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1.
Org Biomol Chem ; 22(2): 296-301, 2024 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-38054263

RESUMO

Alscholarine C (1), featuring an unprecedented pyrroloindoline-containing natural product (PiNP) with a 6/5/5/5 tetracyclic carbon skeleton, and four known PiNPs (2-5), namely demethylalstoscholarinine E (2), Nb-demethylechitamine (3), winphylline A (4), and echitamine (5), were isolated from Alstonia scholaris. Compound 1 was characterized by a hexahydropyrrolo[2,3-b] indole (HPI) core fused to a unique 4-heptylimidazolidine motif, forming an unparalleled 3-heptyl-2a,4a-diazapentaleno[1,6-ab]indene ring system. Their structures were established by spectroscopic analysis, quantum-chemical calculated 13C NMR data with DP4+ probability analyses, and ECD calculations and comparison. A plausible biosynthetic pathway of 1 was proposed. Compound 1 exhibited potential anti-inflammatory activity against LPS-stimulated NO production in RAW264.7 cells.


Assuntos
Alstonia , Produtos Biológicos , Alcaloides de Triptamina e Secologanina , Estrutura Molecular , Alstonia/química , Alcaloides de Triptamina e Secologanina/química , Produtos Biológicos/farmacologia , Espectroscopia de Ressonância Magnética
2.
Org Biomol Chem ; 21(40): 8190-8196, 2023 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-37788053

RESUMO

Alscholarines A and B (1 and 2), two unprecedented rearranged monoterpene indole alkaloids, were isolated from Alstonia scholaris. Alscholarine A (1) features an imidazole ring fused with a rearranged vallesamine-type alkaloid possessing an unparalleled 6/5/6/6 tetracyclic skeleton through an unprecedented C7-C-19 connectivity. Alscholarine B (2), incorporating an unusual 7-oxa-1-azabicyclo[3.2.1]octane moiety, represents a unique rearranged vallesamine-type alkaloid with a 6/5/6/6/5 ring system via an unprecedented C-6-C-20 connectivity. Their structures were established by spectroscopic analysis, X-ray crystallography, and quantum-chemical calculations. Their plausible biosynthetic pathways were proposed. The vasorelaxant and anti-inflammatory activities of them were also evaluated. Compounds 1-3 showed moderate vasorelaxant activities.


Assuntos
Alcaloides , Alstonia , Alstonia/química , Monoterpenos/farmacologia , Alcaloides Indólicos/farmacologia , Alcaloides Indólicos/química , Vasodilatadores , Estrutura Molecular
3.
Phytother Res ; 37(1): 124-139, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36116140

RESUMO

6-Methoxydihydrosanguinarine (6-MDS) is a natural benzophenanthridine alkaloid extracted from Hylomecon japonica (Thunb.) Prantl. It is the first time to explore the effect and mechanism of 6-MDS in breast cancer. Network pharmacology, molecular docking, and molecular dynamics simulation technology were adopted to identify the potential targets and pathways of 6-MDS in breast cancer. Besides, cell proliferation, apoptosis, and western blotting assays were conducted to investigate the effect of 6-MDS on MCF-7 cells. Network pharmacology, molecular docking, and molecular dynamics simulation results confirmed the effect of 6-MDS on resisting breast cancer via the PI3K/AKT/mTOR signaling pathway. In addition, the functional experiments results demonstrated that 6-MDS inhibited proliferation and induced apoptosis and autophagy. The autophagy inhibitor chloroquine and the silence of Atg5 augmented the effect of 6-MDS on promoting apoptosis. Furthermore, 6-MDS suppressed the PI3K/AKT/mTOR signaling pathway, and the PI3K inhibitor LY294002 enhanced these changes and promoted the 6-MDS pro-apoptotic and autophagy effects. 6-MDS triggered the generation of reactive oxygen species. The pretreatment with antioxidant N-acetyl-L-cysteine reversed the changes induced by 6-MDS, including increases in apoptosis and autophagy and inhibition of the PI3K/AKT/mTOR pathway. In conclusion, 6-MDS induces the apoptosis and autophagy of MCF-7 cells by ROS accumulation to suppress the PI3K/AKT/mTOR signaling pathway.


Assuntos
Neoplasias da Mama , Proteínas Proto-Oncogênicas c-akt , Humanos , Feminino , Benzofenantridinas/farmacologia , Benzofenantridinas/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Células MCF-7 , Neoplasias da Mama/tratamento farmacológico , Simulação de Acoplamento Molecular , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Apoptose , Autofagia
4.
Chem Biodivers ; 20(6): e202201197, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37073748

RESUMO

Four undescribed biflavonoid alkaloids, sinenbiflavones A-D, were isolated from Cephalotaxus sinensis using a MS/MS-based molecular networking guided strategy. Their structures were elucidated by series of spectroscopic methods (HR-ESI-MS, UV, IR, 1D, and 2D NMR). Sinenbiflavones A-D are the first examples of amentoflavone-type (C-3'-C-8'') biflavonoid alkaloids. Meanwhile, sinenbiflavones B and D are the unique C-6-methylated amentoflavone-type biflavonoid alkaloids. Sinenbiflavone D showed weak SARS-CoV-2 3CLpro inhibitory activity with 43 % inhibition rate at 40 µM.


Assuntos
Alcaloides , Biflavonoides , COVID-19 , Cephalotaxus , Biflavonoides/química , Estrutura Molecular , Cephalotaxus/química , Espectrometria de Massas em Tandem , SARS-CoV-2 , Alcaloides/química , Espectroscopia de Ressonância Magnética
5.
Org Biomol Chem ; 21(1): 169-178, 2022 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-36472149

RESUMO

Twelve new Cephalotaxus alkaloids (1-12) and nine known analogues (13-21) were isolated and identified from the twigs and leaves of Cephalotaxus sinensis. The structures of the new compounds (1-12) were elucidated by extensive spectroscopic analysis and single-crystal X-ray diffraction analysis. Cephalosine H (8) is the third example of an alkaloid containing the cephalolancine skeleton. Cephalosines J and K (10 and 11) are the rare natural Δ(2)1-alkene-6-hydroxyl homoerythrina-type alkaloids isolated from the Cephalotaxus genus. The racemization of cephalotaxine-type alkaloids is discussed. Alkaloids 6, 7, 11, 16, 18 and 19 exhibited broad and potent cytotoxicities against five human cancer cell lines, with IC50 values ranging from 0.053 to 10.720 µM, highlighting these compounds as promising leads for the development of new antitumor agents.


Assuntos
Alcaloides , Antineoplásicos Fitogênicos , Antineoplásicos , Cephalotaxus , Humanos , Cephalotaxus/química , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Alcaloides/farmacologia , Alcaloides/química , Antineoplásicos/análise , Folhas de Planta/química , Estrutura Molecular
6.
Biosci Biotechnol Biochem ; 86(10): 1343-1348, 2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-35973685

RESUMO

One new compound and 13 known compounds were isolated from Aspergillus niger, a plant endophytic fungus of Pachysandra terminalis collected from Qinling Mountains, Xi'an, China. The structure of new compound 1 was classically determined by extensive spectroscopic analysis. Compounds 5, 6, 8, and 14 were first reported from Aspergillus, while compound 2 was isolated from A. niger for the first time. All isolated compounds were further evaluated for their antioxidant and α-glucosidase inhibitory activities. Compounds 2 and 3 exhibited significant antioxidant activities with IC50 values of 31.64 µm and 24.32 µm, respectively, similar to the positive control ascorbic acid. Additionally, compound 1 displayed remarkable inhibitory activity against α-glucosidase with an IC50 value of 96.25 µm, which was 3.4-fold more potent than that of the positive control acarbose. Compound 1 has great potential for development as a new lead compound owing to its simple structure and remarkable biological activity.


Assuntos
Pachysandra , alfa-Glucosidases , Acarbose , Antioxidantes/farmacologia , Ácido Ascórbico , Aspergillus , Aspergillus niger/metabolismo , Fungos/metabolismo , Estrutura Molecular , Pachysandra/metabolismo , alfa-Glucosidases/metabolismo
7.
Anticancer Drugs ; 32(3): 306-313, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33038083

RESUMO

Breast cancer is one of the most common cancers endangering women's health. SRY-related high-mobility-group box 6 (SOX6) is associated with many cancers, though its role has not been reported in breast cancer. Here, we aimed to explore the expression and function of SOX6 in breast cancer. On the basis of the analysis of SOX6 in The Cancer Genome Atlas, Cancer Cell Line Encyclopedia and Genotype-Tissue Expression databases, we revealed that SOX6 was downregulated in breast cancer, and we verified the results at the cellular level by means of western blotting and quantitative real-time PCR. When SOX6 was overexpressed, the proliferation of breast cancer cells was inhibited, and apoptosis was promoted. Moreover, the methylation level of the SOX6 promoter in breast cancer was significantly higher than that in normal tissues. 5'-Aza-2'-deoxycytidine reversed the high level of methylation that was caused by decreased expression of SOX6. This evidence suggests that SOX6 is a tumor suppressor gene associated with breast cancer. This study could provide a new target for breast cancer treatment.


Assuntos
Neoplasias da Mama/patologia , Fatores de Transcrição SOXD/metabolismo , Apoptose , Proliferação de Células , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Plasmídeos
8.
Phytother Res ; 35(5): 2336-2385, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33617115

RESUMO

Nature gifts medicinal plants with the untapped and boundless treasure of active chemical constituents with significant therapeutic potential that makes these plants a beneficial source in the development of phytomedicines. Genus Cassia, with approximately 500 species, is a large group of flowering plants in the family Fabaceae. Cassia species are widely distributed throughout different regions mainly tropical Asia, North America, and East Africa. In the folk medicinal history, these plants are used as laxative and purgative agents. In the Ayurveda system of medicine, they are used to cure headache and fever. Cassia plants exhibit pharmacological activities at large scales such as antimicrobial, anticancer, antiinflammatory, antioxidant, hypoglycemic, hyperglycemic, antimutagenic, and antivirals. The phytochemical investigations of genus Cassia demonstrate the presence of more than 200 chemical compounds, including piperidine alkaloids, anthracene derivatives (anthraquinones), flavonoids, pentacyclic triterpenoids, sterols, phenylpropanoids, and γ-naphthopyrones. The literature illustrated anthraquinones and flavonoids as major secondary metabolites from this genus. However, some Cassia plants, with rich contents of anthraquinones, still show toxicology properties. As Cassia plants are used extensively in the herbal system of medicine, but only senna dosage forms have achieved the status of the pharmaceutical market as standard laxative agents. In conclusion, further investigations on isolating newer biologically active constituents, unknown underlying mechanisms, toxicology profiles, and clinical studies of Cassia species are needed to be explored. This review article specifies the systematic breach existing between the current scientific knowledge and the fundamentals for the marketization of genus Cassia products.

9.
J Proteome Res ; 19(3): 1154-1168, 2020 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-31940440

RESUMO

Diosgenin (DIO), the starting material for the synthesis of steroidal anti-inflammatory drugs in the pharmaceutical industry, has been previously demonstrated to display pharmaceutical effects against cerebral ischemic reperfusion (I/R). However, the alterations of brain proteome profiles underlying this treatment remain elusive. In the present study, the proteomics analysis of the brain tissues from I/R rats after DIO treatment was performed using an integrated TMT-based quantitative proteomic approach coupled with the liquid chromatography with tandem mass spectrometry technology. A total of 5043 proteins (ProteomeXchange identifier: PXD016303) were identified, of which 58 common differentially expressed proteins were significantly dysregulated in comparison between sham versus I/R and I/R versus DIO. The eight validated proteins including EPG5, STAT2, CPT1A, EIF2AK2, GGCT, HIKESHI, TNFAIP8, and EMC6 by quantitative polymerase chain reaction and western blotting consistently supported the TMT-based proteomic results, which were mainly associated with autophagy and inflammation response. Considering the anti-inflammatory characters of DIO, the biological functions of STAT2 and HIKESHI that are the probable direct anti-inflammatory targets were further investigated during the course of I/R treated with DIO. In addition, the combination of verified STAT2 and HIKESHI in peripheral blood samples from stroke patients resulted in the area under the curve value of 0.765 with P < 0.004 to distinguish stroke patients from healthy controls. Taken together, the current findings first mapped comprehensive proteomic changes after I/R was treated with DIO to better decipher the molecular mechanisms mainly based on the anti-inflammatory aspect underlying this therapeutic effect, providing a foundation for developing potentially therapeutic targets of anti-I/R of DIO and clinically prognostic biomarkers of stroke.


Assuntos
Isquemia Encefálica , Diosgenina , Traumatismo por Reperfusão , Animais , Encéfalo , Isquemia Encefálica/tratamento farmacológico , Proteínas de Transporte , Diosgenina/farmacologia , Humanos , Proteínas de Membrana , Proteômica , Ratos , Reperfusão , Traumatismo por Reperfusão/tratamento farmacológico
10.
Bioorg Chem ; 102: 104136, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32738570

RESUMO

Seventeen monoterpene indole alkaloids, including seven new alkaloids (1-7) and ten known analogues (8-17), were isolated and identified from the leaves of R. vomitoria. The structures of new alkaloids were elucidated by extensive spectroscopic analysis and single-crystal X-ray diffraction analysis. Rauvomitorine I (1) represents the first example of an unprecedented C22 yohimbine-type monoterpene indole alkaloid featuring a carboxymethyl at C-14. The exceedingly rare vobasenal (2-3) and affinisine oxindole (5-6) framework type alkaloids are first reported from the Rauvolfia genus. Most notably, the structure of vobasenal-type alkaloids (2-3) were first determined by single-crystal X-ray diffraction analyses. Alkaloids 1-17 were tested their cytotoxicity against five cancer cell lines, however, none of them showed significant cytotoxicity at a concentration of 40 µM. All the isolated alkaloids were evaluated their acetylcholinesterase (AChE) inhibitory activities. Alkaloid 3 exhibited significant anti-AChE activity with an IC50 value of 16.39 ± 1.41 µM and alkaloids 8 and 10 showed moderate anti-AChE activities whereas the others (2, 9, 13, and 17) were weak inhibitors. This is the first report of vobasenal-type alkaloids as AChE inhibitors, indicating this type of alkaloids may be important sources for the discovery of new AChE inhibitors. A preliminary structure-activity relationship for AChE inhibitory activities showed the presence of the N-methyl group in vobasenal-type alkaloids may be essential for anti-AChE activity. Further molecular docking studies of vobasenal-type alkaloids revealed that interaction with Trp133 and Trp86 residues at hydrophobic subsite are necessary for the AChE inhibitory activities. This study not only enriches the chemical diversity of alkaloids in Apocynaceae plants but also provides new potential leading compounds and versatile scaffolds for the design and development of new AChE inhibitors to treat AD.


Assuntos
Inibidores da Colinesterase/farmacologia , Alcaloides Indólicos/farmacologia , Rauwolfia/química , Acetilcolinesterase/metabolismo , Linhagem Celular Tumoral , Inibidores da Colinesterase/química , Inibidores da Colinesterase/isolamento & purificação , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Humanos , Alcaloides Indólicos/química , Alcaloides Indólicos/isolamento & purificação , Conformação Molecular , Simulação de Acoplamento Molecular , Folhas de Planta/química , Estereoisomerismo , Relação Estrutura-Atividade
11.
Chem Biodivers ; 17(12): e2000647, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33044757

RESUMO

Two new yohimbine-type monoterpene indole alkaloids, rauvines A and B, and six known derivatives were obtained from the leaves of R. vomitoria. The structures of rauvines A and B were determined by extensive spectroscopic analyses, 13 C-NMR, and ECD calculations. This is the first time to determine the absolute configurations of yohimbine-type N-oxides by quantum chemistry calculations (13 C-NMR and ECD calculations). All the isolates were tested for their cytotoxicity against five human cancer cell lines. Rauvine B showed moderate cytotoxicity on human MCF-7 breast, SWS80 colon, and A549 lung cancer cell lines with IC50 values of 25.5, 22.6, and 26.0 µM, respectively.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Alcaloides Indólicos/química , Folhas de Planta/química , Rauwolfia/química , Ioimbina/química , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Linhagem Celular Tumoral , Humanos
12.
Regul Toxicol Pharmacol ; 91: 58-67, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29066336

RESUMO

Sub-acute and chronic toxic effects of total steroidal saponins (TSSN) extracts from Dioscorea zingiberensis C.H. Wright on various internal organs and biochemical indicators have never been studied before and this study is the first of its kind to demonstrate sub-acute and chronic toxicities of TSSN on dogs. Administration of TSSN extracts at doses up to 3000 mg/Kg daily for 14 days, no biochemical and organ changes were observed on the experimental groups of dogs. Further, chronic toxicity study through oral administration of TSSN extracts at the gradual doses of 50, 250 and 500 mg/Kg for 90 days followed by a 2-week recovery assay revealed absence of significant architectural and morphological changes in internal organs which were confirmed through histopathological examination and merely no significant alteration in the biochemical indicators including hematologic and urine analysis and electrocardiogram compared to the control dogs. This toxicological evaluation came across with the finding that the herbal preparation can be considered as nontoxic and animals could tolerate the extracts at doses up to 500 mg/Kg with LD50 greater than 3000 mg/Kg. It may serve as a preliminary scientific evidence for further therapeutic investigations.


Assuntos
Dioscorea/efeitos adversos , Saponinas/efeitos adversos , Esteroides/efeitos adversos , Animais , Cães , Extratos Vegetais/efeitos adversos , Preparações de Plantas/efeitos adversos
13.
Anal Bioanal Chem ; 407(25): 7681-90, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26297456

RESUMO

A novel surface imprinting polymer based on magnetic carbon nanotubes was prepared using dendritic polyethyleneimine as functional monomer to amplify the number of imprinted cavities. The characteristics of resulting polymers were evaluated by transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), and vibrating sample magnetometer (VSM). Results suggest that magnetic nanoparticles are deposited onto the surface of multiwalled carbon nanotubes and the imprinted shell is coated on the surface of magnetic carbon nanotubes with a thickness of approximately 8 nm. Magnetic imprinted polymers are sensitive to magnetic fields and can be easily separated within 3 s using an external magnet. The adsorption results indicate that the obtained imprinted polymers have fast kinetics, an ultrahigh adsorption capacity of 479.9 mg g(-1), and satisfactory selectivity towards the template molecule. The prepared materials have excellent stability with no obvious deterioration after six adsorption-regeneration cycles. In addition, a method for determination of gallic acid (GA) in pomegranate rind was developed, using a combination of the prepared polymers used as solid-phase extraction (SPE) sorbents and high-performance liquid chromatography (HPLC) for rapid isolation and determination of GA. The limit of detection of the proposed method is 0.001 µg mL(-1), and the intra and inter-day relative standard deviations (RSDs) are lower than 3.8% and 5.3%, respectively. The recoveries of GA from pomegranate rind extract are in the range 98.2-103.6% with RSDs lower than 4.3%.


Assuntos
Ácido Gálico/isolamento & purificação , Lythraceae/química , Imãs/química , Impressão Molecular/métodos , Nanotubos de Carbono/química , Polietilenoimina/química , Extração em Fase Sólida/métodos , Adsorção , Cromatografia Líquida de Alta Pressão/métodos
14.
J BUON ; 19(3): 705-12, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25261656

RESUMO

PURPOSE: To investigate whether taipeinine A (JNQ2), a C19-diterpenoid alkaloid prepared from the roots of Aconitum taipeicum, has anticancer effects on hepatocellular carcinoma (HCC) and to study its probable anticancer mechanisms. METHODS: JNQ2 activities were assessed on human HCC cell line (HepG2) by proliferative assay, cell cycle arrest assay, apoptosis analysis, cell invasion assay and Western blot analysis. RESULTS: The antitumor activity tests showed that JNQ2 inhibited the proliferation of HepG2 cells in a dose- and time-dependent manner and blocked the cell cycle at the G1/S phase. High dosage of JNQ2 induced significant apoptosis of tumor cells. The invasiveness of HepG2 cells was also inhibited by JNQ2. The mechanism of JNQ2 antitumor effect at the molecular level was presumed to be the upregulation of the protein expression of Bax and Caspase-3 and the downregulation of the protein expression of Bcl-2 and CCND1. CONCLUSION: Our study suggests that JNQ2 has anticancer effects on HepG2 cells and it is a potential reagent for the treatment of HCC that merits further investigation.


Assuntos
Aconitina/análogos & derivados , Aconitum/química , Antineoplásicos/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Aconitina/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologia , Invasividade Neoplásica
15.
Phytochemistry ; 209: 113610, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36791874

RESUMO

Seven undescribed monoterpene indole alkaloids alstoscholarinines A‒G, along with nineteen known alkaloids, were isolated from the branches of Alstonia scholaris (L.) R. Br. The isolated alkaloids were classified into ten framework types. The structures of the undescribed alkaloids were elucidated by extensive spectroscopic analysis, ECD calculation, and single-crystal X-ray diffraction analysis. Alstoscholarinine A is an unreported and unusual monoterpene indole alkaloid incorporating three nitrogen atoms, characterized by a compact 6/5/6/6/6/5 hexacyclic system bearing a piperidine ring and a unique oxazolidine ring. Alstoscholarinine B represents the first naturally C-17 nor-isositsirikine-type alkaloid. Plausible biosynthetic pathways of alstoscholarinines A and B were proposed. All isolates were evaluated for their vasorelaxant activities against phenylephrine-induced contraction of rat mesenteric arteries. Among them, seven alkaloids showed significant vasorelaxant activities with EC50 values less than 10 µM. Importantly, the akuammicine-type alkaloids in this study showed much better vasorelaxant activities than other framework type alkaloids, indicating that this type of alkaloid may be a valuable source for the discovery of vasodilators. A preliminary structure-activity relationship for vasorelaxant activities of the isolated akuammicine-type alkaloids is also discussed.


Assuntos
Alcaloides , Alstonia , Ratos , Animais , Alstonia/química , Monoterpenos , Vasodilatadores/farmacologia , Estrutura Molecular , Alcaloides Indólicos/farmacologia , Alcaloides Indólicos/química , Alcaloides/farmacologia
16.
Metabolites ; 13(7)2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37512501

RESUMO

In folklore medicine, Conocarpus lancifolius is used to treat various illnesses. The main objective of this study was a comprehensive investigation of Conocarpus lancifolius leaf aqueous extract (CLAE) for its antioxidant, cardioprotective, anxiolytic, antidepressant and memory-enhancing capabilities by using different in vitro, in vivo and in silico models. The in vitro experimentation revealed that CLAE consumed an ample amount of total phenolics (67.70 ± 0.15 µg GAE/mg) and flavonoids (47.54 ± 0.45 µg QE/mg) with stronger antiradical effects through DPPH (IC50 = 16.66 ± 0.42 µg/mL), TAC (77.33 ± 0.41 µg AAE/mg) and TRP (79.11 ± 0.67 µg GAE/mg) assays. The extract also displayed suitable acetylcholinesterase (AChE) inhibitory (IC50 = 110.13 ± 1.71 µg/mL) activity through a modified Ellman's method. The toxicology examination presented no mortality or any signs of clinical toxicity in both single-dose and repeated-dose tests. In line with the cardioprotective study, the pretreatment of CLAE was found to be effective in relieving the isoproterenol (ISO)-induced myocardial injury in rats by normalizing the heart weight index, serum cardiac biomarkers, lipid profile and various histopathological variations. In the noise-stress-induced model for behavior attributes, the results demonstrated that CLAE has the tendency to increase the time spent in the central zone and elevated open arms in the open field and elevated plus maze tests (examined for anxiety assessment), reduced periods of immobility in the forced swimming test (for depression) and improved recognition and working memory in the novel object recognition and Morris water maze tests, respectively. Moreover, the LC-ESI-MS/MS profiling predicted 53 phytocompounds in CLAE. The drug-likeness and ADMET analysis exhibited that the majority of the identified compounds have reasonable physicochemical and pharmacokinetic profiles. The co-expression of molecular docking and network analysis indicated that top-ranked CLAE phytoconstituents act efficiently against the key proteins and target multiple signaling pathways to exert its cardiovascular-protectant, anxiolytic, antidepressant and memory-enhancing activity. Hence, this artifact illustrates that the observed biological properties of CLAE elucidate its significance as a sustainable source of bioactive phytochemicals, which appears to be advantageous for pursuing further studies for the development of new therapeutic agents of desired interest.

17.
Steroids ; 192: 109181, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36642106

RESUMO

Diosgenin was the starting materials to synthesize various hormone drugs and mainly generated from Dioscorea zingiberensis C. H. Wright by acidolysis, enzymolysis, microbiological fermentation, and integrated manner. Only acidic hydrolysis with strong acid such as hydrochloric acid or sulfuric acid was used in practice in diosgenin enterprises due to their feasibility and simplicity, nevertheless finally resulting in a great deal of unmanageable wastewater and severely polluted the surrounding environment. Aiming to provide a comprehensive and up-to date information of researches on diosgenin production from this plant, 151 cases were collected from scientific databases including Web of Science, Pubmed, Science Direct, Wiley, Springer, and China Knowledge Resource Integrated (CNKI). Their advantages and disadvantages with different production methods were analyzed based on these available data in this review paper. Considering the fact that nearly all of diosgenin enterprises were closed for the environmental protection and the life health of the people, this review paper was beneficial for providing useful guidelines to develop novel technologies with environmentally-friendly and cleaner features for diosgenin production or facilitate the transformation of other methods like enzymolysis, microbiological fermentation, or integrated methods from laboratory scale to industry scale.


Assuntos
Dioscorea , Diosgenina , Saponinas , Humanos , Conservação dos Recursos Naturais , Fermentação
18.
Biochem Pharmacol ; 213: 115617, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37211174

RESUMO

Fusion with host cell membrane is the main mechanism of infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we propose that a new strategy to screen small-molecule antagonists blocking SARS-CoV-2 membrane fusion. Using cell membrane chromatography (CMC), we found that harringtonine (HT) simultaneously targeted SARS-CoV-2 S protein and host cell surface TMPRSS2 expressed by the host cell, and subsequently confirmed that HT can inhibit membrane fusion. HT effectively blocked SARS-CoV-2 original strain entry with the IC50 of 0.217 µM, while the IC50 in delta variant decreased to 0.101 µM, the IC50 in Omicron BA.1 variant was 0.042 µM. Due to high transmissibility and immune escape, Omicron subvariant BA.5 has become the dominant strain of the SARS-CoV-2 virus and led to escalating COVID-19 cases, however, against BA.5, HT showed a surprising effectiveness. The IC50 in Omicron BA.5 was even lower than 0.0019 µM. The above results revealed the effect of HT on Omicron is very significant. In summary, we characterize HT as a small-molecule antagonist by direct targeting on the Spike protein and TMPRSS2.


Assuntos
COVID-19 , Harringtoninas , Humanos , SARS-CoV-2
19.
Molecules ; 17(1): 843-50, 2012 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-22252500

RESUMO

An ethyl acetate extract of the roots of Rumex dentatus L. was investigated. Three compounds were identified by their spectroscopic data as chrysophanol (1), 6-methyl-7-acetyl-1, 8-dihydroxy-3-methoxy naphthalene-1-O-ß-D(L)-glucoside (2) and 6-methyl-7-acetyl-1, 8-dihydroxy naphthalene-1-O-ß-D(L)-glucoside (3) were found in the plant for the first time. Compounds 2 and 3 are novel compounds. Their antiproliferation activities were tested by the MTT assay in four cell lines (breast cancer MCF-7, gastric cancer 7901, melanoma A375 and oophoroma SKOV-3).


Assuntos
Antraquinonas/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Glucosídeos/isolamento & purificação , Naftalenos/isolamento & purificação , Raízes de Plantas/química , Rumex/química , Antraquinonas/química , Antraquinonas/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Glucosídeos/química , Glucosídeos/farmacologia , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Naftalenos/química , Naftalenos/farmacologia , Temperatura de Transição
20.
Zhong Yao Cai ; 35(5): 726-8, 2012 May.
Artigo em Zh | MEDLINE | ID: mdl-23213736

RESUMO

OBJECTIVE: To analyze the chemical constituents of petroleum fraction of Aconitum taipeicum. METHODS: The methanol extract of Aconitum taipeicum were extracted by petroleum and then analyzed by GC-MS. The compounds were quantitatively determined by normalization method. RESULTS: Twenty eight compounds were separated and identified. Most of them were alkane, fat acids and their esters and alkenes. The Nonacosane covered 13.057% of the total peaks, while 19-methyl-18,21-Hexatriacontanediether 8.180%, Ethylen eglycol monooctadecy ether 7.851%, 3,7,11,15-Tetramethyl-2-hexadecen-1-ol 7.805%, Metahyl Palmitate 6.676% and so on. CONCLUSION: This is the first report of constituents from the flower, stem and leaf of Aconitum taipeicum. The results will provide foundation for further exploitation and use of Aconitum taipeicum.


Assuntos
Aconitum/química , Alcanos/isolamento & purificação , Ácidos Graxos/isolamento & purificação , Componentes Aéreos da Planta/química , Plantas Medicinais/química , Alcanos/química , Ésteres/química , Ésteres/isolamento & purificação , Ácidos Graxos/química , Álcoois Graxos/química , Álcoois Graxos/isolamento & purificação , Cromatografia Gasosa-Espectrometria de Massas , Estrutura Molecular , Terpenos/química , Terpenos/isolamento & purificação
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