RESUMO
BACKGROUND: Embelia ribes Burm f. (Primulaceae) is a medicinal and vulnerable woody liana distributed throughout India. Embelin, a well-recognized active phytoconstituents in berries, is commonly used in ayurvedic formulations. Due to over-exploitation, the status of the plant is vulnerable. Previous studies on this species mainly focused on its phytochemical analysis, which led to overexploitation and loss of the germplasm. METHODS AND RESULTS: In the present study, 20 RAPD and 18 ISSR markers were employed to assess genetic divergence in 40 genotypes of E. ribes collected from different parts of the Western Ghats of India. In RAPD analysis, all 40 accessions with 20 RAPD primers amplified 282 fragments, with 83.91% average polymorphism and with an average of 14.10 bands per primer. The size of amplicons varied from 200 to 2500 bp. While, ISSR primers produced 203 fragments of which 161 were polymorphic with an average of 11.28 bands per primer with 73.25% average polymorphism. The size of amplicons ranges from 200 to 2500 bp. RAPD and ISSR markers were also assessed by calculating polymorphic information content (PIC) to discriminate the genotypes; the average PIC value for RAPD, ISSR, and combined RAPD + ISSR markers obtained was more than 0.50 suggesting the informativeness of markers. UPGMA analysis based on Jaccard's similarity coefficient for RAPD, ISSR, and RAPD + ISSR data reveals that 40 accessions of E. ribes were depicted in four clusters. The clustering pattern of all individuals in PCoA analysis agreed with the UPGMA dendrograms, which further confirms the genetic relationships explained by cluster analysis. AMOVA analysis of RAPD, ISSR, and combined marker system revealed variation within the population, ranging from 41 to 44%, and among the population, it ranged from 56 to 59%. CONCLUSION: The present study provides an optimized method for evaluating the genetic diversity of Embelia ribes using RAPD and ISSR markers which are useful for further sustainable utilization and conservation of natural populations in the Western Ghats of India.
Assuntos
DNA de Plantas , Embelia , Técnica de Amplificação ao Acaso de DNA Polimórfico , Humanos , DNA , Embelia/genética , Embelia/metabolismo , Marcadores Genéticos/genética , Variação Genética/genética , Índia , Repetições de Microssatélites/genética , Filogenia , Polimorfismo Genético/genética , Técnica de Amplificação ao Acaso de DNA Polimórfico/métodos , DNA de Plantas/genéticaRESUMO
Chronic diseases are a serious health concern worldwide, especially in the elderly population. Most chronic diseases like cancer, cardiovascular ailments, neurodegenerative disorders, and autoimmune diseases are caused due to the abnormal functioning of multiple signaling pathways that give rise to critical anomalies in the body. Although a lot of advanced therapies are available, these have failed to entirely cure the disease due to their less efficacy. Apart from this, they have been shown to manifest disturbing side effects which hamper the patient's quality of life to the extreme. Since the last few decades, extensive studies have been done on natural herbs due to their excellent medicinal benefits. Components present in natural herbs target multiple signaling pathways involved in diseases and therefore hold high potential in the prevention and treatment of various chronic diseases. Embelin, a benzoquinone, is one such agent isolated from Embelia ribes, which has shown excellent biological activities toward several chronic ailments by upregulating a number of antioxidant enzymes (e.g., SOD, CAT, GSH, etc.), inhibiting anti-apoptotic genes (e.g., TRAIL, XIAP, survivin, etc.), modulating transcription factors (e.g., NF-κB, STAT3, etc.) blocking inflammatory biomarkers (e.g., NO, IL-1ß, IL-6, TNF-α, etc.), monitoring cell cycle synchronizing genes (e.g., p53, cyclins, CDKs, etc.), and so forth. Several preclinical studies have confirmed its excellent therapeutic activities against malicious diseases like cancer, obesity, heart diseases, Alzheimer's, and so forth. This review presents an overview of embelin, its therapeutic prospective, and the molecular targets in different chronic diseases.
Assuntos
Benzoquinonas/uso terapêutico , Embelia/química , Cardiopatias/tratamento farmacológico , Neoplasias/tratamento farmacológico , Obesidade/tratamento farmacológico , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/antagonistas & inibidores , Benzoquinonas/química , Doença Crônica , Cardiopatias/metabolismo , Humanos , Neoplasias/metabolismo , Obesidade/metabolismo , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The root of Embelia laeta (L.) Mez., which is called Suanjifeng in Chinese ethnic Yao medicine, is traditionally for inflammation-related diseases, such as oral ulcer, sore throat, enteritis, and rheumatoid arthritis. However, the biological properties and the underlying mechanisms of Embelia laeta still need further studies. AIM OF THIS STUDY: The present study aims to investigate the anti-inflammatory effect and its underlying mechanisms of Embelia laeta. MATERIALS AND METHODS: In this study, except acute toxicity experiments, Kunming (KM) mice of either sex were enrolled to establish inflammatory model induced by xylene, acetic acid and carrageenan, respectively. Mice were randomly divided into different groups and pretreated by oral gavage with different doses of Embelia laeta aqueous extract (ELAE) (2.5, 5, 10 g/kg) and 10 mg/kg of Indo for 7 days. Ear edema, vascular permeability, abdominal writhing, and paw edema degree were detected in related experiments. Moreover, in the carrageenan-induced paw edema mice model, histological changes were detected by H&E staining. MDA, MPO and NO were detected by assay kit. Proinflammatory cytokines of IFN-γ, TNF-α, IL-1ß, IL-6 and PGE2 were detected by ELISA. Additionally, COX-2, iNOS and NF-κB pathway-related proteins were detected by Western blotting. RESULTS: Results showed that the ELAE evoked an obvious dose-dependent inhibition of ear edema induced by xylene, paw edema induced by carrageenan, as well as suppressing the increase of vascular permeability and writhing times elicited by acetic acid. Histopathological analysis indicated that ELAE could significantly decrease the cellular infiltration in paw tissue. ELAE showed antioxidant property through markedly decrease the MDA level and MPO activity in edema paw. In addition, ELAE decreased the proinflammatory cytokines IFN-γ, TNF-α, IL-1ß, IL-6, PGE2 and NO that induced by carrageenan. Western blotting results also showed that ELAE could obviously downregulate the COX-2 and iNOS expression. Further analysis revealed that ELAE also inhibited NF-κB from the cytoplasm to the nucleus and stabilize the conversion of IκBα. CONCLUSION: ELAE had powerful anti-inflammatory property, which might be had a close relationship with mediating proinflammatory cytokines production, decreasing the COX-2 and iNOS expression, and inhibiting the activation of NF-κB signaling pathway.
Assuntos
Ciclo-Oxigenase 2/metabolismo , Embelia/química , Inflamação/tratamento farmacológico , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Carragenina/toxicidade , Ciclo-Oxigenase 2/genética , Citocinas/genética , Citocinas/metabolismo , Edema/induzido quimicamente , Edema/tratamento farmacológico , Feminino , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos/genética , Fator Estimulador de Colônias de Granulócitos/metabolismo , Inflamação/metabolismo , Interleucina-3/genética , Interleucina-3/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , NF-kappa B/genética , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Fitoterapia , Extratos Vegetais/química , Raízes de Plantas/química , Distribuição Aleatória , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Testes de Toxicidade , Xilenos/toxicidadeRESUMO
Three new flavonoid glycosides, embeliaflavosides A-C (1-3), together with eight known flavonoid glycosides (4-11), were isolated from the fruits of Embelia ribes. Their structures were established based on the analyses of spectroscopic data. Compounds 1-11 were evaluated for antioxidant and α-glucosidase inhibitory activities. The results revealed that compounds 1-11 owned significant ABTS radical scavenging activity with IC50 values of 2.52-9.78 µM, and DPPH scavenging activity with IC50 values of 7.56-26.47 µM, respectively. However, α-glucosidase inhibition assay indicated that all the isolates were inactive.[Formula: see text].
Assuntos
Embelia , Ribes , Antioxidantes/farmacologia , Embelia/metabolismo , Flavonoides/farmacologia , Frutas , Inibidores de Glicosídeo Hidrolases/farmacologia , Glicosídeos/farmacologia , Estrutura Molecular , Extratos Vegetais , Ribes/metabolismo , alfa-Glucosidases/metabolismoRESUMO
This study for the first time illustrates a comprehensive picture of the phenolic composition of Embelia adnata and Embelia gardneriana by high-performance liquid chromatography coupled with mass spectrometry analysis with ESI in negative ionisation. The analysis was performed in the methanolic extracts of different parts of these two species separately and identifies 54 individual phenolic compounds present in them. Among this by individual 36 and 28 compounds were recorded from E. adnata and E. gardneriana, respectively, and in this, 10 compounds were common in both the two species. The detected compounds come under the classes flavonoids, flavonoid glycosides, isoflavonoids, benzenoids, coumarins, stilbens, chalcones, polyphenols, gallic acid derivatives, tannins and different derivatives of various organic acids.
Assuntos
Embelia , Flavonoides/química , Polifenóis/química , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Flavonoides/análise , Extratos Vegetais , Polifenóis/análise , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Trimada is well-known polyherbal Ayurvedic formulation used in Indian Traditional medicine since ancient times. It consisted of three inebriant herbs including "Chitraka" (Plumbago zeylanica Linn. Family- Plumabaginaceae), "Musta" (Cyperus rotundus Linn. Family- Cyperaceae) and Vidanga (Embelia ribes Burm. F. Family- Myrsinaceae) in equal ratios as mentioned in Ayurveda. Trimada is traditionally used to increase the functioning of the digestive system and metabolism. Along with these, it also assists in the reduction of cholesterol as well as reduces stomach aches and chest pain. AIM OF THE STUDY: This study is aimed to identify the metabolites present in this polyherbal formulation. Further, the cytotoxicity and interaction potential of the formulation and individual herbs with Cytochrome P450 isozymes (CYP3A4, 2D6, 2C9, 1A2) was evaluated by MTT assay and CYP450 enzyme inhibition. The concentration of heavy metals was also determined. MATERIAL AND METHODS: Ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-QTOF-MS) analysis was performed to detect and identify the phytoconstituents in the formulation. Cytotoxicity of the formulation was evaluated by MTT assay. CYP450 enzyme interaction potential of the individual herbs and the Trimada formulation was carried out through CYP-CO assay and fluorometric high throughput screening (HTS) assay for individual isozymes. The content of heavy metal in the formulation was quantified by Atomic Absorption Spectroscopy. RESULTS: Trimada formulation exhibited lower cytotoxicity to human liver carcinoma cell line (HepG2). CYP-CO assay revealed that the interaction potential of individual herbs and Trimada on the liver microsomes was found to be lesser than the standard inhibitor ketoconazole. Individual herbs and Trimada formulation displayed higher IC50 values than the respective standard inhibitors in the fluorimetric assay. UPLC-QTOF-MS analysis showed the presence of a number of active phytoconstituents including sesquiterpenes, phenolic acids, benzoquinones, triterpenes and flavonoids. The heavy metal concentration in the traditional medicinal herbal formulation was found within the approved limit. CONCLUSIONS: This study suggested that the individual herbs and Trimada formulation exhibited low cytotoxicity and contributes insignificant interaction with CYP450 isozymes. So, the formulation is considered to be safe for its therapeutic management without any potential drug interaction involving CYP 450 isozymes.
Assuntos
Sistema Enzimático do Citocromo P-450/efeitos dos fármacos , Ayurveda , Microssomos Hepáticos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Cromatografia Líquida de Alta Pressão , Cyperus/química , Sistema Enzimático do Citocromo P-450/metabolismo , Embelia/química , Células Hep G2 , Ensaios de Triagem em Larga Escala , Humanos , Concentração Inibidora 50 , Isoenzimas , Metais Pesados/análise , Metais Pesados/química , Metais Pesados/isolamento & purificação , Microssomos Hepáticos/metabolismo , Extratos Vegetais/química , Extratos Vegetais/metabolismo , Plumbaginaceae/químicaRESUMO
A phytochemical study of the methanol extract of the leaves of Embelia schimperi resulted in the isolation of three new alkenylresorcinols, 1: â-â3: , together with the known analogs 4: â-â7: . Their structures were established by a combination of spectroscopic techniques. Compounds 1: â-â7: exhibited moderate cytotoxic activity against human cervical cancer cells HeLa-S3 and more pronounced antimicrobial properties towards bacteria and filamentous fungi. The present study falls into an ongoing research project on the characterization of bioactive phenolic lipids from plants of the family Primulaceae.
Assuntos
Anti-Infecciosos , Embelia , Anti-Infecciosos/farmacologia , Humanos , Compostos Fitoquímicos , Extratos Vegetais/farmacologia , Folhas de PlantaRESUMO
Embelin is a naturally occurring para-benzoquinone isolated from Embelia ribes (Burm. f.) of the Myrsinaceae family. It was first discovered to have potent inhibitory activity (IC50 = 4.2 µM) against α-glucosidase in this study. Then, four series of novel embelin derivatives were designed, prepared and evaluated in α-glucosidase inhibition assays. The results show that most of the embelin derivatives synthesised are effective α-glucosidase inhibitors, with IC50 values at the micromolar level, especially 10d, 12d, and 15d, the IC50 values of which are 1.8, 3.3, and 3.6 µM, respectively. Structure-activity relationship (SAR) studies suggest that hydroxyl groups in the 2/5-position of para-benzoquinone are very important, and long-chain substituents in the 3-position are highly preferred. Moreover, the inhibition mechanism and kinetics studies reveal that all of 10d, 12d, 15d, and embelin are reversible and mixed-type inhibitors. Furthermore, docking experiments were carried out to study the interactions between 10d and 15d with α-glucosidase.
Assuntos
Benzoquinonas/farmacologia , Desenho de Fármacos , Inibidores de Glicosídeo Hidrolases/farmacologia , alfa-Glucosidases/metabolismo , Benzoquinonas/síntese química , Benzoquinonas/química , Relação Dose-Resposta a Droga , Embelia/química , Inibidores de Glicosídeo Hidrolases/síntese química , Inibidores de Glicosídeo Hidrolases/química , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Embelia ribes is a traditional Chinese medicine compound used as a remedy for various diseases. Nevertheless, detailed information regarding its chemical composition is unavailable. Herein, ultra-high-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry was used to characterize the components of E. ribes. A total of 56 compounds, including 16 phenolics, 16 flavonoids, 4 coumarins, 5 fatty acids and 15 other compounds were identified. Furthermore, the total phenolic and total flavonoid content was also assessed; the acetic ether extract of E. ribes was an ideal source of phenolics (308.16 ± 0.00 mg gallic acid equivalents/g of extract) and flavonoids (62.00 ± 0.01 mg rutin equivalents/g of extract). Additionally, acetic ether extract exhibited a high antioxidation effect (ferric reducing activity power: 0.15 ± 0.01 mg/mL; 1,1-diphenyl-2-picrylhydrazyl: 0.18 ± 0.01 mg/mL; 2,2-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid: 0.06 ± 0.01 mg/mL). Further, the nitric oxide concentration in lipopolysaccharide-simulated macrophage RAW 264.7 cells and the pro-inflammatory cytokines (TNF-α and IL-6) were suppressed by acetic ether extract. These findings support the notion that E. ribes is an ideal antioxidant and anti-inflammatory agent.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/farmacologia , Cromatografia Líquida de Alta Pressão/métodos , Embelia/química , Espectrometria de Massas em Tandem/métodos , Animais , Anti-Inflamatórios não Esteroides/química , Antioxidantes/química , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Medicamentos de Ervas Chinesas/química , Flavonoides/análise , Recuperação de Fluorescência Após Fotodegradação , Lipopolissacarídeos/farmacologia , Camundongos , Óxido Nítrico/metabolismo , Fenóis/análise , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Células RAW 264.7RESUMO
Beta-secreatse (BACE-1) and cholinesterases are clinically validated targets of Alzheimer's disease (AD), for which natural products have provided immense contribution. The multifaceted nature of AD signifies the need of multitargeted agents to tackle this disease. In the search of new natural products as dual BACE-1/cholinesterase inhibitors, a library of pure natural products was screened for inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and BACE-1. The screening efforts have identified 1,4-benzoquinone "embelin," a natural product derived from Embelia ribes displaying inhibition of all three enzymes, with IC50 values of 2.5, 5.4, and 2.1 µM, respectively. This screen has also identified isoquinoline alkaloids papaverine and L-tetrahydropalmatine as AChE inhibitors. Kinetic study has shown that embelin inhibits EeAChE and EqBChE with ki values of 4.59 and 0.57 µM, in an uncompetitive and noncompetitive manner, respectively. The interactions of embelin with allosteric peripheral anionic site of cholinesterases, has further supported the results of kinetic study. Embelin has also enhanced the activity of P-gp in LS-180 cells, the efflux pump which is involved in the clearance of amyloid-ß from AD brain. Further, the cell viability study in neuronal cell line has indicated the excellent therapeutic window of embelin. These results are indicative of the fact that embelin is a multitargeted agent playing role in stopping the formation of amyloid-ß oligomers (via inhibition of BACE-1), improves cholinergic-transmission (via inhibition of AChE/BChE) and increases amyloid-ß clearance (via P-gp induction).
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/química , Acetilcolinesterase/química , Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/química , Ácido Aspártico Endopeptidases/química , Benzoquinonas/farmacologia , Butirilcolinesterase/química , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Doença de Alzheimer/tratamento farmacológico , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Ácido Aspártico Endopeptidases/antagonistas & inibidores , Benzoquinonas/química , Butirilcolinesterase/metabolismo , Linhagem Celular , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Embelia/química , Proteínas Ligadas por GPI/antagonistas & inibidores , Proteínas Ligadas por GPI/química , Humanos , Modelos Moleculares , Simulação de Acoplamento Molecular , Estrutura MolecularRESUMO
A new alkylbenzoquinone named embeliquinone (1) together with five known compounds, lupeol (2), 3-O-[6'-O-palmitoyl-ß-d-glucosyl]-spinasta-7,22(23)-diene (3), quercetin (4), (2S,3S,4R,8E)-2-[(2'R)-2'-hydroxy-heneicosanoylamino]-heneicosane-1,3,4-triol-8-ene (5), and ß-sitosterol-3-O-ß-d-glucopyranoside (6) were isolated from the MeOH leaf extract of Embelia rowlandii by using repeated open column chromatography techniques. The structure of the new compound was characterized by analyses of 1D- and 2D-NMR, and MS data. Embeliquinone (1) had moderate anti-cell proliferation activity against A549 cell line with the IC50 value of 21.8 µM. In addition, 1 exhibited weak antibacterial activities against Klebsiella pneumoniae and Staphylococcus aureus with an MIC value of 206.0 µM in both cases.
Assuntos
Antibacterianos/farmacologia , Benzoquinonas/farmacologia , Embelia/química , Células A549 , Antibacterianos/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Benzoquinonas/química , Proliferação de Células/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Células MCF-7 , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Estrutura Molecular , Extratos Vegetais/química , Folhas de Planta/química , Staphylococcus aureus/efeitos dos fármacosRESUMO
BACKGROUND: Embelin is an active compound identified as a novel X-linked inhibitor of apoptosis protein (XIAP) inhibitor from the Embelia ribes that exhibits various medicinal effects including anti-inflammatory and anticancer activities. However, the therapeutic effect of Embelin to human osteosarcoma is not yet determined. OBJECTIVES: In this study, we evaluated the sensitizing potential of Embelin on promoting apoptosis to cause osteosarcoma cell death and inhibiting its invasion. METHODS: We uesd 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide to detect the survival rates of osteosarcoma cells, Western blot to detect the expression of proteins in U-2 OS and MG63 cells, and fluorescence microscope to observe the morphology of apoptotic cells. RESULTS: The survival of osteosarcoma cells decreased, When Embelin was used. Obvious condensed and flared fluorescence was observed, when used high-dose Embelin. There was an increase of caspase-3, cleaved caspase-3, caspase-8, and caspase-9 in Embelin group, while PI3K, AKt, p-AKt, X-linked inhibitor of apoptosis protein, and MMP-9 were downregulated. The invasion of Embelin application was significantly lower than that of the control application. CONCLUSION: Embelin promoted apoptosis via XIAP and PI3K/Akt signaling pathway. XIAP inhibitor Embelin inducing apoptosis could cause osteosarcoma cell death and inhibit its invasion.
Assuntos
Apoptose/efeitos dos fármacos , Benzoquinonas/farmacologia , Osteossarcoma/tratamento farmacológico , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética , Benzoquinonas/química , Proliferação de Células/efeitos dos fármacos , Embelia/química , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Osteossarcoma/genética , Osteossarcoma/patologia , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/antagonistas & inibidoresRESUMO
Nine new alkylresorcinols, designated as embelialkylresorcinols A-I (1-9), along with five known compounds (10-14) were isolated from the fruits of Embelia ribes. Their structures were elucidated by extensive spectroscopic analysis (1D, 2D NMR and HRESIMS), optical rotation data and modified Mosher method. Notably, embelialkylresorcinols A-H (1-8), possessing double aromatic rings linked with an aliphatic chain, are reported from the genus of Embelia (Myrsinaceae) for the first time. Most of the isolated compounds were evaluated for cytotoxic activity, and the results indicated that compounds 3, 5, 6 and 8 displayed moderate cytotoxicity against three human cancer cell lines (Hep3B, A549 and HCC1806) with IC50 values ranging from 23.06 to 41.49⯵M.
Assuntos
Embelia/química , Frutas/química , Resorcinóis/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Humanos , Estrutura Molecular , Resorcinóis/farmacologiaRESUMO
Viral respiratory infections are raising serious concern globally. Asian medicinal plants could be useful in improving the current treatment strategies for influenza. The present study examines the activity of five plants from Bangladesh against influenza virus. MDCK cells infected with influenza virus A/Puerto Rico/8/34 (H1N1) were treated with increasing concentrations of ethyl acetate extracts, and their cytotoxicity (CC50), virus-inhibiting activity (IC50), and selectivity index (SI) were calculated. The ethyl acetate extract of fruits of Embelia ribes Burm. f. (Myrsinaceae) had the highest antiviral activity, with an IC50 of 0.2 µg/mL and a SI of 32. Its major constituent, embelin, was further isolated and tested against the same virus. Embelin demonstrated antiviral activity, with an IC50 of 0.3 µM and an SI of 10. Time-of-addition experiments revealed that embelin was most effective when added at early stages of the viral life cycle (0-1 h postinfection). Embelin was further evaluated against a panel of influenza viruses including influenza A and B viruses that were susceptible or resistant to rimantadine and oseltamivir. Among the viruses tested, avian influenza virus A/mallard/Pennsylvania/10218/84 (H5N2) was the most susceptible to embelin (SI = 31), while A/Aichi/2/68 (H3N2) virus was the most resistant (SI = 5). In silico molecular docking showed that the binding site for embelin is located in the receptor-binding domain of the viral hemagglutinin. The results of this study provide evidence that E. ribes can be used for development of a novel alternative anti-influenza plant-based agent.
Assuntos
Antivirais/farmacologia , Embelia/química , Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza B/efeitos dos fármacos , Influenza Humana/virologia , Extratos Vegetais/farmacologia , Antivirais/química , Benzoquinonas/química , Benzoquinonas/farmacologia , Humanos , Vírus da Influenza A/fisiologia , Vírus da Influenza B/fisiologia , Extratos Vegetais/químicaRESUMO
Natural products have been gaining recognition and are becoming a significant part of research in the area of drug development and discovery. Phytochemicals derived from these sources have been comprehensively studied and have displayed a wide range of activities against many fatal diseases including cancer. One such product that has gained recognition from its pharmacological properties and nontoxic nature is embelin, obtained from Embelia ribes. Amid all the vivid pharmacological activities, embelin has gained its prominence in the area of cancer research. Embelin binds to the BIR3 domain of XIAP, preventing the association of XIAP and caspase-9 resulting in the suppression of cell growth, proliferation and migration of various types of cancer cells. Furthermore, embelin modulates anti-apoptotic pathways by suppressing the activity of NF-κB, PI3-kinase/AKT, JAK/STAT pathway - among others. The present review summarizes the various reported effects of embelin on different types of cancer cells and highlights the cellular mechanisms of action.
Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Benzoquinonas/química , Benzoquinonas/farmacologia , Embelia/química , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Benzoquinonas/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Transdução de Sinais/efeitos dos fármacosRESUMO
The genus Malassezia comprises of extremely lipophilic yeasts secreting lipases as a vital factor for survival. They are emerging as opportunistic pathogens in medical microbiology and dermatology by causing recurring and recalcitrant infection. Combinatorial therapy is a constructive way to combat infectious diseases. In that prospect, totally 16 Indian medicinal plants were screened, among which a maximum degree of antimicrobial activity was ascertained in Embelia ribes. Subsequently embelin was identified as the bioactive principle with antagonistic potential by comparative antimicrobial assay and FTIR analysis. The MIC of embelin was determined as 400 µg/ml exhibiting â¼75% of growth inhibition. Further, a fungistatic activity based on anti-lipase potential (65-89%) of embelin has been clearly substantiated by XTT and lipase assay. In addition, embelin exhibited a synergistic effect with the antifungal drug ketoconazole (KTZ) against four different Malassezia spp. with FIC index of 0.5. Therefore, the combinations of embelin and KTZ may represent a promising therapeutic regimen to treat Malassezia infections with subjugated clinical and environmental toxicity. To the best of our knowledge, this is the first report delineating the anti-lipase activity of embelin and in vitro synergistic interaction between embelin and KTZ against Malassezia spp.
Assuntos
Antifúngicos/farmacologia , Benzoquinonas/farmacologia , Cetoconazol/farmacologia , Malassezia/efeitos dos fármacos , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Benzoquinonas/química , Benzoquinonas/isolamento & purificação , Combinação de Medicamentos , Sinergismo Farmacológico , Embelia/química , Humanos , Índia , Lipase/efeitos dos fármacos , Malassezia/crescimento & desenvolvimento , Malassezia/patogenicidade , Testes de Sensibilidade Microbiana , Triazóis/farmacologiaRESUMO
Embelin (2,5-dihydroxy-3-undecyl-p-benzoquinone) is known for its potent anthelmintic activity, but also for wound-healing, antidiabetic, anticonvulsant, antitumour, anti-inflammatory, analgesic, hepatoprotective, antioxidant, antibacterial and antispermatogenic activities. A high-performance countercurrent chromatography method was developed for the purification of embelin from an extract of the seeds of Embelia schimperi fruit. The optimized solvent system (n-hexane-ethylacetate-ethanol-water, 7:3:7:3) resulted in the isolation of 13.9 mg of embelin, directly from 100 mg of crude extract, in a single step within a short time (40 min). Although the compound appeared to be completely pure when analysed by ultra-performance liquid chromatography (UPLC) with photo diode array detection, the purity was established as ~90% by UPLC-mass spectrometry. Furthermore, we report the fatty acid composition of the seeds of E. schimperi fruit. Nine fatty acids were quantified from the fruit seed extract by gas chromatography-mass spectrometry, with linoleic (46.4%), palmitic (21.5%) and oleic (19.6%) acids making up the largest proportions.
Assuntos
Benzoquinonas/isolamento & purificação , Distribuição Contracorrente/métodos , Embelia/química , Ácidos Graxos/análise , Extratos Vegetais/química , Sementes/química , Benzoquinonas/análise , Benzoquinonas/química , Cromatografia Líquida de Alta Pressão , Cromatografia Gasosa-Espectrometria de MassasRESUMO
BACKGROUND: Embelia ribes is claimed in Indian traditional medical practice to be useful in the treatment of nervous diseases. Embelin, an alkyl substituted hydroxy benzoquinone, is a major active constituent of E. ribes. The present preliminary study was intended to evaluate antipsychotic activity of embelin against apomorphine-induced climbing behaviour in mice and stereotyped behaviour in rats. METHODS: Two doses of embelin (5 and 10mg/kg) were administered once daily for 15days before exposure to apomorphine. On the concluding day of pre-treatment, after apomorphine-injection, the rodents were assessed for climbing and stereotyped behaviours according to the published scoring system. Thereafter, neurotransmitters (dopamine, noradrenaline and serotonin) levels were estimated in rodent brains. RESULTS: Embelin pre-treatment significantly inhibited apomorphine-induced climbing and stereotyped behaviours in mice and rats, respectively. Further, embelin also statistically reversed elevated levels of dopamine, noradrenaline and serotonin neurotransmitters in the brain of mice and rats. Embelin showed more significant results at high dose (10mg/kg) than low dose (5mg/kg) in both the tested models. CONCLUSION: Considering the present pharmacological profile of embelin, it is suggested that embelin possesses antipsychotic activity in the treatment of psychotic disorders. However, further research is warranted for evaluating its exact mechanism of action.
Assuntos
Antipsicóticos/farmacologia , Benzoquinonas/farmacologia , Embelia/química , Transtornos Psicóticos/tratamento farmacológico , Animais , Apomorfina/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Camundongos , Neurotransmissores/metabolismo , Extratos Vegetais/farmacologia , Transtornos Psicóticos/metabolismo , Ratos , Ratos WistarRESUMO
Background Embelin is a benzoquinone reported to possess anticancer activity in several in vivo and in vitro models of carcinogenesis, especially hematopoietic and prostate malignancy. A detailed investigation on the influence of embelin on epithelial malignancy model system, especially colon adenocarcinoma, is lacking. The objective of the current study is to investigate the antiproliferative, antiinvasive and proapoptotic potential of embelin on colon adenocarcinoma cell line HT-29. Methods The effect of embelin (35âµg/mL for 24âh) on cell proliferation was assessed by Sulforhodamine B assay and bromodeoxyuridine incorporation test, antiinvasive effect by Boyden chamber assay and scratch assay. Proapoptotic effects of embelin were determined by studies on DNA fragmentation, annexin V-FITC labeling, TUNEL assay, COMET assay and assay of caspase-3 activity. Influence of embelin on the expression of genes regulating apoptosis (caspase 3 and 9, Bcl-2, Bax, cytochrome C and X-linked inhibitor of apoptosis protein) and migration/invasion (matrix metalloproteinase [MMP]-2 and MMP-9) was investigated by reverse transcription polymerase chain reaction (PCR). Further, the effect of embelin on the levels of reactive oxygen species (ROS), lipid peroxides, nitric oxide, mitochondrial membrane potential and antioxidant status (total reduced glutathione [GSH] and GSH-S-transferase) was evaluated. Results Results implicated that embelin treatment inhibited proliferation (IC50 35âµg/mL), induced DNA fragmentation, phosphatidyl serine externalization, increased caspase expression, decreased cell migration and expression of MMPs in HT-29 cells. Interestingly, embelin exhibited prooxidant effect on HT-29 cells and induced excessive ROS generation resulting in apoptotic cell death. Conclusions To conclude, embelin treatment could be a promising strategy for the chemotherapy of colon cancer.
Assuntos
Adenocarcinoma/metabolismo , Antineoplásicos Fitogênicos/farmacologia , Apoptose , Benzoquinonas/farmacologia , Neoplasias do Colo/metabolismo , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Adenocarcinoma/tratamento farmacológico , Antineoplásicos Fitogênicos/uso terapêutico , Benzoquinonas/uso terapêutico , Linhagem Celular Tumoral , Colo/efeitos dos fármacos , Colo/patologia , Neoplasias do Colo/tratamento farmacológico , Embelia/química , Células HT29 , Humanos , Fitoterapia , Extratos Vegetais/uso terapêuticoRESUMO
BACKGROUND: Like the impressive biological properties of embelin, its chemical aspects have raised the interest of scientists in the field as well. A detailed understanding of the chemistry of embelin is necessary to fully exploit it medicinally. METHODS: Search for embelin isolation and its chemical modifications was carried out using web-based literature searching tools such as Pubmed and Scifinder. Pertinent literature is covered up to 2016. Structures of bioactive embelin derivatives are provided. RESULTS: Pure embelin, obtained from Embelia ribes berries extraction or by total synthesis, was applied for a number of biological assays. Semi-synthetic and total synthetic approaches led to new high affinity embelin-derived inhibitors of crucial protein targets and to new embelin derivatives with improved pharmacological properties (e.g., with better water-solubility or as applications for drug carrier systems). CONCLUSION: This review provides a summary of the rich chemistry of embelin and the latest developments in the field of optimized (semi-)synthetic embelin derivatives including their biological activities.