Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 649
Filtrar
1.
J Agric Food Chem ; 69(36): 10527-10535, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34469148

RESUMO

In the search for new natural resources showing plant disease control effects, we found that the methanol extract of Polyalthia longifolia suppressed fungal disease development in plants. To identify the bioactive substances, the methanol extract of P. longifolia was extracted by organic solvents, and consequently, four new 2-oxo-clerodane diterpenes (1-4), a new 4(3 → 2)-abeo-clerodane diterpene (5), together with ten known compounds (6-16) were isolated and identified from the extracts. Of the new compounds, compound 2 showed a broad spectrum of antifungal activity with moderated minimum inhibitory concentration (MIC) values in a range of 50-100 µg/mL against tested fungal pathogens. Considering with the known compounds, compound 6 showed the most potent antifungal activity with an MIC value in the range of 6.3-12.5 µg/mL. When compound 6 was evaluated for an in vivo antifungal activity against rice blast, tomato late blight, and pepper anthracnose, compound 6 reduced the plant disease by at least 60% compared to the untreated control at concentrations of 250 and 500 µg/mL. Together, our results suggested that the methanol extract of twigs and leaves of P. longifolia and its major compound 6 could be used as a source for the development of eco-friendly plant protection agents.


Assuntos
Diterpenos Clerodânicos , Polyalthia , Antifúngicos/farmacologia , Diterpenos Clerodânicos/farmacologia , Testes de Sensibilidade Microbiana , Extratos Vegetais/farmacologia , Folhas de Planta
2.
Chem Biodivers ; 18(9): e2100517, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34292661

RESUMO

A new neo-clerodane diterpenoid, salvihispin H (1), and six known ones (2-7) were identified from the aerial parts of Salvia hispanica L. The structure and absolute configuration of 1 were elucidated by extensive analysis of spectroscopic (1 H, 13 C, and 2D NMR, and HR-ESI-MS) and single-crystal X-ray diffraction data. The anti-diabetic effects of salvihispin H (1) and salvifaricin (2) were evaluated in diabetic db/db mice. The data showed that 1 and 2 could significantly reduce fasting blood glucose level and improve insulin resistance, and compound 1 exerted glucose-lowering effect more quickly than metformin. In addition, 1 and 2 could also reduce serum TG level in db/db mice. These results demonstrated that compounds 1 and 2 could be considered as potent candidates for the therapy of type 2 diabetes mellitus (T2DM).


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diterpenos Clerodânicos/farmacologia , Hipoglicemiantes/farmacologia , Componentes Aéreos da Planta/química , Salvia/química , Animais , Glicemia/efeitos dos fármacos , Cristalografia por Raios X , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Modelos Animais de Doenças , Diterpenos Clerodânicos/química , Hipoglicemiantes/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Moleculares , Estrutura Molecular
3.
Fitoterapia ; 153: 104979, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34182053

RESUMO

Phytochemical investigation of the leaves and twigs of Croton yanhuii led to the isolation of seven highly modified nor-clerodane diterpenoids (1-7), including three new ones, croyanoids A-C (1-3), along with four known analogues (4-7). Compound 1 incorporates a 5,12-epoxy ring, forming a unique cage-like, 6/6/6/5-fused tetracyclic ring system. Their structures were established by extensive spectroscopic analysis, and the absolute configurations of 1-4 were determined by a combination of circular dichroism (CD) analysis and single-crystal X-ray diffraction. All compounds were tested in an array of bioassays, but were inactive. Crotoeurin A (7), a nor-clerodane dimer with a high yield of 0.2‰ isolated in current study, was considered as a chemotaxonomic marker for this species.


Assuntos
Croton/química , Diterpenos Clerodânicos/química , Células 3T3-L1 , Células A549 , Animais , China , Diterpenos Clerodânicos/isolamento & purificação , Humanos , Camundongos , Estrutura Molecular , Óxido Nítrico , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Folhas de Planta/química , Células RAW 264.7
4.
Biomolecules ; 11(5)2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-34063021

RESUMO

Dietary supplements based on Teucrium chamaedrys L. subsp. chamaedrys aerial parts were banned, due to the hepatotoxicity of furan-containing neo-clerodane constituents. Indeed, the plant leaf content in phenolic compounds could be further exploited for their antioxidant capability. Accordingly, bio-guided fractionation strategies have been applied, obtaining seven partially purified extracts. These latter were chemically investigated through 1D and 2D NMR techniques and tested for their antiradical, reducing and cytotoxic capability. Data acquired highlighted that, through a simple phytochemical approach, a progressive neo-clerodane depletion occurred, while maximizing phenylethanoid glycosides in alcoholic fractions. Thus, although the plant cannot be used as a botanical remedy as such, it is suggested as a source of healthy compounds, pure or in mixture, to be handled in pharmaceutical, nutraceutical and/or cosmeceutical sectors.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Glicosídeos/isolamento & purificação , Metabolômica/métodos , Fenóis/isolamento & purificação , Teucrium/química , Células A549 , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Fracionamento Químico , Diterpenos Clerodânicos/isolamento & purificação , Diterpenos Clerodânicos/toxicidade , Glicosídeos/química , Glicosídeos/farmacologia , Células HeLa , Células Hep G2 , Humanos , Espectroscopia de Ressonância Magnética , Fenóis/química , Fenóis/farmacologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Folhas de Planta/química
5.
Org Lett ; 23(15): 5647-5651, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34170713

RESUMO

Scospirosins A (1) and B (2), two unprecedented spiro ent-clerodane dimers with 6/6/10/6 and 6/6/6/6/6 ring systems, respectively, were isolated from Isodon scoparius. Their structures were unambiguously established by spectroscopic, X-ray crystallographic, and chemical approaches. A bioinspired protecting-group-free strategy for their synthesis was achieved on a gram scale and featured the application of green methods, including neat reaction, sensitized photooxygenation, and electrochemical oxidation. 2 exhibited selective immunosuppressive activity against the proliferation of T lymphocytes (IC50 = 1.42 µM).


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Diterpenos Clerodânicos/síntese química , Diterpenos Clerodânicos/farmacologia , Imunossupressores/farmacologia , Isodon/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Biomimética , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Diterpenos Clerodânicos/análise , Imunossupressores/química , Imunossupressores/isolamento & purificação , Concentração Inibidora 50 , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Linfócitos T/efeitos dos fármacos
6.
PLoS One ; 16(6): e0253572, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34191831

RESUMO

In the present study, in silico predictions and molecular docking were performed on five clerodane diterpenes (1-5) from Polyalthia longifolia seeds to evaluate their potential as xanthine oxidase (XO) inhibitors. The initial screening was conducted by target prediction using TargetNet web server application and only compounds 3 and 4 showed a potential interaction with XO. Compounds 3 and 4 were subsequently subjected to in silico analyses on XO protein structure (PDB: 1N5X) using Schrödinger Release 2020-3 followed by structural modeling & molecular simulation studies to confirm the initial prediction result and identify the binding mode of these compounds to the XO. Molecular docking results revealed that compounds 3 (-37.3 kcal/mol) and 4 (-32.0 kcal/mol) binds more stably to XO than the reference drug allopurinol (-27.0 kcal/mol). Interestingly, two residues Glu 802 and Thr 1010 were observed as the two main H-bond binding sites for both tested compounds and the allopurinol. The center scaffold of allopurinol was positioned by some π-π stacking with Phe 914 and Phe 1009, while that of compounds 3 and 4 were supported by many hydrophobic interactions mainly with Leu 648, Phe 649, Phe 1013, and Leu 1014. Additionally, the docking simulation predicted that the inhibitory effect of compounds 3 and 4 was mediated by creating H-bond with particularly Glu 802, which is a key amino acid for XO enzyme inhibition. Altogether, in vitro studies showed that compounds 3 and 4 had better inhibitory capacity against XO enzyme with IC50 values significantly (p < 0.001) lower than that of allopurinol. In short, the present study identified cleroda-4(18),13-dien-15,16-olide as novel potential XO inhibitors, which can be potentially used for the treatment of gout.


Assuntos
Diterpenos Clerodânicos/farmacologia , Extratos Vegetais/farmacologia , Polyalthia/química , Xantina Oxidase/antagonistas & inibidores , Diterpenos Clerodânicos/química , Diterpenos Clerodânicos/isolamento & purificação , Ensaios Enzimáticos , Gota/tratamento farmacológico , Gota/metabolismo , Humanos , Simulação de Acoplamento Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Sementes/química , Ácido Úrico/metabolismo , Xantina Oxidase/química , Xantina Oxidase/metabolismo
7.
Bioorg Chem ; 112: 104916, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33957537

RESUMO

Three unprecedented dimeric clerodane diterpenoids, dodovisdimers A-C (1-3), along with six known clerodane monomers (4-9), were isolated from Dodonaea viscosa. Compounds 1-3 may be biosynthetically formed via an intermolecular Diels-Alder [4+2] cycloaddition between the coexisting monomers 4-7. The structures of these clerodanes were characterized by spectroscopic techniques, X-ray crystallographic study, and ECD calculations. Some isolates exerted antiviral effects on human influenza A virus (H3N2) in vitro.


Assuntos
Antivirais/farmacologia , Diterpenos Clerodânicos/farmacologia , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Sapindaceae/química , Antivirais/química , Antivirais/isolamento & purificação , Cristalografia por Raios X , Diterpenos Clerodânicos/química , Diterpenos Clerodânicos/isolamento & purificação , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Relação Estrutura-Atividade
8.
Fitoterapia ; 152: 104912, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33933538

RESUMO

The first phytochemical investigation from the stems of Croton krabas resulted in the isolation of three new ent-clerodane diterpenoids, crotonkrabases A-C (1-3), along with two known compounds, 12-oxohardwickiic acid (4) and crotonpyrone B (5). Their structures were elucidated using extensive spectroscopic methods. The structure of 3 was unambiguously proven by X-ray crystallography. Furthermore, the absolute configurations of compounds 1-3 were identified by NOESY and the comparison of their experimental ECD spectra with those of calculated ECD spectra reported in the literature. Compounds 1, 2, and 5 showed antibacterial activities against two Gram-positive bacteria (Bacillus cereus and Bacillus subtilis); whereas compound 4 exhibited weak antibacterial against B. cereus. In addition, compound 4 showed potent α-glucosidase inhibitory activity, which was lower than the reference standard acarbose.


Assuntos
Antibacterianos/farmacologia , Croton/química , Diterpenos Clerodânicos/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Antibacterianos/isolamento & purificação , Bacillus/efeitos dos fármacos , Diterpenos Clerodânicos/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Caules de Planta/química , Tailândia
9.
J Nanosci Nanotechnol ; 21(11): 5399-5407, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-33980349

RESUMO

For the development of drugs that treat SARS-CoV-2, the fastest way is to find potential molecules from drugs already on the market. Unfortunately, there is currently no specific drug or treatment for COVID-19. Among all structural proteins in SARS-CoV, the spike protein is the main antigenic component responsible for inducing host immune responses, neutralizing antibodies, and/or protecting immunity against virus infection. Molecular docking is a technique used to predict whether a molecule will bind to another. It is usually a protein to another or a protein to a binding compound. Natural products are potential binders in several studies involving coronavirus. The structure of the ligand plays a fundamental role in its biological properties. The nuclear magnetic resonance technique is one of the most powerful tools for the structural determination of ligands from the origin of natural products. Nowadays, molecular modeling is an important accessory tool to experimentally got nuclear magnetic resonance data. In the present work, molecular docking studies aimed is to investigate the limiting affinities of trans-dehydrocrotonin molecule and to identify the main amino acid residues that could play a fundamental role in their mechanism of action of the SARS-CoV spike protein. Another aim of this work is all about to evaluate 10 hybrid functionalities, along with three base pairs using computational programs to discover which ones are more reliable with the experimental result the best computational method to study organic compounds. We compared the results between the mean absolute deviation (MAD) and root-mean-square deviation (RMSD) of the molecules, and the smallest number between them was the best result. The positions assumed by the ligands in the active site of the spike glycoprotein allow assuming associations with different local amino acids.


Assuntos
COVID-19 , SARS-CoV-2 , Antivirais , Teoria da Densidade Funcional , Diterpenos Clerodânicos , Humanos , Espectroscopia de Ressonância Magnética , Simulação de Acoplamento Molecular , Peptídeo Hidrolases
10.
Sci Rep ; 11(1): 8074, 2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33850244

RESUMO

Teucrium yemense, a medicinal plant commonly grown in Saudi Arabia and Yemen, is traditionally used to treat infections, kidney diseases, rheumatism, and diabetes. Extraction of the dried aerial parts of the plant with methanol, followed by further extraction with butanol and chromatography, gave twenty novel neoclerodanes. Their structures, relative configurations and some conformations were determined by MS and 1-D and 2-D NMR techniques. Most were fairly conventional but one contained an unusual stable orthoester, one had its (C-16)-(C-13)-(C-14)-(C-15) (tetrahydro)furan unit present as a succinic anhydride and one had a rearranged carbon skeleton resulting from ring-contraction to give a central octahydroindene bicyclic core, rather than the usual decalin. Mechanisms are proposed for the biosynthetic formation of the orthoester and for the ring-contraction. Four novel neoclerodanes increased the glucose-triggered release of insulin from isolated murine pancreatic islets by more than the standard drug tolbutamide, showing that they are potential leads for the development of new anti-diabetic drugs.


Assuntos
Diterpenos Clerodânicos , Insulina , Teucrium , Animais , Ilhotas Pancreáticas , Camundongos
11.
J Enzyme Inhib Med Chem ; 36(1): 749-757, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33715562

RESUMO

Bioassay-guided fractionation of the ethyl acetate extract from Teucrium flavum subsp. glaucum, endowed with inhibitory activity towards the HIV-1 reverse transcriptase-associated RNase H function, led to the isolation of salvigenin (1), cirsimaritin (2) and cirsiliol (3) along with the neo-clerodanes teuflavin (4) and teuflavoside (5). Acid hydrolysis of the inactive teuflavoside provided three undescribed neo-clerodanes, flavuglaucins A-C (7-9) and one known neo-clerodane (10). Among all neo-clerodanes, flavuglaucin B showed the highest inhibitory activity towards RNase H function with a IC50 value of 9.1 µM. Molecular modelling and site-directed mutagenesis analysis suggested that flavuglaucin B binds into an allosteric pocket close to RNase H catalytic site. This is the first report of clerodane diterpenoids endowed with anti-reverse transcriptase activity. Neo-clerodanes represent a valid scaffold for the development of a new class of HIV-1 RNase H inhibitors.


Assuntos
Diterpenos Clerodânicos/farmacologia , Flavonoides/farmacologia , Transcriptase Reversa do HIV/antagonistas & inibidores , Extratos Vegetais/farmacologia , Inibidores da Transcriptase Reversa/farmacologia , Ribonuclease H/antagonistas & inibidores , Teucrium/química , Diterpenos Clerodânicos/química , Diterpenos Clerodânicos/isolamento & purificação , Relação Dose-Resposta a Droga , Flavonoides/química , Flavonoides/isolamento & purificação , Transcriptase Reversa do HIV/genética , Transcriptase Reversa do HIV/metabolismo , Concentração de Íons de Hidrogênio , Hidrólise , Modelos Moleculares , Conformação Molecular , Mutagênese Sítio-Dirigida , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Inibidores da Transcriptase Reversa/química , Inibidores da Transcriptase Reversa/isolamento & purificação , Ribonuclease H/genética , Ribonuclease H/metabolismo , Relação Estrutura-Atividade
12.
Chemistry ; 27(29): 7968-7973, 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-33784436

RESUMO

A concise enantioselective total synthesis of the neoclerodane diterpene (-)-salvinorin A is reported. The stereogenic center at C-12 was installed by catalytic asymmetric propargylation with excellent enantioselectivity, and the remaining six stereogenic centers were set up highly diastereoselectively under substrate control. As for our previous synthesis of racemic salvinorin A, two intramolecular Diels-Alder reactions were applied to generate the tricyclic core. A chemoselective Mitsunobu inversion of a syn 1,2-diol allowed for further streamlining of the original reaction sequence by two steps. Overall, (-)-salvinorin A was synthesized in only 16 steps starting from 3-furaldehyde with 1.4 % total yield. Furthermore, an alternative intramolecular Diels-Alder strategy employing a 2-bromo-1,3-diene moiety was investigated.


Assuntos
Diterpenos Clerodânicos , Catálise , Reação de Cicloadição , Estereoisomerismo
13.
J Nat Prod ; 84(4): 1210-1215, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33677971

RESUMO

An investigation of the chemical composition of Chinese liverworts led to the isolation of six new caged clerodane-type diterpenoids, scaparins A-C (1-3) from Scapania koponenii and scaparins D-F (4-6) from S. verrucosa. An unknown ent-trachylobane diterpenoid (7) and three known terpenoid derivatives (8-10) were obtained from S. verrucosa. The structures of the compounds were established on the basis of physical data (IR, UV, HRESIMS, and 1D and 2D NMR), and the absolute configurations were unequivocally confirmed by comparison of the experimental and calculated electronic circular dichroism spectra. Preliminary bioassays showed that compounds 1-7 exhibited moderate to weak quinone reductase-inducing activity in Hepa-1c1c7 cells.


Assuntos
Hepatófitas/química , Terpenos/química , Animais , Linhagem Celular Tumoral , China , Diterpenos Clerodânicos , Camundongos , Estrutura Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Terpenos/isolamento & purificação
14.
Phytochemistry ; 186: 112731, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33721797

RESUMO

The Lamiaceae plant Ajuga forrestii Diels is a traditional Chinese herbal medicine with abundant glandular trichomes (GTs), but their chemistry and biological functions remain uninvestigated. Here, a panel of six highly functionalized neo-clerodane diterpenoids was localized to the peltate GTs of A. forrestii using laser microdissection coupled with HPLC analysis, indicating that the GTs of A. forrestii are an excellent material for the elucidation of the yet unclear biosynthetic pathway of natural neo-clerodane diterpenoids. In addition, four undescribed neo-clerodane diterpenoids with an acyclic C-9 side chain including two pairs of 1:1 mixture of inseparable diastereomers, ajuforrestins D-G, were isolated from the fresh leaves of A. forrestii together with six known compounds. The structures of the undescribed compounds were elucidated by spectroscopic (including 1D and 2D NMR and HR-ESI-MS) analyses. Biological assays indicated that the major GT compound ajugacumbin B and undescribed ajuforrestins D/E showed antifeedant activity against Helicoverpa armigera, suggesting that neo-clerodanes in A. forrestii should be involved in plant defence against insects. Moreover, the abietane diterpenoid ajuforrestin B exhibited significant anti-inflammatory activity on the secretion of interleukin-2 (IL-2) and cytotoxicity against three cancer cell lines, NCI-H1975, HepG2 and MCF-7, suggesting that ajuforrestin B could positively contribute to the therapeutic effects of this traditional Chinese medicine.


Assuntos
Ajuga , Diterpenos Clerodânicos , Anti-Inflamatórios/farmacologia , Diterpenos Clerodânicos/farmacologia , Estrutura Molecular , Folhas de Planta , Tricomas
15.
J Agric Food Chem ; 69(4): 1251-1258, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33476164

RESUMO

A case of baled alfalfa hay contaminated with multiple weeds induced hepatotoxicity and death in cattle. The hepatotoxic compounds were isolated by bioassay-guided fractionation using a mouse model and identified as salviarin, salvianduline D, rhyacophiline, and 7-hydroxyrhyacophiline. The structure of 7-hydroxyrhyacophiline has not been previously reported. All compounds were found to induce severe acute hepatic necrosis within 24-48 h after a single oral dosage (260-280 mg/kg). The identified diterpenes are known to be found among different Salvia species which led to finding dried plant parts of Salvia reflexa within bales of weedy hay and subsequently a population of S. reflexa was found along the field edges and irrigation ditch banks of the alfalfa hay field. It was thus determined that S. reflexa was responsible for the hepatotoxicity observed in cattle fed the contaminated hay.


Assuntos
Doenças dos Bovinos/etiologia , Diterpenos Clerodânicos/toxicidade , Hepatopatias/veterinária , Extratos Vegetais/toxicidade , Salvia/toxicidade , Ração Animal/efeitos adversos , Ração Animal/análise , Animais , Bovinos , Doenças dos Bovinos/metabolismo , Diterpenos Clerodânicos/química , Diterpenos Clerodânicos/metabolismo , Fígado/efeitos dos fármacos , Hepatopatias/etiologia , Hepatopatias/metabolismo , Camundongos , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/metabolismo , Salvia/química , Salvia/metabolismo
16.
J Ethnopharmacol ; 268: 113550, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33152437

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Mexico is considered an ancestral center of diversity of Salvia species, however many of them lack scientific information. Salvia circinnata Cav. (syn. Salvia amarissima Ortega) is an endemic species used in traditional medicine to treat disorders attributed to a cold state like anxiety in the central nervous system, as well as gastrointestinal ailments and pain relief. AIM OF THE STUDY: To give preclinical evidence about the pharmacological properties of this species by investigating its antinociceptive and anti-inflammatory effects, the chemical nature of at least one metabolite, and a possible mechanism of action and adverse effects, using different experimental models of pain. MATERIAL AND METHODS: Different crude extracts of Salvia circinnata Cav. aerial parts were prepared using increasing polarity and evaluated in the formalin test in mice. This screening allowed to select and evaluate an ethyl acetate extract (EtOAc), as the most bioactive extract, and a metabolite. Antinociceptive and anti-inflammatory activities were confirmed using the plantar test and carrageenan-induced edema. The antinociceptive effects of the extracts were compared to that observed with morphine (1 mg/kg), tramadol (20 mg/kg) or indomethacin (20 mg/kg) as reference drugs. Participation of opioids and TRPV1 receptors was investigated, as well as acute toxicity and adverse effects of sedation and gastric damage. RESULTS: EtOAc (0.1-10 mg/kg) of S. circinnata Cav. showed a dose-dependent and significant antinociceptive activity, associated in part with the presence of a neo-clerodane glycoside amarisolide A (0.01-1 mg/kg), in the neurogenic and inflammatory phases of the formalin test. Central action of both treatments was corroborated in the plantar test, whereas anti-inflammatory effects were confirmed with the extract (1 and 10 mg/kg) and amarisolide A (1 mg/kg) in the carrageenan-induced edema test. An opioid mechanism in both treatments, and the TRPV1 receptor modulation in the extract were involved. No acute toxicity and adverse effects were noticed with the extract and pure compound in comparison to the reference drugs. CONCLUSION: These results provide preclinical evidence of the ethnopharmacological antinociceptive S. circinnata Cav. properties, in which the neo-clerodane diterpene glycoside amarisolide A was partially responsible involving the participation of the opioid receptors, while TRPV1 receptor modulation was implicated in the anti-inflammatory activity may be because of the presence of other constituents. This information supports the use of this species in folk medicine for pain therapy.


Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Diterpenos Clerodânicos/uso terapêutico , Medição da Dor/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Salvia , Analgésicos/isolamento & purificação , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Diterpenos Clerodânicos/isolamento & purificação , Diterpenos Clerodânicos/farmacologia , Relação Dose-Resposta a Droga , Masculino , Camundongos , Medição da Dor/métodos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar
17.
J Nat Med ; 75(1): 201-206, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32970255

RESUMO

A new rearranged clerodane-type diterpene (1), tinobaenzigeride, and a new rearranged clerodane glucoside (2) were isolated from the stems of Tinospora baenzigeri, along with four known compounds (3‒6). Their structures were elucidated by spectroscopic data analysis. In addition, the structure and configuration of 1 was confirmed by single-crystal X-ray diffraction analysis. Compound 1 are a rare example of rearranged clerodanes, since it contains a fully oxygenated tetrahydrofuran moiety. The isolated compounds were evaluated for their cytotoxicity against Hep-G2 and MCF-7 cancer cells, none of them did show any significant activity at 25 µM.


Assuntos
Diterpenos Clerodânicos/química , Tinospora/química , Humanos , Estrutura Molecular , Tailândia
18.
J Cereb Blood Flow Metab ; 41(4): 723-730, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32615886

RESUMO

Salvinorin A (SA) exerts neuroprotection and improves neurological outcomes in ischemic stroke models in rodents. In this study, we investigated whether intranasal SA administration could improve neurological outcomes in a monkey ischemic stroke model. The stroke model was induced in adult male rhesus monkeys by occluding the middle cerebral artery M2 segment with an autologous blood clot. Eight adult rhesus monkeys were randomly administered SA or 10% dimethyl sulfoxide as control 20 min after ischemia. Magnetic resonance imaging was used to confirm the ischemia and extent of injury. Neurological function was evaluated using the Non-Human Primate Stroke Scale (NHPSS) over a 28-day observation period. SA significantly reduced infarct volume (3.9 ± 0.7 cm3 vs. 7.2 ± 1.0 cm3; P = 0.002), occupying effect (0.3 ± 0.2% vs. 1.4 ± 0.3%; P = 0.002), and diffusion limitation in the lesion (-28.2 ± 11.0% vs. -51.5 ± 7.1%; P = 0.012) when compared to the control group. SA significantly reduced the NHPSS scores to almost normal in a 28-day observation period as compared to the control group (P = 0.005). Intranasal SA reduces infarct volume and improves neurological outcomes in a rhesus monkey ischemic stroke model using autologous blood clot.


Assuntos
Diterpenos Clerodânicos/uso terapêutico , AVC Isquêmico/complicações , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/prevenção & controle , Fármacos Neuroprotetores/uso terapêutico , Animais , Coagulação Sanguínea , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/prevenção & controle , AVC Isquêmico/diagnóstico por imagem , Macaca mulatta , Imageamento por Ressonância Magnética , Masculino , Doenças do Sistema Nervoso/diagnóstico por imagem , Resultado do Tratamento
19.
Nat Prod Res ; 35(9): 1421-1427, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-31411058

RESUMO

Phytochemical investigation of Croton crassifolius led to the isolation of two new halimane diterpenoids (1 and 2), a new nor-clerodane diterpenoid (3), along with three known analogues (4-6). Their structures including absolute configurations were elucidated by spectroscopic analysis, single-crystal X-ray diffraction, and CD analysis. All isolates were evaluated for their inhibitory effects on the nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW264.7 macrophage cells, and compound 1 exhibited moderate inhibition of NO production with an IC50 value of 25.8 ± 0.9 µM.


Assuntos
Croton/química , Diterpenos/isolamento & purificação , Animais , Cristalografia por Raios X , Diterpenos/química , Diterpenos/farmacologia , Diterpenos Clerodânicos/química , Diterpenos Clerodânicos/isolamento & purificação , Concentração Inibidora 50 , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/biossíntese , Raízes de Plantas/química , Células RAW 264.7
20.
Nat Prod Res ; 35(2): 298-304, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31204854

RESUMO

Four new neo-clerodanes, crotonolins C-F (3-6), were isolated from the stem bark of Croton oligandrus together with the known clerodane crotonzambefuran A, the abietanes 7-ß-hydroxydehydroabietic acid and 7-oxodehydroabietic acid, and ferulic acid. Their structures were elucidated by spectroscopic analyses including 1D and 2D NMR and HRESIMS and by comparison with previously reported data. The cytotoxicity of the isolated compounds against A549, MCF7, PC3 and PNT2 cells was evaluated using the MTT assay. Only 7-ß-hydroxydehydroabietic acid showed a moderate level of activity against PC3 cells with an IC50 value of 68.9 ± 6.6 µM.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Croton/química , Diterpenos Clerodânicos/química , Diterpenos Clerodânicos/farmacologia , Abietanos/química , Antineoplásicos Fitogênicos/química , Linhagem Celular Tumoral , Ácidos Cumáricos/química , Diterpenos/química , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Estrutura Molecular , Células PC-3 , Casca de Planta/química , Extratos Vegetais/química , Espectrometria de Massas por Ionização por Electrospray
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...