RESUMO
This study aimed to investigate the mechanism of action of myrrh in breast cancer (BC) treatment and identify its effective constituents. Data on the compounds and targets of myrrh were collected from the TCMSP, PubChem, and Swiss Target Prediction databases. BC-related targets were obtained from the Genecard database. A protein-protein interaction (PPI) analysis, gene ontology (GO) enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted on the intersecting targets of the disease and drug. The key targets of myrrh in BC treatment were identified based on the PPI network. The active constituents of myrrh were determined through reverse-screening using the top 20 KEGG pathways. Macromolecular docking studies, molecular dynamic (MD) simulations, and cell assays were utilized to validate the active constituents and critical targets. Network pharmacology indicated that VEGFA, TP53, ESR1, EGFR, and AKT1 are key targets of myrrh. Pelargonidin chloride, Quercetin, and Naringenin were identified as the active constituents of myrrh. Macromolecular docking showed that Quercetin and Naringenin have strong docking capabilities with ESR1. The results of MD simulation experiments align with those of molecular docking experiments. Cell and western blot assays demonstrated that Quercetin and Naringenin could inhibit MCF-7 cells and significantly reduce the expression of ESR1 protein. The findings reveal the active constituents, key targets, and molecular mechanisms of myrrh in BC treatment, providing scientific evidence that supports the role of myrrh in BC therapy. Furthermore, the results suggest that network pharmacology predictions require experimental validation for reliability.
Assuntos
Neoplasias da Mama , Simulação de Acoplamento Molecular , Farmacologia em Rede , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Simulação de Dinâmica Molecular , Células MCF-7 , Flavanonas/farmacologia , Flavanonas/química , Flavanonas/metabolismo , Commiphora/química , Commiphora/metabolismo , Quercetina/farmacologia , Quercetina/química , Quercetina/metabolismo , Mapas de Interação de Proteínas/efeitos dos fármacos , Receptor alfa de Estrogênio/metabolismo , Receptor alfa de Estrogênio/química , Linhagem Celular Tumoral , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/químicaRESUMO
The present study utilized response surface methodology (RSM) to investigate the impact of varying concentrations of carboxymethyl cellulose (CMC: 0.75-1.75 wt%), Commiphora mukul polysaccharide (CMP: 0-1 wt%), and Chitosan Nanofiber (CHNF: 0-1 wt%) on the physical and antimicrobial characteristics of nanocomposite films based on CMC. The optimization process aimed to enhance ultimate tensile strength (UTS), strain at break (SAB), and antibacterial activity, while minimizing water vapor permeability (WVP), solubility, swelling, moisture content, opacity, and total color difference (ΔE). The results revealed that both CMP and CHNF had a positive influence on reducing moisture content, WVP, and increasing UTS. However, higher concentrations of CMP and CHNF had a divergent effect on SAB, ΔE, and swelling. The incorporation of CMP led to increased opacity and solubility, while the inclusion of CHNF resulted in decreased opacity and solubility. Notably, only CHNF addition significantly improved the antibacterial properties of the films. By applying the optimization procedure utilizing RSM, the formulation containing CMC (1.5 wt%), CMP (0.25 wt%), and CHNF (0.75 wt%) demonstrated superior physical, mechanical, and antibacterial properties in the biodegradable film matrix. These findings highlight the potential of utilizing these components to enhance the performance of CMC-based nanocomposite films.
Assuntos
Carboximetilcelulose Sódica , Quitosana , Nanocompostos , Nanofibras , Resistência à Tração , Quitosana/química , Carboximetilcelulose Sódica/química , Nanofibras/química , Nanocompostos/química , Antibacterianos/farmacologia , Antibacterianos/química , Gomas Vegetais/química , Polissacarídeos/química , Solubilidade , Commiphora/química , Permeabilidade , Vapor , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
The utilization of metallic nanoparticles in bio-nanofabrication holds significant potential in the field of applied research. The current study applied and compared integrated ultrasonic-microwave-assisted extraction (US/MICE), ultrasonic extraction (USE), microwave-assisted extraction (MICE), and maceration (MAE) to extract total phenolic content (TPC). In addition, the study examined the antioxidant activity of Commiphora gileadensis (Cg) leaf. The results demonstrated that the TPC of US/MICE exhibited the maximum value at 59.34 ± 0.007 mg GAE/g DM. Furthermore, at a concentration of 10 µg/mL, TPC displayed a significant scavenging effect on DPPH (56.69 %), with an EC50 (6.48 µg/mL). Comprehensive metabolite profiling of the extract using UPLC-qTOF-MS/MS was performed to identify active agents. A total of 64 chromatographic peaks were found, out of which 60 were annotated. The most prevalent classes of metabolites found were polyphenols (including flavonoids and lignans), organic compounds and their derivatives, amides and amines, terpenes, and fatty acid derivatives. Transmission electron microscopy (TEM) revealed the aggregate size of the synthesized nanoparticles and the spherical shape of C. gileadensis-mediated silver nanoparticles (Cg-AgNPs). The nanoparticles had a particle size ranging from 7.7 to 42.9 nm. The Cg-AgNPs exhibited more inhibition zones against S. aureus and E. coli. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of Cg-extract, AgNPs, and Cg-AgNPs were also tested. This study demonstrated the feasibility of using combined ultrasonic-microwave-assisted extraction to separate and extract chemicals from C. gileadensis on a large scale. These compounds have potential use in the pharmaceutical industry. Combining antibacterial and biocompatible properties in materials is vital for designing new materials for biomedical applications. Additionally, the results showed that the biocompatibility of the Ag-NPs using C. gileadensis extracts demonstrated outstanding antibacterial properties.
Assuntos
Antibacterianos , Commiphora , Nanopartículas Metálicas , Micro-Ondas , Extratos Vegetais , Folhas de Planta , Prata , Ondas Ultrassônicas , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Prata/química , Commiphora/química , Nanopartículas Metálicas/química , Folhas de Planta/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Cromatografia Líquida de Alta Pressão , Testes de Sensibilidade Microbiana , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Técnicas de Química SintéticaRESUMO
Plant extracts and essential oils can be alternative environmentally friendly agents to combat pathogenic microbes and malaria vectors. Myrrh is an aromatic oligum resin that is extracted from the stem of Commiphora spp. It is used in medicine as an insecticide, cytotoxic, and aromatic. The current study assessed the effect of Commiphora myrrha resin extracts on the biological potency of the third larval stage of Aedes aegypti, as well as its antioxidant and cytotoxic properties against two types of tumor cells (HepG-2 and Hela cell lines). It also used GC-MS to determine the chemical composition of the C. myrrha resin extracts. Fifty components from the extracted plant were tentatively identified using the GC-MS method, with curzerene (33.57%) typically listed as the primary ingredient, but other compounds also make up a significant portion of the mixture, including 1-Methoxy-3,4,5,7-tetramethylnaphthalene (15.50%), ß-Elemene (5.80%), 2-Methoxyfuranodiene (5.42%), 2-Isopropyl-4,7-Dimethyl-1-Naphthol (4.71%), and germacrene B (4.35%). The resin extracts obtained from C. myrrha exhibited significant efficacy in DPPH antioxidant activity, as evidenced by an IC50 value of 26.86 mg/L and a radical scavenging activity percentage of 75.06%. The 50% methanol extract derived from C. myrrha resins exhibited heightened potential for anticancer activity. It demonstrated substantial cytotoxicity against HepG-2 and Hela cells, with IC50 values of 39.73 and 29.41 µg mL-1, respectively. Notably, the extract showed non-cytotoxic activity against WI-38 normal cells, with an IC50 value exceeding 100 µg mL-1. Moreover, the selectivity index for HepG-2 cancer cells (2.52) was lower compared to Hela cancer cells (3.40). Additionally, MeOH resin extracts were more efficient against the different growth stages of the mosquito A. aegypti, with lower LC50, LC90, and LC95 values of 251.83, 923.76, and 1293.35 mg/L, respectively. In comparison to untreated groups (1454 eggs/10 females), the average daily number of eggs deposited (424 eggs/L) decreases at higher doses (1000 mg/L). Finally, we advise continued study into the possible use of C. myrrha resins against additional pests that have medical and veterinary value, and novel chemicals from this extract should be isolated and purified for use in medicines.
Assuntos
Antioxidantes , Commiphora , Cromatografia Gasosa-Espectrometria de Massas , Larva , Extratos Vegetais , Resinas Vegetais , Commiphora/química , Humanos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Antioxidantes/farmacologia , Antioxidantes/química , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Células HeLa , Resinas Vegetais/química , Larva/efeitos dos fármacos , Células Hep G2 , Inseticidas/farmacologia , Inseticidas/química , Inseticidas/isolamento & purificação , Aedes/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacosRESUMO
Trichinella spiralis infection is a food-borne zoonotic disease caused by nematodes that dwell in the tissues, presenting a significant public health concern. This study aimed to evaluate the effectiveness of different treatments including silver nanoparticles (AgNPs), myrrh biosynthesized AgNPs "AgNPs synthesized using plant-based green technologies", myrrh extract, and myrrh essential oil, as alternative treatments against T. spiralis infection. Parasitological, histopathological, and cytotoxicity assessments were conducted to investigate the effects of various concentrations of these treatments in reducing the populations of adult worms and larvae during both the intestinal and muscular phases of T. spiralis-infected mice. The results showed that the highest antihelminthic efficacy against the intestinal phase of T. spiralis was achieved by myrrh extract (86.66%), followed closely by AgNPs (84.96%) and myrrh AgNPs (82.51%) at higher concentrations (800 mg/kg for myrrh extract, 40 µg/mL for AgNPs, and 40 µg/mL for myrrh AgNPs). While the group treated with myrrh essential oil showed the lowest percentage of adult reduction (78.14%). However, all treatments demonstrated comparable effects in reducing the larvae population in the muscle phase. Histopathological examination of the tissues revealed compelling evidence of the effectiveness of AgNPs, particularly when prepared with myrrh. Additionally, a comprehensive assessment of the cytotoxicity of AgNPs indicated low toxicity levels. This study supports that AgNPs synthesized using plant-based green technologies hold therapeutic potential for the treatment of T. spiralis infection. These findings present a promising avenue for the development of novel antiparasitic drugs that are both effective and safe. RESEARCH HIGHLIGHTS: Myrrh extract has the highest antihelminthic efficacy against the intestinal phase of T. spiralis. Histopathological examination of the tissues revealed compelling evidence of the effectiveness of AgNPs, particularly when prepared with myrrh. During intestinal phase of T. spiralis, varying levels of nanoparticle precipitation were detected in the liver, brain, lung, and intestine. During the muscular phase, the highest amount of AgNPs precipitation was detected in the liver, followed by the brain, and lung.
Assuntos
Nanopartículas Metálicas , Extratos Vegetais , Prata , Trichinella spiralis , Triquinelose , Animais , Trichinella spiralis/efeitos dos fármacos , Prata/farmacologia , Prata/química , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Camundongos , Triquinelose/tratamento farmacológico , Extratos Vegetais/farmacologia , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Commiphora/química , Larva/efeitos dos fármacos , Feminino , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Modelos Animais de Doenças , TerpenosRESUMO
The "ultrasonic-assisted extraction (UAE)" method was utilized in this work to assess how different process parameters affected the yield and recovery of phenolic compounds from the leaf of Commiphora gileadensis, which is one of the medicinal plants with a variety of biological functions. Its leaf is used for a various of therapeutic applications, such as the treatment of bacterial infections, inflammation, and wound healing. The "One-Factor-At-a-Time (OFAT)" approach was employed to examine the impacts of various UAE process parameters on the process of extraction, which include time of extraction, sample/solvent ratio, ultrasonic frequency, and solvent (ethanol) concentration. The extracts were then investigated for the presence of several phytochemicals using analytical techniques such as "Gas Chromatography-Mass Spectroscopy (GC-MS)" and "Fourier Transform Infrared Spectroscopy (FTIR)" studies. The findings showed that the maximum extraction yield, the total phenolic content (TPC), and the total flavonoids content (TFC) of the ethanolic extract of the leaves of C. gileadensis using the UAE method were at 31.80 ± 0.41 %, 96.55 ± 2.81 mg GAE/g d.w. and 31.66 ± 2.01 mg QE/g d.w. accordingly under a procedure duration of 15 min, ultrasonic frequency of 20 kHz, solvent/sample ratio of 1:20 g/mL, and solvent concentration of 40 % v/v. The leaves extract of C. gileadensis included 25 phenolic compounds that were previously unreported, and GC-MS analysis confirmed their presence. Hence, it follows that the UAE technique can successfully extract the phytochemicals from C. gileadensis for a variety of therapeutic uses.
Assuntos
Fracionamento Químico , Commiphora , Fenóis , Folhas de Planta , Ondas Ultrassônicas , Commiphora/química , Folhas de Planta/química , Fenóis/isolamento & purificação , Fracionamento Químico/métodos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Solventes/químicaRESUMO
Six undescribed cadinane sesquiterpenoids (1-6), two undescribed guaiane sesquiterpenoids (7-8), and an undescribed germacrane sesquiterpenoid (9) were isolated from the oleo-gum resin of Commiphora myrrha. Their structures were determined by the analysis of 1D/2D NMR and HRESIMS data, as well as quantum chemical ECD and NMR calculations. All the sesquiterpenoids were evaluated for their NO production inhibitory activity in LPS-stimulated RAW 264.7 mouse monocyte-macrophages. The results revealed that commiphone A (1) and commipholide D (7) exhibited significant inhibitory effect on NO generation with IC50 values of 18.6 ± 2.0 and 37.5 ± 1.5 µM, respectively. Furthermore, 1 and 7 dose-dependently inhibited the mRNA expression of inflammatory cytokines IL-1ß, IL-6 and TNF-α induced by LPS in the RAW264.7 cells, indicating that 1 and 7 possess potent anti-inflammatory activity in vitro.
Assuntos
Commiphora , Sesquiterpenos , Animais , Camundongos , Commiphora/química , Lipopolissacarídeos/farmacologia , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Resinas Vegetais/farmacologia , Resinas Vegetais/química , Anti-Inflamatórios/farmacologia , Estrutura MolecularRESUMO
Trichinellosis is a serious disease with no satisfactory treatment. We aimed to assess the effect of myrrh (Commiphora molmol) and, for the first time, thyme (Thymus vulgaris L.) against enteral and encysted (parenteral) phases of Trichinella spiralis in mice compared with albendazole, and detect their effect on inducible nitric oxide synthase (iNOS) expression. Oral administration of 500 mg/kg of myrrh and thyme led to adult reduction (90.9%, 79.4%), while 1,000 mg/kg led to larvae reduction (79.6%, 71.3%), respectively. Administration of 50 mg/kg of albendazole resulted in adult and larvae reduction (94.2%, 90.9%). Positive immunostaining of inflammatory cells infiltrating intestinal mucosa and submucosa of all treated groups was detected. Myrrh-treated mice showed the highest iNOS expression followed by albendazole, then thyme. On the other hand, both myrrh and thyme-treated groups showed stronger iNOS expression of inflammatory cells infiltrating and surrounding encapsulated T. spiralis larvae than albendazole treated group. In conclusion, myrrh and thyme extracts are highly effective against both phases of T. spiralis and showed strong iNOS expressions, especially myrrh which could be a promising alternative drug. This experiment provides a basis for further exploration of this plant by isolation and retesting the active principles of both extracts against different stages of T. spiralis.
Assuntos
Animais , Antinematódeos/farmacologia , Óxido Nítrico Sintase Tipo II/metabolismo , Thymus (Planta) , Terpenos/farmacologia , Trichinella spiralis/efeitos dos fármacos , Albendazol/farmacologia , Linhagem Celular , Commiphora/química , Fibroblastos/efeitos dos fármacos , Imuno-Histoquímica , Intestino Delgado/parasitologia , Larva/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Músculo Esquelético/parasitologia , Trichinella spiralis/enzimologiaRESUMO
This work has been carried out to investigate the effect of Schistosoma mansoni infection on mice livers after treatment with the ethanolic extract of Citrus reticulata root or the oleo-resin extract from Myrrh of Commiphora molmol tree (Mirazid), as a new antishistosomal drug. Marker enzymes for different cell organelles were measured; succinate dehydrogenase (SDH); lactate dehydrogenase (LDH) and its isoenzymes; glucose-6-phosphatase (G-6-Pase); acid phosphatase (AP) and 5'- nucleotidase. Liver function enzymes; aspartate aminotransferase (AST); alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were also estimated. Parasitological studies through ova count and worm burden will also be taken into consideration. The results showed a marked reduction in SDH, LDH, AST, and ALT enzyme activities and a significant increase in G-6-Pase, AP, 5'- nucleotidase, and ALP after S. mansoni infection. A noticeable alteration in LDH subunits were also noticed. Treatment with C. reticulata or Mirazid improved all the previous enzyme activities with a noticeable reduction in ova count and worm burden.