RESUMO
It's urgent to discover new antibiotics along with the increasing emergence and dissemination of multidrug resistant (MDR) bacterial pathogens. In the present investigation, morusin exhibited rapid bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) by targeting the phospholipid of bacterial inner membrane, increasing membrane rigidity and disrupting bacterial homeostasis together with the membrane permeability, which caused fundamental metabolic disorders. Furthermore, morusin can also accumulate ROS, suppress H2S production, and aggravate oxidative damage in bacteria. Importantly, morusin also inhibited the spread of wounds and reduced the bacterial burden in the mouse model of skin infection caused by MRSA. It's a chance to meet the challenge of existing antibiotic resistance and avoid the development of bacterial resistance, given the multiple targets of morusin.
Assuntos
Staphylococcus aureus Resistente à Meticilina , Morus , Animais , Camundongos , Antibacterianos/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
Seven new formononetin derivatives (1-7) were designed and prepared from formononetin (phase II phytoestrogen). The derivatives 9-butyl-3-(4-methoxyphenyl)-9,10-dihydro-4H,8H-chromeno[8,7-e][1,3]oxazin-4-one (2) and 9-(furan-3-ylmethyl)-3-(4-methoxyphenyl)-9,10-dihydro-4H,8H-chromeno[8,7-e][1,3]oxazin-4-one (7) promoted significant osteoblast formation by modulating the BMP/Smad pathway. Compound 7 exhibited potent antiosteoclastogenesis activity in RANKL-induced RAW264.7 cells and ovariectomy (OVX)-induced osteoporosis in mice by regulation of the RANK/RANKL/OPG pathway. Compound 7 regulated osteoblast and osteoclast simultaneously and showed better effect than the well-known drug ipriflavone in vivo, suggesting 7 as a patented antiosteoporosis candidate.
Assuntos
Isoflavonas , Osteoblastos , Osteoclastos , Osteoporose , Ligante RANK , Isoflavonas/farmacologia , Isoflavonas/química , Animais , Osteoblastos/efeitos dos fármacos , Camundongos , Osteoporose/tratamento farmacológico , Osteoclastos/efeitos dos fármacos , Células RAW 264.7 , Ligante RANK/metabolismo , Ligante RANK/efeitos dos fármacos , Feminino , Estrutura Molecular , Ovariectomia , OsteoprotegerinaRESUMO
Monoterpene indole alkaloids exhibit structural diversity in herbal resources and have been developed as promising drugs owing to their significant biological activities. Confidential identification and quantification of monoterpene indole alkaloids is the key to quality control of target plants in industrial production but has rarely been reported. In this study, quantitative performance of three data acquisition modes of ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry including full scan, auto-MS2 and target-MS2 , was evaluated and compared for specificity, sensitivity, linearity, precision, accuracy, and matrix effect using five monoterpene indole alkaloids (scholaricine, 19-epi-scholaricine, vallesamine, picrinine, and picralinal). Method validations indicated that target-MS2 mode showed predominant performance for simultaneous annotation and quantification of analytes, and was then applied to determine monoterpene indole alkaloids in Alstonia scholaris (leaves, barks) after extraction procedures optimization using Box-Behnken design of response surface methodology. The variations of A. scholaris monoterpene indole alkaloids in different plant parts, harvest periods, and post-handling processes, were subsequently investigated. The results indicated that target-MS2 mode could improve the quantitative capability of ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry for structure-complex monoterpene indole alkaloids in herbal matrices. Alstonia scholaris, monoterpene indole alkaloids, quadrupole time of flight mass spectrometry, qualitative and quantitative analysis, ultra-high-performance liquid chromatography.
Assuntos
Alstonia , Alcaloides de Triptamina e Secologanina , Cromatografia Líquida de Alta Pressão , Alstonia/química , Alcaloides Indólicos/química , Espectrometria de Massas/métodos , MonoterpenosRESUMO
Twelve lupanes including three new compounds named alstoscholarilups A-C (1: -3: ) were isolated from the leaves of Alstonia scholaris. Their structures were elucidated by spectroscopic analysis and ECD calculation. Structurally, compound 1: with a rare A ring-seco skeleton formed lactone and degraded C-3, while 2: with a 28-nor and 3: with a 29-nor-lupane skeleton supported the phytochemical diversity and novelty of the plant. Pharmacologically, compounds 4, 7: , and 10: reduced the serum uric acid (UA) levels of mice significantly.
RESUMO
Benign prostatic hyperplasia (BPH) is a chronic disease that affects the quality of life of older males. Sinomenine hydrochloride (SIN) is the major bioactive alkaloid isolated from the roots of the traditional Chinese medicinal plant Sinomenium acutum Rehderett Wilson. We wondered if the SIN administration exerted a regulatory effect on BPH and its potential mechanism of action. Mice with testosterone propionate-induced BPH subjected to bilateral orchiectomy were employed for in vivo experiments. A human BPH cell line (BPH-1) was employed for in vitro experiments. SIN administration inhibited the proliferation of BPH-1 cells (p < 0.05) by regulating the expression of androgen-related proteins (steroid 5-alpha reductase 2 (SRD5A2), androgen receptors, prostate-specific antigen), apoptosis-related proteins (B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax)) and proliferation-related proteins (proliferating cell nuclear antigen (PCNA), mammalian target of rapamycin, inducible nitric oxide synthase) in vitro. SIN administration decreased the prostate-gland weight coefficient (p < 0.05) and improved the histological status of mice suffering from BPH. The regulatory effects of SIN administration on SRD5A2, an apoptosis-related protein (Bcl-2), and proliferation-related proteins (PCNA, matrix metalloproteinase-2) were consistent with in vitro data. SIN exerted a therapeutic effect against BPH probably related to lowering the SRD5A2 level and regulating the balance between the proliferation and apoptosis of cells. Our results provide an important theoretical basis for the development of plant medicines for BPH therapy.
Assuntos
Hiperplasia Prostática , Animais , Humanos , Masculino , Camundongos , Apoptose , Proliferação de Células , Colestenona 5 alfa-Redutase/metabolismo , Metaloproteinase 2 da Matriz , Proteínas de Membrana , Extratos Vegetais/farmacologia , Antígeno Nuclear de Célula em Proliferação , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Qualidade de Vida , Testosterona/farmacologiaRESUMO
Nanomaterials have received increasing attentions owing to their potential hazards to the environment and human health; however, the multi-generational toxicity of graphene oxide under consecutive multi-generational exposure scenario still remains unclear. In the present study, Caenorhabditis elegans as an in vivo model organism was employed to explore the multi-generational toxicity effects of graphene oxide and the underlying mechanisms. Endpoints including development and lifespan, locomotion behaviors, defecation cycle, brood sizes, and oxidative response were evaluated in the parental generation and subsequent five filial generations. After continuous exposure for several generations, worms grew smaller and lived shorter. The locomotion behaviors were reduced across the filial generations and these reduced trends were following the impairments of locomotion-related neurons. In addition, the extended defecation cycles from the third filial generation were in consistency with the relative size reduction of the defecation related neuron. Simultaneously, the fertility function of the nematode was impaired under consecutive exposure as reduced brood sizes and oocytes numbers, increased apoptosis of germline, and aberrant expression of reproductive related genes ced-3, ced-4, ced-9, egl-1 and ced-13 were detected in exposed worms. Furthermore, the antioxidant enzyme, SOD-3 was significantly increased in the parent and filial generations. Thus, continuous multi-generational exposure to graphene oxide caused damage to the neuron development and the reproductive system in nematodes. These toxic effects could be reflected by indicators such as growth inhibition, shortened lifespan, and locomotion behavior impairment and induced oxidative response.
Assuntos
Proteínas de Caenorhabditis elegans , Grafite , Animais , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Grafite/toxicidade , Longevidade , ReproduçãoRESUMO
CONTEXT: Yi Shen An (YSA) is an investigational composite of traditional Chinese medicine (Reference: 2010L000974) for the treatment of renal disease. OBJECTIVE: To investigate the protective effects of YSA against membranous glomerulonephritis (MGN). MATERIALS AND METHODS: Male Sprague-Dawley rats were injected with cationic bovine serum albumin (C-BSA) to create a model of MGN. Then, rats were orally treated with YSA at doses of 0.25, 0.5, 1 and 2 g/kg for 35 successive days; prednisone (5 mg/kg) was used as a positive control. At the end of the experimental period, we performed a series of tests, including 24 h urinary protein, and biochemical, immunological, antioxidative, coagulation indices, and histopathological examination. RESULTS: YSA-1 g/kg significantly lowered urinary protein from 68.37 to 30.74 mg (p < 0.01). Meantime, total protein (TP) and albumin (ALB) recovered from 66.26 and 20.51 g/L to 76.08 and 35.64 g/L (p < 0.01), respectively. YSA removed the deposition of immunoglobulin G (IgG) and complement 3c (C3c), prevented inter-capillary cell hyperplasia on the glomerular basement membrane (GBM), and reduced electron-dense deposits and fusion of podocytes. In addition, serum IgG and superoxide dismutase were significantly elevated. In contrast, malondialdehyde, total cholesterol, triglyceride, circulating immune complex (CIC), and immunoglobulin M decreased in the YSA-treated group. Moreover, the blood coagulation dysfunction was adjusted. DISCUSSION AND CONCLUSIONS: These findings indicate YSA may exert a therapeutic effect against MGN through the inhibition of CIC formation, and the removal of IgG and C3c deposition from the GBM, thus supporting the development of further clinical trials.
Assuntos
Complexo Antígeno-Anticorpo/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Glomerulonefrite Membranosa/tratamento farmacológico , Animais , Cátions , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/administração & dosagem , Imunoglobulina G/sangue , Masculino , Prednisona/farmacologia , Ratos , Ratos Sprague-Dawley , Soroalbumina Bovina , Superóxido Dismutase/metabolismoRESUMO
CONTEXT: Moringa oleifera Lam. (Moringaceae) (MO) is an important food plant that has high nutritional and medical value. However, there is limited information on whether its seeds can improve sleep. OBJECTIVE: This study investigated the effects of MO seed ethanol extracts (EEMOS) on sleep activity improvement and examined the underlying mechanisms. MATERIALS AND METHODS: Male ICR mice were placed into six groups (n = 12) and treated as follows: Control (sodium carboxymethyl cellulose, 20 mL/kg), estazolam tablets (2 mg/kg), EEMOS (1, 2 g/kg) and kaempferol (1, 2 mg/kg). These samples were successively given intragastric for 14 d. Locomotor activity assay, pentobarbital-induced sleeping and pentetrazol-induced seizures tests were utilized to examine the sedative-hypnotic effects (SHE) of EEMOS. RESULTS: Compared with the control group, the results revealed that EEMOS (2 g/kg) and KA (2 mg/kg) possessed good SHE and could significantly elevate the levels of γ-aminobutyric acid and reduce the levels of glutamic acid in the mouse hypothalamus (p < 0.05). Moreover, SHE was blocked by picrotoxin, flumazenil and bicuculline (p < 0.05). EEMOS (2 g/kg) and KA (2 mg/kg) significantly upregulated the protein expression levels of glutamic acid decarboxylase-65 (GAD65) and α1-subunit of GABAA receptors in the hypothalamus of mice (p < 0.05), not affecting glutamic acid decarboxylase-67 (GAD67) and γ2-subunit expression levels (p > 0.05). Additionally, they cause a significant increase in Cl- influx in human cerebellar granule cells at a concentration of 8 µg/mL (p < 0.05). DISCUSSION AND CONCLUSIONS: These findings demonstrated that EEMOS could improve sleep by regulating GABAA-ergic systems, and encourage further clinical trials to treat insomnia.
Assuntos
Moringa oleifera , Pentobarbital , Animais , Etanol/farmacologia , Glutamato Descarboxilase/metabolismo , Hipnóticos e Sedativos/farmacologia , Quempferóis/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Pentobarbital/farmacologia , Extratos Vegetais/farmacologia , Receptores de GABA-A/metabolismo , Sementes , Sono , Ácido gama-Aminobutírico/metabolismo , Ácido gama-Aminobutírico/farmacologiaRESUMO
CONTEXT: Ferulic acid ethyl ester (FAEE) is abundant in Ligusticum chuanxiong Hort. (Apiaceae) and grains, and possesses diverse biological activities; but the effects of FAEE on osteoporosis has not been reported. OBJECTIVE: This study investigated whether FAEE can attenuate osteoclastogenesis and relieve ovariectomy-induced osteoporosis via attenuating mitogen-activated protein kinase (MAPK). MATERIALS AND METHODS: We stimulated RAW 264.7 cells with receptor activator of NF-κB ligand (RANKL) followed by FAEE. The roles of FAEE in osteoclast production and osteogenic resorption of mature osteoclasts were evaluated by tartrate resistant acid phosphatase (TRAP) staining, expression of osteoclast-specific genes, proteins and MAPK. Ovariectomized (OVX) female Sprague-Dawley rats were administered FAEE (20 mg/kg/day) for 12 weeks to explore its potential in vivo, and then histology was undertaken in combination with cytokines analyses. RESULTS: FAEE suppressed RANKL-induced osteoclast formation (96 ± 0.88 vs. 15 ± 1.68) by suppressing the expression of osteoclast-specific genes, proteins and MAPK signalling pathway related proteins (p-ERK/ERK, p-JNK/JNK and p-P38/P38) in vitro. In addition, OVX rats exposed to FAEE maintained their normal calcium (Ca) (2.72 ± 0.02 vs. 2.63 ± 0.03, p < 0.05) balance, increased oestradiol levels (498.3 ± 9.43 vs. 398.7 ± 22.06, p < 0.05), simultaneously reduced levels of bone mineral density (BMD) (0.159 ± 0.0016 vs. 0.153 ± 0.0025, p < 0.05) and bone mineral content (BMC) (0.8 ± 0.0158 vs. 0.68 ± 0.0291, p < 0.01). DISCUSSION AND CONCLUSIONS: These findings suggested that FAEE could be used to ameliorate osteoporosis by the MAPK signalling pathway, suggesting that FAEE could be a potential therapeutic candidate for osteoporosis.
Assuntos
Ácidos Cafeicos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteoporose Pós-Menopausa/prevenção & controle , Animais , Densidade Óssea/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Ovariectomia , Células RAW 264.7 , Ratos , Ratos Sprague-DawleyRESUMO
Hyperectumine (1), the first C19 benzylisoquinoline alkaloid with a complicated ring system, was isolated from Hypecoum erectum and structurally characterized. Its biosynthetic origin should involve a hybrid pattern of C8 + C8 + C1 + C2, from which a C17 benzylisoquinoline alkaloid might be further attacked by a malonamic acid and undergo decarboxylation and cyclization to produce 1. Compound (-)-1 exhibited moderate anti-inflammatory activity via suppression of LPS-activated inflammatory mediators in RAW 264.7 macrophage cells.
Assuntos
Alcaloides , Benzilisoquinolinas , Alcaloides/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Benzilisoquinolinas/farmacologia , Macrófagos , Camundongos , Células RAW 264.7RESUMO
Neothalfine is a natural bisbenzylisoquinoline alkaloid with the abundant resource in medicinal plants and has not been reported its anti-tumor efficacy. In the present study, the anti-tumor efficacy was investigated and it showed broad-spectrum activity against several cancer cell lines, especially metastatic colorectal cancer (HCT116, SW620, T84) with the IC50 values of 7.2, 5.9, 8.2 nM, respectively, roughly equal to well-known anti-tumor agent docetaxel (4.0, 4.7, 2.7 nM) and nearly 1000 folds than CPT-11 (4.4, 5.1, 6.9 µM). Furthermore, neothalfine inhibited colorectal cell proliferation by resulting in cell cycle arrest at the G2/M phase and induced apoptosis through the dysfunction of mitochondria to trigger intrinsic apoptotic pathway by untargeted metabolomic method, mitochondrial membrane potential, and caspase-3/7 activity assay. Moreover, neothalfine damaged colorectal cancer clonal spheres expansion significantly at the concentration of 3.5 nM with nearly 1000 folds efficacy than CPT-11 (3.0 µM). The results supported that neothalfine might be an anti-tumor lead for further investigation.
Assuntos
Antineoplásicos/farmacologia , Produtos Biológicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Antineoplásicos/química , Produtos Biológicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/secundário , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
CONTEXT: Capsule of alkaloids from the leaf of Alstonia scholaris (L.) R.Br. (Apocynaceae) (CALAS) is a new investigational botanical drug (No. 2011L01436) for bronchitis, post-infectious cough and asthma. OBJECTIVE: To observe the clinical safety and tolerability of CALAS. MATERIALS AND METHODS: Subjects were assigned to eight cohorts, and each received randomly CALAS or placebo in one of single ascending dose (SAD) of 8, 40, 120, 240, 360, 480, or in one of multiple ascending dose (MAD) of 40 or 120 mg, three times daily for 7 days. Each cohort contained two placebo subjects. RESULTS: Sixty-two enrolled volunteers completed the study and no serious adverse events and clinically significant changes in vital signs, electrocardiography, and upper abdominal Doppler ultrasonography were observed. The ratios of treatment-emergent adverse events (TEAEs) were reported in 11/46 (23.91%) of CALAS groups and 3/16 (18.75%) of the placebo group (p > 0.05), respectively, based on the results of SAD and MAD. All TEAEs were mild, transient, and disappeared without any intervention. The TEAEs possibly related to CALAS treatment were as followings: hiccups (4/46: 8%), dry mouth and nausea (3/46: 6%), increased sleep (2/46: 4%), abdominal distension (1/46: 2%), bilirubin elevated (1/46: 2%). DISCUSSION AND CONCLUSIONS: CALAS is safe and well-tolerated with no unexpected or clinically relevant safety concerns up to a single dose of 360 mg and three times daily for 7 days up to 120 mg in healthy Chinese volunteers, supporting further Phase II studies.
Assuntos
Alcaloides/efeitos adversos , Alstonia/química , Adulto , Alcaloides/administração & dosagem , Alcaloides/isolamento & purificação , Povo Asiático , Estudos de Coortes , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Folhas de Planta , Adulto JovemRESUMO
Two new Tricholoma terpenoids, tricholopardins A and B, were isolated from the fruiting bodies of the basidiomycetes Tricholoma pardinum. Their structures were elucidated by spectroscopic methods, as well as electronic circular dichroism and optical rotatory dispersion calculations. Tricholopardin A potently inhibited nitric oxide production in lipopolysaccharide-induced RAW264.7 macrophages with an IC50 of 0.08 µM. Its anti-inflammatory effects on three inflammatory mediators were also evaluated. A plausible biosynthetic pathway for these products is discussed.
Assuntos
Anti-Inflamatórios/isolamento & purificação , Carpóforos/metabolismo , Terpenos/isolamento & purificação , Tricholoma/metabolismo , Animais , Humanos , Espectroscopia de Ressonância Magnética , Camundongos , Óxido Nítrico/biossíntese , Células RAW 264.7 , Células THP-1 , Terpenos/química , Terpenos/farmacologiaRESUMO
Unlike reported bisindoles linked by single bond directly, alstoniasidines A (1) and B (2), from Alstonia scholaris featuring unprecedented skeleton with two indole moieties bridged by a sugar, represented a novel bisindole type having strictosamide-glucopyranose-picraline scaffold. Both compounds exhibited selective cytotoxicity against human glioma stem cells (GSCs) and induced caspase-3 dependent extrinsic apoptosis by increasing the expression of interleukin 1 (IL-1), tumor necrosis factor (TNF-α), and the cleaved caspase-3, while damaged the unlimited proliferation and self-renewal capacity of GSCs. This finding might provide new type of leads for the selective killing of human glioma stem cells.
Assuntos
Alstonia/química , Antineoplásicos/farmacologia , Glioma/tratamento farmacológico , Indóis/farmacologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Açúcares/química , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Glioma/patologia , Humanos , Indóis/química , Indóis/isolamento & purificação , Estrutura Molecular , Folhas de Planta/química , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
Melodinine V (1) with a vincanol-eburenine skeleton, was isolated from Melodinus henryi. The structure was elucidated by extensive spectroscopic methods and further confirmed by the single crystal X-ray diffraction analysis. Melodinine V showed selective cytotoxic activities against human colon cancer cell line HT-29 and inhibited cell proliferation in a concentration-dependent manner. It induced cell cycle arrest at G1 phase and cellular apoptosis by increasing histone-associated DNA fragmentation in the treated HT-29 cells.
Assuntos
Antineoplásicos/farmacologia , Apocynaceae/química , Alcaloides de Triptamina e Secologanina/farmacologia , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Proliferação de Células/efeitos dos fármacos , Células HT29 , Humanos , Alcaloides de Triptamina e Secologanina/química , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria UltravioletaRESUMO
A sensitive and selective ultra high performance liquid chromatography with tandem mass spectrometry method was established and validated for the simultaneous determination of hydroxy-α-sanshool, hydroxy-ß-sanshool, and hydroxy-γ-sanshool in rat plasma after the subcutaneous and intravenous administration of an extract of the pericarp of Zanthoxylum bungeanum Maxim. Piperine was used as the internal standard. The analytes were extracted from rat plasma by liquid-liquid extraction with ethyl acetate and separated on a Thermo Hypersil GOLD C18 column (2.1 mm × 50 mm, 1.9 µm) with a gradient elution system at a flow rate of 0.4 mL/min. The mobile phase consisted of acetonitrile/0.05% formic acid in water and the total analysis time was 4 min. Positive electrospray ionization was performed using multiple reaction monitoring mode for the analytes. The calibration curves of the three analytes were linear over the tested concentration range. The intra- and interday precision was no more than 13.6%. Extraction recovery, matrix effect, and stability were satisfactory in rat plasma. The developed and validated method was suitable for the quantification of hydroxy-α-sanshool, hydroxy-ß-sanshool, and hydroxy-γ-sanshool and successfully applied to a pharmacokinetic study of these analytes after subcutaneous and intravenous administration to rats.
Assuntos
Amidas/farmacocinética , Anestésicos/farmacocinética , Zanthoxylum/química , Amidas/análise , Anestésicos/análise , Cromatografia Líquida de Alta Pressão , Extração Líquido-Líquido , Estrutura Molecular , Espectrometria de Massas em TandemRESUMO
Three new tigliane-type diterpenoids were isolated from the methanolic extract of the twigs and leaves of Croton caudatus, trivially named crotusins A-C (1-3). The structures of compounds 1-3 were elucidated on the basis of extensive spectral methods. These new compounds were highly oxygenated and heavily substituted. Cytotoxic activity against five human tumor cell lines was assessed for compounds 1-3 of which compound 3 showed significant inhibitory activity with IC50 values ranging from 0.49 to 4.19 µM against these cells, while crotusins A and B exhibited moderate activity.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Croton/química , Diterpenos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Diterpenos/química , Diterpenos/isolamento & purificação , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Folhas de Planta/químicaRESUMO
A simple, specific, and sensitive ultra high performance liquid chromatography with tandem mass spectrometry method was developed and validated for the simultaneous quantification of nine compounds including a new compound, rhamnazin-3-Ο-ß-D-(6â³-ß-hydroxy-ß-methyglutaryl)-ß-D-glucoside-4'-Ο-ß-D-glucoside, in rat plasma using baicalin as an internal standard. The plasma samples were pretreated and extracted by protein precipitation with 0.2% formic acid in acetonitrile. The analytes were separated on a Thermo Syncronis C18 column by gradient elution with a mobile phase consisting of acetonitrile and 0.1% aqueous formic acid at a flow rate of 0.25 mL/min. The detection of the analytes was performed on an electrospray ionization interface operating in positive-ion and multiple reaction monitoring acquisition modes. The calibration curves of these analytes showed good linearity (r > 0.99) within the test ranges. The lower limit of quantification ranged from 0.4 to 20.1 ng/mL for the analytes. The intra- and interday precision and accuracy were all within ±15%, and the recoveries were higher than 80.0%. The validated method was successfully applied to a pharmacokinetic study of the nine flavonoids after administration of the Viscum coloratum extracts by intravenous injection.
Assuntos
Flavonoides/sangue , Flavonoides/farmacocinética , Extratos Vegetais/química , Viscum/química , Animais , Cromatografia Líquida de Alta Pressão , Flavonoides/administração & dosagem , Flavonoides/química , Injeções Intravenosas , Masculino , Estrutura Molecular , Extratos Vegetais/administração & dosagem , Extratos Vegetais/sangue , Extratos Vegetais/farmacocinética , Ratos , Ratos Wistar , Espectrometria de Massas em TandemRESUMO
The established tradition of consuming and marketing wild mushrooms has focused attention on mycotoxicity, which has become a global issue. In the present study, we describe the toxins found in a previously unknown poisonous European mushroom Tricholoma terreum. Fifteen new triterpenoids terreolidesâ A-F (1-6) and saponaceolidesâ H-P (8-16) were isolated from the fruiting bodies of the toxic mushroom T. terreum. Terreolidesâ A-C (1-3) possessed a unique 5/6/7 trioxaspiroketal system, whereas terreolides D-F (4-6) possessed an unprecedented carbon skeleton. Two abundant compounds in the mushroom, saponaceolideâ B (7) and saponaceolideâ M (13), displayed acute toxicity, with LD50 values of 88.3 and 63.7â mg kg(-1) when administered orally in mice. Both compounds were found to increase serum creatine kinase levels in mice, indicating that T. terreum may be the cause of mushroom poisoning ultimately leading to rhabdomyolysis.
Assuntos
Tricholoma/metabolismo , Animais , Creatina Quinase/sangue , Cristalografia por Raios X , Feminino , Dose Letal Mediana , Masculino , Camundongos , Camundongos Endogâmicos ICR , Conformação Molecular , Intoxicação Alimentar por Cogumelos , Tricholoma/química , Triterpenos/química , Triterpenos/isolamento & purificação , Triterpenos/toxicidadeRESUMO
Six previously undescribed rigidly monoterpenoid indole alkaloids, alstolactines F-K (1-6), were isolated from Alstonia scholaris. Among them, a pair of cage-like epimers, 1 and 2, featuring a rare 6/5/6/6/7 ring system, represent the first example of C5âC20-olide, while compound 3 possesses unique degraded C18 and C19. The structures of the isolates were established by multiple spectroscopic analyses, quantum computational chemistry methods, and X-ray diffraction. Furthermore, the expression levels of proteins including NLRP3, TLR4, P-p65, NF-ĸB, Notch-2, IL-18, P-p38, and p38 in LPS-induced human normal hepatocyte (LO2) cells could be significantly downregulated by compounds 1-6, which showed potent anti-inflammatory bioactivity.