Synthetic Anti-inflammatory Drugs Research Articles

The Protecting Role of Black Seed Oil and Its Nano-Formulation in LPS-Induced Acute Kidney Injury in Mice: Evaluation of Oxidative Stress, Biochemical & Molecular Parameters.

Acute kidney injury (AKI) is a medical concern that is accompanied by the rapid deterioration of kidney function. It can be triggered by lipopolysaccharide (LPS) of gram-negative bacteria as it activates a complicated immune response, resulting in widespread inflammation and potential organ dysfunction. Black seed oil (BSO) is rich in beneficial constituents and has been widely used owing to its nutritional advantages. This research is aimed to investigate the potential protective effects of BSO and its nano-formulation on AKI induced by LPS. It also aimed to compare their anti-inflammatory activity with indomethacin, a known synthetic anti-inflammatory drug. Forty-eight mice were placed randomly into 8 groups. A single intraperitoneal (i.p.) injection of 2.5 mg/kg B.W. of LPS was used to trigger inflammation, and pretreatment with BSO and its nano-formulation was at 0.2 mL/kg/day for 14 consecutive days. Indomethacin was used as a reference drug and its efficacy was tested alone or in combination with BSO at lower doses. Renal function was assessed using urea, creatinine, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). Also, oxidative and inflammatory markers were assessed by measuring levels of reduced glutathione (GSH), nitric oxide (NO), cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), and toll-like receptor-4 (TLR-4). Histopathological examination of the kidney tissues was also performed. The study showed that BSO and its nano-formulation had anti-inflammatory effects comparable to or better than those of indomethacin. They greatly decreased the oxidative stress and inflammatory markers induced by LPS. Their protective effect against pathological alterations in kidney tissues was significantly noticed. BSO and its nano-formulation could be used as nephroprotective and anti-inflammatory supplements.

Modulation of Phospholipase A2 Membrane Activity by Anti-inflammatory Drugs.

The phospholipase A2 (PLA2) superfamily consists of lipolytic enzymes that hydrolyze specific cell membrane phospholipids and have long been considered a central hub of biosynthetic pathways, where their lipid metabolites exert a variety of physiological roles. A misregulated PLA2 activity is associated with mainly inflammatory-derived pathologies and thus has shown relevant therapeutic potential. Many natural and synthetic anti-inflammatory drugs (AIDs) have been proposed as direct modulators of PLA2 activity. However, despite the specific chemical properties that these drugs share in common, little is known about the indirect modulation able to finely tune membrane structural changes at the precise lipid-binding site. Here, we use a novel experimental strategy based on differential scanning calorimetry to systematically study the structural properties of lipid membrane systems during PLA2 cleavage and under the influence of several AIDs. For a better understanding of the AIDs-membrane interaction, we present a comprehensive and comparative set of molecular dynamics (MD) simulations. Our thermodynamic results clearly demonstrate that PLA2 cleavage is hindered by those AIDs that significantly reduce the lipid membrane cooperativity, while the rest of the AIDs oppositely tend to catalyze PLA2 activity to different extents. On the other hand, our MD simulations support experimental results by providing atomistic details on the binding, insertion, and dynamics of each AID on a pure lipid system; the drug efficacy to impact membrane cooperativity is related to the lipid order perturbation. This work suggests a membrane-based mechanism of action for diverse AIDs against PLA2 activity and provides relevant clues that must be considered in its modulation.

Bergamot Byproducts: A Sustainable Source to Counteract Inflammation.

Chronic inflammation is the result of an acute inflammatory response that fails to eliminate the pathogenic agent or heal the tissue injury. The consequence of this failure lays the foundations to the onset of several chronic ailments, including skin disorders, respiratory and neurodegenerative diseases, metabolic syndrome, and, eventually, cancer. In this context, the long-term use of synthetic anti-inflammatory drugs to treat chronic illnesses cannot be tolerated by patients owing to the severe side effects. Based on this, the need for novel agents endowed with anti-inflammatory effects prompted to search potential candidates also within the plant kingdom, being recognized as a source of molecules currently employed in several therapeutical areas. Indeed, the ever-growing evidence on the anti-inflammatory properties of dietary polyphenols traced the route towards the study of flavonoid-rich sources, such as Citrus bergamia (bergamot) and its derivatives. Interestingly, the recent paradigm of the circular economy has promoted the valorization of Citrus fruit waste and, in regard to bergamot, it brought to light new evidence corroborating the anti-inflammatory potential of bergamot byproducts, thus increasing the scientific knowledge in this field. Therefore, this review aims to gather the latest literature supporting the beneficial role of both bergamot derivatives and waste products in different models of inflammatory-based diseases, thus highlighting the great potentiality of a waste re-evaluation perspective.

The Anti-Inflammatory Effects of Cannabis sativa Extracts on LPS-Induced Cytokines Release in Human Macrophages.

Inflammation is the response of the innate immune system to any type of injury. Although acute inflammation is critical for survival, dysregulation of the innate immune response leads to chronic inflammation. Many synthetic anti-inflammatory drugs have side effects, and thus, natural anti-inflammatory compounds are still needed. Cannabis sativa L. may provide a good source of anti-inflammatory molecules. Here, we tested the anti-inflammatory properties of cannabis extracts and pure cannabinoids in lipopolysaccharide (LPS)-induced inflammation in human THP-1 macrophages. We found that pre-treatment with cannabidiol (CBD), delta-9-tetrahydrocannabinol (THC), or extracts containing high levels of CBD or THC reduced the level of induction of various cytokines. The CBD was more efficient than THC, and the extracts were more efficient than pure cannabinoids. Finally, IL-6, IL-10, and MCP-1 cytokines were most sensitive to pre-treatments with CBD and THC, while IL-1β, IL-8, and TNF-α were less responsive. Thus, our work demonstrates the potential of the use of cannabinoids or/and cannabis extracts for the reduction of inflammation and establishes IL-6 and MCP-1 as the sensitive markers for the analysis of the effect of cannabinoids on inflammation in macrophages.

Medicinal Plants, Phytochemicals and Regulation of the NLRP3 Inflammasome in Inflammatory Bowel Diseases: A Comprehensive Review

Ongoing research explores the underlying causes of ulcerative colitis and Crohn’s disease. Many experts suggest that dysbiosis in the gut microbiota and genetic, immunological, and environmental factors play significant roles. The term “microbiota” pertains to the collective community of microorganisms, including bacteria, viruses, and fungi, that reside within the gastrointestinal tract, with a particular emphasis on the colon. When there is an imbalance or disruption in the composition of the gut microbiota, it is referred to as dysbiosis. Dysbiosis can trigger inflammation in the intestinal cells and disrupt the innate immune system, leading to oxidative stress, redox signaling, electrophilic stress, and inflammation. The Nod-like Receptor (NLR) Family Pyrin Domain Containing 3 (NLRP3) inflammasome, a key regulator found in immunological and epithelial cells, is crucial in inducing inflammatory diseases, promoting immune responses to the gut microbiota, and regulating the integrity of the intestinal epithelium. Its downstream effectors include caspase-1 and interleukin (IL)-1β. The present study investigated the therapeutic potential of 13 medicinal plants, such as Litsea cubeba, Artemisia anomala, Piper nigrum, Morus macroura, and Agrimonia pilosa, and 29 phytocompounds such as artemisitene, morroniside, protopine, ferulic acid, quercetin, picroside II, and hydroxytyrosol on in vitro and in vivo models of inflammatory bowel diseases (IBD), with a focus on their effects on the NLRP3 inflammasome. The observed effects of these treatments included reductions in IL-1β, tumor necrosis factor-alpha, IL-6, interferon-gamma, and caspase levels, and increased expression of antioxidant enzymes, IL-4, and IL-10, as well as regulation of gut microbiota. These effects could potentially provide substantial advantages in treating IBD with few or no adverse effects as caused by synthetic anti-inflammatory and immunomodulated drugs. However, additional research is necessary to validate these findings clinically and to develop effective treatments that can benefit individuals who suffer from these diseases.

Anti-Inflammatory Effect of Red Dragon Fruit (Hylocereus polyrhizus) Peel on Male White Rat

Background: The side effects of synthetic anti-inflammatory drugs have become a known problem in medicine as well as in the general public. These side effects problems drive patients to seek alternatives to common anti-inflammatory drugs, especially natural alternatives. Phytochemicals such as flavonoids, alkaloids, and many different others have been identified as potential anti-inflammatory agents. Red dragon fruit (Hylocereus polyrhizus) is one source of such phytochemicals. Whilst the consumption of the flesh of red dragon fruit is very common, utilization of the peel is very rare and often becomes waste. Objective: This study aimed to explore the potential of red dragon fruit peel as an anti-inflammatory agent. Methods: This experimental study with a control group post-test-only design. This study involved in-vitro (protein denaturation inhibition using bovine serum albumin) and in-vivo (carrageenan-induced inflammation on an air-pouch model on 25 white rats) experiment. Results: This study showed that the red dragon fruit peel extract contains flavonoid, alkaloid, saponin, and tannin compounds. Administration of red dragon fruit peel extract suspension was found to be effective at inhibiting protein denaturation and reducing white blood count in the inflammation exudates, and the effectiveness is increasing along with the dose. Conclusion: It can be concluded that the red dragon fruit peel extract was effective as an anti-inflammatory agent, especially at a higher dose.

In vitro Evaluation of Anti-Inflammatory Activity of "Habanero" Chili Pepper (Capsicum chinense) Seeds Extracts Pretreated with Cellulase.

The aim of this study was to explore the effect of capsaicin and particular phenolic compounds profile from cellulase assisted extracts of Habanero (Capsicum chinense) chili pepper seeds (CPS) on the concentration of cytokines (IL-2, IL-6, TNF-α, IL-1β) in murine macrophages (RAW 264.7) stimulated with lipopolysaccharides (LPS). Capsaicin was quantified by HPLC-DAD, and the phenolic profile was determined by UPLC-MS-QqQ. Anti-inflammatory activity was evaluated by Mouse Cytokine/Chemokine Magnetic Bead Panel 96-well plate assay. Among the 15 different phenolics found in CPS extracts obtained at 120 or 150min of maceration with 2,500 UI/L at 30ºC or 45 ºC in a 1:15 (w:v) proportion, the most abundant was vanillic acid (7.97-12.66µg/g). The extract obtained at 30ºC and 120min, showed similar effects than the observed for synthetic anti-inflammatory drugs indomethacin and dexamethasone, and capsaicin standard. Beyond capsaicin, salicylic, protocatechuic and trans-cinnamic acids as well as vanillin in CPS extracts were correlated with the anti-inflammatory effect. On the other hand, capsaicin and chlorogenic acid contents were potential immunostimulants whose concentration varied depending on the cellulase treatment time.

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.

Exploring the pivotal role of endothelin in rheumatoid arthritis.

A chronic inflammatory disorder, rheumatoid arthritis (RA) is an autoimmune and systemic disease characterized by progressive and prolonged destruction of joints. This results in increased mortality, physical disability and destruction. Cardiovascular disorders are one of the primary causes of mortality in patients with RA. It is multifactorial in nature and includes genetic, environmental and demographic factors which contribute to the severity of disease. Endothelin-1 (ET-1) is a peptide which acts as a potent vasoconstrictor and is generated through vascular smooth muscle and endothelial cells. Endothelins may be responsible for RA, as under certain circumstances they produce reactive oxygen species which further promote the production of pro-inflammatory cytokines. This enhances the production of superoxide anion, which activates pro-inflammatory cytokines, resulting in RA. The aim of this review is to elucidate the role of endothelin in the progression of RA. This review also summarizes the natural and synthetic anti-inflammatory drugs which have provided remarkable insights in targeting endothelin.

FORMULATION AND EVALUATION OF ANTI-INFLAMMATORY EMULGEL OF Brucea javanica (L.) Merr SEED EXTRACTS

Anti-inflammatory drugs are needed to overcome excessive inflammatory reactions that can interfere with activities. The existence of side effects in the use of synthetic anti-inflammatory drugs causes the search for natural drugs with high therapeutic effects and low side effects to continue. Seeds of Makassar (Brucea javanica (L.) Merr) plant are known to have anti-inflammatory activity. Topical anti-inflammatory administration is currently being developed because it can minimize side effects compared to oral. This study aimed to formulate 96% ethanol extract of Makasar fruit seeds in the form of an emulgel and to determine the physical properties and anti-inflammatory activity of the emulgel in vitro. Makasar fruit seeds were extracted by sonication method using 96% ethanol solvent (3 x 35 minutes). The extract was then formulated into an emulgel preparation with an extract concentration of 1%. Emulgel was then tested for its physical properties and anti-inflammatory activity in vitro using protein denaturation inhibition method. The results showed that the physical properties of emulgel base (F0), extract emulgel (F1), and Na-diclofenac emulgel (F2) met the requirements for homogeneity, pH, adhesion, spreadability, and viscosity tests. F0, F1, and F2 had inhibition percentages of 3.74±1.58%,; 23.07±0.72%; and 33.49±0.29, respectively. According to one-way ANOVA statistical test, the three tested groups had significant differences.

Effect of COVID-19 coronavirus infection on the course of rheumatoid arthritis

To date, there are numerous studies on the effect of COVID-19 on the course of autoimmune rheumatic diseases and the value of vaccination in preventing this dangerous viral infection.Objective: to assess the effect of coronavirus infection on the course of rheumatoid arthritis (RA), the severity of infection, the effect of current baseline therapy on infection outcomes, and the role of vaccination against COVID-19.Patients and methods. 134 patients with a reliable diagnosis of RA were interviewed and their outpatient records analysed during the pandemic period from January 2020 to July 2021.Results. Most of the patients were in the older age group (62.7 years on average), had an average disease duration of 13 years, low to moderate RA activity, comorbidities including arterial hypertension, excess body weight, type 2 diabetes mellitus, etc. All patients received synthetic basic anti-inflammatory drugs (BАID) and glucocorticoids (GC). Thirtyseven (27.6%) patients were vaccinated with the Sputnik V vaccine. Their adverse events were represented by soreness at the injection site (n=6) and transient flu-like syndrome (n=6). Worsening of joint syndrome was reported by 1 patient. COVID-19 was suffered by 43 patients, none of whom were vaccinated. 7 patients were hospitalized, 3 patients died (all had severe comorbidities). In the post-infection period, weakness (64%), memory impairment (48.7%), reduced ability to work (38.5%) persisted for a long time (42 days on average), which was due to the long withdrawal of BАID.Conclusion. No exacerbations of the disease were noted in those vaccinated with Sputnik V. COVID-19 was detected in 43 (32.1%) patients, 7 of whom required hospitalization and 3 died. Exacerbation of RA in the post-infection period was associated with prolonged withdrawal of BАID.

Перспективы применения ингибиторов янус-киназ в терапии анкилозирующего спондилита и псориатического артрита

The Janus kinase inhibitors are oral targeted synthetic basic anti-inflammatory drugs that exert their influence on the intracellular signaling system, preventing the activation of inflammatory processes. Now, there are a sufficient number of janus kinase inhibitors that have found application not only in rheumatology, but also in other specialties (gastroenterology, dermatology, hematology, oncology and even veterinary medicine). Thanks to janus kinase inhibitors, suppression of the intracellular signaling pathway of several cytokines simultaneously became available, as a result of which it became possible to exert a complex pathogenic effect. This explains the wide range of applications of these drugs in many areas of medicine. In rheumatology, janus kinase inhibitors are finding new and new applications in the treatment of not only rheumatoid arthritis, but also other diseases. This article presents studies on ankylosing spondylitis and psoriatic arthritis, the results of which demonstrate high rates regarding the use of janus kinase inhibitors for the treatment of these diseases.

In vitro and in silico antioxidant and anti-inflammatory potential of essential oil of Cymbopogon citratus (DC.) Stapf. of North-Western Himalaya

Cymbopogon citratus (DC.) Stapf is an aromatic perennial herb of Gramineae (Poaceae) family and is known for its application in food and healthcare industry. The present study aimed to evaluate anti-inflammatory and antioxidant potential of C. citratus essential oil (CEO) through in vitro and in silico studies. Chemical characterization of CEO was done using Gas chromatography-mass spectrophotometry (GC-MS) method. In vitro antioxidant activity was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and ferric ion reducing antioxidant power (FRAP) assays, while egg albumin denaturation method was used to evaluate in vitro anti-inflammatory activity of CEO. Molecular docking investigation of major phytocompounds of CEO was done using Autodock vina software against human peroxiredoxin 5 (PDB ID: 1HD2) and human cyclooxygenase 2 (PDB ID: 5IKQ) proteins, which were further analyzed through molecular dynamics (MD) simulation using YASARA. GC-MS analysis of CEO showed the presence of geranial (48%) neral (34.04%), β-myrcene (9.77%), geraniol (1.88%), linalool (0.84%), isogeranial (0.81%), β-caryophyllene (0.80%), D-limonene (0.51%) as major constituents. CEO showed significant antioxidant activity with DPPH (IC50-47.53 ± 2.16 µg/ml), FRAP (IC50-30.7 ± 0.31 µM), and ABTS assays (IC50-27.87 ± 0.09 µg/ml). CEO also exhibited significant in-vitro anti-inflammatory activity with IC50-29.71 ± 1.95 µg/ml as compared to that of Diclofenac sodium (IC50-36.52 ± 1.95 µg/ml). Molecular docking revealed that β-caryophyllene showed considerable binding potential with human peroxiredoxin 5 receptor (-6.0 kcal/mol) and human cyclooxygenase 2 receptor (-10.1 kcal/mol). Further, MD simulations demonstrated considerable and stable interactions of β-caryophyllene with 1HD2 and 5IKQ proteins up to 100 ns. Drug-likeness and ADME/T features also showed that β-caryophyllene can be used as a potential candidate to replace the synthetic anti-inflammatory drugs with side effects and also act as natural antioxidants. Communicated by Ramaswamy H. Sarma

In vitro concentration optimization of ethanol extract from Makasar fruit seeds (Brucea javanica L. Merr) as an anti-inflammatory agent

Anti-inflammatory medications are necessary to treat excessive inflammation reactions due to injury, infection, or irritation. The emergence of several adverse effects associated with synthetic anti-inflammatory drugs has prompted the continued use of anti-inflammatory agents derived from natural products with low side effects and a high therapeutic effect. While it is well established that the seeds of the Makassar fruit (Brucea javanica (L.) Merr.)  have anti-inflammatory activity, the optimal concentration of Makasar fruit seed extract for anti-inflammatory activity is unknown. This study aims to determine the optimal Makassar fruit seed extract concentration as an in vitro anti-inflammatory. The seeds of the Makasar fruit were extracted using the sonication method (3 x 35 minutes) in 96% ethanol and then concentrated using a rotary evaporator. The secondary metabolites of Makasar fruit seed extract were then identified in the test tubes, and the anti-inflammatory activity was determined using the protein denaturation inhibition method. The results indicated that the extract produced had a yield of 10.03%. The Makassar fruit seed extract contains secondary metabolites of phenolics, flavonoids, and terpenoids. Makasar fruit seed extract exhibited the optimum anti-inflammatory activity at a concentration of 1%, with a 55.47% inhibition of protein denaturation.

Efficacy and safety of tofacitinib in moderate and severe ulcerative colitis in real clinical practice: three years of observation

Introduction. Tofacitinib is the first member of a new class of targeted synthetic anti-inflammatory drugs for the treatment of ulcerative colitis (UC). The article presents a three-year Russian experience of tofacitinib use for the treatment of moderate and severe UC.Aim of the study. To evaluate the efficacy and safety of tofacitinib therapy in real clinical practice in moderate to severe UC patients during three years of follow-up. Methods. The study included 56 patients with UC who had moderate (60.7%) and severe (35.8%) states of disease, the total lesion was diagnosed in 67.8%, and extraintestinal manifestations in 57.1% of patients. Early achievement of clinical response, clinical and endoscopic, corticosteroid-free remission, and safety were evaluated.Results. Early response to tofacitinib therapy was obtained in 47 (83.9%) patients. Clinical remission was achieved in 36 (64.3%) at week 8 of therapy and clinical response was achieved in 13 (23.2%) patients. The majority of patients who achieved clinical remission at weeks 8 and 12 achieved healing of colon mucosa at week 24. Clinical and endoscopic remission rates after 24 weeks – 44 (78.6%) patients, clinical response in 7 (12.5%) patients, 5 (8.9%) did not respond to TFCB therapy. Corticosteroidfree remission was 77.6%. After 2 years of tofacitinib therapy, remission of UC was maintained in 46 (82.1%). After 36 months, remission of UC was maintained in 45 (80.3%) of the 56 patients who had been started on tofacitinib therapy. The cumulative effect of survival in the treatment of tofacitinib in UC was 87.5% after 6 months and persisted for one year, 82.1% after 2 years, and 80.3% after 3 years.Conclusions. The administration of tofacitinib in UC is effective in achieving rapid clinical response, clinical remission, and mucosal healing in patients who do not respond well to biological therapy.

Adsorption and desorption behavior of natural and synthetic active compounds on hydroxyapatite-based nanocomposites

Nano-hydroxyapatite (nano-Hap) and different Hap-based nanocomposites (NCs) containing nanocarbons with different morphologies (functionalized multiwall carbon nanotubes - fMWCNT, graphene oxide - GO, and fullerene - Ful), and gelatin (Gel) were studied to highlight the modification of their adsorption and desorption properties. The obtained Hap-based NCs were characterized using powder X-ray diffraction, laser diffraction, transmission electron microscopy, and Fourier transform infrared spectroscopy. Moreover, ultraviolet–visible spectroscopy was used to investigate the adsorption and desorption properties of the obtained NCs. The adsorption experiments were performed with both ibuprofen (IBU, synthetic active substance) and anthocyanin (ANTO, natural active substance). The results revealed that the studied additives had little influence on improving the drug adsorption as compared to pure HAP. The adsorption energies were evaluated using density functional theory (DFT), which indicated that the interaction with GO is much stronger than the interaction with Ful, due to the formation of hydrogen bonds. The desorption experiments were carried out in simulated body fluid (SBF). fMWCNT and GO had a positive effect in the case of both natural and synthetic anti-inflammatory drugs, due to the morphology and the intermolecular interactions between the functional groups. The positive effect of Gel was observed in the adsorption studies of both substances, Gel increased the adsorption capacity of the NCs. The release profile of IBU was carried out using various mathematical models (zero-order, first-order, Higuchi, Hixon-Crowell, and Korsmeyer-Peppas).

Evaluation of anti-inflammatory activity of Jasminum sessiliflorum extracts

Medicinal plants are important resources for the development of novel anti-inflammatory agents. Synthetic anti-inflammatory drugs have several adverse effects. Medicinal plants have numerous that are safer well as better substitutes for the prevention and management of various diseases and disorders. The and ethyl acetate extracts of Jasminum were evaluated for their potential as anti-inflammatory agents in by inducing paw edema in rats using . The anti-inflammatory activity of the reference drug was compared with the extracts of Jasminum . The extracts on screening indicated the presence of such as , , , alkaloids, and . The study established significant anti-inflammatory nature of the Jasminum extracts in a manner which is dose-dependent. The results indicate that both the extracts of Jasminum possess anti-inflammatory activity of significance and can be used in the development for novel anti-inflammatory moieties.

Salicylate and Procyanidin-Rich Stem Extracts of Gaultheria procumbens L. Inhibit Pro-Inflammatory Enzymes and Suppress Pro-Inflammatory and Pro-Oxidant Functions of Human Neutrophils Ex Vivo.

Salicylate-rich plants are an attractive alternative to synthetic anti-inflammatory drugs due to a better safety profile and the advantage of complementary anti-inflammatory and antioxidant effects of the co-occurring non-salicylate phytochemicals. Here, the phytochemical value and biological effects in vitro and ex vivo of the stems of one of such plants, Gaultheria procumbens L., were evaluated. The best extrahent for effective recovery of the active stem molecules was established in comparative studies of five extracts. The UHPLC-PDA-ESI-MS3, HPLC-PDA, and UV-photometric assays revealed that the selected acetone extract (AE) accumulates a rich polyphenolic fraction (35 identified constituents; total content 427.2 mg/g dw), mainly flavanols (catechins and proanthocyanidins; 201.3 mg/g dw) and methyl salicylate glycosides (199.9 mg/g dw). The extract and its model components were effective cyclooxygenase-2, lipoxygenase, and hyaluronidase inhibitors; exhibited strong antioxidant capacity in six non-cellular in vitro models (AE and procyanidins); and also significantly and dose-dependently reduced the levels of reactive oxygen species (ROS), and the release of cytokines (IL-1β, IL-8, TNF-α) and proteinases (elastase-2, metalloproteinase-9) in human neutrophils stimulated ex vivo by lipopolysaccharide (LPS) and N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP). The cellular safety of AE was demonstrated by flow cytometry. The results support the application of the plant in traditional medicine and encourage the use of AE for development of new therapeutic agents.

Advanced bioactive lipid nanocarriers loaded with natural and synthetic anti-inflammatory actives

Current research is focused toward the development of a new approach based on efficient bioactive lipid nanocarriers (BLN) in order to obtain enhanced benefit to risk ratios of natural and synthetic actives. For this purpose, the bioactivities of several BLN (prepared with raspberry oil, Rso, and rice bran oil, Rbo) containing a natural extract (willow bark extract, Wbe) or a blend of Wbe and the synthetic anti-inflammatory drug indomethacin (Ind) have been comparatively analysed. BLN exhibited homogeneity regarding the particle size (diameters less than 140 nm), excellent physical stability (negative surface charge of −40 and −48 mV) and high encapsulation efficiency (89 to 91% for salicin from Wbe and 65 to 72.5% for Ind). The association of Wbe together with Ind co-loaded BLN resulted in a noticeable amplification of the antioxidant activity (the scavenging of free oxygen radicals exceeds 90%), a protective effect on L929 cells (low apoptosis values of 11.6 and 15.9%) and a significant ability to reduce the TNF-α and IL-6 inflammatory marker levels. The in vitro release, achieved on BLN-Wbe-Ind based-hydrogels, has revealed a gradual release of both kinds of actives. BLN may represent a valuable strategy for overcoming the side effects of synthetic drugs while treating inflammation-related skin disorders.

First report of anti-inflammatory chromenyl derivatives from the spineless cuttlefish Sepiella inermis

The spineless cuttlefish Sepiella inermis encompasses a major share in the marine fisheries sector, and represents as a culinary delicacy in many cultures. Bioactivity-guided fractionation of methanol:ethyl acetate (MeOH:EtOAc, 1:1) extract of the edible parts of the species ensued in identification of two hexahydro chromenyl analogues namely, methyl 7-ethyl-hexahydro-8a-methyl-2H-chromene-4-carboxylate (1) and methyl 1-acetoxy-hexahydro-3-methyl-3-propyl-1H-isochromene-4-carboxylate (2). The isolated metabolites were checked for their radical scavenging and anti-inflammatory potentials by selective in vitro models. The isochromenyl derivative exhibited potential 2,2-diphenyl-1-picryl-hydrazil and 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (IC50 < 0.45 mg mL−1) radical-scavenging capacities along with pro-inflammatory cyclooxygenase-2 (COX-2) (IC50 0.75 mg mL−1) and 5-lipoxygenase (5-LOX) (IC50 0.77 mg mL−1) inhibitory activities. The titled compounds displayed the selectivity indices (IC50 anti-COX-1/IC50 anti-COX-2) greater than 1.25, in comparison with synthetic anti-inflammatory drug ibuprofen (0.44), which attributed to their greater selectivity towards inducible pro-inflammatory enzyme COX-2.