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Background: Childhood obesity is a growing concern, and non-alcoholic fatty liver disease (NAFLD) is a significant consequence. Currently, there are no approved drugs to treat NAFLD in children. However, a recent study explored the potential of vitamin E enriched with tocotrienol (TRF) as a powerful antioxidant for NAFLD. The aims of the present study were to investigate the effectiveness and safety of TRF in managing children with obesity and NAFLD. Methods: A total of 29 patients aged 10 to 18 received a daily oral dose of 50 mg TRF for six months (January 2020 to February 2022), and all had fatty liver disease were detected by ultrasonography and abnormally high alanine transaminase levels (at least two-fold higher than the upper limits for their respective genders). Various parameters, including biochemical markers, FibroScan, LiverFASt, DNA damage, and cytokine expression, were monitored. Results: APO-A1 and AST levels decreased significantly from 1.39 ± 0.3 to 1.22 ± 0.2 g/L (P = 0.002) and from 30 ± 12 to 22 ± 10 g/L (P = 0.038), respectively, in the TRF group post-intervention. Hepatic steatosis was significantly reduced in the placebo group from 309.38 ± 53.60 db/m to 277.62 ± 39.55 db/m (p = 0.048), but not in the TRF group. Comet assay analysis showed a significant reduction in the DNA damage parameters in the TRF group in the post-intervention period compared to the baseline, with tail length decreasing from 28.34 ± 10.9 to 21.69 ± 9.84; (p = 0.049) and with tail DNA (%) decreasing from 54.13 ± 22.1to 46.23 ± 17.9; (p = 0.043). Pro-inflammatory cytokine expression levels were significantly lower in the TRF group compared to baseline levels for IL-6 (2.10 6.3 to 0.7 1.0 pg/mL; p = 0.047 pg/mL) and TNF-1 (1.73 5.5 pg/mL to 0.7 0.5 pg/mL; p = 0.045). Conclusion: The study provides evidence that TRF supplementation may offer a risk-free treatment option for children with obesity and NAFLD. The antioxidant and anti-inflammatory properties of TRF offer a promising adjuvant therapy for NAFLD treatment. In combination with lifestyle modifications such as exercise and calorie restriction, TRF could play an essential role in the prevention of NAFLD in the future. However, further studies are needed to explore the long-term effects of TRF supplementation on NAFLD in children. Trial registration: The study has been registered with the International Clinical Trial Registry under reference number (NCT05905185) retrospective registration on (15/06/2023). [ABSTRACT FROM AUTHOR]

The development of targeted drug delivery systems has been a pivotal area in nanomedicine, addressing challenges like low drug loading capacity, uncontrolled release, and systemic toxicity. This study aims to develop and evaluate dual-functionalized mesoporous silica nanoparticles (MSN) for targeted delivery of celecoxib, enhancing drug loading, achieving controlled release, and reducing systemic toxicity through amine grafting and imidazolyl polyethyleneimine (PEI) gatekeepers. MSN were synthesized using the sol–gel method and functionalized with (3-aminopropyl) triethoxysilane (APTES) to create amine-grafted MSN (MSN-NH2). Celecoxib was loaded into MSN-NH2, followed by conjugation of imidazole-functionalized PEI (IP) gatekeepers synthesized via carbodiimide coupling. Characterization was conducted using Fourier-transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (1H-NMR). Drug loading capacity, entrapment efficiency, and in vitro drug release at pH 5.5 and 7.4 were evaluated. Cytotoxicity was assessed using the MTT assay on RAW 264.7 macrophages. The synthesized IP was confirmed by FTIR and 1H-NMR. Amine-grafted MSN demonstrated a celecoxib loading capacity of 12.91 ± 2.02%, 2.1 times higher than non-functionalized MSN. In vitro release studies showed pH-responsive behavior with significantly higher celecoxib release from MSN-NH2-celecoxib-IP at pH 5.5 compared to pH 7.4, achieving a 33% increase in release rate within 2 h. Cytotoxicity tests indicated significantly higher cell viability for IP-treated cells compared to PEI-treated cells, confirming reduced toxicity. The dual-functionalization of MSN with amine grafting and imidazolyl PEI gatekeepers enhances celecoxib loading and provides controlled pH-responsive drug release while reducing systemic toxicity. These findings highlight the potential of this advanced drug delivery system for targeted anti-inflammatory and anticancer therapies. [ABSTRACT FROM AUTHOR]

Abstract Background Childhood obesity is a growing concern, and non-alcoholic fatty liver disease (NAFLD) is a significant consequence. Currently, there are no approved drugs to treat NAFLD in children. However, a recent study explored the potential of vitamin E enriched with tocotrienol (TRF) as a powerful antioxidant for NAFLD. The aims of the present study were to investigate the effectiveness and safety of TRF in managing children with obesity and NAFLD. Methods A total of 29 patients aged 10 to 18 received a daily oral dose of 50 mg TRF for six months (January 2020 to February 2022), and all had fatty liver disease were detected by ultrasonography and abnormally high alanine transaminase levels (at least two-fold higher than the upper limits for their respective genders). Various parameters, including biochemical markers, FibroScan, LiverFASt, DNA damage, and cytokine expression, were monitored. Results APO-A1 and AST levels decreased significantly from 1.39 ± 0.3 to 1.22 ± 0.2 g/L (P = 0.002) and from 30 ± 12 to 22 ± 10 g/L (P = 0.038), respectively, in the TRF group post-intervention. Hepatic steatosis was significantly reduced in the placebo group from 309.38 ± 53.60 db/m to 277.62 ± 39.55 db/m (p = 0.048), but not in the TRF group. Comet assay analysis showed a significant reduction in the DNA damage parameters in the TRF group in the post-intervention period compared to the baseline, with tail length decreasing from 28.34 ± 10.9 to 21.69 ± 9.84; (p = 0.049) and with tail DNA (%) decreasing from 54.13 ± 22.1to 46.23 ± 17.9; (p = 0.043). Pro-inflammatory cytokine expression levels were significantly lower in the TRF group compared to baseline levels for IL-6 (2.10 6.3 to 0.7 1.0 pg/mL; p = 0.047 pg/mL) and TNF-1 (1.73 5.5 pg/mL to 0.7 0.5 pg/mL; p = 0.045). Conclusion The study provides evidence that TRF supplementation may offer a risk-free treatment option for children with obesity and NAFLD. The antioxidant and anti-inflammatory properties of TRF offer a promising adjuvant therapy for NAFLD treatment. In combination with lifestyle modifications such as exercise and calorie restriction, TRF could play an essential role in the prevention of NAFLD in the future. However, further studies are needed to explore the long-term effects of TRF supplementation on NAFLD in children. Trial registration The study has been registered with the International Clinical Trial Registry under reference number (NCT05905185) retrospective registration on (15/06/2023).

Abstract Because of the great pharmacological and industrial significance of 1,3,4-thiadiazole and its related compounds, researchers are still very interested in them. For this reason, in this study, we looked at ways to create new hybrid compounds containing carboxamide and 1,3,4-thiadiazole moieties. The thioxoacetamide derivatives used to make these compounds were reacted with various alkylated reagents to produce multiple S-alkyl groups. Additionally, these compounds were reacted with aldehydes to form novel derivatives known as 5-(substituent)-N-phenyl-1,3,4-thiadiazole-2-carboxamide. Here, we used the agar well diffusion method to examine the antibacterial activity of all the produced compounds against a few pathogenic bacteria that were resistant to multiple drugs. Additionally, look into their capacity to lower inflammation through the use of bovine serum albumin in the protein denaturation procedure. The substances were characterized by spectral analysis (IR, 1HNMR, 13CNMR and Elemental Analysis), and efficient as antibacterial agents against all the tested bacterial strains, except for Escherichia coli. Compounds 4a and 8c showed the highest level of inhibition zone against Gram-positive bacteria (Staph. aureus, Bacillus subtilis) at concentration 0.3, 0.4 and 0.5 mg/ml compared with ciprofloxacin at the same concentrations. The results demonstrated that every compound has significant anti-inflammatory activity. At a concentration of 250 µg/ml, compounds 3a, 4c and 8c had the highest percentage inhibition of protein denaturation when (83.24%, 86.44% and 85.14%, respectively) compared to other compounds and diclofenac sodium as reference drug. Comparing compounds 4c and 8c to ciprofloxacin and diclofenac sodium, they showed powerful antibacterial and anti-inflammatory action. Furthermore, an investigation using molecular docking against DHPS from S. aureus (PDB ID: 6CLV) showed a strong connection with the intended protein and an elevated docking score, making it a prime candidate for antibiotics.

Abstract Chronic non-communicable diseases (CNCDs) pose a significant public health challenge. Addressing this issue, there has been a notable breakthrough in the prevention and mitigation of NCDs through the use of antioxidants and anti-inflammatory agents. In this study, we aim to explore the effectiveness of Eupatorium adenophora Spreng leaves (EASL) as an antioxidant and anti-inflammatory agent, and its potential applications. To construct a cellular model of oxidative damage and inflammation, Caco-2 cells were treated with tert-butyl hydroperoxide (t-BHP). The biocompatibility of EASL-AE with Caco-2 cells was assessed using the MTT assay, while compatibility was further verified by measuring LDH release and the protective effect against oxidative damage was also assessed using the MTT assay. Additionally, we measured intracellular oxidative stress indicators such as ROS and 8-OHdG, as well as inflammatory pathway signalling protein NFκB and inflammatory factors TNF-α and IL-1β using ELISA, to evaluate the antioxidant and anti-inflammatory capacity of EASL-AE. The scavenging capacity of EASL-AE against free radicals was determined through the DPPH Assay and ABTS Assay. Furthermore, we measured the total phenolic, total flavonoid, and total polysaccharide contents using common chemical methods. The chemical composition of EASL-AE was analyzed using the LC–MS/MS technique. Our findings demonstrate that EASL-AE is biocompatible with Caco-2 cells and non-toxic at experimental levels. Moreover, EASL-AE exhibits a significant protective effect on Caco-2 cells subjected to oxidative damage. The antioxidant effect of EASL-AE involves the scavenging of intracellular ROS, while its anti-inflammatory effect is achieved by down-regulation of the NFκB pathway. Which in turn reduces the release of inflammatory factors TNF-α and IL-1β. Through LC–MS/MS analysis, we identified 222 compounds in EASL-AE, among which gentianic acid, procaine and L-tyrosine were the compounds with high antioxidant capacity and may be the effective constituent for EASL-AE with antioxidant activity. These results suggest that EASL-AE is a natural and high-quality antioxidant and anti-inflammatory biomaterial that warrants further investigation. It holds great potential for applications in healthcare and other related fields.

Because of the great pharmacological and industrial significance of 1,3,4-thiadiazole and its related compounds, researchers are still very interested in them. For this reason, in this study, we looked at ways to create new hybrid compounds containing carboxamide and 1,3,4-thiadiazole moieties. The thioxoacetamide derivatives used to make these compounds were reacted with various alkylated reagents to produce multiple S-alkyl groups. Additionally, these compounds were reacted with aldehydes to form novel derivatives known as 5-(substituent)-N-phenyl-1,3,4-thiadiazole-2-carboxamide. Here, we used the agar well diffusion method to examine the antibacterial activity of all the produced compounds against a few pathogenic bacteria that were resistant to multiple drugs. Additionally, look into their capacity to lower inflammation through the use of bovine serum albumin in the protein denaturation procedure. The substances were characterized by spectral analysis (IR, 1HNMR, 13CNMR and Elemental Analysis), and efficient as antibacterial agents against all the tested bacterial strains, except for Escherichia coli. Compounds 4a and 8c showed the highest level of inhibition zone against Gram-positive bacteria (Staph. aureus, Bacillus subtilis) at concentration 0.3, 0.4 and 0.5 mg/ml compared with ciprofloxacin at the same concentrations. The results demonstrated that every compound has significant anti-inflammatory activity. At a concentration of 250 µg/ml, compounds 3a, 4c and 8c had the highest percentage inhibition of protein denaturation when (83.24%, 86.44% and 85.14%, respectively) compared to other compounds and diclofenac sodium as reference drug. Comparing compounds 4c and 8c to ciprofloxacin and diclofenac sodium, they showed powerful antibacterial and anti-inflammatory action. Furthermore, an investigation using molecular docking against DHPS from S. aureus (PDB ID: 6CLV) showed a strong connection with the intended protein and an elevated docking score, making it a prime candidate for antibiotics. [ABSTRACT FROM AUTHOR]

Edema is a reliable parameter to evaluate the anti-inflammatory process. Noni (Morinda citrifolia L.) fruit has been shown to decrease inflammation. However, studies on the impact of noni juice on gastric mucosal injury are still limited. Thus, the current study aimed to assess the effect of noni fruit juice as an anti-inflammatory agent in rat paw edema and gastric mucosal injury. The rats were divided into five groups such as control, carrageenan only, carrageenan and diclofenac sodium, carrageenan and 90% noni, and carrageenan + 100% noni. Paw edema was measured, and histopathological examination of the gastric tissues was performed. The administration of noni juice significantly reduced paw edema in the carrageenan + 90% noni and carrageenan + 100% noni groups of rats. Compared to the carrageenan + diclofenac sodium group, the carrageenan + 90% noni and carrageenan + 100% noni groups were not significantly different in reducing paw edema. It suggests that the administration of noni juice can reduce paw edema with the same potential as diclofenac sodium. Gastric mucosal injury in the carrageenan + diclofenac sodium group (scores 2 to 3) was higher than in the carrageenan + 90% noni and carrageenan + 100% noni groups (scores 1 to 2), both of them had significant differences (p [ J Adv Biotechnol Exp Ther 2024; 7(3.000): 498-506]

Introduction: Asthma is a condition of airflow limitation, common throughout the world, with high mortality rates, especially as it still faces some obstacles in its management. As it constitutes a public health challenge, this study aimed to investigate the effect of copaiba oil (e.g., Copaifera langsdorffii), as a treatment resource, at doses of 50 and 100 mg/kg on certain mediators of acute lung inflammation (IL-33, GATA3, FOXP3, STAT3, and TBET) and early mechanisms of lung remodeling (degradation of elastic fiber tissues, collagen deposition, and goblet cell hyperplasia). Methods: Using an ovalbumin-induced acute allergic asthma model in BALB/c mice, we analyzed the inflammatory mediators through immunohistochemistry and the mechanisms of lung remodeling through histopathology, employing orcein, Masson's trichrome, and periodic acid-Schiff staining. Results: Copaiba oil treatment (CO) reduced IL-33 and increased FOXP3 by stimulating the FOXP3/GATA3 and FOXP3/STAT3 pathways. Additionally, it upregulated TBET, suggesting an additional role in controlling GATA3 activity. In the respiratory epithelium, CO decreased the fragmentation of elastic fibers while increasing the deposition of collagen fibers, favoring epithelial restructuring. Simultaneously, CO reduced goblet cell hyperplasia. Discussion: Although additional research is warranted, the demonstrated antiinflammatory and re-epithelializing action makes CO a viable option in exploring new treatments for acute allergic asthma. [ABSTRACT FROM AUTHOR]

Introduction: Obesity is known to lead to the development of metabolic disorders and Erythrina subumbrans (Hassk.) Merr has shown the potential in alleviating some diseases. This study aimed to assess the anti-obesity activity of the ethanol extract of E. subumbrans leaves (EES) in obese Wistar albino rats. Methods: The rats were randomly assigned to eight groups (n = 5): normal group (no obesity inducement, treated with standard feed); high fructose (60%)-induced obesity (obesity induced, no treatment); control-1 group (obesity-induced, treated with orlistat 10.8 mg/kg BW); control-2 group (obesity-induced, treated with Isprinol 45 mg/kg); control-3 group (obesity-induced, treated with metformin 45 mg/kg); three test groups (obesity-induced, treated with EES 100, 200, and 400 mg/kg, respectively). The obesity inducement was conducted for 7 weeks. The rats were observed for body weight (BW), feed residue, feces index, triglycerides, organ index, and leucocyte profile. Results: The screening for secondary metabolites in EES revealed the presence of flavonoids, alkaloids, saponins, polyphenols, and tannins. EES decreased the percentage of BW gain, appetite, organ index (spleen), total fat, triglycerides, and leucocyte profile of the rats. Conclusion: The ethanol extract of the leaves of E. subumbrans has the potential to be developed as an anti-obesity agent, although the molecular mechanism of its pathway modulation is still unknown.

Phlomoides (L.) Moench belongs to the Lamiaceae family. It has recently undergone significant changes in taxonomy, with many species from Eremostachys and Phlomis added to the genus. The aforementioned species were studied in terms of morphological and phytochemical systematics. Species of Phlomoides are distinguished from Phlomis by their densely bearded upper corolla lip and nutlet. However, Eremostachys and Phlomoides have a lot in common morphologically. Plant chemosystematics present iridoids, phenylethanoids, and furanolabdanes as dominant constituents of Phlomoides species. Long-term traditional uses, such as bone fracture therapy, local analgesic, and wound healing actions, pique researchers' interest in these plants. The species and their secondary metabolites have been implicated in drug discovery by their anti-inflammatory and bone-development properties in vitro, in vivo, and clinically. A review of the taxonomic status based on phytochemical and morphological characteristics, as well as the clinical importance of the Phlomoides genus, is presented in the current study to provide a basis for further investigations.

Pei-Chi Lee,1,* Cun-Zhao Li,2,* Chun-Te Lu,3,4,* Min-Han Zhao,2 Syu-Ming Lai,2 Man-Hua Liao,5 Cheng-Liang Peng,6 Hsin-Tung Liu,1 Ping-Shan Lai2 1xTrans Corporate Research and Innovation Center, Taipei City, Taiwan; 2Department of Chemistry, National Chung Hsing University, Taichung, Taiwan; 3Division of Plastic and Reconstructive Surgery, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan; 4Institute of Medicine, School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 5Graduate Institute of Biotechnology, National Chung Hsing University, Taichung, Taiwan; 6Isotope Application Division, National Atomic Research Institute, Taoyuan, Taiwan*These authors contributed equally to this workCorrespondence: Ping-Shan Lai, Department of Chemistry, National Chung Hsing University, No. 145, Xingda Road, Taichung, 402, Taiwan, Tel +886-4-22840411 ext. 428, Fax +886-4-22862547, Email pslai@email.nchu.edu.twPurpose: Larger nanoparticles of bioactive compounds deposit high concentrations in follicular ducts after skin penetration. In this study, we investigated the effects of microcurrent cloth on the skin penetration and translocation of large nanoparticle applied for wound repair applications.Methods: A self-assembly of curcumin-loaded micelles (CMs) was prepared to improve the water solubility and transdermal efficiency of curcumin. Microcurrent cloth (M) was produced by Zn/Ag electrofabric printing to facilitate iontophoretic transdermal delivery. The transdermal performance of CMs combined with M was evaluated by a transdermal system and confocal microscopy. The CMs/iontophoretic combination effects on nitric oxide (NO) production and inflammatory cytokines were evaluated in Raw 264.7 cells. The wound-healing property of the combined treatment was assessed in a surgically created full-thickness circular wound mouse model.Results: Energy-dispersive X-ray spectroscopy confirmed the presence of Zn/Ag on the microcurrent cloth. The average potential of M was measured to be +214.6 mV in PBS. Large particle CMs (CM-L) prepared using surfactant/cosurfactant present a particle size of 142.9 nm with a polydispersity index of 0.319. The solubility of curcumin in CM-L was 2143.67 μg/mL, indicating 250-fold higher than native curcumin (8.68 μg/mL). The combined treatment (CM-L+M) demonstrated a significant ability to inhibit NO production and increase IL-6 and IL-10 secretion. Surprisingly, microcurrent application significantly improved 20.01-fold transdermal performance of curcumin in CM-L with an obvious escape of CM-L from follicular ducts to surrounding observed by confocal microscopy. The CM-L+M group also exhibited a better wound-closure rate (77.94% on day 4) and the regenerated collagen intensity was approximately 2.66-fold higher than the control group, with a closure rate greater than 90% on day 8 in vivo.Conclusion: Microcurrent cloth play as a promising iontophoretic transdermal drug delivery accelerator that enhances skin penetration and assists CMs to escape from follicular ducts for wound repair applications.Keywords: Zn/Ag electrofabrics, iontophoretic, self-assembly, anti-inflammatory agent, skin penetration, drug delivery

This novel study identifies the effective anti-inflammatory phenolic compounds in dandelion and provides mechanistic insights into their interactions with receptor proteins (toll‐like receptor 4, TLR4; co‐receptor myeloid differentiation protein-2, MD-2) using UHPLC-ESI-MS/MS, lipopolysaccharide (LPS)-stimulated THP-1 cell line, fluorescence quenching and anisotropy, molecular docking (single ligand and multi-ligand docking) and molecular dynamics simulation. A 50 % aqueous methanol extract had a greater anti-inflammatory effect and higher chicoric acid content, compared with the 100 % water and 100 % methanol extracts. Chicoric acid, chlorogenic acid, methylophiopogonone A, caffeic acid, gallic acid monohydrate and 4'-O-demethylbroussonin A had relatively high binding energies and contents in all extracts. Chicoric acid competed with chlorogenic acid, 4'-O-demethylbroussonin A and quercetin for MD-2. Among dandelion’s phenolics, chicoric acid most effectively hindered TLR4-MD-2 complex formation, with a quenching constant of 0.62 × 106 L/mol for MD-2 or TLR4 at 320 K, and binding energies of –6.87 and –5.97 kcal/mol, respectively, for MD-2 and TLR4.

Ischemia-reperfusion injury (IRI) is an extremely complicated pathophysiological process, which may occur during the process of myocardial infarction, stroke, organ transplantation and temporary interruption of blood flow during surgery, etc. As key molecules of immune system, macrophages play a vital role in the pathogenesis of IRI. M1 macrophages are pro-inflammatory cells and participate in the elimination of pathogens. M2 macrophages exert anti)inflammatory effect and participate in tissue repair and remodeling and extracellular matrix remodeling. The balance between macrophage phenotypes is of significance for the outcome and treatment of IRI. This article reviewed the role of macrophages in IRI, including the balance between M1/M2 macrophage phenotype, the mechanism of infiltration and recruitment into different ischemic tissues. In addition, the potential therapeutic strategies of targeting macrophages during IRI were also discussed, aiming to provide reference for alleviating IRI and promoting tissue repair. [ABSTRACT FROM AUTHOR]

Dry eye is a common chronic and multifactorial ocular surface disease, seriously affects patients’ quality of life and even vision. Owning to its high prevalence, complicated pathophysiology, prolonged treatment cycle, dry eye has become an important social public problem. Currently, drug therapy for dry eye mainly includes tear substitutes therapy, anti-inflammatory therapy and targeted antibacterial therapy. However, there remains unmet needs in clinical treatment. In recent years, with the insightful research on the pathogenesis of dry eye, advanced progress has been achieved in the research of dry eye agents at home and abroad, with a variety of new anti-inflammatory agent, antioxidants agent and tear film stability drugs coming into view. It should be noted that there is still a lot to explore in the research and development of dry eye drugs, especially for mild and moderate dry eye treatment. Ophthalmologists and researchers should be fully aware of and keep updated on the research progress of new medications for dry eye, in order to better serve the patients. [ABSTRACT FROM AUTHOR]

Introduction: Asthma is a condition of airflow limitation, common throughout the world, with high mortality rates, especially as it still faces some obstacles in its management. As it constitutes a public health challenge, this study aimed to investigate the effect of copaiba oil (e.g., Copaifera langsdorffii), as a treatment resource, at doses of 50 and 100 mg/kg on certain mediators of acute lung inflammation (IL-33, GATA3, FOXP3, STAT3, and TBET) and early mechanisms of lung remodeling (degradation of elastic fiber tissues, collagen deposition, and goblet cell hyperplasia).Methods: Using an ovalbumin-induced acute allergic asthma model in BALB/c mice, we analyzed the inflammatory mediators through immunohistochemistry and the mechanisms of lung remodeling through histopathology, employing orcein, Masson’s trichrome, and periodic acid-Schiff staining.Results: Copaiba oil treatment (CO) reduced IL-33 and increased FOXP3 by stimulating the FOXP3/GATA3 and FOXP3/STAT3 pathways. Additionally, it upregulated TBET, suggesting an additional role in controlling GATA3 activity. In the respiratory epithelium, CO decreased the fragmentation of elastic fibers while increasing the deposition of collagen fibers, favoring epithelial restructuring. Simultaneously, CO reduced goblet cell hyperplasia.Discussion: Although additional research is warranted, the demonstrated anti-inflammatory and re-epithelializing action makes CO a viable option in exploring new treatments for acute allergic asthma.

Background: The management of kidney injuries remains a big challenge and there is an urgent need to explore novel and alternative therapeutic strategies. Methods: The current study focused on the evaluation for the first time of the possible nephroprotective activity of the hydro-alcoholic extract (HE) and supernatant fraction (SUP) of Anogeissus leiocarpus roots against potassium dichromate (K2Cr2O7) induced nephrotoxicity in rats. The renal function parameters, the oxidative stress biomarkers in the nephrotoxic rats induced by the injection of a single dose (15 mg/kg, sc.) of K2Cr2O7, meanwhile treated orally with the HE (500 mg/kg/day) or SUP (100 mg/kg/day) were evaluated. The antioxidant activity was also evaluated in ex vivo and the in vitro anti-inflammatory activity was carried out. Results: The K2Cr2O7-induced nephrotoxicity was evident by the disturbance in the levels of the renal parameters such as urea, creatinine, proteins, electrolytes and the induction of oxidative stress. The majority of the renal parameters were significantly restored when the HE and SUP were administered to the nephrotoxic rats. Remarkably, in vivo the extracts significantly alleviated the oxidative stress by enhancing the antioxidant levels (GSH and CAT), and by lowering the MDA level as well as in ex vivo. Furthermore in vitro, the extracts exhibited a strong anti-inflammatory effect. Conclusion: The promising capacity of the HE and SUP to alleviate the K2Cr2O7-induced nephrotoxicity is mainly due to their antioxidant and anti-inflammatory activities.

Introduction: Naproxen is effective for various musculoskeletal conditions and has a longer half-life, making it a favourable choice for sustained relief. Additionally, there is a potential unmet need for guidelines on the usage of topical Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in the Asia-Pacific region. A study on naproxen 10% gel aims to address this need and increase awareness of its therapeutic potential in the region. Aim: To assess the efficacy and safety of naproxen 10% gel in relieving pain associated with lower back, knee, cervical, synovitis, bursitis, muscle sprain, and tendinitis. Materials and Methods: This prospective, cohort, observational, open-label, single-arm, multicentric study was conducted at 458 centres in India, including Ahmedabad, Bengaluru, Chandigarh, Chennai, Delhi, Guwahati, Hyderabad, Indore, Jaipur, Kolkata, Lucknow, Meerut, Mumbai, Patna, and Pune, between February 2023 and May 2023. The data was collected from outpatient settings/clinics of orthopaedicians and clinicians who have been prescribing topical naproxen 10% gel to their patients. The study included patients aged 18 to 60 years of either sex who were suffering from back pain, muscle pain, sprains, frozen shoulder, arthritis, acute low back ache (non-specific), or pain. The data was captured during the scheduled follow-up visits planned by the treating clinician, with data recorded at 3, 5, 10, and 15 days. At the baseline visit, demographic details (age, sex, weight, height, body mass index, and symptoms), Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale score, pain intensity on movement score, Visual Analogue Scale (VAS), and overall pain score were obtained. Results: Out of 10,587 patients, 10,265 completed the present study. The majority of patients had lower back pain (n=3386, 32.99%) and knee pain (n=3184, 31.02%). The average pain intensity on movement score of patients with bursitis significantly decreased from the baseline to 15 days {mean change {95% Confidence Interval (CI)}: 6.04 (5.89, 6.20); p

The development of targeted drug delivery systems has been a pivotal area in nanomedicine, addressing challenges like low drug loading capacity, uncontrolled release, and systemic toxicity. This study aims to develop and evaluate dual-functionalized mesoporous silica nanoparticles (MSN) for targeted delivery of celecoxib, enhancing drug loading, achieving controlled release, and reducing systemic toxicity through amine grafting and imidazolyl polyethyleneimine (PEI) gatekeepers. MSN were synthesized using the sol–gel method and functionalized with (3-aminopropyl) triethoxysilane (APTES) to create amine-grafted MSN (MSN-NH2). Celecoxib was loaded into MSN-NH2, followed by conjugation of imidazole-functionalized PEI (IP) gatekeepers synthesized via carbodiimide coupling. Characterization was conducted using Fourier-transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (1H-NMR). Drug loading capacity, entrapment efficiency, and in vitro drug release at pH 5.5 and 7.4 were evaluated. Cytotoxicity was assessed using the MTT assay on RAW 264.7 macrophages. The synthesized IP was confirmed by FTIR and 1H-NMR. Amine-grafted MSN demonstrated a celecoxib loading capacity of 12.91 ± 2.02%, 2.1 times higher than non-functionalized MSN. In vitro release studies showed pH-responsive behavior with significantly higher celecoxib release from MSN-NH2-celecoxib-IP at pH 5.5 compared to pH 7.4, achieving a 33% increase in release rate within 2 h. Cytotoxicity tests indicated significantly higher cell viability for IP-treated cells compared to PEI-treated cells, confirming reduced toxicity. The dual-functionalization of MSN with amine grafting and imidazolyl PEI gatekeepers enhances celecoxib loading and provides controlled pH-responsive drug release while reducing systemic toxicity. These findings highlight the potential of this advanced drug delivery system for targeted anti-inflammatory and anticancer therapies.

Background: Melatonin is an indoleamine hormone secreted by the pineal gland at night and has an essential role in regulating human circadian rhythms (the internal 24-h clock) and sleep-wake patterns. However, it has recently gained considerable attention for its demonstrated ability in disease management. This review discusses the major biological activities of melatonin, its metabolites as nutritional supplements, and its bioavailability in food sources. Methods: The information acquisition process involved conducting a comprehensive search across academic databases including PubMed, Scopus, Wiley, Embase, and Springer using relevant keywords. Only the most recent, peer-reviewed articles published in the English language were considered for inclusion. Results: The molecular mechanisms by which melatonin induces its therapeutic effects have been the subject of various studies. Conclusion: While melatonin was initially understood to only regulate circadian rhythms, recent studies indicate that it has a far-reaching effect on various organs and physiological systems, such as immunity, cardiovascular function, antioxidant defense, and lipid hemostasis. As a potent antioxidant, anti-cancer, anti-inflammatory, and immunoregulatory agent, multiple therapeutic applications have been proposed for melatonin.

Natural sources of nanoparticles, such as seaweed, demonstrated their bioefficiency as anti-inflammatory, antibacterial and anticancer medicines. It is a key biodeficient component that is biosynthesised utilising a non-toxic, environmentally acceptable technology that has fascinated researchers worldwide. Using established in-vitro techniques, the anti-inflammatory activity of silver nanoparticles synthesised from Kappaphycusalvarezi aqueous extract was evaluated in this study. UV-Vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy, energy dispersive X-ray (EDX) analysis and transmission electron microscopy (TEM) analysis were used to characterise the nanoparticles. This seaweed's nanoparticles offer solid proof that they are an efficient anti-inflammatory. The bioefficiency of this plant and its nanoparticles may be attributed to chemicals based on flavonoids. [ABSTRACT FROM AUTHOR]

Context Clinical studies have found an association between yerba maté intake and beneficial physiological effects. Nevertheless, no systematic reviews have been conducted to shed light on the data supporting this association. Objective The present systematic review aimed to investigate the physiological effects of yerba maté. Data Sources Searches were performed in 6 databases (Embase, LILACS, Scopus, PubMed, SciELO, Web of Science) and 3 grey literature databases (OpenGrey, ProQuest, Google Scholar). Relevant publications were identified, and the reference lists of included studies were searched manually for randomized clinical trials, nonrandomized clinical trials, and observational studies investigating the physiological effects of yerba maté. Data Extraction Risk of bias was assessed using the Cochrane risk of bias tool for randomized trials and the Cochrane ROBINS-I (Risk Of Bias In Nonrandomized Studies of Interventions) tool. Joanna Briggs Institute critical appraisal tools were used for cross-sectional, case series, cohort, and case-control studies. The overall certainty of the evidence was estimated using the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) working group summary of findings table. Data Analysis Of 1096 studies identified, 32 were included. Studies showed consistent effects of yerba maté intake on metabolism improvement and antioxidant and anti-inflammatory activities in different populations. Benefits for body weight and composition, exercise performance, mood, and appetite, in addition cardio- and neuroprotective effects, were also observed. Risk of bias was categorized as high in 22 studies, moderate in 9 studies, and low in 1 study. The certainty of evidence ranged from moderate to very low. Conclusion The available literature indicates that yerba maté can be used within a balanced and healthy diet for prevention and adjuvant treatment of chronic diseases. Systematic Review Registration PROSPERO registration number CRD42020200196. [ABSTRACT FROM AUTHOR]

Introduction: Naproxen is effective for various musculoskeletal conditions and has a longer half-life, making it a favourable choice for sustained relief. Additionally, there is a potential unmet need for guidelines on the usage of topical Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in the Asia-Pacific region. A study on naproxen 10% gel aims to address this need and increase awareness of its therapeutic potential in the region. Aim: To assess the efficacy and safety of naproxen 10% gel in relieving pain associated with lower back, knee, cervical, synovitis, bursitis, muscle sprain, and tendinitis. Materials and Methods: This prospective, cohort, observational, open-label, single-arm, multicentric study was conducted at 458 centres in India, including Ahmedabad, Bengaluru, Chandigarh, Chennai, Delhi, Guwahati, Hyderabad, Indore, Jaipur, Kolkata, Lucknow, Meerut, Mumbai, Patna, and Pune, between February 2023 and May 2023. The data was collected from outpatient settings/clinics of orthopaedicians and clinicians who have been prescribing topical naproxen 10% gel to their patients. The study included patients aged 18 to 60 years of either sex who were suffering from back pain, muscle pain, sprains, frozen shoulder, arthritis, acute low back ache (non-specific), or pain. The data was captured during the scheduled follow-up visits planned by the treating clinician, with data recorded at 3, 5, 10, and 15 days. At the baseline visit, demographic details (age, sex, weight, height, body mass index, and symptoms), Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale score, pain intensity on movement score, Visual Analogue Scale (VAS), and overall pain score were obtained. Results: Out of 10,587 patients, 10,265 completed the present study. The majority of patients had lower back pain (n=3386, 32.99%) and knee pain (n=3184, 31.02%). The average pain intensity on movement score of patients with bursitis significantly decreased from the baseline to 15 days {mean change {95% Confidence Interval (CI)}: 6.04 (5.89, 6.20); p<0.001}. Post-naproxen treatment, the average pain intensity, WOMAC pain score, VAS, and overall pain score significantly decreased from baseline to day 15 in patients with knee pain and lower back pain. A significant improvement in WOMAC, WOMAC pain (5.42 vs 17.98), WOMAC stiffness (1.49 vs 5.75), and WOMAC physical function score (18.93 vs 56.21) at day 15 was observed in patients with a muscle sprain. Adverse Events (AE) were reported in 173 (1.69%) patients overall, with dryness (n=125) being the most common, followed by erythema (n=20) and pruritus (n=17). Conclusion: Naproxen 10% gel is an effective topical treatment for lower back pain, knee pain, cervical pain, synovitis, bursitis, muscle sprain, and tendinitis. It could prove helpful in patients where the side-effects of oral NSAIDs are to be avoided. [ABSTRACT FROM AUTHOR]

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Background and Purpose: Chronic inflammation is pathogenic and contributes to human diseases, causing a significant threat to public health. The NLR family pyrin domain‐containing protein 3 (NLRP3) is the best‐characterized factor regulating inflammation. Therefore, targeting NLRP3 has the potential to treat inflammatory diseases and improve human health. Experimental Approach: Lipopolysaccharide was used to induce inflammation in cell cultures. Lipopolysaccharide/d‐galactosamine and dextran sulfate sodium salt were used to induce acute liver inflammation and ulcerative colitis respectively in C57BL/6J mice. Western blotting, immunofluorescence, immunoprecipitation, quantitative PCR and enzyme‐linked immunosorbent assay (ELISA) were used to evaluate the activation of the inflammatory response in cell cultures and in mice. Key Results: JNUTS013, a novel sorbicillinoid compound recently synthesized by us, significantly inhibited inflammation both in cell cultures and in mouse models. Mechanistically, JNUTS013 induced proteasome‐dependent degradation of NLRP3. Hence, it suppressed the formation of the NLRP3 inflammasome and the production of downstream inflammatory cytokines and chemokines. The inhibitory effect of JNUTS013 on NLRP3 protein expression was confirmed in mice. Importantly, JNUTS013 failed to ameliorate bowel inflammation in Nlrp3‐/‐ knockout mice, supporting NLRP3 as the biological target by which JNUTS013 inhibits inflammation. Further studies revealed critical chemical moieties of JNUTS013 required for inducing NLRP3 degradation. Conclusion and Implications: This study identifies a novel compound JNUTS013 that inhibits inflammation through inducing NLRP3 protein degradation in vitro and in vivo, which not only supports the development of JNUTS013 as an anti‐inflammation agent but also creates a new way for the treatment of inflammation by chemically inducing NLRP3 degradation. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is a common chronic ocular disease. DED can have a significant impact on visual function, causing disturbances to comfort, daily activities, and general quality of life. The varied nature of DED makes it difficult to point to a specific cause of the syndrome. However, current literature agrees that the inflammation of the cornea and conjunctiva plays a major role in its pathogenesis. Therapies targeted toward inflammation have shown varied success in the treatment of DED. The purpose of this review is to provide an overview of the prevalence and inflammatory pathophysiology of DED and discussion of the available anti-inflammatory therapies including the following: Nonsteroidal anti-inflammatory drugs, corticosteroids, and other hormonal therapies, nonsteroidal immunomodulators, biological tear replacement, antibiotics, dietary supplements, tea tree oil, and intense pulsed light.

Silver nanoparticles (AgNPs) are extensively investigated for their potential physical, chemical, and biological properties. Silver nanoparticles (AgNPs) have several applications in diagnosis, therapy (wound healing, cancer), electronic devices, water treatment, etc. The present study used the cost-effective and ecologically approachable technique to synthesize levan-capped silver nanoparticles of about 22 nm. These silver nanoparticles were subsequently introduced into a gel to create a silver release system with bacteria inhibition activity. The study also aimed to evaluate synthesized Levan-based silver nanoparticles loaded gel for its wound healing property in the excision rat model. Compared to commercial products, levan-based AgNPs were used for in-vitro antimicrobial activities on E. Coli and Staphylococcus aureus and in-vivo wound healing properties.The wound healing property was assessed by area and time of wound closure in rats. In the excision wound model, Levan-based AgNPs exhibited a reduction in wound area that was more as compared to standard and control. In this study, the nanoparticles of silver were spherical and homogeneous in size, which showed bactericidal effects for E. coli and B. subtilis. Levan acts as a coating and reducing agent for silver nanoparticles and acts as an anti-inflammatory agent in the healing process. Carbopol was used for topical formulations such as hydrogel due to high viscosity at low concentration and low toxicity profile. This polymer is anionic that needs to be neutralized with triethanolamine to become jellified, and it has good bio-adhesive properties required for gel formulation. The present challenge of silver nanoparticles (AgNPs) is to maximize their benefits and minimize their toxic effects on humans and the environment. For future perspective, its synthesis, release into the atmosphere, and scaling up production must be considered.

New effective wound healing agents are a priority for modern clinical pharmacology. A promising approach would be to develop medicinal products that promote angiogenesis, which is a critical step in wound healing. The aim of the study was to evaluate the wound healing effect of a medicinal product based on recombinant human angiogenin in gel form in various experimental models. Materials and methods: white outbred male rats were used as experimental ani mals. The study compared healing effects of a regenerating product containing recombinant human angiogenin (0.0025%) in gel form and a reference product in full-thickness excision, incision, and burn wound models. The healing effect of the test product in treating chronic wounds was assessed in a model of alloxan-induced diabetes mellitus. The anti-inflammatory effect of the test product containing recombinant human angiogenin was compared with that of another reference product in a model of adjuvant-induced arthritis. Results: according to the study, the test product based on recombinant human angiogenin exerts higher wound healing effect in treating excision, incision, and burn wounds than the reference product (Solcoseryl gel). Being applied, the test product intensifies tissue repair in chronic wounds in the model of alloxan-induced diabetes. The dissociation of necrotic tissues and the progression towards epithelialisation at wound edges are more rapid. The anti-inflammatory effect of the test product based on recombinant human angiogenin is comparable with that of the reference product (Diclofenac gel). Conclusions: the test product based on recombinant human angiogenin in gel form was found to have pronounced wound healing and anti-inflammatory effects comparable with those of reference products.

The unexplored anti‐inflammatory and wound‐scratching assay of 3‐hydroxy‐2‐(2,5‐dimethoxyphenyl)‐4H‐chromen‐4‐one [3HF(B)] was reported for the first time with the subsequent transdermal drug delivery en route electrospun cellulose acetate nanofiber mat. The higher anti‐inflammatory activity of 3HF(B) was revealed by in vitro protein denaturation assay in comparison to Ibuprofen. The wound scratching assay on NIH3T3 cells disclosed the rapid wound healing potential of 3HF(B) in 18 h. The fabricated cellulose acetate nanofiber's drug encapsulation efficiency was 82.0±1.0 % whereas drug release ability was 91.29±0.3 % at pH 7.4. The initial rapid release of 37.82±1.3 % of the drug was found to be beneficial for quick recovery from the critical phase of symptoms. These results suggest that the cellulose acetate/3HF(B) composite nanofiber's suitability to be employed as a patch in the transdermal drug delivery system with synergetic anti‐inflammatory activity. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is a common chronic ocular disease. DED can have a significant impact on visual function, causing disturbances to comfort, daily activities, and general quality of life. The varied nature of DED makes it difficult to point to a specific cause of the syndrome. However, current literature agrees that the inflammation of the cornea and conjunctiva plays a major role in its pathogenesis. Therapies targeted toward inflammation have shown varied success in the treatment of DED. The purpose of this review is to provide an overview of the prevalence and inflammatory pathophysiology of DED and discussion of the available anti-inflammatory therapies including the following: Nonsteroidal anti-inflammatory drugs, corticosteroids, and other hormonal therapies, nonsteroidal immunomodulators, biological tear replacement, antibiotics, dietary supplements, tea tree oil, and intense pulsed light. [ABSTRACT FROM AUTHOR]

Background & Objective: The effectiveness of intra-articular corticosteroid injection therapy is still debatable, despite numerous studies which demonstrated the benefits of steroid injections. Injection failure can be caused by a variety of technical factors, some of which have been identified in studies, including the accuracy with the injection location is performed and the pattern of corticosteroid distribution. We investigated the non-technical factors that influence the effectiveness of intra-articular corticosteroid injection at the sacroiliac joint (SIJ) in the past. Methodology: It was a prospective cohort study to determine non-technical factors associated with recurrence in patients with SIJ pain who had received multidisciplinary treatment for their ailment. A total of 55 patients met the inclusion and exclusion criteria for the study who were followed up. Patients who had SIJ injections before 9 months and, who had no improvement on the pain scale, or there was a worsening of the pain, or the patient returned with SIJ pain complaints on the same side, were included in the trial. The results were analyzed using logistic regression to determine the likelihood of recurrence. Results: A total of 55 participants was enrolled in the study, with a higher proportion of females (n = 33; 60 %) than males (n = 22; 40 %). Thirty-one patients were returning patients (56.36 %) out of 55 patients. According to the results of the bivariate analysis, age was associated with recurrent SIJ pain. According to the results of the T-test, the mean age of the recurrent patients was 49.32 ± 16.68 y, whereas the mean age of the non-recurrent patients was 56.7 ± 12.76 y. The results of the multivariate analysis revealed that age, NSAID consumption, and unilateral SIJ pain, all had protective values in the context of recurrence of the sacroiliac joint pain. Conclusions: The use of non-steroidal anti-inflammatory drugs (NSAIDs) and the involvement of a single SI joint are protective factors against the recurrence of SI joint pain. [ABSTRACT FROM AUTHOR]

The pharmaceutical industry has a pervasive need for chiral specific molecules with optimal affinity for their biological targets. However, the mass production of such compounds is currently limited by conventional chemical routes, that are costly and have an environmental impact. Here, we propose an easy access to obtain new tetrahydroquinolines, a motif found in many bioactive compounds, that is rapid and cost effective. Starting from simple raw materials, the procedure uses a proline‐catalyzed Mannich reaction followed by the addition of BF3 ⋅ OEt2, which generates a highly electrophilic aza‐ortho‐quinone methide intermediate capable of reacting with different nucleophiles to form the diversely functionalized tetrahydroquinoline. Moreover, this enantioselective one‐pot process provides access for the first time to tetrahydroquinolines with a cis‐2,3 and trans‐3,4 configuration. As proof of concept, we demonstrate that a three‐step reaction sequence, from simple and inexpensive starting compounds and catalysts, can generate a BD2‐selective BET bromodomain inhibitor with anti‐inflammatory effect. [ABSTRACT FROM AUTHOR]

• Synthesis, in silico & in vitro evaluation of 7‑chloro-quinolines as MPO inhibitors. • Derivatives 13k, 13l , and 14 emerged as the most potent MPO inhibitors. • Their ability to inhibit MPO arises from interactions with catalytic triad residues. • 13k, 13l , and 14 demonstrated drug-likeness and favorable pharmacokinetic profiles. Given the central role of the myeloperoxidase (MPO) enzyme in inflammation, MPO inhibition is recognized as a promising pharmacological strategy for managing inflammatory-related diseases. This study describes the synthesis, as well as the in silico and in vitro evaluation, of a series of 7‑chloro-quinolines designed as novel MPO inhibitors. Among the synthetic analogs, compounds 13k, 13l , and 14 emerged as the most potent enzyme inhibitors. The in silico pharmacokinetic and toxicological assessments of these compounds pointed to their drug-likeness and favorable pharmacokinetic profiles but raised some concerns about their potential for toxicity. Additionally, in silico analysis elucidated their binding profiles, which were found to be consistent with prior results for several inhibitors previously described, suggesting that the ability of compounds 13k, 13l , and 14 to inhibit MPO mainly arises from interactions with catalytic triad residues. Furthermore, molecular dynamics indicated that compound 14 , the most potent MPO inhibitor, consistently maintained close interactions within the active site during the simulations, thereby reaffirming complex stability. This study led to the identification of a novel chemical class of 7‑chloro-quinoline MPO inhibitors, highlighting the potential of derivatives 13k, 13l , and 14 as promising candidates for future in vitro and in vivo studies investigating their safety and anti-inflammatory activities. [Display omitted] [ABSTRACT FROM AUTHOR]

The biosynthesis of silver nanoparticles using plant extracts is a safe and efficient method. Human periodontal stem cells (hPDLSCs) can promote periodontal tissue formation for regenerative therapy. The current study aimed to biosynthesize silver nanoparticles (AgNPs) using stem bark extracts from Oroxylum indicum (L) Kurz (OI) as a reducing agent (OI/AgNPs) and investigate the biological properties of OI/AgNPs on human periodontal ligament stem cells (hPDLSCs). The OI/AgNPs were biosynthesized and characterized using UV–vis spectrophotometry (UV‒vis), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), transmission electron microscopy (TEM) and zeta potential analyses. The hPDLSCs were stimulated with hydrogen peroxide (H2O2, H2O2-hPDLSCs) and bacterial lipopolysaccharide (LPS, LPS-hPDLSCs) and encapsulated in the hydrogel. After that, the levels of cell viability, interleukin-1beta (IL-1b), alkaline phosphatase (ALP) activity, and calcium content were measured and compared with quercetin (QT) as a reference flavonoid. The OI/AgNPs were stable spherical nanoparticles with a size range of 21.49 ± 0.32 nm, and biosynthesis enhanced the antioxidant and biological effects of the OI/AgNPs. The accumulation of OI/AgNPs in the cytoplasm of hPDLSCs with high levels of cell viability was demonstrated. OI/AgNPs increased the cell growth of H2O2-hPDLSCs and decreased the levels of IL-1b secretion from LPS-hPDLSCs. The OI/AgNPs increased the ALP activity and calcium content of the hPDLSCs. In conclusion, the biosynthesized OI/AgNPs were noncytotoxic and could protect hPDLSCs against oxidative stress and inflammatory stimuli and promote osteoblastic differentiation; thus, they are applicable for the regenerative treatment of peri‑implantitis.

Through this study, a new series of novel cyclohexanone derivatives were synthesized as a Schiff Bases or chalcones were prepared by depending on the intermediate compound (Cyclohexanone) all new derivatives were characterized that was prepared by Fourier Transform Infrared Spectroscopy (FT-IR) Analysis, 1HNMR spectroscopic data, and the13C NMR spectrum, some the newly prepared derivatives which are important in the field of medical chemistry which were studied as anti-bacterial and anti fungal. [ABSTRACT FROM AUTHOR]

Aim: The goal of this study was to develop colon-targeted nanoparticulate systems of the anti-inflammatory agent Quercetin (QU) and evaluate the formulation for various parameters that would allow the active ingredient to be released at a predetermined time and location with better pharmaceutical and therapeutic properties. Materials and Methods: Quercetin-loaded chitosan nanoparticles were formulated for this purpose using the ionic gelation method by employing Central Composite Design. To coat Eudragit S 100 (ES 100) on an optimised formulation of quercetin loaded chitosan nanoparticles (QLCN), the oil in oil solvent evaporation process was used. Particle size (PS), polydispersity index (PDI), scanning electron microscopy (SEM), and drug release (% DR) were evaluated to characterize the nanoparticles. Results: Quercetin loaded chitosan nanoparticles has an average PS 114.2 ± 1.42 nm and polydispersity index 0.396 ± 0.02, whereas Eudragit coated nanoparticles shows PS 330.2± 0.40 nm and polydispersity index 0.412 ± 0.02. Surface morphology of prepared nanoparticles were confirmed using SEM. According to an in vitro drug release analysis of nanostructured formulations, the ES 100 coating on QLCN inhibits the release of quercetin in the upper gastrointestinal system, demonstrating good colon drug targeting. Conclusion: According to an in vitro release study of nanoparticle formulations, the ES 100 coating on QLCN limits the release of quercetin in the upper gastrointestinal system, demonstrating effective colon drug targeting. [ABSTRACT FROM AUTHOR]

Topical treatments are a potential therapeutic option for the therapy of osteoarthritis, with significant data supporting the effectiveness and safety of topical formulation. Topical gel formulations may offer an alternative to oral formulations to relieve osteoarthritis (OA) pain while decreasing systemic exposure. Topical capsaicin transemulgel may represent an effective and safe alternative. The transemulgel was prepared from aqueous Aloe vera gel and Carbopol 934 with capsaicin in clove oil emulsion. The optimized transemulgel of capsaicin showed a pH of 6.1 ± 0.1 and viscosity of 15263–998 cps. Data from in vitro diffusion demonstrated improved permeability properties. The formulation caused no skin irritation when applied topically. The optimal transemulgel spreadability was found to be 20.23 g·cm/s. In vitro and ex vivo studies of the optimized formulation were performed. The skin irritant test was performed on rat skin with an optimized and marketed formulation. Both showed no irritation on the skin. The transemulgel of the capsaicin with Aloe vera gel was proven to be effective for osteoarthritis therapy. [ABSTRACT FROM AUTHOR]

Agmatine, an endogenous polyamine generated by the gut microbiota, positively affects host lifespan by regulating mononuclear cell or macrophage function. Although the regulatory pathways governing monocyte/macrophage differentiation have been well studied, the influence of the microbiome and its metabolites on monocyte/macrophage function have not been fully elucidated. To address this, we aimed to investigate the mechanisms whereby agmatine inhibits immunometabolic disorders using the colon of ulcerative colitis (UC) model mice. Agmatine (10 mM) attenuated pathological damage to colonic tissue and significantly improved the survival rate of UC model mice. In particular, treatment of UC model mice with 0.4, 2, and 10 mM agmatine resulted in mortality rates of 70 %, 20 %, 10 %, and 0 %, respectively. In a macrophage-depletion model, agmatine regulated the inflammatory microenvironment by affecting macrophages: it reduced the proportion of M1 macrophages and increased that of M2 macrophages in UC model mice. In cultured macrophages, agmatine inhibited lipopolysaccharide-induced inflammatory cytokine and NO secretion, as detected by enzyme-linked immunosorbent assay and the Griess assay, respectively. Agmatine partially reduced inflammatory factor production by inhibiting histone deacetylase, as detected by fluorometric assay. These findings provide evidence that agmatine efficiently suppresses macrophage polarization in UC mice, highlighting its potential as an anti-inflammatory agent against UC., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease of the hair follicles leading to painful lesions, associated with increased levels of pro‐inflammatory cytokines. Numerous guidelines recommend antibiotics like clindamycin and rifampicin in combination, as first‐line systemic therapy in moderate‐to‐severe forms of inflammation. HS has been proposed to be mainly an auto‐inflammatory disease associated with but not initially provoked by bacteria. Therefore, it has to be assumed that the pro‐inflammatory milieu previously observed in HS skin is not solely dampened by the bacteriostatic inhibition of DNA‐dependent RNA polymerase. To further clarify the mechanism of anti‐inflammatory effects of rifampicin, ex vivo explants of lesional HS from 8 HS patients were treated with rifampicin, and its effect on cytokine production, immune cells as well as the expression of Toll‐like receptor 2 (TLR2) were investigated. Analysis of cell culture medium of rifampicin‐treated HS explants revealed an anti‐inflammatory effect of rifampicin that significantly inhibiting interleukin (IL)‐1β, IL‐6, IL‐8, IL‐10 and tumour necrosis factor (TNF)‐α production. Immunohistochemistry of the rifampicin‐treated explants suggested a tendency for it to reduce the expression of TLR2 while not affecting the number of immune cells. [ABSTRACT FROM AUTHOR]

In present study we designed and synthesized a novel series of 1,2,5-oxadiazole-sulfonamide hybrids (4a-4j) in search of more potent anti-inflammatory agents. Title compounds were synthesized by chlorosulfonation of 3,4-diphenyl-1,2,5-oxadiazole (3) followed by condensation with amines and all derivatives were obtained in moderate to good yield. All synthesized hybrids were characterized with spectroscopic techniques and further evaluated for anti-inflammatory potential. The synthesized hybrids were screened in vivo by employing carrageenan-induced paw edema method at 10 mg/kg dose. Among all derivatives, two compounds 4g and 4b displayed better anti-inflammation potential than standard drugs celecoxib and indomethacin. While the anti-inflammation profile of compounds 4h, 4e and 4f during in vivo screening was also comparable to celecoxib and indomethacin. The structure-activity relationship (SAR) was also discussed with the reference of substituent nature. Present results showed that newly synthesized hybrids have significant anti-inflammatory potential and might be played an important role to the development of more potent anti-inflammation agents in future. [ABSTRACT FROM AUTHOR]

[Display omitted] • The sulfoxide was demonstrated as a novel functional group to develop potent IDO1 inhibitors. • 2-Sulfinyl-benzoxazoles are type II IDO1 inhibitors, which interact with ferrous heme cofactor. • 2-Sulfinyl-benzoxazole 22 can suppress the inflammatory process in both LPS stimulated cellular and animal models. Taking advantage of key interactions between sulfoxide and heme cofactor, we used the sulfoxide as the anchor functional group to develop two series of indoleamine 2, 3-dioxygenase 1 (IDO1) inhibitors: 2-benzylsulfinylbenzoxazoles (series 1) and 2-phenylsulfinylbenzoxazoles (series 2). In vitro enzymatic screening shows that both series can inhibit the activity of IDO1 in low micromolar (series 1) or nanomolar (series 2) levels. They also show inhibitory selectivity between IDO1 and tryptophan 2, 3-dioxygenase 2. Interestingly, although series 1 is less potent IDO1 inhibitors of these two series, it exhibited stronger inhibitory activity toward kynurenine production in interferon-γ stimulated BxPC-3 cells. Enzyme kinetics and binding studies demonstrated that 2-sulfinylbenzoxazoles are non-competitive inhibitors of tryptophan, and they interact with the ferrous form of heme. These results demonstrated 2-sulfinylbenzoxazoles as type II IDO1 inhibitors. Furthermore, molecular docking studies supports the sulfoxide being of the key functional group that interacts with the heme cofactor. Compound 22 (series 1) can inhibit NO production in a concentration dependent manner in lipopolysaccharides (LPS) stimulated RAW264.7 cells, and can relieve pulmonary edema and lung injury in LPS induced mouse acute lung injury models. [ABSTRACT FROM AUTHOR]

Nagendra Sastri Yarla,1 Gopal Pathuri,1,2 Hariprasad Gali,2 Simon Terzyan,3 Janani Panneerselvam,1 Parthasarathy Chandrakesan,4 Marcus Tullius Scotti,5 Courtney Houchen,4 Venkateshwar Madka,1 Chinthalapally V Rao1,6 1Center for Cancer Prevention and Drug Development, Hem-Onc Section, Department of Medicine, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; 2College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; 3Laboratory of Biomolecular Structure and Function; Department of Biochemistry and Molecular Biology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; 4Division of Digestive Diseases and Nutrition, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; 5Laboratory of Cheminformatics, Program of Natural and Synthetic Bioactive Products (PgPNSB), Health Sciences Center, Federal University of Paraíba, João Pessoa, PB, Brazil; 6VA Medical Center, Oklahoma City, OK 73104, USACorrespondence: Chinthalapally V Rao Tel +1 405-271-3224Email CV-Rao@ouhsc.eduBackground: Non-steroidal anti-inflammatory drugs, cyclooxygenase (COX)-2 selective inhibitors, have been explored for prevention and treatment of several inflammatory chronic conditions including arthritis, and cancer. However, the long-term use of these drugs is associated with gastrointestinal, renal, and cardiovascular side effects. Later, COX/5-lipoxygenase (5-LOX) dual inhibitors (eg, licofelone) have been developed but did not enter into the market from the clinical trails due to COX-1/2 inhibition-associated side effects. Hence, targeting microsomal prostaglandin E synthase-1 (mPGES-1) and 5-LOX can be an ideal approach while sparing COX-1/2 activities for development of the next generation of anti-inflammatory drugs with better efficacy and safety.Materials and Methods: In silico (molecular modelling) studies were used to design a mPGES-1/5-LOX dual inhibitory and COX-1/2 sparing lead molecule licofelone analogue-9 (LFA-9) by modifying the pharmacophore of licofelone. In vitro cell-free enzymatic (mPGES-1, 5-LOX, COX-1/2) assays using fluorometric/colorimetric methods and cell-based assays (LPS-induced PGE2, LTB4, and PGI2 productions from macrophages) using ELISA technique, isothermal calorimetry, and circular dichroism techniques were performed to determine the mPGES-1/5-LOX inhibitory efficacy and selectivity. Anti-inflammatory efficacy of LFA-9 was evaluated using a carrageenan (inflammogen)-induced rat paw edema model. Infiltration/expression of CD68 immune cells and TNF-α in paw tissues were evaluated using confocal microscope and immunoblot analysis. Anti-cancer effect of LFA-9 was evaluated using colon spheroids in vitro.Results: LFA‐9 inhibited mPGES-1/5-LOX and their products PGE2 and LTB4, spared COX-1/2 and its product PGI2. LFA‐9 bound strongly with human mPGES‐1/5‐LOX enzymes and induced changes in their secondary structure, thereby inhibited their enzymatic activities. LFA-9 inhibited carrageenan-induced inflammation (70.4%) in rats and suppressed CD68 immune cell infiltration (P ≤ 0.0001) and TNF-α expression. LFA-9 suppressed colon tumor stemness (60.2%) in vitro through inhibition of PGE2 (82%) levels.Conclusion: Overall study results suggest that LFA-9 is a mPGES-1/5-LOX dual inhibitor and showed anti-inflammatory and colorectal cancer preventive activities, and warranted detailed studies.Keywords: mPGES-1/5-LOX dual inhibitor, LFA-9, drug design, anti-inflammatory agent, cancer chemoprevention

Implantable insulin infusion systems using the intra-peritoneal route have dramatically changed the management of diabetes paving the way toward the realization of the potential "holy grail" of a fully implantable artificial pancreas. However, the wear duration of delivery catheters is compromised by the foreign body-mediated immune response. Both occlusion material present at the distal catheter tip end and fibrotic encapsulation surrounding the catheters influence the controlled and precise delivery of insulin, which eventually leads to the need for surgical intervention. The novel part of the current work is the investigation of the roles of implant physical properties (catheter size and tip configuration), as well as local inflammation control (through utilization of an anti-inflammatory agent) on the host fibrotic response using a previously developed animal model. The cellular and molecular response, the medication delivery efficacy as well as the ability to flush the catheters were examined and further compared among the different mitigation strategies. Reduction in catheter size as well as tuning the tip configuration from a cone shape to a round shape showed delayed host recognition and delayed propagation of the fibrotic response. However, the round shaped tips had an increased occurrence of lumen occlusion as a result of flow change. It became apparent that changing the physical properties of the catheters was not a long-term solution to catheter obstructions caused by the foreign body reaction. In comparison, control of the local inflammatory response through the use of an anti-inflammatory agent demonstrated a promising strategy for maintenance of catheter functionality without any type of obstructions. These finding will have a large impact toward the development of long-term use catheters for continuous intraperitoneal insulin infusion. [Display omitted] [ABSTRACT FROM AUTHOR]

• Moringa oleifera flower trypsin inhibitor (MoFTI) was evaluated for anti-inflammatory effects • MoFTI (15 or 30 mg/kg i.p.) reduced paw edema only during the second phase, indicating cytokine modulation. • In the peritonitis model, MoFTI (15 or 30 mg/kg) reduced leukocyte migration and plasma extravasation. • It also reduced and the levels of NO, TNF-α, IL-6, IL-17A, IL-4 and IL-10 in peritoneal fluid. The medicinal use of Moringa oleifera flowers to treat inflammations, for examples as constituents of tonics, has been reported. Protease inhibitors isolated from plants have been evaluated as potential anti-inflammatory agents and the edible flowers of Moringa oleifera contain a trypsin inhibitor called MoFTI. In the present work, we evaluated whether MoFTI can be linked to the anti-inflammatory effects reported for M. oleifera flowers. Two mouse models of carrageenan-induced acute inflammation (paw edema and peritonitis) were performed. The animals were intraperitoneally administered MoFTI at 15 or 30 mg/kg. The anti-edematogenic effect was assessed by measuring the paw volume during the first and second phases of edema formation. In the peritonitis model, we evaluated the peritoneal fluid for leukocyte migration, total protein content, cytokine levels, and nitric oxide (NO) concentration. MoFTI reduced paw edema only during the second phase, indicating cytokine modulation. In the peritonitis model, MoFTI reduced leukocyte migration, plasma extravasation (attributed to lower protein content), and the levels of NO and pro-inflammatory [tumor necrosis factor-α, interleukin (IL)-6, and IL-17A] and anti-inflammatory (IL-4 and IL-10) cytokines. In conclusion, MoFTI promoted an anti-inflammatory activity and its action appears to be mediated via cytokine suppression. Hence, MoFTI is an interesting molecule for evaluation in chronic inflammation models, and as a candidate for the development of novel anti-inflammatory drugs. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease is a chronic inflammation caused by the malignant inflammation response and if not treated, could lead to colorectal cancer. One of the researched treatment is mahkota dewa (Phaleria macrocarpa) leaf extract that has flavonoid compound known to reduce inflammation. This study was aimed to prove that mahkota dewa leaf extract could reduce inflammation of mice colon induced with dextran sodium sulfate (DSS) and observe MUC1 expression from colon epithelial crypt of Lieberkuhn. Methods: This was a laboratory experiment using biological material (paraffin block) taken from 28 mice and divided into 5 groups: normal, aspirin, low and high dose mahkota dewa, and negative control. They were processed into immunohistochemistry and stained microscopic slides. Afterwards, they were observed with 400x magnification and 5 field-of-view of mice colon crypt of lieberkuhn. Then MUC1 expression was counted using ImageJ to obtain mean immunohistochemistry score and analyzed with SPSS. Results: There were significant reduction of MUC1 expressions from normal, aspirin, and high dose mahkota dewa groups compared to the negative control group. The result shown MUC1 expression from high dose mahkota dewa (M=149.90,SD=3.81) and aspirin (M=158.92,SD=5.28) were closer to normal group (M=148.02,SD=5.28). There were no significant results between negative (M=175.39,SD=14.30) and low dose mahkota dewa group (M=149.90,SD=5.02). Conclusion: There was a reduction of MUC1 expression in DSS-induced mice colonic epithelial cells for high dose mahkota dewa group. This shown that high dosage mahkota dewa leaf extract could reduce inflammation like aspirin. [ABSTRACT FROM AUTHOR]

Background/Aims: Histamine is an important chemical transmitter involved in inflammatory processes, including asthma and other chronic inflammatory diseases. Its inflammatory effects involve mainly the histamine H4 receptor (H4R), whose role in several studies has already been demonstrated. Our group have explored the effects of 1-[(2,3-dihydro-1-benzofuran-2-yl)methyl]piperazines as antagonists of H4R, and herein the compounds LINS01005 and LINS01007 were studied with more details, considering the different affinity profile on H4R and the anti-inflammatory potential of both compounds. Methods: We carried out a more focused evaluation of the modulatory effects of LINS01005 and LINS01007 in a murine asthma model. The compounds were given i.p. (1-7 mg/kg) to ovalbumin sensitized BALB/c male mice (12 weeks old) 30 min before the antigen challenging, and after 24 h the cell analysis from the bronchoalveolar lavage fluid (BALF) was performed. The lung tissue was used for evaluation by western blot (COX-2, 5-LO, NF-B and STAT3 expressions) and histological analysis. Results: Treatment with the more potent H4R antagonist LINS01007 significantly decreased the total cell count and eosinophils in BALF at lower doses when compared to LINS01005. The expression of COX-2, 5-LO, NF-B and STAT3 in lung tissue was significantly reduced after treatment with LINS01007. Morphophysiological changes such as mucus and collagen production and airway wall thickening were significantly reduced after treatment with LINS01007. Conclusion: These results show important down regulatory effect of novel H4R antagonist (LINS01007) on allergic lung inflammation. [ABSTRACT FROM AUTHOR]

Abstract Background Irritable bowel syndrome (IBS) is one of the most frequent and recurrent gastrointestinal diseases. However, up to now, no pharmacological agent has been approved to treat IBS. Emerging evidence showed that inflammation has a vital role in enhancing nervous system sensitivity and perception of abdominal pain in subjects with IBS. Propolis is an herbal substance with a broad spectrum of antioxidants, anti-inflammatory, and prebiotic properties, which might exert beneficial effects to reduce the severity of IBS. The current clinical trial aims to evaluate the efficacy of propolis supplementation on IBS. Methods This single-center, randomized, double-blind, placebo-controlled clinical trial will be performed to evaluate the effect of propolis supplementation in adult patients with IBS diagnosed with Rome IV criteria. Fifty-two eligible patients will randomly be allocated to receive a propolis tablet (450 mg, containing 100 mg polyphenol compounds) or identical placebo, twice daily for 6 weeks. The primary outcome of the trial is an improvement in IBS severity from baseline to the sixth week of intervention. The secondary outcomes include the change in weight, waist circumference, and IBS quality of life. We will use the paired sample t test or Mann-Whitney U test for the within-group comparison and independent sample t test or Wilcoxon rank-sum and chi-square test or Fisher’s exact test for the between-group comparison. Besides, a multivariable-adjusted mean effect will be computed using the ANCOVA test. Discussion We hypothesize that propolis supplementation would be useful for treating IBS through its antioxidants, anti-inflammatory, and prebiotic properties. This trial will show the results of propolis supplementation, whether positive or negative, on IBS. If the current trial confirms our hypothesis, propolis supplementation can be a new choice in adjunctive therapy of IBS. Trial registration Iranian Registry of Clinical Trials IRCT20190708044154N1. Registered on 26 December 2019. Updated on 13 February 2020. https://en.irct.ir/trial/40983 Sponsor Tabriz University of Medical Sciences, Tabriz, Iran