Inhibition Of Inflammatory Mediators Research Articles

Dietary Phytoactives in the Management of Gastric Cancer - A Mini Review

Abstract: Gastric cancer is the fourth leading cause of morbidity worldwide and is known to affect various gastric organs, including the esophagus, intestine, colon, and pancreas. There are variable factors responsible for the development of gastric tumors, such as environmental factors, EPV, hepatitis B and C, and other genetic factors. Phytoactives, or secondary metabolites of plants, have a wide range of biological impacts, including the capacity to prevent cancer in humans. They have this anticancerous impact because of their multi-target mechanism of action, which also includes antioxidant, anti-proliferative, cell apoptosis, and anti-mutagenic effects. To epitomize the role of vital dietary phytoactives as a new approach for treating gastric cancer and explains various mechanisms for their anticancerous activity. H. pylori-associated gastric tumors are the most common, and Phytoactives such as curcumin, piperine, walnut oil, tea, and others possess anticancer properties. They have shown anticancer activity against gastric tumor cell lines via different mechanisms like cell cycle arrest, apoptosis, inhibition of cell proliferation, adhesion, colonization of cancer cells, inhibition of inflammatory mediators, tumor cell bioenergetics, up and down-regulation of various gene and protein expression, and chelation and scavenging of ROS.

The potential role of Hypericum perforatum in wound healing: A literature review on the phytochemicals, pharmacological approaches, and mechanistic perspectives.

St. John's Wort, commonly known as Hypericum perforatum L., is a flowering plant in the Clusiaceae family that traditionally been employed for treating anxiety, depression, wounds, burns, sunburn, irritation, and stomach ailments. This review provides a synopsis of H. perforatum L. phytoconstituents and their biological effects, highlighting its beneficial therapeutic properties for dermatological indications, as well as its antioxidant, antimicrobial, anti-inflammatory, and anti-angiogenic activity in various applications including wound healing and skin conditions such as eczema, sun burn and minor burns also spastic paralysis, stiff neck and mood disorders as anti-depressant and nerve pains such as neuralgia. The data were collected from several databases as Web of Science PubMed, ScienceDirect, Scopus and Google Scholar using the terms: "H. perforatum L.", "H. perforatum L. /phytochemistry," and "H. perforatum extracts/wound healing" collected from 1994 to 2023. The findings suggest H. perforatum L. acts through various mechanisms and plays a role in each phase of the wound healing process, including re-epithelialization, angiogenesis, wound contraction, and connective tissue regeneration. H. perforatum L. enhances collagen deposition, decreases inflammation, inhibits fibroblast migration, and promotes epithelialization by increasing the number of fibroblasts with polygonal shape and the number of collagen fibers within fibroblasts. H. Perforatum L. extracts modulate the immune response and reduce inflammation were found to accelerate the wound healing process via inhibition of inflammatory mediators' production like interleukin-6, tumor necrosis factor-α, cyclooxygenase-2 gene expression, and inducible nitric oxide synthase. Thus, H. perforatum L. represents a potential remedy for a wide range of dermatological problems, owing to its constituents with beneficial therapeutic properties. H. perforatum L. could be utilized in the development of novel wound healing therapies.

Reviewing Choices of Topical Corticosteroids for Modulating Inflammatory Response in Chronic Wound Management

Chronic wounds, characterized by prolonged inflammatory responses and impaired healing, pose a significant challenge in clinical practice. This review explores the potential of topical glucocorticosteroids in modulating inflammation and promoting wound healing in chronic wounds. We delve into the mechanisms underlying chronic inflammation, emphasizing the crucial role of proinflammatory cytokines, reactive oxygen species, and impaired cellular responses. Topical corticosteroids, known for their anti-inflammatory, anti-mitotic, and immunosuppressive properties, emerge as promising candidates to influence the transition from the inflammatory to the proliferative phase of wound healing. The discussion encompasses the mechanisms of action of topical corticosteroids, focusing on their binding to glucocorticoid receptors, inhibition of inflammatory mediators, and potential adverse effects. We address the importance of selecting the appropriate corticosteroid based on potency, application duration, and patient-specific factors. Various formulations, such as ointments, creams, gels, and foams, are evaluated in terms of their advantages and drawbacks in wound management. While acknowledging the recognized efficacy of topical corticosteroids in chronic wound management, we highlight concerns regarding their standalone use, such as immunosuppression and potential infection masking. Furthermore, we explore the integration of retinoids with corticosteroids as a novel approach to mitigate unwanted effects and enhance wound healing outcomes. Despite emerging studies on combination therapies, careful consideration and clinical judgment remain paramount for further development and implementation. In conclusion, this comprehensive review provides insights into the potential of topical corticosteroids in chronic wound management. As research in this field progresses, the integration of innovative therapeutic strategies, including retinoids, holds promise for improving outcomes in the challenging realm of chronic wound care. Keywords: topical corticosteroids, chronic wound management, inflammation modulation, immunomodulation, retinoids, wound healing outcomes.

Anti-Inflammatory Effects of a Novel Nuclear Factor-κB Inhibitory Derivative Derived from Pyrazolo[3,4-d]Pyrimidine in Three Inflammation Models.

Nuclear factor-κB (NF-κB) plays a central role in inflammatory responses, and its physiologic functions are essential for cell survival and proliferation. Currently, drugs targeting NF-κB inhibition have not yet been applied in clinical practice. We investigated the physiologic effect of a novel NF-κB inhibitory compound, 1H-pyrazolo[3,4-d]pyrimidin-4-amine derivative (INH #1), on three inflammatory animal models. The pharmacokinetics were measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. Acute hepatitis was induced by administrating lipopolysaccharide (LPS) and D-(+)-galactosamine hydrochloride followed by the analysis of survival time and inflammatory mediators. Collagen-induced arthritis (CIA) was induced by immunization with type II collagen (CII), and serum-transfer arthritis (STA) was caused by injecting K/BxN mice serum. Clinical and histologic scores were evaluated in both arthritis models. Immune cell subset analysis, CII-induced interferon-gamma (IFN-γ) production and proliferation, and measurement of anti-CII IgG antibodies were performed in the CIA model. In the acute hepatitis model, INH #1 suppressed tumor necrosis factor-α (TNF-α) production and prevented early death in a dose-dependent manner. INH #1 significantly attenuated arthritis scores and joint inflammation in both arthritis models. Additionally, in the CIA model, dendritic cells (DCs) in the regional lymph nodes were decreased in the treated mice and antigen-induced IFN-γ production and cell proliferation in splenocytes were inhibited, whereas the titers of anti-CII IgG antibodies were comparable regardless of the treatment. Here we revealed that INH #1 exerted anti-inflammatory effects in vivo via inhibition of inflammatory mediators and suppression of cellular immune responses. This compound could be a novel candidate for inhibition of NF-κB in certain inflammatory diseases. SIGNIFICANCE STATEMENT: A novel nuclear factor-κB (NF-κB) inhibitory compound, 1H-pyrazolo[3,4-d]pyrimidin-4-amine derivative (INH #1), which retains physiologically essential NF-κB bioactivity, suppressed inflammation in three different mouse models: the acute hepatitis model, the collagen-induced arthritis model, and the K/BxN serum-transfer arthritis model. These results suggest that this compound could be a novel and potent anti-inflammatory agent.

An Insight into the Mechanism, Safety and Efficacy for Photoprotection and Dermatological Conditions of Polypodium leucotomos Extract

Abstract: Numerous photoprotective techniques have been employed to successfully shield against the harmful effects of ultraviolet radiation. Current photoprotective techniques have limitations due to the amount of topical application, insufficient physical protection, and adverse responses to topical agents. A newer option that offers a promising defense against solar radiation is systemic agents, the well-researched Polypodium leucotomos is significant in this category, and several studies have found to be effective ―oral sunscreenǁ. Polypodium leucotomos (PL) extract has gained significant attention as a potential therapeutic agent in the field of dermatology, particularly in the photoprotection and management of various dermatological conditions. This abstract provides a comprehensive overview of the mechanism, safety, and efficacy of Polypodium leucotomos extract in relation to photoprotection and dermatological conditions. Our primary aim is to review Polypodium leucotomos' photoprotective results from studies that are currently available, and our secondary goal is to describe Polypodium leucotomos' applications in different dermatological conditions. Articles discussing Polypodium leucotomos uses in photoprotection and dermatologic conditions are searched and downloaded from publicly available databases such as PubMed, JSTOR, PLOS, Science Direct, DOAJ, Google Scholar, and Web of Science and evaluate the outcomes of the Polypodium leucotomos effect. Firstly, we delve into the mechanisms underlying the photoprotective properties of PL extract. Extensive research has demonstrated that PL extract exerts its protective effects through multiple pathways, including antioxidant activity, DNA repair stimulation, immunomodulation, and inhibition of inflammatory mediators. These mechanisms collectively contribute to the prevention of photodamage, such as sunburn, DNA damage, and photoaging. Furthermore, we explore the safety profile of PL extract, emphasizing its remarkable tolerability and minimal adverse effects reported in clinical studies. The absence of systemic absorption and its compatibility with other treatments make PL extract a promising option for long-term use in photoprotection and dermatological care. A promising alternative to traditional photoprotection may be Polypodium leucotomos. Additional thorough clinical trials are necessary to ascertain its role and effectiveness more accurately. The efficacy of PL extract in managing various dermatological conditions is also discussed. Multiple studies have demonstrated its beneficial effects in conditions such as vitiligo, melasma, psoriasis, and atopic dermatitis. The anti-inflammatory and immunomodulatory properties of PL extract have shown promise in reducing disease severity, improving skin symptoms, and enhancing the quality of life for patients. Additionally, the abstract highlights the potential future directions and areas of research for PL extract. Investigating its combination therapy with other photoprotective agents, exploring optimal dosage regimens, and further elucidating the molecular mechanisms are areas that warrant attention. In conclusion, this abstract provides an insightful overview of the mechanisms, safety, and efficacy of PL extract in photoprotection and dermatological conditions. The remarkable properties of PL extract, combined with its favorable safety profile, position it as a promising therapeutic intervention in dermatology. Further research and clinical trials are needed to fully exploit its potential and establish its place in the management of various skin conditions.

Labetalol Ameliorates Experimental Colitis in Rat Possibly Through its Effect on Proinflammatory Mediators and Oxidative Stress.

Members of beta blockers drugs possess significant antioxidant activities. The current research is to assess the effect of the labetalol on acetic acid (AA-induced) colitis in rat model. Forty adult Wistar rats were separated into 4 groups, including the negative control group, AA group, AA + sulfasalazine (100 mg/kg/day) group, and AA + labetalol (300 mg/kg/day) group. Colitis was induced in rats by the interrectal installation of 2 mL of 4% (v/v) AA. Sulfasalazine and labetalol were administered orally for 7 days after 2 hours of induction. The following parameters were measured: disease activity index (DAI), histopa-thological changes and colon tissue homogenate concentrations of proinflammatory mediators IL-1β, adhesion molecules ICAM-1, and oxidative stress marker myeloperoxidase (MPO). The treatment with labetalol significantly reduced DAI and histopathological changes induced by AA. Also, labetalol markedly decreased the concentrations of IL-1β, ICAM-1, and MPO in colonic tissue that were increased by AA. The effects of labetalol were significantly lower than that produced by sulfasalazine as standard drug. Labetalol exerts ameliorative effects on disease activity and histopathological features of AA-induced colitis in rats possibly through antioxidant effects and inhibition of inflammatory mediators.

Retraction Note: A new cationic palladium(II) dithiocarbamate exhibits anti-inflammatory, analgesic, and antipyretic activities through inhibition of inflammatory mediators in in vivo models.

Retraction Note: A new cationic palladium(II) dithiocarbamate exhibits anti-inflammatory, analgesic, and antipyretic activities through inhibition of inflammatory mediators in in vivo models.

Molecular and clinical aspects relevant for counseling individuals with clonal hematopoiesis of indeterminate potential.

Clonal hematopoiesis of indeterminate potential (CHIP) has fascinated the medical community for some time. Discovered about a decade ago, this phenomenon links age-related alterations in hematopoiesis not only to the later development of hematological malignancies but also to an increased risk of early-onset cardiovascular disease and some other disorders. CHIP is detected in the blood and is characterized by clonally expanded somatic mutations in cancer-associated genes, predisposing to the development of hematologic neoplasms such as MDS and AML. CHIP-associated mutations often involve DNA damage repair genes and are frequently observed following prior cytotoxic cancer therapy. Genetic predisposition seems to be a contributing factor. It came as a surprise that CHIP significantly elevates the risk of myocardial infarction and stroke, and also contributes to heart failure and pulmonary hypertension. Meanwhile, evidence of mutant clonal macrophages in vessel walls and organ parenchyma helps to explain the pathophysiology. Besides aging, there are some risk factors promoting the appearance of CHIP, such as smoking, chronic inflammation, chronic sleep deprivation, and high birth weight. This article describes fundamental aspects of CHIP and explains its association with hematologic malignancies, cardiovascular disorders, and other medical conditions, while also exploring potential progress in the clinical management of affected individuals. While it is important to diagnose conditions that can lead to adverse, but potentially preventable, effects, it is equally important not to stress patients by confronting them with disconcerting findings that cannot be remedied. Individuals with diagnosed or suspected CHIP should receive counseling in a specialized outpatient clinic, where professionals from relevant medical specialties may help them to avoid the development of CHIP-related health problems. Unfortunately, useful treatments and clinical guidelines for managing CHIP are still largely lacking. However, there are some promising approaches regarding the management of cardiovascular disease risk. In the future, strategies aimed at restoration of gene function or inhibition of inflammatory mediators may become an option.

Roasting Extract of Handroanthus impetiginosus Enhances Its Anticancer Activity in A549 Lung Cancer Cells and Improves Its Antioxidant and Anti-Inflammatory Effects in Normal Cells

The family Bignoniaceae includes Handroanthus impetiginosus trees, which are sparsely distributed in the northeast of Brazil. Natural products play a vital role in the discovery of drugs for various diseases. Many plants have been used as sources of medicines because of their chemical diversity and potent bioactivity. Handroanthus impetiginosus has been used traditionally to cure a wide range of illnesses, such as cancer, oxidative stress, and inflammation. This work highlights the cytotoxicity, cell death, and routes of apoptosis in lung cancer cells (A549) and the anti-inflammatory and antioxidant effects of roasted Handroanthus impetiginosus (lapacho/taheebo) in normal cells. The cell viability assay indicated that puffing roasted taheebo is nontoxic to a normal cell line up to 500 µg/mL but significantly toxic to A549 cells. The roasted lapacho/taheebo also increases reactive oxygen species (ROS) generation in A549 lung cancer cells, and cellular apoptosis via a mitochondrial intrinsic pathway was confirmed. The roasted lapacho/taheebo significantly inhibited both colony formation and cell migration ability, highlighting its potential as an anticancer agent. Additionally, this study demonstrates that roasted taheebo enhanced the expression of genes for BAX accumulation and decreased Bcl-2 gene expression through the p53 signaling pathway. Furthermore, research on the anti-inflammatory properties of roasted taheebo revealed a strong NO inhibition as well as the inhibition of inflammatory mediators (TNF-α, iNOS, COX-2, IL-6, and IL-8) through the NF-κB signaling pathway. However, in H2O2-induced HaCaT cells, roasted taheebo extract significantly reduced oxidative stress by upregulating the level of expression of antioxidative markers (SOD, CAT, GPx, and GST) at 50 μg/mL. As a result, roasted taheebo justifies investigation in animal and clinical trials as a possible source of antioxidants, anti-inflammatory substances, and anti-cancer compounds.

Antiarthritic activity of Physalis peruviana fruit extract via inhibition of inflammatory mediators: Integrated in vitro, in vivo and in silico study

Ethnopharmacological relevanceP. peruviana fruit, native to Andean region, is cultivated worldwide for its adaptability to various soil natures and climatic conditions. It is increasingly consumed for its high nutritional profile and history of ethnomedical uses including treatment of arthritis. Little pharmacological evidences support this folk use except for previous in vitro study that reported significant inhibition of protein denaturation. Aim of the studyThe study aims at providing new in vivo evidence on antiarthritic activity of P. peruviana fruits in vivo that justifies its traditional use through mechanism-based experiment. Material and methodsInhibition of inflammatory mediators is considered one of the key treatments to alleviate painful symptoms of rheumatoid arthritis (RA). Anti-inflammatory activity was assessed against COX-1 and COX-2 activity in vitro.Serum TNFα, IL-1β and IL-6 were traced using in vivo model of adjuvant-induced arthritis. Gross/inflammatory changes in rat paw, relative mass indices of spleen and liver were further investigated together with joint tissue histoarchitecture. Seven metabolites from different phytochemical classes, that were previously reported in P. peruviana fruit, were evaluated in silico against TNF-α target protein (PDB ID: 2AZ5) to assess their inhibitory effect. This was followed by assessment of their drug-likeness based on Lipinski's rule according to their physicochemical and pharmacokinetic properties. ResultsHigh dose of extract (E−1000 mg) improved adjuvant-induced cachexia and attenuated immune-inflammatory responses in paw and serum parameters, with equipotent effect to MTX, in addition to minimal side effect profile on spleen and liver. Histopathological study of knee joint tissues confirmed dose-dependent improvement in arthritic groups treated with P. peruviana fruit extracts. The insilico study recommended steroidal lactones withaperuvin E/C and hydroxywithanolide E as promising lead compounds for inhibiting TNF enzyme as evidenced by docking scores of 6.301, 5.488 and 5.763 kcal/mol, respectively, fitting as well the Lipinski's rule of drug likeness. ConclusionThe study provided novel approach that rationalize folk use of P. peruviana fruit in treatment of arthritis.

Effect of nitro-conjugated linoleic acid on the inflammatory response of murine macrophages activated with lipopolysaccharide derived from Prevotella intermedia.

Nitro-conjugated linoleic acid (NO2-CLA) has been observed to manifest salutary signaling responses, including anti-inflammatory and antioxidant properties. Here, the authors have explored the influence and underlying mechanisms of NO2-CLA on the proinflammatory reaction of murine macrophages that were challenged with lipopolysaccharide (LPS) derived from Prevotella intermedia, a putative periodontopathic bacterium. Treatment of LPS-activated RAW264.7 cells with NO2-CLA notably dampened the secretion of iNOS-derived NO, IL-1β and IL-6 as well as their gene expressions and significantly enhanced the markers for M2 macrophage polarization. NO2-CLA promoted the HO-1 expression in cells challenged with LPS, and tin protoporphyrin IX, an HO-1 inhibitor, significantly reversed the NO2-CLA-mediated attenuation of NO secretion, but not IL-1β or IL-6. We found that cells treated with NO2-CLA significantly increased mRNA expression of PPAR-γ compared to control cells, and NO2-CLA significantly reverted the decrease in PPAR-γ mRNA caused by LPS. Nonetheless, antagonists to PPAR-γ were unable to reverse the NO2-CLA-mediated suppression of inflammatory mediators. In addition, NO2-CLA did not alter the p38 and JNK activation elicited by LPS. Both NF-κB reporter activity and IκB-α degradation caused by LPS were notably diminished by NO2-CLA. NO2-CLA was observed to interrupt the nuclear translocation and DNA binding of p50 subunits caused by LPS with no obvious alterations in p65 subunits. Further, NO2-CLA attenuated the phosphorylation of STAT1/3 elicited in response to LPS. We propose that NO2-CLA could be considered as a possible strategy for the therapy of periodontal disease, although additional researches are certainly required to confirm this.

Calbindin 2-specific deletion of arginase 2 preserves visual function after optic nerve crush

We previously found that global deletion of the mitochondrial enzyme arginase 2 (A2) limits optic nerve crush (ONC)-induced neuronal death. Herein, we examined the cell-specific role of A2 in this pathology by studies using wild type (WT), neuronal-specific calbindin 2 A2 KO (Calb2cre/+ A2 f/f), myeloid-specific A2 KO (LysMcre/+ A2f/f), endothelial-specific A2 KO (Cdh5cre/+ A2f/f), and floxed controls. We also examined the impact of A2 overexpression on mitochondrial function in retinal neuronal R28 cells. Immunolabeling showed increased A2 expression in ganglion cell layer (GCL) neurons of WT mice within 6 h-post injury and inner retinal neurons after 7 days. Calb2 A2 KO mice showed improved neuronal survival, decreased TUNEL-positive neurons, and improved retinal function compared to floxed littermates. Neuronal loss was unchanged by A2 deletion in myeloid or endothelial cells. We also found increased expression of neurotrophins (BDNF, FGF2) and improved survival signaling (pAKT, pERK1/2) in Calb2 A2 KO retinas within 24-hour post-ONC along with suppression of inflammatory mediators (IL1β, TNFα, IL6, and iNOS) and apoptotic markers (cleavage of caspase3 and PARP). ONC increased GFAP and Iba1 immunostaining in floxed controls, and Calb2 A2 KO dampened this effect. Overexpression of A2 in R28 cells increased Drp1 expression, and decreased mitochondrial respiration, whereas ABH-induced inhibition of A2 decreased Drp1 expression and improved mitochondrial respiration. Finally, A2 overexpression or excitotoxic treatment with glutamate significantly impaired mitochondrial function in R28 cells as shown by significant reductions in basal respiration, maximal respiration, and ATP production. Further, glutamate treatment of A2 overexpressing cells did not induce further deterioration in their mitochondrial function, indicating that A2 overexpression or glutamate insult induce comparable alterations in mitochondrial function. Our data indicate that neuronal A2 expression is neurotoxic after injury, and A2 deletion in Calb2 expressing neurons limits ONC-induced retinal neurodegeneration and improves visual function.

Standardized seed extract of Cajanus cajan (L) Millsp. produced antinociceptive and anti-inflammatory actions through inhibition of inflammatory mediators and activation of opioidergic signaling

Background and PurposePeripheral tissue damage and diseases could lead to persistent pain beyond possible resolution suggestive of disease-promoting condition which gives rise to chronic pain. The inability of current medications to manage some chronic inflammatory and painful conditions necessitate the need for better treatment options. Natural products have been a veritable source for the discovery of more efficacious and safer therapeutics. Cajanus cajan (L) Millsp, (Fabaceae) is used in traditional African medicines for the treatment of painful, gut disturbance and inflammatory conditions. Hence, the current study aims to investigate the anti-inflammatory and antinociceptive actions of the ethanol seed extract of Cajanus cajan (CC) in rodents and possible mechanisms of action. MethodsHigh performance liquid chromatography coupled with diode-array detection (HPLC-DAD) was used to identify 8 major flavonoids in CC. Antinociceptive activity was investigated using the acetic acid-induced writhing reflex, biphasic formalin-induced flinching behaviour and supraspinal hot plate-evoked nociception in mice. Carrageenan-induced rat paw oedema test was used to evaluate the anti-inflammatory action of CC in rats. Possible mechanism of antinociception and anti-inflammatory actions were examined using both in vivo model and molecular docking procedures against µ-opioid receptor (MOR), cyclooxygenase-2 (COX-2) and phospholipase A2 (PLA2) proteins, respectively. ResultsThe chromatographic procedure qualitatively and quantitatively confirmed the presence of rutin, quercetin, gallic acid, luteolin, pinostrobin, BiochaninA, formononetin and apigenin in CC. The in vivo nociceptive assay, showed that CC (50, 100, or 200 mg/kg, p.o.) significantly decreased mean number of writhing reflex with peak effect at 50 mg/kg (72% inhibition) when compared with vehicle control in mouse writhing test. Similarly, the biphasic formalin-induced nociception was significantly reduced by CC (50 mg/kg) with 24.61 and 66.73% inhibition of nociceptive reactions in both the early and late phases of formalin-induced inflammatory pain, respectively. In addition, CC significantly increased supraspinal thermally mediated pain threshold with maximum possible effects of 42.25 and 52.16% at CC 50 and 100 mg/kg, respectively, in hot-plate test. Similarly, CC100mg/kg caused time course inhibition of carrageenan-induced paw oedema in rat with peak effect (65.78%, CC 100 mg/kg; 6 h). Interestingly, the antinociceptive action of CC was blocked by the pre-treatment of mice with l-NG-nitro arginine methyl ester (L-NAME) or naloxone. The molecular docking analysis revealed prominent interactions of pinostrobin, physcion and lupeol with MOR, COX-2, and PLA2, respectively. ConclusionFindings from this study showed that Cajanus cajan seeds extract possesses anti-nociceptive and anti-inflammatory through inhibition of inflammatory mediators (PLA2/COX-2) and activation of opioidergic signalling.

Crosslinking of Water-Soluble Cyclodextrin with Hyaluronic Acid for Targeted Drug Delivery

Introduction: Most of the cytotoxic anticancer drugs belong to substances with both low solubility in aqueous fluids and poor cellular uptake, which lead to lack of specific therapy with apparent side effects. Therefore, there is a need to develop a novel drug delivery that can remotely and selectively release their payload. Curcumin(CUR) is an antibiotic, also a powerful inhibitor of the proliferation of several tumor cells.
 Aims: The aim of the present work is to highlight and discussed hyaluronic acid (HA ) to be grafted with Mono-6-deoxyl-6-ethylenediamino-γ-cyclodextrin (ɣ-CD-EDA) to shape a hydrogel that ought to structure inclusion complexes with curcumin, bettering its water-solubility and serving as a model drug delivery system
 Methods: Distinct copolymers had been organized HA grafted with ɣ-cyclodextrin (ɣ-CD-EDA) to form a hydrogel with various HA: ɣ-CD-EDA ratios and characterized,
 by means of 1H-NMR spectroscopy, zeta potential, Thermogravimetry analysis) TGA) Differential scanning calorimetry (DSC), and transmission electron microscopy (TEM). Furthermore, drug loading Encapsulation efficiency (EE%), and release kinetics, and stability. Also, cytotoxicity and uptake were assessed by flow cytometry, MTT assay and confocal laser microscopy. Wound healing activity was once improved using three cell MDA-MB-231, MCF-7, and fibroblast. Measuring the effect of HA-γ-CD-EDA1-CUR, γ-CD-EDA1-CUR, and CUR free on the Production and Secretion of inflammatory cytokines
 Result: CUR loading potential used to be at once correlated with extended HA-ɣ-CD-EDA composition and morphological adjustments have been discovered upon CUR binding. The host substances and their CUR inclusion complexes are no longer cytotoxic, and consequently beneficial for CUR and drug delivery. Moreover, HA-γ-CD-EDA1-CUR, γ-CD-EDA1-CUR, and CUR wound healing activity was once improved, and human promonocytic THP-1 cells produce inflammatory mediators such as IL-1β, IL10,IL8, TNF-α,IRAKI and IL6 results showed that the combination HA-γ-CD-EDA1-CUR could be suitable to reduce inflammation and the complex promoted the anti-inflammatory effect by the inhibition of inflammatory mediators.
 Conclusion: HA grafted with ɣ-cyclodextrin (ɣ-CD-EDA) to form a hydrogel was designed, formulated, and full characterized. Nanoparticles were stable at physiological pH and have released payload. Encapsulation of CUR into polymer increased its selectivity, distribution, and accumulation into the cancer cells. HA-CD-EDA1conjugated curcumin if incorporated in suitable matrix has a potential utility for treatment of wound, and down regulation in THP-1 cells.

Proof-of-Principle Study of Inflammasome Signaling Proteins as Diagnostic Biomarkers of the Inflammatory Response in Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder marked by the death of dopaminergic neurons in the midbrain, the accumulation of α-synuclein aggregates, and motor deficits. A major contributor to dopaminergic neuronal loss is neuroinflammation. The inflammasome is a multiprotein complex that perpetuates neuroinflammation in neurodegenerative disorders including PD. Increases in inflammasome proteins are associated with worsened pathology. Thus, the inhibition of inflammatory mediators has the potential to aid in PD treatment. Here, we investigated inflammasome signaling proteins as potential biomarkers of the inflammatory response in PD. Plasma from PD subjects and healthy age-matched controls were evaluated for levels of the inflammasome protein apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, and interleukin (IL)-18. This was carried out using Simple Plex technology to identify changes in inflammasome proteins in the blood of PD subjects. The area under the curve (AUC) was obtained through calculation of the receiver operating characteristics (ROC) to obtain information on biomarker reliability and traits. Additionally, we completed a stepwise regression selected from the lowest Akaike information criterion (AIC) to assess how the inflammasome proteins caspase-1 and ASC contribute to IL-18 levels in people with PD. PD subjects demonstrated elevated caspase-1, ASC, and IL-18 levels when compared to controls; each of these proteins were found to be promising biomarkers of inflammation in PD. Furthermore, inflammasome proteins were determined to significantly contribute to and predict IL-18 levels in subjects with PD. Thus, we demonstrated that inflammasome proteins serve as reliable biomarkers of inflammation in PD and that inflammasome proteins provide significant contributions to IL-18 levels in PD.

Abstract 4874: Hyperforin induces apoptosis and inhibits invasion via inhibiting AKT/NF-ΚB signaling pathway in colorectal cancer cells

Abstract Recently, the incidence of colorectal cancer (CRC) has been increasing year by year and has become the first incidence cancer in Taiwan. Epidermal growth factor receptor inhibitor (EGFR inhibitor) has been recognized as an important target of CRC. Therefore, targeting EGFR and its related signaling could be a potential strategy to overcome this disease. Hyperforin is a natural prenylated phloroglucinol and has been identified as the major molecule responsible for the antidepressant effects. Previous studies indicated that hyperforin has other potentially pharmacologically meaningful biological properties, including antibacterial ability and inhibition of inflammatory mediators. Numerous studies have also pointed out the anti-tumor potential of hyperforin is associated with the induction of apoptosis signaling. However, whether hyperforin may regulate CRC progression and its underlying mechanism is unclear. In our study, we used the MTT assay to prove the cytotoxicity of CRC cells (HT29 and HCT116 cells) was induced by hyperforin. We then used the flow cytometry to confirmed that hyperforin may induce both extrinsic/intrinsic apoptotic pathways in CRC cells. We further demonstrated hyperforin-induced apoptosis pathways is associated with mitochondrial-dependent apoptosis and death receptor dependent apoptosis. Then, transwell invasion, migration, and wound healing assay results proved the inhibition effect by hyperforin in HT29 and HCT116 cells. Additionally, we suggested that hyperforin can effectively inhibit EGFR downstream genes MEK-ERK and AKT signaling, as well as inhibit the phosphorylation of NF-ΚB and the nuclear translocation in CRC cells. In sum, our results show that hyperforin can inhibit the apoptosis and metastasis ability of CRC cells by inhibiting both AKT/NF- ΚB and ERK/NF-ΚB signaling pathway. Citation Format: Ying-Tzu Chen, I-Tsang Chiang, Yuan Chang, Fei-Ting Hsu. Hyperforin induces apoptosis and inhibits invasion via inhibiting AKT/NF-ΚB signaling pathway in colorectal cancer cells. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4874.

Berberine Suppresses Gestational Diabetes in Streptozotocin-induced Diabetes Mellitus Rats by Suppression of Inflammatory Mediators

Abstract: Background: Gestational diabetes mellitus (GDM) is a serious health condition witnessed among females who experience insulin resistance and glucose intolerance with the onset of pregnancy. Multiple risk factors prevail both to the gestating mother and the growing fetus at the time of pregnancy which may prolong even postpartum. Aim: Berberine, a natural plant extract known for its anti-inflammatory and potent antidiabetic activity was used to clinically suppress the risk factors involved in Gestational diabetes mellitus. Materials and Methods: Female Wistar rats were used as the models for this study. Streptozotocin was administered to induce diabetes in the female rat model. Berberine was administered to the test animals and monitored with regular analysis of body weight, fetal-placental weight and index, Foetal Blood Glucose (FBG), Serum advanced glycation end products (AGEs), and antioxidant enzyme concentrations. Biochemical parameters, lipids, and pro-inflammatory cytokine levels were assayed to study the influence of Berberine. Results: Upon investigating, it was observed that Berberine produced remarkable activity in suppressing glucose intolerance and insulin resistance by targeting multiple criteria, including inflammatory mediators enlisted above. Conclusion: From this study, it is evident that Berberine can be used as a therapeutic agent to treat gestational diabetes. Keywords: Gestational diabetes mellitus, Inflammation, Berberine, Antioxidant, Antidiabetic.

Synthesis and Anti-inflammatory Activity of 5, 6-difluoro-2-Methyl-4H-benzo (d) (1, 3)-Oxazin-4-one(1) and 3-Amino-5,6-difluoro-2-Mehtyl-quinzolin 4(3H)-One(2)

Background: Inflammation is one of the means the human body uses to defend itself in the event of infection, trauma, or exposure to toxic substances and it is closely associated with a number of disease symptoms. Steroidal and non-steroidal anti-inflammatory agents have been the drugs of choice for managing inflammation. However, reports of unpleasant side effects have necessitated a search for new anti-inflammatory agents which have minimal side effects. Inflammation is an adaptive response of body tissues to external challenge or cellular injury. It is generally thought that inflammation is a beneficial host response defense system, but it can become harmful if dysregulated. The complex mediators including proinflammatory and cytotoxic cytokines, growth factors, bioactive lipids, and nitric oxide in the uncontrolled inflammation reaction can sustain or induce a pathologic process involved in different diseases, such as allergy, sepsis, arthritis, the metabolic syndrome, autoimmune diseases, and cancer anti-inflammatory activities of 101 extracts from different parts of 84 traditional medicinal plants were evaluated by a panel of in vitro and in vivo assays. Nuclear factor-kappa B (NF-κB) inhibitory effects were determined by luciferase assay in stably transfected Hela cells. The inhibition of inflammatory mediators on the transcriptional level has emerged as a promising approach for the development of anti-inflammatory drugs Method: The current study is aimed at the synthesis and Anti–inflammatory evaluation of quinazolinone derivatives. The condensation of Methyl-2-amino-5,6-diflorobenzoate with acetic anhydride yielded the cyclic compound 2-methyl 5,6-diflorobenzo [d] [1,3]-oxazine-4-one which further produce 3-Amino-2-Methyl 5,6-difloro quinazolin-4(3H)-ones via the reaction with hydrazine hydrate. The compounds synthesized were unequivocally confirmed by means of Infrared, Nuclear Magnetic Resonance (1H and 13C), Gas Chromatography Mass Spectrophotometry and Elemental analysis. The synthesized compounds were screened for their Anti–inflammatory activity. Result: The two compounds 1 and 2 showed significant activity as an Anti–inflammatory agent. Conclusion: The investigated Compounds exhibited significant Anti–inflammatory activity in the range of 70.56 – 83.80% compared to control.

Combretum hypopilinum exhibited anti-inflammatory activity in LPS-stimulated RAW 264.7 murine macrophages through inhibition of inflammatory mediators and apoptosis

Combretum hypopilinum exhibited anti-inflammatory activity in LPS-stimulated RAW 264.7 murine macrophages through inhibition of inflammatory mediators and apoptosis

Levosimendan Increases Survival in a D-Galactosamine and Lipopolysaccharide Rat Model.

Levosimendan, a calcium sensitizer, has an organ protective profile through the inhibition of inflammatory mediators and cytokines in critical conditions, such as heart failure, ischemia-reperfusion injury, and sepsis. The survival effect of levosimendan for acute liver failure has not been examined yet. Male Sprague-Dawley rats were examined in the D-galactosamine hydrochloride and lipopolysaccharide (GalN/LPS) model. Levosimendan was injected intraperitoneally before GalN/LPS treatment. Survival was monitored for 7 days. For biochemical analyses, liver and blood samples were collected from the rats at 1 and 8 h after GaIN/LPS treatment. The pretreatment of levosimendan at 4 mg/kg significantly increased survival in GalN/LPS rats. In the liver specimen, levosimendan significantly inhibited the activation of nuclear factor-κB (NF-κB) at 1 h, and significantly decreased the mRNA expression of inflammatory mediators, including inducible nitric oxide synthase and tumor necrosis factor-α (TNF-α), at 8 h. In serum, levosimendan decreased the levels of nitrite, a metabolite of nitric oxide, and TNF-α protein, as well as aspartate aminotransferase and alanine aminotransferase. These results indicated that Levosimendan ameliorated liver dysfunction and survival in acute liver failure model rats through the suppression of NF-κB activation.