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Molecules (Basel, Switzerland) Apr 2024Wall () has been used traditionally for the management of arthritis; however, its therapeutic potential warrants further investigation. This study aimed to evaluate the...
Wall () has been used traditionally for the management of arthritis; however, its therapeutic potential warrants further investigation. This study aimed to evaluate the anti-arthritic effects of the aqueous-ethanolic extract of leaves (AeOB) in a rat model of complete Freund's adjuvant (CFA)-induced arthritis. Rats were treated with AeOB (250, 500, and 750 mg/kg), indomethacin (10 mg/kg), or a vehicle control from days 8 to 28 post-CFA injection. Arthritic score, paw diameter, and body weight were monitored at regular intervals. X-ray radiographs and histopathological analysis were performed to assess arthritic severity. Inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP) were quantified by qPCR and icromatography. Phytochemical analysis of AeOB revealed alkaloids, flavonoids, phenols, tannins, Saponins, and glycosides. AeOB also exhibited antioxidant potential with an IC of 73.22 µg/mL in a DPPH assay. AeOB and diclofenac exhibited anti-inflammatory and anti-arthritic activities. Rats treated with AeOB at 750 mg/kg and indomethacin showed significantly reduced arthritic symptoms and joint inflammation versus the CFA control. The AeOB treatment downregulated TNF-α and IL-6 and decreased CRP levels compared with arthritic rats. Radiography and histopathology also showed improved prognosis. These findings demonstrate the anti-arthritic potential of AeOB leaves.
Topics: Animals; Male; Rats; Anti-Inflammatory Agents; Antioxidants; Arthritis, Experimental; C-Reactive Protein; Freund's Adjuvant; Interleukin-6; Phytochemicals; Plant Extracts; Plant Leaves; Sapindaceae; Tumor Necrosis Factor-alpha; Rats, Wistar
PubMed: 38675650
DOI: 10.3390/molecules29081830 -
Pharmaceuticals (Basel, Switzerland) Mar 2024L. (, SN) or black elder is a traditional medicinal plant widely used worldwide for therapeutic and dietary purposes. The aim of the current study was to investigate...
L. (, SN) or black elder is a traditional medicinal plant widely used worldwide for therapeutic and dietary purposes. The aim of the current study was to investigate the anti-inflammatory and antinociceptive activities of black elder fruit and flower extracts (SNFrE and SNFlE, respectively). The primary polyphenol constituents in the flower extract were flavonoids and phenolic acids, while anthocyanins were the main components in the fruit extract. SNFrE revealed pronounced and dose-dependent in vivo anti-inflammatory activity assessed by the cotton pellet-induced granuloma test. Doses of 10, 20, and 50 mg/kg BW of SNFrE reduced the weight of induced granuloma in rats by 20.3%, 20.5%, and 28.4%, respectively. At the highest dose (50 mg/kg BW), SNFrE had significant ( < 0.01) anti-inflammatory activity comparable to that of diclofenac, the reference compound used (10 mg/kg BW). In addition, the in vivo antinociceptive activity of the extracts in mice was estimated using the acetic-acid-induced writhing test. Both extracts at doses of 50 mg/kg BW inhibited the abdominal contractions induced by the acetic acid significantly comparing to the control group ( < 0.01). Our findings indicate that black elder extracts and particularly SNFrE possess anti-inflammatory and antinociceptive activities, providing experimental evidence for the use of in traditional medicine.
PubMed: 38675372
DOI: 10.3390/ph17040409 -
Pharmaceutics Apr 2024Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most prescribed drugs to treat pain or fever. However, oral administration of NSAIDs is frequently...
Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most prescribed drugs to treat pain or fever. However, oral administration of NSAIDs is frequently associated with adverse effects due to their inhibitory effect on the constitutively expressed cyclooxygenase enzyme 1 (COX-1) in, for instance, the gastrointestinal tract. A systemic delivery, such as a buccal delivery, of NSAIDs would be beneficial and additionally has the advantage of a non-invasive administration route, especially favourable for children or the elderly. To investigate the transport of NSAIDs across the buccal mucosa and determine their potential for buccal therapeutic usage, celecoxib, diclofenac, ibuprofen and piroxicam were tested using an established oral mucosa Transwell model based on human cell line TR146. Carboxyfluorescein and diazepam were applied as internal paracellular and transcellular marker molecule, respectively. Calculated permeability coefficients revealed a transport ranking of ibuprofen > piroxicam > diclofenac > celecoxib. Transporter protein inhibitor verapamil increased the permeability for ibuprofen, piroxicam and celecoxib, whereas probenecid increased the permeability for all tested NSAIDs. Furthermore, influence of local inflammation of the buccal mucosa on the transport of NSAIDs was mimicked by treating cells with a cytokine mixture of TNF-α, IL-1ß and IFN-γ followed by transport studies with ibuprofen (+ probenecid). Cellular response to pro-inflammatory stimuli was confirmed by upregulation of cytokine targets at the mRNA level, increased secreted cytokine levels and a significant decrease in the paracellular barrier. Permeability of ibuprofen was increased across cell layers treated with cytokines, while addition of probenecid increased permeability of ibuprofen in controls, but not across cell layers treated with cytokines. In summary, the suitability of the in vitro oral mucosa model to measure NSAID transport rankings was demonstrated, and the involvement of transporter proteins was confirmed; an inflammation model was established, and increased NSAID transport upon inflammation was measured.
PubMed: 38675204
DOI: 10.3390/pharmaceutics16040543 -
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