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1.
Molecules ; 26(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34361745

RESUMO

The edible parts of the plants Camellia sinensis, Vitis vinifera and Withania somnifera were extensively used in ancient practices such as Ayurveda, owing to their potent biomedical significance. They are very rich in secondary metabolites such as polyphenols, which are very good antioxidants and exhibit anti-carcinogenic properties. This study aims to evaluate the anti-cancerous properties of these plant crude extracts on human liver cancer HepG2 cells. The leaves of Camellia sinensis, Withania somnifera and the seeds of Vitis vinifera were collected and methanolic extracts were prepared. Then, these extracts were subjected to DPPH, α- amylase assays to determine the antioxidant properties. A MTT assay was performed to investigate the viability of the extracts of HepG2 cells, and the mode of cell death was detected by Ao/EtBr staining and flow cytometry with PI Annexin- V FITC dual staining. Then, the protein expression of BAX and BCl2 was studied using fluorescent dye to determine the regulation of the BAX and BCl2 genes. We observed that all the three extracts showed the presence of bioactive compounds such as polyphenols or phytochemicals. The W. somnifera bioactive compounds were found to have the highest anti-proliferative activity on human liver cancer cells.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Camellia sinensis/química , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Vitis/química , Withania/química , Alcaloides/química , Alcaloides/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Compostos de Bifenilo/antagonistas & inibidores , Compostos de Bifenilo/química , Morte Celular/efeitos dos fármacos , Flavonoides/química , Flavonoides/isolamento & purificação , Células Hep G2 , Humanos , Picratos/antagonistas & inibidores , Picratos/química , Extratos Vegetais/química , Folhas de Planta/química , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Sementes/química , Transdução de Sinais , Taninos/química , Taninos/isolamento & purificação , Terpenos/química , Terpenos/isolamento & purificação , alfa-Amilases/genética , alfa-Amilases/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
2.
Molecules ; 26(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34361750

RESUMO

The purpose of this work is to investigate the protein kinase inhibitory activity of constituents from Acacia auriculiformis stem bark. Column chromatography and NMR spectroscopy were used to purify and characterize betulin from an ethyl acetate soluble fraction of acacia bark. Betulin, a known inducer of apoptosis, was screened against a panel of 16 disease-related protein kinases. Betulin was shown to inhibit Abelson murine leukemia viral oncogene homolog 1 (ABL1) kinase, casein kinase 1ε (CK1ε), glycogen synthase kinase 3α/ß (GSK-3 α/ß), Janus kinase 3 (JAK3), NIMA Related Kinase 6 (NEK6), and vascular endothelial growth factor receptor 2 kinase (VEGFR2) with activities in the micromolar range for each. The effect of betulin on the cell viability of doxorubicin-resistant K562R chronic myelogenous leukemia cells was then verified to investigate its putative use as an anti-cancer compound. Betulin was shown to modulate the mitogen-activated protein (MAP) kinase pathway, with activity similar to that of imatinib mesylate, a known ABL1 kinase inhibitor. The interaction of betulin and ABL1 was studied by molecular docking, revealing an interaction of the inhibitor with the ABL1 ATP binding pocket. Together, these data demonstrate that betulin is a multi-target inhibitor of protein kinases, an activity that can contribute to the anticancer properties of the natural compound and to potential treatments for leukemia.


Assuntos
Acacia/química , Antineoplásicos Fitogênicos/farmacologia , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-abl/antagonistas & inibidores , Triterpenos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Apoptose/genética , Sítios de Ligação , Caseína Quinase Iépsilon/antagonistas & inibidores , Caseína Quinase Iépsilon/genética , Caseína Quinase Iépsilon/metabolismo , Proliferação de Células/efeitos dos fármacos , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Proteínas de Fusão bcr-abl/genética , Proteínas de Fusão bcr-abl/metabolismo , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Quinase 3 da Glicogênio Sintase/genética , Quinase 3 da Glicogênio Sintase/metabolismo , Humanos , Janus Quinase 3/antagonistas & inibidores , Janus Quinase 3/genética , Janus Quinase 3/metabolismo , Células K562 , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Modelos Moleculares , Quinases Relacionadas a NIMA/antagonistas & inibidores , Quinases Relacionadas a NIMA/genética , Quinases Relacionadas a NIMA/metabolismo , Casca de Planta/química , Extratos Vegetais/química , Ligação Proteica , Conformação Proteica , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/isolamento & purificação , Proteínas Proto-Oncogênicas c-abl/química , Proteínas Proto-Oncogênicas c-abl/genética , Proteínas Proto-Oncogênicas c-abl/metabolismo , Transdução de Sinais , Triterpenos/química , Triterpenos/isolamento & purificação , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
3.
Int J Mol Sci ; 22(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209868

RESUMO

Pancracine, a montanine-type Amaryllidaceae alkaloid (AA), is one of the most potent compounds among natural isoquinolines. In previous studies, pancracine exhibited cytotoxic activity against diverse human cancer cell lines in vitro. However, further insight into the molecular mechanisms that underlie the cytotoxic effect of pancracine have not been reported and remain unknown. To fill this void, the cell proliferation and viability of cancer cells was explored using the Trypan Blue assay or by using the xCELLigence system. The impact on the cell cycle was determined by flow cytometry. Apoptosis was evaluated by Annexin V/PI and by quantifying the activity of caspases (-3/7, -8, and -9). Proteins triggering growth arrest or apoptosis were detected by Western blotting. Pancracine has strong antiproliferative activity on A549 cells, lasting up to 96 h, and antiproliferative and cytotoxic effects on MOLT-4 cells. The apoptosis-inducing activity of pancracine in MOLT-4 cells was evidenced by the significantly higher activity of caspases. This was transmitted through the upregulation of p53 phosphorylated on Ser392, p38 MAPK phosphorylated on Thr180/Tyr182, and upregulation of p27. The pancracine treatment negatively altered the proliferation of A549 cells as a consequence of an increase in G1-phase accumulation, associated with the downregulation of Rb phosphorylated on Ser807/811 and with the concomitant upregulation of p27 and downregulation of Akt phosphorylated on Thr308. This was the first study to glean a deeper mechanistic understanding of pancracine activity in vitro. Perturbation of the cell cycle and induction of apoptotic cell death were considered key mechanisms of pancracine action.


Assuntos
Adenocarcinoma de Pulmão/patologia , Proliferação de Células/efeitos dos fármacos , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Leucemia/patologia , Neoplasias Pulmonares/patologia , Células A549 , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Amaryllidaceae/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Células Hep G2 , Compostos Heterocíclicos de 4 ou mais Anéis/isolamento & purificação , Humanos , Células MCF-7
4.
Molecules ; 26(13)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202760

RESUMO

A phytochemical investigation of the leaves of the medicinal plant Isodon rubescens led to the isolation of the two new degraded abietane lactone diterpenoids rubesanolides F (1) and G (2). Their structures were elucidated based on the analyses of the HRESIMS and 1D/2D NMR spectral data, and their absolute configurations were determined by ECD spectrum calculations and X-ray single crystal diffraction methods. Compounds 1 and 2, with a unique γ-lactone subgroup between C-8 and C-20, were found to form a carbonyl carbon at C-13 by removal of the isopropyl group in an abietane diterpene skeleton. Rubesanolide G (2) is a rare case of abietane that possesses a cis-fused configuration between rings B and C. The two isolates were evaluated for their biological activities against two cancer cell lines (A549 and HL60), three fungal strains (Candida alba, Aspergillus niger and Rhizopus nigricans) and three bacterial strains (Escherichia coli, Staphylococcus aureus and Bacillus subtilis).


Assuntos
Abietanos , Anti-Infecciosos , Antineoplásicos Fitogênicos , Bactérias/crescimento & desenvolvimento , Fungos/crescimento & desenvolvimento , Isodon/química , Lactonas , Neoplasias/tratamento farmacológico , Folhas de Planta/química , Células A549 , Abietanos/química , Abietanos/isolamento & purificação , Abietanos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Células HL-60 , Humanos , Lactonas/química , Lactonas/isolamento & purificação , Lactonas/farmacologia , Neoplasias/metabolismo , Neoplasias/patologia
5.
Molecules ; 26(12)2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34203971

RESUMO

Medicinal plants have been traditionally used to treat cancer in Ethiopia. However, very few studies have reported the in vitro anticancer activities of medicinal plants that are collected from different agro-ecological zones of Ethiopia. Hence, the main aim of this study was to screen the cytotoxic activities of 80% methanol extracts of 22 plants against human peripheral blood mononuclear cells (PBMCs), as well as human breast (MCF-7), lung (A427), bladder (RT-4), and cervical (SiSo) cancer cell lines. Active extracts were further screened against human large cell lung carcinoma (LCLC-103H), pancreatic cancer (DAN-G), ovarian cancer (A2780), and squamous cell carcinoma of the esophagus (KYSE-70) by using the crystal violet cell proliferation assay, while the vitality of the acute myeloid leukemia (HL-60) and histiocytic lymphoma (U-937) cell lines was monitored in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) microtiter assay. Euphorbia schimperiana, Acokanthera schimperi, Kniphofia foliosa, and Kalanchoe petitiana exhibited potent antiproliferative activity against A427, RT-4, MCF-7, and SiSo cell lines, with IC50 values ranging from 1.85 ± 0.44 to 17.8 ± 2.31 µg/mL. Furthermore, these four extracts also showed potent antiproliferative activities against LCLC-103H, DAN-G, A2780, KYSE-70, HL-60, and U-937 cell lines, with IC50 values ranging from 0.086 to 27.06 ± 10.8 µg/mL. Hence, further studies focusing on bio-assay-guided isolation and structural elucidation of active cytotoxic compounds from these plants are warranted.


Assuntos
Medicina Tradicional Africana/métodos , Extratos Vegetais/análise , Plantas Medicinais/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/metabolismo , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/metabolismo , Linhagem Celular Tumoral/efeitos dos fármacos , Etiópia , Humanos , Concentração Inibidora 50 , Extratos Vegetais/química
6.
Fitoterapia ; 153: 104965, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34129921

RESUMO

Chemical investigation of the leaves and stems of Dioscorea bulbifera resulted in isolation of 10 compounds, including three new norclerodane diterpenoids, diosbulbiferins A (1) and B (2) and diosbulbiferinoside A (3), and one new natural congener, diosbulbiferin C (4), along with one new tetrahydrophenanthrene, diosbulbinone (8). Their structures were elucidated by comprehensive analyses of spectroscopic methods, including NMR and mass spectra. The absolute configurations of compounds 1-3 and 8 were deduced by time-dependent density functional theory (TD-DFT) electronic circular dichroism (ECD) spectroscopic analyses. In addition, cytotoxic effects against MCF-7, HepG2, and SK-Mel-2 cancer cells and in vitro anti-inflammatory effects of the isolated compounds in LPS-stimulated BV2 microglial cells were also reported.


Assuntos
Anti-Inflamatórios/farmacologia , Dioscorea/química , Diterpenos/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Diterpenos/isolamento & purificação , Células Hep G2 , Humanos , Células MCF-7 , Camundongos , Microglia/efeitos dos fármacos , Estrutura Molecular , Óxido Nítrico , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Folhas de Planta/química , Caules de Planta/química , Vietnã
7.
Fitoterapia ; 153: 104966, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34144143

RESUMO

Euphorboside A (1), an unusual meroterpenoid glycoside featuring the incorporation of an acylphloroglucinol moiety into a humulene skeleton to form a 6/6/11 ring system, was isolated from the roots of Euphorbia kansuensis. Its structure was elucidated by extensive spectroscopic analysis, chemical methods, and ECD calculations. Compound 1 was screened for the cytotoxicity against nine cancer cell lines, and 1 showed marked inhibitory activities against human colon cancer RKO and human breast cancer MDA-MB-231 cell lines with IC50 values of 3.70 and 4.15 µM, respectively.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Euphorbia/química , Glicosídeos/farmacologia , Sesquiterpenos Monocíclicos/química , Floroglucinol/química , Terpenos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , China , Glicosídeos/isolamento & purificação , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Raízes de Plantas/química , Terpenos/isolamento & purificação
8.
Int J Biol Macromol ; 183: 2262-2271, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34062158

RESUMO

Degenerative diseases such as cancer and cardiovascular diseases, and antimicrobial resistance are becoming prominent health problems needing utmost public health attention. Curative interventions such as the use of pharmaceutical drugs and alternative plant medicines are increasingly being explored. Plant polysaccharides have gained attention for their promising bioactivities such as antioxidant, antimicrobial and anticancer activities. Bioactive plant polysaccharides are also being preferred for their relatively few side effects compared to conventional pharmaceuticals. The elucidation of the bioactive potential of plant polysaccharides in disease treatment entails an understanding of the factors that determine their biofunctional properties using functional and mechanistic assays. This review summarizes the literature on the composition, structural, functional, and mechanistic determinations of the antioxidant, anticancer and antimicrobial activities of plant polysaccharides. The outcome of this review highlights the leading trends in the elucidation of the antioxidant, anticancer and antimicrobial activities of plant polysaccharides and underscores the promising health benefits of plant polysaccharides.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Extratos Vegetais/farmacologia , Plantas , Polissacarídeos/farmacologia , Animais , Antibacterianos/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Antioxidantes/isolamento & purificação , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Plantas/química , Polissacarídeos/isolamento & purificação , Solubilidade , Água/química
9.
Fitoterapia ; 153: 104925, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33984438

RESUMO

Investigation on tannins having antitumor properties led to the isolation of two new C-glycosidic ellagitannins (1 and 2) along with seven known ellagitannins (3-9) and a related polyphenolic constituent (10) from Lawsonia inermis leaves. Our intensive HRESIMS, 1D and 2D NMR, and ECD spectroscopic studies of new tannins have shown that one (1) has a monomer structure of C-glycosidic tannin, and the other (2) has a dimeric structure of 2,3-O-hexahydroxydiphenoyl glucopyranose and a C-glycosidic tannin. Among the known compounds, one (3) is a C-glycosidic tannin that was isolated first of all from nature, five were C-glycosidic tannins, vescalagin (4), 1-O-methylvescalagin (5), castalagin (6), stachyurin (7), and casuarinin (8), and one was an O-glycosidic ellagitannin, tellimagrandin II (9). The remaining phenolic constituent from the leaves was identified as valoneic acid dilactone (10). The ellagitannins 1, and 3-9 demonstrated noticeable cytotoxicity on human oral squamous cell carcinoma cell lines (HSC-2, HSC-4, and Ca9-22), and lower effects on human oral normal cells (HGF, HPC, and HPLF). Tellimagrandin II (9) had the highest tumor-specific cytotoxicity, and also cleaved poly (ADP-ribose) polymerase 1 in HSC-2 cells. These findings showed that L. inermis ellagitannins may be a candidate for the production of anti-oral cancer materials.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Taninos Hidrolisáveis/farmacologia , Lawsonia (Planta)/química , Antineoplásicos Fitogênicos/isolamento & purificação , Carcinoma de Células Escamosas , Linhagem Celular Tumoral , Egito , Ácido Gálico/análogos & derivados , Glucosídeos , Glicosídeos , Humanos , Taninos Hidrolisáveis/isolamento & purificação , Estrutura Molecular , Neoplasias Bucais , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Folhas de Planta/química
10.
Chem Biodivers ; 18(6): e2100089, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33893719

RESUMO

A novel alkali-soluble polysaccharide (AASP) was isolated from Angelica sinensis (Oliv.) Diels under aqueous alkali treatment, and its structural characterization and antitumor activity in Vivo were evaluated in present study. Results of HPGPC and IC revealed that AASP was a neutral polysaccharide containing Ara, Gal and Glc in the mole ratio of 1.00 : 2.26 : 24.43, with the average molecular weight of 4.7 kDa. Periodate oxidation, Smith degradation, methylation, FT-IR, and NMR analyses further demonstrated that a preliminary structure of AASP was proposed as follows: (1→3)-linked arabinose, (1→6)-linked galactose, and (1→), (1→4), (1→6), (1→3,6)-linked glucose with α- and ß-configuration. In Vivo antitumor assays, AASP exhibited prominent antitumor effects on H22 hepatoma cells with an inhibitory ratio of 48.57 % and effectively protected thymuses and spleens of tumor-bearing mice. Besides, AASP displayed a proliferation stimulating activity of immunocytes (splenocytes, peritoneal macrophages and natural killer cells), and an auxo-action for cytokines release (TNF-α, IL-2 and IFN-γ), leading to the apoptosis of H22 solid tumors cells via G0/G1 phase arrested. The above data demonstrated that AASP holds great application potential to be a safe and effective antitumor supplement in the future.


Assuntos
Álcalis/química , Angelica sinensis/química , Antineoplásicos Fitogênicos/farmacologia , Polissacarídeos/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citocinas/antagonistas & inibidores , Citocinas/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neoplasias Hepáticas Experimentais/metabolismo , Neoplasias Hepáticas Experimentais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Solubilidade
11.
Chem Biodivers ; 18(6): e2100115, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33915026

RESUMO

The chemical composition and in vitro antibacterial and cytotoxic activities of the essential oil (EO) of Chiliadenus antiatlanticus (Emb. & Maire) Gómiz, an asteraceous species endemic to the southwest of Morocco, were investigated. The EO yield was 1.07±0.28 %, twenty-seven metabolites were identified representing more than 96.4 % of the total composition. Camphor (35.7 %) and derivatives, borneol (4.9 %) and camphene (4.2 %) together with intermedeol (19.9 %), α-pinene (15.5 %) and (E)-pinocarveol (4.1 %) were the major constituents. An antibacterial activity was noticed against 24 strains (all Gram-positive) out of 71 at MICs values=100 µg/mL. The EO also showed significant toxicity towards liver HepG2 (55.8 % of cell viability) and melanoma B16 4A5 (41.6 % of cell viability) tumor cell lines at 100 µg/mL.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Asteraceae/química , Bactérias Gram-Positivas/efeitos dos fármacos , Óleos Voláteis/farmacologia , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação
12.
Eur J Med Chem ; 220: 113471, 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-33930801

RESUMO

Natural products have long been an important source for discovery of new drugs to treat human diseases. Piperlongumine (PL) is an amide alkaloid isolated from Piper longum L. (long piper) and other piper plants and has received widespread attention because of its diverse biological activities. A large number of PL derivatives have been designed, synthesized and assessed in many pharmacological functions, including antiplatelet aggregation, neuroprotective activities, anti-diabetic activities, anti-inflammatory activities, anti-senolytic activities, immune activities, and antitumor activities. Among them, the anti-tumor effects and application of PL and its derivatives are most extensively studied. We herein summarize the development of PL derivatives, the structure and activity relationships (SARs), and their therapeutic potential on the treatments of various diseases, especially against cancer. We also discussed the challenges and future directions associated with PL and its derivatives in these indications.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Dioxolanos/farmacologia , Hipoglicemiantes/farmacologia , Fármacos Neuroprotetores/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Dioxolanos/química , Dioxolanos/isolamento & purificação , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Estrutura Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Piper/química , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/isolamento & purificação
13.
Chem Biodivers ; 18(6): e2100094, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33860612

RESUMO

Magonia pubescens A. St.-Hil. is a Brazilian species often used in ethnopharmacology for wound and pain healing and seborrhea treatment. For the first time, essential oils (EOs) obtained from M. pubescens inflorescences were studied. The plant materials (Montes Claros, Brazil, 2018) were submitted to different gamma-radiation doses and their chemical compositions were analyzed by GC/MS and GC-FID. The cytotoxic activity of the EOs was evaluated against K562 and MDA-MB-231 cancer cell lines. A total of 30 components were identified, being 24 compounds detected for the first time in M. pubescens. The main obtained components were hotrienol (35.9 %), cis-linalool oxide (17.0 %) and trans-linalool oxide (10.2 %). The chemical composition of the EO was slightly affected by the applied radiation doses. Irradiated and non-irradiated EOs showed cytotoxic activity against both cell lines and the non-irradiated EO sample was the most active against the K562 cell lines (IC50 =22.10±1.98).


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Sapindaceae/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação
14.
Int J Biol Macromol ; 183: 119-131, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-33905802

RESUMO

Hedyotis diffusa polysaccharides, as the main component and an important bioactive substance of Hedyotis diffusa, are effective immunomodulators with various pharmacological activities, including antitumour, anti-inflammatory, antioxidant, anti-fatigue and immunity-enhancing activities. The total polysaccharides extracted from Hedyotis diffusa and Scutellaria barbata have great effects in treating liver cancer, gastric cancer, rectal cancer, glioma and nasopharyngeal carcinoma. Moreover, different materials and extraction methods result in differences in the structure and bioactivity of Hedyotis diffusa polysaccharides. Therefore, this paper summarizes the isolation, purification, structural characteristics, pharmacological activities, and combined action of Hedyotis diffusa polysaccharides to provide a reference for further study.


Assuntos
Hedyotis/química , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Humanos , Fatores Imunológicos/química , Fatores Imunológicos/isolamento & purificação , Fatores Imunológicos/farmacologia , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Relação Estrutura-Atividade
15.
Anticancer Res ; 41(4): 1883-1893, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33813393

RESUMO

BACKGROUND/AIM: Hepatocellular carcinoma (HCC) is a highly prevalent disease and treatment is limited. Therefore, development of new therapeutic agents is urgent. The aim of this study was to investigate the in vitro and in vivo anti-cancer effects of Nardostachys jatamansi root extract (NJRE) against HCC and underlying mechanisms involved in such effects. MATERIALS AND METHODS: Effects of NJRE on viability of HCC cell lines were determined by MTT analysis and annexin/PI apoptosis assays. Expression levels of proteins in MAPK and STAT3 pathways and caspase-3 and PARP after treatment with NJRE in HCC cell lines were determined by western blotting. In a syngeneic model using mouse HCC cells Hepa1-6, inhibition of tumor formation after oral administration of NJRE was determined and expression levels of phospho-ERK and phospho-STAT3 in liver tissues were analyzed by immunohistochemical staining. RESULTS: NJRE reduced the activation of STAT3 by inhibiting the expression of ERK and finally attenuated the proliferation of HCC. CONCLUSION: NJRE has anti-cancer effects against HCC. It has potential to be used in the treatment of human HCC.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Nardostachys , Raízes de Plantas , Fator de Transcrição STAT3/metabolismo , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/patologia , Masculino , Camundongos Endogâmicos C57BL , Nardostachys/química , Fosforilação , Raízes de Plantas/química , Transdução de Sinais , Carga Tumoral/efeitos dos fármacos
16.
Int J Mol Sci ; 22(6)2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33810045

RESUMO

Melanoma is a highly metastatic disease with an increasing rate of incidence worldwide. It is treatment refractory and has poor clinical prognosis; therefore, the development of new therapeutic agents for metastatic melanoma are urgently required. In this study, we created a lung-seeking A375LM5IF4g/Luc BRAFV600E mutant melanoma cell clone and investigated the bioefficacy of a plant sesquiterpene lactone deoxyelephantopin (DET) and its novel semi-synthetic derivative, DETD-35, in suppressing metastatic A375LM5IF4g/Luc melanoma growth in vitro and in a xenograft mouse model. DET and DETD-35 treatment inhibited A375LM5IF4g/Luc cell proliferation, and induced G2/M cell-cycle arrest and apoptosis. Furthermore, A375LM5IF4g/Luc exhibited clonogenic, metastatic and invasive abilities, and several A375LM5IF4g/Luc metastasis markers, N-cadherin, MMP2, vimentin and integrin α4 were significantly suppressed by treatment with either compound. Interestingly, DET- and DETD-35-induced Reactive Oxygen Species (ROS) generation and glutathione (GSH) depletion were found to be upstream events important for the in vitro activities, because exogenous GSH supplementation blunted DET and DETD-35 effects on A375LM5IF4g/Luc cells. DET and DETD-35 also induced mitochondrial DNA mutation, superoxide production, mitochondrial bioenergetics dysfunction, and mitochondrial protein deregulation. Most importantly, DET and DETD-35 inhibited lung metastasis of A375LM5IF4g/Luc in NOD/SCID mice through inhibiting pulmonary vascular permeability and melanoma cell (Mel-A+) proliferation, angiogenesis (VEGF+, CD31+) and EMT (N-cadherin) in the tumor microenvironment in the lungs. These findings indicate that DET and DETD-35 may be useful in the intervention of lung metastatic BRAFV600E mutant melanoma.


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Asteraceae/química , Lactonas/isolamento & purificação , Lactonas/farmacologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Apoptose/genética , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Imuno-Histoquímica , Lactonas/química , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Melanoma/patologia , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Estrutura Molecular , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Proteínas Proto-Oncogênicas B-raf/genética , Espécies Reativas de Oxigênio/metabolismo , Sesquiterpenos/química , Microambiente Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Molecules ; 26(6)2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33808969

RESUMO

BACKGROUND: This study reports on the cytotoxic properties of nordamnacanthal and damnacanthal, isolated from roots of Morinda elliptica on T-lymphoblastic leukaemia (CEM-SS) cell lines. METHODS: MTT assay, DNA fragmentation, ELISA and cell cycle analysis were carried out. RESULTS: Nordamnacanthal and damnacanthal at IC50 values of 1.7 µg/mL and10 µg/mL, respectively. At the molecular level, these compounds caused internucleosomal DNA cleavage producing multiple 180-200 bp fragments that are visible as a "ladder" on the agarose gel. This was due to the activation of the Mg2+/Ca2+-dependent endonuclease. The induction of apoptosis by nordamnacanthal was different from the one induced by damnacanthal, in a way that it occurs independently of ongoing transcription process. Nevertheless, in both cases, the process of dephosphorylation of protein phosphates 1 and 2A, the ongoing protein synthesis and the elevations of the cytosolic Ca2+ concentration were not needed for apoptosis to take place. Nordamnacanthal was found to have a cytotoxic effect by inducing apoptosis, while damnacanthal caused arrest at the G0/G1 phase of the cell cycle. CONCLUSION: Damnacanthal and nordamnacanthal have anticancer properties, and could act as potential treatment for T-lymphoblastic leukemia.


Assuntos
Aldeídos/farmacologia , Antraquinonas/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Morinda/química , Plantas Medicinais/química , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Aldeídos/isolamento & purificação , Antraquinonas/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Fragmentação do DNA , Endodesoxirribonucleases/metabolismo , Humanos , Raízes de Plantas/química , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo
18.
Molecules ; 26(7)2021 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-33801575

RESUMO

Momordica balsamina leaf extracts originating from three different geographical locations were analyzed using reversed-phase liquid chromatography (RP-LC) coupled to travelling wave ion mobility (TWIMS) and high-resolution mass spectrometry (HRMS) in conjunction with chemometric analysis to differentiate between potential chemotypes. Furthermore, the cytotoxicity of the three individual chemotypes was evaluated using HT-29 colon cancer cells. A total of 11 molecular species including three flavonol glycosides, five cucurbitane-type triterpenoid aglycones and three glycosidic cucurbitane-type triterpenoids were identified. The cucurbitane-type triterpenoid aglycones were detected in the positive ionization mode following dehydration [M + H - H2O]+ of the parent compound, whereas the cucurbitane-type triterpenoid glycosides were primarily identified following adduct formation with ammonia [M + NH4]+. The principle component analysis (PCA) loadings plot and a variable influence on projection (VIP) analysis revealed that the isomeric pair balsaminol E and/or karavilagen E was the key molecular species contributing to the distinction between geographical samples. Ultimately, based on statistical analysis, it is hypothesized that balsaminol E and/or karavilagen E are likely responsible for the cytotoxic effects in HT-29 cells.


Assuntos
Antineoplásicos Fitogênicos/química , Flavonóis/química , Glicosídeos/química , Momordica/química , Triterpenos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Cromatografia de Fase Reversa , Flavonóis/isolamento & purificação , Flavonóis/farmacologia , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Células HT29 , Humanos , Concentração Inibidora 50 , Espectrometria de Massas/métodos , Extratos Vegetais/química , Folhas de Planta/química , Análise de Componente Principal , Relação Estrutura-Atividade , Triterpenos/isolamento & purificação , Triterpenos/farmacologia
19.
Molecules ; 26(8)2021 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-33920405

RESUMO

The bioassay-guided fractionation of a CHCl3-MeOH extract from the stems of Cissus trifoliata identified an active fraction against PC3 prostate cancer cells. The treatment for 24 h showed an 80% reduction in cell viability (p ≤ 0.05) by a WST-1 assay at a concentration of 100 µg/mL. The HPLC-QTOF-MS analysis of the fraction showed the presence of coumaric and isoferulic acids, apigenin, kaempferol, chrysoeriol, naringenin, ursolic and betulinic acids, hexadecadienoic and octadecadienoic fatty acids, and the stilbene resveratrol. The exposure of PC3 cells to resveratrol (IC25 = 23 µg/mL) for 24 h induced significant changes in 847 genes (Z-score ≥ ±2). The functional classification tool of the DAVID v6.8 platform indicates that the underlying molecular mechanisms against the proliferation of PC3 cells were associated (p ≤ 0.05) with the process of differentiation and metabolism. These findings provide experimental evidence suggesting the potential of C. trifoliata as a promising natural source of anticancer compounds.


Assuntos
Antineoplásicos Fitogênicos/química , Proliferação de Células/efeitos dos fármacos , Cissus/química , Proteínas de Neoplasias/genética , Transcriptoma , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Apigenina/química , Apigenina/isolamento & purificação , Apigenina/farmacologia , Bioensaio , Sobrevivência Celular/efeitos dos fármacos , Flavanonas/química , Flavanonas/isolamento & purificação , Flavanonas/farmacologia , Flavonas/química , Flavonas/isolamento & purificação , Flavonas/farmacologia , Perfilação da Expressão Gênica , Humanos , Quempferóis/química , Quempferóis/isolamento & purificação , Quempferóis/farmacologia , Masculino , Análise em Microsséries , Proteínas de Neoplasias/classificação , Proteínas de Neoplasias/metabolismo , Células PC-3 , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/isolamento & purificação , Triterpenos Pentacíclicos/farmacologia , Extratos Vegetais/química , Resveratrol/química , Resveratrol/isolamento & purificação , Resveratrol/farmacologia
20.
Biomed Pharmacother ; 138: 111350, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33721752

RESUMO

Cancer is a fatal disease with high mortality and low survival rate worldwide. At present, there is still no known cure for most cancers. Traditional Chinese medicine (TCM) represents a noteworthy reservoir for anticancer agents in drug discovery and development. Curcumae Rhizoma (called Ezhu in Chinese) is widely prescribed in TCM for anticancer therapy owing to its broad-spectrum antineoplastic activities. Especially, the terpenoids isolated from the essential oil of Curcumae Rhizoma form an integral part of cancer research and are well established as a potential anticancer agent. For example, ß-elemene has been developed into a new drug for the treatment of solid tumors in China, and is currently undergoing clinical trials in the United States. The review aims to systematically summarize the recent advances on the anticancer effects and related molecular mechanisms of Curcumae Rhizoma, and its terpenoids (ß-elemene, Furanodiene, Furanodienone, Germacrone, Curcumol, Curdione). In addition, we evaluated and compared the anticancer efficacy and clinical use of the terpenoids with combination therapies and traditional therapies. Therefore, this review provides sufficient evidence for the anticancer therapeutic potential of Curcumae Rhizoma and its terpenoids, and will contribute to the development of potential anticancer drugs.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Curcuma , Medicamentos de Ervas Chinesas/administração & dosagem , Rizoma , Terpenos/administração & dosagem , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Terpenos/isolamento & purificação
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