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Ferulago bernardii Tomk & M. Pimen belongs to Apiaceae family. Various species of the Ferulago genus have antioxidant, anticholinesterase, cytotoxic, and antiproliferative effects. In this study, the essential oil of F. bernardii was extracted using the Clevenger apparatus. The essential oil compounds were identified using GC-MS/FID. The interaction between the essential oil and DNA strands was evaluated through spectrophotometric titration. The molecular mechanism of the interaction between the main components of the essential oil and different DNA strands was assessed using molecular dynamics simulation. Based on the results, 92.03±1.20 % of the essential oil consisted of α-pinene. Therefore, the essential oil could serve as a suitable source of α-pinene. α-pinene is a monoterpene hydrocarbon that has various effects, including anti-inflammatory, antioxidant, antimicrobial, and antitumor properties. The binding constant of the essential oil to DNA strands (Ka ) was determined to be 5.40±0.47×10-3 â M-1 . Molecular dynamics simulation demonstrated that α-pinene could interact with AT and CG rich DNA strands and indirectly stabilize G-Quadruplex. Given the different applications for α-pinene and its high percentage in the essential oil, it is suggested that researchers pay more attention to F. bernardii in the pharmaceutical, cosmetic, and food industries.
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Apiaceae , Óleos Voláteis , Antioxidantes/farmacologia , Antioxidantes/química , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Apiaceae/química , DNARESUMO
PURPOSE: The aim of this study was evaluating the cytotoxic and radiosensitizing effects of Ursolic Acid (UA) and Kamolonol Acetate (KA) on HCT116 cell line and finally investigating the functional role of NF-κB and CCND1 genes in the radiosensitizing activity of UA and KA. MATERIALS AND METHOD: The cytotoxic effects of UA and KA by MTT assay was evaluated on HCT-116. Clonogenic assay was performed to investigate of radiosensitizing effects of UA and KA on HCT116. To assessment the expression levels of NF-κB and CCND1 genes, real-time PCR method was used. RESULTS: The results of MTT assay revealed that UA and KA have cytotoxic effects on HCT116 cell line. According to clonogenic assay, survival fraction of treated cells with UA and KA has been decreased compared to the survival fraction of untreated cells. UA and KA lead to the decrease in the expression level of NF-κB. Synergistic effect of radiosensitizing agents with radiation was only approved for UA and 2â¯Gy of radiation. CONCLUSION: Based on our study, UA and KA have cytotoxic effects on HCT116 cell line. Furthermore, UA may lead to radiosensitization of human colorectal tumor cells by NF-κB1 and CCND1signaling pathways.
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Acetatos/farmacologia , Cumarínicos/farmacologia , Ciclina D1/antagonistas & inibidores , NF-kappa B/antagonistas & inibidores , Radiossensibilizantes/farmacologia , Sesquiterpenos/farmacologia , Triterpenos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Ciclina D1/genética , Ciclina D1/metabolismo , Relação Dose-Resposta a Droga , Células HCT116 , Humanos , Estrutura Molecular , NF-kappa B/genética , NF-kappa B/metabolismo , Relação Estrutura-Atividade , Células Tumorais Cultivadas , Ácido UrsólicoRESUMO
The prevalence of Alzheimer's disease (AD) has become a substantial global concern. Approved AChE inhibitors have been used for symptomatic treatment of AD. Binding of amyloid ß (Aß) to the peripheral anionic site of AChE facilitates the formation of Aß plaques. Blocking this proposed protein-protein interaction by inhibition of the peripheral anionic site of AChE, in addition to increasing the level of ACh, reduces the Aß aggregation and might qualify to slow down the progression of disease besides the palliative treatment. Targeting protein-protein interactions consider as one of the most challenging issues in the realm of drug design in which peptides have potentials to excel in. In the present study, we applied two virtual fragment-based and template-based approaches to design peptidic inhibitors of the PAS of AChE. Based on the in silico studies, high scored peptides p2 (WTWYGYWVW) and p10 (NHRMLTRRY) obtained from fragment-based and template-based design respectively. Regarding in vitro results, p2 (IC50 = 16 ± 3.2 µM) and p10 (IC50 = 23.6 ± 4.9 µM) showed significant AChE inhibitory effects. The molecular mechanism of inhibition studied by Lineweaver-Burk plots was mixed inhibition for both peptides. The in vitro results conformed to the in silico results and showed that both peptides occupied the CAS and PAS of AChE. The comparison of two peptide-design approaches revealed that the fragment-based design had more chemical diversity and showed priority to the template-based design. According to the obtained results, peptidic inhibitors of AChE designed by the proposed fragment-based approach might be more efficient in comparison to traditional approaches.
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Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Inibidores da Colinesterase/química , Peptídeos/síntese química , Sequência de Aminoácidos , Inibidores da Colinesterase/farmacologia , Desenho de Fármacos , Humanos , Modelos Moleculares , Peptídeos/metabolismo , Agregados Proteicos/efeitos dos fármacos , Técnicas de Síntese em Fase Sólida , Relação Estrutura-AtividadeRESUMO
Context: Satureja khuzistanica Jamzad. (Lamiaceae), is known for its antifungal and antioxidant compounds, especially rosmarinic acid (RA).Objective: The study examines the effect of elicitors on RA production and phytochemical properties of S. khuzistanica.Materials and methods: In vitro plants were treated with methyl jasmonate (MeJA) and multi-walled carbon nanotubes (MWCNTs). In vivo plants were treated with MWCNTs and salicylic acid (SA). RA was measured by HPLC. Catalase (CAT), guaiacol peroxidase (POD) and ascorbate peroxidase (APX) were quantified. DPPH and ß-carotene were assayed in in vivo extracts. The antifungal effects of extracts were evaluated against Fusarium solani K (FsK).Results: The highest RA contents of in vitro plants were 50 mg/L MeJA (140.99 mg/g DW) and 250 mg/L MWCNTs (140.49 mg/g DW). The highest in vivo were 24 h MWCNTs (7.13 mg/g DW) and 72 h SA (9.12 mg/g DW). The maximum POD and APX activities were at 100 mg/L MeJA (5 and 4 mg protein, respectively). CAT had the highest activities at 50 mg/L MeJA (2 mg protein). DPPH and ß-carotene showed 50% and 80% inhibition, respectively. The FsK aggregation was the lowest for in vitro extract in number of conidia [1.82 × 1010], fresh weight (6.51 g) and dry weight (0.21 g) that proved RA inhibitory effects. The callus reduces FsK growth diameter to 2.75 on the 5th day.Discussion and conclusions: Application of MeJA, SA, and MWCNTSs could increase RA in S. khuzistanica and highlighted potential characteristics in pharmaceutical and antifungal effects.
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Cinamatos/análise , Cinamatos/farmacologia , Depsídeos/análise , Depsídeos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Reguladores de Crescimento de Plantas/farmacologia , Satureja/química , Satureja/metabolismo , Acetatos/farmacologia , Antifúngicos/análise , Antifúngicos/farmacologia , Antioxidantes/análise , Antioxidantes/farmacologia , Ascorbato Peroxidases/biossíntese , Ascorbato Peroxidases/metabolismo , Catalase/biossíntese , Catalase/metabolismo , Ciclopentanos/farmacologia , Fusarium/crescimento & desenvolvimento , Nanotubos de Carbono , Oxilipinas/farmacologia , Peroxidase/biossíntese , Peroxidase/metabolismo , Compostos Fitoquímicos , Ácido Salicílico/farmacologia , Ácido RosmarínicoRESUMO
Satureja avromanica is an indigenous plant which is frequently used as a spice in Avraman-Kurdistan region of Iran. The present study aimed to investigate the chemical composition, antimicrobial and antioxidant properties of the S. avromanica. In addition, rosmarinic acid and total phenolic content of S. avromanica was assessed by spectrophotometric method and HPTLC. The essential oil and methanolic extract were isolated by hydrodistillation and maceration methods, respectively. A total of 32 compounds representing 98.6% of the essential oil were identified by GC-MS and GC-FID. The main constituents were n-pentacosane (23.8%), spathulenol (11.5%), ß-bourbonen (11.3%) and n-docosane (11.0%). The antibacterial activity of samples were carried out by disc diffusion method and evaluate the minimal inhibitory concentration (MIC) essential oil and methanolic extract were found to be effective against Staphylococcus aureus, Bacillus cereus and Bacillus pumilus. The highest scavenging activity was found for methanolic extract of S. avromanica (21.58 µg/mL) and the total phenolics of methanolic extract of S. avromanica was 95.3 mg GAE/g. The rosmarinic acid content of S. avromanica methanolic extract was 0.83 mg/g plant. Antioxidant activity and rosmarininc acid content of S. avromanica suggests that the essential oil and methanolic extract of S. avromanica has great potential for application as a natural antimicrobial and antioxidant agent to preserve food.
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Laserpitium carduchorum is frequently used as a spice, and in Bane folk medicine, the aerial parts of this are used to treat urinary infections. Variation in the quantity and quality of the essential oil of Iranian L. carduchorum at different developmental growth stages including vegetative, flowering, and seed ripening is reported. In total, 33 compounds were identified and quantified in the oils of vegetative, flowering, and seed ripening stages, representing 97.8%, 98.8%, and 98.7% of the oils, respectively. α-Pinene (45.1, 61.4, and 46.4%), sabinene (16.5, 10.3, and 17.5%), and limonene (6.4, 8.5, and 20.4%) were the main compounds in all samples. The antioxidant activities of different extracts of L. carduchorum at different developmental growth stages were examined by employing various established in vitro experiments including DPPH, FRAP, and TEAC assays. The amounts of total phenolics were also determined spectrophotometerically. Antimicrobial activities of different extracts and essential oils of L. carduchorum at different developmental growth stages were examined against five Gram-positive and four Gram-negative bacteria, as well as two fungi. The results showed that maximum antioxidant and antimicrobial activity of extracts were at the flowering stage of the plant. Maximum antimicrobial activity of essential oils was at seed ripening stage.
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Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antioxidantes/farmacologia , Apiaceae/química , Apiaceae/crescimento & desenvolvimento , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antifúngicos/química , Antifúngicos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Candida albicans/efeitos dos fármacos , Relação Dose-Resposta a Droga , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Saccharomyces cerevisiae/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
One new and five known sesquiterpene coumarins were isolated from the roots of Ferula pseudalliacea. The structures were elucidated by 1D and 2D NMR, and HR-ESIMS data as 4'-hydroxy kamolonol acetate (1), kamolonol (2), szowitsiacoumarin A (3), farnesiferon B (4), farnesiferol C (5), and flabellilobin A (6). The absolute configuration of compounds 1, 2, and 4 was established by comparison of experimental and simulated electronic circular dichroism spectra using time dependence density function theory. 4'-Hydroxy kamolonol acetate and kamolonol showed antibacterial activity against Heliobacter pylori and Staphylococcus aureus at a concentration of 64 µg/mL. Kamolonol, 4'-hydroxy kamolonol acetate, and farnesiferon B displayed a cytotoxic activity in HeLa cells, with an IC50 of 3.8, 4.5, and 7.7 µM, respectively.
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Antibacterianos/farmacologia , Cumarínicos/farmacologia , Ferula/química , Sesquiterpenos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Dicroísmo Circular , Cumarínicos/química , Cumarínicos/isolamento & purificação , Células HeLa , Helicobacter pylori/efeitos dos fármacos , Humanos , Espectrometria de Massas , Testes de Sensibilidade Microbiana , Ressonância Magnética Nuclear Biomolecular , Extratos Vegetais/química , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Staphylococcus aureus/efeitos dos fármacosRESUMO
BACKGROUND: Cancer remains a global burden, with increasing mortality rates. Current cancer treatments involve controlling the transcription of malignant DNA genes, either directly or indirectly. DNA exhibits various structural forms, including the G-quadruplex (G4), a secondary structure in guanine-rich regions. G4 plays a crucial role in cellular processes by regulating gene expression and telomerase function. Researchers have recently identified G4-stabilizing binding agents as promising anti-cancer compounds. Additionally, peptides have emerged as effective anticancer pharmaceuticals due to their ability to form multiple hydrogen bonds, electrostatic interactions, and van der Waals forces. These properties enable peptides to bind to specific areas of DNA chains selectively. However, despite these advancements, designing G4-binding peptides remains challenging due to a lack of comprehensive information. OBJECTIVE: In our present study, we employed an in silico fragment-based approach to design G4- binding peptides. This innovative method combines machine learning classification, molecular docking, and dynamics simulation. METHODS: AutoDock Vina and Gromacs performed molecular docking and MD simulation, respectively. The machine learning algorithm was implemented by Scikit-learn. Peptide synthesis was performed using the SPPS method. The DNA binding affinity was measured by applying spectrophotometric titration. RESULTS: As a result of this approach, we identified a high-scoring peptide (p10; sequence: YWRWR). The association constant (Ka) between p10 and the ctDNA double helix chain was 4.45 × 105 M-1. Molecular modeling studies revealed that p10 could form a stable complex with the G4 surface. CONCLUSION: The obtained Ka value of 4.45 × 105 M-1 indicates favorable interactions. Our findings highlight the role of machine learning and molecular modeling approaches in designing new G4-binding peptides. Further research in this field could lead to targeted treatments that exploit the unique properties of G4 structures.
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DNA , Quadruplex G , Aprendizado de Máquina , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Peptídeos , DNA/química , DNA/metabolismo , Peptídeos/química , Ligação Proteica , Desenho de Fármacos , Humanos , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Simulação por Computador , Sítios de LigaçãoRESUMO
Background: Trichomoniasis is one of the most common sexually transmitted infections worldwide. The growing concern of drug resistance of this infection has cautioned the need for new drug development. We evaluated the potential antiproliferative and apoptotic effect of α-pinene and tannic acid (TA) on Trichomonas vaginalis cells. In addition, the cytotoxicity of agents on Vero cells was investigated. Methods: Trichomonas cells were axenically cultured in TYI-S-33 medium. In vitro antiproliferative activity of α-pinene, TA, and metronidazole was investigated against Trichomonas cells. The assays were carried out in triplicate using microtiter plate and trypan blue staining method. Annexin V/PI staining with flow cytometry was used to evaluate apoptosis induction. In addition, the cytotoxic effect was measured by MTT assay. Results: α-Pinene and TA exhibited significant inhibition of the Trichomonas cells and the lowest IC50 values were 22.9 µg/ml and 140 µg/ml at 48 hours' incubation, respectively. The CC50 was found at 116 µg/ml for α-pinene and 473 µg/ml for TA, after 48 hours of treatment. The flow cytometry study demonstrated that the natural compounds induced apoptosis in Trichomonas cells. After 24 hours of treatment, the induction of apoptosis was 5.2% - 36.6% at concentrations of 3.9 - 62.5 µg/ml for α-pinene and TA induced-apoptosis was 6.1% - 53.8% at concentrations of 125-2000 µg/ml. Conclusion: Although the results show the antiproliferative and apoptotic effect of α-pinene and TA on Trichomonas cells, in vivo studies are needed to further clarify the effects of these compounds.
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Phenylalanine ammonia lyase (PAL) is a key enzyme regulating the biosynthesis of the compounds of the phenylpropanoid pathway. This study aimed to isolate and characterize PAL genes from Ferula pseudalliacea Rech.f. (Apiales: Apiaceae) to better understand the regulation of metabolite production. Three PAL gene isoforms (FpPAL1-3) were identified and cloned using the 3'-RACE technique and confirmed by sequencing. Bioinformatics analysis revealed important structural features, such as phosphorylation sites, physicochemical properties, and evolutionary relationships. Expression analysis by qPCR demonstrated the differential transcription profiles of each FpPAL isoform across roots, stems, leaves, flowers, and seeds. FpPAL1 showed the highest expression in stems, FpPAL2 in roots and flowers, and FpPAL3 in flowers. The presence of three isoforms of PAL in F. pseudalliacea, along with the diversity of PAL genes and their tissue-specific expression profiles, suggests that complex modes of regulation exist for phenylpropanoid biosynthesis in this important medicinal plant. The predicted interaction network revealed associations with key metabolic pathways, emphasizing the multifaceted roles of these PAL genes. In silico biochemical analyses revealed the hydrophilicity of the FpPAL isozyme; however, further analysis of substrate specificity and enzyme kinetics can clarify the specific role of each FpPAL isozyme. These comprehensive results increase the understanding of PAL genes in F. pseudalliacea, helping to characterize their contributions to secondary metabolite biosynthesis.
Assuntos
Ferula , Regulação da Expressão Gênica de Plantas , Fenilalanina Amônia-Liase , Proteínas de Plantas , Fenilalanina Amônia-Liase/genética , Fenilalanina Amônia-Liase/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ferula/genética , Ferula/metabolismo , Filogenia , Flores/genéticaRESUMO
Stachys lavandulifolia Vahl known as "mountain tea", is a perennial flowering plant belonging to the Lamiaceae family and is widespread in Iran, Armenia, Azerbaijan, Iraq, Turkey and Turkmenistan. S. lavandulifolia is widely used in traditional medicine for its analgesic, anti-inflammatory and anxiolytic properties. This plant has different chemical compounds classes including terpenoids, iridoids, flavonoids and phenylethanoids that have been isolated from the aerial parts of it. This review covers the plant botany, traditional medicinal uses and chemical composition of S. lavandulifolia, along with its biological and pharmacological activities including clinical trial data. The information of this review article was obtained from different scientific databases such as Google scholar, Science Direct, Hindawi, SID, Scopus, PubMed, and ACS as well as traditional Persian books. Pharmacological and clinical studies, especially Anxiolytic activity and anti-inflammatory on the plant are relatively low, so these studies are suggested in the future. Also, phytochemical investigation on root of the plant is necessary.
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Wound healing is a complex process orchestrated by interactions between a variety of cell types, including keratinocytes, fibroblasts, endothelial cells, inflammatory cells, and bioactive factors such as extracellular matrix (ECM) components, growth factors, and cytokines. Chronic wounds exhibit delayed proliferative phase initiation, reduced angiogenesis, impaired ECM synthesis, and persistent inflammatory response. Chronic wounds are one of the main challenges to the healthcare system worldwide, with a high cost for medical services. Hence, investigation of new approaches to accelerate wound healing is essential. Phytomedicines are considered as potential agents for improving the wound healing by accelerating epithelization, collagen synthesis, and angiogenesis. These natural compounds have various advantages including availability, ease of application, and high effectiveness in wound managment. This study aimed to investigate the biological effects of saffron or Crocus sativus L. (C. sativus) petal extract on cell survival, migration, and angiogenesis using MTT, scratch and in vitro tube formation assays. Moreover, the expression of collagen type I alpha 1 (COL1A1) and vascular endothelial growth factor (VEGF) were evaluated in human dermal fibroblasts (HDF)s and human umbilical vein endothelial cells (HUVEC)s, respectively. The effect of the C. sativus extract on the skin of diabetic mice was also monitored. The results showed that C. sativus petal extract promoted the viability and migration of HDFs and HUVECs. Moreover, C. sativus petal extract enhanced the formation of tube-like structures by HUVECs cultured on the Matrigel basement membrane matrix, indicating its potential to stimulate angiogenesis. Gene expression studies have shown the the C. sativus extract increases wound healing by upregulation of COL1A1 and VEGF, which are crucial factors involved in collagen deposition, epithelialization, and angiogenesis. Histological analysis revealed that C. sativus petal extract enhanced vascularity and increased the number of fibroblasts and collagen synthesis, ultimately accelerating wound closure compared to wounds treated with eucerin and commercial ointment in diabetic mice. Therefore, C. sativus petal extract has potential as a herbal treatment to improve the healing of diabetic wounds.
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Crocus , Fibroblastos , Células Endoteliais da Veia Umbilical Humana , Extratos Vegetais , Fator A de Crescimento do Endotélio Vascular , Cicatrização , Cicatrização/efeitos dos fármacos , Crocus/química , Animais , Humanos , Extratos Vegetais/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Camundongos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Diabetes Mellitus Experimental/tratamento farmacológico , Colágeno Tipo I/metabolismo , Colágeno Tipo I/genética , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cadeia alfa 1 do Colágeno Tipo I , Flores/química , Neovascularização Fisiológica/efeitos dos fármacos , MasculinoRESUMO
The roots of F. haussknechtii are used by local people in order to treat wounds and urinary infections. Ferula species are rich in bioactive compounds with biological effects. In line with our previous studies about screening antibacterial natural products, five terpenoid derivatives were purified from Ferula haussknechtii. The separation and purification were performed by column chromatography. Their structures were determined by 1 D and 2 D NMR as hawraman 8-p-hydroxybenzoyl-tovarol (1), ferutinin (2), lancerotriol 6-(p-hydroxybenzoate) (3), chimganin (4), and chimgin (5). Then, the antibacterial effects of the purified compounds were evaluated by measuring their MIC values against Gram-positive and Gram-negative bacteria. The results showed that compound (1) had the most antibacterial effect on Bacillus cereus (MIC = 16 µg/mL). The antibacterial effects of F. haussknechtii compounds are in line with their local application and it is suggested that further studies should be conducted to determine their mechanism of action.
Assuntos
Ferula , Terpenos , Humanos , Terpenos/farmacologia , Antibacterianos/química , Ferula/química , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Extratos Vegetais/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
Objectives: Dental caries is one of the most prevalent human diseases worldwide. The disease initiates with bacterial adherence to the tooth surface followed by the formation of dental plaques. Mutans streptococci and Candida albicans are principal oral microorganisms involved in the initiation and development of dental caries. Phytochemicals have been shown to possess promising antimicrobial properties against a wide range of microorganisms and can be used for the prevention and treatment of dental caries. Herein, we reviewed literature on plants that are traditionally used for their antimicrobial properties or possess promising anticariogenic activity. We selected aerial parts of Scrophularia striata (S. striata) and galls of Quercus infectoria (Q. infectoria) and investigated their antimicrobial activity against cariogenic microorganisms. Methods: Water soluble fractions were obtained from hydroalcoholic extracts of S. striata and Q. infectoria and their antimicrobial activity against Streptococcus mutans (S. mutans), Streptococcus sobrinus (S. sobrinus), and Candida albicans (C. albicans) was evaluated separately and in combination. The extracts were then used for preparing an herbal mouthwash whose stability and tannic acid content were evaluated over 60 days. Results: Q. infectoria gall extract possesses efficient antimicrobial activity that was synergistically enhanced in the presence of S. striata extract. Mouthwash prepared using these extracts showed desirable organoleptic characteristics, antimicrobial activity, and stability. Conclusion: Extracts of S. striata and Q. infectoria galls can be used together for preparing dental products with effective anticariogenic properties. Our study highlights the importance of extensive pharmacological investigations when using herbal products alone or in combination with other chemical substances.
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Alzheimer's disease (AD) is the most common cause of dementia worldwide and is classified as a neurodegenerative disorder. From a drug design perspective, natural products (NPs) are more drug-like and are highly compatible with biological systems compared to most synthetic libraries. NPs provide a more efficient and cost-effective approach to new drug discovery. However, the complexity of NPs makes their identification a challenging task. Chimgin, a bicyclic monoterpene with three chiral centers, exhibits a wide range of biological activity. Despite this, the exact structure of chimgin has remained unclear until now. In this study, we quantified the amount of chimgin in Ferula haussknechtii using analytical Reversed-phase high-pressure liquid chromatography equipped with photodiode array detector (RP-HPLC-PDA). Furthermore, we determined the absolute configuration of chimgin through electronic circular dichroism (ECD) spectroscopy and time-dependent density functional theory (TDDFT) calculations. Finally, we evaluated its inhibitory effect on AChE through in vitro and in silico studies. The extraction process yielded an output of 2.82 ± 0.10% with an exact amount of 0.62 ± 0.04 mg of chimgin per 100 g of plant. Based on the results of ECD and TDDFT calculation, the absolute configuration of chimgin was determined to be 1S, 2S, 4S. Chimgin exhibited an inhibitory effect on AChE with an IC50 of 37.43 µM and its mechanism of action was found to be competitive. HighlightsChimgin was isolated from the roots of Ferula haussknechtii.The amount of chimgin in the plant was determined by RP-HPLC-PDA.Its absolute configuration of chimgin was determined using ECD.In vitro acetylcholinesterase activity of the chimgin was evaluated.The docking and molecular dynamic simulation of chimgin was done.Communicated by Ramaswamy H. Sarma.
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INTRODUCTION: Human trichomoniasis is a widespread sexually transmitted disease and the concern of drug resistance in the parasite is growing. Hence, this study was performed to evaluate in vitro antitrichomonal activity of Satureja khuzestanica, carvacrol, thymol, eugenol, and phytochemical evaluation of the S. khuzestanica oil. METHODOLOGY: Extracts and essential oil of S. khuzestanica, and the components were prepared. Then, susceptibility testing was performed using the microtiter plate method and Trichomonas vaginalis isolates. The minimum lethal concentration (MLC) of the agents was determined in comparison with metronidazole. Also, the essential oil was investigated by gas chromatography-mass spectrometry and gas chromatography-flame ionization detector. RESULTS: After 48 hours of incubation, carvacrol and thymol were the most effective antitrichomonal agents with MLC of 100 µg/mL, followed by the essential oil and hexanic extract (MLC = 200 µg/mL), then eugenol and methanolic extract (MLC = 400 µg/mL), in comparison with the metronidazole MLC of 6.8 µg/mL. Overall, 33 identified compounds accounted for 98.72% of the total essential oil composition with carvacrol, thymol, and p-cymene being the major constituents. CONCLUSIONS: The results suggested the potency of S. khuzestanica and its bioactive ingredients against T. vaginalis. Thus, further in vivo studies are required to evaluate the efficacies of the agents.
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Óleos Voláteis , Satureja , Humanos , Timol/farmacologia , Timol/análise , Timol/química , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Antitricômonas , Satureja/química , Eugenol/farmacologia , Metronidazol , Extratos Vegetais/farmacologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Ferula gummosa Boiss., known in Persian as "Baridje," belongs to the Apiaceae family. All parts of this plant, especially the root, contain galbanum. Galbanum, the oleo-gum resin of F. gummosa, is one of the essential traditional herbal medicines in Iran, which is used as a tonic for epilepsy and chorea, memory enhancement, gastrointestinal diseases, and wound healing. AIM OF THE STUDY: We investigated the toxicity, anticonvulsant effects, and molecular modeling of the essential oil (EO) distilled from the oleo-gum resin of F. gummosa. MATERIALS AND METHODS: Gas chromatography-mass spectrometry was used to identify the EO components. The cytotoxicity of EO on HepG2 cell lines was assessed by the MTT method. Male mice were arranged as follows: negative control groups (sunflower oil (10 ml/kg, i.p.) or saline (10 ml/kg, p.o.)), EO groups (0.5, 1, 1.5, and 2.5 ml/kg, p.o.), and positive control groups (ethosuximide (150 mg/kg, p.o.) or diazepam (1.0 or 2 mg/kg, i.p.)). The motor coordination and neurotoxicity of EO were studied using the rota-rod test. Open-field, novel object recognition, and passive avoidance learning tests were used to investigate the effect of EO on locomotor activity and memory function. An acute pentylenetetrazole-induced seizure model was utilized to evaluate the anticonvulsant properties of the EO. The interaction of the EO main components with the GABAA receptor was investigated by coarse-grained molecular dynamics simulations. RESULTS: ß-pinene, sabinene, α-pinene, and ρ-cymene were the main components of EO. The IC50 of the EO at 24, 48, and 72 h was found to be 59.90, 12.96, and 3.93 µl/ml, respectively. No adverse effects were observed in memory, motor coordination, and locomotor activity in mice treated with EO. Administration of EO (1, 1.5, and 2.5 ml/kg) improved survival rates in mice receiving pentylenetetrazole (PTZ; to induce an epileptic seizure). Sabinene was able to bind to the binding site of benzodiazepines at the GABAA receptor. CONCLUSIONS: Acute treatment with the EO of F. gummosa caused antiepileptic effects and could effectively increase the survival rate in PTZ-treated mice with no significant toxicity.
Assuntos
Ferula , Óleos Voláteis , Camundongos , Animais , Óleos Voláteis/toxicidade , Anticonvulsivantes/uso terapêutico , Anticonvulsivantes/toxicidade , Ferula/química , Pentilenotetrazol/toxicidade , Receptores de GABA-ARESUMO
Objectives: In this study we aimed to evaluate the in vitro antibacterial activity and wound healing properties of Achillea millefolium essential oil (AMEO) in full-thickness wound model in rat. The antibacterial activity of AMEO was evaluated against Staphylococcus aureus and Pseudomonas aeruginosa using the broth dilution method. Methods: The 2 cm × 2 cm full-thickness excisional wounds were created on the back of animals. Topical therapy was applied twice a day using 1%, 2%, and 3% w/w AMEO ointments, and the measurement of the wounds area was carried out every 3 days, after that the wound closure percentage was calculated in these days. Hydroxyproline content and histopathological evaluation of wound tissue samples were carried out on day 7 and 14 post wounding. Eucerin was used for the treatment of vehicle control group and negative control group received no treatment. Results: Our results revealed the bacteriostatic activity of AMEO against S. aureus and P. aeruginosa. Wound healing activity evaluation of AMEO showed the significant increase (p < 0.05) in the wound closure percentages in rats treated with AMEO 1% and 2% comparing to those of non-treatment group. In addition, hydroxyproline contents of tissue significantly (p < 0.01) increased in AMEO 1% and 2% comparing to non-treatment group. Histopathological evaluations of wound tissue samples on day 7 and 14 demonstrated higher accumulation of collagen fibers, reduction of edema and inflammation and also formation of tissue appendages in 1% and 2% AMEO treated groups in comparison with non-treatment group. Conclusion: The results of this study indicated that AMEO has the potential to be used as a safe and effective wound healing agent.
RESUMO
Objectives: Dental caries is a prevalent chronic human infection worldwide and several plants have shown anticariogenic properties through antibacterial activity against oral pathogens. The present study aimed to assess anticariogenic activity of Verbascum speciosum, in search of novel agents for the prevention and treatment of dental caries. Methods: Hydro-alcoholic extracts from flowers and total aerial parts of the plant were prepared by maceration. Antibacterial activity of the extracts against Streptococcus mutans (ATCC 35668) and Streptococcus sobrinus (ATCC 27607) was investigated by agar diffusion and microdilution techniques. Inhibitory concentration-fifty values of the flowers' extract against Streptococcus mutans glucosyltransferase enzymes were determined. The total flavonoid content of the extracts was determined using an aluminum chloride reaction. Results: Verbascum speciosum flowers' extract showed significantly higher flavonoid content and antibacterial activity; with minimum inhibitory concentrations of 100 and 200 µg/mL for Streptococcus mutans and Streptococcus sobrinus, respectively. The extract inhibited the synthesis of glucan by cell-associated and extracellular glucosyltransferase enzymes in a dose-dependent manner with higher activity against the extracellular enzyme. Conclusion: This study indicated effective anticariogenic activity of Verbascum speciosum flowers extract. This extract can be considered as an alternative to current anticaries therapies or an additive to dental care products.
RESUMO
Background: Ionizing radiation (IR) is widely used in the treatment of cancer in radiotherapy. One of the main concerns of patients with gastrointestinal cancers undergoing radiotherapy is the harmful side effects of IR on normal tissues. The liver, kidney, and duodenum are usually exposed to high doses of radiation in the treatment of some cancers in abdominal region radiotherapy. We aimed to assess the radioprotective effects of Malva sylvestris L. against IR damages to the abdominal region. Materials and methods: This current study was conducted on 45 rats divided randomly into nine groups of five: A) negative control group, B) sham group, C) irradiation group, D) mallow treatment-1(200gr/kg), E) mallow treatment-2(400gr/kg), F) mallow treatment-3(600gr/kg), G) mallow treatment-4(200gr/kg) plus irradiation, H) mallow treatment-5(400gr/kg) plus irradiation, I) mallow treatment-6(600gr/kg) plus irradiation. Irradiation was performed with a 6Gy x-ray. Histopathological evaluations were performed 10 days after irradiation. Results: The histopathological examination results confirmed that preventive therapy with the effective dose of mallow reduced the liver, kidney, and intestine damage induced by radiation. The dose of 400 mg/kg was more effective than other selected dose in improving the damage caused by irradiation in the studied tissues. Conclusion: This study concludes that Malva sylvestris L. contributed to significant improvements in radiation-induced histological parameters of the liver and kidney and, to a lesser extent, in the intestine. These results collectively indicate that mallow is an effective radioprotective agent.