Potent Anti-inflammatory Drug Research Articles

Colchicine for prevention of post-operative atrial fibrillation: Meta-analysis of randomized controlled trials.

This study intended to assess the efficacy of colchicine for prevention of post-operative atrial fibrillation (AF). Post-operative AF is a common complication of surgery operations. Inflammation plays a crucial role in the pathogenesis of post-operative AF. Colchicine, a potent anti-inflammatory drug, may have a role in mitigating the incidence of post-operative AF. We searched Cochrane Library, Web of Science, PubMed, China National Knowledge Infrastructure (CNKI), Database of Chinese sci-tech periodicals (COVIP), and Wanfang Database for randomized controlled trials (RCTs) comparing colchicine versus placebo, or usual care for prevention of post-operative AF. The main outcome was the occurrence of AF post operation, which includes cardiac surgery, lung surgery, or pulmonary vein isolation. The estimated risk ratio (RR) for the occurrence of post-operative AF was evaluated using a random-effects model. The safety end point was the development of any side effects. A total of 12 RCTs with 2274 patients were eventually included in this meta-analysis, where 1141 patients received colchicine and 1133 patients received placebo or usual care. Perioperative colchicine treatment was related to a decreased incidence of post-operative AF (RR: 0.65; 95% confidence interval [CI]: 0.56 to 0.75, p<0.001). Although the incidence of gastrointestinal side effects was increased with colchicine therapy when compared to placebo (RR = 2.49, 95% CI 1.85 to 3.34, p < 0.001), the incidence of major adverse events was not increased (RR = 0.86, 95% CI 0.46 to 1.60, p = 0.64). In conclusion, the results of our meta-analysis suggest that colchicine treatment could lower the incidence of post-operative AF. Further studies are needed to determine the optimal colchicine treatment regime to minimize the incidence of adverse events.

The effect of dexamethasone and flunixin-meglumine on ovulation, endometrial oedema, and inter-ovulatory interval length in the mare

The use of flunixin-meglumine (a potent non-steroidal anti-inflammatory drug) during the critical period of intrafollicular prostaglandin production before ovulation (24 and 36 h after hCG treatment) results in a high rate of ovulatory failure and formation of haemorrhagic anovulatory follicles (HAF) in the mare. Dexamethasone is commonly used to prevent persistent mating-induced endometritis in susceptible mares, but the effect on ovulation blockage within the pre-ovulatory critical window of intrafollicular prostaglandins production following hCG administration has not been determined. Six mares were followed during four consecutive cycles in a crossover design; once in oestrus with a follicle of >32 mm in diameter, mares were treated with hCG (Hour 0) and assigned to one of 4 groups randomly: 1) FM, mares received 1.7 mg/kg flunixin-meglumine at Hour 24 and 36; 2) CON, mares received no further treatment. 3) DEX1, mares received 0.1 mg/kg dexamethasone at Hour 24, and 4) DEX2, mares received 0.1 mg/kg dexamethasone at Hour 24 and 36. For all groups, ovulation and HAF rates, endometrial oedema profiles and the inter-ovulatory intervals (IOI) were determined and compared statistically. All CON and DEX mares ovulated normally and did not form any HAF. On the contrary, FM mares developed a HAF in 83% of cycles (P < 0.01). The endometrial oedema score was lower following DEX administration than FM (P < 0.05). The mean IOI was longer (P < 0.05) in DEX1 and DEX2 groups (26.5 and 26 days, respectively) than in CON and FM groups (21.5 and 22 days, respectively). In conclusion, dexamethasone treatment given either once or twice during the critical window of hCG-induced ovulation did not block or delay ovulation, but had a similar ovulation rate than untreated control mares. However, the inter-ovulatory intervals of dexamethasone treated mares was longer than control and FM treated mares. Finally, dexamethasone treatment was more effective in reducing endometrial oedema than FM.

In Silico Study and Effects of BDMC33 on TNBS-Induced BMP Gene Expressions in Zebrafish Gut Inflammation-Associated Arthritis

The bone morphogenic protein (BMP) family is a member of the TGF-beta superfamily and plays a crucial role during the onset of gut inflammation and arthritis diseases. Recent studies have reported a connection with the gut-joint axis; however, the genetic players are still less explored. Meanwhile, BDMC33 is a newly synthesized anti-inflammatory drug candidate. Therefore, in our present study, we analysed the genome-wide features of the BMP family as well as the role of BMP members in gut-associated arthritis in an inflammatory state and the ability of BDMC33 to attenuate this inflammation. Firstly, genome-wide analyses were performed on the BMP family in the zebrafish genome, employing several in silico techniques. Afterwards, the effects of curcumin analogues on BMP gene expression in zebrafish larvae induced with TNBS (0.78 mg/mL) were determined using real time-qPCR. A total of 38 identified BMP proteins were revealed to be clustered in five major clades and contain TGF beta and TGF beta pro peptide domains. Furthermore, BDMC33 suppressed the expression of four selected BMP genes in the TNBS-induced larvae, where the highest gene suppression was in the BMP2a gene (an eight-fold decrement), followed by BMP7b (four-fold decrement), BMP4 (four-fold decrement), and BMP6 (three-fold decrement). Therefore, this study reveals the role of BMPs in gut-associated arthritis and proves the ability of BDMC33 to act as a potential anti-inflammatory drug for suppressing TNBS-induced BMP genes in zebrafish larvae.

Anti-Inflammatory Effects of Compounds from Echinoderms.

Chronic inflammation can extensively burden a healthcare system. Several synthetic anti-inflammatory drugs are currently available in clinical practice, but each has its own side effect profile. The planet is gifted with vast and diverse oceans, which provide a treasure of bioactive compounds, the chemical structures of which may provide valuable pharmaceutical agents. Marine organisms contain a variety of bioactive compounds, some of which have anti-inflammatory activity and have received considerable attention from the scientific community for the development of anti-inflammatory drugs. This review describes such bioactive compounds, as well as crude extracts (published during 2010-2022) from echinoderms: namely, sea cucumbers, sea urchins, and starfish. Moreover, we also include their chemical structures, evaluation models, and anti-inflammatory activities, including the molecular mechanism(s) of these compounds. This paper also highlights the potential applications of those marine-derived compounds in the pharmaceutical industry to develop leads for the clinical pipeline. In conclusion, this review can serve as a well-documented reference for the research progress on the development of potential anti-inflammatory drugs from echinoderms against various chronic inflammatory conditions.

Chemical Constituents from Uapaca guineensis (Phyllanthaceae), and the Computational Validation of Their Antileishmanial and Anti-inflammatory Potencies

From the chemical investigations of the root bark of Uapaca guineensis, nine distinct compounds (1–9) have been isolated and characterized as lupeol, betulin, betulinic acid, β-amyryl acetate, physcion, quercetin, rutin, β-sitosterol, and β-sitosterol-3-O-β-D-glucopyranoside, respectively. The structures of all the isolated compounds have been established using their NMR data as well as the comparison of those data with the ones reported in the literature. Interestingly, to the best of our knowledge, except for the lupane-type triterpenoids (1–3) and compounds 4 and 9, all the other compounds are reported for the first time from this genus. Since the plant is widely used for the treatment of skin diseases, leishmaniasis and inflammatory diseases, the antileishmanial and anti-inflammatory potencies of all the isolated compounds have been computationally validated through their ability to inhibit the receptors 1QCC and 2XOX (for the antileishmanial studies) and 6Y3C and 1CX2 (for the anti-inflammatory studies). Furthermore, the ADMET studies of compounds have been done to evaluate their drug-likeness. Results demonstrate that all the isolated compounds showed a better affinity for both receptors’ binding sites than the standard drugs miltefosine and aspirin. Moreover, the compounds would not cause addiction when used as lead molecules whereas, aspirin is predicted to violate the BBB over a long term of usage as a drug. This study gives additional information on the chemistry of U. guineensis and its classification as a potential source of good leads for the development of potent antileishmanial and anti-inflammatory drugs.

Physicochemical In vivo Anti-Inflammatory effect of Tablet containing Fenoprofen

Fenoprofen, a potent nonsteroidal anti-inflammatory drug, is widely used for relief of pain in patients suffering from rheumatic diseases, migraine, sore throat and primary dysmenorrheal. However, this drug has many gastrointestinal side effects produced by its oral administration, such as gastric bleeding and peptic ulcer. These effects were responsible for non-compliance among patients, which ultimately results in treatment failure. The physicochemical properties of Fenoprofen, make it a suitable candidate for transdermal drug delivery, which can overcome the drawbacks of oral administration. In this sense, tablets have been proved to increase the cutaneous absorption of lipophilic drugs when compared to conventional drug delivery systems. The carrageenan test is highly sensitive to nonsteroidal anti-inflammatory drugs and has long been accepted as a useful model to determine the anti-inflammatory effects of natural products. In the present study the anti-inflammatory activity of Fenoprofen and superdisintegrant was investigated by experimental carrageenan animal model. In our study, the induction of carrageenan in the rat hind paw started off the vascular phase of inflammation which was characterized by temporary vasoconstriction and vasodilatation that generated an increase in the size of the edema for all groups.

Synthesis, Anticancer, Antioxidant, Anti-Inflammatory, Antimicrobial Activities, Molecular Docking, and DFT Studies of Sultams Derived from Saccharin.

A series of N-substituted saccharins namely 2-(1,1-dioxido-3-oxobenzo[d]isothiazol-2(3H)-yl) acetonitrile (2) and (alkyl 1,1-dioxido-3-oxobenzo[d]isothiazol-2(3H)-yl) acetate (3a–g) were synthesized, in moderate to excellent yields, from commercially available starting materials by two different approaches and their chemical structures were characterized by spectroscopic techniques (1H-NMR, 13C-NMR, IR, and MS). All the synthesized compounds were evaluated for their anti-inflammatory toward IL-6 and TNF-α, antioxidant, as well as their anticancer activities against hepatic cancer cells. In addition, their anti-fungal and antibacterial activities against both Gram-positive and Gram-negative bacteria were tested. All the tested compounds have exhibited excellent (3a, d, e) to moderate anti-inflammatory activity. Additionally, esters (3b, f) and nitrile (2) showed excellent antioxidant activity. Furthermore, ester 3f, with isopropyl ester, exhibited the highest cytotoxic activity compared to the other esters. Moreover, all compounds were evaluated as selective inhibitors of the human COX-1 enzyme using molecular docking by calculating the free energy of binding, inhibition constant, and other parameters to find out the binding affinity. The molecular study showed that esters (3d, f) and nitrile (2) revealed the highest binding affinities, hence enhancing the inhibition activity with the active site of the COX-1 enzyme. All the tested compounds have more negative Gibbs free, electrostatic, and total intermolecular energies than the standard inhibitor ASA. These results indicate that, all the tested sultams are potent anti-inflammatory drugs as compared to standard inhibitors. Finally, the chemical properties and the quantum factors of synthesized sultams were calculated based on density functional theory (DFT) to predict reactivity, and then correlated with the experimental data. Ester 3f showed the lowest ionization potential and lowest energy gap (Egap = 7.5691 eV), which was correlated with its cytotoxic activity. Furthermore, the spatial electron distribution of HOMO, LUMO were computed and it clearly indicates the electron donation ability of all the tested compounds.

Nanostructured Lipid Carriers for Oral Delivery of a Corticosteroid: Role of Formulation on Biopharmaceutical Performance

Corticosteroids are potent anti-inflammatory and immunosuppressive drugs widely used world-wide for treatment of diverse conditions. However, their use is restricted by their poor bioavailability and high risk-benefit ratio. Therefore, the aim of this study was to develop nanostructred lipid carriers (NLC) of prednisolone acetate (PA) to improve the drug's therapeutic outcome by altering its pharmacokinetic profile and/or allow preferential targeting to inflammatory tissues. PA-loaded NLCs were formulated by solvent injection method using Compritol (solid lipid), oleic acid (liquid lipid) and Tween 80 or Pluronic F68 (surfactant). Formulation conditions, such as liquid lipid concentration, total lipids, drug:lipid ratio and surfactant type were optimized based on particle size (PS), polydispersity index (PDI), and encapsulation efficiency (EE%) results. Optimized formulation was further characterized for its surface morphology, thermal properties, storage stability and anti-inflammatory activity in an animal acute inflammation model. Selected NLCs displayed PS of 170.7 nm, EE% of 67.4%, sustained release over 72 h and good stability for 30 days at refrigeration conditions. PA NLCs displayed superior anti-inflammatory activity of 83.9 ± 4.46% compared to PA suspension (40.5 ± 7.03%) and drug-free NLCs (54.7 ± 6.12%). The current work delineates the potential of NLCs for distinctly improved biopharmaceutical performance of PA.

Synthesis, In Silico, and In Vitro Biological Evaluation of New Furan Hybrid Molecules

Herein, we report the synthesis of new hybrid molecules between furan and N-containing heterocyclic compounds such as pyrrolidine, 1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydroisoquinoline, and piperidine. The obtained compounds were fully characterized using 1H- and 13C-NMR, UV-Vis, and HRMS spectra. All compounds were assessed for their anti-inflammatory, anti-arthritic, antioxidant, reducing power ability, and chelating activity. The less lipophilic molecules H2 (60.1 ± 8.16) and H4 (62.23 ± 0.83) had almost 12 times higher ATA compared with the used ketoprofen (720.57 ± 19.78) standard. The inhibition of albumin denaturation results makes the newly obtained hybrids potential anti-inflammatory drugs, as the expressed values are higher than the ketoprofen standard (126.58 ± 5.00), except H3 (150.99 ± 1.16). All four compounds show significant activity regarding the in vitro biological activities, which makes them great candidates for potential future drugs.

Ivermectin contributes to attenuating the severity of acute lung injury in mice

Ivermectin has been proposed as a potential anti-inflammatory drug in addition to its antiparasitic activity. Here we investigated the potential role of ivermectin in the pathogenesis of acute lung injury (ALI) using the lipopolysaccharide (LPS)- or bleomycin (BLM)-induced mice models. Male C57BL/6 mice were given ivermectin orally every day for the remainder of the experiment at doses of 1 or 2 mg/kg after 24 h of LPS or BLM treatment. Ivermectin reversed severe lung injury caused by LPS or BLM challenge, including mortality, changes in diffuse ground-glass and consolidation shadows on lung CT imaging, lung histopathological scores, lung wet/dry ratio, and protein content in the bronchoalveolar lavage fluid (BALF). Furthermore, ivermectin also reduced total lung BALF inflammatory cells, infiltrating neutrophils, myeloperoxidase activity, and plasma TNF-α and IL-6 levels in mice treated with LPS or BLM. Finally, the mechanism study showed that LPS or BLM administration increased JNK, Erk1/2, and p38 MAPK phosphorylation while decreasing IκBα expression, an inhibitor of NF-κB. However, ivermectin increased IκBα expression but blocked elevated phosphorylated JNK and p38 MAPK, not Erk1/2, in both ALI mice. These findings suggested that ivermectin may alleviate ALI caused by LPS or BLM in mice, partly via lowering the inflammatory response, which is mediated at least by the inhibition of MAPK and NF-κB signaling. Collectively, ivermectin might be used to treat acute lung injury/acute respiratory distress syndrome.

Molecular Modeling of the Spectroscopic, Structural, and Bioactive Potential of Tetrahydropalmatine: Insight from Experimental and Theoretical Approach

Tetrahydropalmatine have been experimentally reported to have promising biological applications, although detailed theoretical investigation on its structural activities regarding its potency as a potential anti-inflammatory drug candidate has not been reported. In that regard, this present work focuses on the experimental and theoretical investigation of tetrahydropalmatine. The studied structure was experimentally isolated followed by detailed theoretical calculations within the framework of density functional theory (DFT) employing the 6-311++G(d,p) basis set. Theoretical and experimental characterization of the structure was observed to agree as different functional groups were analyzed. Molecular electronic properties of the isolated compound were investigated using five different functionals: B3LYP, PBE0, TPSSTPSS, M06-2X, and wB97XD for comparative purposes which present isolated structure to be more reactive at PBE0 and more stable geometry at wB97XD levels of theory. The most intense interaction from perturbation energy analysis was from δ* from PBEO with a stabilization energy of 108120.75 kcal/mol. The anti-inflammatory activity of the studied compound was investigated using the molecular docking simulations from which the results revealed that the proteins with PDB IDs: 4Z69, 5V0V, 6U4X, and 6U5A possess best pose binding affinities of −7.6, −6.8, −6.6 and −6.4 kcal/mol respectively.

Effect of Rumex dentatus on Gastrointestinal Protection and Toxicology in Rodents via Investigating H+/K+-ATPase, Calcium Channels, and PDE Mediated Signaling

This present study aims to delineate Rumex dentatus crude extract (Rd.Cr), n-Hexane, ethyl acetate, aqueous fractions (Rd.n-Hex, Rd.ETAC, and Rd.Aq), and emodin for antidiarrheal, antisecretory effects, anti-spasmodic, gastrointestinal transient time, anti-H. pylori, antiulcer effects, and toxicology. Plant extracts attributed dose-dependent protection against castor oil-induced diarrhea and dose-dependently inhibited intestinal fluid secretions in mice. They decreased the distance transverse by charcoal in the gastrointestinal transit model in rats. In rabbit jejunum preparations, it causes a concentration-dependent relaxation of both spontaneous and K+ (80 mM)-induced contraction, Rd.n-Hex and verapamil were relatively potent against K+-induced contractions and shifted the Ca2+ concentration-response curves (CRCs) to the right, Rd.Cr and Rd.ETAC shifted the isoprenaline-induced inhibitory CRCs to the left, showing potentiating effect similar to papaverine. Rd.n-Hex showed anti-H. pylori effect. Extracts and emodin also show an inhibitory effect against H+/K+-ATPase. Rumex dentatus showed a gastroprotective and antioxidant effect. Histopathological evaluation showed improvement in cellular architecture and decrease in the expression of inflammatory markers such as cyclooxygenase (COX2), tumor necrosis factor (TNF-α), and phosphorylated nuclear factor kappa B (p-NFƙB), validated through immunohistochemistry, ELISA, and western blot techniques. In RT-PCR, it decreases H+/K+-ATPase mRNA levels. Rumex dentatus was analyzed for certain safety aspects and exhibited a relative safety profile as no impairment was observed in kidneys, heart, liver, and brain further assisted by biochemical and hematological analysis. Docking studies revealed that emodin against H+/K+-ATPase pump and voltage gated L-type calcium channel showed E-value of −7.9 and −7.4 kcal/mol, respectively. MD simulations and molecular mechanics Poisson Boltzmann surface area and molecular mechanics Generalized Born surface area MMPBSA/GBSA findings are consistent with the in-vitro, in-vivo, and docking results. In conclusion, Rumex dentatus extracts and its phytoconstituent could be considered a potent antioxidant and anti-inflammatory drug candidates that possess anti-diarrheal, anti-secretary, antispasmodic, anti-H. pylori, and anti-ulcer potential. Toxicity studies were done according to OECD standards 425. It belongs to group 5 (LD50 > 2000 mg/kg), which suggests that it is in the lower toxicity class.

Curcumin loaded hydrogel with anti-inflammatory activity to promote cartilage regeneration in immunocompetent animals

Stable cartilage regeneration in immunocompetent animals remains a huge challenge, mainly ascribing to the in vivo implantation of tissue-engineered cartilage inevitably arousing inflammatory reactions, resulting in cartilage-specific extracellular matrix erosion, chondrogenic niche destruction, and chondrocyte deterioration. Herein, we developed an anti-inflammatory platform, namely, Cur/GelMA hydrogel, by loading a potent anti-inflammatory drug of curcumin (Cur) into gelatin methacryloyl (GelMA) hydrogel. The Cur/GelMA hydrogel exhibited satisfactory Cur release kinetics in vitro and exerted favorable anti-inflammatory effects when cocultured with lipopolysaccharide-induced RAW264.7 macrophages in vitro. Furthermore, the Cur/GelMA hydrogel showed gratifying biocompatibility and supported cartilage regeneration in vitro when colonized with rabbit- and goat-derived chondrocytes. In addition, the in vitro engineered cartilages in the Cur/GelMA hydrogel were able to maintain a cartilaginous phenotype and achieved stable cartilage regeneration when subcutaneously implanted in autologous rabbits and goats for 2 and 4 weeks compared to the GelMA hydrogel. Furthermore, our data revealed that the in vivo-generated cartilage in the Cur/GelMA group apparently alleviated the inflammatory reaction compared to its GelMA counterpart, suggesting that the locally released Cur endowed the Cur/GelMA hydrogel with potent anti-inflammatory capacity. This study provides a reliable anti-inflammatory platform for stable cartilage regeneration in immunocompetent animals, significantly advancing the clinical application of tissue-engineered cartilage.

Aqueous Ginger (Zingiber officinale) Extract Ameliorates the Harmful Effects of High-Dose Lornoxicam in Albino Male Rats.

Lornoxicam is a potent oxicam-class nonsteroidal anti-inflammatory drug (NSAID) with analgesic, anti-inflammatory, and antipyretic effects. Its impacts on many biological functions are not fully understood. We measured various biomarkers in male albino rats provided an oral aqueous ginger extract before IM administration of therapeutic and 2× the therapeutic doses of lornoxicam. The aqueous ginger plant extract was characterized by mass spectroscopy, and its effects were determined by examining free radical scavenging activity, blood parameters, renal and hepatic function, semen quality, proinflammatory cytokines, antioxidant markers, and histopathology. Rats administered lornoxicam had significantly higher liver and kidney function biomarker values, TNF-α, interleukin-6, and sperm abnormalities than the control rats. The overall erythrocyte count, packed cell volume, prostaglandin, and sperm counts were all considerably lower in the experimental animals. Histological changes were found in the liver, spleen, and testes of rats administered lornoxicam alone. In rats, pretreatment with ginger extract reduced the majority of the negative effects of conventional and high dosages of lornoxicam.

Nonsteroidal anti-inflammatory drug exposure and the risk of microscopic colitis

BackgroundMedication consumption has been suggested as a risk factor for microscopic colitis (MC), but studies of varying design have yielded inconsistent results. Our aim was to evaluate the association between medications and MC.MethodsA hybrid cohort of prospectively identified patients undergoing colonoscopy with biopsies for suspicion of MC (N = 144) and patients with MC enrolled within three months of diagnosis into an MC registry (N = 59) were surveyed on medication use. Medication use was compared between patients with and without diagnosis of MC by chi-squared test and binomial logistic regression adjusted for known risk factors of MC: age and gender.ResultsIn total, 80 patients with MC (21 new, 59 registry) were enrolled. Patients with MC were more likely to be older (p = 0.03) and female (p = 0.01) compared to those without MC. Aspirin and other non-steroidal anti-inflammatory drugs were more commonly used among patients who developed MC (p < 0.01). After controlling for age and gender, these medications remained independent predictors of MC with odds ratio for any non-steroidal anti-inflammatory drug use of 3.04 (95% CI: 1.65–5.69). No association between MC and other previously implicated medications including proton pump inhibitors and selective serotonin reuptake inhibitors was found.ConclusionsIn this cohort of patients with chronic diarrhea, we found use of aspirin and non-steroidal anti-inflammatory drugs, but not other implicated medications to be associated with the development of MC. Whether these drugs trigger colonic inflammation in predisposed hosts or worsen diarrhea in undiagnosed patients is unclear. However, we feel that these findings are sufficient to discuss potential non-steroidal anti-inflammatory drug cessation in patients newly diagnosed with MC.

Aspirin attenuates the expression of adhesion molecules, risk of obesity, and adipose tissue inflammation in high-fat diet-induced obese mice

The prevalence of obesity is increasing at an alarming rate and keeps on being one of the significant challenges of this century. Obesity promotes adipose tissue hypertrophy and causes the release of different pro-inflammatory cytokines, playing a significant role in the pathophysiology of metabolic syndrome. Aspirin is known as a potent anti-inflammatory drug, but its role in adipogenesis, adipocyte-specific inflammation, and metabolic syndrome is not well characterized. Thus, in this experiment, we aimed to determine the effect of low-dose aspirin on obesity, obesity-induced inflammation, and metabolic syndrome. High-fat diet-induced obese female mice (Swiss Albino) were used in our study. Mice were fed on a normal diet, a high-fat diet, and a low dose of aspirin (LDA) in the presence of a high-fat diet for 11 weeks. Body weight, lipid profile, adipose tissue size, and inflammatory status were analyzed after that period. The ∆∆CT method was used to calculate the relative mRNA expression of target genes. Treatment with a low dose of aspirin resulted in a significant reduction of body weight, visceral fat mass and serum total cholesterols, serum and adipose tissue triglycerides, and blood glucose levels in high-fat diet-induced obese mice compared to the untreated obese group. Consistent with these biochemical results, a significant reduction in mRNA expression of different genes like PPARγ, GLUT4, IL-6, TNFα, MCP-1, ICAM-I, and VCAM-I associated with adipogenesis and inflammation were noticed. Overall, current study findings indicate that low-dose aspirin reduces obesity, hyperlipidemia, adipocyte-specific inflammation, and metabolic syndrome in high-fat diet-induced obese mice.

Design, characterization and in vivo performance of solid lipid nanoparticles (SLNs)-loaded mucoadhesive buccal tablets for efficient delivery of Lornoxicam in experimental inflammation

Lornoxicam (LRX) is a potent nonsteroidal anti-inflammatory drug (NSAID) used extensively to manage pain and inflammatory conditions. However, the drug possesses poor aqueous solubility (i.e., BCS class II) and a short half-life (3–4 h). Mucoadhesive buccal tablets containing LRX -loaded solid lipid nanoparticles (SLNs) were developed to enhance the drug solubility and bioavailability and achieve a controlled release pattern for a better anti-inflammatory effect. Different LRX-loaded SLNs were prepared using the hot homogenization /ultra-sonication technique and evaluated using size analysis and entrapment efficiency (EE%). Optimized LRX -loaded SLNs formulation showed particle size of 216 ± 7.4 nm, zeta potential of −27.3 ± 4.6 mV, and entrapment efficiency of 92.56 ± 2.3 %. Dried LRX-loaded SLNs alongside mucoadhesive polymers blend (PVP K30 /HPMC K15) were compressed to prepare the mucoadhesive buccal tablets. The tablets showed proper physicochemical properties, good mucoadhesive strength, long mucoadhesive time, suitable pH surface, good swelling capacity, and controlled drug release profile. Furthermore, Fourier transform-infrared (FTIR) spectroscopy, Powder X-Ray diffraction (PXRD), and Scanning electron microscopy (SEM) studies were carried out. The in vivo anti-inflammatory effect of pure LRX, market LRX and optimized mucoadhesive buccal tablet of LRX -loaded SLNs (T3) against carrageenan-induced models were evaluated. T3 showed a significant and early anti-inflammatory response after 1 and 2 h (63.62–77.84 % inhibition) as well as an extended effect after 4 h as compared to pure and market LRX. In parallel, T3 showed the best amelioration of PGE2, COX2, and TNF-α serum levels after 4 h of carrageenan injection.

Kaphaketu Rasa as a Potential Anti-Inflammatory Ayurveda Herbo-Mineral Drug

In the present scenario, people are more prone to various diseases due to poor immunity arising due to lifestyle changes, smoking, and air pollution. Poor lifestyle is responsible for Kapha predominant diseases like Kasa, Shwasa, and other metabolic as well as auto-immune disorders. In Ayurvedic pharmaceutics, Kaphaketu Rasa (KKR) consisting of Aconitum chasmanthum Stapf ex Holmes (Vatsanabha), purified Borax (Tankana), Incinerated Conch shell (Shankha Bhasma), Piper longum Linn., and Zingiber officinale Roxb. Has been indicated for Kapha related diseases. Eight varieties by the name of KKR are documented in Ayurvedic texts. To understand the rationale of mentioning these varieties and to explore the potential areas of its usefulness in contemporary clinical conditions, this study was performed. Information regarding this formulation was collected from the major Ayurveda texts as well as electronic sources for available scientific evidence, commercial availability of the formulation was also checked. The available data supports its use as a potent Kapha pacifying formulation whereas scientific evidence supports its action as an anti-inflammatory, analgesic, antipyretic, antispasmodic, anti-allergic as well as mucolytic agent. However, this formulation needs to be studied through animal and clinical studies to understand and explore its mode of action, drug interactions, dose-response relationships, adverse reactions, etc., in different clinical conditions.

Lornoxicam-Loaded Cubosomes: - Preparation and In vitro Characterization.

Cubosomes are nanosized structures self-assembled nanostructured materials used for controlling the release of the entrapped drug molecule. Lornoxicam (LXM) is a potent analgesic nonsteroidal anti-inflammatory (NSAID) drug with a short half-life (3-4) hours. The present study aims to prepare LXM-loaded cubosomes with well-defined morphology, particle size, PDI, high entrapment efficiency, sustained drug release, and high zeta potential value, as a transdermal drug delivery system.&#x0D; Twelve formulas of LXM-loaded cubosomal dispersions were prepared by a solvent dilution method using Glyceryl monooleate ( GMO) as polar lipid with different stabilizers as Pluronic® F127 or tween 80 and different types of hydrotrope as ethanol or propylene glycol. These formulas were evaluated for their particle size analysis &amp; PDI, E.E. %, and in-vitro drug release to select a group of the optimum formulas, that further characterized by transmission electron microscopy (TEM) and zeta potential analyzer to select the optimum dispersion. FTIR study was used to investigate the compatibility of the drug with excipients.&#x0D; The obtained results indicated that F3, composed of GMO, Pluronic® F127, ethanol, drug, and phosphate buffer solution pH 7.4 in the following per cents 7.28%, 1.82%, 8%, 2%, and 80.9% w/w, respectively, prepared in 20min agitation period, as the optimum formula for its high E.E. % (94.30±0.002%), small particle size (16.3±0.19nm), low PDI (0.06±0.02), and high zeta potential value (-65.9±0.05mV), and well-defined cubic structure. FTIR study indicated no interaction between LXM and other formulas components.&#x0D; This study's conclusion illustrated that LXM-loaded cubosomal dispersion could be considered a promising nano-carrier for transdermal drug delivery.

Commentary for “antagonizing urotensin receptor is a novel therapeutic strategy for glucocorticoid‐induced skeletal muscle atrophy”

In 1950, the discovery of the glucocorticoid cortisone was awarded the Nobel Prize in Physiology and Medicine. Since then, glucocorticoids have been a mainstay in clinical practice. Endogenous glucocorticoids like cortisone are natural hormones released in response to stress or circadian stimuli, whereas synthetic glucocorticoids like dexamethasone are used as potent anti-inflammatory drugs. While synthetic glucocorticoids are the mainstay treatments for many clinical conditions, their chronic daily intake also induces a plethora of concerning adverse effects, including muscle loss. The debilitating effects of chronic daily glucocorticoids in muscle are generally evident quite rapidly and compromise muscle mass, structure and strength in the long term. Glucocorticoid-induced muscle wasting correlates with increased protein catabolism, muscle mass decrease and inhibition of endogenous regenerative potential.1, 2 The neuropeptide urotensin II (UII) and its receptor, UII receptor, are expressed in a variety of tissues, including the skeletal muscle. Impaired regulation of UII and UII receptor have been associated with various pathologies.3 Of relevance for this study, prior studies had reported on the correlation between UII and muscle atrophy and on the finding that UII promotes loss of muscle weight and strength.4 In the study published here, Yin et al., show a novel approach in which a UII receptor antagonist rescues the glucocorticoid-induced skeletal muscle atrophy in mice. The study reports a potentially clinically relevant effect of Palosuran, a potent and selective antagonist of the UII receptor, in preventing dexamethasone-induced muscle atrophy. This experimental study has a huge potential and, if confirmed in clinical studies, could alleviate the muscle wasting experienced by the many people who take glucocorticoids regularly. Though this is the first report using this drug to counteract muscle atrophy, Palosuran has been largely investigated in the context of kidney function, particularly diabetic nephropathy. Experimental studies in rodents have reported on the potential role of UII receptor antagonists in alleviating renal complications in diabetes.5 However, initial clinical studies in humans have provided mixed results with this drug in the treatment of diabetic nephropathy.6, 7 In the study presented here, the Authors investigate a novel context for this drug and detail a large set of compelling experiments to elucidate the muscle atrophy counteraction by Palosuran. Importantly, their pharmacological experiments were complemented by analyses in a transgenic mouse with body-wide germline knockout of the UII receptor gene. Taken together, the findings reported in this study show that UII antagonism improves muscle mass and function in the context of dexamethasone-induced muscle wasting. Several limitations and open questions need further discussion. While inhibition of the UII axis through UII receptor antagonists has shown promising results in experimental animals, a potent and safe antagonist that can be used in humans is yet to be found. While the results by Yin et al, are promising, additional mechanistic and clinical studies are needed to support the novel indication of Palosuran for glucocorticoid-induced muscle loss. For instance, the experiments presented here should be investigated in disease models where chronic glucocorticoid intake is the mainstay treatment. Moreover, many tissues in the body express the UII receptor and therefore a thorough evaluation of toxicity and off-target effects of UII antagonist regimens is warranted. Additionally, it should also be evaluated if Palosuran alters or interacts with the anti-inflammatory action of glucocorticoid drugs. The results presented in this study depict a rather convincing effect of Palosuran on counteracting the loss of muscle mass and strength. However, the study did not address the effects of UII signalling and its counteraction on individual myofiber types, particularly type 2A, 2B and 2X. Moreover, the effects of UII axis activation versus inhibition on muscle bioenergetics remain unknown. Nevertheless, the rich dataset presented in this study supports the novel idea of repurposing UII antagonists to treat or prevent glucocorticoid-induced muscle atrophy. This is a significant advancement not only to potentially reduce the iatrogenic burden of synthetic glucocorticoids but also to further decipher their multifaceted action in health and disease. Drs. Prabakaran, Panta and Quattrocelli contributed to the preparation and collection of original literatures and figures and the writing and editing of manuscript. Drs. Prabakaran, Panta and Quattrocelli were responsible for the structural designs, scientific quality and writing. Not applicable. This work was supported by the following grant support: NIH grants DK121875 (MQ), HL158531 (MQ); CCHMC grants Trustee Award (MQ), Heart Institute Translational Grant (MQ). The authors declare no conflict of interest. The paper was handled by editors and has undergone a rigorous peer-review process. Dr. Mattia Quattrocelli was not involved in the journal's review of/or decisions related to this manuscript. Not applicable. Data sharing is not applicable to this article as no new data were created or analyzed in this study.