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1.
Bioorg Chem ; 100: 103917, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32442817

RESUMO

7-O-galloyltricetiflavan (GTF), a natural flavonoid, is known to exert anti-oxidation and neuroprotective activity, which are related to the prevention of Alzheimer's disease (AD). In this study, three series of GTF hybrids have been designed, synthesized and evaluated as multifunctional agents for treatment AD. The biological assays indicated that most of them showed strong inhibitory effect on self-induced ß-amyloid (Aß) aggregation, and a significant ability to inhibit ChEs. Among them, compound A15 exhibited best inhibition of Aß aggregation (78.81% at 20 µM), potent AChE inhibitory potencies (IC50, 0.56 µM), and compound C4 presented the highest ability to inhibit BuChE (IC50, 5.77 µM). Furthermore, kinetic, molecular modeling and molecular dynamics studies revealed that A15 and C4 could interact with the catalytic active site of AChE and BuChE, respectively. In addition, compounds A15 and C4 could cross the blood-brain barrier in vitro. More importantly, A15 and C4 also showed excellent neuroprotective activities against H2O2-induced human neuroblastoma SH-SY5Y cells damage and nearly no toxicity on SH-SY5Y cells. All of these outstanding in vitro results indicated A15 and C4 as the leading structure worthy of further investigation.

2.
Phytochemistry ; 176: 112414, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32446133

RESUMO

Five undescribed phenolics named pithecellobiumin C-G, along with thirteen known ones were isolated from the twigs and leaves of Archidendron clypearia (Jack) I.C.Nielsen. Their structures were elucidated based on comprehensive spectroscopic analyses, combined with computer-assisted structure elucidation software (ACD/Structure Elucidator) and gauge-independent atomic orbitals (GIAO) NMR chemical shift calculations. The absolute configurations were determined by comparison of experimental and calculated specific rotation and ECD curves. These compounds were tested for their neuroprotective activities against H2O2-induced injury in human neuroblastoma SH-SY5Y cells by MTT assay. Pithecellobiumin C-E exhibited noticeable neuroprotective effect. Further pharmacological study demonstrated that they could prevent cell death through inhibiting the apoptosis induction. Flow cytometry assays also proved that these compounds could attenuate reactive oxygen species (ROS) level and mitochondrial dysfunction in SH-SY5Y cells.

3.
Eur J Med Chem ; 198: 112362, 2020 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-32371334

RESUMO

Chromatographic purification of Elephantopus scaber led to 16 new germacrane-type sesquiterpene lactones (1-16), named elephantopinolide A-P, along with a known analogue (17). Their structures were confirmed by comprehensive spectroscopic analyses, single-crystal X-ray diffraction, and comparison between the experimental and calculated ECD spectra. Their hepatocellular inhibition activities against Hep3B and HepG2 cells were screened by MTT assay, and the structure-activity relationships were examined. The results revealed that 10 (IC50 value of 2.83 µM and 1.98 µM) is more potent than sorafenib. The underlying mechanism study demonstrated that 10 could markedly induce apoptosis accompanied by increased ROS production and decreased mitochondrial membrane potential, resulting in the autophagy and G2/M phase cell arrest in Hep3B and HepG2 cells. Furthermore, signal pathways including MAPKs and AKT may play important roles in 10-induced hepatocellular carcinoma cells death.

4.
Fitoterapia ; 143: 104591, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32276032

RESUMO

Ten undescribed sesquineolignans (1-10), including four sesqui-norlignans (1-4), were isolated from the fruits of Crataegus pinnatifida. Their structures were determined by comprehensive spectroscopic analyses. All compounds were examined for their neuroprotective activities against H2O2-induced cell injury in human neuroblastoma SH-SY5Y cells. Among them, 6 and 8 showed comparable protective effect with 79.36% and 80.72% cell viability compared with the positive control Trolox (78.64%) at 25 µM.

5.
Fitoterapia ; 143: 104559, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32199958

RESUMO

Four undescribed oxylipin vanillyl acetals with four stereogenic carbons were isolated from the herbs of Solanum lyratum. A comprehensive set of spectroscopic methods were used to elucidate the structures and relative configurations of 1-4. The absolute configurations of the naturally occurring compounds are assigned as 7S, 9'S, 10'S, 11'R at the site of six-membered cyclic acetal attachment by electronic circular dichroism (ECD) calculations and the modified Mosher's method. Compounds 1 and 3 displayed moderate selective inhibition against Hep3B and HepG2 cells, respectively. Further Annexin V-FITC/PI staining assay revealed that 1 and 3 might have inhibitory effects on hepatoma cells through induction of apoptosis.

6.
Bioorg Chem ; 96: 103650, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32044515

RESUMO

In the current study, four pairs of new enantiomeric alkaloids (1a/1b-4a/4b) were obtained from the leaves of Isatis indigotica Fortune Ex Land. Their structures were elucidated through spectroscopic methods and quantum mechanical calculations. Biologically, all isolates were evaluated for their neuroprotective effects against H2O2-induced SH-SY5Y cell injury. As a result, 1a and 1b exhibited enantioselective neuroprotective effects, further Annexin V-FITC/PI analysis showed that apoptosis ratios of 1a and 1b were reduced to 20.93% and 17.87%, respectively.

7.
Fitoterapia ; 142: 104501, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32058050

RESUMO

A phytochemical investigation on the leaves of Tripterygium wilfordii Hook. F. was conducted, leading to the isolation of five undescribed dihydro-ß-agarofuran sesquiterpenoids (1-5) and one known analogue (6). Their structures were determined by comprehensive spectroscopic analyses. The absolute configurations of the compounds were determined by comparison of the experimental ECD with the calculated data. In addition, all the compounds were evaluated for their neuroprotective activities against H2O2-induced cell injury in human neuroblastoma SH-SY5Y cells, and 3 showed the better protective effect with 76.63% cell viability comparing with the positive control Trolox (69.84%) at 12.5 µM.

8.
Bioorg Chem ; 95: 103545, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31927316

RESUMO

A phytochemical study on the roots of Daphne genkwa yielded seven new guaiane-type sesquiterpenoids (1-7), daphne A-G. Their structures were elucidated through comprehensive spectroscopic analyses. The absolute configurations were determined by comparison between experimental electronic circular dichroism (ECD) and calculated ECD spectra via time-dependent density functional theory (TDDFT) and the modified Mosher's method. Furthermore, all isolates were evaluated for their neuroprotective activities against H2O2-induced injury in human neuroblastoma SH-SY5Y cells. Among them, compounds 1 (78.42%) and 4 (79.34%) exhibited potent neuroprotective effects against H2O2-induced neurotoxicity at 25 µM. Further Annexin V-FITC/propidium iodide (PI) doubling staining exhibited that the neuroprotective effects of compounds 1 and 4 appeared to be mediated via suppressing cell apoptosis. Flow cytometry assays also proved that compounds 1 and 4 could attenuate mitochondrial dysfunction in SH-SY5Y cells.

9.
Nat Prod Res ; : 1-5, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31741408

RESUMO

Daphne giraldii Nitsche, belongs to Daphne genus, has been reported to exert anti-tumor activities. Our previous study suggested that flavones from Daphne giraldii have significant inhibitory effects on hepatocellular carcinoma (HCC) cells. However, the potential target of this type flavone was still unknown. In this study, 74 flavonoids compounds of Daphne giraldii and 41 potential targets of HCC were analyzed by the network, the most potential target was histone deacetylase 6 (HDAC6). Considering the cytotoxicity, compound 70 (Daphnegiravone D, DGD) was chosen for further confirmation. Molecular docking study revealed that DGD formed high binding affinity with HDAC6. Concomitantly, pharmacological studies indicated that DGD could inhibit the expression of HDAC6 in vitro and in vivo. In this study, network pharmacology along with experimental validation predicted and verified HDAC6 as one of potential targets of flavones, these investigations provide a new insight for further study of Daphne giraldii on HCC treatment.

10.
Planta Med ; 85(16): 1275-1286, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31627219

RESUMO

Breast cancer is one of the most common cancers diagnosed among women worldwide. Estrogen receptor alpha (ERα) is a transcriptional factor that plays an important role in the development and progression of breast cancer. Yuanhuatine, a natural daphnane-type diterpenoid extracted from Daphne genkwa, was reported to exhibit significant cytotoxicity against breast cancer cells. However, the underlying mechanism is still unclear. In this study, we evaluated the cytotoxicity of yuanhuatine on two breast cancer cell lines that are ERα-positive and -negative. The results show that yuanhuatine inhibits the growth of ERα-positive cells (MCF-7) with much stronger inhibitory activity (IC50 = 0.62 µM) compared with positive control tamoxifen (IC50 = 14.43 µM). However, no obvious cytotoxicity was observed in ERα-negative cells (MDA-MB-231). Subsequent experiment also indicated that yuanhuatine markedly induced mitochondrial dysfunction, leading to apoptosis in MCF-7 cells. Molecular docking studies suggest the potential interactions between yuanhuatine and ERα. Immunofluorescence staining and Western blot analysis indicated that yuanhuatine down-regulated the expression of ERα in MCF-7 cells. MPP, a specific ERα inhibitor, significantly enhanced yuanhuatine-induced mitochondrial dysfunction and apoptosis in MCF-7 cells. On the contrary, the treatment with yuanhuatine causes no apoptosis in MM231 cells. Altogether, in vitro and in silico results suggested that ERα down-regulation was involved in yuanhuatine-induced mitochondrial dysfunction and apoptosis in ERα-positive breast cancer cells. Thus, yuanhuatine could be a potential candidate for treating ERα-positive breast cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Daphne/química , Tamoxifeno/farmacologia , Antineoplásicos Fitogênicos/química , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Feminino , Humanos , Células MCF-7 , Mitocôndrias/metabolismo , Simulação de Acoplamento Molecular , Tamoxifeno/química
11.
Bioorg Chem ; 93: 103354, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31629256

RESUMO

Eleven aromatic compounds, including four pairs of undescribed phenylpropanoids and two undescribed dibenzofurans (1a/1b-4a/4b and 5-6), were isolated from the fruits of C. pinnatifida. Their structures were established by extensive spectroscopic analyses. Their relative and absolute configurations were determined by the assistance of quantum chemical calculations of NMR chemical shifts and electronic circular dichroism (ECD). All isolates were screened for the cytotoxicity against two human hepatoma cell lines, HepG2 and Hep3B. It was found that compound 7 exhibited noticeable cytotoxicity against both cells with the IC50 values of 12.24 (HepG2) and 24.90 (Hep3B) µM. Further Annexin VFITC/ PI staining assay suggested that 7 could induce apoptosis in a concentration-dependent manner to exert antiproliferative activities on hepatoma cells.

12.
Fitoterapia ; 137: 104287, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31386898

RESUMO

Phytochemical investigation of the fruit of Crataegus pinnatifida led to the isolation of four pairs of dihydrobenzofuran neolignan enantiomers (1a/1b-4a/4b) including six new compounds (1a/1b, 2a/2b, 3a and 4a). The enantioseparations of the racemates were achieved successfully by chiral chromatographic column. Their structures were established by comprehensive spectroscopic analyses and the absolute configurations were determined by quantum mechanical calculation of electronic circular dichroism (ECD) spectra. All compounds were evaluated in vitro for their cytotoxicity using human hepatocellular carcinoma Hep3B and HepG2 cells. Among them, it was found that 2a had a selective cytotoxicity against Hep3B cells with IC50 value of 25.47 µM, while the IC50 value of its enantiomer 2b on Hep3B cells was 59.37 µM. These results implied that the absolute configurations of 2a and 2b possessed remarkable influences on their cytotoxicity. Further flow cytometry analysis indicated that 2a performed more significant effect on cell apoptosis compared with its enantiomer 2b.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Crataegus/química , Frutas/química , Lignanas/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , China , Células Hep G2 , Humanos , Lignanas/isolamento & purificação , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Estereoisomerismo
13.
Free Radic Res ; 53(6): 655-668, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31185752

RESUMO

Oxidative stress accompanying excessive accumulation of reactive oxygen species (ROS) and mitochondrial dysfunction leads to the occurrence of neurodegenerative diseases. Our previous study showed that Eclalbasaponin I (EcI), a triterpene saponin isolated from Aralia elata (Miq.) Seem. (A. elata), repressed oxidative stress in human neuroblastoma SH-SY5Y cells. However, the detailed mechanism remains unclear. In this study, pretreatment with EcI in SH-SY5Y cells significantly activated the p38-mitogenactivated protein kinase (p38), the extracellular regulated protein kinase (ERK), whereas it did not affect the c-jun NH2 terminal kinases (JNK). In accordance with the initial findings, EcI-induced neuroprotective effect was attenuated by SB203580 (SB, a p38 inhibitor) or FR180204 (FR, an ERK inhibitor), being further confirmed by specific small interfering RNA (siRNA). Inhibition of either p38 or ERK up-regulated the apoptosis induction in EcI- and H2O2-cotreated cells. Furthermore, p38 or ERK suppression enhanced intracellular and mitochondrial ROS generation, decreased the activities of endogenous antioxidant defences as well as the mitochondrial membrane potential (MMP), resulting in dysfunction of mitochondria. In addition, EcI-induced autophagy and mitophagy were obviously down-regulated when p38 or ERK activation was blocked. Cumulatively, these findings supported that EcI-caused mitophagy contributed to the neuroprotective effect through p38 or ERK activation. Mitophagy induction might be an effective therapeutic intervention in neurodegenerative diseases.


Assuntos
Apoptose/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Saponinas/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Aralia/química , Sobrevivência Celular/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/antagonistas & inibidores , Peróxido de Hidrogênio/farmacologia , Imidazóis/farmacologia , Modelos Moleculares , Conformação Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Inibidores de Proteínas Quinases/farmacologia , Pirazóis/farmacologia , Piridazinas/farmacologia , Piridinas/farmacologia , Saponinas/química , Saponinas/isolamento & purificação , Células Tumorais Cultivadas
14.
J Nat Prod ; 82(6): 1510-1517, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31150241

RESUMO

Chromatographic purification of the roots of Daphne genkwa led to 11 new guaiane-type sesquiterpenoids (1-11), named genkwanoids A-K, and six known analogues (12-17). A comprehensive set of spectroscopic methods including IR, UV, HRESIMS, and 1D/2D NMR were used to elucidate the structures and relative configurations of 1-11. The absolute configurations were determined by the optical rotation calculations and the modified Mosher's method. The possible biosynthetic pathways for 1-11 are proposed. Furthermore, the neuroprotective effects of 1-17 on H2O2-induced damage in human neuroblastoma SH-SY5Y cells were screened using an MTT assay. Compounds 9, 10, and 16 exhibited moderate neuroprotective effects, with survival rates of 79.34%, 79.94%, and 75.64% after treatment with 12.5 µM, values that were comparable to the positive control, Trolox (78.65%). Furthermore, annexin V-FITC/PI staining of cells treated with 9, 10, and 16 showed that the neuroprotective effects of these compounds may arise from inhibiting cell apoptosis.

15.
Phytochemistry ; 164: 122-129, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31125862

RESUMO

A phytochemical study on the fruits of Rubus idaeus L. (Rosaceae) yielded eight pairs of enantiomeric lignans, including one undescribed furolactone named (-)-idaeusinol A and six undescribed furofuran derivatives named (+/-)-idaeusinol B-D. The structures of these isolated compounds were elucidated by spectroscopic analyses and a combination of computational techniques including gauge-independent atomic orbital (GIAO) calculation of 1D NMR data and TD-DFT calculation of electronic circular dichroism (ECD) spectra. Bioactivity screenings suggested that (+)-idaeusinol D exhibited the most significant protective effect against H2O2-induced neurotoxicity at the concentration of 25 µM. In contrast, (-)-idaeusinol D, as the enantiomer of (+)-idaeusinol D, showed no effect against H2O2-induced neurotoxicity at both 25 and 50 µM concentration.


Assuntos
Furanos/farmacologia , Lactonas/farmacologia , Fármacos Neuroprotetores/farmacologia , Rubus/química , Sobrevivência Celular/efeitos dos fármacos , Teoria da Densidade Funcional , Relação Dose-Resposta a Droga , Furanos/química , Furanos/isolamento & purificação , Humanos , Peróxido de Hidrogênio/antagonistas & inibidores , Peróxido de Hidrogênio/farmacologia , Lactonas/química , Lactonas/isolamento & purificação , Conformação Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Estereoisomerismo , Relação Estrutura-Atividade , Células Tumorais Cultivadas
16.
Phytochemistry ; 164: 252-261, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31109713

RESUMO

Ten undescribed phenylpropanoid derivatives including four pairs of enantiomers and two 8-9' linked neolignans, together with fifteen known ones were isolated from the fruit of Crataegus pinnatifida Bunge. Their structures were established by comprehensive spectroscopic analyses. Enantiomers were separated successfully by chiral chromatographic column and their absolute configurations were determined by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. The in vitro cytotoxicity of the isolates were evaluated against two human hepatocellular carcinoma, HepG2 and Hep3B cells. Among them, (±)-crataegusanoid A, (±)-crataegusanoid B and crataegusanoid F exhibited moderate cytotoxicity. Interestingly, the different absolute configurations of (±)-crataegusanoid A and B demonstrated enantioselective cytotoxicity in HepG2 cells. Further flow cytometry analysis indicated that both (-)-crataegusanoid A and (-)-crataegusanoid B performed more significant effects on cell apoptosis, autophagy, and cell cycle progression compared with their enantiomers (+)-crataegusanoid A and (+)-crataegusanoid B. In addition, the results revealed that these two pairs of enantiomers induced protective autophagy in HepG2 cells.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Crataegus/química , Frutas/química , Neoplasias Hepáticas/tratamento farmacológico , Fenilpropionatos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Citometria de Fluxo , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologia , Modelos Moleculares , Estrutura Molecular , Fenilpropionatos/química , Fenilpropionatos/isolamento & purificação , Relação Estrutura-Atividade
17.
Planta Med ; 85(8): 648-656, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30974464

RESUMO

Four pairs of ß-carboline enantiomers (1A: /1B: -4A: /4B: ), 2 ß-carboline derivatives (5:  - 6: ) with a single enantiomeric configuration, together with 2 known achiral congeners (7:  - 8: ) were isolated from the stems of Picrasma quassioides. Their structures were elucidated on the basis of extensive spectroscopic analyses and quantum mechanical calculations. Compound 5: possesses a 4,5-seco ß-carboline framework and represents the first example of this type of ß-carboline alkaloids from nature. A possible biosynthetic pathway is proposed to generate the racemate 4: and the enantiomerically pure compounds 5: and 6: . All isolates were screened for their cytotoxicity against hepatocellular carcinoma Hep3B and HepG2 cells, which revealed that enantiomeric compounds 4A: and 4B: had distinctive effects in HepG2 cells. Further investigation showed that 4B: could induce apoptosis in HepG2 cells.


Assuntos
Alcaloides/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Carbolinas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Picrasma/química , Alcaloides/química , Alcaloides/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Carbolinas/química , Carbolinas/farmacologia , Cromatografia , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Humanos , Estrutura Molecular , Estereoisomerismo
18.
Steroids ; 146: 57-64, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30951756

RESUMO

Timosaponin AIII (TAIII), a steroidal saponin isolated from the rhizome of Anemarrhena asphodeloides, exerted cytotoxic effect in many cancer cell lines. However, the effect of TAIII on resistant tumor cancer cells was unclear. In this study, MTT assay showed that TAIII exhibited significant cytotoxicity against A549/Taxol and A2780/Taxol cells in vitro. Annexin V-FITC/PI staining revealed that TAIII induced apoptosis in A549/T and A2780/T cells. Furthermore, Western blot analysis demonstrated that TAIII inhibited the expressions of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), mammalian target of rapamycin (mTOR) as well as Ras, Raf, mitogen-activated protein kinase (MEPK), extracellular regulated protein kinases (ERK) in two taxol-resistant cancer cell lines. Besides, in vivo studies demonstrated that TAIII inhibited tumor growth in a nude mouse xenograft model. Additionally, TAIII (2.5 and 5 mg/kg) also down-regulated the protein expressions of PI3K/AKT/mTOR and Ras/Raf/MEK/ERK pathways in vivo. Taken together, these findings demonstrated that TAIII exhibited significant anti-tumor effect on taxol-resistant cells.

19.
Bioorg Chem ; 88: 102926, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31005021

RESUMO

A pair of new cycloneolignan enantiomers (1a and 1b) were isolated from the leaves of Isatis indigotica Fortune. Their structures were elucidated by extensive spectroscopic data analysis, including 1D and 2D NMR, HRESIMS, MS/MS analysis, together with theoretical electronic circular dichroism (ECD) calculations. Compounds 1a and 1b were then evaluated for their neuroprotective effects against MPP+-induced SH-SY5Y cell injury. As a result, compounds 1a (77.64%) and 1b (78.62%) exhibited moderate neuroprotective activity at the concentration of 12.5 µM compared with that of MPP+ treated group (62.00% at 1 mM) by MTT assay. Furthermore, Annexin V-FITC/PI analysis showed that apoptosis ratios of 1a and 1b were reduced to 10.99% and 9.31%, respectively.

20.
Nat Prod Res ; : 1-4, 2019 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-30856004

RESUMO

Vibsane-type diterpenes, the characteristic compounds of Viburnum odoratissimum, exhibited significant cytotoxicity in many cancer cells. To search for the potential target of vibsane-type diterpenes on lung cancer, we combined methods of network pharmacology prediction and experimental verification. 80 active ingredients, 23 potential targets and 39 related pathways were analyzed through constructing the compound-target network and target-pathway network, and the potential target (EGFR) and key pathway (PI3K/Akt) were identified. Vibsanol C, an isolated vibsane-type diterpene with excellent cytotoxicity against lung cancer cells was chosen for further confirmation. Molecular docking study and drug affinity responsive target stability (DARTS) approach further indicated that EGFR is a direct target of Vibsanol C. Moreover, mechanistic studies revealed Vibsanol C might affect PI3K/Akt pathway by Western blot analysis. In conclusion, this study successfully predicted and confirmed the potential target of Vibsane-type diterpenes on lung cancer.

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