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(A) The inflammatory cascade; (B) The inflammatory cascade. The arrows in the figure represents process. The arrows in the figure represents process

(A) The inflammatory cascade; (B) The inflammatory cascade. The arrows in the figure represents process. The arrows in the figure represents process

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Inflammation is one of the common events in the majority of acute as well as chronic debilitating diseases and represent a chief cause of morbidity in today’s era of modern lifestyle. If unchecked, inflammation leads to development of rheumatoid arthritis, diabetes, cancer, Alzheimer’s disease, and atherosclerosis along with pulmonary, autoimmune a...

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... is a result of activated cellular elements and the existence of various biochemical mediators like cytokines (e.g., Interleukin-1, TNF-α), Kinases (p38 kinase, JNKs, MAP kinase), transcription factors (e.g., NF-κB) and matrix metalloproteinases (MMPs) [2]. The inflammatory cascade is shown in Figure 1A,B. Int. ...
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... 2019, 20, x FOR PEER REVIEW 4 of 38 (A) Figure 1. Cont. ...

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... Neutrophils may be under active preparation during this time period for the release of NETs for a faster resolution of the inflammatory response. On the other hand, in the air pouch inflammation induced by carrageenan, fewer neutrophils in the air pouch at early stages should not be entirely attributed to a strong antiinflammatory effect of candidate drugs [29]. We hope that the findings of our study can help researchers to better interpret experiment results when using air pouch inflammation models to evaluate the effect of anti-inflammatory drugs, and to choose the model that can best answer the research question in place. ...
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Deciphering the complex and redundant process of acute inflammation remains challenging. The failure of numerous clinical trials assessing anti-inflammation agents which had promising preclinical effects inevitably questions the validity of current animal models of inflammation. This study aimed to better understand the process of immune inflammatory response and to select more suitable models to evaluate the effect of potential anti-inflammatory drugs. Zymosan and λ-carrageenan are the most used representatives of particulate and soluble irritants that trigger acute inflammation in the air pouch inflammation model. When zymosan was used, the number of exudate cells first increased at 4 h-8 h, followed by a drop at 12 h-24 h. While, the changes in number of leukocytes in peripheral blood and proportion of neutrophils in bone marrow have the opposite trend. Meanwhile, neutrophils released neutrophil extracellular traps (NETs) to clean zymosan particles. In contrast, the cell migration response to carrageenan increased during 4 h to 24 h, no obvious NETs were observed, and the number of leukocytes in peripheral blood increased and the proportion of neutrophils in bone marrow decreased slightly. This study indicated that although both zymosan and carrageenan are sterile irritants, the characteristics of the inflammatory response induced by each other were different. In the acute phase of inflammation, zymosan-stimulated neutrophils were mobilized, recruited, and engulfed, and then died by NETs. Carrageenan stimulated the production of cytokines/chemokines by neutrophils or macrophages, but did not lead to an obvious death by releasing NETs. Graphical Abstract
... However, the duration and intensity of inflammation vary between the two. Acute inflammation is more of a transient and restrained reaction, while chronic inflammation models persist for extended periods and usually harmonize the disease process [69]. ...
... In addition, it demonstrates good reproducibility and acts on several inflammatory pathways, making it a good model for preliminary analyses. Furthermore, this nonantigenic phlogistic agent acts locally in a bi-phasic manner, enabling the model to predict a probable biological target of the tested drug [69]. In the first hour following carrageenan injection, the injection trauma and the release of inflammatory mediators, such as histamine, serotonin, and bradykinin, account for most of the early acute phase of inflammation. ...
... However, the concentration of carrageenan injected highly affects the edema response, whereas the maximum response is too arduous to inhibit. Hence, the solution must be precisely prepared to avoid deviation from the expected response [69]. ...
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The emerging field of nanotechnology has paved the way for revolutionary advancements in drug delivery systems, with nanosystems emerging as a promising avenue for enhancing the therapeutic potential and the stability of various bioactive compounds. Among these, cannabidiol (CBD), the non-psychotropic compound of the Cannabis sativa plant, has gained attention for its therapeutic properties. Consequently, researchers have devoted significant efforts to unlock the full potential of CBD’s clinical benefits, where various nanosystems and excipients have emerged to overcome challenges associated with its bioavailability, stability, and controlled release for its transdermal application. Therefore, this comprehensive review aims to explain CBD’s role in managing acute inflammatory pain and offers an overview of the state of the art of existing delivery systems and excipients for CBD. To summarize this review, a summary of the cannabinoids and therapeutical targets of CBD will be discussed, followed by its conventional modes of administration. The transdermal route of administration and the current topical and transdermal delivery systems will also be reviewed. This review will conclude with an overview of in vivo techniques that allow the evaluation of the anti-inflammatory and analgesic potentials of these systems.
... Furthermore, this study showed that the extracts of PDH inhibited paw edema in rats induced by carrageenan. Carrageenan induces edema in two phases with several mediators including histamine, serotonin, 5hydroxytryptamine, prostaglandins, bradykinin, cyclooxygenase, TNFα, IL-1 and IL-6 involved (Umare et al., 2014;Karim et al., 2019;Patil et al., 2019). ...
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Background: : Pangdahai (matured, ripened, and dried seeds of Scaphium affine (Mast.) Pierre) is widely used in managing several diseases in countries like China, Vietnam, Japan, and India. This study evaluated the anti-inflammatory effects of the crude extracts (ethanol and aqueous) and isolated compounds of Pangdahai. Methods: : Xylene-induced ear edema in mice, carrageenan-induced paw edema in rats, and nitric oxide (NO) assay were used to evaluate and screen the crude extracts and isolated compounds from the ethanolic extracts of Pangdahai. TNF-α and IL-1β levels in the tissues of rat foot and ear were determined by ELISA. The cytotoxicity of the isolated compounds was also determined by MTT assay. Molecular docking studies using targets involved in the inflammatory process were also used to further evaluate the compounds. Results: : Both aqueous and ethanol extracts demonstrated significant anti-inflammatory effect and markedly attenuated vascular permeability in mice induced by acetic acid in a dose-independent manner. The ethanol extract also significantly inhibited levels of IL-1β and TNF-α. Four (4) compounds exhibited significant inhibitory effects on NO release without cytotoxicity on RAW 264.7 macrophage. These compounds also showed good binding affinities for COX-2, PLA2, IRAK-4 and NIK. Conclusions: This study validates, provides scientific evidence and justification for the use of the aqueous de-coctions of Pangdahai in pharyngitis traditionally. (+)-Pinoresinol, tiliroside, Z-caffeic acid, and 3,4-dihydrox-ybenzoic acid (protocatechuic acid) isolated from Pangdahai showed anti-inflammatory activities, which might be responsible for the actions of Pangdahai. Tiliroside showed high binding affinity comparable to the native ligands of inflammatory mediators. List of abbreviations COX-2 cyclooxygenase-2 DMSO Dimethylsulfoxide DMEM Dulbecco's modified eagle medium ELISA enzyme-linked immunosorbent assay FBS Fetal Bovine Serum IL Interleukin iNOS inducible nitric oxide synthase IRAK-4 Interleukin-1 Receptor-Associated Kinase-4 LPS Lipopolysaccharide NIK NF-κB-Inducing Kinase NO nitric oxide NSAIDs non-steroidal anti-inflammatory agents NTF Tumor necrosis factor OD Optical density PBS Phosphate buffered saline PDH Pangdahai
... Highly digestible and with essential amino acids (EAAs) [21] EAAs Arginine (Arg), Cysteine (Cys), Glycine (Gly), Glutamine (Glu), Proline (Pro), Tyrosine (Tyr) [22] Lipids 20-30 g/dry weight [23] Fatty acids C14:0, C16:0, C18:0, C18:1, C18:2 [22] Carbohydrates and fibers 6-10 g/dry weight [24] Vitamins B1, B2, B3, B6, B12, C, A, D, E, K [8,23,25] Minerals Ca, Zn, Fe, Mg, Cu, Na, K, Ca, P, Mn, I [23,26] inflammatory markers, including nuclear factor-kappa B (NF-κB) and C-reactive protein (CRP), and to ameliorate conditions associated with inflammation, such as colitis and arthritis. [40] Furthermore, these same or similar BACs have exhibited promising anti-cancer properties, affecting mechanisms such as cell cycle arrest, induction of apoptosis, and the reduction of tumor cell migration. [33,41,42] Moreover, research has revealed that the inclusion of insect-based diets can effectively inhibit tumor growth, reduce tumor size, and enhance the effectiveness of chemotherapy drugs. ...
Article
The utilization of edible insects (EIs) as an alternative source of nutrients and functional foods has gained substantial recognition in recent years, opening doors to sustainable food production, improved dietary health, and unique food experiences. EIs are rich in bioactive compounds (BACs) encompassing proteins, peptides, PUFA, vitamins, and antioxidants. These BACs have a wide array of health-enhancing qualities, from antioxidant, anti-inflammatory, antimi-crobial and immune system-modulating effects. Furthermore, the potential of EIs extends to the management or mitigation of health conditions like obesity, diabetes, cardiovascular diseases, and malnutrition. The incorporation of EIs into food systems has evolved beyond traditional consumption, with applications in the development of functional foods, dietary supplements, and food ingredients. In this context, this critical review aims to amalgamate the most recent developments in the realm of EIs-based food products, in addition to elucidating the most efficient process intensification procedures for the extraction and recovery of these BACs. The sustainable utilization of EIs calls for a careful examination of several crucial considerations, including consumer acceptance or allergenicity. In this respect, intensified technologies have emerged to maximize the potential of BACs derived from EIs, while simultaneously enhancing their functionality, stability , and regulatory approval within the ambit of food products.
... Moreover, Esmaeili et al. [140] investigated the anti-inflammatory impact through the paw edema test, the anti-nociceptive effect assessed via the hot plate, and the formalin test of nanoemulsion-based gels (NG) that incorporate clove and cinnamon EOs in an in vivo model. The suppression of carrageenan-induced paw edema in rats serves as a model for evaluating the effectiveness of anti-inflammatory medications [144]. Cinnamon-NG exhibited a greater suppression of rat paw edema induced by carrageenan compared to the other groups, which included clove-NG, control, and blank gel groups. ...
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Plants have proven to be important sources for discovering new compounds that are useful in the treatment of various diseases due to their phytoconstituents. Clove (Syzygium aromaticum L.), an aromatic plant widely cultivated around the world, has been traditionally used for food preservation and medicinal purposes. In particular, clove essential oil (CEO) has attracted attention for containing various bioactive compounds, such as phenolics (eugenol and eugenol acetate), terpenes (β-caryophyllene and α-humulene), and hydrocarbons. These constituents have found applications in cosmetics, food, and medicine industries due to their bioactivity. Pharmacologically, CEO has been tested against a variety of parasites and pathogenic microorganisms, demonstrating antibacterial and antifungal properties. Additionally, many studies have also demonstrated the analgesic, antioxidant, anticancer, antiseptic, and anti-inflammatory effects of this essential oil. However, CEO could degrade for different reasons, impacting its quality and bioactivity. To address this challenge, encapsulation is viewed as a promising strategy that could prolong the shelf life of CEO, improving its physicochemical stability and application in various areas. This review examines the phytochemical composition and biological activities of CEO and its constituents, as well as extraction methods to obtain it. Moreover, encapsulation strategies for CEO and numerous applications in different food fields are also highlighted.
... In the current study, DPPH transformation from a violet to yellow color indicated that AeOB has the ability to scavenge free radicals, which are the cause of oxidative stress in RA. ROS can cause tissue damage and endothelial dysfunction by acting as signaling molecules in inflammatory diseases [30]. Therefore, it can be assumed that one of the primary mechanisms to suppress the expression of genes responsible for producing inflammatory cytokines and the cyclooxygenase enzyme (COX-2) in RA is a decline in oxidative stress caused by AeOB. ...
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Onosma bracteatum Wall (O. bracteatum) has been used traditionally for the management of arthritis; however, its therapeutic potential warrants further investigation. This study aimed to evaluate the anti-arthritic effects of the aqueous–ethanolic extract of O. bracteatum leaves (AeOB) in a rat model of complete Freund’s adjuvant (CFA)-induced arthritis. Rats were treated with AeOB (250, 500, and 750 mg/kg), indomethacin (10 mg/kg), or a vehicle control from days 8 to 28 post-CFA injection. Arthritic score, paw diameter, and body weight were monitored at regular intervals. X-ray radiographs and histopathological analysis were performed to assess arthritic severity. Inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP) were quantified by qPCR and icromatography. Phytochemical analysis of AeOB revealed alkaloids, flavonoids, phenols, tannins, Saponins, and glycosides. AeOB also exhibited antioxidant potential with an IC50 of 73.22 µg/mL in a DPPH assay. AeOB and diclofenac exhibited anti-inflammatory and anti-arthritic activities. Rats treated with AeOB at 750 mg/kg and indomethacin showed significantly reduced arthritic symptoms and joint inflammation versus the CFA control. The AeOB treatment downregulated TNF-α and IL-6 and decreased CRP levels compared with arthritic rats. Radiography and histopathology also showed improved prognosis. These findings demonstrate the anti-arthritic potential of AeOB leaves.
... Prostaglandins are the primary mediators of the second phase of carrageenaninduced inflammation, which begins around 3 h after carrageenan administration. 61 Injection of carrageenan-induced edema in rat paw and an efficient anti-inflammatory drug will be able to reduce the carrageenan-induced edema, which was measured by volume displacement of mercury by the edematous paw. Table 5 presents volume displacement and percent inhibition of inflammation by indomethacin and ZnO NPs. ...
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In the present study, ZnO nanoparticles were synthesized by using aqueous extracts of Aerva persica roots. Characterization of as-prepared ZnO nanoparticles was carried out using different techniques, including powder X-ray diffraction (XRD), UV−vis diffuse reflectance spectroscopy (DRS), Fourier transform infrared (FTIR) spectroscopy, field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM) and BET surface area analysis. Morphological analysis confirmed the small, aggregated flake-shaped morphology of as-synthesized ZnO nanostructures. The as-prepared ZnO nanoparticles were analyzed for their potential application as anti-inflammatory (using in vivo inhibition of carrageenan induced paw edema) and antioxidant (using in vitro radical scavenging activity) agents. The ZnO nanoparticles were found to have a potent antioxidant and anti-inflammatory activity comparable to that of standard ascorbic acid (antioxidant) and indomethacin (anti-inflammatory drug). Therefore, due to their ecofriendly synthesis, nontoxicity, and biocompatible nature, zinc oxide nanoparticles synthesized successfully from roots extract of the plant Aerva persica with potent efficiencies can be utilized for different biomedical applications.
... a similar result was obtained in PMa-activated human neutrophils (ic 50 = 4.6 µM) (Figure 3a). this fact may result due to MPO-ii accumulation, an intermediate unable to oxidize halides to halogen acids [5,73,94], irreversible inactivation of the enzymatic heme group [93], inhibition of upstream pathways [42,93], or cell death [93]. to the best of our knowledge, there is no data in the literature on effect of ebselen on MPO-chlorinating activity. ...
... then, we analyzed the effects of DD on MPO activity in vivo. We initially assessed whether DD inhibits MPO activity and the associated damage using well-established acute inflammation models: carrageenan-induced inflammation in mouse peritoneal cavity and paw [94,95], both used to assess the anti-inflammatory effects of natural and synthetic compounds [95]. carrageenan induces an intense inflammatory response in the peritoneal cavity, characterized by plasma exudation and leukocyte migration, especially neutrophils [74]. ...
... The percentage of inflammation was determined by comparing the amount of oedema to the normal volume of the rear paw. Meanwhile, the percentage of inflammation inhibition was calculated by comparing the percent inflammation in the test group to the control group ( Patil et al., 2019;Akpinar, 2021). ...
Article
Background: Eggshells are one of the most common culinary wastes, yet using eggshell membrane detritus in medical treatments remains largely unexplored. Objective: This study aims to assess the anti-inflammatory potential of eggshell membrane hydrolysate. Method: Eggshell membrane hydrolysate was prepared using acid-base hydrolysis. The intraplantar carrageenan-induced inflammation model was used to test the anti-inflammatory effect. The experimental group consisted of a control, comparison (4.5 mg/kg BW diclofenac-Na, 4.5 mg/kg BW hyaluronic acid, and 45 mg/kg BW collagen), and eggshell membrane hydrolysates (9, 22.5, 45 and 90 mg/kg BW). Observations of inflammation, percentage of inflammation, and percentage of inhibition of inflammation were measured every 30 minutes for 180 minutes. Statistical analysis was performed using the t-test and also trendline analysis. Result: The findings revealed that collagen and hyaluronic acid demonstrated the ability to suppress inflammation compared to controls (p < 0.05). Compared to the control group, the group that received eggshell membrane hydrolysate at doses of 9, 22.5, 45, and 90 mg/kg BW also exhibited inhibition of inflammation (p < 0.05). Furthermore, increasing the dosage of eggshell membrane hydrolysate correlated with an increase in the percentage of inflammation inhibition in carrageenan-induced rats. Conclusion: Eggshell membrane hydrolysate has the potential to act as an anti-inflammatory agent.
... Often accompanied by pain [1,2], they are a significant problem that affects numerous people worldwide [3]. Chronic inflammation results in a long-term damage that leads to tissue and organ dysfunction [4,5]. Current therapy options for inflammatory diseases primarily include steroidal and nonsteroidal anti-inflammatory drugs (NSAIDs), as well as opioid analgesics for pain control. ...
... Current therapy options for inflammatory diseases primarily include steroidal and nonsteroidal anti-inflammatory drugs (NSAIDs), as well as opioid analgesics for pain control. Corticosteroid use frequently results in hypertension, hyperglycemia, and osteoporosis [5,6]. Chronic NSAIDs use, on the other hand, has been associated with gastrointestinal issues, bleeding, and kidney damage [2,5,7]. ...
... Corticosteroid use frequently results in hypertension, hyperglycemia, and osteoporosis [5,6]. Chronic NSAIDs use, on the other hand, has been associated with gastrointestinal issues, bleeding, and kidney damage [2,5,7]. Thus, it is necessary to seek for new anti-inflammatory and antinociceptive drugs with increased potency and fewer side effects. ...
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Sambucus nigra L. (S. nigra, SN) or black elder is a traditional medicinal plant widely used worldwide for therapeutic and dietary purposes. The aim of the current study was to investigate the anti-inflammatory and antinociceptive activities of black elder fruit and flower extracts (SNFrE and SNFlE, respectively). The primary polyphenol constituents in the flower extract were flavonoids and phenolic acids, while anthocyanins were the main components in the fruit extract. SNFrE revealed pronounced and dose-dependent in vivo anti-inflammatory activity assessed by the cotton pellet-induced granuloma test. Doses of 10, 20, and 50 mg/kg BW of SNFrE reduced the weight of induced granuloma in rats by 20.3%, 20.5%, and 28.4%, respectively. At the highest dose (50 mg/kg BW), SNFrE had significant (p < 0.01) anti-inflammatory activity comparable to that of diclofenac, the reference compound used (10 mg/kg BW). In addition, the in vivo antinociceptive activity of the extracts in mice was estimated using the acetic-acid-induced writhing test. Both extracts at doses of 50 mg/kg BW inhibited the abdominal contractions induced by the acetic acid significantly comparing to the control group (p < 0.01). Our findings indicate that black elder extracts and particularly SNFrE possess anti-inflammatory and antinociceptive activities, providing experimental evidence for the use of S. nigra in traditional medicine.