RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The rhizome of Dryopteris crassirhizoma Nakai (Dryopteridaceae, RDC), a traditional East Asian herbal medicine, possesses a broad spectrum of medicinal properties, including anti-inflammatory, anticancer, antibacterial, and antiviral activities. AIM OF THE STUDY: This study investigates the 30% ethanolic extract of RDC's antiviral potential against human coronavirus OC43 (HCoV-OC43), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and its variants infections. MATERIALS AND METHODS: A 30% ethanolic extract of RDC or its components, filixic acid ABA (PubChem CID: 15081408) and dryocrassin ABBA (PubChem CID: 3082025) were treated with Human Coronavirus infection (HCoV-OC43, SARS-CoV-2 and its variants). The base peak chromatogram of RDC was evaluated using UPLC-Q/TOF Mass to identify the RDC, and the quantitative analysis of RDC compounds was performed using LC-MS/MS. A cytopathic effect (CPE) reduction assay, Western blot, immunofluorescence staining of viral protein expression, and qRT-PCR were performed to quantify the viral RNA copy numbers and determine the antiviral activity. The time-of-addition assay, the virus attachment, penetration, and virucidal assays, and SARS-CoV-2 Mpro and PLpro activity assay were used to elucidate the mode of action. RESULTS: RDC exhibited dose-dependent inhibition of HCoV-OC43-induced cytopathic effects, reducing viral RNA copy numbers and viral protein levels. Time-of-addition assays indicated that RDC targets the early stages of the HCoV-OC43 life cycle, inhibiting virion attachment and penetration with virucidal activity. Notably, filixic acid ABA and dryocrassin ABBA, constituents of RDC, reduced HCoV-OC43 viral RNA loads. Furthermore, RDC effectively blocked viral entry in pseudotyped lentivirus assays, involving spike proteins of SARS-CoV-2 Delta plus and South Africa variants, as well as control lentiviral particles expressing vesicular stomatitis virus glycoprotein G. Additionally, RDC demonstrated inhibition of SARS-CoV-2 infection and its variants by targeting viral proteases, namely main protease (Mpro) and papain-like protease (PLpro). CONCLUSIONS: These findings underscore RDC's multistage approach to targeting viral infections by impeding virus entry and inhibiting viral protease activity. Therefore, RDC holds promise as a potent, broad-spectrum anticoronaviral therapeutic agent.
Asunto(s)
Antivirales , Dryopteris , Extractos Vegetales , Rizoma , SARS-CoV-2 , Internalización del Virus , Antivirales/farmacología , Antivirales/aislamiento & purificación , Internalización del Virus/efectos de los fármacos , Extractos Vegetales/farmacología , Dryopteris/química , Humanos , SARS-CoV-2/efectos de los fármacos , Coronavirus Humano OC43/efectos de los fármacos , Animales , Proteasas 3C de Coronavirus/antagonistas & inhibidores , Proteasas 3C de Coronavirus/metabolismo , Chlorocebus aethiops , Células VeroRESUMEN
Two endophytic fungi Trichoderma afroharzianum (HP-3) and Alternaria alstroemeriae (HP-7) were isolated and purified from the fresh root of Dryopteris crassirhizoma. Chemical investigation of the two fungi resulted in the isolation of two new phenols 2,4-dihydroxy-3-farnesyl-5-methoxy benzoic acid (1) and 2-hydroxyphenethyl 2-phenylacetate (2), together with 22 known compounds. Their structures were elucidated by NMR, UV, IR, HRESIMS, and comparison to the literature data. Compounds 15 and 16 showed significant antibacterial activity against Micrococcus lysodeikticus with MIC value of 6.25 µg/mL, while 8 and 14 displayed moderate inhibitory activities against several plant pathogenic fungi and clinically important bacterial strains. This is the first study to report the isolation, identification, and antimicrobial properties of metabolites from endophytic fungi of D. crassirhizoma. Our findings may provide lead compounds for the development of new antibacterial agents.
Asunto(s)
Antiinfecciosos , Dryopteris , Dryopteris/química , Hongos , Antiinfecciosos/farmacología , Antibacterianos/química , Bacterias , FenolesRESUMEN
A new fructofuranoside glycerol, dryoptkirbioside (1), along with thirteen known compounds (2-14), was isolated from the MeOH extract of Dryopteris kirbi rhizomes by silica gel column chromatography, Sephadex LH-20 column chromatography, and semipreparative HPLC. The structure of the new compound was determined by analyses of its spectroscopic data including nuclear magnetic resonance (NMR), and high-resolution electrospray ionisation mass spectrometry (HR-ESI-MS) and chemical conversions. The hexane-soluble portion and the EAFA fraction showed strong activities against lung (A549), breast (MCF-7), and cervical (HeLa) human cancer cell lines (IC50 values ranging from 4.0 to 8.8â µg/mL). Aspidinol P (5) and aspidinol B (6) exhibited moderate to low cytotoxicity on the three cell lines (IC50 values ranging from 20.4 to 58.7â µM). The MeOH extract and hexane-soluble portion had excellent activities against Staphylococcus aureus and Bacillus subtilis (MICs 11.7 and 23.4â µg/mL), whereas the AcOEt- and BuOH-soluble portions were significantly active on S. aureus (MICs 46.9 and 93.8â µg/mL). The main fractions EAFB , EAFC and nBFB displayed excellent activity against S. aureus (MICs 11.7 and 23.4â µg/mL). Aspidinol B (6) had significant activity, while aspidinol P (5) was moderately active against S. aureus and B. subtilis (MICs 42.0 and 89.5â µM).
Asunto(s)
Dryopteris , Humanos , Dryopteris/química , Glicerol , Hexanos , Rizoma , Staphylococcus aureus , Células HeLa , Extractos Vegetales/químicaRESUMEN
Nine undescribed phloroglucinol derivatives (dryatraols A-I) with five different backbones and three known dimeric acylphloroglucinols were isolated from the rhizome of Dryopteris atrata (Wall. Ex Kunze) Ching (Dryopteridaceae). Dryatraol A contains an unprecedented carbon skeleton-a butyrylphloroglucinol and a rulepidanol-type sesquiterpene are linked via a furan ring to form a 6/5/6/6 ring system. Dryatraols B and C are the first examples of monomeric phloroglucinols coupled with the aristolane-type sesquiterpene through the C-C bond. Dryatraol D features a rare spiro [benzofuran-2',5â³-furan] backbone. Dryatraols E-I are five undescribed adducts with a butyrylphloroglucinol or filicinic acid incorporated into the germacrene-type sesquiterpene via a pyran ring. These undescribed structures were determined by comprehensively analysing the spectroscopic data, X-ray diffraction results, and electronic circular dichroism calculations. The result of in vitro antiviral activity evaluation indicated that dryatraol C displayed the strongest antiviral effect against both respiratory syncytial virus and influenza A virus (H1N1), with IC50 values of 11.9 µM and 5.5 µM, respectively. Dryatraols F-H exhibited considerable inhibitory activity against herpes simplex virus type 1 (HSV-1), with IC50 values ranging from 2.6 to 6.3 µM. Analysis of the inhibitory mechanism using a time-of-addition assay revealed that dryatraol G may inhibit the replication of HSV-1 by interfering with the late stage of the viral life cycle.
Asunto(s)
Dryopteris , Herpesvirus Humano 1 , Subtipo H1N1 del Virus de la Influenza A , Dryopteris/química , Floroglucinol , Antivirales/química , Furanos/farmacología , Estructura MolecularRESUMEN
Nine previously undescribed compounds including six tocopherol derivatives (1-6) and three acylphloroglucinol derivatives (7-9) were isolated and characterized from the plants of Dryopteris crassirhizoma. Their structures with absolute configurations were determined by extensive spectroscopic analyses, including IR, HRESIMS, NMR, and calculated electronic circular dichroism (ECD). Compounds 1 and 2 are the first tocopheroid derivatives possessing unique 2,5-dimethylcyclopent-4-ene-1,3-dione carbon skeleton, and compounds 3-6 were new 5a-norcyclopentenones having a spirofused bicyclic carbon skeleton. The biosynthetic pathway of compounds 1-6 was postulated. When combined with fluconazole (FLC), compound 3 showed significant antifungal activity against standard Candida albicans with MIC50 value of 1.19 µg/mL (FLC: 3.41 µg/mL). Furthermore, the anti-plant pathogenic fungi and bacterial activities have been evaluated in vitro, compounds 5 and 8 showed anti-Verticillium dahlia and Sclerotinia sclerotiorum with MIC value of 50 µg/mL, respectively. Compounds 1 and 5 exhibited moderate antibacterial activities against Micrococcus luteus with MIC value of 50 µg/mL, respectively.
Asunto(s)
Dryopteris , Dryopteris/química , Tocoferoles , Estructura Molecular , Antifúngicos/farmacología , Antifúngicos/química , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , AntibacterianosRESUMEN
Ten novel meroterpenoids, dryoptins/11â³-epi-dryoptins A~E (1: ~10: ) with an unprecedented skeleton consisting of dimeric or trimeric acylphloroglucinols and dehydrotheonelline, two undescribed acylphloroglucinol-nerolidol meroterpenoids (11: ~12: ), and ten known acylphloroglucinol derivatives (13: ~22: ), were isolated from D. crassirhizoma. The novel structures including absolute configurations were established by comprehensive spectroscopic analyses and quantum chemical electronic circular dichroism (ECD) calculations. A biosynthetic pathway of 1: ~10: was assumed. The trimeric acylphloroglucinol meroterpenoids 7: /8: showed significant antifungal activity against standard Candida albicans with a MIC50 value of 1.61 µg/mL [fluconazole (FLC): 3.41 µg/mL], and when combined with FLC, the principal components 20: and 21: exhibited strong antifungal activities against FLC-resistant C. albicans with MIC50 values of 8.39 and 7.16 µg/mL (FLC: > 100 µg/mL), respectively. Moreover, compounds 2, 5: /6, 18, 19: , and 21: exhibited inhibitory effects against several pathogenic fungi and bacteria, with MIC50 values of 6.25 ~ 50 µg/mL.
Asunto(s)
Antifúngicos , Dryopteris , Antifúngicos/farmacología , Dryopteris/química , Fluconazol/farmacología , Candida albicans , Dicroismo CircularRESUMEN
Two new cadinane-type sesquiterpenoid glycosides, dryopteristerpeneA (1) and dryopteristerpeneB (2), were isolated from the aqueous extract of Dryopterisfragrans. Their structures were determined by spectroscopic data analysis and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 exhibited inhibition on nitric oxide production in lipopolysaccharide induced RAW 264.7 macrophages with their IC50 values of 60.5 and 59.8 µM, respectively.
Asunto(s)
Dryopteris , Sesquiterpenos , Dryopteris/química , Glicósidos/farmacología , Glicósidos/química , Estructura Molecular , Sesquiterpenos/farmacología , Sesquiterpenos/química , Antiinflamatorios/farmacología , Lipopolisacáridos/farmacología , Óxido NítricoRESUMEN
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to more than 5 million deaths worldwide to date. Due to the limited therapeutic options so far available, target-based virtual screening with LC/MS support was applied to identify the novel and high-content compounds 1-4 with inhibitory effects on SARS-CoV-2 in Vero E6 cells from the plant Dryopteris wallichiana. These compounds were also evaluated against SARS-CoV-2 in Calu-3 cells and showed unambiguous inhibitory activity. The inhibition assay of targets showed that compounds 3 and 4 mainly inhibited SARS-CoV-2 3CLpro, with effective Kd values. Through docking and molecular dynamics modeling, the binding site is described, providing a comprehensive understanding of 3CLpro and interactions for 3, including hydrogen bonds, hydrophobic bonds, and the spatial occupation of the B ring. Compounds 3 and 4 represent new, potential lead compounds for the development of anti-SARS-CoV-2 drugs. This study has led to the development of a target-based virtual screening method for exploring the potency of natural products and for identifying natural bioactive compounds for possible COVID-19 treatment.
Asunto(s)
Antivirales/farmacología , Productos Biológicos/farmacología , Pruebas de Sensibilidad Microbiana/métodos , Floroglucinol/farmacología , SARS-CoV-2/efectos de los fármacos , Terpenos/farmacología , Cromatografía Líquida de Alta Presión , Cromatografía Liquida , Cristalografía por Rayos X , Sistemas de Liberación de Medicamentos , Dryopteris/química , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Simulación del Acoplamiento Molecular , Estructura Molecular , Realidad VirtualRESUMEN
Twenty-four racemic acylphloroglucinol meroterpenoids including eighteen unusual stuctures (3 â¼ 10, 13, 14, and 17 â¼ 24), and a major component filixic acid ABA (25), were isolated from Dryopteris crassirhizoma. Structurally, the dimeric acylphloroglucinol derivatives possess unprecedented skeletons of mixed acylphloroglucinol and sesquiterpene biosynthetic origin. The stereochemistries of six reported meroterpenoids with undefined chiral centers were reassigned. Two intriguing methods by analyzing a) the regularity of chemical shift variation of protons and carbons around the stereogenic centers, and b) pyridine-induced deshielding effect of hydroxy groups, to discriminate relative configurations of flexible long-chain alcohol with chiral centers separated by three or seven covalent bonds, were successfully applied. A non-enzymatic biosynthesis of 1 â¼ 24 was assumed based on a rare single-crystal cluster formed with two diastereomeric enantiomer pairs (±1/±2) and chiral HPLC analyses. Meroterpenoids 13 and 14 showed obvious inhibitory effects on NO production in LPS-induced RAW264.7, and suppressed the expression of iNOS, COX-2, IL-1ß, and IL-18. Their anti-inflammatory activity was closely related to the inhibition of the formation and function of inflammasomes. Additionally, the known 25 showed antiviral efficacy against the influenza viruse A/Puerto Rico/8/1934 (H1N1).
Asunto(s)
Antiinflamatorios/farmacología , Antivirales/farmacología , Dryopteris/química , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Floroglucinol/farmacología , Terpenos/farmacología , Animales , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Antivirales/química , Antivirales/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Inflamasomas/efectos de los fármacos , Inflamasomas/metabolismo , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Ratones , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Floroglucinol/química , Floroglucinol/aislamiento & purificación , Células RAW 264.7 , Estereoisomerismo , Relación Estructura-Actividad , Terpenos/química , Terpenos/aislamiento & purificaciónRESUMEN
Dryopteris ramosa (D. ramosa) is one of the most traded medicinally important plants of Himalayan region. Apart from other uses, D. ramosa is traditionally also used to treat gastric ulcers and as a laxative. The present study was designed to investigate the role of methanolic crude extract of Dryopteris Ramosa (MEDR) in acute toxicity, against loperamide induced constipated mice model, antiulcer effect of methanolic extract of D. Ramosa and cholinomimetic like effect of methanolic extract of D. Ramosa. The crude extract was investigated for the presence of active compounds (secondary metabolites) such as alkaloids, flavonoids, carbohydrates, glycosides, terpenoids, phenolic compounds, saponins, and tannins following the standard methods. The antiulcer effect was investigated in mice using the ethanol induced ulcer model at various doses i.e. 50 mg/kg, 100 mg/kg and 200 mg/kg doses. Constipation was induced in the mice via loperamide (3mg/kg body weight). The control group received normal saline. Different doses of plant extracts (50, 100, 150 and 200 mg/kg body weight/day) were administered for 7 days. Various parameters like feeding characteristics, gastrointestinal transit ratio, body weight, fecal properties and the possible mechanism of action of D. Ramosa on intestinal motility were monitored. Various Phytochemicals like saponins, glycosides, flavonoids, tannins, phenols, carbohydrate, alkaloids and triterpenes were found in D. Ramosa. The acute toxicity study showed that MEDR was associated with no mortality except mild and moderate sedation at the highest tested doses (1500 and 2000 mg/kg). MEDR also showed significant antiulcer activity against ethanol-induced ulcerogenesis. The extract enhanced the intestinal motility, normalized the body weight of constipated mice and increased the fecal volume which are indications of laxative property of the herb. The 200 mg/kg body weight dose of the extract was found effective. The presence of various Phytochemicals such as flavonoids, glycosides and tannins might be responsible for the antiulcer activity of D. Ramosa. This study provides the scientific background for the folkloric use of D. Ramosa as antiulcer agent. The laxative action of the extract compares positively with Duphalac, (standard laxative drug). These findings have therefore evidence scientific background to the folkloric use of the herb as a laxative agent.
Asunto(s)
Estreñimiento/prevención & control , Dryopteris/química , Laxativos/farmacología , Extractos Vegetales/farmacología , Plantas Medicinales/química , Úlcera Gástrica/prevención & control , Alcaloides/farmacología , Animales , Estreñimiento/inducido químicamente , Etanol , Flavonoides/farmacología , Motilidad Gastrointestinal/efectos de los fármacos , Laxativos/química , Loperamida , Metanol/química , Ratones , Fitoterapia/métodos , Extractos Vegetales/química , Extractos Vegetales/toxicidad , Saponinas/farmacología , Úlcera Gástrica/inducido químicamente , Taninos/farmacología , Pruebas de Toxicidad Aguda/métodosRESUMEN
AIMS: Oxido-inflammatory stress has been implicated as the main targets in alleviating diabetic complications induced by hyperglycaemia. Dryopteris dilatata: a bioactive plant serves great medicinal benefits in ethnopharmacology to ameliorate pathological conditions. This study investigated the protective effects of ethanol extract of Dryopteris dilatata (EEDD) in alloxan-induced diabetic rats through mechanism involving inhibition of oxidative stress and liver and kidney inflammatory markers. METHODOLOGY: Male Wistar rats were made diabetic via alloxan monohydrate (100 mg/kg) administration intraperitoneally. Diabetic rats were post-treated with EEDD (800 mg/kg) and Metformin (50 mg/kg) orally for two weeks. Fasting blood sugar (FBS), body and organ weight change, markers of oxidative stress, liver and kidney inflammation were evaluated. RESULTS: Our results revealed that EEDD significantly reduced alloxan-induced hyperglycaemia in the diabetic rats after 5, 10 and 15 days of treatment. Markers of oxidative injury were also significantly ameliorated in the pancreas, liver and kidney of the diabetic rats following treatment with EEDD. However, liver and kidney injury markers were significantly attenuated with marked decreased organ weight in the diabetic rats after treatment with EEDD. CONCLUSION: Here in, we found that Dryopteris dilatata could be used as nutraceuticals in the prevention and treatment of diabetes and its related complications through positively modulating oxidative stress and liver and kidney inflammatory markers.
Asunto(s)
Antioxidantes/farmacología , Diabetes Mellitus Experimental/prevención & control , Dryopteris/química , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Alanina Transaminasa/metabolismo , Fosfatasa Alcalina , Aloxano , Animales , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Aspartato Aminotransferasas/metabolismo , Glucemia/metabolismo , Catalasa/metabolismo , Creatinina/sangre , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/inducido químicamente , Etanol/química , Riñón/efectos de los fármacos , Riñón/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Páncreas/efectos de los fármacos , Páncreas/metabolismo , Fitoterapia/métodos , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Ratas Wistar , Superóxido Dismutasa/metabolismo , Urea/sangreRESUMEN
By various chromatographic methods, 30 phloroglucinols (1-30) were isolated from a methanol extract of Dryopteris crassirhizoma, including two new dimeric phloroglucinols (13 and 25). The structures of the isolates were confirmed by HR-MS, 1D, and 2D NMR as well as by comparison with the literature. The protein tyrosine phosphatase 1B (PTP1B) effects of the isolated compounds (1-30) were evaluated using sodium orthovanadate and ursolic acid as a positive control. Among them, trimeric phloroglucinols 26-28 significantly exhibited the PTP1B inhibitory effects with the IC50 values of 1.19 ± 0.13, 1.00 ± 0.04, 1.23 ± 0.05 µM, respectively. In addition, the kinetic analysis revealed compounds 26-28 acted as competitive inhibitors against PTP1B enzyme with Ki values of 0.63, 0.61, 1.57 µM, respectively. Molecular docking simulations were performed to demonstrate that these active compounds can bind with the catalytic sites of PTP1B with negative binding energies and the results are in accordance with that of the kinetic studies. In vitro and in silico results suggest that D. crassirhizoma rhizomes together with compounds 26-28 are potential candidates for treating type 2 diabetes.
Asunto(s)
Dryopteris/química , Simulación del Acoplamiento Molecular , Floroglucinol/farmacología , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidores , Rizoma/química , Espectroscopía de Resonancia Magnética con Carbono-13 , Dominio Catalítico , Cinética , Floroglucinol/química , Floroglucinol/aislamiento & purificación , Proteína Tirosina Fosfatasa no Receptora Tipo 1/metabolismo , Espectroscopía de Protones por Resonancia MagnéticaRESUMEN
Dryopteris crassirhizoma (DC) has a wide range of pharmacological effects, including antibacterial, antiinfluenza virus, antitumor, antireverse transcriptase and antioxidant effects. However, the inhibitory effect of DC on allergic inflammatory response remains unclear; therefore, the current study used an experimental ovalbumin (OVA)induced allergic asthma mouse model and phorbol myristate acetate (PMA) and A23187stimulated HMC1 cells to reveal the effects of DC in regulating airway inflammation and its possible mechanism. Allergic asthma was initiated in BALB/c mice via exposure to OVA emulsified in aluminum, on days 1 and 14. Thereafter, the mice were treated with DC or dexamethasone (Dex) orally, before being challenged, from days 15 to 26. Subsequently, the mice were challenged with OVA on days 27, 28 and 29. The results of histological analysis indicated that the administration of DC decreased the number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) and suppressed eosinophilic infiltration, mucus production and collagen deposition in the lung tissue. DC treatment increased the level of T helper type 1 (Th1) cytokines (IL10 and interferon (IFN)γ) and decreased the levels Th2 cytokines (IL4, IL5 and IL13) and proinflammatory cytokines (IL6 and TNFα). Furthermore, DC treatment inhibited the activation of NFκB signaling (NFκB, pNFκB, IκB and pIκB), both in BALF and lung homogenates. Serum levels of total IgE and OVAspecific IgE and IgG1 were significantly lower after DC treatment compared with after OVA treatment. However, the antiinflammatory effect of OVAspecific IgG2a was higher after DC treatment. In addition, DC treatment attenuated the production of proinflammatory cytokines, including IL6 and TNFα, and the activation of NFκB signaling (NFκB and pNFκB), in PMA and calcium ionophore A23187stimulated HMC1 cells. In summary, the current study demonstrated that DC acts a potent antiallergic and antiinflammatory drug by modulating the Th1 and Th2 response and reducing the allergic inflammatory reaction in PMA and A23187stimulated HMC1 cells via NFκB signaling in an OVAinduced allergic asthma model.
Asunto(s)
Antialérgicos/administración & dosificación , Antiinflamatorios/administración & dosificación , Asma/inducido químicamente , Asma/tratamiento farmacológico , Dryopteris/química , FN-kappa B/metabolismo , Fitoterapia/métodos , Extractos Vegetales/administración & dosificación , Transducción de Señal/efectos de los fármacos , Animales , Asma/metabolismo , Líquido del Lavado Bronquioalveolar , Calcimicina/farmacología , Línea Celular Tumoral , Citocinas/metabolismo , Modelos Animales de Enfermedad , Humanos , Pulmón/patología , Masculino , Mastocitos/efectos de los fármacos , Mastocitos/metabolismo , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/efectos adversos , Acetato de Tetradecanoilforbol/farmacologíaRESUMEN
BACKGROUND: Dryopteris cycadina has diverse traditional uses in the treatment of various human disorders which are supported by pharmacological studies. Similarly, the phytochemical studies of this plant led to the isolation of numerous compounds. METHODOLOGY: The present study deals with α-glucosidase inhibition of various kaempferol derivates including kaempferol-3, 4/-di-O-α- L-rhamnopyranoside 1, kaempferol-3, 5-di-O-α-L-rhamnoside 2 and kaempferol-3,7-di-O-α- L-rhamnopyranoside 3. RESULTS: The results showed marked concentration-dependent inhibition of the enzyme when assayed at different concentrations and the IC50 values of compounds 1-3 were 137±9.01, 110±7.33, and 136±1.10 mM, respectively far better than standard compound, acarbose 290±0.54 mM. The computational studies revealed strong docking scores of these compounds and augmented the in vitro assay. CONCLUSION: In conclusion, the isolated kaempferol derivatives 1-3 from D. cycadina exhibited potent α- glucosidase inhibition.
Asunto(s)
Dryopteris/química , Inhibidores de Glicósido Hidrolasas/química , Quempferoles/química , Extractos Vegetales/química , alfa-Glucosidasas/metabolismo , Acarbosa/normas , Secuencia de Aminoácidos , Sitios de Unión , Inhibidores de Glicósido Hidrolasas/metabolismo , Humanos , Enlace de Hidrógeno , Quempferoles/metabolismo , Simulación del Acoplamiento Molecular , Estructura Molecular , Fitoquímicos/química , Fitoquímicos/metabolismo , Extractos Vegetales/metabolismo , Unión Proteica , Conformación ProteicaRESUMEN
Dryopteris crassirhizoma rhizomes are used as a traditional medicine in Asia. The EtOAc extract of these roots has shown potent xanthine oxidase (XO) inhibitory activity. However, the main phloroglucinols in D. crassirhizoma rhizomes have not been analyzed. Thus, we investigated the major constituents responsible for this effect. Bioassay-guided purification isolated four compounds: flavaspidic acid AP (1), flavaspidic acid AB (2), flavaspidic acid PB (3), and flavaspidic acid BB (4). Among these, 1 showed the most potent inhibitory activity with a half-maximal inhibitory concentration (IC50) value of 6.3 µM, similar to that of allopurinol (IC50 = 5.7 µM) and better than that of oxypurinol (IC50 = 43.1 µM), which are XO inhibitors. A comparative activity screen indicated that the acetyl group at C3 and C3' is crucial for XO inhibition. For example, 1 showed nearly 4-fold higher efficacy than 4 (IC50 = 20.9 µM). Representative inhibitors (1-4) in the rhizomes of D. crassirhizoma showed reversible and noncompetitive inhibition toward XO. Furthermore, the potent inhibitors were shown to be present in high quantities in the rhizomes by a UPLC-QTOF-MS analysis. Therefore, the rhizomes of D. crassirhizoma could be used to develop nutraceuticals and medicines for the treatment of gout.
Asunto(s)
Dryopteris/química , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Floroglucinol/análogos & derivados , Floroglucinol/farmacología , Xantina Oxidasa/antagonistas & inhibidores , Butirofenonas/química , Butirofenonas/farmacología , Humanos , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/enzimología , Rizoma/química , Xantina Oxidasa/metabolismoRESUMEN
The stems of Dryopteris crassirhizoma, one of the main components of Lianhua-Qingwen Formula (LQF) was traditionally used for heat-clearing and detoxifying. Dryocrassin ABBA is a key antiviral component in the herbal medicine while the compound is hard to get in large amounts with the features of homologous compounds, polyphenol groups, and low contents. Therefore, the present work aims to seek influenza H7N9 virus inhibitors from natural source by synthesis of dryocrassin ABBA and its analogues. As a result, total synthesis of the compound was achieved in nine steps with an over-all yield of 4.6%. Neuraminidases (NAs) inhibitory activities of the synthesized product and its analogues were evaluated afterward. Comparing with the positive control, OSV (9.6⯵M), it was very exciting that dryocrassin ABBA and its analogues (b5 and e2) showed better NAs inhibitory activity against Anhui H7N9 with IC50 values of 3.6⯵M, 2.5⯵M and 1.6⯵M. For the highly resistant Shanghai N9, these compounds can also show medium inhibitory activities. Docking results indicated the direct interaction of synthesized 3 hits with the key K294 by hydrogen bonds, but no direct interaction of OSV with the key K294 was observed in Shanghai N9. This study suggested that dryocrassin ABBA and its analogues especially AB, which consisted of polyphenol groups may have beneficial effects on treating avian influenza H7N9 virus.
Asunto(s)
Antivirales/farmacología , Compuestos de Bencilideno/farmacología , Ciclohexanonas/farmacología , Farmacorresistencia Viral/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Subtipo H7N9 del Virus de la Influenza A/efectos de los fármacos , Neuraminidasa/antagonistas & inhibidores , Antivirales/síntesis química , Antivirales/química , Compuestos de Bencilideno/síntesis química , Compuestos de Bencilideno/química , Ciclohexanonas/síntesis química , Ciclohexanonas/química , Relación Dosis-Respuesta a Droga , Dryopteris/química , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Subtipo H7N9 del Virus de la Influenza A/enzimología , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Estructura Molecular , Neuraminidasa/metabolismo , Relación Estructura-ActividadRESUMEN
Platelets are an important component of the initial response to vascular endothelial injury; however, platelet dysfunction induces the acute clinical symptoms of thrombotic disorders, which trigger severe cardiovascular diseases such as myocardial infarction, ischemia, and stroke. In this study, we investigated the Dryopteris crassirhizoma's antiplatelet activity. A water extract of D. crassirhizoma (WDC) was partitioned into dichloromethane (DCM), ethyl acetate, n-butyl alcohol, and water. Among these four fractions, the DCM fraction potently inhibited the collagen-stimulated platelet aggregation in a concentration-dependent manner. From this fraction, five different acylphloroglucinol compounds and one flavonoid were isolated by activity-guided column chromatography. They were identified by comparing their mass, 1H-, and 13C-NMR spectral data with those reported in the literature. Quantifying the six compounds in WDC and its DCM fraction by high-performance liquid chromatography (HPLC) revealed that butyryl-3-methylphloroglucinol (compound 4) was the most abundant in these samples. Additionally, butyryl-3-methylphloroglucinol showed the strongest inhibitory activity in the collagen- and arachidonic acid (AA)-induced platelet aggregation, with inhibition ratios of 92.36% and 89.51% in the collagen and AA-induced platelet aggregation, respectively, without cytotoxicity. On the active concentrations, butyryl-3-methylphloroglucinol significantly suppressed the convulxin-induced platelet activation. Regarding the structure-activity relationships for the five acylphloroglucinol compounds, our results demonstrated that the functional butanonyl, methoxy, and hydroxy groups in butyryl-3-methylphloroglucinol play important roles in antiplatelet activity. The findings indicate that acylphloroglucinols, including butyryl-3-methylphloroglucinol from D. crassirhizom, possess an antiplatelet activity, supporting the use of this species for antiplatelet remedies.
Asunto(s)
Plaquetas/fisiología , Dryopteris/química , Animales , Cromatografía Líquida de Alta Presión , Masculino , Cloruro de Metileno/química , Estructura Molecular , Extractos Vegetales/química , Activación Plaquetaria , Agregación Plaquetaria , ConejosRESUMEN
AIM: To evaluate the anti-invasive effect of ethanol extracts of rhizome of Dryopteris crassirhizoma (EEDC) in matrix invasion and formation of functional invadopodia and to determine the anti-tumor effect of EEDC in a mouse model of mandibular invasion by gingival squamous cell carcinoma (SCC). METHODS: The rhizome of D crassirhizoma was extracted in ethanol. The anti-invasive effect of EEDC was analyzed with a Matrigel-coated transwell invasion and 3D culture system. Crucial factors related to the control of cancer cell invasion by EEDC were determined using a human protease array. Molecular evidence supporting the anti-invasive effect of EEDC in oral SCC (OSCC) cells used an invadopodia-mediated extracellular matrix (ECM) degradation; an in vivo athymic mouse model was also provided. RESULTS: EEDC treatment (10 µg/mL) suppressed transwell migration and invasion of HSC-3 OSCC cells without cytotoxicity. Decreased levels of matrix metalloprotease (MMP)-7, kalikrein 10, cathepsin V, MMP-2, and cathepsin D were also found in EEDC-treated HSC-3 cells based on human protease array. The anti-invasive effects of EEDC involved the suppression of invadopodia-mediated ECM degradation via inhibition of globular-actin elongation. The anti-invasive effect resulting from disturbance of functional invadopodia formation by EEDC was observed even at a low concentration of 5 µg/mL. The phosphorylation of cortactin involved in functional invadopodia formation was decreased at EEDC concentrations that inhibited invadopodia formation. The anti-tumor effect of EEDC was also observed in a mouse xenograft model. Administration of EEDC resulted in inhibition of tumor growth and progression. CONCLUSIONS: EEDC represents a potential anti-invasive and anti-tumor agent in cancer control.
Asunto(s)
Actinas/metabolismo , Antineoplásicos/farmacología , Carcinoma de Células Escamosas/tratamiento farmacológico , Dryopteris/química , Invasividad Neoplásica/prevención & control , Extractos Vegetales/farmacología , Polimerizacion/efectos de los fármacos , Animales , Carcinoma de Células Escamosas/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Fosforilación/efectos de los fármacosRESUMEN
Rhizome of the fern Dryopteris crassirhizoma Nakai is used as an antiviral drug in China. The objective was to characterize physicochemical properties, structural features and antioxidant and immunological activities of D. crassirhizoma polysaccharides. An acidic polysaccharide fraction (DCP-3) was obtained from Dryopteris crassirhizoma Nakai by purification with DEAE-52 and Sephadex G-100. DCP-3 was a novel triple-helical polysaccharide with an average MW of 273.2â¯kDa. This fraction was mainly composed of galactose (36.65%), xylose (34.75%), arabinose (17.07%) and mannose (9.22%). DCP-3 had strong activity for scavenging DPPH radical (IC50: 2.04â¯mg/mL), hydroxyl radical (IC50: 1.70â¯mg/mL), and superoxide anions (IC50: 4.20â¯mg/mL) and also was capable of reducing ferric ions. In addition, nitric oxide production was enhanced in RAW264.7 macrophages stimulated by DCP-3. Based on these bioactivities, we inferred that DCP-3 was a functional component of D. crassirhizoma and may confer antivirus activity, with potential applications in functional food and drug industries.
Asunto(s)
Antioxidantes/farmacología , Dryopteris/química , Factores Inmunológicos/farmacología , Polisacáridos/farmacología , Rizoma/química , Animales , Antioxidantes/química , Compuestos de Bifenilo/química , Supervivencia Celular/efectos de los fármacos , Radical Hidroxilo/química , Factores Inmunológicos/química , Ratones , Óxido Nítrico/biosíntesis , Picratos/química , Polisacáridos/química , Células RAW 264.7 , Superóxidos/química , TemperaturaRESUMEN
Enzootic bovine haematuria, caused by long-term ingestion of ferns, is a chronic disease of hill cattle characterized by neoplastic lesions in the urinary bladder. Objectives of this study were to investigate the toxicity potential of long-term feeding of the fern Dryopteris nigropalaceae and effect of allyl isothiocyanate (AITC) to ameliorate fern toxicity and the associated pathological changes. The LC-MS analysis of the fern showed presence of ptaquiloside (4.5⯱â¯1.0⯵g/g) and pterosin B (39⯱â¯9.1⯵g/g). Groups of animals were fed dried fern powder at the dose of 20% w/w in normal feed and treated with and without AITC at graded doses. Long term feeding of fern induced inflammatory and pre-neoplastic lesions in urinary bladder. The important lesions included cystitis, squamous metaplasia and high-grade dysplasia. Urothelium showed positive immunoreactions for nuclear expression of H-ras and p53. However, no mutation suggestive of neoplastic change was observed on partial mRNA sequences analyses of exon 2 of H-ras and 5 or 7&8 of p53 genes. Strikingly, AITC showed dose-dependent amelioration of pre-neoplastic changes in fern-fed animals. In conclusion, AITC is shown to limit pre-neoplastic changes caused by D. nigropalaceae feeding in guinea pigs.