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Pharmaceutics Mar 2024Cationic dendritic amphiphiles were prepared through the linkage of interesting hydrophobic molecules such as cholesterol or vitamin E to the focal point of carbosilane...
Cationic dendritic amphiphiles were prepared through the linkage of interesting hydrophobic molecules such as cholesterol or vitamin E to the focal point of carbosilane dendrons. These new dendritic systems self-assembled in saline, producing micellar aggregates with hydrodynamic diameters ranging from 6.5 to 9.2 nm, and critical micelle concentrations of approximately 5 and 10 μM for second- and third-generation systems, respectively. The assemblies were able to encapsulate drugs of different charges (anionic, neutral, and cationic). Surprisingly, a 92% encapsulation efficiency for diclofenac was achieved in micelles prepared from second-generation dendrons. Toxicity measurements on peripheral blood mononuclear cells indicated different behavior depending on the generation, corresponding to the micellar regime. In contrast to the third-generation system, the second-generation system was non-toxic up to 20 μM, opening a window for its use in a micellar regimen, thereby operating as a drug delivery system for different biomedical applications.
PubMed: 38675112
DOI: 10.3390/pharmaceutics16040451 -
Heliyon Apr 2024The need to explore the abundance of natural products cannot be overemphasized particularly in the management of various disease conditions. In traditional medical...
The need to explore the abundance of natural products cannot be overemphasized particularly in the management of various disease conditions. In traditional medical practice, has been widely adopted in the management of various inflammatory disorders. The objective of this investigation was to isolate the bioactive principles from the stem-bark and root of and assess the anti-inflammatory () activity of both the crude extracts and the isolated compounds. Following extraction with the methanol, the extract was subjected to gravity column chromatography and the resultant fractions was further purified to obtained pure compounds. The structural elucidation of the compounds were based on data obtained from 1H to 13C nuclear magnetic resonance (NMR) spectroscopies as well as fourier transform infrared (FT-IR). Using diclofenac as a control drug, the albumin denaturation assay was used to determine the anti-inflammatory activity of the extracts and isolates. Three distinct compounds characterized are vernoamyoside D, luteolin-7-α-o-glucuronide, and vernotolaside, a new glycoside. When compared to diclofenac, which has an IC of 167.8 μg/mL, luteolin-7-α-o-glucuronide, vernoamyoside D, and vernotolaside all showed significant inhibitions with respective IC values 549.8, 379.5, and 201.7 μg/mL. Vernotolaside is reported for the first time from the root. The assertion that the plant is used in traditional medicine for the management of inflammatory disorder is somewhat validated by the confirmation of the existence of the compounds with the biochemical actions. Further validation of the isolated compounds would be required in animal studies.
PubMed: 38665563
DOI: 10.1016/j.heliyon.2024.e29518 -
Heliyon Apr 2024In this study, a novel series of pyridine-based thiadiazole derivatives () were synthesized as prospective anti-inflammatory agents by combining substituted carboxylic...
In this study, a novel series of pyridine-based thiadiazole derivatives () were synthesized as prospective anti-inflammatory agents by combining substituted carboxylic acid derivatives of 5-substituted-2-amino-1,3,4-thiadiazole with nicotinoyl isothiocyanate in the presence of acetone. The newly synthesized compounds were characterized by FTIR, H NMR, C NMR, and mass spectrometry. First, the compounds underwent rigorous testing for acute toxicity and anti-inflammatory activity and the results revealed that three compounds-, , and , displayed no acute toxicity and significant anti-inflammatory activity, surpassing the efficacy of the standard drug, diclofenac. Notably, , which featured benzoic acid substitution, emerged as the most potent anti-inflammatory agent among the screened compounds. To further validate these findings, an docking study was carried out against COX-2 bound to diclofenac (PDB ID: 1pxx). The computational analysis demonstrated that , and , exhibited substantial binding affinity, with the lowest binding energies (-8.5 and -8.4, kcal/mol) compared to diclofenac (-8.4 kcal/mol). This alignment between and data supported the robust anti-inflammatory potential of these derivatives. Moreover, molecular dynamics simulations were conducted, extending over 100 ns, to examine the dynamic interactions between the ligands and the target protein. The results solidified 's position as a leading candidate, showing potent inhibitory activity through strong and sustained interactions, including stable hydrogen bond formations. This was further confirmed by RMSD values of 2-2.5 Å and 2-3Ǻ, reinforcing 's potential as a useful anti-inflammatory agent. The drug likeness analysis of through SwissADME indicated that most of the predicted parameters including Lipinski rule were within acceptable limits. While these findings are promising, further research is necessary to elucidate the precise relationships between the chemical structures and their activity, as well as to understand the mechanisms underlying their pharmacological effects. This study lays the foundation for the development of novel anti-inflammatory therapeutics, potentially offering improved efficacy and safety profiles.
PubMed: 38655368
DOI: 10.1016/j.heliyon.2024.e29390 -
EXCLI Journal 2024Minimization of intra-operative opioid use is an area of ongoing research interest with several potential benefits to the patient. Pre-emptive analgesia, defined as the...
Minimization of intra-operative opioid use is an area of ongoing research interest with several potential benefits to the patient. Pre-emptive analgesia, defined as the administration of an analgesic before surgery to prevent establishment of central sensitization of pain, is one avenue that has been explored to achieve this. A retrospective observational study was undertaken to examine the effect of pre-emptive paracetamol on intra-operative opioid requirements. The medical and operative data of 156 patients who underwent day-case wide local excision and sentinel lymph node biopsy with and without regional block surgery at our center between October 2019 and May 2022 was carried out. Data were collected on demographics, total intra-operative and immediate post-operative opioid consumption. 57 patients did not receive pre-emptive paracetamol while 90 did. Baseline characteristics were similar. Our results showed a statistically significant reduction in morphine (p <0.029) and remifentanil (p <0.007) consumption in patients who received a regional block and pre-emptive paracetamol. Those who did not receive a regional block and were given pre-emptive paracetamol had a decrease in OxyNorm (p <0.022) requirements. A combination of general anesthesia (GA), regional block and pre-emptive paracetamol reduced intra-operative consumption of Fentanyl, OxyNorm, diclofenac, dexketoprofen, and clonidine (P <0.001) when compared to just GA alone. Use of pre-emptive paracetamol in reduction of intra-operative opioid requirements showed promising results but larger studies may strengthen the evidence for this association. A multimodal analgesic approach that utilizes pre-emptive paracetamol can be a viable method to decrease intra-operative of analgesic requirements.
PubMed: 38655093
DOI: 10.17179/excli2023-6804 -
Scientific Reports Apr 2024Advanced oxidation processes are the most efficient tool to thwart the overaccumulation of harmful organic compounds in the environment. In this direction bioinspired...
Advanced oxidation processes are the most efficient tool to thwart the overaccumulation of harmful organic compounds in the environment. In this direction bioinspired metal complexes may be a viable solution for oxidative degradations in water. However, their synthesis is often elaborated and their scalability consequently low. This study presents alternative easy-to-synthesize bioinspired metal complexes to promote degradations in water. The metals employed were iron and manganese ions, hence cheap and highly accessible ions. The complexes were tested toward Phenol, Estrone, Triclosan, Oxybenzone, Diclofenac, Carbamazepine, Erythromycin, Aspartame, Acesulfame K, Anisole and 2,4-Dinitrotoluene. The reaction favoured electron-rich compounds reaching a removal efficiency of over 90%. The central ion plays a crucial role. Specifically, Mn(II) induces a non-radical pathway while iron ions a predominant radical one (OH is predominant). The iron systems resulted more versatile toward contaminants, while the manganese ones showed a higher turn-over number, hence higher catalytic behaviour.
PubMed: 38653989
DOI: 10.1038/s41598-024-59381-0 -
Environmental Toxicology and... Jun 2024Understanding interactions between legacy and emerging environmental contaminants has important implications for risk assessment, especially when mutagens and...
Understanding interactions between legacy and emerging environmental contaminants has important implications for risk assessment, especially when mutagens and carcinogens are involved, whose critical effects are chronic and therefore difficult to predict. The current work aimed to investigate potential interactions between benzo[a]pyrene (B[a]P), a carcinogenic polycyclic aromatic hydrocarbon and legacy pollutant, and diclofenac (DFC), a non-steroidal anti-inflammatory drug and pollutant of emerging concern, and how DFC affects B[a]P toxicity. Exposure to binary mixtures of these chemicals resulted in substantially reduced cytotoxicity in human HepG2 cells compared to single-chemical exposures. Significant antagonistic effects were observed in response to high concentrations of B[a]P in combination with DFC at IC and ⅕ IC. While additive effects were found for levels of intracellular reactive oxygen species, antagonistic mixture effects were observed for genotoxicity. B[a]P induced DNA strand breaks, γH2AX activation, and micronuclei formation at ½ IC concentrations or lower, whereas DFC induced only low levels of DNA strand breaks. Their mixture caused significantly lower levels of genotoxicity by all three endpoints compared to those expected based on concentration additivity. In addition, antagonistic mixture effects on CYP1 enzyme activity suggested that the observed reduced genotoxicity of B[a]P was due to its reduced metabolic activation as a result of enzymatic inhibition by DFC. Overall, the findings further support the growing concern that co-exposure to environmental toxicants and their non-additive interactions may be a confounding factor that should not be neglected in environmental and human health risk assessment.
Topics: Humans; Diclofenac; Benzo(a)pyrene; Hep G2 Cells; Carcinogens, Environmental; Reactive Oxygen Species; Cyclooxygenase 1; Cell Survival; Cyclooxygenase Inhibitors; Cyclooxygenase 2; DNA Damage; Cyclooxygenase 2 Inhibitors; Histones
PubMed: 38642625
DOI: 10.1016/j.etap.2024.104453 -
Journal of Hazardous Materials Jun 2024SARS-CoV-2 pandemic affected lifestyle habits, and the mental health and wellbeing of people around the world. In this manuscript, two towns (Paulton and Radstock) and...
SARS-CoV-2 pandemic affected lifestyle habits, and the mental health and wellbeing of people around the world. In this manuscript, two towns (Paulton and Radstock) and two cities (Bath and Bristol) in Southwest England (> 1 million people) were monitored for two years using Wastewater-Based Epidemiology to assess impacts of COVID (including management measures such as lockdowns and movement restrictions) on community lifestyle choices: illicit drugs, legal stimulants, abused pharmaceuticals and pain pharma usage. Results were triangulated with key dates captured during the pandemic (national lockdowns, restrictions and social distancing measures, etc.). This highlighted a reduction in cocaine intake (as benzoylecgonine) (community average: -36 %) during the first lockdown and an increase in illicit drugs usage after the 3rd national lockdown (community averages for amphetamine: +8 %, cocaine/benzoylecgonine: +39 %, ketamine:+70 %) when restrictions were removed, and social interaction and recreational activities increased. There was a reduction in the intake of caffeine (as 1,7-dimethylxanthine) (community average:-39 %) after 3rd national lockdown coinciding with pubs reopening while nicotine intake (via cotinine) remained stable indicating lack of impact of COVID on smoking habits. Pain pharma often used in pain management resulting from injuries linked with sport activities (naproxen and diclofenac) showed decrease in usage due to lockdown restrictions in physical exercise and access to gyms/sport facilities.
Topics: COVID-19; Humans; Life Style; Illicit Drugs; Wastewater; England; Wastewater-Based Epidemiological Monitoring; SARS-CoV-2; Recreational Drug Use; Pandemics; Substance-Related Disorders
PubMed: 38640675
DOI: 10.1016/j.jhazmat.2024.134264 -
Journal of Hazardous Materials Jun 2024SARS-CoV-2 pandemic had a significant impact on the society, economy, and health of people around the world with consequences that need to be better understood for...
SARS-CoV-2 pandemic had a significant impact on the society, economy, and health of people around the world with consequences that need to be better understood for future pandemic preparedness. This manuscript provides insights into the usage of pharmaceuticals for pain treatment management throughout SARS-CoV-2 pandemic. Four towns and cities with a total population of > 1 million people covering an area of 2000 km in South West England were monitored for twenty-four months. Results showed different patterns in pain pharma usage, with small towns having higher population normalised daily loads (PNDLs) than big cities for majority of pain killers studied. This is likely due to demographics of these cities with smaller cities having older population. Per capita consumption of non-steroidal anti-inflammatory drugs (NSAIDs) increased compared to pre-pandemic usage in line with SARS-CoV-2 infections (ibuprofen and acetaminophen), while body pain drugs (diclofenac and naproxen) decreased in line with restrictions and closure of sports facilities. Changes in population normalised daily intake (PNDI) of pain killers were particularly apparent during the 1st and 3rd national lockdown. Comparison of PNDIs with prescriptions highlighted differences related to medication availability (OTC drugs) and patients' nonadherence (prescribed drugs). In addition, several instances of direct disposal events across the catchments were observed which raises an issue of lack of pharma compliance and general understanding of potential environmental impacts from pharma usage.
Topics: Humans; COVID-19; Anti-Inflammatory Agents, Non-Steroidal; Longitudinal Studies; England; Analgesics; SARS-CoV-2; Pain; Pain Management; Wastewater; Wastewater-Based Epidemiological Monitoring; Ibuprofen; Pandemics
PubMed: 38636235
DOI: 10.1016/j.jhazmat.2024.134121 -
Cureus Mar 2024This study aims to quantitatively assess the anti-inflammatory and antioxidant activities of the ethanolic extract of seeds.
AIM
This study aims to quantitatively assess the anti-inflammatory and antioxidant activities of the ethanolic extract of seeds.
MATERIALS AND METHODS
Around 30 seeds of were collected, crushed, and powdered; 10 gm of powder was added to 100 ml of ethanolic extract and boiled for further analysis. Egg albumin denaturation assay and hydroxyl radical scavenging assay were done to evaluate the anti-inflammatory and antioxidant activity, respectively. An independent t-test was used to compare the anti-inflammatory and antioxidant potential of the ethanolic extract of using SPSS Statistics version 22.0 (IBM Corp. Released 2013. IBM SPSS Statistics for Windows, Version 22.0; Armonk, NY: IBM Corp.), and values less than 0.05 are considered statistically significant.
RESULTS
The seeds of have potent anti-inflammatory and antioxidant properties. Both anti-inflammatory and antioxidant properties improved with higher concentrations and were comparable to the control substances diclofenac sodium, vitamin E, and ascorbic acid, respectively. The most significant anti-inflammatory and antioxidant effect was observed at a dosage of 50 μL, with a p-value of 0.001.
CONCLUSION
To conclude, we found that the ethanolic extract of has anti-inflammatory and antioxidant activity, which can further be used for the improvement of pharmaceuticals.
PubMed: 38633945
DOI: 10.7759/cureus.56391 -
RSC Advances Apr 2024In recent times, there has been considerable interest in utilizing aqueous biphasic systems (ABSs) containing natural deep eutectic solvents (NADESs) for the extraction...
Harnessing the power of natural deep eutectic solvents (choline chloride/sucrose) and polypropylene glycol in the formation of aqueous biphasic systems and the application of these systems in drug extraction.
In recent times, there has been considerable interest in utilizing aqueous biphasic systems (ABSs) containing natural deep eutectic solvents (NADESs) for the extraction of various substances. In this study, we focused on investigating the phase behavior of ABSs composed of poly(propylene) glycol 400 and NADESs (specifically, choline chloride/sucrose with molar ratios of 2 : 1 and 1 : 1). By analyzing the compositions of tie-lines, it was observed that these ABSs, which consist of four components, exhibit characteristics similar to ternary systems. To examine the influence of molar ratios on phase separation, the binodal model was applied to the obtained binodal data. The NRTL and UNIQUAC models were employed to establish correlations for the tie-lines. Moreover, we examined the extraction capabilities of the aforementioned ABSs for three commonly used drugs: diclofenac potassium, acetaminophen, and salicylic acid. To assess the efficiency of extraction, partition coefficients and extraction efficiencies were calculated for each drug. The results revealed that the extraction efficiency of these drugs into the polymer-rich top phase is dependent on their hydrophobicity. Furthermore, we employed the Diamond-Hsu equation, along with its modified version, to establish correlations between the experimental partition coefficients of the drugs and NADES overall concentrations.
PubMed: 38633497
DOI: 10.1039/d3ra07066b