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1.
Molecules ; 26(18)2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34577160

RESUMO

Seventeen new carbazole alkaloid derivatives, including a trimeric carbazole racemate, (±)-microphyltrine A (1), 15 dimeric carbazole racemates, (±)-microphyldines A-O (2-16), and a C-6-C-3″-methyl-linked dimeric carbazole, microphyldine P (17), were isolated from the leaves and stems of Murraya microphylla (Merr. et Chun) Swingle. The structures of the new compounds were elucidated on the basis of HRESIMS and NMR data analysis. The optically pure isomers of these isolated carbazole alkaloids were obtained by chiral HPLC separation and their absolute configurations were determined by electronic circular dichroism (ECD) data analysis.


Assuntos
Alcaloides/química , Alcaloides/farmacologia , Carbazóis/química , Carbazóis/farmacologia , Murraya/química , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Morte Celular/efeitos dos fármacos , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Humanos , Isomerismo , Macrófagos/efeitos dos fármacos , Microglia/efeitos dos fármacos , Óxido Nítrico/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Caules de Planta/química , Espectroscopia de Prótons por Ressonância Magnética
2.
Sci Rep ; 11(1): 9691, 2021 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-33963198

RESUMO

The excessive usage of antibiotics in humans and veterinary medicine has lead to the emergence of antibiotic resistance and now requires the use of novel antibiotics. There has been increased interest towards plants as source of drugs because of their pharmacological potency and long traditional usage. The aim of the current study was to evaluate bioactive components, antioxidant, and anti-inflammatory activities of the leaf extracts of Murraya paniculata, a plant traditionally used in Indian medicinal system. Evaluations were made for phytochemical analysis, antioxidant, membrane stabilizing, and antimicrobial activities. The methanol extract displayed the highest flavonoid and phenolic content, the acetone extract demonstrated considerable ABTS inhibitory activity (IC50value:555.18 ± 1.68 µg/mL) and the hexane extract exhibited highest H2O2 radical scavenging activity (IC50value: 509.84 ± 3.03 µg/mL). The aqueous extract displayed 19.4 ± 0.66% RBC hemolysis and 80.5 ± 0.66% protection caused by hypotonic solution at high concentration of the extract. The fractions of hexane extract revealed a higher zone of inhibition than crude extract. The major components found in the fractions were cyclohexane (40.11%) and 3-(6-Methoxy-3-methyl-2-benzofuranyl) Cyclohexanone (13.68%) as analyzed by GC-MS/MS technique. The current results validate the traditional use of the M. paniculata and warrant its potential in drug development programs in further investigations.


Assuntos
Anti-Infecciosos/química , Antioxidantes/química , Excipientes/química , Murraya/química , Extratos Vegetais/química , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Descoberta de Drogas , Excipientes/farmacologia , Flavonoides/química , Flavonoides/farmacologia , Humanos , Fenóis/química , Fenóis/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia
3.
Molecules ; 26(5)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33652969

RESUMO

Cytotoxic flavonoids of Murraya tetramera were investigated in this study. A novel flavonoid and twelve known flavonoids, including seven flavones (1-7), three flavanones (8-10), and three chalcones (11-13) were isolated from the leaves and twigs of Murraya tetramera. Chemical structures were elucidated by NMR combined with MS spectral analysis, and the new compound (6) was confirmed as 3',5'-dihydroxy-5,6,7,4'-tetramethoxyflavone. Furthermore, all the isolated flavonoids were evaluated for their cytotoxicities against murine melanoma cells (B16), and human breast cancer cells (MDA-MB-231) by CCK-8 assay. Among them, compounds 7, 13, and 5 exhibited potent cytotoxic activities against B16 cell lines (IC50 = 3.87, 7.00 and 8.66 µg/mL, respectively). Compounds 5, 13, and 12 displayed potent cytotoxicities against MDA-MB-231 cell lines (IC50 = 3.80, 5.95 and 7.89 µg/mL, respectively). According to the correlation of the structure and activity analysis, 5-hydroxyl and 8-methoxyl substituents of the flavone, 8-methoxyl substituent of the flavanone, and 3',5'-methoxyl substituents of the chalcone could be critical factors of the high cytotoxicity. The results indicated that the active flavonoids have potential to be developed as leading compounds for treating cancers.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Flavonoides/farmacologia , Murraya/química , Animais , Antineoplásicos Fitogênicos/química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Chalconas/química , Chalconas/farmacologia , Feminino , Flavonoides/química , Humanos , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/patologia , Camundongos , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química
4.
Parasit Vectors ; 14(1): 1, 2021 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-33388087

RESUMO

BACKGROUND: Insect growth regulators (IGRs) can control insect vector populations by disrupting growth and development in juvenile stages of the vectors. We previously identified and described the curry tree (Murraya koenigii (L.) Spreng) phytochemical leaf extract composition (neplanocin A, 3-(1-naphthyl)-L-alanine, lumiflavine, terezine C, agelaspongin and murrayazolinol), which disrupted growth and development in Anopheles gambiae sensu stricto mosquito larvae by inducing morphogenetic abnormalities, reducing locomotion and delaying pupation in the mosquito. Here, we attempted to establish the transcriptional process in the larvae that underpins these phenotypes in the mosquito. METHODS: We first exposed third-fourth instar larvae of the mosquito to the leaf extract and consequently the inherent phytochemicals (and corresponding non-exposed controls) in two independent biological replicates. We collected the larvae for our experiments sampled 24 h before peak pupation, which was 7 and 18 days post-exposure for controls and exposed larvae, respectively. The differences in duration to peak pupation were due to extract-induced growth delay in the larvae. The two study groups (exposed vs control) were consequently not age-matched. We then sequentially (i) isolated RNA (whole larvae) from each replicate treatment, (ii) sequenced the RNA on Illumina HiSeq platform, (iii) performed differential bioinformatics analyses between libraries (exposed vs control) and (iv) independently validated the transcriptome expression profiles through RT-qPCR. RESULTS: Our analyses revealed significant induction of transcripts predominantly associated with hard cuticular proteins, juvenile hormone esterases, immunity and detoxification in the larvae samples exposed to the extract relative to the non-exposed control samples. Our analysis also revealed alteration of pathways functionally associated with putrescine metabolism and structural constituents of the cuticle in the extract-exposed larvae relative to the non-exposed control, putatively linked to the exoskeleton and immune response in the larvae. The extract-exposed larvae also appeared to have suppressed pathways functionally associated with molting, cell division and growth in the larvae. However, given the age mismatch between the extract-exposed and non-exposed larvae, we can attribute the modulation of innate immune, detoxification, cuticular and associated transcripts and pathways we observed to effects of age differences among the larvae samples (exposed vs control) and to exposures of the larvae to the extract. CONCLUSIONS: The exposure treatment appears to disrupt cuticular development, immune response and oxidative stress pathways in Anopheles gambiae s.s larvae. These pathways can potentially be targeted in development of more efficacious curry tree phytochemical-based IGRs against An. gambiae s.s mosquito larvae.


Assuntos
Anopheles/efeitos dos fármacos , Anopheles/genética , Perfilação da Expressão Gênica , Larva/efeitos dos fármacos , Murraya/química , Compostos Fitoquímicos/farmacologia , Animais , Biologia Computacional , Feminino , Inseticidas/farmacologia , Larva/genética , Redes e Vias Metabólicas/efeitos dos fármacos , Mosquitos Vetores/efeitos dos fármacos , Compostos Fitoquímicos/química , Folhas de Planta/química
5.
Int J Vitam Nutr Res ; 91(5-6): 396-410, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32580686

RESUMO

The present study aimed to examine the chemoprotective effect of Hydroethanolic Murraya koenigii leaves extract (HEMKLE) on murine skin carcinogenesis model. For the study, male LACA mice divided into four groups (n = 15 per group). Group I (Control), Group II (DMBA/TPA), Group III (HEMKLE), and Group IV (HEMKLE + DMBA/TPA). Skin tumors were induced in Group II (DMBA/TPA) and Group IV (HEMKLE + DMBA/TPA) by topical application of 7, 12 dimethylbenz[a]anthracene (DMBA) [500 nmol/100 µL of acetone, twice a week for two weeks] and 12-O-tetradecanoyl phorbol-13-acetate (TPA) [1.7 nmol/100 µL of acetone, twice a week for eighteen weeks] and HEMKLE (200 mg/kg b. w.) was administered orally (instilled by oral gavage). The chemoprotective response of HEMKLE was evident by inhibition in tumor incidence, mean tumor volume, mean tumor burden, total number of tumors, and tumor size in Group IV (HEMKLE + DMBA/TPA) when compared to Group II (DMBA/TPA). HEMKLE administration also decreased the reactive oxygen species (ROS) and lipid peroxidation (LPO) levels and increased the antioxidants enzyme activities in Group IV (HEMKLE + DMBA/TPA) when compared to Group II (DMBA/TPA) that suggests its antioxidant potential. HEMKLE administration also increased the mRNA and protein expression of caspase-9 and caspase-3 and decreased the mRNA and protein expression of Bcl-2 in Group IV (HEMKLE + DMBA/TPA) when compared to Group II (DMBA/TPA) that suggest its apoptosis-inducing effect on DMBA/TPA induced skin carcinogenesis.


Assuntos
Murraya , Neoplasias Cutâneas , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Animais , Carcinogênese , Camundongos , Extratos Vegetais , Folhas de Planta , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/prevenção & controle
6.
Sci Rep ; 10(1): 20096, 2020 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-33208840

RESUMO

Murraya koenigii (MK) leaf being a rich source of bioactive secondary metabolites has received inordinate attention in drug development research. Formation of secondary plant metabolite(s) in medicinal plants depends on several factors and in this study the cause of variation in bioavailability and content of a vital bioactive phytochemical, mahanine in the MK leaves from different geographical locations of varying soil properties and weather parameters was determined. Accordingly, MK leaves and soil samples around the plant base in quintuplicate from each site across five states of India at similar time point were collected. Mahanine content was determined and compared among samples from different regions. The quantitative analysis data comprised that MK-leaves of southern part of India contains highest amount of mahanine, which is 16.9 times higher than that of MK-leaves of north-eastern part of India (which measured as the lowest). The results suggested that pH, conductivity and bacterial populations of the soil samples were positively correlated with mahanine content in the MK-leaves. For examples, the average soil pH of the southern India sites was in basic range (8.8 ± 0.6); whereas that of the north-east India sites was in slightly acidic ranges (6.1 ± 0.5) and mean soil conductivity value for the north east India soils was 78.3 ± 16.3 µS/cm against mean value of 432.4 ± 204.5 µs/cm for south India soils. In conclusion, this study proclaims that higher level of bioactive phytochemical, mahanine in MK leaves depending upon geographical location, weather suitability and soil's physiochemical and microbial parameters of its cultivation sites.


Assuntos
Carbazóis/metabolismo , Murraya/química , Compostos Fitoquímicos/metabolismo , Extratos Vegetais/metabolismo , Folhas de Planta/química , Solo/química , Carbazóis/isolamento & purificação , Índia , Compostos Fitoquímicos/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Tempo (Meteorologia)
7.
Chem Biodivers ; 17(11): e2000490, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32960486

RESUMO

The phytochemical investigation of the leaves and stems of Murraya tetramera C.C. Huang, a traditional folk medicine used as an anti-inflammatory agent, yielded 19 simple carbazole alkaloids, two of which (1-ethoxy-3-methyl-9H-carbazol-2-ol (1) and 7-hydroxy-2,8-dimethoxy-6-methyl-9H-carbazole-1-carbaldehyde (2)) are new ones. The structures of the new compounds were determined by extensive spectroscopic analysis including NMR and HR-EI-MS experiments, as well as comparison with the reported data. Most of the isolates showed potent inhibitory effects on NO production in LPS-stimulated BV-2 microglial cells with IC50 values ranging from 5.1 to 15.1 µM.


Assuntos
Alcaloides/química , Anti-Inflamatórios/química , Carbazóis/química , Murraya/química , Óxido Nítrico/metabolismo , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Carbazóis/isolamento & purificação , Carbazóis/farmacologia , Linhagem Celular , Lipopolissacarídeos/farmacologia , Espectroscopia de Ressonância Magnética , Medicina Tradicional , Camundongos , Microglia/citologia , Microglia/efeitos dos fármacos , Microglia/metabolismo , Conformação Molecular , Murraya/metabolismo , Folhas de Planta/química , Folhas de Planta/metabolismo , Caules de Planta/química , Caules de Planta/metabolismo
8.
J Complement Integr Med ; 18(1): 51-57, 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32745070

RESUMO

OBJECTIVES: Aqueous leaves extracts of Murraya koenigii (M. koenigii) and Aegle marmelos (A. marmelos) were prepared and effect of the extracts on inhibiting alpha-amylase playing essential roles on converting starch into glucose have been examined using in vitro assays. METHODS: Alpha amylase inhibitory assay was used to asses the in vitro antidiabetic activity of the extracts. Gas chromatography-mass spectrometry (GC-MS) analysis was performed to identify the volatile molecules of the extracts. Identified molecule were converted as ligand and docked against human pancreatic α-amylase (0.95 Å; PDB ID: 5U3A) using Autodock tool. RESULTS: The data analyzes suggested that the alpha-amylase inhibition potential of the extract obtained from M. koenigii was stronger than that of the A. marmelos at low concentrations (<1 mg/mL), whereas both the extracts depicted similar inhibition effects on the enzyme at high concentration (>1 mg/mL). The phytochemicals present in both the plant extracts were identified by using their respective GC-MS data and the data analyzes revealed that the extracts of M. koenigii and A. Marmelos seemed to consist of about 20 and 24 diverse chemical molecules, respectively. Through the molecular docking studies, azulene of M. koenigii and hydroxycyclodecadiene of A. marmelos showed higher binding affinity on alpha-amylase. CONCLUSIONS: Concentration-dependent alpha-amylase inhibition effects of the extracts were observed and M. koenigii contains more alpha-amylase inhibitory effects due to the presence of azulene. This is primary lead to find out the better anti diabetic natural based drug to the society after clinical trial.


Assuntos
Aegle/química , Inibidores Enzimáticos/farmacologia , Murraya/química , Extratos Vegetais/farmacologia , alfa-Amilases/antagonistas & inibidores , Humanos , Hipoglicemiantes/farmacologia , Simulação de Acoplamento Molecular , Compostos Fitoquímicos/farmacologia , Folhas de Planta/química
9.
IET Nanobiotechnol ; 14(6): 449-456, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32755953

RESUMO

Immobilised magnetic nanoparticles are extensively used owing to their superparamagnetic nature, surface interaction, and binding specificity with the appropriate portentous substances. The present research focuses on the development of a portentous, robust carrier, which integrates the silica-coated amino-functionalised magnetic nanoparticle (AF-MnP) with the plant extracts of Cynodon dactylon (L1) and Muraya koenigii (L2) for the stable and enhanced removal of hazardous hexavalent chromium pollutant in the wastewater. Vibrating sample magnetometer (Ms - 45 emu/g) determines the superparamagnetic properties; Fourier-transform infrared spectroscopy determines the presence of functional groups such as NH2, Si-O-Si, C=C; high-resolution transmission electron microscopy, field emission scanning electron microscope and energy-dispersive X-ray spectroscopy determine the size of the green adsorbents in the range of 20 nm and the presence of elements such as Fe, N, and Si determines the efficacy of the synthesised silica-coated AF-MnP. The AF-MnP-L1 shows the maximum adsorption capacity of 34.7 mg/g of sorbent calculated from the Langmuir isotherm model and the process follows pseudo-second-order kinetics. After treatment, the adsorbents can be easily separated from the solution in the presence of an external magnetic field and are reused for nine cycles after acid treatment with the minimal loss of adsorption efficiency.


Assuntos
Cromo , Nanopartículas de Magnetita/química , Extratos Vegetais , Dióxido de Silício/química , Poluentes Químicos da Água , Cromo/isolamento & purificação , Cromo/metabolismo , Cynodon/química , Concentração de Íons de Hidrogênio , Murraya/química , Extratos Vegetais/química , Extratos Vegetais/metabolismo , Águas Residuárias/química , Poluentes Químicos da Água/isolamento & purificação , Poluentes Químicos da Água/metabolismo
10.
Biomed Res Int ; 2020: 4638132, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32851075

RESUMO

Murraya koenigii is well documented in the Indian ancient medical text "Charaka Samhita." The carbazole alkaloid "mahanine" from this plant exhibited anticancer activity against several cancers. Here, we have taken a comprehensive study to standardize the method for the preparation of a mahanine-enriched fraction (MEF) with the highest yield and defined markers. Our optimized method produced MEF having the highest amount of mahanine, a major marker, with excellent in vitro antiproliferative activity against ovarian and breast cancer cells as evidenced by decreased cell viability by MTT assay. Moreover, it exhibited condensed and fragmented nuclei by DAPI staining and increased annexin V-/PI-stained cells after MEF treatment, indicating apoptosis. It also exhibited good efficacy in ovarian and breast cancer syngeneic mice models, with an ED50 of 300 mg/kg body weight (BW). MEF is stable up to 40°C for ≥3 months. Its biological activity remains unchanged at a wide range of pH (1-10) for up to ~3 hours, indicating a safe oral route of administration. Additionally, the comparative pharmacokinetics of MEF and mahanine in rats showed a 31% higher bioavailability of mahanine in MEF-fed rats compared to rats fed with mahanine alone. Furthermore, mice fed with MEF at 5000 mg/kg BW single dose, 300-1500 mg/kg BW/day for 14 days, and 300 mg/kg BW/day for 28, 90, and 180 days for subacute, subchronic, chronic studies, respectively, did not show any significant clinical signs of toxicity, behavioral changes, mortality, organ weights, serum biochemistry, and hematological parameters indicating no/minimum toxicity for up to 180 days. To the best of our knowledge, this is the first report showing the pH/temperature stability and chronic toxicity studies of MEF along with in vivo efficacy against breast cancer. Taken together, our study will enhance the commercial value of this highly potential medicinal plant and will be helpful as a reference material for its clinical development.


Assuntos
Carbazóis/farmacologia , Proliferação de Células/efeitos dos fármacos , Murraya/química , Neoplasias/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Apoptose/efeitos dos fármacos , Carbazóis/efeitos adversos , Carbazóis/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Camundongos , Neoplasias/patologia , Farmacocinética , Extratos Vegetais/efeitos adversos , Extratos Vegetais/química , Plantas Medicinais/efeitos adversos , Plantas Medicinais/química , Ratos , Especiarias/efeitos adversos , Especiarias/análise
11.
Lipids Health Dis ; 19(1): 198, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32859217

RESUMO

BACKGROUND: LI85008F is a proprietary combination of leaf extracts of Moringa oleifera, Murraya koeingii, and extract of Curcuma longa rhizome. This herbal extract combination is an effective weight loss supplement for overweight and obese subjects. The present study aimed to investigate the thermogenic potential of the LI85008F in high-fat diet (HFD)-induced obese Sprague Dawley rats. METHODS: Seven rats received a regular diet (RD), and twenty-one rats received a high-fat diet (HFD) for 56 days. On day 28, the HFD-fed rats were randomized into three groups (n = 7). Starting from day 29 through day 56, one HFD-fed group received daily oral gavage of 0.5% Carboxymethylcellulose Sodium (CMC) alone (HFD), and the remaining two groups received 100 and 250 mg/kg LI85008F (LI85008F-100 and LI85008F-250, respectively). Body weight, fat mass, fat cell size, liver weight, liver triglyceride were measured. The energy metabolism parameters were measured using indirect calorimetry. In serum, the metabolic and endocrine markers were analyzed. The adipogenic and thermoregulatory proteins expression in the white adipose tissue (WAT) were analyzed using an immunoblot assay. RESULTS: Supplementation with both doses of LI85008F significantly increased resting energy expenditure (REE) in the obese rats. The LI85008F-250 rats showed significant up-regulation of uncoupling protein-1 (UCP-1) expression, as compared with the HFD rats. LI85008F significantly reduced body weight gain, fat mass, fat cell size, liver weight, and hepatic triglycerides. Serum triglyceride, total cholesterol, glucose, leptin, and fat cell markers were significantly reduced in LI85008F-supplemented rats compared to the HFD rats. CONCLUSION: The present data suggest that LI85008F reduces body fat mass and controls body weight gain via increasing energy metabolism in combination with reduced lipogenesis in diet-fed obese rats.


Assuntos
Curcuma/química , Moringa oleifera/química , Murraya/química , Obesidade/metabolismo , Extratos Vegetais/química , Folhas de Planta/química , Animais , Western Blotting , Calorimetria Indireta , Dieta Hiperlipídica , Metabolismo Energético/efeitos dos fármacos , Masculino , Obesidade/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Preparações de Plantas/uso terapêutico , Ratos , Ratos Sprague-Dawley
12.
FASEB J ; 34(9): 12338-12353, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32729134

RESUMO

Thermosensitive transient receptor potential vanilloid 2 (thermoTRPV2) is a nonselective Ca2+ -permeable cation channel broadly expressed, and is implicated in the pathology of diseases such as diabetes and pancreatitis. However, the physiological and pharmacological functions of TRPV2 channels have not been extensively investigated because of the absence of specific modulators. In this study, we report a pair of natural coumarin derivative enantiomers (-)-murraxocin (B304-1) and (+)-murraxocin (B304-2) from Murraya exotica for their selective inhibition of TRPV2 channels expressed in HEK293 cells and native TRPV2 currents in differentiated brown adipocytes. Whole-cell patch clamp recordings confirmed the enantiomers B304-1 and B304-2 could selectively inhibit the agonist mediated activation of TRPV2 current with IC50 values of 22.2 ± 7.8 µM and 3.7 ± 0.7 µM, respectively. Molecular docking and site-directed mutagenesis revealed a key residue I600 of TRPV2 critical for the binding of the enantiomers. Furthermore, B304-1 and B304-2 significantly reversed TRPV2 agonist-induced inhibition of mouse brown adipocyte differentiation. Taken together, our identification of two natural coumarin enantiomers provides valuable tools and chemical leads for further elucidation of TRPV2 channel function, and pharmacological modulation of thermoTRPV2 in brown adipocytes may represent a new therapeutic strategy for treatment of energy imbalance or metabolic disorders.


Assuntos
Cumarínicos/farmacologia , Murraya/química , Canais de Cátion TRPV/antagonistas & inibidores , Adipócitos Marrons/citologia , Adipócitos Marrons/efeitos dos fármacos , Animais , Diferenciação Celular/efeitos dos fármacos , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Mutagênese Sítio-Dirigida , Raízes de Plantas/química , Estereoisomerismo , Canais de Cátion TRPV/química , Canais de Cátion TRPV/fisiologia
13.
BMC Complement Med Ther ; 20(1): 222, 2020 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32664977

RESUMO

BACKGROUND: Statins are considered as standard drugs to control cholesterol levels, but their use is also associated with renal hypertrophy, hemorrhagic stroke, hepatomegaly, and myopathy. Murraya koenigii is an herb that is used in traditional cuisine and as a medicine in South Asia. Here we assessed the antidyslipidemic and antiatherosclerotic effects of this spice in repeated heated mix vegetable oils (RHMVO)-induced atherosclerotic models. METHODS: Aqueous extract of M. koenigii leaves (Mk LE) was prepared and its phytoconstituents were determined. Rabbits were divided into 5 groups (n = 10). Except for the control group, all the other four groups were treated with RHMVO for 16 weeks (dose = 2 ml/kg/day) to induce dyslipidemia and atherosclerosis. These groups were further treated for 10 weeks either with 300 and 500 mg/kg/day Mk LE, lovastatin, RHMVO, or left untreated. Body and organ weights were measured along with oxidative stress and tissue damage parameters. Lipid profile and hepatic function markers were studied. Atheroma measurement and histopathological examination were also performed in control and treated groups. RESULTS: Mk LE significantly (p < 0.05) attenuated RHMVO-induced dyslipidemia and atheroma formation. Furthermore, fat accumulation and lipid peroxidation in hepatic tissues were reduced by Mk LE in a dose-dependent manner. Our results indicated that the antidyslipidemic effects of Mk LE in 500 mg/kg/day dose were comparable to lovastatin. Additionally, oxidative stress markers were reduced much more significantly in Mk LE-500 than in the statin group (p < 0.05). CONCLUSIONS: This study recommends Mk LE as a potent antioxidant and lipid-lowering natural medicine that can attenuate the RHMVO-induced atherosclerotic in optimal doses and duration. Therefore, Mk LE can be accessible, cheap, and free of adverse effects alternate to statins.


Assuntos
Aterosclerose/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Peroxidação de Lipídeos/efeitos dos fármacos , Murraya , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Óleos Vegetais/efeitos adversos , Animais , Modelos Animais de Doenças , Temperatura Alta , Masculino , Extratos Vegetais/química , Folhas de Planta , Coelhos
14.
Phytochemistry ; 177: 112416, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32531519

RESUMO

Fifteen previously undescribed coumarin derivatives, murratins A-M, including two pairs of coumarin enantiomers with a cyclopropane unit, two benzocoumarins, a dimeric coumarin, and eight C-8-substituted coumarins, together with six known analogues were isolated from the extract of the leaves and twigs of Murraya exotica L., a medicinal plant named "Jiulixiang" in Chinese. Their structures were elucidated on the basis of comprehensive analysis of 1D and 2D NMR and HRMS spectroscopic data, and the absolute configurations were assigned via comparison of the specific rotations, the ECD exciton coupling method, comparison of experimental and calculated ECD data, and the ECD data of in situ formed transition metal complexes. All the isolates were evaluated for their inhibitory effects on lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells, and five coumarin derivatives showed moderate inhibitory activities. The possible mechanism for NO inhibition of undescribed bioactive compounds was deduced to interact with iNOS protein via molecular docking. The above results shed some light on a better understanding of the traditional anti-inflammation effect of M. exotica and coumarins are disclosed to be its potential anti-inflammatory constituents.


Assuntos
Murraya , Anti-Inflamatórios , Cumarínicos , Simulação de Acoplamento Molecular , Estrutura Molecular , Óxido Nítrico , Folhas de Planta
15.
Food Funct ; 11(4): 3493-3505, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32248216

RESUMO

Curry leaves (Murraya koenigii) are a leafy spice used in Indian cookery for its fragrant aroma. Many bioactive functional compounds have been identified, and among them carbazole alkaloids have attracted wide attention due to their multi-dimensional medicinal value. Even though it has been established that the carbazole alkaloid is responsible for the anti-ulcer effect showed by this culinary herb, there is no further evidence to say which phytochemical is responsible for this. In the present study, we investigated the gastro-protective effects and mechanism of girinimbine, a major carbazole alkaloid present in curry leaves. Rats were administered with ethanol to produce gastric ulcers, and the prophylactic effect of girinimbine was evaluated. A macroscopic and histological examination was carried out to examine the lesions. Furthermore, the mucus production, NO production, PGE2 synthesis, mucosal nonprotein sulphydryls, glutathione (GSH) level, lipid peroxidation (MDA) level and COX inhibition were assessed. In addition, in particular, TNF-α and IL-6, two important cytokines, were evaluated. Immunohistochemical and gene expression studies were conducted to determine the HSP70 and iNOS biomarkers. Our results indicated that girinimbine significantly reduced the ulcer index and totally safeguarded the mucosa from lesions. The protective effect of girinimbine was complemented through the restoration of the reduced GSH and NP-SH level. This was associated with a reduction of MDA, which was elevated by the administration of ethanol. Pre-treatment of the ethanol induced ulcer with girinimbine reduced the NO concentration in the plasma and elevated PGE2 together with a decreased level of TNF-α and IL-6. Girinimbine had shown suppressing effects on COX-2 enzymes, but not on COX-1. In addition, significantly upregulated HSP70 and downregulated iNOS were observed in girinimbine treated rat tissue at both the transcriptional and translational level. Our results clearly indicated that girinimbine displayed a significant gastro-protection effect, via the capacity to inhibit inflammatory responses and antioxidant potential.


Assuntos
Alcaloides/farmacologia , Anti-Inflamatórios/farmacologia , Antiulcerosos/farmacologia , Antioxidantes/farmacologia , Murraya , Úlcera Péptica/prevenção & controle , Animais , Citocinas/efeitos dos fármacos , Modelos Animais de Doenças , Etanol , Feminino , Masculino , Camundongos , Camundongos Endogâmicos , Úlcera Péptica/induzido quimicamente , Folhas de Planta , Ratos , Ratos Sprague-Dawley , Cicatrização/efeitos dos fármacos
16.
Hum Antibodies ; 28(3): 185-190, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32116245

RESUMO

BACKGROUND: Recent studies have highlighted the role of natural elements in reduction of cancer cell growth and apoptosis. Koenimbine, a natural product isolated from Murraya koenigii (L) Spreng is a substance with cytotoxic effects on cancer cells. AIM: The effects of koenimbine on HT-29 and SW48 colon cancer cells were evaluated by MTT and Annexin V assays. Expression levels of Wnt/ß-catenin pathway genes were quantified by real time PCR. RESULTS: The IC50 values of koenimbine in HT-29 and SW48 was calculated to be 50 µg/ml based on the results of MTT assay. This value was 75 µg/ml in IEC-18 cells which were used as normal control. Annexin V assays revealed induction of cell apoptosis and necrosis in HT-29 and SW48 cells but not IEG18 cells by koenimbine. Koenimbin treatment resulted in significant down-regulation of CYCLD1 expression in SW48 cell line, but up-regulation of this gene in HT29 cell line. Expression of TBLR1, DKK1, GSK3B and ß-catenin was significantly decreased after koenimbin treatment in HT-19 cell line. Moreover, expression of DKK1 and GSK3B was significantly decreased after koenimbin treatment in SW-40 cell line. TCF4 expression was not detected in any of cell lines either before or after treatment with koenimbin. CONCLUSION: The current in vitro study showed the cytotoxic effects of koenimbin on two colon cancer cell lines and the effects of this substance on expression of selected genes from Wnt-ß catenin pathway. Future in vivo studies are needed before suggestion of this substance as an anti-cancer drug.


Assuntos
Antineoplásicos , Carbazóis/farmacologia , Neoplasias do Colo , Extratos Vegetais/farmacologia , Antineoplásicos/farmacologia , Regulação para Baixo , Humanos , Murraya , Regulação para Cima , Via de Sinalização Wnt/efeitos dos fármacos
17.
Sci Rep ; 10(1): 5113, 2020 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-32198447

RESUMO

Candida albicans is a commensal fungus in humans, mostly found on the mucosal surfaces of the mouth, gut, vagina and skin. Incidence of ever increasing invasive candidiasis in immunocompromised patients, alarming occurrence of antifungal resistance and insufficient diagnostic methods demand more focused research into C. albicans pathogenicity. Consequently, in the present study, oleic acid from Murraya koenigii was shown to have the efficacy to inhibit biofilm formation and virulence of Candida spp. Results of in vitro virulence assays and gene expression analysis, impelled to study the protein targets which are involved in the molecular pathways of C. albicans pathogenicity. Proteomic studies of differentially expressed proteins reveals that oleic acid induces oxidative stress responses and mainly targets the proteins involved in glucose metabolism, ergosterol biosynthesis, lipase production, iron homeostasis and amino acid biosynthesis. The current study emphasizes anti-virulent potential of oleic acid which can be used as a therapeutic agent to treat Candida infections.


Assuntos
Antifúngicos/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Candidíase/tratamento farmacológico , Ácido Oleico/farmacologia , Candida albicans/genética , Farmacorresistência Fúngica/genética , Proteínas Fúngicas/análise , Proteínas Fúngicas/genética , Humanos , Testes de Sensibilidade Microbiana , Membrana Mucosa/microbiologia , Murraya/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Proteômica , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Virulência/efeitos dos fármacos
18.
Acta Virol ; 64(1): 93-99, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32180423

RESUMO

Epstein-Barr virus (EBV), a B lymphotrophic herpesvirus associated with various forms of tumors, exhibits several latency phases with expressed EBV nuclear antigen 1 (EBNA-1). In the search of novel EBV-inhibiting targets, to curb the menace of EBV-borne lymphotropic transformations, EBNA-1 protein might serve as a best target for novel  antiviral natural compounds. This study is thus aimed to explore the inhibitory potential of Muuraya koengii bioactive compounds isomahanine, murrayanol and mahanimbine against the EBNA-1 of EBV. 3D structure of EBNA-1 was retrieved from the PDB data bank with further optimization of both the protein and ligands. In-silico inhibitory potential of the selected M. koengii bio-compounds against EBNA-1 as well as the molecular properties of the derivatives against EBNA-1 were assessed. Murrayanol seems to be a potent inhibitory drug to target EBNA-1 with a promising binding energy of -7.21 with two hydrogen bonds. Drug likeliness parameters recorded murrayanol to be the most promising of the tested compounds, followed by isomahanine. Molecular docking evaluations show that EBNA-1 might be inhibited with M. koengii biocompounds. Keywords: EBV; EBNA; M. koengii; in-silico.


Assuntos
Antivirais/química , Antígenos Nucleares do Vírus Epstein-Barr/química , Murraya/química , Compostos Fitoquímicos/química , Herpesvirus Humano 4 , Simulação de Acoplamento Molecular
19.
Int J Hyg Environ Health ; 226: 113471, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32078924

RESUMO

There is an increasing trend of developing various low-cost biogenic sorbents for the efficient and economical removal of noxious metals . Curry leaf powder (CLP), a promising non-toxic biosorbent containing several bioactive compounds was prepared by the pulverization of the dried leaves for the effective removal of Lead (Pb) and Cadmium (Cd). Various batch sorption experiments were carried out under constant temperature (25 °C), different pH (4.5-10.5), initial concentrations (50-200 mg L-1), adsorbent dosages (0.10-0.40 g) and contact times (0-60 min) to understand the optimum experimental conditions and simultaneously evaluate the adsorption isotherms and removal kinetics of CLP. Adsorption equilibrium was established in less than an hour interval (50 min). The pseudo-equilibrium process was best described by the pseudo-second-order kinetic (R2 ≥ 0.99), Freundlich and Langmuir isotherm model (R2 ≥ 0.94). The removal rate of Pb and Cd gradually increased (15.7 and 12.7 mg g-1 for Pb and Cd) at 100 mg L-1 of initial concentration till 60 min of contact period in a single contaminant system, the effect was non-significant for multiple adsorbent dosage systems (p > 0.05; t-test) though. The regeneration potential of the exhausted biosorbent was excellent upto 5 cycles with the better efficiency observed for Pb. The obtained results explicitly validated the probable utilization of CLP as a promising green adsorbent for metal removal . Future study may highlight the decontamination aspects of emerging contaminants with such green bio sorbents in large scale as well as mimicing the stomach conditions.


Assuntos
Cádmio/química , Chumbo/química , Murraya , Preparações de Plantas/química , Polifenóis/química , Pós/química , Poluentes Químicos da Água/química , Adsorção , Análise Custo-Benefício , Química Verde/economia , Cinética , Folhas de Planta , Reciclagem , Purificação da Água/economia , Purificação da Água/métodos
20.
Biomed Res Int ; 2020: 7821913, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32104704

RESUMO

Murraya koenigii is a well-known Indian medicinal herb, and a carbazole alkaloid (mahanine) from this plant causes apoptosis in cancer cells. Here, we investigated how seasonal and geographical variations influence carbazole alkaloids composition and medicinal property of this plant against cancer cells in vitro and in vivo. Leaflets were collected from various places in different seasons for three years. A mahanine-enriched fraction (MEF) was prepared in two steps using ethanol and water. The best plant was selected based on the highest percent of mahanine. MEF prepared from leaflets of nine different locations showed a different concentration of identified markers (mahanine, mahanimbine, and koenimbine) which exhibited differential reduced metabolic activity against ovarian cancer, mahanine being the best. Our systematic study revealed that mahanine content was highest during September-December. Interestingly, MEF from southern part (tropical zone) exhibited 43 ± 2.5% mahanine compared to 2.7 ± 1.3% in northeastern part (subtropical zone) with five folds higher activity against PA1. Moreover, MEF reduced metabolic activity of sixteen cancer cell lines from nine different origins and significantly reduced tumor mass in lung and ovarian cancer xenograft models. Taken together, this is the first report demonstrating the marker's content in these leaflets is highly dependent on location/season. A positive correlation between biological activity and mahanine concentration was established in MEF. Such a comprehensive study suggests that the selection of location and suitable season for collection of any plant materials with biologically active stable markers in sufficient quantity play a decisive role in determining the fate of their medicinal property.


Assuntos
Alcaloides , Antineoplásicos Fitogênicos , Carbazóis , Murraya , Neoplasias Experimentais/tratamento farmacológico , Estações do Ano , Células A549 , Alcaloides/química , Alcaloides/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Carbazóis/química , Carbazóis/farmacologia , Feminino , Células HCT116 , Células HeLa , Humanos , Camundongos , Camundongos Nus , Murraya/química , Murraya/crescimento & desenvolvimento , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
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