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1.
Molecules ; 26(17)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34500636

RESUMO

The African pumpkin (Momordica balsamina) contains bioactive phenolic compounds that may assist in reducing oxidative stress in the human body. The leaves are mainly consumed after boiling in water for a specific time; this hydrothermal process and conditions of the gastrointestinal tract may affect the presence and bioactivity of phenolics either positively or negatively. In this study, the effects of hydrothermal processing (boiling) and in vitro simulated human digestion on the phenolic composition, bioaccessibility and bioactivity in African pumpkin were investigated in comparison with those of spinach (Spinacia oleracea). A high-resolution ultra-performance liquid chromatography, coupled with diode array detection, quadrupole time-of-flight and mass spectrometer (UPLC-DAD-QTOF-MS) was used to profile phenolic metabolites. Metabolites such as 3-caffeoylquinic acid, 5-caffeoylquinic acid, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid were highly concentrated in the boiled vegetable extracts compared to the raw undigested and all digested samples. The majority of African pumpkin and spinach extracts (non-digested and digested) protected Deoxyribonucleic acid (DNA), (mouse fibroblast) L929 and human epithelial colorectal adenocarcinoma (Caco-2) cells from 2,2'-Azobis(2-methylpropionamidine) dihydrochloride (AAPH)-induced oxidative damage. From these results, the consumption of boiled African pumpkin leaves, as well as spinach, could be encouraged, as bioactive metabolites present may reduce oxidative stress in the body.


Assuntos
Cucurbita/química , Digestão/efeitos dos fármacos , Momordica/química , Fenóis/química , Fenóis/farmacologia , Folhas de Planta/química , Animais , Antioxidantes/química , Células CACO-2 , Linhagem Celular Tumoral , Flavonoides/química , Humanos , Camundongos , Oxirredução/efeitos dos fármacos , Extratos Vegetais/química , Polifenóis/química , Ácido Quínico/análogos & derivados , Ácido Quínico/química , Spinacia oleracea/química , Verduras/química
2.
Environ Toxicol ; 36(11): 2196-2205, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34272816

RESUMO

Plant-derived compounds and/or extracts have proven to be beneficial for the treatment of a broad spectrum of cancers with minimal side effects. In this study, we investigated whether a crude acetone extract of Momordica balsamina (MBE) can interfere with the metastatic ability of HT-29 colorectal cancer (CRC) cells. The phytochemical composition of MBE was determined by ultra-performance liquid chromatography and cytotoxic effects by the MTT and acridine orange/ethidium bromide staining assays. The effect of MBE on the formation of reactive oxygen species was assessed using the DCFH2 -DA assay. Wound healing assay, transwell cell invasion assay, cell adhesion assay, and the extracellular matrix-cell adhesion array were used to assess the antimetastatic effects of MBE. The effect of MBE on the expression of TNF-α, NF-κB, TIMP-3, MMP-2, and MMP-9 was assessed by western blot analysis. Our results showed that MBE consists of a mixture of compounds without a known anticancer activity in CRC and exhibits cytotoxicity against HT-29 cells. MBE also suppressed reactive oxygen species formation, cell invasion, cell migration, and cell adhesion. The reduction of cell invasion was associated with the downregulation of TNF-α, NF-κB, MMP2, and MMP9 and upregulation of TIMP-3 proteins. We concluded that MBE inhibits the metastatic ability of HT-29 CRC cells in vitro.


Assuntos
Neoplasias do Colo , Momordica , Acetona , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias do Colo/tratamento farmacológico , Células HT29 , Humanos , Extratos Vegetais/farmacologia
3.
Molecules ; 26(9)2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-34063700

RESUMO

Momordica charantia is a popular vegetable associated with effective complementary and alternative diabetes management in some parts of the world. However, the molecular mechanism is less commonly investigated. In this study, we investigated the association between a major cucurbitane triterpenoid isolated from M. charantia, 3ß,7ß,25-trihydroxycucurbita-5,23(E)-dien-19-al (THCB) and peroxisome proliferator activated receptor gamma (PPARγ) activation and its related activities using cell culture and molecular biology techniques. In this study, we report on both M. charantia fruit crude extract and THCB in driving the luciferase activity of Peroxisome Proliferator Response Element, associated with PPARγ activation. Other than that, THCB also induced adipocyte differentiation at far less intensity as compared to the full agonist rosiglitazone. In conjunction, THCB treatment on adipocytes also resulted in upregulation of PPAR gamma target genes expression; AP2, adiponectin, LPL and CD34 at a lower magnitude compared to rosiglitazone's induction. THCB also induced glucose uptake into muscle cells and the mechanism is via Glut4 translocation to the cell membrane. In conclusion, THCB acts as one of the many components in M. charantia to induce hypoglycaemic effect by acting as PPARγ ligand and inducing glucose uptake activity in the muscles by means of Glut4 translocation.


Assuntos
Momordica/química , PPAR gama/metabolismo , Triterpenos/química , Células 3T3-L1 , Adipócitos/citologia , Animais , Diferenciação Celular , Membrana Celular/metabolismo , Glucose/metabolismo , Hepatócitos/citologia , Hipoglicemia/tratamento farmacológico , Insulina/química , Ligantes , Camundongos , Células Musculares/citologia , Domínios Proteicos , Rosiglitazona/farmacologia , Triterpenos/farmacologia
4.
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
5.
Int J Mol Sci ; 22(5)2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33808007

RESUMO

Obesity and its associated conditions, such as type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), are a particular worldwide health problem at present. Momordica cochinchinensis (MC) is consumed widely in Southeast Asia. However, whether it has functional effects on fat-induced metabolic syndrome remains unclear. This study was conducted to examine the prevention effect of Momordica cochinchinensis aril (MCA) on obesity, non-alcoholic fatty liver and insulin resistance in mice. MCA protected the mice against high-fat diet (HFD)-induced body weight gain, hyperlipidemia and hyperglycemia, compared with mice that were not treated. MCA inhibited the expansion of adipose tissue and adipocyte hypertrophy. In addition, the insulin sensitivity-associated index that evaluates insulin function was also significantly restored. MCA also regulated the secretion of adipokines in HFD-induced obese mice. Moreover, hepatic fat accumulation and liver damage were reduced, which suggested that fatty liver was prevented by MCA. Furthermore, MCA supplementation suppressed hepatic lipid accumulation by activation of the AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-alpha (PPAR-alpha) signaling pathway in the human fatty liver HuS-E/2 cell model. Our data indicate that MCA altered the microbial contents of the gut and modulated microbial dysbiosis in the host, and consequently is involved in the prevention of HFD-induced adiposity, insulin resistance and non-alcoholic fatty liver disease.


Assuntos
Frutas/química , Microbioma Gastrointestinal/efeitos dos fármacos , Momordica/química , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Obesidade/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Dieta Hiperlipídica/efeitos adversos , Masculino , Camundongos , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade/induzido quimicamente , Obesidade/metabolismo , Obesidade/patologia , Extratos Vegetais/química
6.
Food Chem ; 347: 129041, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33508585

RESUMO

In the present study, spine gourd slices were dried in a convective dryer at 40, 50, 60 and 70 °C temperature. The change in quality of spine guard was determined by analyzing the change in proximate, minerals, functional group, chlorophyll, ascorbic acid, and antioxidant characteristics. Increase in drying temperature changed the protein (4.62-12.88 g/100 g), fiber (3.14-3.53 g/100 g), total phenolic (14.85-14.99 mg gallic acid equivalent/g) and total flavonoid (30.1-64.8 mg quercetin equivalent/100 g) content while reduction occurred in fat (4.02-3.07 g/100 g), carbohydrate (76.13-55.22 g/100 g), chlorophyll (0.34-0.100 mg/g), ascorbic acid (29.94-4.50 mg/100 g) and antioxidant activity (96.58-85.06%). Mineral content of fresh SG differed significantly with dried samples (p < 0.05), while variable effects were associated with the change in drying temperatures. Changes in functional groups were analyzed by Fourier transform infrared spectrophotometer. The observed parameters were optimized using principal component analysis. The sample dried at 40 °C was superior in quality whereas higher protein and antioxidants were found at 70 °C.


Assuntos
Antioxidantes/química , Minerais/análise , Momordica/química , Ácido Ascórbico/análise , Clorofila/análise , Dessecação , Momordica/metabolismo , Análise de Componente Principal , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura
7.
Protoplasma ; 258(2): 347-360, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33083915

RESUMO

The infrageneric delimitation of Momordica, a medicinally important genus of Cucurbitaceae, is ill-defined until date. Momordica chromosomes are extremely small and are difficult to stain and visualize because of the dense cytoplasmic background. We have conducted karyomorphometric analysis by EMA method in five Indian Momordica species, and the nuclear genome sizes were estimated by flow cytometry for the first time. The somatic chromosome numbers ranged from 2n = 18 to 56 in the species. We have resolved previously disputed chromosome numbers in M. cymbalaria and M. dioica as 2n = 18 (lowest) and 2n = 56, respectively. Chromosome counts in the other species were re-confirmed as 2n = 22 in M. charantia, 2n = 28 in M. cochinchinensis and 2n = 56 in M. subangulata. The largest genome size was recorded in M. cymbalaria (3.74 pg 2C-1), while the smallest size (0.72 pg 2C-1) was detected in M. charantia var. charantia. The nuclear genome sizes were analysed in comparison to chromosome numbers and total chromosome lengths of the species. Karyomorphometric indices showed comparable symmetric karyotypes in the species except in M. cymbalaria having tendency towards asymmetry. The UPGMA phenogram and principle component analysis based on nuclear DNA contents and karyomorphometric parameters demonstrated interspecies differences, intraspecific distinction within M. charantia varieties and highlighted distinction of M. cymbalaria. This study was further supported by the rDNA ITS sequence-based phylogenetic analysis which revealed the monophyletic origin of the Indian members of Momordica and clarified the intraspecies relationship among the studied members. As a whole, the study brought out new insights on species diversification within the genus Momordica in India and would benefit further studies on biosystematics and plant breeding programmes.


Assuntos
Núcleo Celular/metabolismo , DNA de Plantas/genética , DNA Ribossômico/genética , Momordica/genética , Índia , Filogenia
8.
Eur J Nutr ; 60(4): 1819-1832, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32860532

RESUMO

BACKGROUND: Momordica saponin extract (MSE) was found to not only improve longevity and neuroprotection but also alleviate fat accumulation in Caenorhabditis elegans in our previous study. However, the lipid-lowering activity of MSE alone could not fully explain its ability to improve health, so the antistress effects of MSE were further studied. METHODS: Using C. elegans as an in vivo animal, the lifespan of MSE-treated C. elegans under various stressors (H2O2, paraquat and heat) and normal conditions was studied. Furthermore, the antioxidant activities of MSE were discussed. To study the underlying mechanisms, the expression of stress resistance genes and the resistance of related mutants to H2O2 stress were tested. RESULTS: MSE significantly improved the lifespan of C. elegans under stress and normal conditions. Meanwhile, the mobility of C. elegans was also improved. Moreover, the activities of SOD and CAT and the ratio of GSH/GSSG were elevated. Consistently, the levels of ROS and lipid oxidation (the NEFA and MDA content) were reduced. Furthermore, MSE treatment upregulated the expression of the sod-3, sod-5, clt-1, clt-2, hsp-16.1 and hsp-16.2 genes. All biomarkers indicated that the antistress and anti-aging activities of MSE were due to its strong antioxidant activities. Finally, MSE induced nuclear DAF-16::GFP localization. Studies with mutants revealed that skn-1 and hsf-1 were involved in the activity of MSE, which might upregulate the expression of downstream stress-responsive genes. CONCLUSIONS: Therefore, in addition to its lipid-lowering property, the ability of MSE to improve healthspan was also attributed to the stress resistance effect. Together, MSE might serve as a lead nutraceutical in geriatric research.


Assuntos
Proteínas de Caenorhabditis elegans , Momordica , Saponinas , Envelhecimento , Animais , Antioxidantes/farmacologia , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Peróxido de Hidrogênio , Longevidade , Momordica/metabolismo , Estresse Oxidativo , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio , Saponinas/farmacologia
9.
BMC Complement Med Ther ; 20(1): 365, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33238969

RESUMO

BACKGROUND: Momordica cochinchinensis (Cucurbitaceae) is a nutritionally and medicinally important fruit restricted to South East Asia with diverse morphological and genetic variations but there is limited information on its medicinal potential. METHODS: M. cochinchinensis aril from 44 different samples in Australia, Thailand and Vietnam were extracted using different solvents and tested for its anticancer potential. Anticancer activity of M. cochinchinensis aril on breast cancer (MCF7 and BT474) and melanoma (MM418C1 and D24) cells were compared to control fibroblasts (NHDF). The cytotoxicity of the cells following treatment with the aril extract was determined using CCK-8 assay. Biochemical and morphological changes were analysed using flow cytometry, confocal and transmission electron microscopy to determine the mechanism of cell death. RESULTS: The water extract from the aril of M. cochinchinensis elicited significantly higher cytotoxicity towards breast cancer and melanoma cells than the HAE extract. The IC50 concentration for the crude water extract ranged from 0.49 to 0.73 mg/mL and induced both apoptotic and necrotic cell death in a dose- and time-dependant manner with typical biochemical and morphological characteristics. The greatest cytotoxicity was observed from Northern Vietnam samples which caused 70 and 50% melanoma and breast cancer cell death, respectively. CONCLUSIONS: The water extract of M. cochinchinensis aril caused significant apoptosis and necrosis of breast cancer and melanoma cells, with varieties from Northern Vietnam possessing superior activity. This highlights the potential of this fruit in the development of novel anticancer agents against such tumours, with specific regions on where to collect the best variety and extraction solvent for optimum activity.


Assuntos
Antineoplásicos/farmacologia , Momordica , Extratos Vegetais/farmacologia , Apoptose/efeitos dos fármacos , Ásia Sudeste , Austrália , Linhagem Celular Tumoral , Frutas , Humanos , Células MCF-7
10.
IET Nanobiotechnol ; 14(2): 172-179, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32433036

RESUMO

Bio-fabrication of gold nanoparticles (AuNPs) has several advantages like biocompatibility, less toxicity, and eco-friendly in nature over their chemical and physical methods. Currently, the authors fabricated AuNPs using aqueous root extract of Momordica dioica (M. dioica) and explored their anticancer application with mechanistic approaches. Different biophysical techniques such as UV-visible spectroscopy, Fourier transform infrared, X-ray diffraction, transmission electron microscopy, selected area electron diffraction, and dynamic light scattering were employed for AuNPs characterisation. The synthesised AuNPs were mono-dispersed, crystalline in nature, anionic surface (-23.9 mV), and spherical particle of an average diameter of 9.4 nm. In addition, the AuNPs were stable in buffers solutions and also biocompatible towards normal human cells (human vascular endothelial cells and human lung cells). The AuNPs were exhibited anticancer activity against different cancer cell lines such as human breast cancer cells, human cervical cancer cells (HeLa) and human lung cancer cells. Further, the pro-apoptotic genes such as Bcl2 were down-regulated and BAX, Caspase-3, -8, and -9 were up-regulated in HeLa cells as compared to untreated cells. Annexin-V-FITC assay results showed that the AuNPs were induced apoptosis by accumulation of intracellular reactive oxygen species. To their knowledge, this is the first report on the synthesis of bioactive metal nanoparticles from M. dioica and it may open up new avenues in therapeutic applications.


Assuntos
Apoptose/efeitos dos fármacos , Ouro/farmacologia , Nanopartículas Metálicas/química , Momordica/metabolismo , Neoplasias do Colo do Útero/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Feminino , Ouro/metabolismo , Células HeLa , Células Endoteliais da Veia Umbilical Humana , Humanos , Células MCF-7 , Extratos Vegetais/química , Extratos Vegetais/metabolismo
11.
J Mol Graph Model ; 98: 107619, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32311663

RESUMO

Alpha-momorcharin (α-MMC), trichosanthin (TCS), and momordica anti-HIV protein of 30 kD (MAP30) are potential anti-tumor drug candidates but have cytotoxicity to normal cells. The binding of these proteins to LRP1 receptor and the subsequent endocytosis are essential to their cytotoxicity, but this binding process remains largely unknown. This study, in-silico analysis of the binding patterns, was conducted via the protein-protein docking software, ZDOCK 3.0.2 package, to better understand the binding process. Specifically, α-MMC, TCS and MAP30 were selected and bound to binding subunits CR56 and CR17 of LRP1. After docking, the 10 best docking solutions are retained based on the default ZDOCK scores and used for structural assessment. Our results showed that, α-MMC bound to LRP1 stably at the amino acid residues 1-20, at which 8 residues formed 21 hydrogen bonds with 15 residues of CR56 and 10 residues formed 15 hydrogen bonds with 12 residues of CR17. In contrast, TCS and MAP30 bound mainly to LRP1 at the residues 1-57/79-150 and residues 58-102, respectively, which were functional domains of TCS and MAP30. Since residues 1-20 are outside the functional domain of α-MMC, α-MMC is considered more suitable to attenuate by mutating the receptor binding site. Thus, our analysis lays the foundation for future genetic engineering work on α-MMC, and makes important contributions to its potential clinical use in cancer treatment.


Assuntos
Momordica , Tricosantina , Linhagem Celular Tumoral , Ligantes , Proteínas Inativadoras de Ribossomos
12.
Zhongguo Zhong Yao Za Zhi ; 45(2): 374-382, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-32237321

RESUMO

The aim of this paper was to obtain low toxicity and high efficiency anti-tumor Chinese medicine through screening the combination ratios of Momordicae Semen and Epimedii Folium, and to explore the anti-tumor mechanism of the combination of two drugs by observing their effect on apoptosis-related proteins in cancer cells. Methyl thiazolyl tetrazolium(MTT) assay was used to observe the effect of drug combination on the proliferation of tumor cells from different tissue sources. The effects of the combination of the two drugs on tumor cells were analyzed by Compusyn software. Plate cloning assay was used to observe the effect of combination of these two drugs on the proliferation of A549 cells in vitro. The expression of reactive oxygen species(ROS) and apoptotic proteins p53, Bcl-2 and Bax were compared by using ROS kit and Western blot. Lewis lung cancer model was used to observe the anti-tumor effect of drugs in vivo. The results showed that the anti-tumor effect of their ethanol extract was more significant than that of water extract, and the anti-proliferation effect was strongest when the ratio was 1∶1(P<0.05). Compusyn analysis showed that the combination of the two drugs had synergistic effect. Further studies showed that after combined use, the number of clonogen formation in A549 cells was significantly reduced(P<0.01); ROS production was increased; the expression of apoptosis-related protein p53 was up-regulated, and the ratio of Bcl-2/Bax was decreased. In vivo animal study showed that the tumor inhibition rate was 53.06%(P<0.05) in the high dose group. As compared with the single use of the two drugs, the combination of the two drugs had more significant anti-proliferative effect on tumors, and the optimum ratio was 1∶1. The combination of the two drugs at a ratio of 1∶1 inhibited the proliferation of various tumor cells, and had no significant effect on normal liver cells LO2 when compared with other ratios. Therefore, it can be preliminarily inferred that the combination of the two drugs may have the effect of synergism and detoxification. Further studies showed that the combination of the two drugs can significantly inhibit the proliferation of A549 cells, and its mechanism may be related to the activation of endogenous apoptotic pathway. In vivo experiments also showed that the tumor inhibition rate increased with the increase of drug concentration.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Epimedium/química , Neoplasias Pulmonares/tratamento farmacológico , Momordica/química , Células A549 , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Neoplasias Experimentais/tratamento farmacológico , Folhas de Planta/química , Sementes/química
13.
Biomed Pharmacother ; 121: 109611, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31731196

RESUMO

BACKGROUND: Our previous studies have showed that p-Hydroxylcinnamaldehyde (CMSP) could induce the differentiation of ESCC cells via the cAMP-RhoA-MAPK signalling pathway, which suggests a new potential strategy for ESCC treatment. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent inducer of apoptosis in several tumour cells by binding to the death receptors DR4 and DR5. However, TRAIL has little effect on oesophageal squamous cell carcinoma (ESCC) cells due to the loss of the receptors. The present study determined the effect of CMSP, the firstly found chemical constituent of Cochinchinamomordica seed (CMS), on TRAIL-induced apoptosis and its mechanism in ESCC cells. METHODS: MTS assays were performed to examine the CMSP- and TRAIL-mediated inhibition of ESCC cell growth. Flow cytometry and Hoechst 33258 staining assays were used to detect apoptosis in ESCC cells treated with CMSP combined with TRAIL. Western blotting was used to determine the effect of CMSP on the expression of p38, p-p38, DR4, DR5, Bid and caspase-3/8 in ESCC cells treated with CMSP combined with TRAIL. Additionally, immunodeficient Balb-c/null mouse model was used to determine the chemotherapeutic efficacy of CMSP and TRAIL against ESCC tumour xenograft growth in vivo. RESULTS: We found that the combination of CMSP and TRAIL had a greater inhibitory effect on ESCC cell viability in vitro than CMSP or TRAIL alone. CMSP enhanced the TRAIL-induced apoptosis in ESCC cells by upregulating the expression of DR4 and DR5 via the p38 MAPK signalling pathway. Furthermore, the increased expression of DR4 and DR5 upon TRAIL-induced apoptosis in ESCC cells was mediated at least in part by subsequent caspase-3 and caspase-8 activation. Moreover, the in vivo model showed that tumour growth was significantly slower in CMSP and TRAIL combination-treated mice than in mice treated with CMSP or TRAIL alone. CONCLUSION: Taken together, our findings indicate that CMSP as an extract from TCM, might be as a potential sensitizer of TRAIL and thus provide a novel strategy for the clinical treatment of ESCC.


Assuntos
Cinamatos/farmacologia , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Momordica/química , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/fisiologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Humanos , Sistema de Sinalização das MAP Quinases/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/análise , Sementes/química
14.
Nat Prod Res ; 34(6): 823-829, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30557059

RESUMO

Two new lignans mubezhisol (1) and mubezhisal (2), together with twenty six known compounds (3-28) were isolated from water-soluble fraction from the semens of Momordica cochinchinensis. In the subsequent action evaluation, four saponins (4, 6, 13, 27), six lignans (1, 2, 16, 17, 22, 23), and one naphthoquinone (24) exhibited the significant cytotoxicity. The results indicated that various saponins and lignans were mainly responsible for the antitumor activities of Momordicae Semen.


Assuntos
Antineoplásicos/isolamento & purificação , Lignanas/farmacologia , Momordica/química , Saponinas/farmacocinética , Antineoplásicos/química , Antineoplásicos/farmacologia , Lignanas/isolamento & purificação , Extratos Vegetais/química , Saponinas/isolamento & purificação , Saponinas/farmacologia , Sementes/química , Solubilidade , Água
15.
Molecules ; 24(21)2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31683690

RESUMO

Gac fruit (Momordica cochinchinensis Spreng) is a popular tropical fruit in southeast Asia. What is amazing is that its seeds (Momordicae Semen) and arils are traditional herbs with anti-tumor activity, and have protected human health for more than 1000 years. In recent years, its anti-tumor activity has received extensive attention and research. This manuscript summarized the chemical composition of saponins, fatty acids, volatile constituents, proteins, peptides, and other components from Momordicae Semen (MSE). The effect and mechanism of MSE and its extract on breast cancer, gastric cancer, lung cancer, esophagus cancer, melanomas, and human cervical epithelial carcinoma were discussed. In addition, its antioxidant, anti-inflammatory, and other pharmacological effects were also analyzed. We hope that this review will provide new ideas for the treatment of cancer and other diseases, and become a reference for the further research into complementary and alternative medicine.


Assuntos
Antineoplásicos/farmacologia , Frutas/química , Momordica/química , Clima Tropical , Animais , Anti-Inflamatórios/farmacologia , Frutas/anatomia & histologia , Humanos , Compostos Fitoquímicos/química
16.
Fitoterapia ; 139: 104360, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31629869

RESUMO

Five new lignans mubiesins A - E (1-5), together with twenty-seven known compounds (6-32), were isolated from the cytotoxicity and anti-inflammation portions of Momordica cochinchinensis seeds which were widely used for various tumors and inflammations. Their structures were elucidated by extensive spectroscopic analyses (HR-MS, UV, CD, IR, 1D-NMR, and 2D-NMR). Their cytotoxic and anti-inflammatory activities were evaluated in vitro. Various lignans and saponins showed the significant activities, they could obviously inhibit the growth of tumor cells and the release of NO and TNF-α in RAW 264.7 cells induced by LPS.


Assuntos
Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Lignanas/farmacologia , Momordica/química , Saponinas/farmacologia , Sementes/química , Animais , Anti-Inflamatórios/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , China , Humanos , Lignanas/isolamento & purificação , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Células RAW 264.7 , Saponinas/isolamento & purificação
17.
J Phys Chem B ; 123(43): 9104-9110, 2019 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-31580077

RESUMO

Nerve growth factor (NGF) is an endogenously produced polypeptide that promotes the differentiation, survival, and repair of neurons in the central and peripheral nervous systems. While trophic proteins hold promise for the treatment of neuronal injury and disease, use of NGF is limited by its large molecular weight, lack of permeability through the blood-brain barrier, and peripheral side effects. Previously, we found that an extract of the Momordica cochinchinensis seed stimulated PC-12 neurite outgrowth. Bioactivity-guided fractioning of the seed extract suggested that the NGF mimetic agent was one of few defined proteins from this plant: one group being the defense Knottins and the other group of the lowest mass is the potent trypsin inhibitor MCoTI-II. Here, the NGF mimetic potential of this latter protein was investigated using two concurrent but different approaches. A biological study used recombinant purified MCoTI-II, which when tested in rat PC-12 cells grown on collagen, failed to initiate outgrowth relative to the positive control 7S NGF. In a separate computational study, the possibility was investigated such that MCoTI-II could exert an effect through binding to the serine protease γ-NGF subunit of the 7S NGF complex, analogous to its binding to its native receptor trypsin. Molecular dynamics simulations showed that MCoTI-II can bind stably to γ-NGF for >350 ns. Modeling indicated that this interaction could sterically inhibit 7S NGF complex formation, potentially altering the equilibrium between inactive complexed and free active NFG protein. In conclusion, the biological study now excludes the MCoTI-II protein as the NGF mimetic factor in the Momordica extract, an important and required step to identify the active component in this seed. On the other hand, the theoretical study has revealed a novel observation that may be of use in the development of strategies to affect NGF activity.


Assuntos
Ciclotídeos/metabolismo , Miniproteínas Nó de Cistina/metabolismo , Fatores de Crescimento Neural/metabolismo , Crescimento Neuronal , Extratos Vegetais/metabolismo , Animais , Biomimética , Simulação por Computador , Ciclotídeos/química , Miniproteínas Nó de Cistina/química , Simulação de Dinâmica Molecular , Momordica/química , Fatores de Crescimento Neural/química , Células PC12 , Ligação Proteica , Conformação Proteica , Ratos , Serina Endopeptidases/metabolismo
18.
J Med Chem ; 62(21): 9976-9982, 2019 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-31657920

RESUMO

We have derivatized Momordica saponins (MS) I and II through their coupling at C3 glucuronic acid site with dodecylamine. The derivatives show significantly different immunostimulant activity profiles from their respective natural parent saponins. In particular, adjuvant VSA-1 (5), the derivative of MS I, potentiates a significantly higher IgG2a responose than the corresponding natural product. Its IgG1 and IgG2a production is similar to that of GPI-0100, indicating a potential mixed and antigen-specific Th1/Th2 immune response, which is different from the Th2 immunity induced by the natural saponin MS I. In addition, toxicity evaluations show that adjuvant VSA-1 (5) is much less toxic than the widely used natural saponin mixture Quil A. These results prove that derivatizing Momordica saponins can be a viable way for easy access to structurally defined saponin immunostimulants with favorable adjvuant activity and low toxicity.


Assuntos
Adjuvantes Imunológicos/química , Momordica/química , Saponinas/química , Adjuvantes Imunológicos/farmacologia , Animais , Imunidade Humoral/efeitos dos fármacos , Imunização , Camundongos
19.
J Biol Chem ; 294(49): 18662-18673, 2019 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-31656227

RESUMO

Cucurbitacins are highly oxygenated triterpenoids characteristic of plants in the family Cucurbitaceae and responsible for the bitter taste of these plants. Fruits of bitter melon (Momordica charantia) contain various cucurbitacins possessing an unusual ether bridge between C5 and C19, not observed in other Cucurbitaceae members. Using a combination of next-generation sequencing and RNA-Seq analysis and gene-to-gene co-expression analysis with the ConfeitoGUIplus software, we identified three P450 genes, CYP81AQ19, CYP88L7, and CYP88L8, expected to be involved in cucurbitacin biosynthesis. CYP81AQ19 co-expression with cucurbitadienol synthase in yeast resulted in the production of cucurbita-5,24-diene-3ß,23α-diol. A mild acid treatment of this compound resulted in an isomerization of the C23-OH group to C25-OH with the concomitant migration of a double bond, suggesting that a nonenzymatic transformation may account for the observed C25-OH in the majority of cucurbitacins found in plants. The functional expression of CYP88L7 resulted in the production of hydroxylated C19 as well as C5-C19 ether-bridged products. A plausible mechanism for the formation of the C5-C19 ether bridge involves C7 and C19 hydroxylations, indicating a multifunctional nature of this P450. On the other hand, functional CYP88L8 expression gave a single product, a triterpene diol, indicating a monofunctional P450 catalyzing the C7 hydroxylation. Our findings of the roles of several plant P450s in cucurbitacin biosynthesis reveal that an allylic hydroxylation is a key enzymatic transformation that triggers subsequent processes to produce structurally diverse products.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Momordica/química , Proteínas de Plantas/metabolismo , Triterpenos/metabolismo , Hidroxilação , Isoformas de Proteínas , Software
20.
Curr Med Chem ; 26(24): 4585-4605, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31284852

RESUMO

Gac, Momordica cochinchinensis (Lour.) Spreng. belongs to the Cucurbitaceae family. It is more considered as a super fruit. The demand for this plant is growing in countries where its reputation is high, including traditional countries of gac culture and countries fond of super fruits and food supplements. In these latter countries, the industrial strategy aims at producing high added value in food supplements or nutritional rich preparations. However, when marketing is not the driving force and claims have to be related to scientific data, the situation of gac is less "heavenly", mainly because its most remarkable properties are in the field of micronutrients. These latter components are indeed very important for health but their supplementation on healthy populations brings no significant advantage. This paper proposes to review aspects important for the nutritional reputation of this plant: where it comes from, how it is cultured to have an optimal nutritional composition, what is its composition and how it can impact health of consumers, in which products it is used and what are the regulations to use it in different markets. One important goal of this review is to give a critical and scientific approach to confirm data on this fruit, which has been promoted by marketing departments injecting so many wrong and unverified information. Missing data will be highlighted and potential positive applications are proposed all along the text.


Assuntos
Momordica/química , Anti-Inflamatórios/química , Antioxidantes/química , Antioxidantes/uso terapêutico , Carotenoides/química , Carotenoides/uso terapêutico , Suplementos Nutricionais/análise , Frutas/química , Frutas/metabolismo , Humanos , Momordica/metabolismo , Neoplasias/tratamento farmacológico , Polifenóis/química , Polifenóis/uso terapêutico , Vitaminas/química
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