moistened food to induce periodontitis for 8 weeks, and the ligatures were then removed. YH23537 and YH14642 were administered for 4 weeks, and clinical periodontal parameters such as plaque index (PI), gingival index (GI), probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BoP) were determined before and 1, 2, 3, and 4 weeks after treatment. YH23537 inhibited IL-6 and IL-8 secretion in a dose-dependent manner in hGF cells stimulated with LPS. The IC50 values for YH23537 were 43 and 54 µg/ml for IL-6 and IL-8, respectively, while the values for YH14642 were 104 and 117 µg/ml, respectively. In the animal study, clinical parameters including GI, PD, CAL, and BoP were significantly increased after 8 weeks of ligature-induced periodontitis. The YH23537 300 and YH23537 900 mg groups had significant improvements in CAL from 1 to 4 weeks after treatment in comparison to the placebo group. GR values in the YH23537 900 mg group were decreased throughout the treatment period. GI values were also reduced significantly after 4-week treatment with 300 and 900 mg of YH23537. YH23537 at 300 mg doses showed comparable efficacy for CAL and GR with 1,000 mg of YH14642. YH23537 showed therapeutic efficacy against periodontitis in dogs, mediated by anti-inflammatory effects. These findings indicate that YH23537 has the potential for further development as a new drug for patients suffering from periodontal disease.
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BACKGROUND: Coffee is one of the most commonly consumed beverages worldwide. Accumulating clinical evidence has shown an inverse relationship between coffee and liver cirrhosis. We investigated the protective effect of coffee against liver fibrosis and underlying molecular mechanisms using a dimethylnitrosamine (DMN)-induced liver fibrosis model. RESULTS: Coffee administration significantly prevented the deterioration of body weight, organ weight, and serum biochemistry by DMN treatment. Histopathological examination revealed that necrosis/inflammation and fibrotic septa decreased significantly in coffee-treated rats compared to those treated with DMN and water. Coffee administration also significantly inhibited the accumulation of hydroxyproline (P < 0.001) and the production of malondialdehyde (P < 0.05), as well as stellate cell activation caused by DMN injection. Coffee protected the depletion of glutathione, superoxide dismutase, and catalase in liver tissue. In addition, coffee treatment inhibited the gene expression of inducible nitric oxide synthase, transforming growth factor (TGF)-beta, tumor necrosis factor-alpha, interleukin-1, and platelet-derived growth factor (PDGF)-beta in liver tissues, and lowered the concentration of TGF-beta and PDGF-beta in liver. Coffee inhibited NO production by macrophages. CONCLUSION: Coffee exerts protective effects against liver fibrosis via antioxidant action and the suppression of fibrogenic cytokines, TGF-beta and PDGF-beta.
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Antioxidantes/uso terapéutico , Café , Cirrosis Hepática/tratamiento farmacológico , Hígado/efectos de los fármacos , Fitoterapia , Extractos Vegetales/uso terapéutico , Animales , Antioxidantes/farmacología , Peso Corporal/efectos de los fármacos , Coffea , Citocinas/genética , Citocinas/metabolismo , Dimetilnitrosamina , Modelos Animales de Enfermedad , Expresión Génica , Células Estrelladas Hepáticas/efectos de los fármacos , Hidroxiprolina/sangre , Hígado/enzimología , Hígado/patología , Cirrosis Hepática/inducido químicamente , Macrófagos/efectos de los fármacos , Masculino , Malondialdehído/sangre , Necrosis/prevención & control , Óxido Nítrico/biosíntesis , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Tamaño de los Órganos/efectos de los fármacos , Extractos Vegetales/farmacología , Factor de Crecimiento Derivado de Plaquetas/genética , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Ratas , Ratas Sprague-Dawley , SemillasRESUMEN
AIM: To evaluate the efficacy of Myelophil, an extract containing Astragali Radix and Salviae Radix, for reducing complications induced by 5-fluorouracil (5-FU) in a gastrointestinal cancer model. METHODS: We injected 5-FU into mice and then administered Myelophil to examine the ability of the drug to treat the side effects of 5-FU in mice. Peripheral blood counts, histological examinations, and colony-forming assays of bone marrow were conducted, followed by swimming tests and assessment of survival times. RESULTS: Myelophil restored red and white blood cells and platelets in blood, and recovered cell density in bone marrow to levels comparable to those observed within the control group. In addition, Myelophil significantly increased colony-forming unit granulocyte-macrophage (CFU-GM) and CFU-erythroid (CFU-E) compared to the control group. We confirmed that interleukin-3 gene expression was upregulated by Myelophil in spleen cells. Myelophil administration also doubled the survival rate of mice that were severely myelosuppressed as a result of 5-FU injection at a lethal dose of 70%. Finally, the swimming performance of mice significantly improved as a result of Myelophil treatment. CONCLUSION: These results provide experimental evidence in support of clinical applications of Myelophil to minimize 5-FU-induced myelosuppression and improve general post-chemotherapy health.
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Enfermedades de la Médula Ósea/prevención & control , Médula Ósea/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Animales , Antimetabolitos Antineoplásicos , Conducta Animal/efectos de los fármacos , Médula Ósea/patología , Enfermedades de la Médula Ósea/sangre , Enfermedades de la Médula Ósea/inducido químicamente , Enfermedades de la Médula Ósea/patología , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Recuento de Eritrocitos , Fluorouracilo , Células Madre Hematopoyéticas/efectos de los fármacos , Interleucina-3/genética , Interleucina-3/metabolismo , Recuento de Leucocitos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Recuento de Plaquetas , Bazo/efectos de los fármacos , Bazo/metabolismo , Factores de TiempoRESUMEN
UNLABELLED: Trichosanthes kirilowii tuber is one of most popular herbal plant of East Asia, which has been prescribed for patients with diabetes, rigorous coughing, breast abscesses, and cancer-related symptoms. AIM OF THE STUDY: To investigated the anticancer properties of the methanol extract of Trichosanthes kirilowii tuber (TKE), focusing on cell cycle arrest and microtubule instability in HepG2 cells. MATERIALS AND METHODS: Cell growth and death were checked using a CCK-8 assay and a LDH release assay respectively. Cell cycle was analyzed by FACS after PI staining. Immunofluorescence, Western blot, real-time PCR for tubulin were performed. RESULTS: TKE treatment inhibited cell growth at around 25 microg/mL of IC50 in a CCK-8 assay and a LDH release assay, but did not result in cell death. We found that TKE induced cell cycle arrest at the G2/M phase in a time-dependent manner. However, an immunofluorescence assessment of beta-tubulin revealed a dramatically reduced amount of polymerized tubulin after TKE treatment. Furthermore, TKE treatment radically decreased the polymerized portion of soluble tubulin in a dose-dependent manner, as did colchicine; the effects, however, were opposite to those of paclitaxel in comparative analysis of polymerized to soluble tubulin. We also found that TKE treatment moderately affected alpha-tubulin protein production, but not that of beta-tubulin and its gene expression using a Western assay and real-time PCR. CONCLUSIONS: Anticancer mechanisms of TKE linked to the inhibition of tubulin polymerization, through which it exerts cell cycle arrest at the G2/M phase in the HepG2 cell line.
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Antineoplásicos Fitogénicos/farmacología , Neoplasias Hepáticas/tratamiento farmacológico , Extractos Vegetales/farmacología , Trichosanthes/química , Antineoplásicos Fitogénicos/administración & dosificación , División Celular/efectos de los fármacos , Línea Celular Tumoral , Colchicina/farmacología , Relación Dosis-Respuesta a Droga , Asia Oriental , Técnica del Anticuerpo Fluorescente , Fase G2/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Medicina Tradicional de Asia Oriental , Paclitaxel/farmacología , Extractos Vegetales/administración & dosificación , Factores de Tiempo , Tubulina (Proteína)/efectos de los fármacos , Tubulina (Proteína)/metabolismoRESUMEN
AIM: CGX, a modified traditional Chinese herbal drug whose name means "liver cleaning," is used to treat various liver disorders. This study investigated the protective effects of CGX and its mechanisms. MATERIAL AND METHODS: After pretreating ICR mice twice daily with CGX (po, 50 or 100mg/kg) or distilled water for three consecutive days, acute liver injury was induced by a single injection of CCl(4) (ip, 10mL/kg of 0.2% in olive oil) (n=8 per group). RESULTS: Pretreatment with CGX significantly attenuated the elevation in biochemical parameters, such as alanine transaminase (ALT), aspartate transaminase (AST), and lactate dehydrogenase (LDH) in serum, and the malondialdehyde concentrations in liver tissue. Pretreatment with CGX significantly restored the reduction of catalase activity and glutathione (GSH) content, but not superoxide dismutase (SOD) activity, and it inhibited the CCl(4)-induced high expression of iNOS and TNF-alpha in hepatic tissue. CONCLUSION: This study showed that CGX has hepatoprotective effects against free radical-induced acute injury via primarily antioxidative properties.
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Antioxidantes/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Medicamentos Herbarios Chinos/farmacología , Animales , Antioxidantes/administración & dosificación , Tetracloruro de Carbono , Catalasa/efectos de los fármacos , Catalasa/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/fisiopatología , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/administración & dosificación , Regulación de la Expresión Génica/efectos de los fármacos , Glutatión/efectos de los fármacos , Glutatión/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Pruebas de Función Hepática , Masculino , Ratones , Ratones Endogámicos ICR , Óxido Nítrico Sintasa de Tipo II/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo II/metabolismo , Superóxido Dismutasa/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Factor de Necrosis Tumoral alfa/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Notoginseng Radix and Rehmanniae Radix Preparata have been widely used traditionally for treating inflammatory diseases. This research studies the therapeutic effects of YH23537, the extracts of Notoginseng Radix and Rehmanniae Radix Preparata, on pain and cartilage degeneration in an experimental osteoarthritis (OA) model. Male Wistar rats were inoculated intra-articularly with 3 mg of monosodium iodoacetate (MIA) in the right intra-articular. Four days later, the animals were administrated orally with YH23537 daily for 24 days. Tactile allodynia and weight bearing were measured. Macroscopic and microscopic observations for articular cartilage were performed at the end of the experiment. Protein expression in the joint was determined by immunohistochemistry. The effects of YH23537 on mRNA levels in chondrocytes stimulated with interleukin (IL)-1ß were analyzed using random polymerase chain reaction. OA induction was confirmed by significant decrease of paw withdrawal latency, paw withdrawal threshold, and weight bearing compared with the normal group at 3 days after MIA injection. The YH23537-treated groups displayed significant increases in pain thresholds and weight bearing throughout the observation period. The damage to articular cartilage was significantly lessened visually and histopathologically by YH23537 treatment. YH23537 suppressed the expression of metalloproteinase-3, nitrotyrosine, IL-1ß and IL-6 increased in OA joints. YH23537 upregulated tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-3 in IL-1ß-stimulated human OA chondrocytes. The protein levels of the NF-κBp65 and HIF-2α in the joint tissues were reduced by YH23537. YH23537 exerted antinociceptive effects and cartilage protective effects in experimental OA rats by suppressing oxidative injury, inflammatory mediators, and inducing anabolic factors. We suggest that YH23537 may have efficacy for treating OA in humans.
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Antiinflamatorios/farmacología , Enfermedades de los Cartílagos/tratamiento farmacológico , Osteoartritis/tratamiento farmacológico , Dolor/tratamiento farmacológico , Panax , Extractos Vegetales/farmacología , Rehmannia , Administración Oral , Animales , Antiinflamatorios/efectos adversos , Antiinflamatorios/uso terapéutico , Enfermedades de los Cartílagos/inducido químicamente , Cartílago Articular/efectos de los fármacos , Modelos Animales de Enfermedad , Yodoacetatos , Masculino , Osteoartritis/inducido químicamente , Dimensión del Dolor , Fitoterapia , Extractos Vegetales/administración & dosificación , Extractos Vegetales/uso terapéutico , Ratas , Ratas WistarRESUMEN
Hericium erinaceum is a medicinal and edible mushroom with anti-microbial and anti-cancer activities. To evaluate the immunoregulatory functions of H. erinaceum, we prepared water extract from H. erinaceum (WEHE) and investigated its ability to activate macrophages and to induce nitric oxide (NO) production in macrophages. Rat peritoneal macrophages stimulated with 1 to 100 mug/ml of WEHE for 24, 48, or 72 h produced NO in a time- and dose-dependent manner. Reverse transcription-polymerase chain reaction demonstrated that WEHE augmented the steady-state level of inducible NO synthase (iNOS) mRNA in both the peritoneal macrophages and a murine macrophage cell-line, RAW 264.7. Electrophoretic mobility shift assay showed that WEHE increased DNA binding activity of the transcription factor NF-kappaB, which is responsible for iNOS gene expression. Furthermore, its trans-acting activity was confirmative as determined by in vitro transfection assay using a reporter gene construct, p(NF-kappaB)(3)-CAT, whose expression is solely regulated by the activity of NF-kappaB. Concomitantly with the activation of NF-kappaB, WEHE markedly decreased intracellular IkappaBalpha level as demonstrated by Western blot assay. These results suggested that WEHE induces iNOS gene expression followed by NO production in macrophages via enhancing the activation of transcription factor, NF-kappaB.
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Agaricales/química , Productos Biológicos/farmacología , Activación de Macrófagos/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico/metabolismo , Animales , Productos Biológicos/química , Productos Biológicos/aislamiento & purificación , Línea Celular , Proteínas de Unión al ADN/metabolismo , Relación Dosis-Respuesta a Droga , Ensayo de Cambio de Movilidad Electroforética , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Proteínas I-kappa B/metabolismo , Lipopolisacáridos/farmacología , Macrófagos Peritoneales/citología , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/metabolismo , Masculino , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Unión Proteica/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Solubilidad , Agua/químicaRESUMEN
AIM: To evaluate the therapeutic effect of Chunggan extract (CGX), a modified traditional Chinese hepatotherapeutic herbal, on the dimethylnitrosamine (DMN)-induced chronic liver injury model in rats. METHODS: Liver injuries were induced in Wistar rats by injection of DMN (ip, 10 mg/mL per kg) for 3 consecutive days per week for 4 wk. The rats were administered with CGX (po, 100 or 200 mg/kg per day) or distilled water as a control daily for 4 wk starting from the 15(th) d of the DMN treatment. Biochemical parameters (serum albumin, bilirubin, ALP, AST and ALT), lipid peroxides, hydroxyproline, as well as histological changes in liver tissues were analyzed. In addition, gene expression of TNF-alpha, TGF-beta, TIMP-1, TIMP-2, PDGF-beta, and MMP-2, all of which are known to be associated with liver fibrosis, were analyzed using real-time PCR. RESULTS: CGX administration restored the spleen weight to normal after having been increased by DMN treatment. Biochemical analysis of the serum demonstrated that CGX significantly decreased the serum level of ALP (P < 0.05), ALT (P < 0.01), and AST (P < 0.01) that had been elevated by DMN treatment. CGX administration moderately lowered lipid peroxide production and markedly lowered hydroxyproline generation caused by DMN treatment in accordance with histopathological examination. DMN treatment induced a highly up-regulated expression of TNF-alpha, TGF-beta, TIMP-1, TIMP-2, PDGF-beta, and MMP-2. Of these, the gene expression encoding PDGF-beta and MMP-2 was still further enhanced 2 wk after secession of the 4-wk DMN treatment, and was remarkably ameliorated by CGX administration. CONCLUSION: CGX exhibits hepatotherapeutic proper-ties against chronic hepatocellular destruction and consequential liver fibrosis.
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Medicamentos Herbarios Chinos/farmacología , Cirrosis Hepática/prevención & control , Hígado/efectos de los fármacos , Animales , Dimetilnitrosamina , Medicamentos Herbarios Chinos/uso terapéutico , Expresión Génica , Hidroxiprolina/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Hígado/patología , Hepatopatías/sangre , Hepatopatías/tratamiento farmacológico , Hepatopatías/patología , Masculino , Tamaño de los Órganos , Ratas , Ratas Wistar , Bazo/patologíaRESUMEN
AIM: To evaluate the pharmaceutical safety of a Chinese herbal formula, chunggan extract (CGX), traditionally prescribed as a hepatotherapeutic drug via systemic acute and subacute toxicological study. METHODS: Twenty male dogs and 20 female dogs were fed doses 50 times and 4 times greater than the clinically-recommended drug dosages in an acute and a subacute toxicological study, respectively. Adverse effects were examined by comparing the differences between normal and drug-administered groups using clinical signs, necropsies, histopathologic findings, haematology, urinalysis, and biochemical analysis. RESULTS: In the acute study no change in the body weight, diarrhoea, apetite, mortality rate and histopathology of major organs was observed in male or female dogs with a single administration of CGX at 5 g/kg. No drug-induced abnormalities at analysis of histopathology, haematology, urinalysis, and biochemistry were found with any dose of this drug. CONCLUSION: CGX is supposed to be very safe when used in a clinical application with a wide therapeutic index.
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Medicamentos Herbarios Chinos/toxicidad , Animales , Peso Corporal/efectos de los fármacos , Perros , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/uso terapéutico , Ingestión de Alimentos/efectos de los fármacos , Femenino , Humanos , Riñón/efectos de los fármacos , Riñón/patología , Hígado/efectos de los fármacos , Hígado/patología , Hepatopatías/tratamiento farmacológico , Masculino , Fitoterapia/efectos adversos , SeguridadRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Hyangaa-Pyeongwi san is the most well known description in Traditional Chinese Medicine for treating functional gastrointestinal disorders. Functional dyspepsia (FD) is a main concern of intimidating quality of life (QoL) in recent days. Although many medicines have been developed to improve FD symptoms as well as QoL, there are no potential drugs and treatments for FD. The aim of this study is to investigate the effects of Hyangaa-Pyeongwi san (HPS) on QoL of patients with FD. METHODS: This study was designed as a randomized, double blinded, placebo controlled, and parallel group trial. Participants received either placebo or HPS (9.68g of HPS at once, three times daily) for 4-weeks, and the efficacy evaluations were performed by assessing the Nepean Dyspepsia Index (NDI) and functional dyspepsia-quality of life (FD-QoL) at 0-, 4- and 8-weeks. RESULTS: Total of 170 patients participated and were randomly allocated into placebo or HPS groups. Total symptom score of NDI decreased after 4-weeks trial in both groups (p>0.05). HPS significantly improved QoL scores, especially in the area of 'interference and eat/drink' in NDI (p=0.0031) as well as 'liveliness status', 'role-functioning status', and total score in FD-QoL (p=0.026 for liveliness status and p=0.035 for role-functioning status). This significant improvement of FD-QoL had lasted for 4-weeks. CONCLUSION: HPS treatment is markedly effective in improving QoL in patients with FD. Moreover, we observed that this improvement had lasted for 4 weeks after finishing the trial through the follow-up study.
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Dispepsia/tratamiento farmacológico , Preparaciones de Plantas/uso terapéutico , Calidad de Vida , Adulto , Anciano , Método Doble Ciego , Femenino , Humanos , Masculino , Medicina Tradicional de Asia Oriental , Persona de Mediana Edad , Fitoterapia , Adulto JovenRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia capillaris and Artemisia iwayomogi, both members of the Compositae family, have been indiscriminately used for various liver disorders as traditional hepatotherapeutic medicines in Korea for many years. AIM OF THE STUDY: In this study, the anti-hepatofibrotic effects of Artemisia capillaris and Artemisia iwayomogi were comparatively analyzed using a carbon tetrachloride (CCl(4))-induced liver fibrosis rat model. MATERIALS AND METHODS: Hepatic fibrosis was induced via a 10-week course of intraperitoneal CCl(4) injections (50% dissolved in olive oil, 2mL/kg, twice per week). Water extract of Artemisia capillaris (AC) or Artemisia iwayomogi (AI) was orally administered six times per week from the 5th to the 10th week. RESULTS: AI (50mg/kg) significantly attenuated the CCl(4)-induced excessive release of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) in serum (p<0.05), and hydroxyproline and malondialdehyde (MDA) contents in liver tissue (p<0.05). Further, AI markedly ameliorated the depletion of total antioxidant capacity (TAC), glutathione (GSH), and superoxide dismutase (SOD) in liver tissue (p<0.01). Unexpectedly, AC did not exert any effects on the above parameters. Histopathological and immunohistochemical analyses revealed that AI drastically reduced inflammation, necrosis, fatty infiltration, collagen accumulation, and activation of hepatic satellite cells in liver tissue. These changes were not observed with AC treatment. Several critical genes of fibrosis-related cytokines including transforming growth factor beta (TGF-ß), platelet-derived growth factor beta (PDGF-ß), and alpha smooth muscle actin (α-SMA) were more prominently downregulated by AI compared to AC treatment. CONCLUSION: Our results show that AI exerts greater hepatoprotective and anti-fibrotic effects as compared with AC via enhancing antioxidant capacity and downregulating fibrogentic cytokines.
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Antioxidantes/uso terapéutico , Artemisia , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Cirrosis Hepática/tratamiento farmacológico , Hígado/efectos de los fármacos , Fitoterapia , Extractos Vegetales/uso terapéutico , Fosfatasa Alcalina/sangre , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Tetracloruro de Carbono , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Enfermedad Crónica , Colágeno/metabolismo , Citocinas/genética , Citocinas/metabolismo , Modelos Animales de Enfermedad , Regulación hacia Abajo , Hígado Graso/tratamiento farmacológico , Glutatión/metabolismo , Hidroxiprolina/metabolismo , Inflamación/tratamiento farmacológico , Corea (Geográfico) , Hígado/metabolismo , Cirrosis Hepática/metabolismo , Cirrosis Hepática/patología , Masculino , Malondialdehído/metabolismo , Extractos Vegetales/farmacología , Ratas , Ratas Sprague-Dawley , Superóxido Dismutasa/metabolismo , Transaminasas/sangreRESUMEN
Chunggan extract (CGX) is a hepatotherapeutic herbal formula which has been traditionally used for patients suffering from various hepatic disorders. This study aimed to elucidate antifibrotic effect and mechanisms of CGX in thioacetamide (TAA) model. Hepatic fibrosis was induced in 45 Sprague-Dawley rats by TAA (200 mg kg(-1), intraperitoneally [ip]) on twice per week for 12 weeks. CGX (100 or 200 mg kg(-1), per oral [po]) was administrated once a day throughout the experiment. CGX treatment ameliorated serum biomarkers. CGX administration significantly attenuated distortion of histopathologic finding, and accumulation of hydroxyproline and malondialdehyde (MDA). CGX treatment significantly decreased transforming growth factor-beta (TGF-ß) concentrations and inactivated hepatic stellate cells (HSCs). CGX treatment drastically restored glutathione (GSH) system, while inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-α) significantly down-regulated in liver tissue. CGX showed antifibrotic effect in thioacetamide-induced chronic liver injury model. Its corresponding mechanisms may be mediated via anti-oxidative stress property sustaining GSH system and inhibition of ROS production.
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Medicamentos Herbarios Chinos/uso terapéutico , Glutatión/metabolismo , Cirrosis Hepática Experimental/prevención & control , Hígado/efectos de los fármacos , Tioacetamida/farmacología , Animales , Biomarcadores/sangre , Medicamentos Herbarios Chinos/administración & dosificación , Hígado/enzimología , Hígado/metabolismo , Hígado/patología , Cirrosis Hepática Experimental/inducido químicamente , Cirrosis Hepática Experimental/metabolismo , Pruebas de Función Hepática , Masculino , Medicina Tradicional Coreana , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-DawleyRESUMEN
AIM OF THE STUDY: Amomum xanthoides is a well-known traditional herbal medicine mainly for diverse digestive system disorders in Asia for a long time. In the present study, we investigate the effects and action mechanism of methanol fraction of Amomum xanthoides (MFAX) on thioacetamide (TAA)-induced liver fibrosis in rat model. MATERIALS AND METHODS: TAA (200mg/kg, ip on twice a week for 14 weeks) treated rats were orally administered with MFAX (25, 50 or 100mg/kg) once a day from the 7th week until 14th week. RESULT: Significantly elevated serum bilirubin, liver tissue hydroxyproline and malondialdehyde (MDA) in liver fibrosis were ameliorated by MFAX treatment. Further, MFAX treatment attenuated the reactive oxygen species (ROS) levels and restored glutathione (GSH) content and glutathione-peroxidase (GPx) activity. Histopathological data showed that MFAX treatment inhibited collagen accumulation and activation of hepatocyte stellate cells (HSCs) in the liver tissue. Compared to the TAA group, activation of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-ß), platelet-derived growth factor beta (PDGF-ß) mRNAs and the level of pro-fibrotic cytokines PDGF-ß and connective tissue growth factor (CTGF) in the liver tissue were attenuated in MFAX treated groups. CONCLUSION: The above evidences collectively indicate that MFAX is a potential herb which can be used as an anti-hepatofibrotic remedy.
Asunto(s)
Amomum/química , Antioxidantes/metabolismo , Cirrosis Hepática/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Tioacetamida/toxicidad , Animales , Secuencia de Bases , Peso Corporal/efectos de los fármacos , Células Cultivadas , Cromatografía en Capa Delgada , Cartilla de ADN , Glutatión/metabolismo , Inmunohistoquímica , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/metabolismo , Malondialdehído/metabolismo , Metanol/química , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
CGX, a traditional herbal drug, has been prescribed for patients suffering from various liver diseases, including hepatitis B, alcoholic liver disease, and fatty liver. We investigated whether CGX has hepatoprotective effects against lipopolysaccharide/D-galactosamine (LPS/D-GalN)-induced acute liver injury and its underlying mechanism(s). Mice were administered CGX orally for 7 days prior to an injection of LPS (5 µg/kg)/D-GalN (700 mg/kg). Complete blood count, serum diagnostic markers, antioxidant activities, caspase activity, and histopathological examinations were conducted 8 h after the injection. To evaluate the immunological mechanism of CGX, serum TNF-α and IL-10 were investigated 1.5 h after LPS/D-GalN injection. CGX pretreatment (100, 200, and 400 mg/kg) inhibited the elevation of serum AST and ALT levels as well as histopathological alterations. Moreover, CGX pretreatment inhibited activation of caspase-3/7. CGX attenuated LPS/D-GalN-induced lipid peroxidation with concomitant improvement in total antioxidant activities (superoxide dismutase, catalase, and glutathione peroxidase). CGX elevated the antioxidant capacity of the liver in both the pathological and normal conditions. Furthermore, LPS/D-GalN-induced alterations of neutrophil and lymphocyte populations were ameliorated and serum TNF-α was decreased significantly by CGX. From these data we conclude that CGX protects the liver from LPS/D-GalN-induced hepatitis through antioxidant mechanisms as well as immune modulation.
Asunto(s)
Antioxidantes/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Galactosamina/toxicidad , Medicina de Hierbas , Factores Inmunológicos/farmacología , Lipopolisacáridos/toxicidad , Extractos Vegetales/farmacología , Animales , Caspasas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Linfocitos/efectos de los fármacos , Linfocitos/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Neutrófilos/efectos de los fármacos , Neutrófilos/patología , Oxidorreductasas/metabolismo , Transaminasas/sangreRESUMEN
In the present study, we investigate the effect of Korean ginseng root extract (KG) on cisplatin-induced pica in a rat model. Rats were treated with KG before (25, 50, and 100 mg/kg) or after (12.5, 25, and 50 mg/kg) a single intraperitoneal injection of cisplatin (7 and 6 mg/kg, respectively). We examined intake of kaolin and normal food as an indicator of the emetic stimulus every 24 h for 120 h. Changes in body weight, haematology and histopathology were additionally assessed. Pre-treatment with KG (25 and 50 mg/kg) significantly attenuated cisplatin-induced kaolin intake (24, 48, and 72 h) and markedly improved intake of normal food by rats at 48, 72, 96, and 120 h. Cisplatin-induced kaolin intake was markedly decreased upon post-treatment of rats with KG (12.5, 25, and 50 mg/kg) at 24 h. Notably, post-treatment with the lowest KG dose resulted in a significant anti-pica effect and improved food intake until 72 h. The magnitude of body weight reduction was significantly diminished in rats pre-treated/post-treated with 25, 50, and 12.5 mg/kg KG. The anti-pica effects of KG were further confirmed with haematological and histopathological findings. Our findings collectively indicate that KG improves the resistance of rats against emesis.
Asunto(s)
Antineoplásicos/toxicidad , Cisplatino/toxicidad , Panax/química , Pica/fisiopatología , Extractos Vegetales/uso terapéutico , Raíces de Plantas/química , Vómitos/tratamiento farmacológico , Animales , Anorexia/inducido químicamente , Anorexia/tratamiento farmacológico , Peso Corporal/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Masculino , Extractos Vegetales/farmacología , Ratas , Ratas Sprague-Dawley , Vómitos/inducido químicamenteRESUMEN
We examined how chemotherapy-induced myelotoxicity and the associated leukopaenia affect cancer metastasis in an animal model. Myelotoxicity was induced by a single injection of 5-fluorouracil (5-FU) or Cisplatin, administered to 7-week-old BALB/c mice. CT-26 murine colon carcinoma cells were injected into the lateral tail vein on days 0, 1, 3, 5, and 7 after anticancer drug injection. On day 14 after cancer cell injection, the number of pulmonary colonies was measured in a double-blind setting. Compared with Cisplatin, 5-FU induced severe leukopaenia and bone marrow suppression, while on day 5, both drugs induced severe myelotoxicity. The number of pulmonary colonies did not correlate with the severity of leukopaenia, regardless of the type or time of drug injection, except in the group pretreated with Cisplatin (3 days prior to cancer cell injection). Our results suggest that chemotherapy-induced myelotoxicity does not increase the incidence of cancer metastasis in this animal model.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antineoplásicos/toxicidad , Médula Ósea/efectos de los fármacos , Cisplatino/toxicidad , Neoplasias del Colon/tratamiento farmacológico , Fluorouracilo/toxicidad , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Experimentales/tratamiento farmacológico , Adenocarcinoma/patología , Animales , Médula Ósea/patología , Línea Celular Tumoral , Neoplasias del Colon/patología , Modelos Animales de Enfermedad , Leucopenia/inducido químicamente , Leucopenia/patología , Neoplasias Pulmonares/secundario , Masculino , Ratones , Ratones Endogámicos BALB C , Trasplante de Neoplasias , Neoplasias Experimentales/patologíaRESUMEN
We investigated the antioxidant effects of Panax ginseng C.A. Meyer on healthy volunteers. In a double-blind randomized controlled design, 82 participants (21 men and 61 women) who were considered healthy by both objective and subjective health standard were divided into three groups, the control group and the groups received P. ginseng extract (1 or 2g/day) for 4 weeks. Serum level of reactive oxygen species (ROS), malondialdehyde (MDA), total antioxidant capacity (TAC), the activities of catalase, superoxide dismutase (SOD), glutathione reductase (GSH-Rd), and peroxidase (GSH-Px), and total glutathione content were determined before and after the trial. Administration of P. ginseng led to significant decreases in the levels of serum ROS and MDA. Notably, the total glutathione content and GSH-Rd activity considerably improved in the groups that received 2g of P. ginseng. No significant alterations were observed in TAC, catalase, SOD, and GSH-Px activities. In conclusion, our findings indicate that P. ginseng was shown to have antioxidant property. It enhanced the antioxidant defense mechanism in healthy populations and the results may reinforce the use of P. ginseng as a potential antioxidant supplement.
Asunto(s)
Antioxidantes/farmacología , Panax/química , Extractos Vegetales/farmacología , Humanos , PlacebosRESUMEN
Radiotherapy induces untargeted effects on normal tissues such as bone marrow. So alteration of microenvironment by ionizing irradiation is supposed to influence dynamic host-cancer ecosystem affecting cancer behavior including metastasis. Herein, the incidence of lung metastasis after high-dose irradiation has been investigated using mice model having real-time condition of leucopenia. C57BL/6 mice were pre-exposed to a X-irradiation dose of 6 Gy on previous days 2, 5, 7, 10. Complete hematological parameters including lymphocyte subpopulation in blood and lung tissues were analyzed. Additionally, a group of mice including a non-irradiated group were inoculated with B16F10 cells (3 × 10(5)/200 µl) via tail vein at the same day, and lung metastasized colonies were compared among groups at day 14 of post-inoculation. We observed that (i) total leucocytes and platelet were gradually depleted by day 10; (ii) lung tissue showed gradual infiltration of leucocytes including neutrophils and lymphocytes; (iii) pulmonary colonies were maximum and minimum on day 5 and 10 respectively; (iv) lymphocyte subpopulation analysis showed most number of natural killer (NK) cells in lung tissues on day 10; (v) gene expression of platelet/endothelial cell adhesion molecule (PECAM) in lung tissues peaked on day 5. To sum-up the study, severity of leucopenia did not influence the incidence of metastasis but blood platelets and microenvironment alteration of targeting tissue may be responsible factors for lung metastasis in our experimental model.
Asunto(s)
Modelos Animales de Enfermedad , Células Asesinas Naturales/efectos de la radiación , Leucopenia/etiología , Neoplasias Pulmonares/etiología , Neoplasias Pulmonares/secundario , Melanoma Experimental/patología , Rayos X/efectos adversos , Animales , Humanos , Células Asesinas Naturales/patología , Leucopenia/patología , Depleción Linfocítica , Masculino , Ratones , Ratones Endogámicos C57BL , Neutrófilos/patología , Neutrófilos/efectos de la radiación , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/genética , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Células Tumorales CultivadasRESUMEN
CGX is a potential hepatoprotective herbal medicine used to treat various chronic liver disorders. The purpose of the study was to evaluate the pharmaceutical safety of CGX via a systemic 13-week repeated dose toxicity test in beagle dogs. Male and female beagle dogs were divided into four groups and two animals each from the control and high-dose group (400 mg/kg) were allocated into recovery groups. The dogs were administered with CGX (0, 100, 200, 400 mg/kg) for 13 weeks. During the experimental period, the dogs were observed for signs of gross toxicity and for behavioral changes; body weight and food consumption were measured. An ophthalmologic examination and urinalysis were performed at 0 and 13th week and blood biochemistry and hematological parameters analyses were performed at 0, 6th, and 13th week. A histopathological examination was also performed at the end of the experiment. There were no CGX-induced abnormalities in clinical signs, organ weights, food consumption, hematological, urine, and blood biochemical parameters, or histopathological findings in any of the groups during or after the 13 weeks. We demonstrated the safety of CGX for 13-week repeated dose and considered that it is safe for chronic clinical use.
Asunto(s)
Medicamentos Herbarios Chinos/toxicidad , Sustancias Protectoras/toxicidad , Animales , Conducta Animal/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Pruebas de Química Clínica , Perros , Medicamentos Herbarios Chinos/química , Femenino , Pruebas Hematológicas , Masculino , Tamaño de los Órganos/efectos de los fármacos , Sustancias Protectoras/química , Pruebas de Toxicidad CrónicaRESUMEN
Concanavalin A (Con A)-induced acute liver injury model is well established as a model of T cell-mediated liver injury, in which T cells and NKT cells exert their cytotoxicity towards liver cells. In this study, we investigated the protective effects of CGX, a traditional Korean medicine against Con A-induced liver injury and its underlying mechanisms. After pretreatment with CGX (po, 50, 100 or 200 mg/kg) or distilled water once daily during 7 days, Con A (15 mg/kg) was injected intravenously. Thereafter serum level of AST and ALT, lipid peroxidation and cytokines in the liver tissue, and immune cell population in blood and the spleen were analyzed. CGX treatment reduced serum ALT, AST level in a dose-dependent manner. CGX treatment significantly decreased the lipid peroxidation and glutathione depletion in the liver tissue, and also lowered tissue levels of tumor necrotic factor-α and interferon-γ. CGX treatment attenuated the compositional alteration of Tc, Th, NKT, and B cells in blood as well as in the spleen. These results suggest that CGX has hepatoprotective property against Con A-induced liver injury through antioxidant action and immune regulation.