Drug Diclofenac Research Articles

Unveiling the anxiolytic and analgesic effects of citronellal in Swiss mice: in vivo and in silico insights into COX and GABAA receptor pathways.

This study aims to evaluate the analgesic and anxiolytic effects of citronellal (CTL) in Swiss mice using two new sensitive and economic mouse models along with possible molecular mechanisms through in silico studies. For this, we employed marble displacement and spiked-field apparatus to check the anxiolytic and analgesic effects, respectively. In silico studies were done against cyclooxygenase (COX) enzymes and GABAA receptor subunits. Findings suggest that the test sample CTL significantly reduced the number of marbles displaces (NMD), square crosses (NSC), paw massages (NPM), and escaping attempts (NEA) in animals than the control group. CTL exhibited better effects in the perforated-field study compared to the reference drug diclofenac sodium. In both cases, CTL (200mg/kg) significantly reduced the test parameters when combined with the standard drugs (diazepam or diclofenac sodium). In in silico studies, CTL showed binding affinities of - 5.5, - 5.2, - 4.8, and - 4.8kcal/mol with the COX1, COX2, and GABAA receptors (α2 and α3 subunits), respectively. Taken together, CTL may exert anxiolytic- analgesic-like effects on mice, possibly through the GABAA receptor and COXs interaction pathways. These new tools might be used to check the anxiolytic and analgesic properties of a wide variety of test substances.

NEW BIARYL DERIVATIVES OF DICLOFENAC DRUG: SYNTHESIS, MOLECULAR DOCKING AND THEIR BIOLOGICAL ACTIVITY STUDY AS ANTICANCER AND ANTIOXIDANT AGENTS

In this work, a series of diclofenac derivatives were synthesized via the Suzuki-Miyaura reaction and evaluated in vitro as anticancer and antioxidant agents. Structures of synthesized compounds were characterized by FT- IR, 1H NMR, 13C NMR spectra, and elemental analysis. The products have been screened in vitro for their anticancer activity against both cell lines HdFn and MCF-7 as well as they were investigated for their antioxidant activity. The cytotoxicity assay results revealed that derivatives 3a and 3d exhibited good inhibition for cell lines MCF-7 with IC50 values 33.1 and 38.2 µM, respectively while 3a and 3c exhibited acceptable inhibition for HdFn with IC50 values 68.7 and 72.6µM, respectively compared to the Tamoxifine drug. Molecular docking study of the target compounds confirmed the results of the cytotoxicity test. In addition, results of the DPPH investigation revealed good antioxidant activity for derivatives 3a, 3c and 3d with inhibition percentages of 83.14, 82.42, and 78.16%, respectively compared to ascorbic acid. For citation: Abdul-Rida N.A., Mohammed K.T. New biaryl derivatives of diclofenac drug: synthesis, molecular docking and their biological activity study as anticancer and antioxidant agents. ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2024. V. 67. N 12. P. 47-53. DOI: 10.6060/ivkkt.20246712.7071.

In vitro Cyclooxygenase inhibitory activity and GC-MS profiling of bioactive compounds in Bauhinia racemosa Lam.

Non-steroidal anti-inflammatory drugs (NSAIDs) are a common treatment for chronic pain and inflammation. While NSAIDs have been shown to reduce inflammation and pain associated with them, they have an array of side effects. Researchers investigated the COX inhibitory action of NSAIDs. They revealed that there are two distinct COX enzymes: COX-1 and COX2. Developing COX inhibitors has remained critical for producing innovative and safe anti-inflammatory drugs. Bauhinia racemosa Lam belonging to the family Fabaceae has a wide range of medicinal properties. The plant is used to treat various diseases in traditional medicine, but there is less knowledge based on clinical efficacy as an anti-inflammatory agent. In the present study Bauhinia racemosa Lam hydroalcoholic extract were screened for COX inhibition and GC-MS analysis was done to screen phytochemicals. The results obtained were found to inhibit 89% of COX activity significantly as compared to standard drug (Diclofenac sodium). GC-MS analysis revealed a total of ten potent bioactive compounds. The samples were identified by comparing retention time and peak area to literature and interpreting mass spectra. Results observed from the study suggest that the hydroalcoholic extract of Bauhinia racemosa Lam possess anti-inflammatory activity and can be utilized as an alternate source for NSAIDs. Keywords: COX, Bauhinia racemosa Lam, Anti-inflammatory, NSAIDs.

Nano-strategies for advancing oral drug delivery: Porous silicon particles and cyclodextrin encapsulation for enhanced dissolution of poorly soluble drugs

Development of novel active pharmaceutical ingredients (API) for oral use often face challenges due to low bioavailability. Nanoparticle-based drug delivery systems and cyclodextrin (CD) encapsulation offer promising solutions by enhancing API solubility or dissolution rates. Porous silicon nanoparticles have shown potential to encapsulate APIs in their amorphous form within the pores, improving their dissolution rates compared to crystalline counterparts. A novel synthesis approach, circumventing the expensive and tedious synthesis from Si wafer material, has been developed using centrifugal Chemical Vapor Deposition (cCVD). Herein, various cCVD Si particles were evaluated for their ability to enhance the dissolution rate of the model drugs celecoxib (CEL), phenytoin (PHT), griseofulvin (GRI), diclofenac (DCF) and naproxen (NAP). Our findings demonstrate increased dissolution rates of all tested APIs when formulated with cCVD Si particles, compared to free API in pH 7.4 or pH 2.0. Particle characteristics were largely retained after loading, and the solid state of the loaded APIs were evaluated using Differential Scanning Calorimetry (DSC). Dissolution kinetics were influenced by the particle properties, mass loading and API characteristics. Loading of CD-CEL, −GRI and −DCF complexes into the cCVD Si particles showed a potential for further enhanced dissolution rates, representing the first reported investigation of this combination. In conclusion, the cCVD Si particles are promising for improving the dissolution rate of poorly soluble drugs, potentially due to precipitation of amorphous or metastable forms. Further enhancements were observed upon loading CD-drug complexes, thereby offering promising strategies for optimizing drug bioavailability.

Revolutionizing fast disintegrating tablets: Harnessing a dual approach with porous starch and sublimation technique

This study investigates the transformation of neat starch (NS) from mung beans into porous starch (PS) for the formulation of fast-disintegrating tablets (FDTs) using the sublimation technique, contrasting their performance with superdisintegrants such as sodium starch glycolate (SSG) and croscarmellose sodium (CS). Camphor was used as a sublimating agent. The interaction between drug and excipients was analyzed using Fourier-transform infrared spectroscopy (FTIR), while preformulation assessments were conducted on powder blends. Model drug Diclofenac sodium (DL)-loaded FDTs were prepared via direct compression technique. Thermal behavior and crystalline properties were evaluated using differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD), respectively. Compressibility of tablets was assessed through Heckel and Kawakita analyses. Post-compression evaluations encompassed hardness, thickness, in vitro disintegration, and dissolution studies. FTIR analysis indicated the absence of chemical interactions among constituents, while precompression analyses confirmed favorable flow properties of the blends. Heckel analysis supported the material's notable compressibility. Microscopic examination revealed the formation of pores on the tablet surface due to the sublimation process. Integration of PS significantly accelerated the disintegration time of FDTs, with durations ranging from 50 to 82 s, compared to 76–104 s for NS-FDTs. While PS-FDTs exhibited a longer disintegration time compared to SSG, they demonstrated faster disintegration compared to croscarmellose sodium. A significant disparity (p<0.01) in drug release at 60 min was observed between SSG and PS-FDTs, with DP3 achieving 97.65 % drug release. Most batches followed the Korsmeyer-Peppas model, except for DN2 and DN3, which adhered to Higuchi-matrix drug release kinetics. Stability assessments after 90 days revealed no significant differences (p>0.05). Conclusively, this study highlights the effectiveness of PS and the sublimation method in creating FDTs with enhanced drug release properties.

Anti-inflammatory activity and molecular docking studies of the hydromethanolic leaf extract of Baphia longipedicellata brumitt in rats

Background: Almost all Baphia species of the Fabaceae family have a long history in traditional China due to their potent anti-inflammatory properties Baphia longipedicellata (B. longipedicellata) is a relatively novel plant comprised mainly of stigmasterol, which has a rich history in Chinese medicine and is a principal active component in numerous Chinese herbs such as maidong, the banxia-baizhu-tianma decoction and Qingfengteng which are all native to China and well known for its use in inflammatory diseases, asthma and diabetes management.Aim of the study: The study was meticulously designed to evaluate the anti-inflammatory activity of Baphia longipedicellata in rats. What sets this study apart is its unique approach to predicting the mechanism of anti-inflammatory action through docking studies.Materials and Methods: Preliminary phytochemical screening and oral acute toxicity were carried out for the hydromethanolic extract of Baphia longipedicellata (HMBL). Phytocompounds in the extract were identified using high-performance Liquid Chromatography (HPLC). Carrageenan and egg albumin-induced paw edema models in rats were evaluated to ascertain the extract's anti-inflammatory potential.Molecular docking experiments were carried out to evaluate the binding affinity of HPLC-selected compounds to cyclooxygenase-2 (COX-2) and tumour necrosis Factor-alpha (TNF-alpha).Results and Discussion: Preliminary phytochemical screening revealed the presence of saponin, tannins, cardiac glycosides, alkaloids, terpenoids, etc. Results obtained from this study showed that the LD50 was greater than 2000 mg/kg, and there were no observable toxic effects or mortality following its acute exposure.HPLC of HMBL profiled, Curcumin, Lutein, Stigmasterol, Beta-Sitosterol, Chrysarobin, Quercetin, and Napabucasin,HMBL extract at all treatment doses showed a significant reduction in both carrageenan and egg albumin-induced hind paw edema in a dose-dependent manner, comparable to the standard drug Diclofenac. Peak anti-oedematogenic activity was observed at the 6th-hour post-carrageenan injection with 28.50, 42.06, and 36.90 % inhibition for HMBL (100, 200, or 400 mg/kg) and 5th-hour post-egg-albumin injection with 61.22, 66.88, and 48.06 % inhibition.The molecular docking study showed that all the isolated HPLC compounds inhibited COX-2 and TNF-alpha.Conclusion Ultimately, the hydro-methanolic leaf extract of B. longipedicellata exhibits potent anti-inflammatory activity via COX 2 and TNF-alpha inhibition. Thus, it would be a viable phytotherapeutic option for treating inflammatory conditions.

3,4-Dihydropyrimidine-2(1H)-one/thione Derivatives as Anti-inflammatory and Antioxidant Agents: Synthesis, Biological Activity, and Docking Studies

aims: A series of sixteen new 4-(substituted phenyl) - 6-(substituted phenylamino)-3, 4-dihydropyrimidine-2(1H)-ones/thiones derivatives have been synthesized in two step reaction. background: Free radicals are widely known to play a significant part in the inflammatory process. Many non-steroidal anti-inflammatory medicines have been shown to work as radical scavengers or as inhibitors of free radical generation. Inflammation is a part of the vascular tissues&amp;#039; complicated biological reaction to adverse stimuli like bacteria, damaged cells, or irritants. The organism&amp;#039;s protective response to damaging stimuli is inflammation, which aims to get rid of them and start the healing process. The inflammatory response has several advantageous effects, such as stopping the spread of dangerous substances to nearby tissues, getting rid of cell waste and infections, and getting the body ready for repair objective: To synthesize new derivatives as anti-inflammatory and antioxidant agents. method: In first step chalcones (I1-I6) was obtained and in the second step, these chalcones were reacted with urea and thiourea in the presence of potassium hydroxide to obtain the corresponding pyrimidinones and thiopyrimidinones. The structures of the synthesized compounds 4-(substituted phenyl)-6-(substituted phenylamino)-3,4-dihydropyrimidine-2(1H)-ones/thione derivatives are investigated by means of TLC (visualized it in Iodine chamber), IR, mass, 1H-NMR spectral and elemental analysis. The title compounds evaluated for anti-inflammatory as well as antioxidant activity. Anti-inflammatory activity in vivo was carried out by carrageenan induced rat-paw edema method and compared with standard drug diclofenac sodium and antioxidant activity was measured by DPPH, FRAP and Hydrogen peroxide (H2O2) method and compared with standard ascorbic acid. result: Electron donating groups showed better antioxidant activity as compared to electron withdrawing ones in both activities. All the compounds exhibited good to moderate activity. Compound DHPM8 shows better antioxidant activity and compound DHPM6 shows better anti-inflammatory activity while compound DHPM11 shows minimum antioxidant as well as anti-inflammatory activity than other compounds. conclusion: To better understanding, we have performed molecular docking simulation. The molecular docking studies revealed that all synthesized compound were showed good receptor binding interaction in which compound 9 had highest docking score of 9.8 due to interaction with CYS36, PRO153, TYR130, GLY45, LEU152, ARG469, LYS468 and GLU465. other: NA

Anti-Inflammatory And Immunomodulating Activity of the 1(10) Β-Epoxy-5,7α,6β(Н)-Guai-3(4),11(13)-Dien-6,12-Olide

BACKGROUND: The article discusses the results of studies of the anti-inflammatory and immunomodulatory activity of the sesquiterpene lactone 1(10)β-epoxy-5,7α,6β(Н)-guai-3(4),11(13)-diene-6,12-olide (hereinafter referred to as epoxyguaianolide). AIM: The article discusses the results of studies of the anti-inflammatory and immunomodulatory activity of the sesquiterpene lactone 1(10)β-epoxy-5,7α,6β(Н)-guai-3(4),11(13)-diene-6,12-olide. MATERIALS AND METHODS: A non-steroidal anti-inflammatory drug diclofenac sodium at a dose of 25 mg/kg (ampoules, 2 mL each, manufactured by Germany) was used as a reference drug in models of acute aseptic inflammation and cotton ball granuloma. On the model of cyclophosphamide immunosuppression, the immunomodulator levamisole at a dose of 3 mg/kg, was used as a reference drug. The immunomodulating effect of the test samples was studied on outbred adult male rats and outbred mice. We calculated the arithmetic mean, the mean square error of the arithmetic mean, the significance of the difference between the mean Рt according to the student’s t-test (TTEST), and the significance of the difference in Pf variances according to the Fisher f-test. RESULTS: The results of the experiments indicate the presence of a pronounced immunomodulatory activity in epoxyguaianolide. When interacting with cells of the immune system, epoxyguaianolide activated the studied parameters in animals with immunosuppression, whereas in intact animals, it did not affect the above parameters. On the model of cyclophosphamide immunosuppression, it was found that epoxyguaianolide has a pronounced immunomodulatory effect, manifested in an increase in the number of T-lymphocytes and a subpopulation of theophylline-resistant T-lymphocytes, an increase in the number of theophylline-sensitive T- and B-lymphocytes, activation of phagocytosis processes, and increased cell migration. This action of epoxyguaianolide eliminates the minimal possibility of hyperactivation of the immune system, which is an important condition for its use as an immunotropic agent. CONCLUSIONS: The conducted experiments made it possible to recommend epoxyguaianolide for clinical trials as an immunomodulating agent in the treatment of chronic inflammatory diseases accompanied by secondary immunodeficiencies.

Photodegradation potential of selected non-steroidal anti-inflammatory drugs in a middle-order Alpine river downstream of a wastewater treatment plant, during a year of enduring water scarcity

The year 2022 was characterised by significant water shortages and droughts in Italy, with the most pronounced impact observed in the North-Western regions, including Piemonte. In conditions of water scarcity, treated wastewater undergoes little dilution by natural flows and this can deeply affect the chemistry of water-poor rivers and streams. However, increased pollution by wastewater would be partially offset by fast photodegradation of pollutants in shallow water and by the longer time allowed to photochemical reactions if water flows more slowly. We assessed the latter phenomena in the Stura di Lanzo, a middle-order Alpine river tributary of the largest Italian river, the Po, and affected by a wastewater treatment plant (WWTP). In 2022, the concentration values of the photochemically significant parameters nitrate, nitrite, and DOC were usually higher downstream of the WWTP outlet, which could slightly favour indirect photodegradation reactions. Direct and indirect photodegradation was assessed for the non-steroidal anti-inflammatory drugs paracetamol, diclofenac, and naproxen, all undergoing rather fast photoreactions. Photochemistry model results show that the three compounds would undergo 10–40 % photodegradation in spring and summer along the stretch separating the wastewater outlet from the confluence of Stura into the Po. Photodegradation would continue in the latter, but other WWTPs might contribute additional pollution in the meanwhile. Albeit significant, photodegradation could only partially promote the elimination of the contaminants.

Anelosimuseximius bioinspired ZnO nano cobwebs for environmental remediation of drugs and endocrine disruptors from water

The pollution of wastewater with pharmaceuticals and endocrine-disrupting chemicals (EDCs) in populated areas poses a growing threat to humans and ecosystems. To address this serious problem, various one-dimensional (1D) hierarchical ZnO-based nanostructures inspired by Anelosimus eximius cobwebs were developed and successfully grown on a glass substrate through simple hydrothermal synthesis. The nanorods (nr) obtained during primary growth were chemically etched with KOH (ZnOnr-KOH), followed by the secondary growth of nano cobweb-like (ncw) structures using polyethyleneimine (ZnOnr/ncw). These structures were further decorated by the photoreduction of Ag nanoparticles (ZnOnr/ncw/Ag). The feasibility of ZnO-based 1D nanostructures to remove pollutants was demonstrated by degrading commonly prescribed pharmaceutical drugs (diclofenac and carbamazepine) in a miniature cuvette reactor. The photocatalytic activities for drug degradation generally decreased in the order ZnOnr/ncw/Ag > ZnOnr/ncw > ZnOnr-KOH. Additionally, the suitability of the samples for scaling up and practical application was demonstrated by photocatalytic degradation of the hormone estriol (E3) in a flow-through photoreactor. The photocatalytic degradation efficiency of E3 followed the same trend observed for drug degradation, with the complete elimination of the endocrine disruptor achieved by the best-performing ZnOnr/ncw/Ag within 4 h, due to optimized charge transfer and separation at the heterostructure interface.

Mechanochemically synthesized flower-like bismuth oxyhalides: An electrochemical platform for diclofenac detection

The emerging drug diclofenac (DICF) has been found to penetrates aquatic systems at alarming concentrations and poses serious and irreversible ecotoxicological threats around the world. In this work, we present the solid-state mechanochemical synthesis of 3D flower-like bismuth oxyhalides (BiOX, where X = Cl, Br, and I) as electrode materials for electrochemical detection of DICF. The characteristics of the flower-like BiOX are systematically investigated using spectroscopic and microscopic techniques. The BiOI-modified glassy carbon electrode (GCE) exhibits superior electrochemical performance for DICF detection compared to the pristine GCE, BiOCl/GCE, and BiOBr/GCE. The 3D flower-like architecture of BiOI facilitates favorable electrocatalytic activities due to its abundant electroactive sites, good conductivity, large surface area, and fast ion diffusion. Notably, the BiOI/GCE displays wide linear ranges (0.5–11.3 & 11.3−76), a low limit of detection (0.11 μM), high sensitivity (1.33 μA μM–1 cm–2), excellent repeatability (2.91 %), good reproducibility (2.88 %), and anti-interfering ability (<±5 %). To validate the practicality of the fabricated BiOI/GCE, the quantitative detection of DICF in human urine and river water is demonstrated and achieves acceptable recovery values. This study introduces an innovative approach to design and produce electrode materials with distinct properties, enabling enhanced electrocatalysis for various electrochemical sensing applications.

Photocatalytic Degradation of Selected Non-Opioid Analgesics Driven by Solar Light Exposure

The residues of pharmaceutical compounds are often resistant to degradation, causing an environmental problem. Our research aimed to perform a study of the photocatalytic and photoelectrocatalytic degradation of non-opioid analgesic paracetamol and some of the non-steroidal anti-inflammatory drugs (NSAIDs) (ketoprofen, naproxen, diclofenac, and ibuprofen). Semiconductor WO3, Fe2O3, and WO3/Fe2O3 photocatalysis using solar energy lamps were applied for this purpose. As a result of the photocatalytic processes, high decomposition efficiency was obtained for ketoprofen (97%) and naproxen (70%). Low photodegradation yields were achieved for diclofenac. Under the used measurement conditions, both paracetamol and ibuprofen were not degraded.

Global modeling of photochemical reactions in lake water: A comparison between triplet sensitization and direct photolysis

The equivalent monochromatic wavelength (EMW) approximation allowed us to predict the photochemical lifetimes of the lipid regulator metabolite clofibric acid (CLO, triplet sensitization) and of the non-steroidal anti-inflammatory drug diclofenac (DIC, direct photolysis ​+ ​triplet sensitization) in lakes worldwide. To do so, we used large lake databases that collect photochemically significant parameters such as water depth and dissolved organic carbon, which allow for a preliminary assessment of some photoreactions. Extension to other photoreactions is currently prevented by the lack of important parameters such as water absorption spectrum, suspended solids, nitrate, nitrite, pH, and inorganic carbon on a global scale. It appears that triplet-sensitized CLO photodegradation would be strongly affected by the dissolved organic carbon values of the lake water and, for this reason, it would be fastest in Nordic environments. By contrast, direct photolysis (DIC) would be highly affected by sunlight irradiance and would proceed at the highest rates in the tropical belt. Interestingly, the predicted lifetimes of CLO and DIC are shorter than the residence time of water in the majority of global lake basins, which suggests a high potential for photoreactions to attenuate the two contaminants on a global scale. Photodegradation of DIC and CLO would also be important in waste stabilization ponds, except for elevated latitudes during winter, which makes these basins potentially cost-effective systems for the partial removal of these emerging contaminants from wastewater.

Self-healing hydrogel from poly(aspartic acid) and dextran with antibacterial property for burn wound healing

Designing hydrogel dressing with intrinsic antibacterial property to promote skin injury recovery remains a significant challenge. In this research, poly(aspartic hydrazide) with grafted betaine (PAHB) was designed and reacted with oxidized dextran (OD) to fabricate biodegradable PAHB/OD hydrogel and its application as wound dressing was systematically investigated. The PAHB/OD hydrogels exhibited fast gelation, strong tissue adhesion, preferable mechanical properties and biocompatibility. The grafted betaine endowed the hydrogel with antibacterial property and antibacterial rate enhanced through photothermal performance of composited CuS nanoparticles under near infrared (NIR) radiation. The CuS composited PAHB/OD hydrogel (CuS/hydrogel) with microporous morphology was used as burn wound dressing with loaded anti-inflammatory drug diclofenac sodium (DS) in mouse model. The results showed the DS loaded CuS/hydrogel (CuS@DS/hydrogel) promoted the tissue regeneration and suppressed the inflammatory response. The histological analysis and immunohistochemical expression confirmed the CuS@DS/hydrogel promote angiogenesis of the burn wound by regulating the expression of inflammatory cytokines (IL-6 and CD68) and vascular endothelial growth factor (VEGF). Overall, the CuS@DS/hydrogel hydrogel is a promising candidate as wound dressing due to its tissue adhesive, antioxidant, antibacterial and anti-inflammatory activities.

Effects of Non-steroidal Anti-inflammatory Drugs (Ibuprofen and Diclofenac) and Their Mixtures on the Growth of Three Green Algae

Ibuprofen (IBU) and diclofenac (DFN) are the most widely consumed non-steroidal anti-inflammatory (NSAIDs) worldwide. Since they are not completely metabolized in the human body, the unaltered active ingredients can reach aquatic ecosystems through domestic effluents. The aim of this study was to analyse the toxic effects of IBU and DFN, individually and in mixtures, on three freshwater green algae strains, the international standard strain Raphidocelis subcapitata and two native strains, Ankistrodesmus fusiformis and Tetradesmus obliquus. Bioassays were carried out according to the 72-h algal growth inhibition test. The concentration-response curve of the mixture was compared to predicted effects based on both the concentration addition (CA) and the independent action (IA) models. The two drugs tested individually were toxic to all three algal strains, with EC50 values &lt;100 mg L-1. According to these values, the most sensitive strain was R. subcapitata (IBU = 20 mg L-1 and DFN = 8 mg L-1). The most resistant strain was T. obliquus (IBU = 74.1 mg L-1 and DFN = 92.7 mg L-1) and the A. fusiformis strain showed intermediate sensitivity (IBU = 26.7 mg L-1 and DFN = 14.6 mg L-1). The mixtures showed a synergistic effect on R. subcapitata, an additive effect on A. fusiformis, and an antagonistic effect on T. obliquus. Neither the CA nor the IA model was appropriate for predicting the toxicity of the mixtures. In conclusion, IBU and DFN showed toxic effects on the algae growth at the concentrations tested. Individual and mixed toxicity was different according to the species. These differences could be species-specific, showing the importance of including native strains in ecotoxicological studies to evaluate the potential effects of pollutants in regional aquatic environments.

Exploration for the opioidergic, GABAergic and histaminergic potentials of synthesized Schiff’s base derivatives: An in-vivo approach

Herein, five Schiff’s base analogs (designated as AK1 to AK5) were synthesized and screened for their analgesic and anti-inflammatory efficacies. All compounds exhibited analgesic activity at selected doses from 45.31 % to 75.75 %, while the standard drug diclofenac sodium produced result as 86.33 %. Compounds AK1, AK3, AK4 and AK5 were found significantly P<0.001 effective at a dose of 25 mg/kg body weight (b.w). Similarly, in tail immersion test the produced percentage activity were in range from 40.19 % to 62.35 %. in which the compounds AK1, AK2, AK4 and AK5 were significantly P<0.01 effective at dose 12.5 mg/kg b.w, while at this dose significance level of efficacy of AK3 was P<0.05. Similarly, at administering doses of 25 mg/kg b.w all compounds were effective with significance level P<0.001, n = 8. Administration of the synthesized Schiff’s bases at the tested doses significantly reduced paw edema as compared to control. Results of paw edema at 3rd hour was significant P<0.001. AK4 and AK5 were subjected to mechanistic approaches by GABAergic, opiodergic and histaminergic pathways. In GABAergic pathway bicuculline caused a partial reversal of writhings responses indicating the involvement of GABA receptors and therefore the tested compounds may have act through GABAergic pathway. The naloxone caused a mild reversal in the tail immersion test and indicated that some other mechanisms are additionally involved in mode of action of these compounds. Additionally a mild response was observed while studying its action involving histaminergic pathway.

Efficient photocatalytic degradation of diclofenac drug using the Zn1-x-yPrxAlyO photocatalyst under UV light irradiation.

Herein, we report the efficient photocatalytic degradation of the diclofenac drug using the Zn1-x-yPrxAlyO photocatalyst [x, y] = (0.00, 0.00), (0.03, 0.01), (0.03,0.03) under UV light irradiation. The analysis of the structure reveals that the Pr3+ and Al3+ cations insertion into the ZnO lattice leads to a decrease in the lattice constant (a and c), Zn-O bond length, strain lattice, and crystallite size. These alterations are linked to the high degree of atomic disorder triggered by the dopants, which produce stress and strain in the ZnO structure. The Raman measurements confirmed the structural phase and showed changes in the position and intensity of the E2High mode, associated with oxygen vibrations and material crystallinity. The presence of the dopants reduces the concentration of VZn and VO++ type defects while increasing the levels of VO, VO+, and Oi defects, as observed from the fitting of the Photoluminescence spectra. Furthermore, it was noted that de Pr3+ and Al3+ cations insertion into ZnO increases the optical band gap, which is associated with the Moss-Burstein effect. The micrograph images show that dopants transform the morphology from quasi-spherical particles to irregular cluster structures. The textural analysis indicated that an increase in the concentration of Al3+ in the ZnO lattice led to a higher surface area, likely enhancing photocatalytic activity. The sample containing 3% Pr3+ and 3% Al3+ showed the highest photocatalytic activity and degraded up to 71.42% of diclofenac. In addition, experiments with scavengers revealed that hydroxyl radicals are the main species involved in the drug's photodegradation mechanism. Finally, the Zn1-x-yPrxAlyO compound is highly recyclable and stable.

In vitro antioxidant and anti-inflammatory activities of selected polyherbal formulations sold in Nigeria

Background and aims: Nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroid analgesics are recommended to alleviate or reduce pain. Regrettably, many of these drugs may induce bleeding, dyspepsia, cardiac complications, renal issues, and various short- or long-term adverse effects. Consequently, there has been an escalation in the endeavor to develop natural anti-inflammatory medications, driven by the growing number of individuals seeking natural therapies to manage their pain. The polyherbal formulations (Yoyo and Dr. Iguedo Goko bitters) have not assessed their antioxidant and anti-inflammatory activities; hence, this study "in vitro antioxidant and anti-inflammatory activities of selected polyherbal formulations sold in Nigeria." Methods: The evaluation of antioxidant activity was performed using three assays: 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals, hydrogen peroxide (H2 O2 ) scavenging activity, and ferric reducing antioxidant power. In vitro, anti-inflammatory efficacy was investigated using the human red blood cell (HRBC) membrane stabilization technique. Results: The DPPH radical scavenging ability result was observed; the IC50 value of Yoyo bitters (40.63±0.90 % at 250 µg/mL) was highest, while Dr. Goko bitters (3.26±0.21% at 50 µg/mL) was lowest. Meanwhile, the positive control (ascorbic acid) had an IC50 value of 93.54±0.57% at 250 µg/mL. The ferric-reducing antioxidant power of the samples was highest in Dr. Goko bitters, 1.96±0.02 % at 250 µg/mL, and lowest in Dr. Goko and Yoyo bitters, 0.46±0.01% at 100 and 50 µg/mL, respectively. The hydrogen peroxide free radical scavenging activity of the samples was highest in Yoyo bitters, 58.0.3±0.60 % at 250 µg/mL, and lowest in Dr. Goko bitters, 7.28±0.02 % at 50 µg/mL. The anti-inflammatory findings indicate that Yoyo bitters exhibited the highest percentage protection (89.46±6.11%) at a concentration of 1000 μg/mL, while the lowest percentage protection (26.62±1.13%) was observed at a concentration of 200 μg/mL. The reference standard diclofenac sodium has a percentage of 90.46±1.44 at a concentration of 1000 μg/mL. Meanwhile, the poly-herbal formulations had the highest and lowest total phenolic concentrations in Yoyo bitters (97.52±1.43 mg GAE/g at 250 µg/mL), and Dr. Goko bitters (47.3±1.44 mg GAE/g at 50 µg/mL), respectively. Conclusion: The findings suggest that the formulations might not have effective antioxidant and anti-inflammatory activities when compared with the reference standard drugs (ascorbic acid and diclofenac sodium), respectively.

Magnetic Polysaccharide Mesenchymal Stem Cells Exosomes Delivery Microcarriers for Synergistic Therapy of Osteoarthritis.

Osteoarthritis (OA) is a prevalent degenerative disease that afflicts more than 250 million people worldwide, impairing their mobility and quality of life. However, conventional drug therapy is palliative. Exosomes (Exo), although with the potential to fundamentally repair cartilage, face challenges in their efficient enrichment and delivery. In this study, we developed magnetic polysaccharide hydrogel particles as microcarriers for synergistic therapy of OA. The microcarriers were composed of modified natural polysaccharides, hyaluronic acid (HAMA), and chondroitin sulfate (CSMA), and were generated from microfluidic electrospray in combination with a cryogelation process. Magnetic nanoparticles with spiny structures capable of capturing stem cell Exo were encapsulated within the microcarriers together with an anti-inflammatory drug diclofenac sodium (DS). The released DS and Exo from the microcarriers had a synergistic effect in alleviating the OA symptoms and promoting cartilage repair. The in vitro and in vivo results demonstrated the excellent performance of the microcarrier for OA treatment. We believe this work has potential for Exo therapy of OA and other related diseases.

Evaluation of the anti-inflammatory, antinociceptive, and antipyretic potential of ethanolic extract of Aristida depressa Retz through in vitro, in vivo, and in silico models.

Uncontrolled inflammation is a crucial factor in the development of many diseases. Anti-inflammatory molecules based on natural sources are being actively studied, among which Aristida depressa Retz (Ar.dp) has been traditionally used as a paste to heal inflammation. The present study aimed to evaluate the anti-inflammatory, analgesic, and antipyretic potential of an ethanolic extract of A. depressa through a battery of in vivo and in vitro models. The ethanolic extract of A. depressa was prepared by maceration and chemically characterized using high-performance liquid chromatography, which revealed the presence of quercetin, vanillic acid, chlorogenic acid, p-coumaric acid, m-coumaric acid, ferulic acid, cinnamic acid, and sinapic acid; its antioxidant capacity was then screened with the DPPH in vitro assay, which indicated moderate scavenging capacity. A protein denaturation assay was next performed to evaluate the in vitro anti-inflammatory potential of Ar.dp, which showed significant inhibition (44.44%) compared to the standard drug (diclofenac sodium), with 89.19% inhibition at a concentration of 1mg/mL. The in vivo safety profile of Ar.dp was evaluated in accordance with the OECD-425 acute toxicity guidelines and found to be safe up to 5g/kg. The in vivo anti-inflammatory potentials of Ar.dp were evaluated at three different doses (125, 250, and 500mg/kg) in acute (carrageenan-induced edema: 84.60%, histamine-induced paw edema: 84%), sub-chronic (cotton-pellet-induced granuloma: 57.54%), and chronic (complete-Freund's-adjuvant-induced arthritis: 82.2%) models. Our results showed that Ar.dp had significant (p < 0.05) anti-inflammatory effects over diclofenac sodium in the acute and chronic models. Histopathology studies indicated reduced infiltration of paw tissues with inflammatory cells in Ar.dp-treated animals. Similarly, Ar.dp showed significant (p < 0.05) analgesic (yeast-induced-pyrexia model: 23.53%) and antipyretic (acetic-acid-induced writhing model: 51%) effects in a time-dependent manner. In silico studies on the interactions of COX-1 and COX-2 with the eight ligands mentioned earlier confirmed the inhibition of enzymes responsible for inflammation and fever. Based on the findings of the present study, it is concluded that Ar.dp has anti-inflammatory, analgesic, and antipyretic properties that are likely linked to its pharmacologically active phenolic bioactive molecules.