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Heliyon May 2024Non-steroid anti-inflammatory drugs (NSAIDs) are a class of prescription drugs with antipyretic, analgesic, anti-inflammatory, and antiplatelet effects. However,...
INTRODUCTION
Non-steroid anti-inflammatory drugs (NSAIDs) are a class of prescription drugs with antipyretic, analgesic, anti-inflammatory, and antiplatelet effects. However, long-term use of NSAIDs will disrupt the intestinal mucosal barrier, causing erosion, ulcers, bleeding, and even perforation. Pure total flavonoids from Citrus (PTFC) is extracted from the dried peel of Citrus, showing a protective effect on intestinal mucosal barrier with unclear mechanisms.
METHODS
In the present study, we used diclofenac (7.5 mg kg, i.g.) to induce a rat model of NSAIDs-related intestinal lesions. PTFC (50, 75, 100 mg·kg-1 d-1, i.g.) was administered 9 days before the initial diclofenac administration, followed by co-administration on the last 5 days. Exosomes were identified by western blotting and transmission electron microscopy (TEM), and then co-cultured with IEC-6 cells. The expression of long non-coding RNA (lncRNA) H19, autophagy-related 5 (Atg5), ZO-1, Occludin, and Claudin-1 were detected by quantitative real-time PCR (qRT-PCR). The expression of light chain 3 (LC3)-I, LC3-II, ZO-1, Occludin and Claudin-1 proteins was tested by western blotting. The localization of both exosomes and autophagosomes was examined by immunofluorescent technique.
RESULTS
The treatment of PTFC attenuated intestinal mucosal mechanical barrier function disturbance in diclofenac-induced NSAIDs rats. IEC-6 cells co-cultured with NSAIDs rats-derived exosomes possessed the lowest levels of protective autophagy, and severe intestinal barrier injuries. Cells co-cultured with the exosomes extracted from rats administrated PTFC exhibited an improvement of autophagy and intestinal mucosal mechanical barrier function. The prevention effect was proportional to the concentration of PTFC administered.
CONCLUSION
PTFC ameliorated NSAIDs-induced intestinal mucosal injury by down-regulating exosomal lncRNA H19 and promoting autophagy.
PubMed: 38707329
DOI: 10.1016/j.heliyon.2024.e29797 -
Ecotoxicology and Environmental Safety Jun 2024Discharging pharmaceutically active drugs into water and wastewater has become a significant environmental threat. Traditional methods are unable to effectively remove...
Discharging pharmaceutically active drugs into water and wastewater has become a significant environmental threat. Traditional methods are unable to effectively remove these compounds from wastewater, so it is necessary to search for more effective methods. This study investigates the potential of MIL-101(Cr)-NH as a preferable and more effective adsorbent for the adsorption and removal of pharmaceutically active compounds from aqueous solutions. By utilizing its large porosity, high specific surface area, and high stability, the structural and transport properties of three pharmaceutically active compounds naproxen (NAP), diclofenac (DIC) and sulfamethoxazole (SMX)) studied using molecular dynamics simulation. The results indicate that the MIL-101(Cr)-NH adsorbent is suitable for removing drug molecules from aqueous solutions, with maximum adsorption capacities of 697.75 mg/g for naproxen, 704.99 mg/g for diclofenac, and 725.51 mg/g for sulfamethoxazole.
Topics: Water Pollutants, Chemical; Naproxen; Metal-Organic Frameworks; Sulfamethoxazole; Diclofenac; Molecular Dynamics Simulation; Adsorption; Water Purification; Wastewater; Pharmaceutical Preparations
PubMed: 38701652
DOI: 10.1016/j.ecoenv.2024.116333 -
Bioactive Materials Aug 2024Enhancing the regeneration of cartilage defects remains challenging owing to limited innate self-healing as well as acute inflammation arising from the overexpression of...
Enhancing the regeneration of cartilage defects remains challenging owing to limited innate self-healing as well as acute inflammation arising from the overexpression of reactive oxygen species (ROS) in post-traumatic microenvironments. Recently, stem cell-derived exosomes (Exos) have been developed as potential cell-free therapy for cartilage regeneration. Although this approach promotes chondrogenesis, it neglects the emerging inflammatory microenvironment. In this study, a smart bilayer-hydrogel dual-loaded with sodium diclofenac (DC), an anti-inflammatory drug, and Exos from bone marrow-derived mesenchymal stem cells was developed to mitigate initial-stage inflammation and promote late-stage stem-cell recruitment and chondrogenic differentiation. First, the upper-hydrogel composed of phenylboronic-acid-crosslinked polyvinyl alcohol degrades in response to elevated levels of ROS to release DC, which mitigates oxidative stress, thus reprogramming macrophages to the pro-healing state. Subsequently, Exos are slowly released from the lower-hydrogel composed of hyaluronic acid into an optimal microenvironment for the stimulation of chondrogenesis. Both and assays confirmed that the dual-loaded bilayer-hydrogel reduced post-traumatic inflammation and enhanced cartilage regeneration by effectively scavenging ROS and reprogramming macrophages. The proposed platform provides multi-staged therapy, which allows for the optimal harnessing of Exos as a therapeutic for cartilage regeneration.
PubMed: 38699244
DOI: 10.1016/j.bioactmat.2024.04.017 -
Journal of Oleo Science 2024Launaea sarmentosa, also known as Sa Sam Nam, is a widely used remedy in Vietnamese traditional medicine and cuisine. However, the chemical composition and bioactivity...
Launaea sarmentosa, also known as Sa Sam Nam, is a widely used remedy in Vietnamese traditional medicine and cuisine. However, the chemical composition and bioactivity of its essential oil have not been elucidated yet. In this study, we identified 40 compounds (98.6% of total peak area) in the essential oil via GC-MS analysis at the first time. Among them, five main compounds including Thymohydroquinone dimethyl ether (52.4%), (E)-α-Atlantone (9.0%), Neryl isovalerate (6.6%), Davanol D2 (isomer 2) (3.9%), and trans-Sesquisabinene hydrate (3.9%) have accounted for 75.8% of total peak area. The anti-bacterial activity of the essential oil against 4 microorganisms including Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa has also investigated via agar well diffusion assay. The results showed that the essential oil exhibited a strong antibacterial activity against Bacillus subtilis with the inhibition zones ranging from 8.2 to 18.7 mm. To elucidate the anti-bacterial effect mechanism of the essential oil, docking study of five main compounds of the essential oil (Thymohydroquinone dimethyl ether, (E)-α-Atlantone, Neryl isovalerate, Davanol D2 (isomer 2), and trans-Sesquisabinene hydrate) against some key proteins for bacterial growth such as DNA gyrase B, penicillin binding protein 2A, tyrosyl-tRNA synthetase, and dihydrofolate reductase were performed. The results showed that the main constituents of essential oil were highly bound with penicillin binding protein 2A with the free energies ranging -27.7 to -44.8 kcal/mol, which suggests the relationship between the antibacterial effect of essential oil and the affinity of main compounds with penicillin binding protein. In addition, the free energies of main compounds of the essential oil with human cyclooxygenase 1, cyclooxygenase 2, and phospholipase A2, the crucial proteins related with inflammatory response were less than diclofenac, a non-steroidal antiinflammatory drug. These findings propose the essential oil as a novel and promising anti-bacterial and anti-inflammatory medicine or cosmetic products.
Topics: Molecular Docking Simulation; Anti-Bacterial Agents; Oils, Volatile; Bacillus subtilis; Staphylococcus aureus; Pseudomonas aeruginosa; Escherichia coli; Tetrahydrofolate Dehydrogenase; DNA Gyrase; Sesquiterpenes; Microbial Sensitivity Tests; Gas Chromatography-Mass Spectrometry; Pentanoic Acids; Hemiterpenes
PubMed: 38692900
DOI: 10.5650/jos.ess23254 -
Water Research Jun 2024Separate collection and treatment of urine optimizes nutrient recovery and enhances micropollutant removal from municipal wastewater. One typical urine treatment train... (Comparative Study)
Comparative Study
Separate collection and treatment of urine optimizes nutrient recovery and enhances micropollutant removal from municipal wastewater. One typical urine treatment train includes nutrient recovery in three biological processes: anaerobic storage, followed by aerobic organics degradation concurrently with nitrification. These are usually followed by activated carbon adsorption to remove micropollutants. However, removing micropollutants prior to nitrification would protect nitrifiers from potential inhibition by pharmaceuticals. In addition, combining simplified biological treatment with activated carbon adsorption could offer a cheap and robust process for removing micropollutants where nutrient recovery is not the first priority, as a partial loss of ammonia occurs without nitrification. In this study, we investigated whether activated carbon adsorption could also take place between the three biological treatment steps. We tested the effectiveness of micropollutant removal with activated carbon after each biological treatment step by conducting experiments with anaerobically stored urine, organics-depleted urine, and nitrified urine. The urine solutions were spiked with 19 pharmaceuticals: amisulpride, atenolol, atenolol acid, candesartan, carbamazepine, citalopram, clarithromycin, darunavir, diclofenac, emtricitabine, fexofenadine, hydrochlorothiazide, irbesartan, lidocaine, metoprolol, N-acetylsulfamethoxazole, sulfamethoxazole, trimethoprim, venlafaxine, and two artificial sweeteners, acesulfame and sucralose. Batch experiments were conducted with powdered activated carbon (PAC) to determine how much activated carbon achieve which degree of micropollutant removal and how organics, pH, and speciation change from ammonium to nitrate influence adsorption. Micropollutant removal was also tested in granular activated carbon (GAC) columns, which is the preferred technology for micropollutant removal from urine. The carbon usage rates (CUR) per person were lower for all urine solutions than for municipal wastewater. The results showed that organics depletion would be needed when micropollutant removal was the sole aim of urine treatment, as the degradation of easily biodegradable organics prevented clogging of GAC columns. However, CUR did hardly improve with organics-depleted urine compared to stored urine. The lowest CUR was achieved with nitrified urine. This resulted from the additional organics removal during nitrification and not the lower pH or the partial conversion of ammonium to nitrate. In addition, we showed that the relative pharmaceutical removal in all solutions was independent of the initial pharmaceutical concentration unless the background organics matrix changed considerably. We conclude that removal of micropollutants in GAC columns from organics-depleted urine can be performed without clogging, but with the drawback of a higher carbon usage compared to removal from nitrified urine.
Topics: Adsorption; Water Pollutants, Chemical; Nitrification; Charcoal; Anaerobiosis; Waste Disposal, Fluid; Wastewater; Urine; Pharmaceutical Preparations; Water Purification
PubMed: 38692253
DOI: 10.1016/j.watres.2024.121615 -
Frontiers in Immunology 2024Skin injuries represent a prevalent form of physical trauma, necessitating effective therapeutic strategies to expedite the wound healing process. Hesperidin, a...
INTRODUCTION
Skin injuries represent a prevalent form of physical trauma, necessitating effective therapeutic strategies to expedite the wound healing process. Hesperidin, a bioflavonoid naturally occurring in citrus fruits, exhibits a range of pharmacological attributes, including antimicrobial, antioxidant, anti-inflammatory, anticoagulant, and analgesic properties. The main objective of the study was to formulate a hydrogel with the intention of addressing skin conditions, particularly wound healing.
METHODS
This research introduces a methodology for the fabrication of a membrane composed of a Polyvinyl alcohol - Sodium Alginate (PVA/A) blend, along with the inclusion of an anti-inflammatory agent, Hesperidin (H), which exhibits promising wound healing capabilities. A uniform layer of a homogeneous solution comprising PVA/A was cast. The process of crosslinking and the enhancement of hydrogel characteristics were achieved through the application of gamma irradiation at a dosage of 30 kGy. The membrane was immersed in a Hesperidin (H) solution, facilitating the permeation and absorption of the drug. The resultant system is designed to deliver H in a controlled and sustained manner, which is crucial for promoting efficient wound healing. The obtained PVA/AH hydrogel was evaluated for cytotoxicity, antioxidant and free radical scavenging activities, anti-inflammatory and membrane stability effect. In addition, its action on oxidative stress, and inflammatory markers was evaluated on BJ-1 human normal skin cell line.
RESULTS AND DISCUSSION
We determined the effect of radical scavenging activity PVA/A (49 %) and PVA/AH (87%), the inhibition of Human red blood cell membrane hemolysis by PVA/AH (81.97 and 84.34 %), hypotonicity (83.68 and 76.48 %) and protein denaturation (83.17 and 85.8 %) as compared to 250 μg/ml diclofenac (Dic.) and aspirin (Asp.), respectively. Furthermore, gene expression analysis revealed an increased expression of genes associated with anti-oxidant and anti-inflammatory properties and downregulated TNFα, NFκB, iNOS, and COX2 by 67, 52, 58 and 60%, respectively, by PVA/AH hydrogel compared to LPS-stimulated BJ-1 cells. The advantages associated with Hesperidin can be ascribed to its antioxidant and anti-inflammatory attributes. The incorporation of Hesperidin into hydrogels offers promise for the development of a novel, secure, and efficient strategy for wound healing. This innovative approach holds potential as a solution for wound healing, capitalizing on the collaborative qualities of PVA/AH and gamma irradiation, which can be combined to establish a drug delivery platform for Hesperidin.
Topics: Hesperidin; Polyvinyl Alcohol; Humans; Alginates; NF-kappa B; Tumor Necrosis Factor-alpha; Hydrogels; Signal Transduction; Anti-Inflammatory Agents; Wound Healing; Cyclooxygenase 2; Nitric Oxide Synthase Type II; Antioxidants; Inflammation
PubMed: 38686374
DOI: 10.3389/fimmu.2024.1347420 -
Chemosphere Jun 2024The treatment of waterborne micropollutants, such as diclofenac, presents a significant challenge to wastewater treatment plants due to their incomplete removal by...
The treatment of waterborne micropollutants, such as diclofenac, presents a significant challenge to wastewater treatment plants due to their incomplete removal by conventional methods. Ozonation is an effective technique for the degradation of micropollutants. However, incomplete oxidation can lead to the formation of ecotoxic by-products that require a subsequent post-treatment step. In this study, we analyze the susceptibility of micropollutant ozonation products to enzymatic digestion with laccase from Trametes versicolor to evaluate the potential of enzymatic treatment as a post-ozonation step. The omnipresent micropollutant diclofenac is used as an example, and the enzymatic degradation kinetics of all 14 detected ozonation products are analyzed by high-performance liquid chromatography coupled with high-resolution mass spectrometry (HPLC-HRMS) and tandem mass spectrometry (MS). The analysis shows that most of the ozonation products are responsive to chemo-enzymatic treatment but show considerable variation in enzymatic degradation kinetics and efficiencies. Mechanistic investigation of representative transformation products reveals that the hydroxylated aromatic nature of the ozonation products matches the substrate spectrum, facilitating their rapid recognition as substrates by laccase. However, after initiation by laccase, the subsequent chemical pathway of the enzymatically formed radicals determines the global degradability observed in the enzymatic process. Substrates capable of forming stable molecular oxidation products inhibit complete detoxification by oligomerization. This emphasizes that it is not the enzymatic uptake of the substrates but the channelling of the reaction of the substrate radicals towards the oligomerization of the substrate radicals that is the key step in the further development of an enzymatic treatment step for wastewater applications.
Topics: Diclofenac; Laccase; Ozone; Water Pollutants, Chemical; Wastewater; Oxidation-Reduction; Kinetics; Chromatography, High Pressure Liquid; Tandem Mass Spectrometry; Waste Disposal, Fluid; Water Purification; Polyporaceae
PubMed: 38677613
DOI: 10.1016/j.chemosphere.2024.142112 -
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