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1.
Pharmaceuticals (Basel) ; 14(10)2021 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-34681210

RESUMEN

Allergic rhinitis (AR) is a chronic inflammatory condition affecting the nasal mucosa of the upper airways. Herein, we investigated the effects of extracts from Gardenia jasminoides (GJ), a traditional herbal medicine with anti-inflammatory properties, on AR-associated inflammatory responses that cause epithelial damage. We investigated the inhibitory effects of water- and ethanol-extracted GJ (GJW and GJE, respectively) in an ovalbumin-induced AR mouse model and in splenocytes, differentiated Th2 cells, and primary human nasal epithelial cells (HNEpCs). Administering GJW and GJE to ovalbumin-induced AR mice improved clinical symptoms including behavior (sneezing and rubbing), serum cytokine levels, immune cell counts, and histopathological marker levels. Treatment with GJW and GJE reduced the secretion of Th2 cytokines in Th2 cells isolated and differentiated from the splenocytes of these mice. To investigate the underlying molecular mechanisms of AR, we treated IL-4/IL-13-stimulated HNEpCs with GJW and GJE; we found that these extracts significantly reduced the production of mitochondrial reactive oxygen species via the uncoupling protein-2 and periostin, a biomarker of the Th2 inflammatory response. Our results suggest that GJ extracts may potentially serve as therapeutic agents to improve the symptoms of AR by regulating the Th2 inflammatory response of the nasal epithelium.

2.
Front Pharmacol ; 12: 698887, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34512334

RESUMEN

This study evaluated the efficacy and safety of Banha-sasim-tang (BST) in patients with functional dyspepsia (FD). BST (Banxia-xiexin-tang in traditional Chinese medicine and Hange-shashin-to in Kampo medicine) is traditionally prescribed for the treatment of dyspepsia with epigastric stiffness and gastric fullness in China, Japan, and Korea. Patients with FD were randomly administered an oral dose (10 g) of BST syrup or placebo, twice a day for 4 weeks. The primary outcome was the symptom checklist part of the Nepean dyspepsia index (NDI). The secondary outcomes were the quality of life (QoL) part of the NDI, functional dyspepsia-related QoL (FD-QoL), and visual analog scale (VAS). A total of 60 patients with FD were screened, and 50 were randomized into BST group (n = 25) and placebo group (n = 25). Two patients in the placebo group withdrew before the start of the treatment. Administration of BST syrup resulted in improvement in the symptom-related NDI score in the BST group compared with that in the control group; however, the difference was not significant. BST syrup significantly improved "fullness after eating" index of NDI at follow-up time point (2.88 ± 2.65 vs 4.78 ± 2.69, p = 0.0081). In the total score of the QoL section of the NDI and FD-QoL scales, there was no significant improvement in the BST group compared to that in the placebo group. With regard to improvement in overall FD symptoms, the VAS scale showed improvement in both groups, but the difference was not significant. Interestingly, follow-up investigation showed a significantly beneficial effect of BST on FD symptoms, when compared to placebo. Significant improvement observed in VAS score (39.60 ± 22.29 vs 52.17 ± 20.55, p = 0.048). This indicated that the effect of BST lasted even after the completion of the medication regimen. Overall, our data suggest that while BST showed no significant improvement in the symptom-related NDI score and the QoL related scores in NDI and FD-QoL after 4 weeks of treatment, it effectively improved the VAS score and fullness after eating-related symptoms in the follow-up visit. Clinical Trial Registration:https://cris.nih.go.kr; Identifier KCT 0002013.

3.
Am J Chin Med ; 49(4): 1001-1016, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33827386

RESUMEN

The molecular mechanism underlying the anticancer effects of Anemarrhena asphodeloides (A. asphodeloides) on colon cancer is unknown. This is the first study evaluating the anticancer effect of A. asphodeloides extract (AA-Ex) in serum-starved colorectal cancer cells. Changes in cell proliferation and morphology in serum-starved MC38 and HCT116 colorectal cancer cells were investigated using MTS assay. Cell cycle and apoptosis were investigated using flow cytometry, and cell cycle regulator expression was determined using qRT-PCR. Apoptosis regulator protein levels and mitogen-activated protein kinase (MAPK) phosphorylation were assessed using western blotting. AA-Ex sensitively suppressed proliferation of serum-starved colorectal cancer cells, with MC38 and HCT116 cells showing greater changes in proliferation after treatment with AA-Ex under serum starvation than HaCaT and RAW 264.7 cells. AA-Ex inhibited cell cycle progression in serum-starved MC38 and HCT116 cells and increased the expression of cell cycle inhibitors (p53, p21, and p27). Furthermore, AA-Ex induced apoptosis in serum-starved MC38 and HCT116 cells. Consistently, AA-Ex suppressed the expression of the anti-apoptotic molecule Bcl-2 and upregulated pro-apoptotic molecules (cytochrome c, cleaved caspase-9, cleaved caspase-3, and cleaved-PARP) in serum-starved cells. AA-Ex treatment under serum starvation decreased AKT and ERK1/2 phosphorylation in the cell survival signaling pathway but increased p38 and JNK phosphorylation. Furthermore, AA-Ex treatment with serum starvation increased the levels of the transcription factors of the p38 and JNK pathway. Serum starvation sensitizes colorectal cancer cells to the anticancer effect of A. asphodeloidesvia p38/JNK-induced cell cycle arrest and apoptosis. Hence, AA-Ex possesses therapeutic potential for colon cancer treatment.


Asunto(s)
Anemarrhena , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Extractos Vegetales/farmacología , Línea Celular Tumoral , Células HCT116 , Humanos , República de Corea
4.
J Med Food ; 23(7): 760-771, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32380876

RESUMEN

It is well known that nonalcoholic fatty liver disease (NAFLD) is a common disease worldwide because of unhealthy changes in dietary habits. In this study, we determined the effects of Tenebrio molitor Linnaeus, 1758 extract (TML) and Allomyrina dichotoma Linnaeus, 1771 larvae extract (ADL) in cellular and animal models. In vitro, TML and ADL treatments did not cause cytotoxicity, but attenuated the accumulation of lipid in HepG2 cells induced by free fatty acids. In vivo, mice were orally treated with TML and ADL for 10 weeks during high-fat diet feeding. TML and ADL administration significantly reduced the weight of body, liver tissue, and adipose tissue. Serum lipid profiles, hepatic functional parameters, and glucose levels were ameliorated by TML and ADL. Moreover, TML and ADL suppressed increased lipogenesis and inflammation-related makers, and improved antioxidant enzyme activity. In liver tissue, the decreased lipid accumulation by administration of TML and ADL was observed using Oil Red O and Hematoxylin and Eosin staining. Therefore, we suggest that TML and ADL may be having a therapeutic potential and is used to develop a therapeutic agent for NAFLD.


Asunto(s)
Productos Biológicos/farmacología , Insectos , Hígado/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico , Animales , Dieta Alta en Grasa/efectos adversos , Células Hep G2 , Humanos , Metabolismo de los Lípidos , Lipogénesis , Hígado/metabolismo , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo
5.
Front Pharmacol ; 11: 447, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32346367

RESUMEN

INTRODUCTION: Stress is a well-known factor for inflammation in diverse organs/tissues. Stress also leads to liver injury, which was supported by clinical observations and animal studies. We herein investigated the hepatoprotective property of an herbal formula (called as CGplus) consisting of Artemisia gmelinii Weber ex Stechm. (syn, Artemisia iwayomogi Kitamura), Wurfbainia villosa var. xanthioides (Wall. ex Baker) Skornick. & A.D.Poulsen (syn, Amomum xanthioides Wallich), and Salvia miltiorrhiza Bunge against stress-induced hepatic damage. METHODS: Male BALB/c mice were orally administered water extract of CGplus (0, 50, 100, or 200 mg/kg) daily for 5 days, and then subjected to immobilization stress for 6 h on the 5th day. RESULTS: Acute immobilization stress elevated remarkably serum concentrations of stress hormones (corticosterone and adrenaline) and two hepatic injury parameters (ALT and AST), while these alterations were significantly attenuated by the administration of CGplus. The increases of oxidative parameters (ROS, NO, lipid peroxidation, and protein carbonyl) and deviation of IL-1ß and IL-10 in opposite directions in hepatic tissues were significantly normalized by CGplus. Pre-treatment with CGplus also notably ameliorated the abnormal activation of toll-like receptor 4 (TLR4), CD14, and lipopolysaccharide-binding protein (LPB) as well as infiltration of neutrophils in hepatic tissues. CONCLUSION: These results suggest that an herbal formula (CGplus) derived from traditional pharmaceutical theory has a potent protective effect against stress-induced hepatic injury via regulation of pro- (IL-1ß) and anti-inflammatory (IL-10) cytokines.

6.
J Med Food ; 23(5): 491-498, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32186941

RESUMEN

Changing consumption patterns and increasing health awareness, especially in Europe, are resulting in an increased demand for sesame seeds. In 2016, Asia imported the highest quantity of sesame seeds, followed by Europe and North America. We examined, for the first time, the effects of treatment with sesame oil and sesamin in hearing impairment models. Sesame oil exhibited an ameliorative effect on auditory impairment in a hair cell line in zebrafish and mice. In ototoxic zebrafish larvae, neuromasts and otic cells increased in numbers because of sesame oil. Furthermore, auditory function in noise-induced hearing loss (NIHL) was studied through auditory brainstem response to evaluate the therapeutic effects of sesame oil. Sesame oil reduced the hearing threshold shift in response to clicks and 8, 16-kHz tone bursts in NIHL mice. Auditory-protective effect of sesame oil was seen in zebrafish and mice; therefore, we used chromatographic analysis to study sesamin, which is the major effective factor in sesame oil. To investigate its effects related to auditory function, we studied the hearing-related gene, Tecta, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide (MTT) assay. Auditory cell proliferation was induced by treatment with sesame oil and sesamin using Tecta (Tectorin Alpha) regulation. The expression of Tecta increases in the apex area of the cochlear hair cells as they grow, and their activity is enhanced by sesame oil and sesamin. These results provide a novel mechanistic insight into the sesame oil activities and suggest that sesamin, the key constituent in sesame oil, is responsible for its auditory function related benefits, including protection of auditory cells and reversal of their impairments.


Asunto(s)
Dioxoles/análisis , Dioxoles/uso terapéutico , Células Ciliadas Auditivas/efectos de los fármacos , Pérdida Auditiva Provocada por Ruido/tratamiento farmacológico , Lignanos/análisis , Lignanos/uso terapéutico , Aceite de Sésamo/uso terapéutico , Animales , Línea Celular , Expresión Génica , Larva , Ratones , Pez Cebra
7.
Sci Rep ; 10(1): 2658, 2020 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-32060346

RESUMEN

The neurovascular unit, which includes neurons, glial cells, and vascular cells, plays crucial roles in the onset and progression of Alzheimer's disease (AD). Therefore, effective drugs against AD should be able to target the multi-cellular neurovascular unit and the therapeutic relationships among neurovascular cells should be defined. Here, we examined the therapeutic effects of Ukgansan (UGS), an herbal remedy with multi-targeting capabilities, using in vitro neurovascular unit models and an in vivo model of AD. In addition, we compared the therapeutic networks induced by UGS and its components in different neurovascular cell types. We found that UGS and its components protected neurovascular cells against diverse damaging agents and improved the behavioral patterns of AD model mice. A comparison of UGS- or its components-induced therapeutic networks, constructed from high-throughput data on gene expression, pathway activity, and protein phosphorylation, revealed similarities among neurovascular cell types, especially between BV-2 microglia and HBVP (human brain vascular pericytes). These findings, together with the functional connections between neurovascular cells, can explain the therapeutic effects of UGS. Furthermore, they suggest underlying similarities in the therapeutic mechanisms in different neurovascular cell types.


Asunto(s)
Medicina Tradicional de Asia Oriental , Neuronas/citología , Enfermedad de Alzheimer/tratamiento farmacológico , Animales , Línea Celular , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Ratones , Fosforilación , Mapas de Interacción de Proteínas/efectos de los fármacos
8.
Gut Liver ; 13(6): 683-689, 2019 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-30970447

RESUMEN

Background/Aims: Pancreatic ductal adenocarcinoma (PDA) is associated with an extremely poor prognosis. This study assessed the genetic diversity among patients with PDA and compared their mutational profiles before and after treatment. Methods: Tumors and matched blood samples were obtained from 22 PDA patients treated with neoadjuvant chemoradiation therapy. The somatic mutations were analyzed with comprehensive cancer gene panel (CCP). In addition, the biopsy samples obtained at diagnosis and the surgically resected samples after treatment were compared for seven patients. The CCP provided formalin-fixed paraffin-embedded sample-compatible multiplexed target selection for 409 genes implicated in cancer. Results: Assessments of the MLH1, MLH3, MSH2, and PMS2 genes showed that the four patients with the highest relative burdens of mutations harbored somatic mutations in at least three of these genes. Genes in the histone-lysine N-methyltransferase 2 (KMT2) family, such as KMT2D, KMT2A, and KMT2C, were frequently mutated in tumor samples. Survival was worse in patients with ARID1A gene mutations than those without ARID1A gene mutations. Mutation patterns were compared between tissue samples before and after neoadjuvant treatment in seven patients who underwent surgical resection. The allelic fraction of mutations in KRAS codon 12 was lower in the surgically resected samples than in the endoscopic ultrasonography-guided fine needle aspiration biopsy samples of six patients. The number of mutant alleles of the histone lysine methyltransferase gene WHSC1 also decreased after treatment. Conclusions: These results indicate that tumor tissue from PDA patients is genetically diverse and suggest that ARID1A mutations may be a potential prognostic marker for PDA.


Asunto(s)
Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/terapia , Mutación/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Anciano , Carcinoma Ductal Pancreático/mortalidad , Quimioradioterapia , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Neoplasias Pancreáticas/mortalidad , Tasa de Supervivencia
9.
Phytomedicine ; 59: 152789, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31009851

RESUMEN

BACKGROUND: Anemarrhena asphodeloides has been widely used in traditional medicine for thousands of years; it has been reported to improve learning and memory, and to reduce inflammation. However, the role of A. asphodeloides in enhancing the immune response has remained unclear. PURPOSE: This study aimed to evaluate the effect of A. asphodeloides extract (AA-Ex) on enhancing the immune response in macrophages and to identify the active compounds causing these effects. STUDY DESIGN/METHODS: To determine the enhancing immune response of AA-Ex and its active compounds, cell proliferation and cell cycle of RAW 264.7 cells were analyzed by MTS assay and flow cytometry. The gene expression of p53, p27, cyclin D2, and cyclin E2 was measured by real-time PCR. To evaluate the anti-inflammatory effects of AA-Ex and its active compounds, the production of nitric oxide (NO), reactive oxygen species (ROS), and pro-inflammatory cytokines was analyzed by Griess reagent, flow cytometry, and real-time PCR. The phosphorylation of p38, c-Jun N-terminal kinase, inhibitory kappa B alpha, and p65 was examined by western blot analysis. RESULTS: AA-Ex increased cell proliferation by extending the cell cycle S-phase; timosaponin B and timosaponin B-II affected cell proliferation and the cell cycle as active compounds of A. asphodeloides. Next, we determined that A. asphodeloides displayed anti-inflammatory effects, including the inhibition of the production of NO, ROS, and pro-inflammatory cytokines through the suppression of mitogen-activated protein kinase and nuclear factor kappa B phosphorylation downstream of the toll-like receptor 4 signaling pathway. Moreover, we identified that timosaponin B and timosaponin B-II were the active compounds for these effects. CONCLUSION: Our results suggest that A. asphodeloides promotes the immune response and has anti-inflammatory effects. Moreover, timosaponin B and B-II played important roles as the active compounds of A. asphodeloides in enhancing the immune and anti-inflammatory responses in this model.


Asunto(s)
Anemarrhena/química , Antiinflamatorios/farmacología , Extractos Vegetales/farmacología , Animales , Antiinflamatorios/química , Antiinflamatorios/inmunología , Citocinas/genética , Citocinas/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Ratones , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Fosforilación/efectos de los fármacos , Extractos Vegetales/inmunología , Plantas Medicinales/química , Células RAW 264.7 , Especies Reactivas de Oxígeno/metabolismo , Saponinas/farmacología , Transducción de Señal/efectos de los fármacos , Esteroides/farmacología , Receptor Toll-Like 4/metabolismo
10.
NeuroRehabilitation ; 44(1): 25-35, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30741701

RESUMEN

BACKGROUND: Intermanual transfer of learning is an important movement basis for a keyboard and instrument playing movement. However, the issue of where neural plastic mechanism occurs in the brain after intermanual transfer training remains both controversial and unresolved. OBJECTIVE: The aim of present study is to investigate the neuroplastic mechanism associated with the interlimb transfer learning from non-dominant hand to dominant hand. METHODS: Twenty healthy right-handed adults were classified into either the control group (no-training) or the experimental group (training serial button-press motor task, SPMT), 5 days a week for two consecutive weeks. SPMT involved pressing the numbers 1, 2, 3, and 4 in a random sequence, which was presented in the monitor screen. Outcome measures included movement accuracy (MA), movement time (MT), and the fMRI data using a 3T MRI scanner. Repeated measures of analysis of variance (ANOVA) and non-parametric tests were used at p <0.05. RESULTS: Motor performances in the MA and MT were significantly more improved in the experimental group than in the control group (p <0.05). Neuroimaging data revealed a distributed subcortical and cortical motor network including the SMA-thalamus (VL/VL)-basal ganglia-cerebellum loop, suggesting a differential and time-dependent neural network utilized during intermanual transfer learning. CONCLUSION: Pre-training intermanual transfer learning involved a form of declarative (or explicit) motor learning, which was primarily mediated by the cortical motor network, whereas post-training involved a form of procedural knowledge, which activated subcortical and cortical motor network regions, including the SMA-thalamus (VL/VL)-basal ganglia-cerebellum loop.


Asunto(s)
Lateralidad Funcional/fisiología , Imagen por Resonancia Magnética/métodos , Destreza Motora/fisiología , Plasticidad Neuronal/fisiología , Desempeño Psicomotor/fisiología , Transferencia de Experiencia en Psicología/fisiología , Adulto , Ganglios Basales/fisiología , Cerebelo/fisiología , Femenino , Mano/fisiología , Humanos , Masculino , Estudios Prospectivos , Tálamo/fisiología , Adulto Joven
11.
Nutrients ; 11(1)2019 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-30626089

RESUMEN

Sensorineural hearing loss (SNHL) is one of the most common causes of disability, affecting over 466 million people worldwide. However, prevention or therapy of SNHL has not been widely studied. Avocado oil has shown many health benefits but it has not yet been studied in regards to SNHL. Therefore, we aimed to investigate the efficacy of avocado oil on SNHL in vitro and in vivo and elucidate its mode of action. For the present study, we used enhanced functional avocado oil extract (DKB122). DKB122 led to recovery of otic hair cells in zebrafish after neomycin-induced otic cell damage. Also, DKB122 improved auditory sensory transmission function in a mouse model of noise induced-hearing loss and protected sensory hair cells in the cochlea. In addition, RNA sequencing was performed to elucidate the mechanism involved. KEGG pathway enrichment analysis of differentially expressed genes showed that DKB122 protected House Ear Institute-Organ of Corti 1 (HEI-OC1) cells against neomycin-related alterations in gene expression due to oxidative stress, cytokine production and protein synthesis.


Asunto(s)
Aminoácidos/biosíntesis , Regulación de la Expresión Génica/efectos de los fármacos , Células Ciliadas Auditivas/efectos de los fármacos , Pérdida Auditiva Sensorineural , Persea/química , Fitoterapia , Aceites de Plantas/farmacología , Animales , Percepción Auditiva/efectos de los fármacos , Cóclea/citología , Cóclea/efectos de los fármacos , Cóclea/metabolismo , Células Ciliadas Auditivas/metabolismo , Células Ciliadas Auditivas/fisiología , Pérdida Auditiva Provocada por Ruido/tratamiento farmacológico , Pérdida Auditiva Provocada por Ruido/genética , Pérdida Auditiva Provocada por Ruido/metabolismo , Pérdida Auditiva Provocada por Ruido/fisiopatología , Pérdida Auditiva Sensorineural/tratamiento farmacológico , Pérdida Auditiva Sensorineural/genética , Pérdida Auditiva Sensorineural/metabolismo , Pérdida Auditiva Sensorineural/fisiopatología , Redes y Vías Metabólicas/efectos de los fármacos , Redes y Vías Metabólicas/genética , Ratones , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Aceites de Plantas/uso terapéutico , Análisis de Secuencia de ARN , Pez Cebra
12.
J Altern Complement Med ; 24(5): 463-471, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29641212

RESUMEN

OBJECTIVES: Pharmacotherapy among children with attention-deficit/hyperactivity disorder (ADHD) is effective, but many patients suffer from secondary psychiatric problems even after improvement of ADHD core symptoms. Hippotherapy have been used as adjunct treatment options for physical and psychosocial rehabilitation as well as to ameliorate core symptoms. The aim of this study was to investigate the effects of Hippotherapy versus pharmacotherapy for children with ADHD. DESIGN: Thirty-four participants with ADHD were randomly assigned at a 1:1 ratio to either 24 sessions of a twice-weekly hippotherapy or pharmacotherapy. To assess therapeutic effects, the ADHD Rating Scale (ARS) was used pretreatment and posttreatment as the primary outcome measure. Secondary outcomes included the Child Behavior Checklist (CBCL), Self-Esteem Scale (SES), Pediatric Quality of Life Inventory (PedsQL) child and parent report version, Developmental Coordination Disorder Questionnaire (DCDQ), Clinical Global Impressions-Severity (CGI-S), and quantitative electroencephalography. RESULTS: Both groups showed marked improvements in ADHD symptoms, CGI-S. No significant differences between groups were detected regarding treatment outcome except thought problem subscales of CBCL. Twelve weeks of hippotherapy improved attention, impulsivity/hyperactivity, and quality of life. CONCLUSION: This trial is promising, but further studies are required to evaluate the long-term clinical effectiveness of hippotherapy. The study is registered with ClinicalTrials.gov, number NCT 02482649.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Trastorno por Déficit de Atención con Hiperactividad/terapia , Terapía Asistida por Caballos , Inhibidores de Captación Adrenérgica/uso terapéutico , Clorhidrato de Atomoxetina/uso terapéutico , Estimulantes del Sistema Nervioso Central/uso terapéutico , Niño , Conducta Infantil , Electroencefalografía , Femenino , Humanos , Masculino , Metilfenidato/uso terapéutico
13.
J Med Food ; 21(6): 560-567, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29569973

RESUMEN

Black raspberry extract (BRE) has been widely used for treating prostate and urinary diseases and hyperlipidemia in Asia due to its significant lipid-lowering effects. The aim of this investigation was to evaluate the antihypercholesterolemia activity of BRE and the potential molecular mechanisms responsible for its antihypercholesterolemia activity by regulation of proprotein convertase subtilisin/kexin type 9 (PCSK9) expression in the human liver cell line HepG2. Reporter-based functional assay was used to identify herbal extracts that suppress PCSK9 expression in the HepG2 cells. Quantitative real-time polymerase chain reaction, Western blot analysis, and immunofluorescence staining were used to evaluate whether BRE modulates low-density lipoprotein receptor (LDLR) expression by repressing the hepatic expression of PCSK9. The LDLR activity of the HepG2 cells was determined using an LDL uptake assay. Our finding revealed that BRE modulates LDLR expression by suppressing the hepatic expression of PCSK9. We found that the combination of simvastatin and BRE caused the synergic induction of LDLR expression and LDL-C uptake, whereas simvastatin alone increased the expression of PCSK9 in the HepG2 cells. These results clearly demonstrated that the BRE from black raspberry suppressed simvastatin-induced PCSK9 expression and improved LDL-C uptake by hepatocytes through the induction of LDLR expression. These results suggest that the suppression of PCSK9 expression by BRE may potentiate the hypolipidemic effect of statins.


Asunto(s)
Extractos Vegetales/farmacología , Proproteína Convertasa 9/metabolismo , Receptores de LDL/metabolismo , Rubus/química , Regulación hacia Abajo/efectos de los fármacos , Frutas/química , Células Hep G2 , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Humanos , Proproteína Convertasa 9/genética , Receptores de LDL/genética , Regulación hacia Arriba/efectos de los fármacos
14.
Complement Ther Med ; 35: 133-139, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29154058

RESUMEN

INTRODUCTION: This systematic review aimed to assess the clinical evidence for the widespread use of herbal medicines in treating acute otitis media. METHODS: Eleven electronic databases, including MEDLINE, EMBASE, and the CENTRAL were searched, without language limitations. All randomised controlled trials involving the use of herbal medicines, alone or in combination with conventional therapies, for acute otitis media were included. RESULTS: We identified 4956 studies, of which seven randomised clinical trials met the inclusion criteria. The overall risk of bias of the included trials was relatively high or unclear. Treatment with Longdan-xiegan decoction or Shenling-baizhu powder, combined with antibiotics, appeared to be more effective than treatment with antibiotics alone in terms of the proportion of patients with total symptom recovery. Moreover, combination treatment of Sinupret® and antibiotics facilitated the recovery of middle ear conditions and hearing acuity. CONCLUSIONS: Despite some indications of potential symptom improvement, the evidence regarding the effectiveness and efficacy of herbal medicine for acute otitis media is inconclusive due to the poor quality of trials included. Moreover, we only analysed seven trials in this review. Therefore, to properly evaluate the effectiveness of herbal medicine for acute otitis media, systematic reviews based on more rigorously designed randomized trials are warranted in the future.


Asunto(s)
Otitis Media/tratamiento farmacológico , Fitoterapia , Extractos Vegetales/uso terapéutico , Antibacterianos/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Magnoliopsida , Plantas Medicinales
15.
J Med Food ; 20(12): 1222-1232, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29090980

RESUMEN

Hyacinth bean, Dolichos lablab or Lablab purpureus, has been used for centuries in India and China as an edible pod and animal forage, as well as to treat diarrhea and other gastrointestinal disease in traditional Korean medicine. Recently, we have demonstrated that D. lablab extract (DLL-Ex) prevented free fatty acid-induced lipid accumulation in an in vitro cellular nonalcoholic fatty liver disease (NAFLD) model. In this study, we, thus, aimed at clarifying the hepatoprotective effects of DLL-Ex in a high-fat diet-induced in vivo animal NAFLD model, as well as at elucidating underlying mechanisms of identified effects. Sixty, 6-week-old, male C57BL/6J mice were randomly divided into six groups: a control group fed a low-fat diet, four high-fat diet (HFD) groups, three receiving daily oral supplementation of DLL-Ex (25, 50, and 100 mg/kg/day), and one HFD group receiving daily oral supplementation of MILK (100 mg/kg/day). Effects of DLL-Ex supplementation were evaluated by histopathological and histochemical assessments. DLL-Ex supplementation inhibited HFD-induced increases in body weight and body fat mass and ameliorated increases in body weight, manifested as decreased liver function tests, lower serum triglycerides and cholesterol levels, and increased serum adiponectin levels. The expression of hepatic genes involved in lipid droplet accumulation and in fatty acid uptake was also decreased. We provide evidence of a protective effect of DLL-Ex against HFD-induced fatty liver disease in an animal model.


Asunto(s)
Dolichos/química , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Extractos Vegetales/administración & dosificación , Sustancias Protectoras/administración & dosificación , Animales , Peso Corporal/efectos de los fármacos , Colesterol/metabolismo , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Humanos , Hígado/efectos de los fármacos , Hígado/metabolismo , Pruebas de Función Hepática , Masculino , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Triglicéridos/metabolismo
16.
Trials ; 18(1): 525, 2017 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-29121988

RESUMEN

BACKGROUND: Functional dyspepsia (FD) refers to the presence of one or more gastrointestinal symptoms including postprandial fullness, epigastric pain, burning, and early satiety without an organic explanation for chronic symptoms. FD causes considerable discomfort in patients and affects their everyday activity and productivity. Because most conventional treatments have limited efficacy, numerous patients seek alternatives such as herbal medicines. In this proposed study, we will conduct a clinical trial of an herbal drug, Banha-sasim-tang (BST). Furthermore, participants will be limited to those classified as having an excess pattern by using an instrument of pattern identification for FD to determine the efficacy of BST in a specific subset of patients. METHODS: This randomized, blinded, parallel-group clinical trial of BST versus placebo will consist of 4 weeks of oral administration of BST or placebo and a 4-week follow-up period. The Korean version of the symptom-based questionnaire of the Nepean Dyspepsia Index (NDI-K) will be used as the primary outcome measure. Secondary outcome measures will include the quality-of-life (QoL) evaluation from the NDI-K, the FD-related QoL (FD-QoL) scale, assessment of gastric myoelectrical dysrhythmias (GMA), and a Visual Analog Scale (VAS) analysis. DISCUSSION: The results of this trial are expected to provide relevant evidence demonstrating that BST can be used as an effective treatment in a specific subset of FD subjects. TRIAL REGISTRATION: KCT 0002013 . Registered at Clinical Research Information Service in the Republic of Korea on 18 August 2016.


Asunto(s)
Dispepsia/tratamiento farmacológico , Fármacos Gastrointestinales/uso terapéutico , Preparaciones de Plantas/uso terapéutico , Adulto , Anciano , Protocolos Clínicos , Dispepsia/clasificación , Dispepsia/diagnóstico , Dispepsia/fisiopatología , Femenino , Fármacos Gastrointestinales/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Preparaciones de Plantas/efectos adversos , Calidad de Vida , República de Corea , Proyectos de Investigación , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
17.
BMC Complement Altern Med ; 17(1): 154, 2017 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-28288606

RESUMEN

BACKGROUND: Asian traditional herbal preparations are frequently considered for the contamination with undeclared toxic or hazardous substances. The aim of this study was to determine the toxic heavy metals, pesticides and sulfur dioxide in decoctions that is a common form of final utilization in Korea. METHODS: A total of 155 decoctions composed of multi-ingredient traditional herbs were randomly sampled from Seoul in Korea between 2013 and 2014. For each decoction, the concentrations of four heavy metals (arsenic, cadmium, lead and mercury), 33 pesticides and sulfur dioxide were analyzed using inductively coupled plasma mass spectrometry (ICP-MS), mercury analyzer, gas chromatography/nitrogen phosphorous detector (GC/NPD), gas chromatography/micro electron capture detector (GC/µECD), and Monier-Williams method respectively. RESULTS: One hundred fifty-two of One hundred fifty-five decoctions (98.1%) contained one of three heavy metals (96.1% for As, 97.4% for Cd, and 90.3% for Pb, 0.0% for Hg). Their average concentrations (77.0 ± 79.7 ug/kg for As, 20.4 ± 23.7 ug/kg for Cd, and 68.8 ± 76.5 ug/kg for Pb) were approximately 20% of the maximum allowable limits of vegetable or ginseng beverage described in the Korean Food Standard Codex while their 95th percentile concentrations were below than the guideline for them. None of 33 pesticides was detected in 155 decoction samples, and only one sample showed over limit of detection for residual sulfites. CONCLUSIONS: This study support that the contained status of toxic heavy metals, pesticides and sulfur dioxide in herbal decoctions are currently within safe level in Korea, and provide a reference data for the further studies focused on the safety herbal preparations.


Asunto(s)
Agroquímicos/análisis , Contaminación de Medicamentos/estadística & datos numéricos , Metales Pesados/análisis , Extractos Vegetales/análisis , Plantas Medicinales/química , Sulfitos/análisis , Espectrometría de Masas , Residuos de Plaguicidas/análisis , República de Corea
18.
Theranostics ; 7(3): 562-572, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28255351

RESUMEN

Perfluorocarbon nanoemulsions (PFCNEs) have recently been undergoing rigorous study to investigate their ability to improve the therapeutic efficacy of tumor ablation by high intensity focused ultrasound (HIFU). For precise control of PFCNE delivery and thermal ablation, their accumulation and distribution in a tumor should be quantitatively analyzed. Here, we used fluorine-19 (19F) magnetic resonance imaging (MRI) to quantitatively track PFCNE accumulation in a tumor, and analyzed how intra-tumoral PFCNE quantities affect the therapeutic efficacy of HIFU treatment. Ablation outcomes were assessed by intra-voxel incoherent motion analysis and bioluminescent imaging up to 14 days after the procedure. Assessment of PFCNE delivery and treatment outcomes showed that 2-3 mg/mL of PFCNE in a tumor produces the largest ablation volume under the same HIFU insonation conditions. Histology showed varying degrees of necrosis depending on the amount of PFCNE delivered. 19F MRI promises to be a valuable platform for precisely guiding PFCNE-enhanced HIFU ablation of tumors.


Asunto(s)
Técnicas de Ablación/métodos , Carcinoma/diagnóstico por imagen , Carcinoma/terapia , Imagen por Resonancia Magnética con Fluor-19/métodos , Fluorocarburos/administración & dosificación , Hipertermia Inducida/métodos , Sonicación/métodos , Animales , Carcinoma/patología , Modelos Animales de Enfermedad , Emulsiones/administración & dosificación , Histocitoquímica , Ratones Endogámicos BALB C , Ratones Desnudos , Trasplante Heterólogo , Resultado del Tratamiento
19.
BMJ Open ; 6(11): e011250, 2016 11 24.
Artículo en Inglés | MEDLINE | ID: mdl-27884841

RESUMEN

OBJECTIVES: This systematic review aimed to assess the clinical evidence supporting the use of herbal medicines (HMs) for the treatment of otitis media with effusion (OME). DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, EMBASE, Cochrane Library, AMED, CINAHL and three trial registries were searched up to January 2015. We also searched five Korean medical databases (KoreaMed, RISS, OASIS, DBPIA and KISS) and three Chinese databases (CNKI, Wanfang and VIP). STUDY ELIGIBILITY CRITERIA: This study included randomised clinical trials that reported the effects of HM for OME. The primary outcome was the complete resolution of OME at 2 or 3 months post randomisation. Secondary outcomes included the partial or complete resolution at all possible time points and hearing test. Three authors independently screened the titles and abstracts, selected studies and extracted the data relating to trial quality, characteristics and results. RESULTS: A total of 2141 potentially relevant studies were identified, of which 17 randomised clinical trials met our inclusion criteria. Most were evaluated as having a high or unclear risk of bias. Tongqiao tablets, Tongqiao huoxue decoctions and Tsumura-Saireito were associated with a lower complete or partial resolution rate when compared with conventional medicines (CMs) (p=0.02, p=0.0001, and p=0.04, respectively), and similar outcomes were observed with Huanglong tonger pills, Erzhang decoctions and Shenling baizhu powder when combined with CM versus CM alone (p<0.00001, p=0.02, and p=0.05, respectively). Tongqiao huoxue decoction plus CM appeared to be more effective than CM in terms of improving the pure tone threshold levels (p=0.0007). Tsumura-Saireito was found to affect the proportion of patients with normalised tympanometry (p=0.03). CONCLUSIONS: Despite some indications of potential symptom improvement, the evidence regarding the effectiveness and efficacy of HMs for OME is of poor quality and therefore inconclusive. PROTOCOL REGISTRATION NUMBER: CRD42013005430.


Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Otitis Media con Derrame/tratamiento farmacológico , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto
20.
J Med Food ; 19(5): 495-503, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-27152979

RESUMEN

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease that is rising in prevalence worldwide. Therapeutic strategies for patients with NAFLD are limited by a lack of effective drugs. In this report, we show that Dolichos lablab water extract (DLL-Ex) protects against free fatty acid (FFA)-induced lipid accumulation and attenuates expression of genes involved in lipid droplet accumulation in cellular NAFLD models. The hepatoprotective effects and underlying mechanism of DLL-Ex were assessed using an in vitro cellular model in which NAFLD was simulated by inducing excessive FFA influx into hepatocytes. HepG2 cells were treated with DLL-Ex and FFAs for 24 h, after which intracellular lipid content was observed by using Nile Red and Oil Red O staining. Quantitative real-time polymerase chain reaction was used to measure expression levels of genes related to FFA-mediated cellular energy depletion. Western blotting was used to measure protein levels of phosphorylated c-Jun N-terminal kinase, AMP-activated protein kinase alpha (AMPKα), and peroxisome proliferator-activated receptor γ coactivator 1 alpha. In HepG2 cells, DLL-Ex inhibited expression of CD36, which regulates fatty acid uptake, as well as BODIPY-labeled fatty acid uptake. Additionally, DLL-Ex significantly attenuated FFA-mediated cellular energy depletion and mitochondrial membrane depolarization. Furthermore, DLL-Ex enhanced phosphorylation of AMPK, indicating that AMPK is a critical regulator of DLL-Ex-mediated inhibition of hepatic lipid accumulation, possibly through its antioxidative effect. These results demonstrate that DLL-Ex exerts potent anti-NAFLD activity, suggesting that it could be a potential adjuvant treatment for patients with NAFLD.


Asunto(s)
Dolichos/química , Metabolismo de los Lípidos/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Proteínas Quinasas Activadas por AMP/genética , Proteínas Quinasas Activadas por AMP/metabolismo , Ácidos Grasos no Esterificados/metabolismo , Células Hep G2 , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos/genética , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/metabolismo , PPAR gamma/genética , PPAR gamma/metabolismo , Fosforilación
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