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1.
PLoS One ; 19(4): e0300115, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38662724

RESUMO

The biogenic approach for the synthesis of metal nanoparticles provides an efficient eco-friendly alternative to chemical synthesis. This study presents a novel route for the biosynthesis of silver nanoparticles using aqueous sandalwood (SW) leaf extract as a source of reducing and capping agents under mild, room temperature synthesis conditions. The bioreduction of Ag+ to Ago nanoparticles (SW-AgNPs) was accompanied by the appearance of brown color, with surface plasmon resonance peak at 340-360 nm. SEM, TEM and AFM imaging confirm SW-AgNP's spherical shape with size range of 10-32 nm. DLS indicates a hydrodynamic size of 49.53 nm with predominant negative Zeta potential, which can contribute to the stability of the nanoparticles. FTIR analysis indicates involvement of sandalwood leaf derived polyphenols, proteins and lipids in the reduction and capping of SW-AgNPs. XRD determines the face-centered-cubic crystalline structure of SW-AgNPs, which is a key factor affecting biological functions of nanoparticles. This study is novel in using cell culture methodologies to evaluate effects of SW-AgNPs on proliferating cells originating from plants and human cancer. Exposure of groundnut calli cells to SW-AgNPs, resulted in enhanced proliferation leading to over 70% higher calli biomass over control, enhanced defense enzyme activities, and secretion of metabolites implicated in biotic stress resistance (Crotonyl isothiocyanate, Butyrolactone, 2-Hydroxy-gamma-butyrolactone, Maltol) and plant cell proliferation (dl-Threitol). MTT and NRU were performed to determine the cytotoxicity of nanoparticles on human cervical cancer cells. SW-AgNPs specifically inhibited cervical cell lines SiHa (IC50-2.65 ppm) and CaSki (IC50-9.49 ppm), indicating potential use in cancer treatment. The opposing effect of SW-AgNPs on cell proliferation of plant calli (enhanced cell proliferation) and human cancer cell lines (inhibition) are both beneficial and point to potential safe application of SW-AgNPs in plant cell culture, agriculture and in cancer treatment.


Assuntos
Proliferação de Células , Nanopartículas Metálicas , Extratos Vegetais , Folhas de Planta , Santalum , Prata , Nanopartículas Metálicas/química , Humanos , Prata/química , Prata/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Santalum/química , Folhas de Planta/química , Folhas de Planta/metabolismo , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral
2.
Z Naturforsch C J Biosci ; 78(1-2): 9-25, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36069757

RESUMO

Santalum genus belongs to the family of Santalaceae, widespread in India, Australia, Hawaii, Sri Lanka, and Indonesia, and valued as traditional medicine, rituals and modern bioactivities. Sandalwood is reported to possess a plethora of bioactive compounds such as essential oil and its components (α-santalol and ß-santalol), phenolic compounds and fatty acids. These bioactives play important role in contributing towards biological activities and health-promoting effects in humans. Pre-clinical and clinical studies have shown the role of sandalwood extract as antioxidant, anti-inflammatory, antibacterial, antifungal, antiviral, neuroleptic, antihyperglycemic, antihyperlipidemic, and anticancer activities. Safety studies on sandalwood essential oil (EO) and its extracts have proven them as a safe ingredient to be utilized in health promotion. Phytoconstituents, bioactivities and traditional uses established sandalwood as one of the innovative materials for application in the pharma, food, and biomedical industry.


Assuntos
Óleos Voláteis , Santalum , Humanos , Santalum/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia
3.
Appl Microbiol Biotechnol ; 105(23): 8795-8804, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34738171

RESUMO

Santalenes and santalols from Santalum album are the main components of the valuable spice sandalwood essential oil, which also has excellent pharmacological activities such as antibacterial, anti-inflammatory, and antitumor. Firstly, we constructed biosynthesis pathways of santalenes by synthetic biology strategy. The assembled biosynthetic cassettes were integrated into the multiple copy loci of δ gene in S. cerevisiae BY4742 with assistance of pDi-CRISPR, and 94.6 mg/L santalenes was obtained by shake flask fermentation of engineered yeast. Secondly, a selected optimized P450-CPR redox system was integrated into the chromosome of the santalenes-producing strain with a single copy, and 24.6 mg/L santalols were obtained. Finally, the yields of santalenes and santalols were increased to 164.7 and 68.8 mg/L, respectively, by downregulating ERG9 gene. This is the first report on the de novo synthesis of santalols by P450-CPR chimera in S. cerevisiae. Meanwhile, the optimized chimeric CYP736A167opt-46tATR1opt exhibits higher activity to oxidize santalenes into santalols. It would provide a feasible solution for the optimal biosynthesis of santalols. KEY POINTS: • First-time de novo synthesis of santalols by P450-CPR chimera in S. cerevisiae. • Truncated 46tATR1 has higher activity than that of CPR2. • Yields of santalenes and santalols were increased by downregulating ERG9 gene.


Assuntos
Sesquiterpenos Policíclicos/metabolismo , Saccharomyces cerevisiae/metabolismo , Vias Biossintéticas/genética , Engenharia Metabólica , Saccharomyces cerevisiae/genética , Santalum/química
4.
Food Funct ; 12(5): 2312-2322, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33617622

RESUMO

Sandalwood (santalum spicatum) seed oil (SSO) is rich in ximenynic acid. The aim of the present study was to investigate the effect of SSO on high-fat/high-sucrose diet (HFHSD) induced insulin resistance (IR) in comparison with fish oil (FO), sunflower oil (SO) and linseed oil (LO). Fifty male Sprague-Dawley rats were randomly divided into five dietary groups: standard chow diet (controls), HFHSD plus 7% SSO, HFHSD plus 7% FO, HFHSD plus 7% SO and HFHSD plus 7% LO. After 12 weeks of feeding, the rats were sacrificed, and the serum parameters, hepatic lipids and underlying molecular mechanisms were studied. SSO, FO or LO significantly prevented glucose intolerance, hyperglycaemia, obesity, and hepatic lipid accumulation, and decreased the homeostasis model assessment of IR (HOMA-IR) and the serum levels of pro-inflammatory factors (IL-6, IL-1ß and TNF-α) compared with SO. In addition, SSO activated the PI3K/AKT insulin signaling pathway and down-regulated the JNK/NF-κB inflammatory signaling pathway in the liver. In summary, our results proved that SSO exerted an ameliorative effect on IR by regulating the hepatic inflammation related blockage of the insulin signaling pathway in the rats.


Assuntos
Resistência à Insulina/fisiologia , Fígado/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Óleos de Plantas/farmacologia , Santalum/química , Animais , Peso Corporal/efeitos dos fármacos , Masculino , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Sementes/química
5.
Phytother Res ; 35(4): 1991-2004, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33166007

RESUMO

Neuroinflammation is an inflammatory response in the nervous system that is associated with various neurological diseases including Alzheimer's diseases and others. Many studies evaluated the anti-inflammatory potential of Santalum album (S. album) extract, but none of them analyzed its effects against neuroinflammatory response in vitro. In addition, the precise mechanism underlying the anti-inflammatory effect of the extract has not yet been elucidated. Therefore, in this study, we investigated the effect of S. album extract on modulation of toll-like receptor 3 (TLR3) agonist polyinosnic-polycytidylic acid (PolyI:C)-induced neuroinflammatory response in human neuroblastoma cells. The TLR3-mediated immune response was differentially modulated by S. album extract in SH-SY5Y cells. In addition, treatment of cells with the conditioned medium (CM) of S. album extract significantly increased the mRNA levels of IFN-ß, IFN-α, MxA and OAS-1 and decreased IL-6, CXCL8, CCL2 and IP-10. S. album extract has indirectly affected the expression of IFNs and inflammatory cytokines in SH-SY5Y cells. Furthermore, the extract was able to modulate PolyI:C-induced inflammatory response in Caco2 cells. Overall, S. album was capable to attenuate PolyI:C-induced neuroinflammatory effect through the induction of TLR2, TLR4 and the modulation of TLR negative regulators of the TRAF3, IRF3 and NF-κB pathways.


Assuntos
Anti-Inflamatórios/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Extratos Vegetais/química , Santalum/química , Receptor 3 Toll-Like/metabolismo , Anti-Inflamatórios/farmacologia , Humanos , Fármacos Neuroprotetores/farmacologia
6.
Biomolecules ; 9(11)2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31731771

RESUMO

Natural products from plants, such as chemopreventive agents, attract huge attention because of their low toxicity and high specificity. The rational drug design in combination with structure-based modeling and rapid screening methods offer significant potential for identifying and developing lead anticancer molecules. Thus, the molecular docking method plays an important role in screening a large set of molecules based on their free binding energies and proposes structural hypotheses of how the molecules can inhibit the target. Several peptide-based therapeutics have been developed to combat several health disorders, including cancers, metabolic disorders, heart-related diseases, and infectious diseases. Despite the discovery of hundreds of such therapeutic peptides however, only few peptide-based drugs have made it to the market. Moreover, the in silico activities of cyclic peptides towards molecular targets, such as protein kinases, proteases, and apoptosis related proteins have not been extensively investigated. In this study, we explored the in silico kinase and protease inhibitor potentials of cyclosaplin, and studied the interactions of cyclosaplin with other apoptosis-related proteins. Previously, the structure of cyclosaplin was elucidated by molecular modeling associated with dynamics that were used in the current study as well. Docking studies showed strong affinity of cyclosaplin towards cancer-related proteins. The binding affinity closer to 10 kcal/mol indicated efficient binding. Cyclosaplin showed strong binding affinities towards protein kinases such as EGFR, VEGFR2, PKB, and p38, indicating its potential role in protein kinase inhibition. Moreover, it displayed strong binding affinity to apoptosis-related proteins and revealed the possible role of cyclosaplin in apoptotic cell death. The protein-ligand interactions using LigPlot displayed some similar interactions between cyclosaplin and peptide-based ligands, especially in case of protein kinases and a few apoptosis related proteins. Thus, the in silico analyses gave the insights of cyclosaplin being a potential apoptosis inducer and protein kinase inhibitor.


Assuntos
Simulação de Acoplamento Molecular , Peptídeos Cíclicos/química , Proteínas de Plantas/química , Inibidores de Proteínas Quinases/química , Proteínas Quinases/química , Santalum/química , Humanos , Simulação de Dinâmica Molecular
7.
BMC Complement Altern Med ; 19(1): 306, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31711477

RESUMO

BACKGROUNDS: The chemical composition of many essential oils indicates that they have sedative and hypnotic effects, but there is still a lack of systematic studies on the sedative and hypnotic effects of essential oils. In addition, aromatherapy does not seem to have the side effects of many traditional psychotropic substances, which is clearly worthwhile for further clinical and scientific research. The clinical application of essential oils in aromatherapy has received increasing attention, and detailed studies on the pharmacological activities of inhaled essential oils are increasingly needed. HYPOTHESIS/PURPOSE: As insomniacs are usually accompanied by symptoms of depression and anxiety of varying degrees, based on the theory of aromatherapy of Traditional Chinese Medicine, this experiment is to study a Compound Anshen essential oil that is compatible with Lavender essential oil, Sweet Orange essential oil, Sandalwood essential oil and other aromatic medicine essential oils with sedative and hypnotic effects, anti-anxiety and anti-depression effects. To study the sedative and hypnotic effects of Compound Anshen essential oil inhaled and the main chemical components of Compound Anshen essential oil, and to compare and analyze the pharmacodynamics of diazepam, a commonly used drug for insomnia. METHODS: The Open field test and Pentobarbital-induced sleep latency and sleep time experiments were used to analyze and compare the sedative and hypnotic effects of inhaling Compound Anshen essential oil and the administration of diazepam on mice. The changes of 5-HT and GABA in mouse brain were analyzed by Elisa. The main volatile constituents of Compound Anshen essential oil were analyzed by gas chromatography-mass spectrometry (GC-MS). RESULTS: Inhalation of Compound Anshen essential oil can significantly reduce the spontaneous activity of mice, reduce latency of sleeping time and prolong duration of sleeping time. The results of enzyme-linked immunosorbent assay showed that Compound Anshen essential oil can increase the content of 5-HT and GABA in mouse brain. The main volatile chemical constituents of the Compound Anshen essential oil are D-limonene (24.07%), Linalool (21.98%), Linalyl acetate (15.37%), α-Pinene (5.39%), and α-Santalol (4.8%). CONCLUSION: The study found that the inhalation of Compound Anshen essential oil has sedative and hypnotic effect. This study provides a theoretical basis for further research and development of the sedative and hypnotic effects of Compound Anshen essential oil based on the theory of aromatherapy.


Assuntos
Aromaterapia , Hipnóticos e Sedativos/administração & dosagem , Óleos Voláteis/administração & dosagem , Óleos de Plantas/administração & dosagem , Distúrbios do Início e da Manutenção do Sono/terapia , Administração por Inalação , Animais , Encéfalo/metabolismo , Citrus sinensis/química , Feminino , Humanos , Lavandula/química , Masculino , Camundongos , Camundongos Endogâmicos ICR , Óleos Voláteis/química , Óleos de Plantas/química , Santalum/química , Serotonina/metabolismo , Sono , Distúrbios do Início e da Manutenção do Sono/metabolismo , Distúrbios do Início e da Manutenção do Sono/fisiopatologia , Ácido gama-Aminobutírico/metabolismo
8.
Chem Biodivers ; 15(12): e1800405, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30362637

RESUMO

This study aimed to determine the antimicrobial activity of 247 essential oil combinations against the reference strains of wound pathogens. Essential oil combinations were investigated for antimicrobial activity against five pathogens. The minimum inhibitory concentration (MIC) assay was used and the fractional inhibitory concentration index (ΣFIC) calculated to determine interactions between selected oils. Twenty-six combinations displayed broad-spectrum antimicrobial activity against all five reference strains and several displayed synergy against more than one pathogen. The combination of Santalum austrocaledonicum (sandalwood) with Commiphora myrrha (myrrh) displayed noteworthy antimicrobial activity against all five reference strains and synergy against four (MIC values 0.03-1.00 mg/ml and ΣFIC values 0.19-1.00 mg/ml) pathogens. No antagonism was observed. Santalum spp. and Vetiveria zizanioides essential oils contributed the most to antimicrobial activity in combination. Essential oil combinations are presented as a viable option in wound therapy.


Assuntos
Anti-Infecciosos/química , Óleos Voláteis/química , Anti-Infecciosos/farmacologia , Vetiveria/química , Vetiveria/metabolismo , Commiphora/química , Commiphora/metabolismo , Farmacorresistência Bacteriana/efeitos dos fármacos , Sinergismo Farmacológico , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Óleos Voláteis/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Santalum/química , Santalum/metabolismo , Staphylococcus aureus/efeitos dos fármacos
9.
Sheng Wu Gong Cheng Xue Bao ; 34(6): 862-875, 2018 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-29943532

RESUMO

Santalene and santalol are the main components of valuable perfume sandalwood essential oil, and have good antibacterial, anti-oxidation and anti-tumor activities. Commercial sandalwood essential oil is mainly extracted from sandalwood tree that grows slowly and is difficult to cultivate. In addition, the extraction recovery of sandalwood essential oil from sandalwood tree is too low to meet the market demand. These factors make sandalwood essential oil expensive. An option is to use genetic engineering and molecular biological methods to heterologously express related synthase of santalene and santalol in microbial host. In this paper, the biosynthesis progress of santalene and santalol synthase, as well as the optimization of mevalonate metabolic pathways in the hosts are summarized. Furthermore, the strategies of applying protein engineering technology to carry out orthomutation of santalene synthase were also discussed, to provide reference for the optimal biosynthesis of santalene and santalol.


Assuntos
Óleos de Plantas/química , Santalum/química , Sesquiterpenos/metabolismo , Microbiologia Industrial , Redes e Vias Metabólicas , Ácido Mevalônico/metabolismo , Sesquiterpenos Policíclicos , Engenharia de Proteínas
10.
Molecules ; 22(7)2017 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-28698478

RESUMO

In our continuing study on a survey of biologically active natural products from heartwood of Santalum album (Southwest Indian origin), we newly found potent fish toxic activity of an n-hexane soluble extract upon primary screening using killifish (medaka) and characterized α-santalol and ß-santalol as the active components. The toxicity (median tolerance limit (TLm) after 24 h at 1.9 ppm) of α-santalol was comparable with that of a positive control, inulavosin (TLm after 24 h at 1.3 ppm). These fish toxic compounds including inulavosin were also found to show a significant antifungal effect against a dermatophytic fungus, Trichophyton rubrum. Based on a similarity of the morphological change of the immobilized Trichophyton hyphae in scanning electron micrographs between treatments with α-santalol and griseofulvin (used as the positive control), inhibitory effect of α-santalol on mitosis (the antifungal mechanism proposed for griseofulvin) was assessed using sea urchin embryos. As a result, α-santalol was revealed to be a potent antimitotic agent induced by interference with microtubule assembly. These data suggested that α-santalol or sandalwood oil would be promising to further practically investigate as therapeutic agent for cancers as well as fungal skin infections.


Assuntos
Antimitóticos/farmacologia , Óleos de Plantas/farmacologia , Sesquiterpenos/farmacologia , Animais , Antifúngicos/farmacologia , Antifúngicos/toxicidade , Antimitóticos/química , Divisão Celular/efeitos dos fármacos , Flavonoides/farmacologia , Flavonoides/toxicidade , Fundulidae/genética , Fundulidae/crescimento & desenvolvimento , Óleos de Plantas/química , Sesquiterpenos Policíclicos , Santalum/química , Sesquiterpenos/química , Sesquiterpenos/toxicidade
11.
J Chromatogr A ; 1495: 64-75, 2017 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-28343686

RESUMO

In the fields of essential oils and fragrances, samples often consist of mixtures of compounds with similar structural and physical characteristics (e.g. mono- and sesquiterpenoids), whose correct identification closely depends on the synergic combination of chromatographic and mass spectral data. This sample complexity means that new GC stationary phases with different selectivities are continually being investigated. Ionic liquids (ILs) are of great interest as GC stationary phases in this field because of their selectivity (significantly different than that of currently phases) and their high temperature stability. A first generation of IL GC columns was found to be competitive when applied to these field, in terms of selectivity and efficiency, compared to conventional columns (polydimethylsiloxane, (e.g. OV-1), methyl-polysiloxane 5%-phenyl (e.g. SE-52), 7%-cyanopropyl, 7%-phenyl polysiloxane (e.g. OV-1701), and polyethylen glycol (e.g. PEG-20M). However, these columns showed significant activity towards polar or active analytes, which primarily affected their quantitative performance. A new generation of highly-inactive columns coated with three of the most widely-used ionic liquid GC stationary phases has recently been introduced; these phases are SLB-IL60i (1,12-di(tripropylphosphonium) dodecane bis(trifluoromethylsulfonyl) imide [NTf2], SLB-IL76i (tri-(tripropylphosphonium-hexanamido)-triethylamine [NTf2]), and SLB-IL111i (1,5-di (2,3-dimethyllimidazolium) pentane [NTf2]). This study carefully tested the new inert IL columns, in view of their routine application in the fragrance and essential oil fields. They were found to have unusually high selectivity, comparable to that of first-generation IL columns, while their inertness and efficiency were competitive with those of currently-used conventional columns. The IL column performance of first and second generations was compared, through the quali-quantitative analysis of components in a group of different complexity samples; these included the Grob test, a standard mixture of "suspected" skin allergens, and the essential oils of chamomile and sandalwood.


Assuntos
Cromatografia Gasosa-Espectrometria de Massas , Líquidos Iônicos/química , Óleos Voláteis/análise , Alérgenos/análise , Farneseno Álcool/análise , Óleos Voláteis/química , Extratos Vegetais/química , Sesquiterpenos Policíclicos , Santalum/química , Santalum/metabolismo , Sesquiterpenos/análise , Estereoisomerismo
12.
J Chromatogr A ; 1417: 96-103, 2015 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-26410184

RESUMO

The present research deals with the multi-collection of the most important sesquiterpene alcohols belonging to sandalwood essential oil, as reported by the international regulations: (Z)-α-santalol, (Z)-α-trans bergamotol, (Z)-ß-santalol, epi-(Z)-ß-santalol, α-bisabolol, (Z)-lanceol, and (Z)-nuciferol. A versatile multidimensional preparative system, based on the hyphenation of liquid and gas chromatography techniques, was operated in the LC-GC-GC-prep or GC-GC-GC-prep configuration, depending on the concentration to be collected from the sample, without any hardware or software modification. The system was equipped with a silica LC column in combination with polyethylene glycol-poly(5% diphenyl/95% dimethylsiloxane)-medium polarity ionic liquid or ß-cyclodextrin based GC stationary phases. The GC-GC-GC-prep configuration was exploited for the collection of four components, by using a conventional split/splitless injector, while the LC-GC-GC-prep approach was applied for three low abundant components (<5%), in order to increase the quantity collected within a single run, by the LC injection of a high sample amount. All target compounds, whose determination is hampered by the unavailability of commercial standards, were collected at milligram levels and with a high degree of purity (>87%).


Assuntos
Cromatografia Gasosa/métodos , Cromatografia Líquida/métodos , Óleos Voláteis/análise , Dimetilpolisiloxanos , Sesquiterpenos Monocíclicos , Óleos de Plantas/análise , Sesquiterpenos Policíclicos , Polietilenoglicóis , Santalum/química , Sesquiterpenos/análise , Dióxido de Silício , beta-Ciclodextrinas/análise
13.
Anticancer Res ; 35(6): 3137-45, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26026073

RESUMO

Effective management of tumorigenesis requires development of better anticancer agents with greater efficacy and fewer side-effects. Natural products are important sources for the development of chemotherapeutic agents and almost 60% of anticancer drugs are of natural origin. α-Santlol, a sesquiterpene isolated from Sandalwood, is known for a variety of therapeutic properties including anti-inflammatory, anti-oxidant, anti-viral and anti-bacterial activities. Cell line and animal studies reported chemopreventive effects of sandalwood oil and α-santalol without causing toxic side-effects. Our laboratory identified its anticancer effects in chemically-induced skin carcinogenesis in CD-1 and SENCAR mice, ultraviolet-B-induced skin carcinogenesis in SKH-1 mice and in vitro models of melanoma, non-melanoma, breast and prostate cancer. Its ability to induce cell-cycle arrest and apoptosis in cancer cells is its most reported anticancer mechanism of action. The present review discusses studies that support the anticancer effect and the mode of action of sandalwood oil and α-santalol in carcinogenesis.


Assuntos
Carcinogênese/efeitos dos fármacos , Óleos de Plantas/uso terapêutico , Santalum/química , Neoplasias Cutâneas/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Humanos , Camundongos , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Neoplasias Cutâneas/induzido quimicamente
14.
J Nat Prod ; 78(6): 1357-62, 2015 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-25993496

RESUMO

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, with no major advancements in treatment over the past 40 years. The current study explores the biological effects of East Indian sandalwood oil (EISO) and its two major constituents, α- and ß-santalol, against a variety of HNSCC lines. All three agents exhibited cytotoxic effects and caused accumulation of cells in the G2/M phases of the cell cycle. Additionally, treatment with these agents caused formation of multipolar mitotic spindles similar to those observed upon treatment of cells with compounds that affect microtubule polymerization. Indeed, the santalols, as well as EISO, inhibited the polymerization of purified tubulin, indicating for the first time that these compounds have the ability to directly bind to tubulin and affect microtubule formation. Modeling studies suggest that the santalols can weakly bind to the colchicine site on tubulin, and topical administration of EISO to a HNSCC xenograft inhibited tumor growth with no observed toxicities. Therefore, santalols can directly interact with tubulin to inhibit the polymerization of microtubules, similarly to established classes of chemotherapeutic agents, albeit with greatly reduced potency that is not associated with the classic toxicity associated with most other compounds that interact directly with tubulin.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Bucais/tratamento farmacológico , Santalum/química , Sesquiterpenos/farmacologia , Tubulina (Proteína)/metabolismo , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Colchicina/farmacologia , Fase G2/efeitos dos fármacos , Humanos , Microtúbulos/efeitos dos fármacos , Mitose/efeitos dos fármacos , Modelos Moleculares , Estrutura Molecular , Sesquiterpenos Policíclicos , Sesquiterpenos/química , Estereoisomerismo
15.
Chem Pharm Bull (Tokyo) ; 62(12): 1192-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25450628

RESUMO

A rare type of sesquiterpene with a spiro bicyclic system (1) and seven new (2-8) and four known (9-12) ß-santalol derivatives were isolated from the heartwood of Santalum album (Santalaceae). The structures of these new compounds were determined by analysis of extensive spectroscopic data. The isolated compounds and derivatives were evaluated for their cytotoxic activity against HL-60 human promyelocytic leukemia cells, A549 human lung adenocarcinoma cells, HSC-2 and HSC-4 human oral squamous cell carcinoma cell lines, and TIG-3 normal human diploid fibroblasts. cis-ß-Santalol (9) and ß-santaldiol (10) induced apoptotic cell death in HL-60 cells.


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Santalum/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Ativação Enzimática/efeitos dos fármacos , Células HL-60 , Humanos , Conformação Molecular , Sesquiterpenos Policíclicos , Madeira/química
16.
Peptides ; 54: 148-58, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24503375

RESUMO

Small cyclic peptides exhibiting potent biological activity have great potential for anticancer therapy. An antiproliferative cyclic octapeptide, cyclosaplin was purified from somatic seedlings of Santalum album L. (sandalwood) using gel filtration and RP-HPLC separation process. The molecular mass of purified peptide was found to be 858 Da and the sequence was determined by MALDI-ToF-PSD-MS as 'RLGDGCTR' (cyclic). The cytotoxic activity of the peptide was tested against human breast cancer (MDA-MB-231) cell line in a dose and time-dependent manner. The purified peptide exhibited significant antiproliferative activity with an IC50 2.06 µg/mL. In a mechanistic approach, apoptosis was observed in differential microscopic studies for peptide treated MDA-MB-231 cells, which was further confirmed by mitochondrial membrane potential, DNA fragmentation assay, cell cycle analysis and caspase 3 activities. The modeling and docking experiments revealed strong affinity (kcal/mol) of peptide toward EGFR and procaspase 3. The co-localization studies revealed that the peptide sensitizes MDA-MB-231 cells by possibly binding to EGFR and induces apoptosis. This unique cyclic octapeptide revealed to be a favorable candidate for development of anticancer agents.


Assuntos
Apoptose/efeitos dos fármacos , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Santalum/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Caspase 3/metabolismo , Linhagem Celular Tumoral , Fragmentação do DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Receptores ErbB/metabolismo , Feminino , Humanos , Concentração Inibidora 50 , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Simulação de Acoplamento Molecular , Peptídeos Cíclicos/isolamento & purificação , Plântula/química
17.
Nat Prod Commun ; 9(9): 1365-8, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25918813

RESUMO

Four commercial qualities of Hawaiian sandalwood oil produced from wood of Santalum paniculatum originating from the island of Hawaii ("The Big Island") were analyzed using GC and GC-MS. Main constituents of the oils were (Z)-α-santalol (34.5-40.4%) and (Z)-ß-santalol (11.0-16.2%). An odor evaluation of the oils was carried out against East Indian sandalwood oil. In addition, the chemical composition of Hawaiian sandalwood oil was compared with four different Santalum species originating from East India, New Caledonia, Eastern Polynesia and Australia, respectively.


Assuntos
Óleos de Plantas/química , Santalum/química , Sesquiterpenos/química , Austrália , Cromatografia Gasosa-Espectrometria de Massas , Havaí , Óleos de Plantas/classificação , Sesquiterpenos/classificação
18.
Biosens Bioelectron ; 50: 431-6, 2013 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-23896523

RESUMO

The human estrogen receptor alpha (ERα) mediates the proliferative action of hormones in breast cancer cells by regulating the expression of target genes to control cellular functions. Current methodologies do not permit a real-time assessment of these processes in living cells. We overcome this limitation using electrical cell-substrate impedance sensing for measuring ERα-regulated signaling processes indicative of the onset of cell proliferation to target them for compound screenings. We report that hormone like odorants regulate, similarly as natural estrogen, ERα-mediated gene expression involved in mitogenic and developmental processes in MCF7 breast cancer cells. An odorant concentration-dependent switch in cell responses was detectable already 10-15 h post-stimulation, providing rapid quantification of hormonal activity before cell division occurred. Though ERα exhibits complex regulatory roles our non-invasive approach captures its activity for accelerated screenings of compounds promoting breast cancer cell proliferation expanding the analysis of ERα signaling networks.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Receptor alfa de Estrogênio/metabolismo , Regulação Neoplásica da Expressão Gênica , Odorantes/análise , Santalum/química , Técnicas Biossensoriais , Linhagem Celular Tumoral , Proliferação de Células , Espectroscopia Dielétrica , Feminino , Humanos , Transdução de Sinais , Transcriptoma
19.
Lipids ; 48(2): 105-13, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23275078

RESUMO

The aim of the present study was to investigate the effect of sandalwood seed oil on fatty acid (FA) profiles and inflammatory factors in rats. Fifty male Sprague-Dawley rats were randomly divided into five different dietary groups: 10 % soybean oil (SO), 10 % olive oil (OO), 10 % safflower oil (SFO), 10 % linseed oil (LSO) and 8 % sandalwood seed oil blended with 2 % SO (SWSO) for 8 weeks. The SWSO group had a higher total n-3 polyunsaturated fatty acids (PUFA) levels but lower n-6:n-3 PUFA ratios in both adipose tissue and liver than those in the SO, OO and SFO groups (p < 0.05). Although the SWSO group had a much lower 18:3n-3 level (4.51 %) in their dietary lipids than the LSO group (58.88 %), the levels of docosahexaenoic acid (DHA: 22:6n-3) in liver lipids and phospholipids of the SWSO group (7.52 and 11.77 %) were comparable to those of the LSO group (7.07 and 13.16 %). Ximenynic acid, a predominant acetylenic FA in sandalwood seed oil, was found to be highly incorporated into adipose tissue (13.73 %), but relatively lower in liver (0.51 %) in the SWSO group. The levels of prostaglandin F(2α), prostaglandin E2, thromboxane B2, leukotriene B4, tumor necrosis factor-α and interleukin-1ß in both liver and plasma were positively correlated with the n-6:n-3 ratios, suggesting that increased n-6 PUFA appear to increase the formation of pro-inflammatory cytokines, whereas n-3 PUFA exhibit anti-inflammatory activity. The present results suggest that sandalwood seed oil could increase tissue levels of n-3 PUFA, DHA and reduce the n-6:n-3 ratio, and may increase the anti-inflammatory activity in rats.


Assuntos
Citocinas/imunologia , Eicosanoides/imunologia , Ácidos Graxos/metabolismo , Óleos de Plantas/farmacologia , Santalum/química , Sesquiterpenos/farmacologia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Citocinas/análise , Citocinas/sangue , Eicosanoides/análise , Eicosanoides/sangue , Ácidos Graxos/análise , Ácidos Graxos Ômega-3/análise , Ácidos Graxos Ômega-3/metabolismo , Fígado/efeitos dos fármacos , Fígado/imunologia , Fígado/metabolismo , Masculino , Ácidos Oleicos/química , Ácidos Oleicos/farmacologia , Óleos de Plantas/química , Ratos , Ratos Sprague-Dawley , Sementes/química , Sesquiterpenos/química
20.
Bol. latinoam. Caribe plantas med. aromát ; 12(1): 81-91, ene. 2013. ilus, tab
Artigo em Inglês | LILACS | ID: lil-722510

RESUMO

Sandalwood (Santalum album L.) is used in various traditional systems of medicine, like Ayurveda, Siddha and Unani medicine to treat a wide range of ailments. In Unani medicine, Safed Sandal is used to treat gastric ulcers, hence the present study was undertaken to confirm this claim. A limit test as per OECD guidelines was conducted at a dose of 5000 mg/kg to determine the acute toxic dose of Hydro-alcoholic extract from S. album stem (SASE). Two test doses of SASE (250 and 500 mg/kg) were subjected to screening of anti-ulcer activity by three in-vivo models namely – water immersion - restrain stress, ethanol and indomethacin induced gastric ulceration models in albino wistar rats. A proton-pump inhibitor, Omeprazole 10 mg/kg and H2 receptor antagonist, Ranitidine 50 mg/kg were employed as standard drugs. The results revealed an increase in gastric protection as a significant decrease (p < 0.001) in average number of ulcers, severity of ulcers and cumulative ulcer index was observed in the test groups. Histopathological evidences supported the above findings. The observed anti-ulcer effect of SASE at 500 mg/kg was comparable to that of standard drugs used in the experiments indicating significant anti-ulcer potential especially at higher concentration.


Sándalo (Santalum album L.) se utiliza en diversos sistemas de medicina tradicional, como el Ayurveda, Siddha y Unani para tratar una amplia gama de dolencias. En la medicina Unani, Safed Sandal se usa para tratar úlceras gástricas, por lo tanto, el presente estudio se realizó para confirmar esta afirmación. Una prueba de límite según las directrices de la OCDE se llevó a cabo a una dosis de 5000 mg/kg para determinar la dosis tóxica aguda del extracto hidroalcohólico del tallo de S. álbum (SASE). Dos dosis de prueba de SASE (250 y 500 mg/kg) se sometieron al estudio de la actividad anti-úlcera por tres modelos in vivo, a saber: la inmersión en agua – estrés de restricción, y la ulceración gástrica inducida por etanol e indometacina, en ratas Wistar albinas. Un inhibidor de la bomba de protones, omeprazol 10 mg/kg y el antagonista de los receptores H2, ranitidina 50 mg/kg fueron empleados como fármacos estándar. Los resultados revelaron un aumento de la protección gástrica como una disminución significativa (p < 0.001) en el número promedio de úlceras, la gravedad de las úlceras y el índice de úlcera acumulativo se observó en los grupos de prueba. Evidencias histopatológicas apoyaron las conclusiones anteriores. El efecto anti úlcera observado por efecto de SASE a 500 mg/kg fue comparable a la de fármacos estándar utilizados en los experimentos que indican un significativo potencial anti-úlcera, especialmente a mayores concentraciones.


Assuntos
Ratos , Antiulcerosos/farmacologia , Extratos Vegetais/farmacologia , Santalum/química , Modelos Animais de Doenças , Solução Hidroalcoólica , Indometacina , Ratos Wistar
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