RESUMEN
The investigation focused on the impact of Withania somnifera (ashwagandha) extract (WSE) on age-related mechanisms affecting skeletal muscle sarcopenia-related muscle atrophy in aged mice. Beyond evaluating muscular aspects, the study explored chronic low-grade inflammation, muscle regeneration, and mitochondrial biogenesis. WSE administration, in comparison to the control group, demonstrated no significant differences in body weight, diet, or water intake, affirming its safety profile. Notably, WSE exhibited a propensity to reduce epidermal and abdominal fat while significantly increasing muscle mass at a dosage of 200 mg/kg. The muscle-to-fat ratio, adjusted for body weight, increased across all treatment groups. WSE administration led to a reduction in the pro-inflammatory cytokines TNF-α and IL-1ß, mitigating inflammation-associated muscle atrophy. In a 12-month-old mouse model equivalent to a 50-year-old human, WSE effectively preserved muscle strength, stabilized grip strength, and increased muscle tissue weight. Positive effects were observed in running performance and endurance. Mechanistically, WSE balanced muscle protein synthesis/degradation, promoted fiber differentiation, and enhanced mitochondrial biogenesis through the IGF-1/Akt/mTOR pathway. This study provides compelling evidence for the anti-sarcopenic effects of WSE, positioning it as a promising candidate for preventing sarcopenia pending further clinical validation.
Asunto(s)
Extractos Vegetales , Sarcopenia , Withania , Humanos , Animales , Ratones , Lactante , Persona de Mediana Edad , Sarcopenia/tratamiento farmacológico , Sarcopenia/prevención & control , Atrofia Muscular/tratamiento farmacológico , Atrofia Muscular/etiología , Atrofia Muscular/prevención & control , Etanol , Inflamación , Peso CorporalRESUMEN
This study aimed to identify and elucidate the mechanism underlying the protective effect of tricin-enriched Zizania latifolia (Z. latifolia) extract (ETZL) against free fatty acid (FFA)-induced lipid accumulation in vitro and non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet and fructose diet (HFD/F) in vivo. ETZL treatment significantly lowered body weight gain and decreased adipose tissue, lipid, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels in HFD/F-fed mice. ETZL acted on phosphorylated acetyl-CoA carboxylase (ACC) and anti-peroxisome proliferator-activated receptor α (PPARα) by activating the adenosine monophosphate-activated protein kinase (AMPK) pathway and inhibiting sterol regulatory element-binding proteins-1 (SREBP)/fatty acid synthase (FAS) signaling to inhibit de novo adipogenesis and increase fatty acid oxidation. In addition, treatment with ETZL increased nuclear factor erythroid-2-related factor 2 (Nrf2) levels to activate the antioxidant pathway. FFA-induced oxidative stress and fatty acid accumulation in HepG2 cells confirmed the improvement in fat accumulation through the AMPK and Nrf2 pathway activities of ETZL. These results suggest that ETZL ameliorates NAFLD by regulating lipid metabolism and defending against oxidative stress via AMPK-dependent pathways.
RESUMEN
Alzheimer's disease (AD) is a worldwide problem. Currently, there are no effective drugs for AD treatment. Scrophularia buergeriana Miquel (SB) is a traditional herbal medicine used in Korea to treat various diseases. Our previous studies have shown that ethanol extract of SB roots (SBE, Brainon®) exhibits potent anti-amnesic effects in Aß1-42- or scopolamine-treated memory impairment mice model and neuroprotective effects in a glutamate-induced SH-SY5Y cell model. In this study, we evaluated the therapeutic effects of Brainon® and its mechanism of action in senescence-accelerated mouse prone 8 (SAMP8) mice. Brainon® (30 or 100 mg/kg/day) was orally treated to six-month-old SAMP8 mice for 12 weeks. Results revealed that Brainon® administration effectually ameliorated cognitive deficits in Y-maze and passive avoidance tests. Following the completion of behavioral testing, western blotting was performed using the cerebral cortex. Results revealed that Brainon® suppressed Aß1-42 accumulation, Tau hyperphosphorylation, oxidative stress, and inflammation and alleviated apoptosis in SAMP8 mice. Brainon® also promoted synaptic function by downregulating the expression of AChE and upregulating the expression of p-CREB/CREB and BDNF. Furthermore, Brainon® restored SAMP8-reduced expression of ChAT and -dephosphorylated of ERK and also decreased AChE expression in the hippocampus. Furthermore, Brainon® alleviated AD progression by promoting mitophagy/autophagy to maintain normal cellular function as a novel finding of this study. Our data suggest that Brainon® can remarkably improve cognitive deficiency with the potential to be utilized in functional food for improving brain health.
RESUMEN
Depending on the extraction method, numerous compounds that have specific pharmacological effects can be obtained from M. alba L. There is a growing scientific interest in health problems related to aging. Efforts to develop safe immune-enhancing pharmaceuticals are increasing. This review aims to summarize and critically discuss the immunity enhancement effects and pharmaceutical efficacy of M. alba L. extracts. The scientific database search was conducted using Google Scholar, Web of Science, and PubMed until May 2021. Additional articles were identified and obtained from references in the retrieved articles. Ethanol or methanol extraction of various parts of M. alba L. identified a large amount of phenols and flavonoids, which are effective for immunosuppression, antioxidants, and cardiovascular diseases, and are antibacterial, and anticancer. Water extraction of M. alba L. enhanced the innate immune response based on immune cell activation. A polysaccharide and an alkaloid related to increased macrophage activity were isolated from M. alba L. fruit extracts. M. alba L. fruit water extracts primarily induced the production of pro-inflammatory substances, in model organisms, via TLR4 in immune cells. Water extracts have been shown to be effective in pathogen defense and tumor suppression by enhancing macrophage activity. Based on our literature review on the bioactivity of M. alba L. fruit extracts, particularly in relation to their immunity enhancement activity, we anticipate that M. alba-derived pharmaceuticals will have excellent potential in future medical research.
RESUMEN
Binge drinking patterns easily produce a state of oxidative stress that disturbs liver function. Eventually, this leads to alcoholic liver disease. A safe and effective therapy for alcoholic liver disease remains elusive. Enzyme-treated Z. latifolia extract (ETZL) was studied as a potential agent for treating alcohol-induced liver disease. In addition, its underlying mechanisms were elucidated. In the binge model, ETZL was pretreated with alcohol (5 g/kg) three times at 12-h intervals. Our results showed that ETZL pretreatment decreased the serum levels of ALT, AST, ALP, and TG. ETZL treatment appeared to prevent an increase in hepatic TG and MDA levels, and there was a decrease in total GSH following alcohol treatment. Histopathological examination showed that lipid droplets were significantly reduced in the ETZL group compared to the control group. ETZL also exhibited radical scavenging activity. It significantly reduced t-BHP-induced cytotoxicity and the production of reactive oxygen species (ROS) in HepG2 cells. ETZL also enhanced NRF2 nuclear translocation and increased expression of the downstream target genes HO-1, NQO1, and GCLC as an antioxidant defense. Finally, ETZL treatment significantly reduced cell death. Our study suggests that ETZL ameliorates binge ethanol-induced liver injury by upregulating the antioxidant defense mechanism.
RESUMEN
Wild ginseng (Panax ginseng) adventitious root cultures were prepared by elicitation using methyl jasmonate and investigated further to find new secondary metabolites. Chromatographic fractionation of wild ginseng adventitious root cultures led to the isolation of eleven compounds. The chemical structures of isolated compounds were identified as four known flavanone derivatives (1-4), one new curcubinoyl derivative, jasmogin A (5) and six new curcubinoyl-flavanone conjugates, jasmoflagins A-F (6-11) by extensive spectroscopic analysis. Newly isolated curcubinoyl derivatives showed inhibitory activity against lipopolysaccharide-stimulated nitric oxide production in RAW 264.7 macrophages. Therefore, our present study suggested that elicitor stimulated plant cell cultures might contribute to the production of new metabolites.
Asunto(s)
Flavonoides/farmacología , Ginsenósidos/farmacología , Macrófagos/efectos de los fármacos , Óxido Nítrico/metabolismo , Panax/química , Raíces de Plantas/química , Animales , Lipopolisacáridos/farmacología , Ratones , Células RAW 264.7RESUMEN
Plant cell cultures have been exploited to provide stable production and new secondary metabolites for better pharmacological activity. Fractionation of adventitious root cultures of Echinacea purpurea resulted in the isolation of eleven constituents, including three new compounds. The structures of the three new compounds were determined to be an alkylamide (1), a polyacetylene (2) and a lignan (3) on the basis of combined spectroscopic analysis. To discover new types of antiresorptive agents, we screened for new compounds that regulate osteoclast differentiation, and survival. Among three new compounds, echinalkamide (compound 1) had considerably inhibitory effects on RANKL-induced osteoclast differentiation, and on proliferation of osteoclasts and efficiently attenuated osteoclastic bone resorption without toxicity. In addition, echinalamide treatment inhibited the osteoclast-specific gene expression level. Echinalkamide achieved this inhibitory effect by disturbing phosphorylation of MAPK and activation of osteoclast transcription factors c-Fos and NFATc1. Conclusionally, our study investigated that echinalkamide remarkably inhibited osteoclast differentiation and osteoclast specific gene expression through repression of the MAPK-c-Fos-NFATC1 cascade.
Asunto(s)
Conservadores de la Densidad Ósea/farmacología , Resorción Ósea/prevención & control , Echinacea/química , Osteogénesis/efectos de los fármacos , Fitoterapia , Animales , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Conservadores de la Densidad Ósea/aislamiento & purificación , Resorción Ósea/tratamiento farmacológico , Evaluación Preclínica de Medicamentos , Regulación de la Expresión Génica/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Factores de Transcripción NFATC/efectos de los fármacos , Factores de Transcripción NFATC/metabolismo , Óxido Nítrico/biosíntesis , Fosforilación/efectos de los fármacos , Raíces de Plantas/química , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Ligando RANK/farmacología , Células RAW 264.7 , Transcripción Genética/efectos de los fármacos , Factor de Necrosis Tumoral alfa/biosíntesis , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
A ginsenoside F2-enhanced mixture (SGL 121) increases the content of ginsenoside F2 by biotransformation. In the present study, we investigated the effect of SGL 121 on nonalcoholic fatty liver disease (NAFLD) in vitro and in vivo. High-fat, high-carbohydrate-diet (HFHC)-fed mice were administered SGL 121 for 12 weeks to assess its effect on improving NAFLD. In HepG2 cells, SGL 121 acted as an antioxidant, a hepatoprotectant, and had an anti-lipogenic effect. In NAFLD mice, SGL 121 significantly improved body fat mass; levels of hepatic triglyceride (TG), hepatic malondialdehyde (MDA), serum total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL); and activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In HepG2 cells, induced by oxidative stress, SGL 121 increased cytoprotection, inhibited reactive oxygen species (ROS) production, and increased antioxidant enzyme activity. SGL 121 activated the Nrf2/HO-1 signaling pathway and improved lipid accumulation induced by free fatty acids (FFA). Sterol regulatory element-binding protein-1 (SREBP-1) and fatty acid synthase (FAS) expression was significantly reduced in NAFLD-induced liver and HepG2 cells treated with SGL 121. Moreover, SGL 121 activated adenosine monophosphate-activated protein kinase (AMPK), which plays an important role in the regulation of lipid metabolism. The effect of SGL 121 on the improvement of NAFLD seems to be related to its antioxidant effects and activation of AMPK. In conclusion, SGL 121 can be potentially used for the treatment of NAFLD.
Asunto(s)
Ginsenósidos/farmacología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Antioxidantes/farmacología , Dieta Alta en Grasa , Ácidos Grasos no Esterificados/metabolismo , Ginsenósidos/metabolismo , Células Hep G2 , Humanos , Metabolismo de los Lípidos/efectos de los fármacos , Lipogénesis/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Previous studies have confirmed the anti-melanogenic effect of the aerial part of Pueraria lobata, however, due to its inherent color, P. lobata has limited commercial use. In this study, an extract (GALM-DC) of the aerial part of P. lobata having improved color by the use of activated carbon was obtained. Furthermore, the active compound neobavaisoflavone (NBI) was identified from GALM-DC. The effect of NBI on melanogenesis, tyrosinase activity, α-glucosidase activity, and mechanism of action in melanocytes was investigated. Tyrosinase activity, melanin contents and the expression of melanin-related genes and proteins were determined in B16F10 cells. NBI reduced melanin synthesis and tyrosinase activity. Furthermore, NBI treatment reduced the mRNA and protein expression levels of MITF, TRP-1, and tyrosinase. NBI also works by phosphorylating and activating proteins that inhibit melanogenesis, such as GSK3ß and ERK. Specific inhibitors of Akt/GSK-3ß (LY294002) and MEK/ERK (PD98059) signaling prevented the inhibition of melanogenesis by NBI. NBI inhibited melanin production through the regulation of MEK/ERK and Akt/GSK-3ß signaling pathways in α-MSH-stimulated B16F10 cells. NBI suppresses tyrosinase activity and melanogenesis through inhibition of α-glucosidase activity. Besides, NBI significantly reduced melanogenesis in a reconstructed human 3D skin model. In conclusion, these results suggest that NBI has potential as a skin-whitening agent for hyperpigmentation.
Asunto(s)
Regulación de la Expresión Génica/efectos de los fármacos , Isoflavonas/farmacología , Melaninas/metabolismo , Melanocitos/efectos de los fármacos , Melanoma Experimental/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Piel/efectos de los fármacos , Animales , Técnicas de Cultivo de Célula , Quinasas MAP Reguladas por Señal Extracelular/genética , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Glucógeno Sintasa Quinasa 3 beta/genética , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Melanocitos/metabolismo , Melanocitos/patología , Melanoma Experimental/metabolismo , Melanoma Experimental/patología , Ratones , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Piel/metabolismo , Piel/patologíaRESUMEN
Excessive intake of high-lipid foods and lifestyle changes can easily cause hyperlipidemia. Hyperlipidemia is clinically considered a major risk factor for cardiovascular disease, which is the second leading cause of death worldwide. In this study, the effects of a Vitis labrusca extract (HP01) on coagulation, platelet aggregation, and lipid metabolism were investigated in hyperlipidemic rats. A rat model of high-fat diet- (HFD-) induced hyperlipidemia was used. Hemostatic parameters and lipid levels were investigated after HP01 treatment of hyperlipidemic rats. Different doses of HP01 (200 mg/kg/day and 400 mg/kg/day, p.o.) were administered for 3 weeks, and prothrombin time (PT), activated partial thromboplastin time (aPTT), and platelet aggregation and bleed time (BT) were determined. The levels of thromboxane B(2) (TXB(2)) and serotonin were measured using enzyme-linked immunosorbent assay kits. Simultaneously, hepatic function and blood fat indexes, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), malondialdehyde (MDA), and glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were also measured. In comparison with the data obtained for rats in the untreated HFD group, HP01 (200 mg/kg) treatment prolonged PT but did not affect aPTT. HP01 treatment did not alter plasma TXB(2), PGI2, or serotonin levels. However, HP01 showed some effects in improving liver function by reducing the levels of hepatic lipids. ALT, MDA, and hepatic TG levels significantly decreased, whereas GSH, GPx, CAT, and SOD levels significantly increased. These results confirm the HP01 extract will improve thromboplastic and the liver metabolic disorders in hyperlipidemia by oxidative stress response.
RESUMEN
HPC 03 is herbal formula that consists of extracts from Angelica gigas, Cnidium officinale Makino and Cinnamomum cassia Presl. The present study evaluated the estrogenic potential of HPC 03 by using in vitro and in vivo models. The regulatory mechanisms of HPC 03 in estrogen-dependent MCF-7 cells were assessed. HPC 03 induced the proliferation of estrogen receptor-positive MCF-7 cells, and the proliferation was blocked by the addition of the estrogen antagonist tamoxifen. The estrogen receptorα/ß luciferase activities were significantly increased by HPC 03 treatment, which also increased the mRNA expression of the estrogen-responsive genes Psen2, Pgr and Ctsd Also, we evaluated the ameliorative effects of HPC 03 on menopausal symptoms in ovariectomized rats. HPC 03 treatment in OVX rats significantly affected the uterine weight, increased the expression of estrogen-responsive genes Pgr and Psen2 in uterus, increased bone mineral density loss in the femur and inhibited body weight increase. Serum E2, collagen type 1 and osteocalcin were significantly increased, while serum LH, FSH and ALP were decreased compared with OVX rats. HPC 03 may be a promising candidate for the treatment of menopause, but further research is necessary to determine whether the observed effects also occur in humans.
Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Estrógenos/farmacología , Extractos Vegetales/farmacología , Angelica/química , Animales , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Cinnamomum aromaticum/química , Cnidium/química , Femenino , Humanos , Técnicas In Vitro , Ovariectomía , Ratas , Ratas Sprague-Dawley , Receptores de Estrógenos/metabolismo , Células Tumorales CultivadasRESUMEN
Fraxin isolated from Acer tegmentosum is reported to exert potent anti-oxidative stress action. However, pharmacological activities of fraxin remain to be elucidated. This study investigated the potential hepatoprotective effects of fraxin and the underlying signaling mechanism involved. Treatment with fraxin significantly lowered the serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in a CCl4-induced hepatotoxicity rat model. In the fraxin-treated group, glutathione (GSH) significantly increased, while the malondialdehyde (MDA) in the liver significantly decreased. Fraxin also showed radical-scavenging activity. Furthermore, it significantly reduced the t-BHP-induced cytotoxicity and production of reactive oxygen species (ROS) in Hep G2. Fraxin protected Hep G2 cells through Nrf2 pathway-dependent HO-1 expression. The results of this study indicate that fraxin shows potent hepatoprotective effects in vitro and in vivo, presumably through direct antioxidant activity and the Nrf2-mediated antioxidant enzyme system.
Asunto(s)
Antioxidantes/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Cumarinas/farmacología , Estrés Oxidativo/efectos de los fármacos , Animales , Antioxidantes/química , Biopsia , Tetracloruro de Carbono/efectos adversos , Supervivencia Celular/efectos de los fármacos , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Cromatografía Líquida de Alta Presión , Cumarinas/química , Modelos Animales de Enfermedad , Expresión Génica , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/metabolismo , Células Hep G2 , Humanos , Masculino , Factor 2 Relacionado con NF-E2/metabolismo , Oxidación-Reducción/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Ratas , Especies Reactivas de Oxígeno/metabolismoRESUMEN
OBJECTIVES: The Cnidium monnieri fruits (CMF) were studied how they act on immune system as a novel immunostimulator against the infectious disease. METHODS: Macrophages were treated with CMF, and nitric oxide (NO) and tumour necrosis factor-α (TNF-α) were measured, and phagocytosis of macrophages was detected using FITC-labelled Escherichia coli. The protective effect of CMF against E. coli infection in mice was examined. The survival rate was monitored daily for up to 5 days. And then the viable bacteria count of serum and the immunological mediator (NO, TNF-α, interleukin (IL)-12 and IL-6) of serum, splenocyte and peritoneal macrophages were analysed. KEY FINDINGS: The CMF significantly enhanced the concentrations of NO and TNF-α and the phagocytosis activity in macrophages. The oral administration of CMF for five consecutive days before infection prolonged the survival rate. Treatment with CMF significantly stimulated the phagocytosis of peritoneal macrophages and induced the immunological mediator of serum, splenocyte and peritoneal macrophages against the E. coli infection. CONCLUSIONS: The host-protective effects of CMF might be archived by improving immune response, and CMF could act to prevent pathogenic microbial infections with immunomodulation.
Asunto(s)
Adyuvantes Inmunológicos/farmacología , Cnidium/química , Infecciones por Escherichia coli/tratamiento farmacológico , Escherichia coli/patogenicidad , Frutas/química , Macrófagos/efectos de los fármacos , Fagocitosis/efectos de los fármacos , Extractos Vegetales/farmacología , Adyuvantes Inmunológicos/aislamiento & purificación , Animales , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Escherichia coli/inmunología , Infecciones por Escherichia coli/sangre , Infecciones por Escherichia coli/inmunología , Infecciones por Escherichia coli/microbiología , Interacciones Huésped-Patógeno , Interleucina-12/sangre , Interleucina-6/sangre , Macrófagos/inmunología , Macrófagos/metabolismo , Macrófagos/microbiología , Masculino , Ratones , Ratones Endogámicos ICR , Óxido Nítrico/sangre , Fitoterapia , Extractos Vegetales/aislamiento & purificación , Plantas Medicinales , Células RAW 264.7 , Bazo/efectos de los fármacos , Bazo/inmunología , Bazo/metabolismo , Bazo/microbiología , Factores de Tiempo , Factor de Necrosis Tumoral alfa/sangreRESUMEN
Morus alba L. is a traditional herb with a long history of consumption, both as an edible fruit and as medicine. However, its safety evaluation has not yet been established. The objective of this study was to evaluate subchronic oral toxicity and genotoxicity of M. alba L. fruits (MFE). The subchronic toxicity after daily oral administration of MFE at 0, 40, 200, and 1000 mg/kg for 90 d was examined in Sprague Dawley (SD) rats. MFE administration did not lead to death, adverse effects, change in food and water consumption, and body weight gain. Significant toxic effects were not found within the parameters of organ weight, biochemical values, and hematological and urine analysis between the control and the MFE group. The genotoxicity of MFE was assayed by Ames test in Salmonella typhimurium strains TA98, TA102, and TA1535. No genotoxicity was found in all the tested strains. Thus in this study, a no-observed-adverse-effect level for MFE in 90 d repeated oral toxicity study in rats was determined to be greater than 1000 mg/kg regardless of gender. The results also suggested that MFE does not have a genotoxicity potential.
Asunto(s)
Frutas , Morus , Extractos Vegetales/toxicidad , Administración Oral , Animales , Daño del ADN , Femenino , Masculino , Pruebas de Mutagenicidad , Nivel sin Efectos Adversos Observados , Tamaño de los Órganos/efectos de los fármacos , Extractos Vegetales/farmacología , Ratas , Ratas Sprague-Dawley , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genética , Pruebas de Toxicidad SubcrónicaRESUMEN
BACKGROUND: Kudzu (Pueraria thunbergiana) root has long been used in Traditional Chinese Medicine. However, the vine of the kudzu plant has been considered waste material. This study aimed to investigate the hepatoprotective properties of the kudzu vine. METHODS: We created 0 %, 30 %, 70 %, and 95 % ethanolic kudzu vine extracts. The isoflavone contents of kudzu vine extract were quantified by high-performance liquid chromatography. Tertiary-butylhydroperoxide (t-BHP) was added to human liver-derived HepG2 cells, and the production of reactive oxygen species was measured in the presence and absence of kudzu vine extract. Antioxidant activity was evaluated in all kudzu vine extracts using a hydroxyradical scavenging assay. Thirty-five male Sprague-Dawley rats were divided into seven groups (n = 5); two groups were not given any extract or drug, one group was treated with 50 mg/kg silymarin orally for 5 days, and the remaining four groups were respectively treated with 100 mg/kg of 0%, 30%, 70%, or 95% ethanolic extract of kudzu vine orally once daily for 5 days. On day 5 the treatment groups and one untreated group were fed 0.75 ml/kg carbon tetrachloride (CCl4) to induce liver damage. Blood and liver tissue samples were collected 24 h after CCl4 administration for measurement of plasma alanine aminotransferase and aspartate aminotransferase, and concentration of malondialdehyde and glutathione in liver tissue. RESULTS: Puerarin was the most abundant isoflavone in kudzu vine extract. Kudzu vine extract significantly reduced the cytotoxicity and production of reactive oxygen species induced by t-BHP in a dose-dependent manner. Treatment with 0 % and 30 % ethanolic extracts of kudzu vine significantly lowered the plasma levels of alanine aminotransferase and aspartate aminotransferase in a CCl4-induced hepatotoxicity rat model (P < 0.05). Glutathione was significantly elevated in the 30 % ethanolic extract-treated group (P < 0.05), while the malondialdehyde level in liver tissue was significantly decreased in the 0 % and 30 % ethanolic extract-treated groups (P < 0.05). CONCLUSIONS: The kudzu vine is potentially highly beneficial in treating liver damage, as it scavenges reactive free radicals and boosts the endogenous antioxidant system.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Hígado/efectos de los fármacos , Sustancias Protectoras/uso terapéutico , Pueraria/química , Animales , Antioxidantes/metabolismo , Antioxidantes/uso terapéutico , Tetracloruro de Carbono , Medicamentos Herbarios Chinos , Depuradores de Radicales Libres/metabolismo , Células Hep G2 , Humanos , Isoflavonas/análisis , Isoflavonas/uso terapéutico , Masculino , Ratas Sprague-Dawley , terc-ButilhidroperóxidoRESUMEN
Myrrh has been used since ancient times for the treatment of various diseases such as inflammatory diseases, gynecological diseases, and hemiplegia. In the present study, we investigated the effects of aqueous extracts of myrrh resin (AEM) on scopolamine-induced memory impairments in mice. AEM was estimated with (2E,5E)-6-hydroxy-2,6-dimethylhepta-2,4-dienal as a representative constituent by HPLC. The oral administration of AEM for 7 days significantly reversed scopolamine-induced reduction of spontaneous alternation in the Y-maze test. In the passive avoidance task, AEM also restored the decreased latency time of the retention trial by scopolamine treatment. In addition, Western blot analysis and Immunohistochemistry revealed that AEM reversed scopolamine-decreased phosphorylation of Akt and extracellular signal-regulated kinase (ERK). Our study demonstrates for the first time that AEM ameliorates the scopolamine-induced memory impairments in mice and increases the phosphorylation of Akt and ERK in the hippocampus of mice brain. These results suggest that AEM has the therapeutic potential in memory impairments.
RESUMEN
Morus alba L. fruits have long been used in traditional medicine by many cultures. Their medicinal attributes include cardiovascular, hepatoprotective, neuroprotective and immunomodulatory actions. However, their mechanism of macrophage activation and anti-cancer effects remain unclear. The present study investigated the molecular mechanisms of immune stimulation and improved chemotherapeutic effect of M. alba L. fruit extract (MFE). MFE stimulated the production of cytokines, nitric oxide (NO) and tumor necrosis factor-α (TNF-α) and tumoricidal properties of macrophages. MFE activated macrophages through the mitogen-activated protein kinase (MAPKinase) and nuclear factor-κB (NF-κB) signaling pathways downstream from toll-like receptor (TLR) 4. MFE was shown to exhibit cytotoxicity of CT26 cells via the activated macrophages, even though MFE did not directly affect CT26 cells. In a xenograft mouse model, MFE significantly enhanced anti-cancer activity combined with 5-fluorouracil and markedly promoted splenocyte proliferation, natural killer (NK) cell activity, cytotoxic T lymphocyte (CTL) activity and IFN-γ production. Immunoglobulin G (IgG) antibody levels were significantly increased. These results indicate the indirect anti-cancer activity of MFE through improved immune response mediated by TLR4 signaling. M. alba L. fruit extract might be a potential anti-tumor immunomodulatory candidate chemotherapy agent.
Asunto(s)
Antineoplásicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Fluorouracilo/farmacología , Macrófagos/inmunología , Morus/metabolismo , Neoplasias/inmunología , Extractos Vegetales/farmacología , Linfocitos T Citotóxicos/inmunología , Receptor Toll-Like 4/inmunología , Proteínas Adaptadoras del Transporte Vesicular/genética , Proteínas Adaptadoras del Transporte Vesicular/inmunología , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Femenino , Frutas/metabolismo , Células Asesinas Naturales/inmunología , Sistema de Señalización de MAP Quinasas/inmunología , Activación de Macrófagos/efectos de los fármacos , Activación de Macrófagos/inmunología , Ratones , Ratones Endogámicos BALB C , Proteínas Quinasas Activadas por Mitógenos/inmunología , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/inmunología , FN-kappa B/inmunología , Trasplante de Neoplasias , Neoplasias/tratamiento farmacológico , Óxido Nítrico/biosíntesis , Óxido Nítrico/inmunología , Interferencia de ARN , ARN Interferente Pequeño/genética , Receptor Toll-Like 2/genética , Receptor Toll-Like 2/inmunología , Receptor Toll-Like 4/genética , Trasplante Heterólogo , Factor de Necrosis Tumoral alfa/biosíntesis , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
Breast cancer is one of the most common cancers worldwide, and the second most fatal cancer in women after lung cancer. Because there are instances of cancer resistance to existing therapies, studies focused on the identification of novel therapeutic drugs are very important. In this study, we identified a natural anticancer agent from Lantana camara, a flowering plant species of the genus Verbena. The extract obtained from the L. camara exhibited cell death properties in the human breast cancer cell line, MCF-7. We found that the apoptosis induced by treatment with the L. camara extract was regulated by the Bcl-2 family. Bid and Bax was increased and Bcl-2 was decreased by L. camara extract. L. camara extract modulated cleavage of caspase-8, and caspase-9, as well as poly (ADP-ribose) polymerase (PARP). Our results support the potential use of the L. camara extract as an anti-breast cancer drug.
Asunto(s)
Apoptosis/efectos de los fármacos , Neoplasias de la Mama/patología , Caspasa 8/efectos de los fármacos , Caspasa 9/efectos de los fármacos , Lantana , Extractos Vegetales/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/efectos de los fármacos , Adenocarcinoma/enzimología , Adenocarcinoma/patología , Antineoplásicos/farmacología , Apoptosis/fisiología , Proteína Proapoptótica que Interacciona Mediante Dominios BH3/efectos de los fármacos , Proteína Proapoptótica que Interacciona Mediante Dominios BH3/metabolismo , Neoplasias de la Mama/enzimología , Caspasa 8/metabolismo , Caspasa 9/metabolismo , Ciclo Celular/efectos de los fármacos , Ciclo Celular/fisiología , Línea Celular Tumoral , Femenino , Humanos , Técnicas In Vitro , Poli(ADP-Ribosa) Polimerasas/efectos de los fármacos , Poli(ADP-Ribosa) Polimerasas/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Proteína X Asociada a bcl-2/efectos de los fármacos , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Phytochemical investigation of the fruits of Morus alba afforded seventeen pyrrole alkaloids including five new compounds. The structures of five new pyrrole alkaloids, named morroles B-F (4, 5, 7, 16 and 17), were determined on the basis of spectroscopic interpretations. 4-[Formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl]butanoate (2) was synthesized by chemical reaction but first isolated from nature. Among isolated compounds, compounds 6 and 14 significantly inhibited pancreatic lipase activity.
Asunto(s)
Alcaloides/aislamiento & purificación , Frutas/química , Lipasa/antagonistas & inhibidores , Morus/química , Páncreas/enzimología , Pirroles/aislamiento & purificación , Alcaloides/química , Alcaloides/farmacología , Animales , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Páncreas/efectos de los fármacos , Pirroles/química , Pirroles/farmacología , PorcinosRESUMEN
Since pyrimethamine, the general therapeutic drug for toxoplasmosis, presents several adverse side effects, the need to develop and evaluate new drugs for the condition is critical. In this study, anti-Toxoplasma gondii activities of 3-[{2-((E)-furan-2-ylmethylene)hydrazinyl}methylene]-1,3-dihydroindol-2-one (ATT-5126) and 6-trifluoromethyl-2-thiouracil (KH-0562) were evaluated in vitro using a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and in vivo by measuring amount of the tachyzoites in mice ascites. Biochemical parameters such as lipid peroxidation (LPO), glutathione (GSH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were also evaluated in livers of mice at 4 days post-infection. As a result, the ATT-5126 and KH-0562 showed anti-T. gondii activity in vitro. Treatment of ATT-5126 or KH-0562 decreased the amount of tachyzoites in T. gondii infected ICR mice. The relative weight of liver and spleen increased by T. gondii infection were decreased by treatment of ATT-5126 or KH-0562. The levels of LPO, ALT and AST, which are biochemical parameters involved in liver injury, were also significantly recovered by treatment of ATT-5126 or KH-0562 (p<0.05). In particular, the recovered levels by KH-0562 were similar to those of pyrimethamine-treated group (p<0.05). However, the level of GSH, which is an antioxidant indicator, showed insignificant statistics. The results suggest that KH-0562 show anti-T. gondii activities in vitro and in vivo with low hepatotoxicity. Therefore, KH-0562 may be a useful candidate for treating T. gondii infection.