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Vitamin C is used in modern medicine supplements for treatment of various disorders associated with oxidative stress, inflammation and immune dysregulation. In this review article, experimental and clinical results regarding the effects of vitamin C on respiratory immunologic, and allergic diseases are reviewed. Various databases and appropriate keywords are used to search the effect of vitamin C on respiratory diseases until the end of May 2022. Books, theses and articles were included. These studies assessed the effects of vitamin C on respiratory disorders including asthma, chronic obstructive pulmonary disease (COPD), lung infection and lung cancer. Vitamin C showed relaxant effect on tracheal smooth muscle via various mechanisms. The preventive effects of vitamin C were mediated by antioxidant, immunomodulatory and anti-inflammatory mechanisms in the experimental animal models of different respiratory diseases. Some clinical studies also indicated the effect of vitamin C on lung cancer and lung infections. Therefore, vitamin C could be used a preventive and/or relieving therapy in respiratory diseases.
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Asma , Neoplasias Pulmonares , Neumonía , Enfermedad Pulmonar Obstructiva Crónica , Enfermedades Respiratorias , Animales , Ácido Ascórbico/farmacología , Ácido Ascórbico/uso terapéutico , Asma/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , VitaminasRESUMEN
Zataria multiflora (Z. multiflora) is used in traditional and modern medicine for therapeutic objectives especially in respiratory disorders. Therefore, updated experimental and clinical studies on the effects of Z. multiflora on respiratory, allergic, and immunologic disorders are reviewed. Various electronic search engines including PubMed, Science Direct, Scopus, and Google Scholar were searched using appropriate keywords until the end of November 2021. Books, thesis-hard copies of some articles were also included. The effects of Z. multiflora on respiratory disorders including asthma, chronic obstructive pulmonary disease (COPD), lung infection, and lung cancer were shown. Extracts of Z. multiflora showed the relaxant effect with various mechanisms. The preventive effects of Z. multiflora were also demonstrated by mechanisms such as antioxidant, immunomodulatory, and antiinflammatory properties in the experimental animal models of different respiratory diseases. Carvacrol and thymol are probably responsible for the therapeutic effect of plant among 56 constituents of Z. multiflora. In addition, bronchodilatory and preventive effects of the plant and its constituents on asthma, COPD, lung disorders due to noxious agents and allergic and immunologic disorders were shown in the clinical studies. Therefore Z. multiflora and its constituents may be considered as a preventive and/or relieving therapy in various respiratory diseases.
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Hipersensibilidad , Lamiaceae , Animales , Antiinflamatorios/farmacología , Humanos , Fitoterapia , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéuticoRESUMEN
BACKGROUND: Natural products (NPs) have long been recognized for their potential to modulate the immune system, offering a natural and holistic approach to enhancing immune function. In recent years, the immunomodulation effects of various natural products have attained significant attention. PURPOSE: This article provides an overview of the role of natural products in immunomodulation, exploring their mechanisms of action, common types of NPs with immunomodulation properties, clinical applications, as well as considerations for their safety and efficacy. METHODS: Extensive research has been conducted to compile important discoveries on the immunomodulatory properties of NPs through thorough searches of multiple databases such as PubMed, Science Direct, and Scopus up until January 2024. RESULTS: By decreasing the levels of Th2 cytokines and pro-inflammatory cytokines, the results suggested that NPs have the ability to modulate the immune system. Therefore, NPs alleviate inflammation in various disorders such as asthma and cancer. Furthermore, the observed increase in CD4 cells and IFN-É£/IL4 levels, along with an increased IFN-c/IL4 ratio, indicates a stimulatory effect of NPs on Th1 activity in various inflammatory conditions. Therefore, NPs regulate the immune system by inhibiting T-cells and decreasing the growth of young B-cell lymphoma cells. CONCLUSION: Reviewing studies indicated that NPs have the potential to serve as immunomodulatory candidates for treating disorders characterized by immune dysregulation. However, additional experimental and clinical studies are necessary before these agents can be implemented in clinical settings.
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This paper provides a complete protocol for studying the effects of inhaled paraquat (PQ), a toxic herbicide that has negative effects systemically and on the lungs. The protocol aims to evaluate the effects of aerosolized PQ exposure on lung and systemic injury in an animal model, which will provide significant information for therapeutic interventions for PQ-induced pulmonary and systemic damage. The protocol involves the following key components: 1. Study groups: By including control, non-treated aerosolized PQ-exposed, and treated PQ-exposed animals with various agent groups in the experiment, lung and systemic injury in each group could be evaluated, and different measured parameters could be compared among groups. 2. PQ exposure: Animals in the PQ-exposed groups are subjected to PQ aerosol inhalation, simulating occupational or accidental exposure in farmers working with this herbicide. 3. Assessment measures: To determine the degree of lung and systemic injury and its physiological effects, several assessments, such as biochemical markers, histopathological analysis, and functional tests, are used. The protocol offers reliable and accurate results by using standardized methods and data collection. The effect of PQ exposure on lung and systemic injury could be evaluated by statistical analysis of the collected data, which also makes it easier to identify possible protective agents or interventions. This comprehensive evaluation protocol provides an essential basis for studying the mechanisms behind PQ-induced lung and systemic injury and assessing the effectiveness of preventative or therapeutic strategies in minimizing its adverse effects.
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One of the main causes of death on the globe is cancer. Peroxisome-proliferator-activated receptors (PPARs) are nuclear hormone receptors, including PPARα, PPARδ and PPARγ, which are important in regulating cancer cell proliferation, survival, apoptosis, and tumor growth. Activation of PPARs by endogenous or synthetic compounds regulates tumor progression in various tissues. Although each PPAR isotype suppresses or promotes tumor development depending on the specific tissues or ligands, the mechanism is still unclear. PPARs are receiving interest as possible therapeutic targets for a number of disorders. Numerous clinical studies are being conducted on PPARs as possible therapeutic targets for cancer. Therefore, this review will focus on the existing and future uses of PPARs agonists and antagonists in treating malignancies. PubMed, Science Direct, and Scopus databases were searched regarding the effect of PPARs on various types of cancers until the end of May 2023. The results of the review articles showed the therapeutic influence of PPARs on a wide range of cancer on in vitro, in vivo and clinical studies. However, further experimental and clinical studies are needed to be conducted on the influence of PPARs on various cancers.
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The link between occupational respiratory diseases (ORD) and exposure to harmful factors that are present in the workplace has been well shown. Factors such as physical activity, age and duration of occupational exposure playing important roles in ORD severity, should be identified in the workplace, their effects on workers health should be studied, and ultimately, exposure to them must be minimized. We carried out a literature review by searching PubMed, Scopus, and Web of Science databases to retrieve studies published from 1999 until the end of April 2023 reporting the prevalence and inducers of ORD in Iran. In Iranian workers, several ORD such as interstitial lung disease, silicosis, occupational asthma, pulmonary inflammatory diseases, chronic obstructive pulmonary diseases, and lung cancers have been reported. It was indicated that ORD mainly occur due to repeated and prolonged exposure to noxious agents in the workplace. We also extracted the prevalence of ORD in different regions of Iran from the retrieved reports. Based on our literature review, the prevalence of ORD among Iranian workers highlights the importance of regular assessment of the risk of exposure to noxious agents in the workplace to develop measures for preventing potential adverse effects.
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The current study investigated how carvacrol (C) can prevent behavioral and brain oxidative changes, along with systemic inflammation caused by inhaled paraquat (PQ). Control rats exposed to saline solution, whereas six rat groups were subjected to PQ aerosols at a concentration of 54â¯mg/m3 in 16 days. The PQ-exposed groups received saline (PQ group), C at dosages of 20 (C-L) and 80â¯mg/kg/day (C-H), dexamethasone at a dosage of 0.03â¯mg/kg/day, pioglitazone at dose of 5 and 10â¯mg/kg/day (Pio-L and Pio-H), and a combination of C-L + Pio-L. Various parameters were assessed following the end of the treatment duration. There were marked elevation in total and differential white blood cell counts (WBCs), and malondialdehyde levels in the blood, hippocampus, and cerebral tissue but, thiol, superoxide dismutase (SOD), and catalase (CAT) exhibited a notable decrease (p < 0.05 to p < 0.001). The escape delay and traveled distance exhibited enhancement, however, on the probe day, the duration spent in the target quadrant and the time taken to enter the dark room at 3, 24, 48, and 72â¯hours post an electrical shock, showed a reduction in the PQ group (P<0.05 to P<0.001). Inhaled PQ-induced changes were significantly improved in C, Pio, Dexa, and C-L + Pio-L treated groups (P<0.05 to P<0.001). The effects of C-L + Pio-L on most measured variables were higher than C-L and Pio-L (P<0.05 to P<0.001). C improved PQ-induced changes similar to dexamethasone and C-L showed additive effects when administered in combination with Pio.
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The present study aimed to investigate the effect of Crocus sativus (Cs) on paraquat (PQ)-induced learning and memory deficits as well as brain and lung oxidative stress and systemic inflammation, and oxidative stress in rats. Rats were exposed to saline (Ctrl) or PQ (PQ groups) aerosols. PQ groups were treated with 0.03 mg/kg/day dexamethasone (Dexa), 20 and 80 mg/kg/day Cs-L and Cs-H, 5 mg/kg/day pioglitazone (Pio), and Cs-L+Pio for 16 days during PQ exposure period. Learning and memory abilities were assessed by Morris water maze (MWM) and passive avoidance tests. PQ group showed increased numbers of total and differential WBCs in blood, and increased malondialdehyde (MDA), in the serum, brain, and lung but reduced thiol, catalase (CAT), and superoxide dismutase (SOD) levels compared to the control group (for all, p < 0.001). The escape latency and traveled distance were increased in the PQ group. However, the time spent in the target quadrant in the MWM test and the latency to enter the dark room were reduced after receiving an electrical shock (p < 0.05 to P<0.001). In all treated groups, measured values were improved compared to PQ group (p < 0.05 to p < 0.001). The combination of Cs-L+Pio showed more pronounced effects compared to either treatment alone (p < 0.05 to p < 0.001). These findings suggest that Cs has neuroprotective properties and may be beneficial in the treatment of neurodegenerative diseases induced by noxious agents such as PQ.
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The effects of safranal and pioglitazone alone and their combination on inhaled paraquat (PQ)-induced systemic oxidative stress and inflammation as well as behavioral changes were examined in rats. In this study, animals were exposed to saline (Ctrl) or PQ (PQ groups) aerosols. PQ exposed animals were treated with dexamethasone, 0.8 and 3.2 mg/kg/day safranal (Saf-L and Saf-H), 5 mg/kg/day pioglitazone (Pio), and Saf-L + Pio for 16 days during PQ exposure period. PQ group showed increased numbers of total and differential WBCs in blood and bronchoalveolar lavage fluid (BALF), increased malondialdehyde (MDA), in the serum BALF and brain reduced thiol, catalase (CAT), and superoxide dismutase (SOD) levels compared to the control group (for all, p < 0.001). The escape latency and traveled distance were enhanced, but the time spent in the target quadrant in the probe day and the latency to enter the dark room 3, 24, 48, and 72 h after receiving an electrical shock, (in the shuttle box test) were decreased in the PQ group (p < 0.05 to P < 0.001). In all treated groups, all measure values were improved compared to PQ group (p < 0.05 to p < 0.001). In combination treated group of Saf-L + Pio, most measured values were more improved than the Saf-L and Pio groups (p < 0.05 to p < 0.001). Saf and Pio improved PQ-induced changes similar to dexamethasone but the effects produced by combination treatments of Saf-L + Pio were more prominent than Pio and Saf-L alone, suggesting a potentiating effect for the combination of the two agents.
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Lesión Pulmonar Aguda , Ciclohexenos , Paraquat , Edema Pulmonar , Terpenos , Ratas , Animales , Paraquat/toxicidad , Pulmón , Pioglitazona/farmacología , Estrés Oxidativo , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Dexametasona/farmacología , Dexametasona/uso terapéuticoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The herbicide paraquat (PQ) is highly toxic, capable of inducing severe lung inflammation and oxidative stress, resulting in lung fibrosis and respiratory failure. Previous research has demonstrated a range of pharmacological effects associated with Crocus sativus. L (Cs) through its anti-inflammatory, antioxidant and immunomodulatory properties. Pharmacological studies support the widespread use of Cs in traditional medicine to treat respiratory disorders such as coughs and asthma. AIM OF STUDY: This study aimed to investigate the preventive impact of Cs extract and pioglitazone (Pio) on lung inflammation, oxidative stress, pathological alterations, and tracheal reactivity induced by inhaled PQ in rats as compared to dexamethasone (Dexa). METHODS: The control (Ctrl) group of rats was administered with saline aerosol, while the remaining six groups received PQ aerosol eight times every other day. The six PQ exposure groups were treated daily during the exposure period to PQ with either; saline alone, low dose Cs, High dose Cs, Pio alone, Pio combined with low dose Cs, or Dexa of 16 days. RESULTS: In the PQ group, the levels of superoxide dismutase (SOD), catalase (CAT), and thiol in the bronchoalveolar lavage fluid (BALF) were declined whereas, the levels of MDA, total and differential WBC, and lung tissue levels of tumor necrosis factor (TNF-α) and Interleukin 10 (IL-10), tracheal responsiveness (TR) to methacholine and lung pathological changes were enhanced. The measured variables showed significant improvement in all treated groups, except for a few variables in Cs (L). The combined Cs (L) + Pio showed higher effects than Cs (L) and Pio alone. For all comparisons, p values were <0.05 to <0.001. CONCLUSIONS: The results showed preventive effect of Cs comparable to that of Dexa and the potential additive preventive capabilities of the Cs and Pio indicate that the involvement of the PPARγ receptor is implicated in the effects induced by Cs.
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Various nanoparticles are used in the discovery of new nanomedicine to overcome the shortages of conventional drugs. Therefore, this article presents a comprehensive and up-to-date review of the effects of nanoparticle-based drugs in the treatment of respiratory disorders, including both basic and clinical studies. Databases, including PubMed, Web of Knowledge, and Scopus, were searched until the end of August 2022 regarding the effect of nanoparticles on respiratory diseases. As a new tool, nanomedicine offered promising applications for the treatment of pulmonary diseases. The basic composition and intrinsic characteristics of nanomaterials showed their effectiveness in treating pulmonary diseases. The efficiency of different nanomedicines has been demonstrated in experimental animal models of asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis (PF), lung cancer, lung infection, and other lung disorders, confirming their function in the improvement of respiratory disorders. Various types of nanomaterials, such as carbon nanotubes, dendrimers, polymeric nanomaterials, liposomes, quantum dots, and metal and metal oxide nanoparticles, have demonstrated therapeutic effects on respiratory disorders, which may lead to new possible remedies for various respiratory illnesses that could increase drug efficacy and decrease side effects.
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BACKGROUND: Acute lung injury (ALI) remains a significant source of morbidity and mortality in critically ill patients and currently there is no efficient therapy for this condition. The aim of this research was to evaluate the protective activity of nano-curcumin (nano-CU) as a natural anti-inflammatory and antioxidant agent, against inhaled paraquat (PQ)-induced lung injury. METHODS: One group of rats was exposed to saline (control group, Ctrl) and six groups to PQ aerosol (54 mg/m3 on alternate days 8 times, each time for 30 min) treated with drinking water alone (group PQ), 2 and 8 mg/kg nano-CU (nano + CU(L) and nano + CU(H)), 5 mg/kg pioglitazone (PIO), nano-CU(L) + PIO or 0.03 mg/kg dexamethasone (Dexa) for 16 days after PQ exposure period. PIO and Dexa were intraperitoneal (ip) injected and nano-CU was administered orally (po), (6 rats in each group). RESULTS: In the PQ group, total and differential WBC counts, malondialdehyde (MDA) in the bronchoalveolar lavage fluid (BALF), interferon gamma (INF-γ) and interleukin 10 (IL-10) levels in the lung tissues, lung pathological changes, and tracheal responsiveness were increased but the BALF thiol, catalase (CAT) and superoxide dismutase (SOD) levels were reduced. In treated groups with nano-CU(H) and PIO + nano-CU(L), all measured variables, in Dexa and nano-CU(L) treated groups, most variables and in the PIO group only a few variables were improved. The improvement of most variables in the PIO + nano-CU(L) group was significantly higher than in the PIO and nano-CU(L) groups alone. CONCLUSIONS: Nano-CU ameliorated lung damage induced by inhaled PQ similar to dexa and a synergic effect between nano-CU and PIO was observed, suggesting, a possible PPAR-γ receptor-mediated effect of curcumin.
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Lesión Pulmonar Aguda , Curcumina , Ratas , Animales , Paraquat/toxicidad , Curcumina/farmacología , Pulmón , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/patologíaRESUMEN
The effect of Curcuma longa (Cl) ethanolic extract, nano-curcumin (Cu) and a PPARγ activator, pioglitazone on inhaled paraquat (PQ)-induced systemic inflammation and oxidative stress was examined in the present study. Control rats were exposed to normal saline and PQ groups to 27 and 54 mg/m3 (PQ-L and PQ-H) aerosols. Nine other PQ-H groups were treated with Curcuma longa (Cl, 150 and 600 mg/kg/day), nano-curcumin (Cu, 2 and 8 mg/kg/day), pioglitazone (Pio, 5 and 10 mg/kg), low dose of Pio + Cl and Cu and dexamethasone (0.03 mg/kg/day) for 16 days after PQ exposure period (n = 8). Total and differential WBC counts, malondialdehyde (MDA) and TNF-α levels were increased but thiol, catalase (CAT), superoxide dismutase (SOD), IL-10 and IFN-γ levels were decreased in the blood in the both PQ groups (p < 0.05 to p < 0.001). Treatment with Dexa and both doses of Cl, Cu, and Pio improved all measured variables compared to the PQ-H group (p < 0.05 to p < 0.001). The improvements of most variables in the treated group with low dose of Pio + Cl and Cu were higher than the effects of three agents alone. Systemic inflammation and oxidative stress induced by inhaled PQ were improved by Cl, Cu and Pio. In addition, a synergic effect between Pio with those of Cl and Cu was shown, suggesting PPARγ mediated effects of the plant and its derivative Cu.
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Curcumina , Paraquat , Ratas , Animales , Paraquat/toxicidad , Paraquat/uso terapéutico , Curcumina/farmacología , Pioglitazona/farmacología , Pioglitazona/uso terapéutico , PPAR gamma/metabolismo , PPAR gamma/farmacología , PPAR gamma/uso terapéutico , Curcuma , Estrés Oxidativo , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Hipoglucemiantes/farmacologíaRESUMEN
OBJECTIVE: This study intended to perform a synthesizing procedure for amorphous calcium phosphate (ACP) through a green template by the usage of brown rice (BR). MATERIALS AND METHODS: ACP nanoparticles were obtained by application of a sol-gel method and comprehensively characterized using X-ray powder diffraction (XRD), zeta potential, fourier-transform infrared spectroscopy (FTIR), field emission scanning electron microscope (FESEM), and atomic force microscopy (AFM). Cytotoxic activity of ACP was evaluated in human epithelial type 2 (HEp-2) cell lines. The antibacterial effects of nanoparticles were appraised against Gram-positive Streptococcus mutans and Enterococcus faecalis. RESULTS: The procedures for the evaluation of the characterization outcomes, dispersion, and stability of our product were confirmed by observing the smooth and uniformed surfaces of ACP. The zeta potential value of the synthesized sample was -22 mV, which indicates its acceptable stable condition caused by electrostatic repulsion. The cytotoxicity of the ACP nanoparticles was investigated in HEp-2 cells, and results showed no cytotoxicity for the synthesized nanoparticles. Also, the obtained minimum inhibitory concentration (MIC) of ACP nanoparticles in opposition to S. mutans and E. faecalis was 15 and 20 µg/ml, respectively, indicating the resistance of E. faecalis in comparison to S. mutans and MBC for synthesized nanoparticles against S. mutans and E. faecalis strains was 20 and 25 µg/ml. CONCLUSION: The present study showed that this compound has no toxicity on the examined cell line. Also, the antibacterial properties of the synthesized ACP were approved by the obtained data, which enables the application of this material for therapeutic purposes in the pharmaceutical industry.
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The harmful effects of various noxious agents (NA) are well-known and there are reports regarding the induction of various lung disorders due to exposure to these agents both in animal and human studies. In addition, various studies have shown the effects of natural products (NP) on NA-induced lung disorders. The effects of various NP, including medicinal plants and their derivatives, on lung injury induced by NA, were reviewed in this study. The improving effects of various NP including medicinal plants, such as Aloe vera, Anemarrhena asphodeloides, Avena sativa, Crocus sativus, Curcuma longa, Dioscorea batatas, Glycyrrhiza glabra, Gentiana veitchiorum, Gentiopicroside, Houttuynia cordata, Hibiscus sabdariffa, Hochu-ekki-to, Hippophae rhamnoides, Juglans regia, Melanocarpa fruit juice, Mikania glomerata, Mikania laevigata, Moringa oleifera, Myrtus communis L., Lamiaceae, Myrtle, Mosla scabra leaves, Nectandra leucantha, Nigella sativa, Origanum vulgare L, Pulicaria petiolaris, Paulownia tomentosa, Pomegranate seed oil, Raphanus sativus L. var niger, Rosa canina, Schizonepeta tenuifolia, Thymus vulgaris, Taraxacum mongolicum, Tribulus Terrestris, Telfairia occidentalis, Taraxacum officinale, TADIOS, Xuebijing, Viola yedoensis, Zataria multiflora, Zingiber officinale, Yin-Chiao-San, and their derivatives, on lung injury induced by NA were shown by their effects on lung inflammatory cells and mediators, oxidative stress markers, immune responses, and pathological changes in the experimental studies. Some clinical studies also showed the therapeutic effects of NP on respiratory symptoms, pulmonary function tests (PFT), and inflammatory markers. Therefore, the results of this study showed the possible therapeutic effects of various NP on NA-induced lung disorders by the amelioration of various features of lung injury. However, further clinical studies are needed to support the therapeutic effects of NP on NA-induced lung disorders for clinical practice purposes.
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The health benefits of Allium cepa (A. cepa) have been proclaimed for centuries. Various pharmacological and therapeutic effects on respiratory, allergic, and immunologic disorders are shown by A. cepa and its constituents. Flavonoids such as quercetin and kaempferol, alk(en)yl cysteine sulfoxides including S-methyl cysteine sulfoxide and S-propyl cysteine sulfoxide, cycloalliin, thiosulfinates, and sulfides are the main compounds of the plant. A. cepa displays broad-spectrum pharmacological activities including antioxidant, anti-inflammatory, antihypertensive, and antidiabetic effects. Our objective in this review is to present the effects of A. cepa and its constituents on respiratory, allergic, and immunologic disorders. Different online databases were searched to find articles related to the effect of A. cepa extracts and its constituents on respiratory, allergic, and immunologic disorders until the end of December 2020 using keywords such as onion, A. cepa, constituents of A. cepa, therapeutic effects and pharmacological effects, and respiratory, allergic, and immunologic disorders. Extracts and constituents of A. cepa showed tracheal smooth muscle relaxant effects, indicating possible bronchodilator activities or relieving effects on obstructive respiratory diseases. In experimental animal models of different respiratory diseases, the preventive effect of various extracts and constituents of A. cepa was induced by their antioxidant, immunomodulatory, and anti-inflammatory effects. The preventive effects of the plant and its components on lung disorders induced by exposure to noxious agents as well as lung cancer, lung infection, and allergic and immunologic disorders were also indicated in the experimental and clinical studies. Therefore, this review may be considered a scientific basis for development of therapies using this plant, to improve respiratory, allergic, and immunologic disorders.
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The binding of small molecules with histone-DNA complexes can cause an interference in vital cellular processes such as cell division and the growth of cancerous cells that results in apoptosis. It is significant to study the interaction of small molecules with histone-DNA complex for the purpose of better understanding their mechanism of action, as well as designing novel and more effective drug compounds. The fluorescence quenching of ct-DNA upon interaction with Berberine has determined the binding of Berberine to ct-DNA with Ksv = 9.46 × 107 M-1. Ksv value of ct-DNA-Berberine in the presence of H1 has been observed to be 3.10 × 107 M-1, indicating that the H1 has caused a reduction in the binding affinity of Berberine to ct-DNA. In the competitive emission spectrum, ethidium bromide (EB) and acridine orange (AO) have been examined as intercalators through the addition of Berberine to ct-DNA complexes, which includes ctDNA-EB and ctDNA-AO. Although in the presence of histone H1 , we have observed signs of competition through the induced changes within the emission spectra, yet there has been apparently no competition between the ligands and probes. The viscosity results have confirmed the different behaviors of interaction between ctDNA and Berberine throughout the binary and ternary systems. We have figured out the IC50 and viability percent values at three different time durations of interaction between Berberine and MCF7 cell line. The molecular experiments have been completed by achieving the results of MTT assay, which have been confirmed to be in good agreement with molecular modeling studies.Communicated by Ramaswamy H. Sarma.
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Berberina/metabolismo , Fenómenos Biofísicos , ADN/metabolismo , Histonas/metabolismo , Animales , Berberina/química , Berberina/farmacología , Unión Competitiva , Bovinos , Muerte Celular/efectos de los fármacos , ADN/química , Etidio/química , Histonas/química , Humanos , Concentración 50 Inhibidora , Cinética , Células MCF-7 , Simulación del Acoplamiento Molecular , Concentración Osmolar , Yoduro de Potasio/farmacología , Estructura Secundaria de Proteína , Dispersión de Radiación , Cloruro de Sodio/farmacología , Espectrometría de Fluorescencia , Termodinámica , ViscosidadRESUMEN
DNA is the primary target of many anticancer drugs involved in important intercellular processes, especially in transcriptional regulation, and histone is known to inhibit gene expression. Small molecules can bind to histone-DNA and impair the cell division, growth, inhibition, and apoptosis in cancer cells. In this research, the interaction of a histone H1-calf thymus DNA (ct DNA) complex and propyl acridone (PA) was investigated in Tris-HCl buffer, pH 6.8, using multi-spectroscopic, viscosity, and molecular modeling techniques. The Stern Volmer plot of the (H1-ct DNA) PA complex demonstrated two sets of binding sites with various binding affinities at three different temperatures. Thermodynamic parameters (ΔH° < 0 and ΔS° < 0) indicated that hydrogen bonds and van der Waals forces played the main roles in the binding of the drug to H1-ct DNA. The interaction between PA and ct DNA as well as (H1-ct-DNA) in the presence of acridine orange and ethidium bromide showed two different interaction behaviors in ternary systems. According to results from UV absorption spectroscopy and melting temperature (Tm) measurements, the binding mode of PA with ct DNA and the (H1-ct DNA) complex was indicative of an intercalative binding for the binary system and of both intercalative with groove binding with molecular fraction for the ternary system. Furthermore, the PA-induced detectable changes in the circular dichroism spectrum of ct DNA as well as changes in its viscosity. All of the experimental results proved that the intercalative binding between PA and ct DNA as well as the (H1-ct DNA) complex as binary and ternary systems must be predominant. The results obtained from experimental data were in good agreement with molecular modeling with regard to the determination of the binding site of PA to ct DNA in the absence and presence of histone H1.
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Acridonas/química , ADN/química , Histonas/química , Modelos Moleculares , Análisis Espectral , Conformación Molecular , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Estructura Molecular , Unión Proteica , Relación Estructura-Actividad , ViscosidadRESUMEN
This article describes, for the first time, the effect of three different sizes of silver nanoparticles on the binding of curcumin to lysozyme as examined by spectroscopic and zeta potential techniques at physiological conditions. The binding constants of curcumin to lysozyme in the presence of silver nanoparticles were measured. Based on the results of synchronous fluorescence and three-dimensional fluorescence spectroscopy, the presence of the different sizes of silver nanoparticles caused conformational changes in lysozyme during the binding of curcumin. Such changes were also observed when increasing the curcumin concentration. The results of fluorescence resonance energy transfer theory indicated that different sizes of silver nanoparticles could change the binding distance between curcumin and lysozyme. Based on the red edge excitation shift approach, we concluded that the limited mobility around the Trp residues decreased in the presence of silver nanoparticles with bigger size. Under resonance light scattering, the aggregation of curcumin on lysozyme in the presence of silver nanoparticles can play a major role in functional proteins. Communicated by Ramaswamy H. Sarma.
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Curcumina/metabolismo , Nanopartículas del Metal/química , Muramidasa/metabolismo , Tamaño de la Partícula , Plata/química , Electricidad Estática , Dicroismo Circular , Transferencia Resonante de Energía de Fluorescencia , Conformación Molecular , Dispersión de Radiación , Espectrometría de FluorescenciaRESUMEN
The present study was designed to investigate the influence of two indispensable and two dispensable amino acids, including methionine, histidine, cysteine and proline, on the binding interaction between human serum albumin (HSA) and an antibiotic agent lomefloxacin (LMF). The fluorescence quenching experiments showed that the intrinsic emission of HSA was considerably quenched following binding to LMF in all the systems. Furthermore, in all the interactions the maximum wavelength of HSA was slightly decreased. The spectral changes observed in the binding systems we e all attributed to the alteration of the micro-environment around the tryptophan and tyrosine residues of HSA. The Kb values o HSA-LMF complex in the absence and presence of histidine, methionine, cysteine and proline have been obtained 6.02 × 105, 4.83 × 105, 5.05 × 105, 4.94 × 105 and 6.20 × 105 M-1 respectively. The various kind of Kb values showed the different interaction behavior between HSA and LMF in the absence and presence of amino acids mentioned. The data gathered by isothermal titration calorimetry (ITC) studies revealed that although all the binding interactions were exothermic, the amount of the heat exchanged during the HSA-LMF interaction increased in the presence of the amino acids especially cysteine. In the present study, the binding kinetics and affinity of LMF to HSA in the absence and presence of the amino acids were studies using stopped-flow circular dichroism and ITC techniques respectively. The results of these two techniques revealed that the bindig affinity and binding rate of the LMF-HSA interaction decreased in the presence of histidine, methionine and cysteine. In the presence of proline, the binding process of LMF-HSA was sped up and the affinity of LMF to HSA slightly increased. All the experimental results were then supported by the data collected from molecular modeling studies using density functional theory. Communicated by Ramaswamy H. Sarma.