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Toxicological studies are important to investigate the genotoxic effects of various substances. Allium cepa can be used as test model for this purpose. This review summarizes the scope and applications for this A. cepa test model. For this, an up-to-date (April 2023) literature search was made in the Science Direct, PubMed, and Web of Science databases to find published evidence on studies performed using A. cepa as a test model. Out of 3,748 studies, 74 fit the inclusion criteria. The results showed that the use of the test model A. cepa contributed considerably to measuring the toxicological potential of plant extracts, proving the efficacy of the test as a potent bioindicator of toxic effects. In addition, 27 studies used more than one test system to verify the toxicological potential of extracts and fractions. Studies have shown that the A. cepa model has the potential to replace other test systems that make use of animals and cell cultures, besides having other advantages such as low cost, ease of execution, and good conditions for the observation of chromosomes. In conclusion, the A. cepa test can be considered one of the potential biomonitoring systems in toxicological studies of crude extracts.
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Bulleyaconitine A (BLA) is a promising candidate for treating rheumatoid arthritis (RA) with diverse pharmacological activities, including anti-inflammatory, analgesic and bone repair. Herein, the long-acting bulleyaconitine A microspheres (BLA-MS) were developed to treat RA comprehensively by forming drug reservoirs in joint cavities. The BLA-MS were prepared by emulsion/solvent evaporation method. The particle size and distribution were assessed by SEM. The crystalline state was investigated by DSC and PXRD. The drug loading (DL), encapsulation efficiency (EE) and cumulative release in vitro were determined by HPLC. The DL and EE were 23.93 ± 0.38 % and 95.73 ± 1.56 % respectively, and the cumulative release was up to 69 days with a stable release curve. The pharmacodynamic results in collagen induced arthritis (CIA) rats showed a noticeable reduction in paw thickness (5.66 ± 0.32 mm), and the decreasing expression level of PGE2, TNF-α and IL-6 which diminished the infiltration of inflammatory cells, thereby alleviating the progression of erosion and repairing the damaged bones (BV/TV (Bone Volume / Total Volume): 81.97 %, BS/BV (Bone Surface / Bone Volume): 6.08 mm-1). In conclusion, intra-articular injection of BLA-MS should have a promising application in the treatment of RA and may achieve clinical transformation in the future.
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Aconitina , Artrite Experimental , Artrite Reumatoide , Liberação Controlada de Fármacos , Microesferas , Animais , Aconitina/análogos & derivados , Aconitina/administração & dosagem , Aconitina/química , Aconitina/farmacocinética , Injeções Intra-Articulares , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Masculino , Ratos , Tamanho da Partícula , Preparações de Ação Retardada , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antirreumáticos/administração & dosagem , Antirreumáticos/farmacocinética , Antirreumáticos/químicaRESUMO
Marine natural products offer immense potential for drug development, but the limited supply of marine organisms poses a significant challenge. Establishing aquaculture presents a sustainable solution for this challenge by facilitating the mass production of active ingredients while reducing our reliance on wild populations and harm to local environments. To fully utilize aquaculture as a source of biologically active products, a cell-free system was established to target molecular components with protein-modulating activity, including topoisomerase II, HDAC, and tubulin polymerization, using extracts from aquaculture corals. Subsequent in vitro studies were performed, including MTT assays, flow cytometry, confocal microscopy, and Western blotting, along with in vivo xenograft models, to verify the efficacy of the active extracts and further elucidate their cytotoxic mechanisms. Regulatory proteins were clarified using NGS and gene modification techniques. Molecular docking and SwissADME assays were performed to evaluate the drug-likeness and pharmacokinetic and medicinal chemistry-related properties of the small molecules. The extract from Lobophytum crassum (LCE) demonstrated potent broad-spectrum activity, exhibiting significant inhibition of tubulin polymerization, and showed low IC50 values against prostate cancer cells. Flow cytometry and Western blotting assays revealed that LCE induced apoptosis, as evidenced by the increased expression of apoptotic protein-cleaved caspase-3 and the populations of early and late apoptotic cells. In the xenograft tumor experiments, LCE significantly suppressed tumor growth and reduced the tumor volume (PC3: 43.9%; Du145: 49.2%) and weight (PC3: 48.8%; Du145: 7.8%). Additionally, LCE inhibited prostate cancer cell migration, and invasion upregulated the epithelial marker E-cadherin and suppressed EMT-related proteins. Furthermore, LCE effectively attenuated TGF-ß-induced EMT in PC3 and Du145 cells. Bioactivity-guided fractionation and SwissADME validation confirmed that LCE's main component, 13-acetoxysarcocrassolide (13-AC), holds greater potential for the development of anticancer drugs.
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Antozoários , Antineoplásicos , Apoptose , Aquicultura , Produtos Biológicos , Animais , Antozoários/química , Antineoplásicos/farmacologia , Humanos , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Camundongos , Desenvolvimento de Medicamentos , Ensaios Antitumorais Modelo de Xenoenxerto , Simulação de Acoplamento Molecular , Masculino , Tubulina (Proteína)/metabolismo , Camundongos NusRESUMO
The development of natural substances derived from nature poses a significant challenge as technologies for the extraction and characterization of active principles advance. Hispolon has received a lot of attention in recent years, ascribable to its wide range of biological activities. It is a phenolic molecule that was extracted from several mushroom species such as Phellinus igniarius, Phellinus linteus, Phellinus lonicerinus, Phellinus merrillii, and Inonotus hispidus. To provide a comprehensive overview of the pharmacological activities of hispolon, this review highlights its anticancer, anti-inflammatory, antioxidant, antibacterial, and anti-diabetic activities. Several scientific research databases, including Google Scholar, Web of Science, PubMed, SciFinder, SpringerLink, Science Direct, Scopus, and, Wiley Online were used to gather the data on hispolon until May 2024. The in vitro and in vivo studies have revealed that hispolon exhibited significant anticancer properties through modifying several signaling pathways including cell apoptosis, cycle arrest, autophagy, and inhibition of angiogenesis and metastasis. Hispolon's antimicrobial activity was proven against many bacterial, fungal, and viral pathogens, highlighting its potential use as a novel antimicrobial agent. Additionally, hispolon displayed potent anti-inflammatory activity through the suppression of key inflammatory mediators, such as inducible NO synthase (iNOS), tumor necrosis factor-α (TNF-α), and cyclooxygenases-2 (COX-2), and the modulation of mitogen-activated protein kinases (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways. The antioxidant potential of hispolon was attributed to its capacity to neutralize reactive oxygen species (ROS) and to increase the activity of antioxidant enzymes, indicating a possible involvement in the prevention of oxidative stress-related illnesses. Hispolon's antidiabetic activity was associated with the inhibition of aldose reductase and α-glucosidase. Studies on hispolon emphasized its potential use as a promising scaffold for the development of novel therapeutic agents targeting various diseases, including cancer, infectious diseases, inflammatory disorders, and diabetes.
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Anti-Inflamatórios , Antineoplásicos , Antioxidantes , Animais , Humanos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/farmacologia , Antioxidantes/isolamento & purificação , Antineoplásicos/farmacologia , Antineoplásicos/isolamento & purificação , Hipoglicemiantes/farmacologia , Hipoglicemiantes/isolamento & purificação , Imino Açúcares/farmacologia , Imino Açúcares/química , Transdução de Sinais/efeitos dos fármacos , CatecóisRESUMO
Thymol (THY), as the natural monoterpene phenol, acts against oxidative stress and inflammatory processes. This study aimed to evaluate the anti-inflammatory effects and possible molecular mechanisms of THY via formalin-induced mouse and egg albumin-induced chick models alongside molecular docking and molecular dynamic (MD) simulations. THY (7.5, 15, and 30 mg/kg) was investigated, compared to celecoxib and ketoprofen (42 mg/kg), as anti-inflammatory standards. THY dose-dependently and significantly (p < 0.05) decreased paw-licking and edema diameter parameters in formalin (phases I and II) and egg albumin-induced models. Moreover, THY (15 mg/kg) exerted better anti-inflammatory effects in combination with the standard drug ketoprofen than alone and with celecoxib. In silico studies demonstrated elevated binding affinities of THY with cyclooxygenase-2 (COX-2) than the COX-1 enzyme, and the ligand binds at a similar location where ketoprofen and celecoxib interact. The results of MD simulations confirmed the stability of the test ligand. THY exerted anti-inflammatory effects on Swiss mice and young chicks, possibly by interacting with COX-2. As a conclusion, THY might be a hopeful drug candidate for the management of inflammatory disorders.
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BACKGROUND: Sclareol (SCL), a labdane diterpene compound found in Salvia sclarea L., exhibited therapeutic effects. This study investigated the potential interaction between SCL and diazepam (DZP) in modulating sedation in the thiopental sodium-induced sleeping animal model, supported by in-silico molecular docking analysis. METHODS: The control, sclareol (5, 10 and 20â¯mg/kg), and the reference drugs [diazepam: 3â¯mg/kg and Caffeine (CAF): 10â¯mg/kg] were used in male albino mice. Then, sodium thiopental (40â¯mg/kg, i.p.) was administrated to induce sleep. The latent period, percentage of sleep incidence and modulation of latency were measured. Further, homology modeling of human γ-aminobutyric acid (GABA) was conducted examine the binding mode of GABA interaction with SCL, DZP, and CAF compounds RESULTS: SCL (low dose) slightly increased the sleep latency, while the higher dose significantly prolonged sleep latency. DZP, a GABAA receptor agonist, exhibited strong sleep-inducing properties, reducing sleep latency, and increasing sleeping time. Caffeine (CAF) administration prolonged sleep latency and reduced sleeping time, consistent with its stimulant effects. The combination treatments involving SCL, DZP, and CAF showed mixed effects on sleep parameters. The molecular docking revealed good binding affinities of SCL, DZP, and CAF for GABAA receptor subunits A2 and A5. CONCLUSIONS: Our findings highlighted the complex interplay between SCL, DZP, and CAF in regulating sleep behaviors and provided insights into potential combination therapies for sleep disorders.
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Diazepam , Hipnóticos e Sedativos , Simulação de Acoplamento Molecular , Sono , Tiopental , Animais , Masculino , Hipnóticos e Sedativos/farmacologia , Camundongos , Diazepam/farmacologia , Sono/efeitos dos fármacos , Tiopental/farmacologia , Diterpenos/farmacologia , Cafeína/farmacologia , Simulação por Computador , Receptores de GABA-A/metabolismo , Humanos , Relação Dose-Resposta a Droga , Latência do Sono/efeitos dos fármacosRESUMO
Caffeine and purine derivatives represent interesting chemical moieties, which show various biological activities. Caffeine is an alkaloid that belongs to the family of methylxanthine alkaloids and it is present in food, beverages, and drugs. Coffee, tea, and some other beverages are a major source of caffeine in the human diet. Caffeine can be extracted from tea or coffee using hot water with dichloromethane or chloroform and the leftover is known as decaffeinated coffee or tea. Caffeine and its derivatives were synthesized via different procedures on small and large scales. It competitively antagonizes the adenosine receptors (ARs), which are G protein-coupled receptors largely distributed in the human body, including the heart, vessels, brain, and kidneys. Recently, many reports showed the effect of caffeine derivatives in the treatment of many diseases such as Alzheimer's, asthma, parkinsonism, and cancer. Also, it is used as an antioxidant, anti-inflammatory, analgesic, and hypocholesterolemic agent. The present review article discusses the synthesis, reactivity, and biological and pharmacological properties of caffeine and its derivatives. The biosynthesis and biotransformation of caffeine in coffee and tea leaves and the human body were summarized in the review.
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Cafeína , Purinas , Animais , Humanos , Cafeína/química , Cafeína/metabolismo , Cafeína/farmacologia , Café/química , Café/metabolismo , Purinas/química , Purinas/biossíntese , Purinas/farmacologia , Purinas/metabolismoRESUMO
This work aimed to evaluate the effect of different extraction solvents on the polyphenolic content, antioxidant and antibacterial activity of Pistacia lentiscus stems. The results obtained show that the extraction yield depends strongly on the polarity of the solvent and the extraction method. The ethanolic extract had the highest yield in both extraction methods investigated, namely Soxhlet (R = 9.89%) and cold maceration (R = 9.20%). The free radical scavenging activity of the extracts showed that the ethanolic extract had the highest antioxidant activity in both extraction methods with an IC50 = 0.023 mg/mL (cold maceration) and an IC50 = 0.034 mg/ml (Soxhlet). The HPLC analysis of the extracts indicates that gallic acid and catechin are the major phenolic compounds. The FTIR results showed that the shift of the stretching is responsible for O-H and C-H bonding. The GC-MS analysis revealed the presence of stearic acid and palmitic acid methyl ester as main compounds. The bacterial analysis of the extracts showed that the aqueous extract represents the most active one against Staphylococcus aureus and Pseudomonas aeruginosa; on the other hand, no antifungal activity was appreciated. Overall, the results indicate that the investigated extracts might be considered valuable sources of bioactive compounds.
The study provides an overview of the yield, phenolic composition, and biological activities of Pistacia lentiscus stems. No information is available on research conducted to compare extraction techniques and solvent effects on the recovery of phenolic components, flavonoids, and antioxidant activity; only one paper has reported so far the phenolic characterization of Pistacia lentiscus stems. The data can be useful for future in vivo studies to support their antioxidant and antimicrobial properties. In addition, the sample preparation technique used in this study can provide a basis for the extraction of similar phenolic compounds in other parts of the plant.
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INTRODUCTION: This study focuses on the development of novel antimicrobial agents. A Schiff base ligand, 6-(2-(4-hydroxy-3-methoxybenzylideneamino)-2-(4-hydroxyphenyl)acetamido)-3,3-dimethyl-7-oxo- 4-thia-1-azabicyclo [3.2.0] heptane-2-carboxylic acid, synthesized through the condensation of amoxicillin and vanillin in methanol, served as the foundation. Polydentate mixed ligand complexes were then formed by reacting the Schiff base with metal ions (Fe(II), Co(II), Ni(II), Cu(II), and Zn(II)) and nicotinamide in specific ratios. METHODS: Characterization involved various techniques, such as 1H-NMR, FT-IR, UV-Vis, and elemental analysis for the ligand, and Atomic Absorption, FT-IR, UV-Vis, magnetic susceptibility, and conductance measurements for the Schiff base-metal ion complexes. RESULTS: Quantum chemical features of both ligands and metal complexes were computed, refining their electronic and molecular structures theoretically. Antimicrobial activity against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Salmonella typhi, Acinetobacter baumannii, and Pseudomonas aeruginosa was assessed for the starting materials, ligands, and synthesized complexes, revealing significant effects on certain species. In-silico binding modes with Escherichia coli (PDB ID: 5iq9) were determined through molecular docking. CONCLUSION: This study underscores the potential applications of the Schiff base ligands and their metal complexes in developing new antimicrobial agents.
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Purpose: To determine predictors for missing trifecta in patients who underwent flexible ureteroscopy (FURS) for treatment of renal and upper ureteric calculi. Patients and Methods: The data of adult patients with renal or upper ureteral stones who underwent FURS from June 2021 through December 2022 were retrospectively reviewed. Stone-free status (no residual stones > 3 mm) was evaluated after 3 months with non-contrast CT. Modified Clavien classification was used to grade complications. A stone-free status after a single intervention of FURS without complications was defined as trifecta. Patients were divided into two groups (trifecta and non-trifecta). Risk factors for missing trifecta were compared between both groups using univariate and multivariate analyses. Results: Three hundred twenty-three patients with mean age 48.9 ± 13 years and mean stone length 16 ± 5.9 mm were included. The trifecta criteria were applicable for 250 patients (71%). On multivariate analysis, risk factors for missing trifecta were stone multiplicity (OR: 3.326, 95%CI: 1.933-5.725) and non-experienced surgeons (OR: 1.819, 95%CI: 1.027-3.220). Conclusions: Multiple stones and performance of FURS by non-experienced surgeons are the independent risk factors for missing trifecta of FURS.
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Objective: Disintegrating cystine and calcium oxalate monohydrate stones present a formidable challenge owing to their hardness and distinct composition. This study aimed to establish optimal laser settings for these hard stones lithotripsy. Patients and Methods: Cystine and calcium oxalate monohydrate stones were extracted from two patients. Two experiments were conducted in vitro by utilizing a 272 µm laser fiber with variable settings to disintegrate the cystine and calcium oxalate monohydrate stones. In the first experiment, energy was adjustable while frequency was constant, whereas the second experiment involved constant energy with adjustable frequency on each type of stone and each experiment was repeated three times to ensure robustness and reliability. Results: Our findings indicated that for cystine stones, use of higher total power with high energy and low frequency proved to be effective. Conversely, for calcium oxalate monohydrate stones, settings involving higher total power with low energy and high frequency demonstrated superior efficacy and safety. Conclusion: Holmium (Ho: YAG) laser settings with higher total power, high energy, and low frequency effectively disintegrate cystine stones despite increased heat, which was measured by a thermometer with a thermocouple. For calcium oxalate monohydrate stones, higher total power, high frequency, and low energy settings are recommended and safe.
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Recently, nanotechnology has emerged as an extensively growing field. Several important fabricated products including Carbon nanotubes (CNTs) are of great importance and hold significance in several industrial sectors, mainly food industry. Recent developments have come up with methodologies for the prevention of health complications like lack of adequate nutrition in our diet. This review delves deeper into the details of the food supplementation techniques and how CNTs function in this regard. This review includes the challenges in using CNTs for food applications and their future prospects in the industry. Food shortage has become a global issue and limiting food resources put an additional burden on the farmers for growing crops. Apart from quantity, quality should also be taken into consideration and new ways should be developed for increasing nutritional value of food items. Food supplementation has several complications due to the biologically active compounds and reaction in the in vivo environment, CNTs can play a crucial role in countering this problem through the supplementation of food by various processes including; nanoencapsulation and nanobiofortification thus stimulating crop growth and seed germination rates. CNTs also hold a key position in biosensing and diagnostic application for either the quality control of the food supplements or the detection of contagions like toxins, chemicals, dyes, pesticides, pathogens, additives, and preservatives. Detection such pathogens can help in attaining global food security goal and better production and provision of food resources. The data used in the current review was collected up to date as of March 31, 2024 and contains the best of our knowledge. Data collection was performed from various reliable and authentic literatures comprising PubMed database, Springer Link, Scopus, Wiley Online, Web of Science, ScienceDirect, and Google Scholar. Research related to commercially available CNTs has been added for the readers seeking additional information on the use of CNTs in various economic sectors.
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Introduction: D-pinitol, a naturally occurring inositol, has diverse biological activities like antioxidant, antimicrobial and anticancer activities. This study aimed to evaluate anti-inflammatory effect of d-pinitol in a chick model. Additionally, in silico studies were performed to evaluate the molecular interactions with cyclooxygenase-2 (COX-2). Methods: The tested groups received d-pinitol (12.5, 25, and 50 mg/kg) and the standard drugs celecoxib and ketoprofen (42 mg/kg) via oral gavage prior to formalin injection. Then, the number of licks was counted for the first 10 min, and the paw edema diameter was measured at 60, 90, and 120 min. Results and Discussion: The d-pinitol groups significantly (p < 0.05) reduced the number of paw licks and paw edema diameters, compared to negative control. When d-pinitol was combined with celecoxib, it reduced inflammatory parameters more effectively than the individual groups. The in silico study showed a promising binding capacity of d-pinitol with COX-2. Taken together, d-pinitol exerted anti-inflammatory effects in a dose-dependent manner, possibly through COX-2 interaction pathway.
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St. John's Wort, commonly known as Hypericum perforatum L., is a flowering plant in the Clusiaceae family that traditionally been employed for treating anxiety, depression, wounds, burns, sunburn, irritation, and stomach ailments. This review provides a synopsis of H. perforatum L. phytoconstituents and their biological effects, highlighting its beneficial therapeutic properties for dermatological indications, as well as its antioxidant, antimicrobial, anti-inflammatory, and anti-angiogenic activity in various applications including wound healing and skin conditions such as eczema, sun burn and minor burns also spastic paralysis, stiff neck and mood disorders as anti-depressant and nerve pains such as neuralgia. The data were collected from several databases as Web of Science PubMed, ScienceDirect, Scopus and Google Scholar using the terms: "H. perforatum L.", "H. perforatum L. /phytochemistry," and "H. perforatum extracts/wound healing" collected from 1994 to 2023. The findings suggest H. perforatum L. acts through various mechanisms and plays a role in each phase of the wound healing process, including re-epithelialization, angiogenesis, wound contraction, and connective tissue regeneration. H. perforatum L. enhances collagen deposition, decreases inflammation, inhibits fibroblast migration, and promotes epithelialization by increasing the number of fibroblasts with polygonal shape and the number of collagen fibers within fibroblasts. H. Perforatum L. extracts modulate the immune response and reduce inflammation were found to accelerate the wound healing process via inhibition of inflammatory mediators' production like interleukin-6, tumor necrosis factor-α, cyclooxygenase-2 gene expression, and inducible nitric oxide synthase. Thus, H. perforatum L. represents a potential remedy for a wide range of dermatological problems, owing to its constituents with beneficial therapeutic properties. H. perforatum L. could be utilized in the development of novel wound healing therapies.
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Hypericum , Compostos Fitoquímicos , Extratos Vegetais , Cicatrização , Hypericum/química , Cicatrização/efeitos dos fármacos , Humanos , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/química , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologiaRESUMO
Gastrodin, a bioactive compound derived from the rhizome of the orchid Gastrodia elata, exhibits a diverse range of biological activities. With documented neuroprotective, anti-inflammatory, antioxidant, anti-apoptotic, and anti-tumor effects, gastrodin stands out as a multifaceted therapeutic agent. Notably, it has demonstrated efficacy in protecting against neuronal damage and enhancing cognitive function in animal models of Alzheimer's disease, Parkinson's disease, and cerebral ischemia. Additionally, gastrodin showcases immunomodulatory effects by mitigating inflammation and suppressing the expression of inflammatory cytokines. Its cytotoxic activity involves the inhibition of angiogenesis, suppression of tumor growth, and induction of apoptosis. This comprehensive review seeks to elucidate the myriad potential effects of Gastrodin, delving into the intricate molecular mechanisms underpinning its pharmacological properties. The findings underscore the therapeutic potential of gastrodin in addressing various conditions linked to neuroinflammation and cancer.
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Álcoois Benzílicos , Glucosídeos , Fármacos Neuroprotetores , Álcoois Benzílicos/farmacologia , Álcoois Benzílicos/química , Glucosídeos/farmacologia , Glucosídeos/química , Humanos , Animais , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Gastrodia/química , Antioxidantes/farmacologia , Antioxidantes/química , Apoptose/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/metabolismoRESUMO
Natural approach became a high demand for the prevention and treatment of such diseases for their proven safety and efficacy. This study is aimed to perform comparative phytochemical analysis of white pitaya (Hylocereus undatus) peel, pulp and seed extracts via determination of total flavonoid content, phenolic content, and antioxidant capacity, coupled with HPLC-ESI/MS-MS analysis. Further, we evaluated the synergistic cytotoxic potential with Cisplatin against cervical cancer cells with investigation of underlying mechanism. The highest content of phenolics and antioxidants were found in both seed and peel extracts. The HPLC-ESI/MS-MS revealed identification of flavonoids, phenolic acids, anthocyanin glycosides, lignans, stilbenes, and coumarins. The cytotoxicity effects were evaluated by MTT assay against prostate, breast and cervical (HeLa) and Vero cell lines. The seed and peel extracts showed remarkable cytotoxic effect against all tested cell lines. Moreover, the selectivity index confirmed high selectivity of pitaya extracts to cancer cells and safety on normal cells. The combined therapy with Cisplatin effectively enhanced its efficacy and optimized the treatment outcomes, through the apoptotic ability of pitaya extracts in HeLa cells, as evaluated by flow cytometry. Besides, RT-PCR and western blotting analysis showed downregulation of Bcl-2 and overexpression of P53, BAX among HeLa cells treated with pitaya extracts, which eventually activated apoptosis process. Thus, pitaya extract could be used as adjuvant therapy with cisplatin for treatment of cervical cancer. Furthermore, in-vivo extensive studies on the seed and peel extracts, and their compounds are recommended to gain more clarification about the required dose, and side effects.
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Apoptose , Cactaceae , Cisplatino , Sinergismo Farmacológico , Frutas , Extratos Vegetais , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Neoplasias do Colo do Útero , Humanos , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/metabolismo , Frutas/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Cromatografia Líquida de Alta Pressão/métodos , Células HeLa , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos , Feminino , Animais , Cactaceae/química , Apoptose/efeitos dos fármacos , Cisplatino/farmacologia , Células Vero , Chlorocebus aethiops , Sementes/química , Antineoplásicos Fitogênicos/farmacologia , Flavonoides/farmacologia , Flavonoides/análise , Antioxidantes/farmacologia , Fenóis/farmacologia , Fenóis/análise , Metabolômica/métodosRESUMO
Gigantol, a bibenzyl compound extracted from various medicinal plants, has shown a number of biological activities, making it an attractive candidate for potential medical applications. This systematic review aims to shed light on gigantol's promising role in inflammation treatment and its underlying mechanisms. Gigantol exhibits potential anti-inflammatory properties in pre-clinical pharmacological test systems. It effectively reduced the levels of pro-inflammatory markers and arachidonic acid metabolites through various pathways, such as NF-κB, AKT, PI3K, and JNK/cPLA2/12-LOX. The in-silico investigations demonstrated that the MMP-13 enzyme served as the most promising target for gigantol with highest binding affinity (docking score = -8.8 kcal/mol). Encouragingly, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis of gigantol confirmed its compatibility with the necessary physiochemical, pharmacokinetic, and toxicity properties, bolstering its potential as a drug candidate. Gigantol, with its well-documented anti-inflammatory properties, could be a promising agent for treating inflammation in the near future.
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Introduction: Cheilanthes tenuifolia is an evergreen ornamental small fern, belonging to the family Pteridaceae, that grows in warm and rocky regions worldwide. Many species of Cheilanthes genus are evidently endowed with important phytochemicals and bioactivities. This study aimed to perform a preliminary phytochemical analysis of Cheilanthes tenuifolia leaves alongside an evaluation of free radical scavenging, anti-inflammatory, antimicrobial, and clot lysis activities of extract fractions. Materials and methods: A preliminary phytochemical analysis was done after fractionation of ethanolic extract (ECT) with n-hexane (HCT) and chloroform (CCT). Then, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, egg albumin and RBC membrane stabilization tests, disc diffusion, and human blood clot lysis assays were performed. Results: Phytochemical investigations suggested that the plant is rich in alkaloids, glycosides, tannins, and flavonoids. All obtained fractions exhibited concentration-dependent radical scavenging, inhibition of egg protein denaturation and RBC membrane lysis capacities. Except for antifungal tests, ECT exhibited better DPPH radical scavenging, anti-inflammatory, antibacterial, and clot lysis capacities than HCT and CCT fractions. However, all fractions exhibited a mild anti-inflammatory activity. Conclusion: C. tenuifolia might be a good source of antioxidant, anti-microbial, and anti-atherothrombotic agents. Further studies are required to isolate and characterize the active principles liable for each bioactivity, along with possible molecular interactions.
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Inflammation is a complex and necessary mechanism of an organ's response to biological, chemical and/or physical stimuli. In recent years, investigations on natural compounds with therapeutic actions for the treatment of different diseases have increased. Among these compounds, bromelain is highlighted, as a cysteine protease isolated from the Ananas comosus (pineapple) stem. This review aimed to evaluate the anti-inflammatory activity of bromelain, as well as its pathways on inflammatory mediators, through a systematic review with in vitro studies on different cell lines. The search was performed in PubMed, Science Direct, Scopus, Cochrane Library and Web of Science databases. Bromelain reduced IL-1ß, IL-6 and TNF-α secretion when immune cells were already stimulated in an overproduction condition by proinflammatory cytokines, generating a modulation in the inflammatory response through prostaglandins reduction and activation of a cascade reactions that trigger neutrophils and macrophages, in addition to accelerating the healing process.
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The healing of wounds is the flagging concern in chronic wound cases especially when accompanied by pathogenic, diabetic comorbidities. Matrix metalloproteinases are associated with widespread pathological ailments, and the selective inhibitors for metalloproteinases can be of great interest in wound healing strategies. In the present research study, six constituents of Symplocos racemosa Roxb were evaluated for the docking aptitudes on human matrix metalloproteinase MMP 2 (PDB ID: 1QIB) and MMP 9 (PDB ID: 4H1Q) utilising Autodock Vina followed by the visualisation using Discovery studio (DS). The Pymol was used to generate the poses and the best binding pose was chosen for the docking aptitudes. 2D interactions and the 3D poses of the docked complex were accomplished using DS and LigPlot + software respectively. Working on SWISS ADME and OSIRIS software accomplished the physicochemical characteristics, absorption, distribution, metabolism, excretion, molecular properties, bioactivity score, and toxicity predictions. The molecule's physiochemical investigations discovered that all of the ligands comply with Lipinski's rule of five except compound 6, which deviated with two violations. Docking studies against 4H1Q revealed that compounds 1, 3, 5 and 6 exhibited maximum interactions with the target protein, with the free binding energies of -8.3 kJ Mol-1, -9.3 kJ Mol-1, -7.2 kJ Mol-1 and -11.0 kJ Mol-1 respectively. In case of the 1QIB target, compounds 1, 3 and 6 displayed remarkable binding energies of -8.7 kJ mol-1, -9.0 kJ mol-1 and -8.8 kJ mol-1. Bioactivity prediction study revealed that all of the selected Phytoconstituents displayed incredible Bioactivity scores. None of the selected chemical compounds was found to be irritant to the skin as discovered by toxicity studies. The contacts of the ligand-protein complex during the simulation studies revealed that the H-bond interactions of the ligands with LEU188, ALA189, GLN402, ARG420, MET422, PRO421, and ARG424 of 4H1Q were stable for more than 30% of the simulation time. It was thus concluded that the tested compounds predominantly compounds 1, 5 and 6 might rank among the vital supplementary lead drugs in chronic wounds and healing complexities. It is also worth noting the potential aptitude of the compound 3, however, its toxicity concern must be considered.