RESUMO
Alzheimer's diseases (AD) and other infectious diseases caused by drug-resistance bacteria have posed a serious threat to human lives and global health. With the aim to search for human acetylcholinesterase (hAChE) inhibitors and antibacterial agents from medicinal plants, 16 phloroglucinol oligomers, including two new phloroglucinol monomers (1a and 1b), four new phloroglucinol dimers (3a, 3b, 4b, and 5a), six new phloroglucinol trimers (6a, 6b, 7a, 7b, 8a, and 8b), and two naturally occurring phloroglucinol monomers (2a and 2b), along with two known congeners (4a and 5b), were purified from the leaves of tropic Rhodomyrtus tomentosa. The structures and absolute configurations of these new isolates were unequivocally established by comprehensive analyses of their spectroscopic data (NMR and HRESIMS), ECD calculation, and single crystal X-ray diffraction. Structurally, 3a/3b shared a rare C-5' formyl group, whereas 6a/6b possessed a unique C-7' aromatic ring. In addition, 7a/7b and 8a/8b were rare phloroglucinol trimers with a bis-furan and a C-6' hemiketal group. Pharmacologically, the mixture of 3a and 3b showed the most potent human acetylcholinesterase (hAChE) inhibitory activity with an IC50 value of 1.21 ± 0.16 µM. The molecular docking studies of 3a and 3b in the hAChE binding sites were performed, displaying good agreement with the in vitro inhibitory effects. In addition, the mixture of 3a and 3b displayed the most significant anti-MRSA (methicillin-resistant Staphylococcus aureus) with MIC and MBC values of both 0.50 µg/mL, and scanning electron microscope (SEM) studies revealed that they could destroy the biofilm structures of MRSA. The findings provide potential candidates for the further development of anti-AD and anti-bacterial agents.
Assuntos
Antibacterianos , Inibidores da Colinesterase , Staphylococcus aureus Resistente à Meticilina , Floroglucinol , Humanos , Acetilcolinesterase , Antibacterianos/farmacologia , Simulação de Acoplamento Molecular , Estrutura Molecular , Floroglucinol/análogos & derivados , Floroglucinol/química , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Extratos Vegetais/químicaRESUMO
Two undescribed dammarane triterpenoid saponins, cypaliurusides O and P (1 and 2), were isolated from the ethanol extracts of the leaves of Cyclocarya paliurus. Bioactivity assay results showed that compound 1 has potential cytotoxic activities against selected human cancer cell lines in vitro, with IC50 values ranging from 14.55 ± 0.55 to 22.75 ± 1.54 µM. Compound 1 showed better antitumor activity against HepG2 cells with IC50 of 14.55 ± 0.55 µM. In addition, compound 2 showed no obvious antitumor activity.
Assuntos
Juglandaceae , Saponinas , Triterpenos , Humanos , Triterpenos/farmacologia , Extratos Vegetais , Linhagem Celular , Saponinas/farmacologia , Folhas de Planta , DamaranosRESUMO
A new oleanane-type triterpenoid saponin, 21ß, 22α-di-O-angeloyl-15α, 16α, 28-trihydroxyolean-12-ene 3ß-O-α-L-rhamnopyranosyl-(1â3)-α-D-xylopyranosyl-(1â3)-ß-D-glucopyranoside (1), together with five known compounds (2-5), were isolated from Camellia nitidissima. Their structures were elucidated based on spectroscopic methods, including extensive NMR and MS spectra. Compound 1 showed potential inhibitory activity on α-glucosidase with the IC50 values of 185.9 ± 44.5 µmol/L.
Assuntos
Camellia , Saponinas , Triterpenos , Saponinas/farmacologia , Saponinas/química , alfa-Glucosidases , Triterpenos/química , Camellia/química , Estrutura MolecularRESUMO
Previous in vivo and in vitro studies revealed that esculetin (Fig. 1) has anti-hepatitis B virus (anti-HBV) activity as well as a protective effect on liver damage caused by duck hepatitis B virus. We designed and synthesized a series of esculetin derivatives, introduced side chains containing various amino groups into site 7 of the parent structure, and synthesized C-4 and C-8 substituted derivatives with the goal of investigating their anti-HBV activities. In vitro anti-HBV activity was performed against HepG2.2.15 cells by using Enzyme-Linked Immunosorbent Assay(ELISA) kit and cytotoxicity was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay with lamivudine as the positive control. The results demonstrated that several compounds showed moderate anti-HBV activity, while the introduction of morpholine groups could significantly inhibit the expression of hepatitis B e antigen (HBeAg) and the introduction of the 2-methylimidazole group could significantly inhibit the expression of Hepatitis B surface antigen (HBsAg). Among all tested compounds, compound 4a demonstrated the best anti-HBeAg activity (IC50 = 15.8 ± 4.2 µM), while compound 6d demonstrated the best anti-HBsAg activity (IC50 = 21.4 ± 2.8 µM). Compounds 6b and 6c showed moderate anti-HBV activity and HBsAg inhibition. Compounds 4b showed moderate anti-HBV activity and an inhibitory effect on HBeAg. In addition, compounds 4a, 4c, 4d, 6b, 6c and 6d showed improved metabolic stability. This study provides useful guidance for the discovery of anti-HBV drugs, which merits further investigation.
RESUMO
Diabetes mellitus is caused by chronic inflammation and affects millions of people worldwide. Cyclocarya paliurus leaves have been widely used in traditional folk tea as a remedy for diabetes, but the antidiabetic constituents remain to be further studied. The α-glucosidase inhibitory and anti-inflammatory activities were examined to evaluate their effects on diabetes mellitus, and bioassay-guided separation of C. paliurus leaves led to the identification of twenty dammarane saponins, including eleven new dammarane saponins (1-11). The structures of the isolates were elucidated by spectroscopic methods. Bioactivity assay results showed that compounds 1 and 2 strongly inhibited α-glucosidase activity, with IC50 values ranging from 257.74 µM, 282.23 µM, and strongly inhibited the release of NO, with IC50 values of 9.10 µM, 9.02 µM. Moreover, compound 2 significantly downregulated the mRNA expression of iNOS, COX-2, IL-1ß, NF-κB, IL-6 and TNF-α in LPS-mediated RAW 264.7 cells and markedly suppressed the protein expression of iNOS, NF-κB/p65, and COX-2. Dammarane glucoside 2 exhibited the strongest α-glucosidase inhibitory and anti-inflammatory activities. In addition, the structure-activity relationships (SARs) of the dammarane saponins were investigated. In summary, C. paliurus leaves showed marked α-glucosidase inhibitory and anti-inflammatory activities, and dammarane saponins are responsible for regulating α-glucosidase, inflammatory mediators, and mRNA and the protein expression of proinflammatory cytokines, which could be meaningful for discovering new antidiabetic agents.
Assuntos
Anti-Inflamatórios/farmacologia , Citocinas/antagonistas & inibidores , Inibidores de Glicosídeo Hidrolases/farmacologia , Juglandaceae/química , Triterpenos/farmacologia , alfa-Glucosidases/metabolismo , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Citocinas/genética , Relação Dose-Resposta a Droga , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Camundongos , Estrutura Molecular , Folhas de Planta/química , Células RAW 264.7 , Relação Estrutura-Atividade , Triterpenos/química , Triterpenos/isolamento & purificação , DamaranosRESUMO
Although clinically approved hepatitis B virus (HBV) polymerase inhibitors (lamivudine-3TC, entecavir, etc.) serve as effective therapeutics, the virus can easily generate resistance to them. Therefore, the treatment of HBV infection remains a public health problem. Numerous studies have shown that natural products have prospective anti-HBV activity. The purpose of this study was to isolate and extract des(rhamnosyl) verbascoside from Lindernia ruellioides (Colsm.) Pennell and explore its anti-HBV and hepatoprotective effects. Anti-HBV activity was evaluated in HepG2.2.15 cells, a human hepatocellular carcinoma cell line with HBV-stable infection, and its protective effect was evaluated in HL-7702 cells, a normal human liver cell line. HepG2.2.15 cells maintained normal growth morphology within the selected concentration range of des(rhamnosyl) verbascoside. It also inhibited the expression of HBV antigens and HBV DNA in a dose- and time-dependent manner in vitro. Further, western blot experiments showed that it could downregulate HBV X protein (HBx) expression in a dose-dependent manner. In the H2 O2 -induced hepatocyte injury model, the cell-survival rate of the HL-7702 cells with the highest drug dose reached 85.25%, which was significantly improved compared with that of the model group. Most of the cells returned to normal morphology, showing polygonal or fusiform structures. Thus, it may be stated that des(rhamnosyl) verbascoside exhibits anti-HBV activity and hepatoprotective effects in vitro and may exert an anti-HBV effect via antigen inhibition, HBV DNA secretion, and HBx protein expression.
Assuntos
Antivirais , Carcinoma Hepatocelular , Glucosídeos/farmacologia , Vírus da Hepatite B/efeitos dos fármacos , Lamiales/química , Neoplasias Hepáticas , Fenóis/farmacologia , Antivirais/farmacologia , Células Hep G2 , Humanos , Substâncias Protetoras/farmacologia , Replicação Viral/efeitos dos fármacosRESUMO
Two new tetralone derivatives, named cyclopalosides A (1) and B (2), were isolated from the leaves of Cyclocarya paliurus by column chromatography on silica gel, reversed-phase C18 silica gel and preparative HPLC. Their chemical structures were established on the basis of extensive analyses of spectroscopic data. Their structural characteristic is tetralone glycoside with a caffeoyl unit. The antioxidant activities of compound 1 were evaluated by using hydroxyl, superoxide anion, and DPPH radical scavenging assay.
Assuntos
Juglandaceae/química , Folhas de Planta/química , Tetralonas/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Compostos de Bifenilo , Estrutura Molecular , Picratos , Tetralonas/químicaRESUMO
Coumarins are widely present in a variety of plants and have a variety of pharmacological activities. In this study, we isolated a coumarin compound from Microsorium fortunei (Moore) Ching; the compound was identified as esculetin by hydrogen and carbon spectroscopy. Its anti-hepatitis B virus (HBV) activity was investigated in vitro and in vivo. In the human hepatocellular liver carcinoma 2.2.15 cell line (HepG2.2.15) transfected with HBV, esculetin effecting inhibited the expression of the HBV antigens and HBV DNA in vitro. Esculetin inhibited the expression of Hepatitis B virus X (HBx) protein in a dose-dependent manner. In the ducklings infected with duck hepatitis B virus (DHBV), the levels of DHBV DNA, duck hepatitis B surface antigen (DHBsAg), duck hepatitis B e-antigen (DHBeAg), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) decreased significantly after esculetin treatment. Summing up the above, the results suggest that esculetin efficiently inhibits HBV replication both in vitro and in vivo, which provides an opportunity for further development of esculetin as antiviral drug.
Assuntos
Antivirais/farmacologia , Vírus da Hepatite B/efeitos dos fármacos , Extratos Vegetais/farmacologia , Umbeliferonas/farmacologia , Animais , Antivirais/química , Antivirais/uso terapêutico , Biomarcadores , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , DNA Viral , Patos , Hepatite B/sangue , Hepatite B/tratamento farmacológico , Hepatite B/virologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/fisiologia , Humanos , Espectroscopia de Ressonância Magnética , Extratos Vegetais/química , Umbeliferonas/química , Umbeliferonas/uso terapêuticoRESUMO
Five caffeoyl phenylethanoid glycosides, including two new ones linderruelliosides A (1) and B (2), were isolated from the leaves and stems of Lindernia ruellioides. Their structures were elucidated on the basis of spectroscopic methods, including extensive NMR and MS spectra. In addition, all these compounds were tested for their anti-HBV activity. Compounds 1, 3, and 4 showed anti-HBV activities, with IC50 values of 54.87, 30.74, and 69.02 µM for HBsAg and 26.70, 5.17, and 7.08 µM for HBeAg, respectively.
Assuntos
Antivirais/farmacologia , Vírus da Hepatite B/efeitos dos fármacos , Scrophulariaceae/química , Antivirais/química , Linhagem Celular , China , Antígenos de Superfície da Hepatite B/análise , Humanos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura Molecular , Extratos Vegetais/química , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Infravermelho , Espectrofotometria UltravioletaRESUMO
Eleven triterpene acids including 10 new compounds (kadcoccinic acids A-J, 1-10) were isolated from the stems of Kadsura coccinea. Except for 10, these compounds feature a rearranged lanostane skeleton with a 6/6/5/6 tetracyclic ring system, and compounds 1 and 2 are the first examples of 2,3-seco-6/6/5/6-fused tetracyclic triterpenoids. Their structures were established primarily by spectroscopic and spectrometric methods. Additionally, the absolute configuration of 3 was determined by single-crystal X-ray diffraction. Several of the compounds isolated were tested for their anti-HIV-1 and cytotoxic activities.
Assuntos
Fármacos Anti-HIV/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Kadsura/química , Triterpenos/isolamento & purificação , Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Feminino , HIV-1/efeitos dos fármacos , Células HL-60 , Humanos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Caules de Planta/química , Triterpenos/química , Triterpenos/farmacologiaRESUMO
Four previously undescribed phloroglucinols, including three pairs of enantiomers, (±)-rhodotomentodimer F, (±)-rhodotomentodimer G, and (±)-rhodotomentomonomer E, and one phloroglucinol-sesquiterpene meroterpenoid, rhodotomentodione E, together with one previously reported congener, (±)-rhodomyrtosone A, were obtained from the leaves of Rhodomyrtus tomentosa. The structures including absolute configurations of previously undescribed isolates were elucidated by extensive spectroscopic analysis (HRESIMS and NMR), ECD calculations, and single-crystal X-ray diffraction. (±)-Rhodotomentodimer F is a rare phloroglucinol derivative conjugated by a ß-triketone moiety and an unprecedented resorcinol unit via the formation of a rare bis-furan ring system, whereas (±)-rhodotomentomonomer E shares a rearranged pentacyclic scaffold. Pharmacologically, (±)-rhodotomentomonomer E showed the strongest human acetylcholinesterase (hAChE) inhibitory effect with an IC50 value of 1.04 ± 0.05 µM. Molecular formula studies revealed that hydrogen bonds formed between hAChE residues Glu202, Ser203, Ala204, Gly121, Gly122, Tyr337, and His447 and (±)-rhodotomentomonomer E played crucial roles in its observed activity. These findings indicated that the leaves of Rhodomyrtus tomentosa can supply a rich source of hAChE inhibitors. These inhibitors might potentially be utilized in the therapeutic strategy for Alzheimer's disease, offering promising candidates for further research and development.
RESUMO
An undescribed dammarane triterpenoid saponin Cypaliuruside F was isolated from the leaves of Cyclocarya paliurus in our preliminary study. The MTT assay, flow cytometry, cell scratch, and DAPI staining were used to detect the antitumor effects of Cypaliuruside F on HepG2 cells. Subsequently, network pharmacology and molecular docking analysis were used to analyse the key targets of Cypaliuruside F against HCC. In addition, a Western blot was performed to determine the effects of Cypaliuruside F on the expression of key proteins in HepG2 cells. The experimental results indicated that the damarane triterpenoid saponin Cypaliuruside F from Cyclocarya paliurus inhibits the proliferation of HepG2 cells by inducing apoptosis and cell cycle arrest. These changes may promote the apoptosis of HepG2 cells by inhibiting the expression of mTOR, STAT3, and Bcl-2 while activating Bax.
RESUMO
Three new triterpenoids, kadcotriones A-C (1-3), together with the biogenetically related lanostane-type triterpenoid (4), were isolated from Kadsura coccinea. Compound 1 features a 12,14ß-dimethyl 6/6/6-fused tricyclic skeleton, while 2 and 3 are characterized by a 6/6/5-ring system. Their structures were determined by NMR and electronic circular dichroism spectroscopic methods. Compounds 2 and 4 exhibited anti-HIV-1 activities with EC50 values of 30.29 and 54.81 µM, respectively.
Assuntos
Fármacos Anti-HIV/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Kadsura/química , Triterpenos/isolamento & purificação , Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Dicroísmo Circular , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , HIV-1/efeitos dos fármacos , Estrutura Molecular , Caules de Planta/química , Triterpenos/química , Triterpenos/farmacologiaRESUMO
Five new dibenzocyclooctadiene lignans, schisphenlignans A-E (1-5), together with eight known ones, were isolated from the stems of Schisandra sphenanthera. The structures of 1-5 were elucidated based on the analysis of their NMR, MS and circular dichroism (CD) spectra. Some isolates were tested for their acute activities on insulin sensitivity in 3T3-L1 differentiated adipocytes, but none of them showed significant bioactivity with 10 µM administration of the tested compounds.
Assuntos
Ciclo-Octanos/química , Ciclo-Octanos/farmacologia , Lignanas/química , Lignanas/farmacologia , Caules de Planta/química , Schisandra/química , Células 3T3-L1 , Animais , Ciclo-Octanos/isolamento & purificação , Insulina/metabolismo , Resistência à Insulina , Lignanas/isolamento & purificação , CamundongosRESUMO
OBJECTIVE: To study the chemical constituents of Rubus parvifoliu. METHODS: The constituents were isolated by column chromatography and their structures were elucidated through spectroscopic analysis such as 1H-NMR, 13C-NMR, FT-IR, et al. RESULTS: Seven compounds were isolated from the roots of Rubus parvifolius L., they were identified as p-sitosterol (I), lauric acid (II), O-nitrophenol (III), beta-daucosterol (IV), euscaphic acid (V), camelliagenin A (VI) and(+) -catech in (VII). CONCLUSION: Compounds III and VII are isolated from the plant for the first time.
Assuntos
Catequina/isolamento & purificação , Nitrofenóis/isolamento & purificação , Compostos Organofosforados/isolamento & purificação , Plantas Medicinais/química , Rosaceae/química , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Catequina/química , Estrutura Molecular , Nitrofenóis/química , Compostos Organofosforados/química , Raízes de Plantas/química , Caules de Planta/química , Sitosteroides/química , Sitosteroides/isolamento & purificação , Triterpenos/química , Triterpenos/isolamento & purificaçãoRESUMO
Undescribed phloroglucinol derivatives, rhotomensones A-G, and a known derivative rhodomyrtosone B, were isolated from the leaves of Rhodomyrtus tomentosa. Rhotomensones A-D and G have unreported structural characteristics, in which rhotomensone A substitutes a benzene ring, rhotomensones B-D are bonded with a 2-methylbutanoyl group, and rhotomensone G has two fewer carbons. The structures of these compounds were determined by NMR spectroscopy, circular dichroism (CD) spectroscopy and X-ray crystallography. The inhibitory activities against α-glucosidase of rhotomensones E and F were evaluated in vitro, with IC50 values of 0.50 ± 0.14 mg/mL and 0.07 ± 0.02 mg/mL. Moreover, rhodomyrtosone B showed significant antibacterial activity against some bacteria, with MIC values ranging from 0.50 to 16.00 µg/mL.
Assuntos
Myrtaceae , Floroglucinol , Antibacterianos/farmacologia , Floroglucinol/farmacologia , Extratos Vegetais , Folhas de PlantaRESUMO
Thirteen undescribed dammarane triterpenoid saponins (cypaliurusides A-M), including eleven seco-dammarane type triterpenoids, were isolated from Cyclocarya paliurus. Each of these compounds has the unique feature of having a monosaccharide attached to C-11, rather than C-12, compared to the same type of saponins found in this plant. The structures of them were determined by comprehensive analysis of 1D, 2D NMR and HRESIMS data. Cypaliuruside J showed significant α-glucosidase inhibitory effect with IC50 value of 2.22 ± 0.13 µM. In addition, Cypaliurusides F and K exhibited modest cytotoxic activities against selected human cancer cell lines in vitro, with IC50 values ranging from 4.61 ± 0.13 to 15.23 ± 3.88 µM.
Assuntos
Juglandaceae , Saponinas , Triterpenos , Folhas de Planta , Saponinas/farmacologia , Triterpenos/farmacologia , DamaranosRESUMO
A decoction of Plumeria rubra flowers has been used traditionally for the treatment of diabetes in China and Mexico. Chemical investigations on the bioactive constituents of these flowers led to the isolation of 30 compounds, including the four new compounds, one iridoiod (1), two triterpenoids (4, 5), and a long-chain δ-lactone (16). In addition, 26 known compounds (2, 3, 6-15, 17-30) are also reported. All of these compounds were identified on the basis of spectroscopic data interpretation and the absolute configurations of compound 4, 5, 16 were determined by Mosher's method. Compounds 1-4, 7, 8 and 16 showed moderate to significant inhibitory activities against α-glucosidase and protein tyrosine phosphatase 1B, with 4 having IC50 values of 19.45 µM and 0.21 µM, respectively.
Assuntos
Apocynaceae/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Lactonas/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Terpenos/farmacologia , China , Flores/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Lactonas/isolamento & purificação , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Terpenos/isolamento & purificaçãoRESUMO
Two new triterpenoids, schisphendilactone A and B (1 and 2), together with three known triterpenoids, were isolated from the stems of Schisandra sphenanthera. Their structures were elucidated by spectroscopic methods, and the absolute configuration of 1 was determined by single-crystal X-ray diffraction. Compound 2 showed moderate inhibitory activity against SW480 cancer cell line, and compound 5 exhibited promising anti-HIV-1 activity with EC50 value of 0.52 µg ml(-1) and therapeutic index value of 117.12.
Assuntos
Fármacos Anti-HIV , Antineoplásicos Fitogênicos , Medicamentos de Ervas Chinesas , Schisandra/química , Triterpenos , Fármacos Anti-HIV/isolamento & purificação , Fármacos Anti-HIV/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , Efeito Citopatogênico Viral , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Caules de Planta/química , Estereoisomerismo , Triterpenos/isolamento & purificação , Triterpenos/farmacologiaRESUMO
Three new phenolic compounds, yunnanensins A-C (1-3), together with fourteen known ones (4-17), were isolated from the leaves and stems of Parakmeria yunnanensis. The structures of new compounds were established on the basis of extensive spectroscopic analyses. Several compounds showed weak anti-HIV-1 activity.