RESUMO
The tuberous roots of Ophiopogon japonicus and Liriope spicata are used for the same therapeutic purpose in traditional Chinese medicine and are collectively referred to as maidong medicine. Interestingly, it was observed that the price of tuberous roots varies depending on their location on the plant, and fibrous roots are usually discarded post-harvest. Mislabeling might be of concern due to similarities in morphological features between the two species. Moreover, paclobutrazol has been observed to be heavily applied during the production, and therefore might be of health concern. Overall, maidong might suffer from quality inconsistencies while its metabolomic complexity is influenced by growing region and cultivation practices, botanical species, and plant parts. To address these challenges, this study employed High-Performance Thin Layer Chromatography (HPTLC) approach, in which sample preparation and derivatization procedure were optimized to enable to capture more detailed and comprehensive metabolomic fingerprints. By integrating with rTLC algorithm and Multivariate Data Analysis (MVDA), an improved quality assessment was achieved. Samples were collected from four production regions and supplemented with commercial products from markets. The optimized HPTLC analysis recognized species- and region-specific metabolomic patterns of maidong, uncovering a 4% of mislabelled cases. Moreover, findings highlight the underexplored therapeutic potential of fibrous roots, and comparable therapeutic efficacy between different root types. Additionally, complemented by Liquid Chromatography-Mass Spectrometry (LC-MS) for paclobutrazol residue evaluation, 24.66% of the commercial maidong samples surpassed maximum residue limits of paclobutrazol, raising safety concerns. This research represents a significant analytical advancement, offering a robust, cost-effective, and comprehensive method for maidong quality control, and paving the way for more strict residue regulation and updates to herbal pharmacopoeias and monographs.
Assuntos
Liriope (Planta) , Ophiopogon , Ophiopogon/química , Cromatografia em Camada Fina , Liriope (Planta)/química , Metabolômica , Controle de QualidadeRESUMO
Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder that causes excess lipid accumulation in the liver and is the leading cause of end-stage liver disease. Liriope platyphylla is a medicinal herb that has long been used to treat cough, obesity, and diabetes. However, the effect of Liriope platyphylla on NAFLD has not been studied. The aim of this study was to investigate the effect of Liriope platyphylla root ethanolic extract (LPE) on hepatic lipid accumulation in high-fat diet (HFD)-induced obese mice. Six-week-old C57BL/6 male mice were fed a HFD for 8 weeks and then treated with LPE (100 or 250 mg/kg/day) by oral gavage for another 8 weeks. Body weight gain and liver weight were significantly lower in the 250 mg/kg LPE-treated HFD group than in the vehicle-treated HFD group. Histological analysis of liver sections demonstrated that LPE treatment reduced lipid accumulation compared to the vehicle treatment. The serum total cholesterol, AST, and ALT levels significantly decreased in the LPE-treated HFD group compared to those in the vehicle-treated HFD group. The LPE significantly decreases the protein expression levels of SREBP1, ACC, p-ACC, FAS, and SCD1, which are involved in lipogenesis, and PPARγ, CD36/FAT, and FATP5, which are involved in fatty acid uptake, both in vivo and in vitro. Thus, LPE may attenuate HFD-induced NAFLD by decreasing lipid accumulation by inhibiting lipogenesis and fatty acid uptake.
Assuntos
Dieta Hiperlipídica , Etanol/química , Lipídeos/sangue , Lipogênese , Liriope (Planta)/química , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Raízes de Plantas/química , Animais , Ácidos Graxos/metabolismo , Regulação da Expressão Gênica , Células Hep G2 , Humanos , Lipogênese/genética , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Obesos , Extratos Vegetais/farmacologia , Triglicerídeos/sangue , Aumento de PesoRESUMO
Although significant progress has been made in the treatment of lung cancer, it remains the leading cause of cancerassociated mortality. Liriopesides B (LPB) is a natural product isolated from the tuber of Liriope platyphylla, whose effective substances have exhibited antitumor activity in several types of cancer. However, the functions of LPB in nonsmall cell lung cancer (NSCLC) require further investigation. Therefore, the present study aimed to investigate whether LPB influences the pathogenic effects of NSCLC. In the present study, it was demonstrated that LPB reduced proliferation, and induced apoptosis and cell cycle arrest in nonsmall cell lung cancer cells. CCK8 and colony formation assays demonstrated that LPB decreased cell viability and proliferation of H460 and H1975 cells in a dosedependent manner. Flow cytometry revealed that LPB significantly induced apoptosis of NSCLC cells, along with changes in the expression of apoptosisassociated proteins, including an increase in Bax, caspase3, and caspase8 expression, and a decrease in Bcl2 and Bclxl expression. LPB inhibited the progression of the cell cycle from the G1 to the S phase. Furthermore, autophagy was increased in cells treated with LPB. Finally, the expression of programmed deathligand 1 was significantly decreased by LPB. In conclusion, the results of the present study highlight a potential novel strategy for the clinical treatment of NSCLC.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Compostos de Espiro/farmacologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Compostos Heterocíclicos de 4 ou mais Anéis/química , Humanos , Liriope (Planta)/química , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Compostos de Espiro/químicaRESUMO
Acute myeloid leukemia (AML) is a malignant disease originating from hematopoietic stem cells (HSC). Chemotherapy and/or HSC transplantation is unsatisfactory due to serious side effects, multidrug resistance, and high relapse rate. Thus, alternative strategies are urgently needed to develop more effective therapies. Liriope muscari baily saponins C (DT-13) is a novel compound isolated from Liriope muscari (Decne.) Baily, and exhibited a potent cytotoxicity against several solid tumors. However, the anti-AML activity of DT-13 and the potential mechanisms are still unknown. This study is the first to demonstrate that DT-13 had preferential cytotoxicity against AML cells, and remarkably inhibited proliferation and colony forming ability. Moreover, DT-13 induced the death receptor pathway-dependent apoptosis of HL-60 and Kasumi-1 cells by up-regulating Fas, FasL, DR5 and TRAIL as well as promoted the cleavage of caspase 8, caspase 3 and PARP. Meanwhile, DT-13 induced the differentiation with morphological change related to myeloid differentiation, elevated NBT and α-NAE positive cell rates, differentiation markers CD11b and CD14 as well as level of transcription factors C/EBPα and C/EBPß. RNA-sequencing analysis revealed that KLF2 may be one of the potential targets regulated by DT-13. Further studies indicated that KLF2 played a critical role in DT-13-induced apoptosis and differentiation. Moreover, activation of AMPK-FOXO was proved to be the upstream of KLF2 pathway that contributed to the induction of apoptosis and differentiation by DT-13. Additionally, restoration of KLF2 by DT-13 was highly correlated with the AMPK-related histone acetylation mechanisms. Finally, DT-13 exhibited an obvious anti-AML effect in NOD/SCID mice with the engraftment of HL-60 cells. Our study suggests that DT-13 may serve as a novel agent for AML by AMPL-KLF2-mediated apoptosis and differentiation.
Assuntos
Proteínas Quinases Ativadas por AMP/efeitos dos fármacos , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Fatores de Transcrição Kruppel-Like/efeitos dos fármacos , Leucemia Mieloide Aguda/patologia , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Humanos , Liriope (Planta)/química , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Ensaio Tumoral de Célula-TroncoRESUMO
BACKGROUND: Tumor metastasis is a terrifying characteristic of cancer. Numerous studies have been conducted to overcome metastasis by targeting tumor microenvironment (TME). However, due to complexity of tumor microenvironment, it remained difficult for accurate targeting. Dwarf-lillytruf tuber monomer-13 (DT-13) possess good potential against TME. OBJECTIVE: As TME is supportive for tumor metastasis, alternatively it is a challenging for therapeutic intervention. In our present study, we explored molecular mechanism through which TME induced cell migration and how DT-13 interferes in this mechanism. METHODS: We used a novel model of co-culture system which is eventually developed in our lab. Tumor cells were co-cultured with hypoxia induced cancer-associated fibroblasts (CAF) or with chemically induced cancer-associated adipocytes (CAA). The effect of hypoxia in conditioned medium for CAF was assessed through expression of α-SMA and HIF by western blotting while oil red staining was done to assess the successful chemical induction for adipocytes (CAA), the effect of TME through conditioned medium on cell migration was analyzed by trans-well cell migration, and cell motility (wound healing) analyses. The expression changes in cellular proteins were assessed through western blotting and immunofluorescent studies. RESULTS AND CONCLUSION: Our results showed that tumor microenvironment has a direct role in promoting breast cancer cell migration by stromal cells; moreover, we found that DT-13 restricts this TME regulated cell migration via targeting stromal cells in vitro. Additionally we also found that DT-13 targets NMII-A for its effect on breast cancer cell migration for the regulation of stromal cells in TME.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Cadeias Pesadas de Miosina/metabolismo , Saponinas/farmacologia , Animais , Neoplasias da Mama/imunologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Fibroblastos Associados a Câncer/efeitos dos fármacos , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Linhagem Celular Tumoral , Movimento Celular/imunologia , Feminino , Humanos , Liriope (Planta)/química , Camundongos , Cadeias Pesadas de Miosina/genética , Transdução de Sinais , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologiaRESUMO
The tuberous roots of Liriope platyphylla (Liriopis Tuber; LT) is traditionally used in Korean Medicine for treating colds, cough, and sputum production. In this study, we investigated the effect of spicatoside A isolated from LT methanol extract on ovalbumin (OVA)-sensitized/challenged asthmatic mice. For induction of allergic asthma, BALB/c mice were sensitized with OVA by an intraperitoneal injection at three times a week, and then challenged into the nasal cavities using a nebulizer. Spicatoside A at dose of 1mg/kg body weight was treated in mice with an oral administration once daily for a week during OVA challenge. The concentrations of OVA-specific IgE, IL-4, IL-5 and IL-13 were measured in the sera or bronchoalveolar lavage fluids (BALF) of mice by enzyme-linked immunosorbent assay (ELISA). The numbers of total cells, macrophages, lymphocytes, neutrophils and eosinophils were counted in BALFs using Diff-Quik staining, and histopathological changes of lung tissues were observed by hematoxylin and eosin (H&E), Periodic acid Schiff (PAS) and Masson's trichrome staining. The purity of spicatoside A was 98.1% with a white powder (yield: 465.6mg). The treatment of spicatoside A in asthmatic mice significantly decreased the production of allergic mediator, OVA-specific IgE and Th2 cytokines, IL-4, IL-5 and IL-13 in sera and BALF. The numbers of inflammatory cells such as macrophages, lymphocytes, neutrophils and eosinophils in BALF of asthmatic mice were significantly reduced by the treatment of spicatoside A. Furthermore, the treatment of spicatoside A in asthmatic mice inhibited the structural damages of lung tissues with thickened bronchiolar epithelium and infiltration of inflammatory cells, the accumulation of mucus by the goblet cells hyperplasia and collagen in the bronchioles. These results suggest that spicatoside A of LT has a preventive effect on allergic asthma through the inhibition of lung inflammation and allergic response.
Assuntos
Asma/induzido quimicamente , Liriope (Planta)/química , Ovalbumina/farmacologia , Saponinas/farmacologia , Animais , Asma/metabolismo , Líquido da Lavagem Broncoalveolar , Citocinas/metabolismo , Modelos Animais de Doenças , Imunoglobulina E/metabolismo , Inflamação/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
The hydrogen peroxide generation system was used to analyze the scavenging activity of hydrogen peroxide by Liropes Radix from different origins by HPLC-UV-CL. The UV-CL fingerprints of Liropes Radix from different origins were evaluated,and the HPLC-UV and LC-CL fingerprints were systematically analyzed and evaluated. The results showed that the ether fractions of Liriope spicata var. prolifera and L. muscari had good scavenging activity of hydrogen peroxide,and the total activity of different origins varied greatly,while the similar samples had similar activities. The total antioxidant activity of L. muscari is higher than that of L. spicata var.prolifera. The similarity analysis of the two fingerprints was carried out by two different analytical methods. The chemical fingerprints and the active fingerprints have different characteristics. The contribution of each fingerprint to the total peak area and total activity is also different. There are significant differences between the two different fingerprint clustering results.
Assuntos
Medicamentos de Ervas Chinesas , Sequestradores de Radicais Livres/química , Peróxido de Hidrogênio/isolamento & purificação , Liriope (Planta)/química , Extratos Vegetais/química , Cromatografia Líquida de Alta Pressão , Compostos Fitoquímicos/química , Raízes de Plantas/químicaRESUMO
Hepatitis E virus (HEV) is the causative agent of hepatitis E in humans worldwide. Although hepatitis E is self-limiting without chronic infection development, HEV infection often leads to severe liver diseases causing high mortality in pregnant women in addition to chronic hepatitis and cirrhosis in immunosuppressed patients. In this study, we investigated the effect of a Liriope platyphylla ethanol extract (LPE) on HEV replication. Interestingly, LPE suppressed replication of the genotype 3 HEV replicon. Sequential solvent fractionation revealed that the ethyl acetate (EA) fraction of LPE exerts the most potent inhibitory effects. With the aid of activity-guided fractionation and multi-step column chromatography, spicatoside A was subsequently isolated in the EA fraction of LPE and specifically shown to exert inhibitory effects on replication of the genotype 3 HEV replicon. In addition, spicatoside A interfered with replication of the HEV genotype 3 strain 47832c and expression of HEV ORF2 capsid proteins. Our findings clearly support the potential utility of spicatoside A as an effective anti-HEV agent.
Assuntos
Etanol/química , Vírus da Hepatite E/efeitos dos fármacos , Liriope (Planta)/química , Extratos Vegetais/química , Saponinas/química , Saponinas/farmacologia , Células A549 , Animais , Antivirais/química , Antivirais/farmacologia , Linhagem Celular Tumoral , Genótipo , Vírus da Hepatite E/patogenicidade , Humanos , Extratos Vegetais/farmacologia , Replicação Viral/efeitos dos fármacosRESUMO
Constipation is an acute or chronic illness attributed to various causes, ranging from lifestyle habits to side effects of a disease. To improve the laxative effects of some traditional medicines, herbal mixtures of Liriope platyphylla, Glycyrrhiza uralensis, and Cinnamomum cassia (LGC) were evaluated for their mechanism of action and therapeutic effects in loperamide (Lop)-induced constipated Sprague Dawley rats by examining alterations in excretion parameters, histological structure, mucin secretion, and related protein levels. Food intake and water consumption were constant for all animals. We observed that the Lop+LGC-treated group had significantly greater excretion of stool and urine than was observed in the Lop+Vehicle-treated group. Administration of LGC in the constipation model restored the intestinal transit ratio to normal levels, and increased the number of goblet cells, mucosal layer, and muscle thickness. Mucin secretion was greater in the Lop+LGC-treated group than in the Lop+Vehicle-treated group, and the expression of MUC2 and AQP8 genes were also increased. In addition, reverse transcription polymerase chain reaction and Western blot revealed an increase in the muscarinic acetylcholine receptors (mAChRs) in the Lop+LGC-treated group compared to the Lop+Vehicle-treated group. Furthermore, compared with the Lop+Vehicle-treated group, treatment with LGC reduced the phosphorylation of PKC and PI3K, and expression of Gα protein, but increased levels of IP3. Our results suggest that the traditional herbal mixture of LGC induces a potent laxative effect in Lop-induced constipation through mucosal tissue changes and mucin production. We also demonstrated that the laxative effect of LGC is closely related to the expression of mAChR and its downstream signals, suggesting the possibility of developing a constipation-laxative agent using LGC.
Assuntos
Cinnamomum aromaticum/química , Constipação Intestinal/tratamento farmacológico , Glycyrrhiza uralensis/química , Laxantes/administração & dosagem , Liriope (Planta)/química , Extratos Vegetais/administração & dosagem , Animais , Aquaporinas/genética , Aquaporinas/metabolismo , Constipação Intestinal/induzido quimicamente , Constipação Intestinal/genética , Constipação Intestinal/metabolismo , Sinergismo Farmacológico , Loperamida/efeitos adversos , Masculino , Mucina-2/genética , Mucina-2/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Emerging hallmark of cancer is reprogrammed cellular metabolism, increased glycolytic metabolism is physiological characteristic of human malignant neoplasms. Saponin monomer 13 of the dwarf lilyturf tuber (DT-13) is the main steroidal saponin from Liriopes Radix, which has been reported to exert anti-inflammation and anti-tumor activities but low toxicity to normal tissue. However, the effect of DT-13 on metabolism process is still unclear. PURPOSE: This study aims to characterize the role of DT-13 in glucose metabolism in colorectal cancer cells, and investigate whether the metabolism process is involved in the anti-cancer response of DT-13. METHODS: Colony formation assay was employed to determine anti-proliferative effect induced by DT-13 at 2.5, 5, 10 µM. Apoptosis and cell cycle arrest were detected by Annexin V/PI staining and PI staining, respectively. Genetic inhibition of glycolytic metabolism was carried out by knockdown of GLUT1. Orthotopic implantation mouse model of colorectal cancer was used to assess in vivo antitumor effect of DT-13 (0.625, 1.25, 2.5 mg/kg). The chemoprevention effect of DT-13 (10mg/kg) was evaluated by using C57BL/6J APCmin mice model. Glycolytic-related key enzymes and AMPK pathway were detected by using quantitative real-time PCR, western blotting, and immunohistochemical staining. RESULTS: Our results showed that cell proliferation was significantly inhibited by DT-13 in a dose-dependent manner. DT-13 inhibited glucose uptake, ATP generation, and reduced lactate production. Furthermore, DT-13 remarkably inhibited GLUT1 expression in both mRNA and protein levels. Knocking down of GLUT1 led to reduced inhibition of glucose uptake after DT-13 treatment. Moreover, deletion of GLUT1 decreased inhibitory ratio of DT-13 on cancer growth. Orthotopic implantation mouse model of colorectal cancer further confirmed that DT-13 inhibited colorectal cancer growth via blocking GLUT1 in vivo. In addition, C57BL/6J APCmin mice model revealed that DT-13 dramatically reduced the total number of spontaneous adenomas in intestinal, which further confirmed the anti-tumor activity of DT-13 in colorectal cancer. Furthermore, the mechanistically investigation showed DT-13 activated AMPK and inhibited m-TOR to block cancer growth in vitro. CONCLUSION: DT-13 is a potent anticancer agent for colorectal cancer.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Saponinas/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Feminino , Transportador de Glucose Tipo 1/antagonistas & inibidores , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Glicólise , Humanos , Liriope (Planta)/química , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Red Liriope platyphylla extract (EtRLP) has been used as an oriental medicine for treatment of several chronic conditions, such as neurodegenerative disorders, diabetes, and obesity. To investigate the laxative activity of EtRLP, the levels of key constipation markers and their molecular regulators were examined following administration of EtRLP in constipation Sprague Dawley (SD) rats treated with loperamide (Lop). Compared with the Lop+Vehicletreated group, the excretion levels of urine and stool were significantly enhanced in the Lop+EtRLPtreated group, even though feeding levels were kept constant. There was a significant improvement in histological structure, cytological ultrastructure and mucin secretion in transverse colon sections from the Lop+EtRLPtreated group, compared with the Lop+Vehicletreated group. The Lop+EtRLPtreated group exhibited a rapid recovery of the muscarinic acetylcholine receptor (mAChR) signaling pathway and of the endoplasmic reticulum (ER) stress response, compared with Lop+Vehicletreated group. Spicatoside A, one of the key components detected in EtRLP, recovered the levels of inositol triphosphate (IP3) and Gα in primary rat intestinal smooth muscle cells (pRISMCs). Taken together, the present results indicated that spicatoside Acontaining EtRLP had therapeutic effects against Lopinduced constipation in SD rats via improvement of the mAChR downstream signaling pathway and the ER stress response.
Assuntos
Constipação Intestinal/tratamento farmacológico , Constipação Intestinal/patologia , Estresse do Retículo Endoplasmático , Laxantes/uso terapêutico , Liriope (Planta)/química , Receptores Muscarínicos/metabolismo , Saponinas/uso terapêutico , Transdução de Sinais , Animais , Colo/efeitos dos fármacos , Colo/patologia , Colo/ultraestrutura , Defecação/efeitos dos fármacos , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Flavonoides/análise , Laxantes/farmacologia , Masculino , Modelos Biológicos , Fenóis/análise , Ratos Sprague-Dawley , Saponinas/química , Saponinas/farmacologiaRESUMO
An analytical method based on UFLC-QTRAP-MS/MS was established for simultaneous determination of thirty-three components including steroidal saponins, homoisoflavonoids, amino acids and nucleosides in Ophiopogonis Radix. Thirty-three target components of commercial medicinal materials of Maidong were comparative analysis. Synergi™ Hydro-RP 100î¦ column (2.0 mm × 100 mm, 2.5 µm) was used with 0.1% formic acid solution-0.1% formic acid acetonitrile for gradient elution at a flow rate of 0.4 mL·min⻹. In addition, multiple reaction monitoring (MRM) mode was employed. The data were comprehensively processed and analyzed with hierarchical clustering analysis(HCA), principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA) methods. All components showed good linearity(r>0.999 0) within the tested ranges. The average recoveries were between 96.23%-102.0%, and the relative standard deviation(RSD) were less than 5%. The results showed that there were significant differences in components between Ophiopogonis Radix and Liriopes Radix, with seven components obviously different. This method was useful for providing basis for the comprehensive evaluation and intrinsic quality control of Ophiopogonis Radix and Liriopes Radix , and may provide a new method reference for the identification of Ophiopogonis Radix and Liriopes Radix.
Assuntos
Medicamentos de Ervas Chinesas/análise , Liriope (Planta)/química , Ophiopogon/química , Saponinas/análise , Cromatografia Líquida de Alta Pressão , Compostos Fitoquímicos/análise , Raízes de Plantas/química , Espectrometria de Massas em TandemRESUMO
O. japonicus and L. spicata var. prolifera are distinguished as sources of highly promising yin-tonifying medicinals, namely Ophiopogonis Radix and Liriopes Radix. Liriopes Radix is generally medicinally used as a substitute for Ophiopogonis Radix in various prescriptions due to their extremely similar nature. Ophiopogonis Radix and Liriopes Radix are both very rich in bioactive polysaccharides, especially ßfructans. Over the past twelve years, except for work on physical entrapment and chemical modification of obtained ßfructans, the vast majority of studies are carried out to investigate the bioactivities of O. japonicus polysaccharides (OJP) and L. spicata var. prolifera polysaccharides (LSP), mainly including anti-diabetes, immunomodulation, anti-inflammation, antioxidation, anti-obesity, cardiovascular protection, etc. In addition, OJP and LSP are considered to have the potential to regulate intestinal flora. The main purpose of this review is to provide systematically reorganized information on structural characteristics and bioactivities of OJP and LSP to support their further therapeutic potentials and sanitarian functions.
Assuntos
Liriope (Planta)/química , Ophiopogon/química , Polissacarídeos/uso terapêutico , Animais , Humanos , Polissacarídeos/químicaRESUMO
Structures and in vitro hypoglycemic activities of polysaccharides from different species of Maidong were studied. The primary structures of polysaccharides were elucidated on the basis of GC, GC-MS, infrared, NMR and periodate oxidation-Smith degradation. Liriope spicata polysaccharide (LSP), Ophiopogon japonicus polysaccharide (OJP) and Liriope muscari polysaccharide (LMP) were composed of ß-fructose and α-glucose. The average molecular weights of LSP, OJP and LMP were 4742, 4925 and 4138Da with polydispersity indexes of 1.1, 1.2 and 1.1, respectively. The backbones of polysaccharides were formed by Fruf-(2â, â2)-Fruf-(6â, â6)-Glcp-(1â and â1, 2)-Fruf-(6â with a molar ratio of 5.0:18.2:1.0:5.3 (LSP), 6.8:15.8:1.0:5.8 (OJP), 8.3:12.3:1.0:3.9 (LMP), respectively. The RT-PCR and western blot analysis indicated that LSP, LMP and OJP increased the expression of PI3K, AKT, InsR, PPARγ and decreased the expression of PTP1B in mRNA level and protein level in IR HepG2 cells. Furthermore, glucose consumption was increased after treated with polysaccharides. These results revealed that LSP, OJP and LMP had potential anti-diabetic effects.
Assuntos
Hipoglicemiantes/farmacologia , Liriope (Planta)/química , Ophiopogon/química , Polissacarídeos/farmacologia , Células Hep G2 , HumanosRESUMO
Vinorelbine (NVB) is a semi-synthetic vinca alkaloid that is approved for the clinical therapy of lung cancer. However, the clinical application of NVB was limited because of the acquisition of resistance and inacceptable toxicity. Therefore, it is of great interest to develop low-cytotoxic drugs that can synergize with NVB. DT-13, a saponin monomer 13 of the Dwarf lilyturf tuber, showed inhibitory effects on tumor metastasis and angiogenesis in the previous studies. Here, we found that DT-13 combined with NVB exhibited synergistic effect to inhibit the cell proliferation in human lung cancer NCI-H1299 cells rather than human embryonic lung fibroblasts WI-38. The combination of DT-13 and NVB significantly inhibited the colony formation, induced cellular and nuclear morphological changes, and triggered cell cycle arrest at mitotic phase. Furthermore, MAPK signaling pathway was activated by the combination treatment, and the activation of ERK was required for the induction of mitotic arrest. Taken together, DT-13 combined with NVB exhibited synergistic anticancer effect in NCI-H1299 cells, and DT-13 may be a candidate agent for adjuvant chemotherapy of NVB in lung cancer.
Assuntos
Liriope (Planta)/química , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Mitose/efeitos dos fármacos , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Vimblastina/análogos & derivados , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo , Vimblastina/farmacologia , VinorelbinaRESUMO
The laxative effects of aqueous extract of Liriope platyphylla (AEtLP) on loperamide (Lop)induced constipation have been reported; however, the key compounds and the mechanism underlying these effects remain unclear. Therefore, the laxative effects of five candidates derived from L. platyphylla: Diosgenin (DG), 5-hydroxymethylfurfural (5-HMF), adenosine (AD), hydroxypropyl cellulose (HPC) and uridine (UD) were investigated by examining the alteration of G protein α (Gα) expression, protein kinase C (PKC) phosphorylation and inositol triphosphate (IP3) concentration levels in the 5-hydroxytryptamine (5HT; serotonin) receptor signaling pathway. Primary rat intestine smooth muscle cells (pRISMCs), intestinal epithelial cells (IEC)18 and B35 cells were cotreated with Lop and the five compounds in order to screen the candidates. AEtLP, prucalopride (PCP) and bisacodyl (BS) served as positive controls. In pRISMCs, Gα expression levels were recovered in the majority of candidatetreated groups, whereas PKC phosphorylation recovery was observed only in the DG, 5HMF and AD treatment groups. In IEC18 cells, the AD treatment group mimicked the effects of PCP on PKC phosphorylation levels, whereas the DG, 5HMF, HPC and UD treatment groups mimicked the effects of AEtLP and BS. In B35 cells, a greater upregulation of PKC phosphorylation levels were observed in the UD treatment group compared with the PCP and BS treatment groups, whereas DG, 5HMF and AD treatment reduced the PKC phosphorylation levels to a greater extent than AEtLP treatment. However, effects similar to AEtLP, PCP and BS on Gα expression levels were not detected in any treatment groups in IEC18 and B35 cells. Furthermore, the level of IP3 was enhanced only in pRISMCs, in which all five candidates were effective, while the greatest concentration was observed in the UD treatment group. In conclusion, the results of the present study suggest that UD may be considered the compound with the greatest laxative activity, which may regulate the 5HT receptor signaling pathway.
Assuntos
Colo Transverso/efeitos dos fármacos , Laxantes/química , Laxantes/farmacologia , Liriope (Planta)/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Receptores de Serotonina/metabolismo , Animais , Células Cultivadas , Colo Transverso/citologia , Colo Transverso/metabolismo , Constipação Intestinal/tratamento farmacológico , Constipação Intestinal/metabolismo , Feminino , Laxantes/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacosRESUMO
Liriope (Liliaceae) species have been used as folk medicines in Asian countries since ancient times. From Liriope plants (8 species), a total of 132 compounds (except polysaccharides) have been isolated and identified, including steroidal saponins, flavonoids, phenols, and eudesmane sesquiterpenoids. The crude extracts or monomeric compounds from this genus have been shown to exhibit anti-tumor, anti-diabetic, anti-inflammatory, and neuroprotective activities. The present review summarizes the results on phytochemical and biological studies on Liriope plants. The chemotaxonomy of this genus is also discussed.
Assuntos
Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Hipoglicemiantes/farmacologia , Liriope (Planta)/química , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Animais , Flavonoides/farmacologia , Humanos , Medicina Tradicional , Fenóis/farmacologia , Fitoterapia , Saponinas/farmacologia , Sesquiterpenos/farmacologiaRESUMO
In the present study, the anti-inflammatory and antisepticemic activities of a water extract of Liriope platyphylla (LP) were investigated. We first estimated the scavenging activity of DPPH and the hydroxyl radical and total phenolic contents of LP. Results indicated that LP, a rich source of phenolic compounds, showed a remarkable radical scavenging capacity. A MTT assay showed that LP treatment did not affect the toxicity against the RAW 264.7 macrophage cells, up to the concentration of 500[Formula: see text][Formula: see text]g/mL. Treatment of LP significantly attenuated the production of inflammatory mediators, such as nitric oxide (NO), interleukin-6 (IL-6), tumor-necrosis factor (TNF)-[Formula: see text] and prostaglandin (PG)E2 in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages cells. Moreover, LP contributed to the down-regulation of inducible NO synthase (iNOS) and TNF-[Formula: see text] mRNA expression, as well as cyclooxygenase-2 (COX-2) protein expression. A western blotting assay further showed that LP inhibited activation of mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-[Formula: see text]B. In an animal experiment using an LPS-induced septicemia model in C57BL/6 mice, oral administration of LP (40[Formula: see text]mg/kg body weight) markedly reduced the level of TNF-[Formula: see text] and IL-6 in serum and protected against LPS-induced lethal shock in mice. Taken together, the results of treatments of LP on inhibited LPS-induced inflammatory responses in both in vitro and in vivo models and indicate it may be a promising neutraceutical or medicinal agent to prevent or cure inflammation-related disease.
Assuntos
Antibacterianos , Anti-Inflamatórios , Endotoxemia/tratamento farmacológico , Lipopolissacarídeos/efeitos adversos , Liriope (Planta)/química , Macrófagos/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Administração Oral , Animais , Modelos Animais de Doenças , Endotoxemia/metabolismo , Sequestradores de Radicais Livres/análise , Sequestradores de Radicais Livres/isolamento & purificação , Mediadores da Inflamação/metabolismo , Interleucina-6/metabolismo , Macrófagos/metabolismo , Camundongos , Fenóis/análise , Fenóis/isolamento & purificação , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , Células RAW 264.7 , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Metabolic stress induces autophagy as a protective mechanism in tumorigenesis and development. Conversely, excessive autophagy in nutrient-deprived cancer cells would be beneficial for cancer therapy. DT-13, the saponin monomer 13 of the Dwarf lilyturf tuber, inhibited tumor metastasis and angiogenesis in previous studies. However, there is scarcity of data regarding the effect of DT-13 on autophagy process. Here, we demonstrated that DT-13 induced autophagy in human cancer cell lines and caused significant cell apoptosis under nutrient starvation. We firstly showed that DT-13 increased the accumulation of GFP-LC3 puncta and induced the expression of LC3-II in a dose- and time-dependent manner. DT-13 also upregulated the expression of Beclin-1, Atg-3 and Atg-7, and induced autophagic flux in human gastric cancer BGC-823 cells. We next found that low-toxic concentrations of DT-13 significantly induced apoptosis under nutrient deprivation. We finally demonstrated that the PI3K/Akt/mTOR signal pathway was involved in the cytotoxic effect of DT-13. Our data indicated that DT-13 was a novel autophagy inducer and might be considered in future treatment of cancer.
Assuntos
Autofagia/efeitos dos fármacos , Liriope (Planta)/química , Saponinas/farmacologia , Apoptose/efeitos dos fármacos , Autofagossomos/efeitos dos fármacos , Autofagossomos/metabolismo , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Humanos , Proteínas Associadas aos Microtúbulos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Saponinas/química , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Fatores de Tempo , Regulação para Cima/efeitos dos fármacos , Vacúolos/efeitos dos fármacos , Vacúolos/metabolismoRESUMO
Ophiopogon japonicus is a herbaceous perennial plant in Liliaceae, and its tubers are used in traditional Japanese medicine as Bakumondo, prescribed for treating cough, sputum, and thirst. Liriope is a genus of ornamental plants related to Ophiopogon, and its tubers are used in folk medicine as well. Although tubers from both genera are traded in Korean and Chinese markets, only O. japonicus is defined as the plant of origin for Bakumondo in the Japanese Pharmacopoeia [1], and Liriope tubers cannot legally be used as Bakumondo in Japan. Ophiopogon plants can be distinguished clearly from Liriope by their fruit color and by the morphological characteristics of their flowers. However, the tubers of both species are greatly similar, making it very difficult to differentiate the two genera by the appearance of their tubers. We, therefore, investigated the most appropriate DNA regions to use for practical and accurate identification of Ophiopogon and Liriope tubers. The sequence of the gene for the large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (rbcL) was found to be suitable for discriminating Ophiopogon and Liriope tubers. The identification procedure was simplified using restriction enzyme digestion of the amplified rbcL fragment. The detection limit for Liriope contamination was estimated by performing the procedure using mixed samples of powdered Ophiopogon and Liriope tubers.