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1.
Nutrients ; 11(10)2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31615016

RESUMO

Platycodon grandiflorus root extract (PGE) has shown various properties, such as anti-hyperlipidemia, anti-diabetic, and anti-obesity, but mostly in animal studies. Therefore, we conducted a preliminary study on the anti-obesity effect of PGE in 108 Korean adults (aged 20-60 years, 30 kg/m2 ≥ body mass index ≥ 23 kg/m2). The participants were randomly assigned to four groups and were administered the placebo, PGE571 (571 mg as PGE), PGE1142 (1142 mg as PGE), and PGE2855 (2855 mg as PGE), independently, for 12 weeks. Body composition, nutrient intake, computed tomography scan, and plasma adipokines, as well as hepatic/renal function markers, were assessed. The PGE571 group revealed a significant decrease in body fat mass and body fat percentage when compared with the placebo group. Moreover, the total abdominal and subcutaneous fat areas were significantly decreased following PGE (PGE2855 group) supplementation. These results provide useful information on the anti-obesity effect of PGE for overweight and obese adult humans.


Assuntos
Sobrepeso/tratamento farmacológico , Extratos Vegetais/farmacologia , Platycodon/química , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/química , Adulto Jovem
2.
Biomed Pharmacother ; 120: 109496, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31610427

RESUMO

Cisplatin (DDP) is a first-line drug for non-small cell lung cancer (NSCLC), but its efficacy and applications are constrained by intolerance and serious side effects. Platycodon grandiflorus (PG) is usually used as lung medicinal drug to enhance other drug's effect on lung diseases. Therefore, present study aim to investigate anti-NSCLC effect of PG with DDP and mechanism involved in the combination for the first time. The results showed that compared with DDP group, the combined groups (DDP combined with 1, 2 and 4 g/kg of PG) reduced the tumor luminescence density by 26.0%, 78.2% and 32.8% respectively, and decreased the death rates, lung index, pathological damage and inflammation in lung tissue. Protein analysis of lung tissue showed that its anticancer effect may be associated with tumor cell apoptosis. Therefore, vitro studies showed that PG combined with DDP down-regulated the expression of p-Akt and PI3K and improved the protein expression of cleaved-caspase 9 in A549 cell and PG promotes the apoptosis of DDP and these mechanisms were related by inhibition of the PI3K/Akt signaling pathway. Our study confirms that the combination of PG and DDP will help enhance efficacy of DDP and is important for improving platinum-based chemotherapy.


Assuntos
Cisplatino/uso terapêutico , Fosfatidilinositol 3-Quinases/metabolismo , Extratos Vegetais/farmacologia , Platycodon/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células A549 , Animais , Cisplatino/administração & dosagem , Sinergismo Farmacológico , Quimioterapia Combinada , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Nus , Neoplasias Experimentais/tratamento farmacológico , Extratos Vegetais/administração & dosagem
3.
J Med Food ; 22(11): 1100-1109, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31566484

RESUMO

Adipocytes regulate lipid metabolism according to physiological energy requirements. A dysfunctional lipid metabolism can lead to obesity and its complications such as hepatic steatosis, diabetes, and hyperlipidemia. In our study, the impact of Platycodon grandiflorus root ethanol extract (PGH) on lipid excretion and thermogenesis-related markers in diet-induced obesity mice was analyzed. Our data show that PGH elevated fatty acid uptake in epididymal adipose tissue by increasing Cd36, Slc27a1, Ffar2, and Ffar4 expression, which led to decreased blood free fatty acid concentrations. Moreover, PGH normalized body weight and fat mass in diet-induced obese mice by increasing lipolysis (Plin1, Atgl, and Hsl) and fatty acid oxidation. Changes in the levels of browning-related genes, enzyme activity of carnitine palmitoyltransferase, and the overall transcriptome (Bmp4, Cidec, Ucp3, Sirt3, and Cox4i1) led to promote brown adipose tissue-like features (browning) in epididymal white adipose tissue and enhanced energy expenditure. Our results suggest that PGH promotes lipid excretion and thermogenic function in high-fat diet-induced obese mice, which are mediated by regulation of fat metabolism.


Assuntos
Metabolismo dos Lipídeos , Lipólise , Extratos Vegetais/farmacologia , Platycodon/química , Termogênese , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Peso Corporal , Metabolismo Energético , Ácidos Graxos/metabolismo , Regulação da Expressão Gênica , Masculino , Camundongos Endogâmicos C57BL , Camundongos Obesos , Raízes de Plantas/química , Distribuição Aleatória , Transcriptoma
4.
Int J Biol Macromol ; 141: 1220-1227, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31521659

RESUMO

This study aimed to investigate the potential protective effects of Platycodon grandiflorus polysaccharide (PGPS) on carbonyl cyanide 3-chlorophenylhydrazone (CCCP)-induced mitochondrial apoptosis in 3D4/21 cells. Apoptosis-related indicators such as cell viability, apoptosis rate, mitochondrial membrane potential (MMP), and apoptosis-related protein were examined. Results indicated that PGPSt can inhibit CCCP-induced cell damage, with cell-survival rate reaching 81% and apoptotic rate decreasing to 23%. Nuclear deformation was also significantly reduced in the PGPSt group, and changes in MMP were inhibited by PGPSt. Further analyses showed that the protein expression of Caspase-9 and Bcl-2 increased and the expression of cleaved Caspase-3 decreased, indicating that PGPSt significantly inhibited the CCCP-induced change in apoptotic protein expression. All these results suggested that PGPSt can antagonize 3D4/21 cell apoptosis by restoring MMP, protecting the integrity of nuclear morphology, and increasing Bcl-2 expression.


Assuntos
Apoptose/efeitos dos fármacos , Citoproteção/efeitos dos fármacos , Hidrazonas/toxicidade , Platycodon/química , Polissacarídeos/farmacologia , Caspase 3/metabolismo , Caspase 9/metabolismo , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
5.
Integr Cancer Ther ; 18: 1534735419876341, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31517546

RESUMO

Background: Inflammatory response and inflammation-induced vascular hyper-permeability were established leading to the abnormalities of the pulmonary microenvironment in pre-metastasis stage of breast cancer. Ruyiping is a commonly used compound drug for clinical treatment of breast cancer metastasis, and Platycodon grandiflorum is mainly used to treat pulmonary inflammatory diseases. Therefore, this study used ruyiping combined with Platycodon grandiflorum (abbreviated as RP) to investigate their inhibitory effect on pre-metastatic microenvironment of lung in 4T1 tumor-bearing mice. Study Design and Methods: The permeability of lung tissue was detected by Evans blue method. The localization of S100A8/A9 in lung tissue was obtained by double-labeling immunofluorescence staining. The level of fibrinogen in pre-metastatic microenvironment of lung as well as the levels of pro-inflammatory factors (interleukin [IL]-1ß and IL-6) and chemokines (CXCL2 and CXCL5) in bronchoalveolar lavage fluid was detected by ELISA (enzyme-linked immunosorbent assay). Results: From the experimental results, RP could protect the integrity of microvascular, inhibit the release of S100A8/A9, reduce the extravasation of fibrinogen, and decrease the expressions of IL-1ß, IL-6, CXCL2, and CXCL5. Conclusions: RP could inhibit the extravasation of fibrinogen by protecting pulmonary vascular integrity and then interrupted its interaction with carcinoma in situ, thereby inhibiting the formation of inflammatory pre-metastatic microenvironment.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Substâncias Protetoras/farmacologia , Microambiente Tumoral/efeitos dos fármacos , Animais , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Quimiocina CXCL2/metabolismo , Quimiocina CXCL5/metabolismo , Modelos Animais de Doenças , Feminino , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Neoplasias Pulmonares/metabolismo , Medicina Tradicional Chinesa/métodos , Camundongos , Camundongos Endogâmicos BALB C , Platycodon/química
6.
J Med Food ; 22(10): 993-999, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31298611

RESUMO

Obesity is caused by an energy imbalance between food intake and energy expenditure, and has detrimental effects on human health. Platycodon (Platycodon grandiflorum) widely grows in Korea, Japan, and China. It has long been used for food and as a medicinal product. However, the mechanism of the improvement of obesity by platycodon was still not clear. Therefore, we investigated the detailed mechanisms of the antiobesity activity of platycodon extracts. Twenty mice (C57BL/6J) were placed into five groups. The test group received 1 g/kg platycodon extracts. The positive control group received 10 mg/kg orlistat, while the negative control and normal control groups received phosphate-buffered saline. The extracts were given orally daily for 8 weeks. The in vivo treatment of platycodon extracts reduced body weight gain by 7.5%, improved plasma lipid profiles. In the groups given platycodon extracts, leptin was significantly decreased whereas adiponectin was increased. Furthermore, platycodon extracts downregulated lipogenic gene (e.g., lipoprotein lipase, acetyl-CoA carboxylase, and fatty acid synthase) expression and increased lipolysis genes (e.g., carnitine palmitoyltransferase 1α, hormone-sensitive lipase, and uncoupling proteins 2) in liver and white adipose tissue. In addition, platycodon extracts inhibited the expression of key adipogenic transcriptional factors. In conclusion, we have demonstrated that platycodon extracts ameliorate high-fat diet-induced obesity and its related metabolic disease by regulating multiple pathways. Dietary supplementation of platycodon extracts as a functional food and medicinal ingredients may be suitable for prevention and treatment of obesity.


Assuntos
Fármacos Antiobesidade/farmacologia , Obesidade/tratamento farmacológico , Extratos Vegetais/farmacologia , Platycodon/química , Adipogenia/efeitos dos fármacos , Adiponectina/sangue , Tecido Adiposo Branco/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Leptina/sangue , Lipídeos/sangue , Lipogênese/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Fitoterapia , Ganho de Peso/efeitos dos fármacos
7.
Phytomedicine ; 59: 152900, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30974310

RESUMO

BACKGROUND: Extracts derived from natural products have been used to produce health supplements or therapeutic agents in oriental medicine. Although these extracts contain various bioactive compounds, their applications are generally limited to a few previously known diseases. To effectively expand their use for the treatment of other conditions, systematic analysis should be conducted for repurposing. PURPOSE: The purpose of the present study was to investigate the new therapeutic efficacies of the Platycodon grandiflorum and ginseng extract using the CMAP-based gene expression analysis. METHODS: In the present study, we analyzed the expression patterns of differentially expressed genes (DEGs) from extracts as the basis for drug repurposing. Cells were treated with extracts or single compounds derived from nine natural products. DEG analysis indicated that the gene expression patterns of cells treated with P. grandiflorum and ginseng extracts were highly similar to those of cells treated with different types of Histone deacetylase (HDAC) inhibitors. To identify the new mechanism of these extracts, we carried out cell viability assay, TUNEL assay, HDAC enzyme activity assay and immunoblot analysis. RESULTS: In vitro experiments at the dose of 50 µg/ml of each extract did not affect cell death rate but significantly inhibited HDAC activity. Each extract was found to inhibit HDAC enzymatic activity and induce the expression of the p21. Furthermore, our results revealed that each extract stimulated cell death and inhibited cell proliferation. CONCLUSION: These findings demonstrate the HDAC-inhibiting activity of P. grandiflorum and ginseng extracts and further validate the effectiveness of DEG similarity-based repurposing of natural products.


Assuntos
Produtos Biológicos/farmacologia , Reposicionamento de Medicamentos/métodos , Inibidores de Histona Desacetilases/farmacologia , Extratos Vegetais/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Panax/química , Platycodon/química , Transcriptoma/efeitos dos fármacos
8.
Molecules ; 24(7)2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30934739

RESUMO

Platycodon grandiflorus is a plant widely used in traditional Chinese medicine, of which polysaccharides are reported to be the main components responsible for its bio-functions. In this work, the inulin-type fructan (PGF) was obtained by DEAE anion exchange chromatography from the water extracted from P. grandifloras. Characterization was performed with methanolysis, methylation, and NMR and the results showed that PGF is a ß-(2-1) linked fructan, with terminal glucose and with a degree of polymerization of 2⁻10. In order to study its biofunctions, the prebiotic and immunomodulation properties were assayed. We found that PGF exhibited good prebiotic activity, as shown by a promotion on six strains of lactobacillus proliferation. Additionally, the PGF also displayed direct immunomodulation on intestinal epithelial cells and stimulated the expressions of anti-inflammatory factors. These results indicated that the inulin from P. grandiflorus is a potential natural source of prebiotics as well as a potential intestinal immunomodulator, which will be valuable for further studies and new applications.


Assuntos
Frutanos/química , Frutanos/farmacologia , Imunomodulação/efeitos dos fármacos , Platycodon/química , Prebióticos , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Frutanos/isolamento & purificação , Concentração de Íons de Hidrogênio , Espectroscopia de Ressonância Magnética , Suínos
9.
J Agric Food Chem ; 67(5): 1470-1477, 2019 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-30652865

RESUMO

The Platycodon grandiflorum root, Platycodi radix, a common vegetable, and its extract with glycosylated saponins, platycosides, have been used as food items and food health supplements for pulmonary diseases and respiratory disorders. Enzymes convert glycosylated saponins into deglycosylated saponins, which exhibit higher biological activity than glycosylated saponins. In this study, ß-glucosidase from the hyperthermophilic bacterium Dictyoglomus turgidum converted platycosides in the Platycodi radix extract into deglucosylated platycosides. In addition, the enzyme completely converted platycoside E (PE), platycodin D3 (PD3), and platycodin D (PD) in Platycodi radix extract into deglucosylated platycodin D (deglu PD), which was first identified by nuclear magnetic resonance. The anti-inflammatory activities of deglu PD and deglucosylated Platycodi radix extract were higher than those of PE, PD3, PD, Platycodi radix extract, and baicalein, an anti-inflammatory agent. Therefore, deglucosylated Platycodi radix extract is expected to be used as improved functional food supplements.


Assuntos
Anti-Inflamatórios/química , Proteínas de Bactérias/química , Ácido Oleanólico/análogos & derivados , Extratos Vegetais/química , Saponinas/química , Triterpenos/química , beta-Glucosidase/química , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Bactérias/enzimologia , Proteínas de Bactérias/metabolismo , Biocatálise , Biotransformação , Glicosilação , Ácido Oleanólico/química , Ácido Oleanólico/metabolismo , Ácido Oleanólico/farmacologia , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacologia , Platycodon/química , Saponinas/metabolismo , Saponinas/farmacologia , Triterpenos/metabolismo , Triterpenos/farmacologia , beta-Glucosidase/metabolismo
10.
Phytomedicine ; 52: 254-263, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30599906

RESUMO

BACKGROUND: Platycodi Radix (root of Platycodon grandiflorum) and its active compound platycodin D (PD) has been previously shown to possess anti-obesity properties, but the underlying mechanisms remain poorly understood. PURPOSE: The present study was aimed to evaluate the anti-obese effect of PD and reveal its mechanism of action. STUDY DESIGN/METHODS: Genetically obese db/db mice were orally treated with PD for 4 weeks, and body weight gain, adipose tissue weight, serum parameters were measured. Then, assays on adipogenic factors, thermogenic factors, and AMP-activated protein kinase (AMPK) pathway were performed in PD-treated 3T3-L1 murine adipocytes, human adipose-derived mesenchymal stem cells (hAMSCs), and primary cultured brown adipocytes. RESULTS: PD treatment attenuated body weight gain, suppressed white adipose tissue weight and improved obesity-related serum parameters in db/db mice. Two major adipogenic factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα) were decreased by PD treatment in WAT of db/db mice, 3T3-L1 adipocytes and hAMSCs. In BAT of db/db mice and primary cultured brown adipocytes, PD treatment elevated the expressions of uncoupled protein 1 (UCP1) and peroxisome proliferator-activated receptor γ coactivator 1 α (PCG1α), the key regulators of BAT-associated thermogenesis. In addition, PD activated AMPKα both in vivo and in vitro. However, when AMPK was inhibited by compound C, PD treatment failed to suppress adipogenic factors and increase thermogenic factors. CONCLUSIONS: PD improved obesity in db/db mice by AMPK-associated decrease of adipogenic markers including PPARγ and C/EBPα. PD increased thermogenic factors such as UCP1 and PGC1α in db/db mice and primary cultured brown adipocytes. AMPK inhibition nullified the effects of PD, suggesting its anti-adipogenic and thermogenic actions were dependent on AMPK pathway activation.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos Marrons/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Obesidade/tratamento farmacológico , Saponinas/farmacologia , Termogênese/efeitos dos fármacos , Triterpenos/farmacologia , Células 3T3-L1 , Tecido Adiposo Marrom/citologia , Tecido Adiposo Branco/citologia , Animais , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Humanos , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos , Camundongos Knockout , PPAR gama/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Platycodon/química , Proteína Desacopladora 1/metabolismo
11.
J Asian Nat Prod Res ; 21(5): 419-425, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-29966448

RESUMO

The EtOH extract of the roots of Platycodon grandiflorum afforded two new triterpene saponins platycoside P (1) and platycoside Q (2). Their structures were elucidated based on spectroscopic means and hydrolysis products. These compounds were evaluated for inhibitory activity against LPS-induced TNF-α production in RAW 246.7 macrophages. Compounds 1 and 2 showed inhibitory activity with the inhibition ratios (%) of 38.6 and 44.1 at 50 µM, respectively.


Assuntos
Platycodon/química , Saponinas/química , Saponinas/farmacologia , Triterpenos/química , Triterpenos/farmacologia , Animais , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Camundongos , Estrutura Molecular , Raízes de Plantas/química , Células RAW 264.7
12.
Food Chem Toxicol ; 123: 412-423, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30399386

RESUMO

Allergic airway inflammation is an increasing global health problem, and novel strategies to prevent or ameliorate the condition are needed. The endoplasmic reticulum (ER) is involved in protein synthesis and maturation, and is a susceptible to sub-organelle stress including inflammation and ROS-amplifying signaling. Here, the effects of Platycodi Radix extracts (PRE) on house dust mite (HDM) extract (Dematophagoides pteronyssius)-induced asthma were investigated. Following 50, 100, or 200 mg/kg-PRE-treatment, the infiltration of inflammatory cells, ER stress, and NF-κB signaling were controlled. The expression of inflammatory cytokines and mucin5AC was also inhibited in the presence of PRE. Consistently, in the HDM-exposed human bronchial epithelial cells, ER stress and its associated ROS were significantly increased along with NF-κB signaling, which was also attenuated by PRE and its components. This study suggests that PRE might be useful as a therapeutic/preventive agent in HDM-associated allergic airway inflammation. ER stress and its associated ROS signaling involved in inflammation provide additional mechanistic insight into the underlying molecular mechanism.


Assuntos
Antioxidantes/administração & dosagem , Asma/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Platycodon/química , Pyroglyphidae/imunologia , Animais , Antioxidantes/química , Asma/genética , Asma/imunologia , Asma/metabolismo , Citocinas/genética , Citocinas/imunologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Feminino , Humanos , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/genética , NF-kappa B/imunologia , Extratos Vegetais/química , Espécies Reativas de Oxigênio/imunologia
13.
Talanta ; 192: 486-491, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30348422

RESUMO

Species of herbaceous flowering perennial plant of the family Campanulaceae such as Platycodon grandiflorum (P. grandiflorum) and Codonopsis lanceolata (C. lanceolata) widely used in traditional medicine to treat different diseases. In spite of different medicinal results after consumption of the plants, it is hard to distinguish between two of them, because of their similar morphological characteristics. In this study, a gas chromatography-mass spectrometry (GC-MS) - based metabolite profiling approach was performed and examined to discriminate tuberous roots of P. grandiflorum and C. lanceolate for medicinal purposes. Two basic approaches for sample preparation, headspace solid-phase microextraction (HS-SPME) and solvent extraction were adopted. Multivariate statistical techniques, such as orthogonal partial least-squares discriminant analysis (OPLS-DA) plots showed significant differences between P. grandiflorum and C. lanceolata for polar primary and volatile organic metabolites. A number of potential candidates were suggested as the chemomarkers for discrimination of two plants.


Assuntos
Codonopsis/metabolismo , Cromatografia Gasosa-Espectrometria de Massas/métodos , Metabolômica/métodos , Raízes de Plantas/metabolismo , Platycodon/metabolismo , Codonopsis/química , Análise Discriminante , Análise dos Mínimos Quadrados , Raízes de Plantas/química , Platycodon/química , Microextração em Fase Sólida , Compostos Orgânicos Voláteis/análise
14.
Molecules ; 23(11)2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30388815

RESUMO

Platycodon grandiflorum (PG) is widely used in Asia for its various beneficial effects. Although many studies were conducted to understand the molecular mechanisms of PG, it is still unclear how the combinations of multiple ingredients work together to exert its therapeutic effects. The aim of the present study was to provide a comprehensive review of the systems-level mechanisms of PG by adopting network pharmacological analysis. We constructed a compound⁻target⁻disease network for PG using experimentally validated and machine-leaning-based prediction results. Each target of the network was analyzed based on previously known pharmacological activities of PG. Gene ontology analysis revealed that the majority of targets were related to cellular and metabolic processes, responses to stimuli, and biological regulation. In pathway enrichment analyses of targets, the terms related to cancer showed the most significant enrichment and formed distinct clusters. Degree matrix analysis for target⁻disease associations of PG suggested the therapeutic potential of PG in various cancers including hepatocellular carcinoma, gastric cancer, prostate cancer, small-cell lung cancer, and renal cell carcinoma. We expect that network pharmacological approaches will provide an understanding of the systems-level mechanisms of medicinal herbs and further develop their therapeutic potentials.


Assuntos
Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Platycodon/química , Biologia Computacional/métodos , Medicina Tradicional do Leste Asiático , Modelos Biológicos , Compostos Fitoquímicos/análise , Extratos Vegetais/análise , Transdução de Sinais/efeitos dos fármacos
15.
Nutrients ; 10(9)2018 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-30235825

RESUMO

Although cisplatin is a potent chemotherapeutic agent against cancers, its clinical application is seriously limited by its severe side effects of nephrotoxicity. Previous studies reported that saponins isolated from the roots of Platycodon grandiflorum (PGS) exerted protective effects in various animal models of renal injury, with no confirmation on cisplatin-induced injury. This study was designed to investigate the protective effect of PGS (15 and 30 mg/kg) on cisplatin-induced kidney injury in mice. The levels of serum creatinine (CRE) and blood urea nitrogen (BUN), and renal histopathology demonstrated the protective effect of PGS against cisplatin-induced kidney injury. PGS exerted anti-inflammation effects via suppressing nuclear factor-kappa B (NF-κB) activation and alleviating the cisplatin-induced increase in inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) in kidney tissues. The expressions of phosphorylation of phosphatidylinositol 3-kinase/protein kinase B and its downstream apoptotic factors, such as Bcl-2 and caspase families were regulated by PGS in a dose-dependent manner. In conclusion, PGS exerted kidney protection effects against cisplatin-induced kidney injury by inhibiting the activation of NF-κB and regulating PI3K/Akt/apoptosis signaling pathways in mice.


Assuntos
Lesão Renal Aguda/prevenção & controle , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Cisplatino , Mediadores da Inflamação/metabolismo , Rim/efeitos dos fármacos , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Platycodon , Proteínas Proto-Oncogênicas c-akt/metabolismo , Saponinas/farmacologia , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/enzimologia , Lesão Renal Aguda/patologia , Animais , Anti-Inflamatórios/isolamento & purificação , Citoproteção , Modelos Animais de Doenças , Rim/enzimologia , Rim/patologia , Masculino , Camundongos Endogâmicos ICR , Platycodon/química , Saponinas/isolamento & purificação , Transdução de Sinais/efeitos dos fármacos
16.
Biomed Pharmacother ; 107: 867-877, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30257399

RESUMO

The root of Platycodon grandiflorus (Jacq.) A. DC. (P. grandiflorus), Platycodonis Radix, has been commonly applied to prevent and treat human diseases including bronchitis, asthma and excessive phlegm. Platycodin D (PD), one of the most important therapeutic components of P. grandiflorus, has been reported to possess protective effect against alcohol and carbon tetrachloride induced hepatotoxicity. In this study, we examined the protective efficacy of PD on acetaminophen (APAP)-induced liver injury and possible underlying mechanisms in C57BL/6J mice. Administration of PD prior to APAP intoxication significantly ameliorated the increase in serum transferases, interleukin 1ß (IL-1ß), IL-6, tumor necrosis factor alpha (TNF-α), and hepatic malondialdehyde (MDA) and the depletion of glutathione (GSH) in mice. PD pretreatment decreased the expression of heme oxygenase-1 (HO-1), cyclooxygenase-2 (COX-2) and nuclear factor kappa B (NF-κB) in presence of APAP. Moreover, PD treatment noticeably reduced APAP-induced hepatocyte necrosis and apoptosis evidenced by evaluating physiological and histological hepatocyte changes in mice. Finally, PD pretreatment significantly diminished c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinases 1 and 2 (ERK1/2), and p38 phosphorylation induced by APAP. Collectively, PD pretreatment effectively protects hepatocytes against APAP-induced hepatotoxicity in mice through ameliorating oxidative stress, inflammatory response, and hepatocyte apoptosis.


Assuntos
Acetaminofen/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Hepatócitos/efeitos dos fármacos , Saponinas/farmacologia , Triterpenos/farmacologia , Analgésicos não Entorpecentes/toxicidade , Animais , Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Glutationa/metabolismo , Hepatócitos/patologia , Inflamação/induzido quimicamente , Inflamação/prevenção & controle , Fígado/efeitos dos fármacos , Fígado/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Platycodon/química , Substâncias Protetoras/isolamento & purificação , Substâncias Protetoras/farmacologia , Saponinas/isolamento & purificação , Triterpenos/isolamento & purificação
17.
J Agric Food Chem ; 66(44): 11663-11671, 2018 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-30259737

RESUMO

TAS2R14 is of great potential as a therapeutic target against asthma, and the discovery of TAS2R14 agonists can be very valuable for treating this disease. Herein, we developed a strategy using virtual screening and affinity screening based on a fabricated biosensor combined with UPLC-MS analysis to screen TAS2R14 agonists from Platycodon grandiflorum. By ligand-based virtual screening, 16 best-fit candidates were yielded. A novel TAS2R14-functionalized high-electron-mobility transistor (HEMT) sensor was applied to detect and fish out the potential TAS2R14 agonists from P. grandiflorum extracts. Those components captured by the immobilized TAS2R14 were eluted and characterized on UPLC-QTOF MS. As a result, six potential TAS2R14 agonists were screened out and identified. Among them, platycodin L was confirmed to be a special agonist of TAS2R14 for the first time and had an EC50 of 15.03 ± 1.15 µM via intracellular calcium mobilization assay ( n = 6). The results indicated that the proposed strategy was efficient to discover TAS2R14 agonists from the herb directly.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Espectrometria de Massas/métodos , Extratos Vegetais/química , Platycodon/química , Receptores Acoplados a Proteínas-G/agonistas , Avaliação Pré-Clínica de Medicamentos/instrumentação , Extratos Vegetais/isolamento & purificação , Raízes de Plantas/química , Receptores Acoplados a Proteínas-G/metabolismo
18.
Phytother Res ; 32(11): 2235-2246, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30039882

RESUMO

Acute liver injury (ALI) induced by acetaminophen (APAP) overdose is the most common cause of drug-induced liver injury. Saponins from Platycodon grandiflorum (PGSs) ameliorate alcohol-induced hepatotoxicity and enhance human lung carcinoma cell death via AMPK signaling pathway. However, whether PGS could protect from APAP-induced ALI through AMPK activation and its downstream signals is still poorly elucidated. This work investigated the protective effect and the underlying mechanisms of PGS against APAP-induced liver toxicity in mouse. PGS was administered at 15 or 30 mg/kg i.g./day for 1 week before a single injection of APAP (250 mg/kg, i.p.) 1 hr after last treatment of PGS. Serum alanine/aspartate aminotransferases, liver tumor necrosis factor-α and interleukin-1ß levels, liver malondialdehyde formation, liver glutathione depletion, cytochrome P450 E1, and 4-hydroxynonenal levels were measured to demonstrate the protective efficacy of PGS against APAP-induced ALI. Liver histological observation provided further evidence on PGS's protective effects. PGS treatment altered the phosphorylation of AMPK and PI3K/Akt, as well as the downstream signals including Bcl-2 family, caspase, and NF-κB in a dose-dependent manner. In conclusion, we demonstrate that PGS exhibits a significant liver protection against APAP-induced ALI, mainly through NF-κB and AMPK/PI3K/Akt signaling pathways.


Assuntos
Acetaminofen/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Platycodon/química , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Aldeídos/metabolismo , Animais , Aspartato Aminotransferases/sangue , Sistema Enzimático do Citocromo P-450/metabolismo , Glutationa/metabolismo , Interleucina-1beta/metabolismo , Fígado/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos ICR , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Raízes de Plantas/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
19.
Molecules ; 23(7)2018 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-30041412

RESUMO

Platycodi Radix (PR) is the root of Platycodon grandiflorum (Jacq.) A. DC., which has been used for a long time in China to treat pulmonary diseases. The present study aimed to evaluate the quality of PR samples collected from 23 regions of 11 provinces in China. Eight saponins were quantified using HPLC coupled with evaporative light scattering detection (HPLC-ELSD). The samples with the highest total contents of saponins were from southern China, such as Yunnan, Guangxi, Jiangxi, and Guangzhou. The fingerprint analysis of PR samples was conducted by HPLC-UV method. Nineteen common peaks were selected and the similarity values varied from 0.607 to 0.921. These findings indicated that the saponins contents of PR from different regions varied significantly, with PR samples from southern China having the highest contents of saponins. These comprehensive methods were successful in evaluating the quality of PR samples from northern and southern China, which will serve as a guide for the development of PR as a clinical medication.


Assuntos
Compostos Fitoquímicos/química , Raízes de Plantas/química , Platycodon/química , China , Cromatografia Líquida de Alta Pressão , Estabilidade de Medicamentos , Medicamentos de Ervas Chinesas/química , Reprodutibilidade dos Testes , Saponinas/química
20.
Food Chem Toxicol ; 118: 94-104, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29723585

RESUMO

Lower physical performance is an important risk factor in hypokinetic-related chronic disease, metabolic syndrome, and muscle atrophy. Our previous research demonstrated that Platycodon grandiflorum-derived saponin (PS) protects against eccentric exercise-induced muscle damage and mitochondrial function-related peroxisomal acyl-coenzme A oxidase (ACOX-1) and carnitine palmitoyltransferase (CPT-1) in high-fat diet-induced non-alcoholic steatohepatitis, and it inhibits osteoclast differentiation. However, the effects of PS on physical performance remain unknown. Therefore, we investigated whether PS enhances physical activity and skeletal muscle function. Supplementation with PS (2 mg/kg for 4 weeks) increased grip strength, wheel running repetition, and time to exhaustion in treadmill and swimming exercises. Marked increases in the synthesis of skeletal muscle proteins and muscle stem cell-related paired-box 7 (PAX7) were observed, and a decrease in the negative regulator myostatin was associated with enhanced muscle regeneration. Furthermore, PS induced expression of mitochondrial function proteins, including OXPHOS-III and -IV, in vivo and in vitro. These results suggest that PS enhances exercise function by ameliorating skeletal muscle protein synthesis and mitochondrial function.


Assuntos
Mitocôndrias Musculares/efeitos dos fármacos , Proteínas Musculares/biossíntese , Músculo Esquelético/efeitos dos fármacos , Condicionamento Físico Animal , Platycodon/química , Saponinas/farmacologia , Animais , Linhagem Celular , Masculino , Camundongos Endogâmicos ICR , Mitocôndrias Musculares/metabolismo , Músculo Esquelético/metabolismo , Miostatina/metabolismo , Fosforilação Oxidativa , Fator de Transcrição PAX7/biossíntese
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