Inflammatory Enzymes Research Articles

DDDR-18. TARGETTING GLIOBLASTOMA MULTIFORME USING A MULTIACTION ANTICANCER ANTI-INFLAMMATORY THERAPEUTIC STRATEGY

Abstract Glioblastoma multiforme (GBM) represents a significant challenge in adult brain tumor management, characterized by its aggressive nature and poor prognosis despite multimodal therapies. Current standard chemotherapy, Temozolomide (TMZ), offers limited survival benefits. In a recent breakthrough, the cyclic peptide cyclo-((2-Nal)-Leu-Ser-(2-Nal)-Arg) acetate (c2), initially developed for prostate cancer, demonstrates remarkable promise against GBM. By selectively inhibiting the inflammatory phospholipase enzyme sPLA2IIA, c2 significantly impedes GBM cell proliferation, surpassing TMZ efficacy in multiple resistant cell lines. Moreover, c2 exhibits potential to inhibit tumor growth and metastasis, confirmed in 3D tumoroid and wound healing assays. Mechanistic insights reveal modulation of crucial cellular pathways, including viral entry, cytoskeletal structure, and signaling cascades. Preclinical investigations demonstrate c2’s ability to penetrate the blood-brain barrier and attenuate tumor progression markers. At multiple levels, c2 is shown to target inhibition of ERBB2 and EGFR signalling and also have impacts on HIF1-NF-kB axis. This study proposes c2 as a potent anti-GBM candidate, warranting evaluations for its pharmacological profile, safety, and efficacy. With its potential to address the urgent need for effective GBM therapies, c2 holds promise as a significant advancement in GBM treatment, offering hope for improved patient outcomes.

Involvement of Molecular Mechanism and Biological Activities of Pemirolast: A Therapeutic Review

: This review paper aims to investigate the therapeutic benefits of pemirolast across different medical conditions, including asthma, allergic rhinitis, cancer, conjunctivitis, etc. The prevalence of allergic conditions has risen in recent decades, primarily attributed to environmental factors. This paper explores the role of pemirolast in managing and mitigating these diseases, shedding light on its potential applications in the context of evolving environmental influences. : This review paper investigates the diverse biological activities exhibited by pemirolast, encompassing its roles as an antimicrobial, analgesic, antiviral, anti-inflammatory, antioxidant, antihistamine, mast cell stabilizer, anti-tubercular, anticancer, anti-asthmatic, anti-malarial, diuretic, antianxiety, and antifungal agent. The positive outcomes of pemirolast application in various diseases are highlighted, showcasing its potential across a spectrum of medical conditions. : The pharmacological impact of pemirolast extends to diverse inflammatory mediators, enzymes, and hormones associated with various diseases. Pemirolast demonstrates inhibitory effects on key elements such as eosinophil activation, histamine, leukotriene, IgE, mast cells, basophils, prostaglandin, interleukin, T-helper cells, macrophage T-cells, neutrophils, tryptase, T-lymphocytes, interferons I-III, Amyloid β (Aβ) peptide, dsRNA transcription, GABA, dopamine, serotonin, and norepinephrine. This comprehensive exploration underscores pemirolast inhibitory actions across disorders, emphasizing its potential therapeutic relevance in diverse pathological conditions. : This review paper illuminates pemirolast potassium's versatile biological and therapeutic applications across various diseases. The potential synergies of combining pemirolast with buspirone, ritanserin, theophylline, and capreomycin are explored, showcasing its ability to elicit beneficial responses in addressing diverse ailments.

Radical-Scavenging Violet Phosphorus Nanosheets for Attenuating Hyperinflammation and Promoting Infected Wound Healing.

Antibacterial therapy targeting the regulation of macrophage polarization may be a useful approach for normalizing the immune environment and accelerating wound healing. Inspired by black phosphorus-based nanoplatforms, more stable yet less-explored violet phosphorus nanosheets (VPNSs) are expected to provide a superior solution for effectively combating bacterial infections. In this study, an average thickness of 5-7nm VPNSs arefabricated through the liquid-phase exfoliation method to serve as an immunoregulatory dressing for the treatment of infected wounds. VPNSs attenuated excessive reactive oxygen species (ROS) and reduced the accumulation of proinflammatory M1 macrophages, showing notable antioxidant and anti-inflammatory properties. Comprehensive RNA sequencing further elucidated the potential immunoregulatory mechanisms of VPNSs, including modulation of the inflammatory response and enzyme regulator activity. Additionally, the inherent photothermal properties of the VPNSs contributed significantly to their antibacterial efficacy. When combined with near-infrared laser irradiation, VPNSs showed remarkable effectiveness in reducing infection-related complications and expediting wound healing in infected skin wound models. The rapid promotion of wound healing through ROS clearance, the regulation of macrophage polarization, and hyperthermia generation underscores the potential of the violet-phosphorus-based nanoplatforms as clinically viable agents for treating infected wounds. This study suggests that VPNSs are promising candidates for clinical anti-infective and anti-inflammatory applications.

Role of Callistemon citrinus Leaf Phytosomes Against Oxidative Stress and Inflammation in Rats Fed with a High-Fat-Fructose Diet.

Phytosomes are used as vehicles that carry plant extracts. They exhibit biological activities and possess better bioavailability, bioabsorption, and lower toxicity than drugs. Obesity is an inflammatory state in which oxidative stress is present, which triggers severe effects on the body's organs. This study aimed to evaluate the impact of the extract and phytosomes of Callistemon citrinus on oxidative stress and inflammation in the liver and heart of Wistar rats fed with a high-fat-fructose diet. Phytosomes containing the extract of leaves of C. citrinus were prepared. The antioxidant, pro-inflammatory enzymes, and biomarkers of oxidative stress were evaluated. Among the groups, only the high-fat-fructose group presented an increase in the COX-2, 5-LOX, and MPO inflammatory enzymes, while the XO enzyme exhibited decreased activity. The groups were fed a hypercaloric diet for 15 weeks while orlistat, C. citrinus extract, and phytosomes were administered at three different concentrations, exhibiting enzyme activities similar to those of the control group. It was also observed that the lowest concentration of phytosomes had a comparable effect to the other concentrations. Callistemon citrinus extract can modulate the activities of enzymes involved in the inflammation process. Furthermore, small doses of phytosomes can serve as anti-inflammatory agents.

Synthesis of Low-Molecular-Weight Fucoidan Analogue and Its Inhibitory Activities against Heparanase and SARS-CoV-2 Infection.

Heparan sulfate (HS) is ubiquitous on cell surfaces and is used as a receptor by many viruses including SARS-CoV-2. However, increased activity of the inflammatory enzyme heparanase (HPSE), which hydrolyses HS, in patients with COVID-19 not only increases the severity of symptoms but also may facilitate the spread of the virus by degrading HS on the cell surface. Therefore, synthetic HPSE blockades, which can bind to SARS-CoV-2 spike protein (SARS-CoV-2-S) and inhibit viral entry, have attracted much attention. This study investigated the development of a new dual-targeting antiviral agent against HPSE and SARS-CoV-2-S using fucoidan as a structural motif. It was found that all-sulfated fucoidan derivative 10, which exhibited the highest binding affinity to SARS-CoV-2-S among 13 derivatives, also showed the highest inhibitory activity against HPSE. Based on this, a newly designed and synthesized fucoidan analogue 16, in which the octyl group of 10 was changed to a cholestanyl group, was found to show higher activity than 10 but did not inhibit factor Xa associated with undesired anticoagulant effects. The binding affinity of 16 to SARS-CoV-2-S was significantly increased approximately 400-fold over that of 10.Furthermore, 16 effectively inhibited infection by the SARS-CoV-2 Wuhan strain and two Omicron subvariants.

Synthesis of Low‐Molecular‐Weight Fucoidan Analogue and Its Inhibitory Activities against Heparanase and SARS‐CoV‐2 Infection

Heparan sulfate (HS) is ubiquitous on cell surfaces and is used as a receptor by many viruses including SARS‐CoV‐2. However, increased activity of the inflammatory enzyme heparanase (HPSE), which hydrolyses HS, in patients with COVID‐19 not only increases the severity of symptoms but also may facilitate the spread of the virus by degrading HS on the cell surface. Therefore, synthetic HPSE blockades, which can bind to SARS‐CoV‐2 spike protein (SARS‐CoV‐2‐S) and inhibit viral entry, have attracted much attention. This study investigated the development of a new dual‐targeting antiviral agent against HPSE and SARS‐CoV‐2‐S using fucoidan as a structural motif. It was found that all‐sulfated fucoidan derivative 10, which exhibited the highest binding affinity to SARS‐CoV‐2‐S among 13 derivatives, also showed the highest inhibitory activity against HPSE. Based on this, a newly designed and synthesized fucoidan analogue 16, in which the octyl group of 10 was changed to a cholestanyl group, was found to show higher activity than 10 but did not inhibit factor Xa associated with undesired anticoagulant effects. The binding affinity of 16 to SARS‐CoV‐2‐S was significantly increased approximately 400‐fold over that of 10. Furthermore, 16 effectively inhibited infection by the SARS‐CoV‐2 Wuhan strain and two Omicron subvariants.

Development of a New Isoxsuprine Hydrochloride-Based Hydroxylated Compound with Potent Antioxidant and Anti-Inflammatory Activities.

The scientific community actively pursuits novel compounds with biological activities. In this context, our study utilized the predicted data mining approach (PDMA), which can efficiently screen out biotransformable precursor candidates to produce new bioactive compounds. The PDMA was applied to Bacillus megaterium tyrosinase (BmTYR) to form new bioactive hydroxyl compounds from isoxsuprine hydrochloride (isoxsuprine). The results show that isoxsuprine could be biotransformed by BmTYR to form a new compound, 3''-hydroxyisoxsuprine. 3''-Hydroxyisoxsuprine exhibited 40- fold and 10-fold higher potent antioxidant and anti-inflammation activities than the precursor, isoxsuprine. The 3''-hydroxyisoxsuprine effectively mitigates the hyperimmune response in RAW 264.7 macrophages by inhibiting the upregulation of pro-inflammatory cytokine (IL-1β and IL-6) and inflammatory enzyme COX-2 gene expression triggered by LPS stimulation. This study illustrates that PDMA is an effective strategy for screening known natural and chemical compounds and for generating new bioactive compounds through biotransformation. Our newly produced compound has potential future applications in pharmacology and biotechnology.

New Therapeutic Rargets for Cynodon Dactylon in Atherosclerosis: Attenuation of TMAO Generation and Down-regulation of TLR-4 in Rats

Purpose: Atherosclerosis (AS) is a chronic disease with worldwide incidence. The current study was conducted to highlight the molecular pathogenesis of AS and equal effectiveness of cynodon dactylon’s ethanolic extract (CDE) on the AS-induced injuries. Methods: Atherosclerosis was induced experimentally in healthy male rats with a hypercholesterolemic diet (HCD) for 24 weeks. The HCD-received animals were either treated with normal saline or various doses of CDE and/or atorvastatin. After 24 weeks of the treatment period, the effects of HCD on lipid profile, oxidative/nitrosative stress status, inflammatory enzymes (LDH, ALP and CKMB) activities, trimethylamine oxide (TMAO) concentration in serum along with the expression of TLR-4 (qPCR) and CD31 (Immunohistochemistry) in coronary and aorta were analyzed Results: CDE was able to reduce the HCD-enhanced cholesterol and triglycerides. The HCDelevated activities of LDH, ALP and CK-MB were declined by CDE. The antioxidant potency of CDE was comparable with atorvastatin on HCD-induced oxidative/nitrosative stress. The serum concentration of TMAO was lowered (1.7-fold) by CDE in a dose-dependent manner, while CD31 expression in the endothelial of coronary arterials and aorta in CDE and atorvastatin-received animals was remarkably increased. The up-regulated expression of TLR-4 (2.5-fold) at mRNA level was regulated significantly (p < 0.05) and returned to normal level by CDE treatment. Conclusion: Results of the current study indicate that the up-regulation of TLR-4 as a main inflammatory gene and elevation of TMAO are involved in the pathophysiology of AS. Moreover, the protective effects of CDE on AS may be attributed to its anti-inflammatory and hypolipidemic properties.

Carotenoids from cyanobacteria modulate iNOS and inhibit the production of inflammatory mediators: Promising agents for the treatment of inflammatory conditions

Cyanobacteria are green multiproduct refineries of increasing interest for different industrial prospects. In this work, eleven cyanobacteria strains isolated from the Cape Verde archipelago were explored for their biotechnological applications in the field of inflammation. A biorefinery approach was employed to produce carotenoid-targeted extracts, further profiled by HPLC-PDA and explored for their ability to i) scavenge important physiological free radicals of oxygen (superoxide anion radical, O2•-) and nitrogen (nitric oxide, •NO) involved in the inflammatory process ii) slow-down post-inflammatory hyperpigmentation and iii) modulate the activity of inflammatory cytokine-producing enzymes, in enzymatic and cell systems comprising RAW 264.7 cells. The studied strains turned out to be important carotenoid producers (70.47–186.71 μg mg−1dry extract), mainly represented by β-carotene and zeaxanthin. The targeted-extracts stood-out for their potential to slow-down the inflammatory process through a multitarget approach: scavenging •NO and O2•-, reducing inflammatory cytokines production through lipoxygenase inhibition, and modulating the inducible nitric oxide synthase in LPS-stimulated RAW 264.7 cells, with strains of the order Nodosilineales revealing to be worth of further biotechnological exploitation.

Modulation of M1/M2 Cytokines and Inflammatory Enzymes by Persicaria Species Leaf Extracts in Lipopolysaccharide-stimulated RAW 264.7 Cell Macrophages.

Investigating the impacts of plant-based substances on the regulation of pro-inflammatory M1 and anti-inflammatory M2 cytokines could have significant implications for immune-related health conditions. Seven Persicaria plant species from sub-Saharan Africa were specifically selected for analysis, based on their traditional use in treating inflammation. To investigate the inhibitory effects of methanol leaf extracts from selected plants on enzymes involved in chronic inflammation. The inhibition of nitric oxide production, acetylcholinesterase activity, and 15-lipoxygenase activity was assessed using the Griess reagent method, Ellman's colorimetric method, and the ferrous oxidation-xylenol orange assay. The quantity of M1/M2 cytokines released was quantified using a flow cytometer. At a concentration of 50 µg/mL, the methanol extracts of P. limbata exhibited the highest NO inhibition (97.67%), followed by P. nepalensis (93.06%) and P. setosula (92.78%). The NO inhibition caused by the plant extracts was correlated directly with the decrease in NO release by the LPS-stimulated macrophages. Furthermore, the pro-inflammatory enzyme assays indicated that the methanol extracts of P. setosula exhibited the highest enzyme inhibitory activity (LOX 89.59%, AChE 72.12 %). This was followed by P. limbata (with 92.76% for LOX and 56.93% for AChE) and P. nepalensis (with 88.16% for LOX and 47.17% for AChE). Cytokine assays revealed that the extracts of P. limbata had significant dose-dependent suppressive effects on IFN-γ and TNF-α expression while promoting the secretion of IL-2, IL-4, IL-6, and IL-10. Extracts of P. limbata contain immunomodulatory compounds that could be further explored as potential remedies to target the molecular drivers of chronic inflammation.

Spray drying of a zinc complexing agent for inhalation therapy of pulmonary fibrosis

Pulmonary fibrosis, a disabling lung disease, results from the fibrotic transformation of lung tissue. This fibrotic transformation leads to a deterioration of lung capacity, resulting in significant respiratory distress and a reduction in overall quality of life. Currently, the frontline treatment of pulmonary fibrosis remains limited, focusing primarily on symptom relief and slowing disease progression. Bacterial infections with Pseudomonas aeruginosa are contributing to a severe progression of idiopathic pulmonary fibrosis.Phytic acid, a natural chelator of zinc, which is essential for the activation of metalloproteinase enzymes involved in pulmonary fibrosis, shows potential inhibition of LasB, a virulence factor in P. aeruginosa, and mammalian metalloproteases (MMPs). In addition, phytic acid has anti-inflammatory properties believed to result from its ability to capture free radicals, inhibit certain inflammatory enzymes and proteins, and reduce the production of inflammatory cytokines, key signaling molecules that promote inflammation. To achieve higher local concentrations in the deep lung, phytic acid was spray dried into an inhalable powder. Challenges due to its hygroscopic and low melting (25 °C) nature were mitigated by converting it to sodium phytate to improve crystallinity and powder characteristics. The addition of leucine improved aerodynamic properties and reduced agglomeration, while mannitol served as carrier matrix. Size variation was achieved by modifying process parameters and were evaluated by tools such as the Next Generation Impactor (NGI), light diffraction methods, and scanning electron microscopy (SEM). An inhibition assay for human MMP-1 (collagenase-1) and MMP-2 (gelatinase A) allowed estimation of the biological effect on tissue remodeling enzymes. The activity was also assessed with respect to inhibition of bacterial LasB. The formulated phytic acid demonstrated an IC50 of 109.7 µg/mL for LasB with viabilities > 80 % up to 188 µg/mL on A549 cells. Therefore, inhalation therapy with phytic acid-based powder shows promise as a treatment for early-stage Pseudomonas-induced pulmonary fibrosis.

Ulva lactuca polysaccharides combined with fecal microbiota transplantation ameliorated dextran sodium sulfate-induced colitis in C57BL/6J mice.

Fecal microbiota transplantation (FMT) of healthy donors improves ulcerative colitis (UC) patients by restoring the balance of the gut microbiota. However, donors vary in microbial diversity and composition, often resulting in weak or even ineffective FMT. Improving the efficacy of FMT through combination treatment has become a promising strategy. Ulva lactuca polysaccharides (ULP) have been found to benefit host health by regulating gut microbiota. The effect of the combination of ULP and FMT in ameliorating UC has not yet been evaluated. The present study found that supplementation with ULP combined with FMT showed better effects in ameliorating UC than supplementation with FMT alone. Results suggested that FMT or ULP combined with FMT alleviated the symptoms of UC in mice, as evidenced by prevention of body weight loss, improvement of disease activity index and protection of the intestinal mucus. Notably, ULP in combination with FMT was more effective than FMT in reducing levels of cytokines and related inflammatory enzymes. In addition, ULP combined with FMT effectively restored the dysbiosis induced by dextran sulfate sodium (DSS) and further enriched probiotics (such as Bifidobacterium). The production of short-chain fatty acids, especially acetic acid, was also significantly enriched by ULP combined with FMT. Supplementation of ULP combined with FMT could significantly ameliorate DSS-induced colitis in mice by inhibiting inflammation and restoring dysbiosis of gut microbiota. These results suggested that ULP combined with FMT has potential application in ameliorating UC. © 2024 Society of Chemical Industry.

The Potential Health Benefits of Gallic Acid: Therapeutic and Food Applications.

Gallic acid (GA), a phenolic acid found in fruits and vegetables, has been consumed by humans for centuries. Its extensive health benefits, such as antimicrobial, antioxidant, anticancer, anti-inflammatory, and antiviral properties, have been well-documented. GA's potent antioxidant capabilities enable it to neutralize free radicals, reduce oxidative stress, and protect cells from damage. Additionally, GA exerts anti-inflammatory effects by inhibiting inflammatory cytokines and enzymes, making it a potential therapeutic agent for inflammatory diseases. It also demonstrates anticancer properties by inhibiting cancer cell growth and promoting apoptosis. Furthermore, GA offers cardiovascular benefits, such as lowering blood pressure, decreasing cholesterol, and enhancing endothelial function, which may aid in the prevention and management of cardiovascular diseases. This review covers the chemical structure, sources, identification and quantification methods, and biological and therapeutic properties of GA, along with its applications in food. As research progresses, the future for GA appears promising, with potential uses in functional foods, pharmaceuticals, and nutraceuticals aimed at improving overall health and preventing disease. However, ongoing research and innovation are necessary to fully understand its functional benefits, address current challenges, and establish GA as a mainstay in therapeutic and nutritional interventions.

Novel formulations ameliorate osteoarthritis in rats by inhibiting inflammation and oxidative stress.

The study tested new oral plant-based formulations (F) on rats with monosodium iodoacetate (MIA)-induced osteoarthritis, measuring inflammation, antioxidant levels, paw size, stride, and analyzing knee joint images. Fifty-six female Sprague Dawley rats were allocated into 8 groups: (1) Control, (2) MIA (OA induced with MIA), (3) MIA + F1 [curcuminoids+gingerols+acetyl-11-keto-β boswellic acid (AKBA)], (4) MIA + F2 (curcuminoids+Withania glycosides+AKBA), (5) MIA + F3 (curcuminoids+total withanolides+AKBA), (6) MIA + F4 (curcuminoids, AKBA), (7) MIA + UCII (type II collagen), and (8) MIA + GCHON (Glucosamine Chondroitin). Treatments F1 to F4 reduced right joint diameter and improved stride length and paw area in OA rats. Despite improvements with treatments F1 to F4, there was no significant difference between these groups (p > .05). In OA animals, F1 to F4 treatments decreased MDA levels and increased antioxidant enzymes activities (p < .001). This was done by reducing levels of inflammatory markers and enzymes like IL-1β, IL-6, MMP-8, TNF-α, CRP, COMP, and LOX-5, while increasing the anti-inflammatory cytokine IL-10. In conclusion, these plant-based treatments significantly reduced osteoarthritis severity, slowed disease progression by reducing inflammation, and protected joints from damage, showing a protective effect in rats with induced osteoarthritis, likely due to their anti-inflammatory and antioxidant properties.

The General and Systemic Consequences of Obesity in Cats and Dogs

Obesity, is a life-threatening condition common among various animals, is a multisystemic disorder that may affect the gastrointestinal system, urinary system, reproductive system, respiratory system, and musculoskeletal system. According to various studies, more than 50% of cats and dogs are obese. Many proinflammatory and inflammatory cytokines, hormones, and enzymes play a part in the production of fat tissues that lead to obesity. Excessive deposition of fats give rise to conditions involving inflammation, oxidative stress and damage, immunomodulation, hyperlipidemia, dyslipidemia, neoplasia, hypothyroidism, and insulin resistance. This review paper acquires the knowledge of various scientific manuscripts to discuss the development and consequences of obesity in pets especially cats and dogs.

Rosuvastatin repurposing for prophylaxis against ethanol-induced acute gastric ulceration in rats: a biochemical, histological, and ultrastructural perspective.

Ethanol (EtOH) consumption is frequently associated with acute and chronic gastrointestinal disorders. Rosuvastatin (RSV), a third-generation statin, has demonstrated certain biological functions beyond its lipid-lowering properties. This study is designed to explore the gastroprotective impact of RSV in a rat model of EtOH-induced gastric ulceration in a dose-dependent manner through the evaluation of oxidant/antioxidant biomarkers, inflammatory myeloperoxidase (MPO) enzyme activity, and prostaglandin E2 (PGE2) levels in gastric tissues, along with histopathological examination of the gastric tissues. Therefore, 40 adult male rats were randomly divided into five equal groups as control, EtOH (gastric ulcer), RSV-low dose plus EtOH and RSV-high dose plus EtOH. The EtOH rat model of gastric ulceration was achieved by intragastric administration of a single dose of EtOH. Seven days before EtOH administration, rats were orally administered either omeprazole (20mg/kg/day) or RSV (10mg/kg/day or 20mg/kg/day). RSV administration enhanced the antioxidant glutathione reduced, countered oxidative malondialdehyde, augmented cytoprotective PGE2, suppressed inflammatory MPO enzyme activity in gastric tissues, decreased ulcer index scoring, increased the percentage of ulcer inhibition, and reversed the associated histological and ultrastructural abnormalities, additionally, RSV treatment resulted in weak positive nuclear staining for the inflammatory nuclear factor kappa B in a dose-dependent manner. It is concluded that RSV demonstrates gastroprotective potential, attributable at least in part, to its antioxidant and anti-inflammatory properties, as well as its ability to promote ulcer protection through the maintenance of mucosal content and PGE2 levels. Thus, RSV therapy emerges as a safe option for patients with gastric ulcers.

Galangin: A Promising Flavonoid for the Treatment of Rheumatoid Arthritis-Mechanisms, Evidence, and Therapeutic Potential.

Rheumatoid Arthritis (RA) is a chronic autoimmune disease characterized by progressive joint inflammation and damage. Oxidative stress plays a critical role in the onset and progression of RA, significantly contributing to the disease's symptoms. The complex nature of RA and the role of oxidative stress make it particularly challenging to treat effectively. This article presents a comprehensive review of RA's development, progression, and the emergence of novel treatments, introducing Galangin (GAL), a natural flavonoid compound sourced from various plants, as a promising candidate. The bioactive properties of GAL, including its anti-inflammatory, antioxidant, and immunomodulatory effects, are discussed in detail. The review elucidates GAL's mechanisms of action, focusing on its interactions with key targets such as inflammatory cytokines (e.g., TNF-α, IL-6), enzymes (e.g., SOD, MMPs), and signaling pathways (e.g., NF-κB, MAPK), which impact inflammatory responses, immune cell activation, and joint damage. The review also addresses the lack of comprehensive understanding of potential treatment options for RA, particularly in relation to the role of GAL as a therapeutic candidate. It highlights the need for further research and clinical studies to ascertain the effectiveness of GAL in RA treatment and to elucidate its mechanisms of action. Overall, this review provides valuable insights into the potential of GAL as a therapeutic option for RA, shedding light on its multifaceted pharmacological properties and mechanisms of action, while suggesting avenues for future research and clinical applications.

Impact of silymarin-supplemented cookies on liver enzyme and inflammatory markers in non-alcoholic fatty liver disease patients.

Nonalcoholic fatty liver disease (NAFLD) is a growing public health concern characterized by fat accumulation and severe disorders like nonalcoholic steatohepatitis (NASH), which are influenced by obesity, inflammatory processes, and metabolic pathways. This research investigates the potential of silymarin-supplemented cookies in managing NAFLD by evaluating their impact on liver enzyme activity, inflammatory markers, and lipid profiles. A clinical trial in Lahore, Pakistan, involved 64 NAFLD patients. Participants were divided into placebo and three treatment groups, with the latter receiving silymarin-supplemented cookies for 3 months. The study assessed liver enzyme levels and inflammatory markers, at baseline and after the intervention, utilizing statistical analyses to evaluate differences. The lipid profile and renal function test (RFT) were also measured at baseline and after 3 months in each group for safety assessment. After 3 months, the treatment groups indicated more significant decreases in liver enzymes compared to the placebo group (p ≤ .05). Treatment 3 showed significant reductions in alanine aminotransferase (ALT) (64.39-49.38 U/L) and aspartate aminotransferase (AST) (61.53-45.38 U/L). Treatment 3 also showed improvements in alkaline phosphatase (ALP) levels and the AST/ALT ratio. Additionally, the treatment group demonstrated a significant reduction in inflammatory markers. Treatment 3 showed a significant decrease in C-reactive protein (CRP) (6.32-3.39 mg/L) and erythrocyte sedimentation rate (ESR) (38.72-23.86 mm/h), indicating that individuals with NAFLD may benefit from the intervention's potential benefits in lowering inflammation. The study revealed that an intervention significantly improved the inflammatory markers, liver enzymes, and lipid profiles of NAFLD participants, suggesting potential benefits for liver health.

Platycodon D reduces obesity and non-alcoholic fatty liver disease induced by a high-fat diet through inhibiting intestinal fat absorption.

Platycodin D (PD) has been reported to treat metabolic diseases, including non-alcoholic fatty liver disease. In addition, platycodin D has been reported to activate intestinal 5'AMP-activated protein kinase (AMPK) phosphorylation levels, thereby reducing lipid absorption. Therefore, the aim of this study is to explore whether PD activation of intestinal AMPK and reduced lipid absorption can improve non-alcoholic fatty liver disease. Clean-grade male C57/BL mice were fed a high-fat diet (HFD) (containing 60% calories) for 16 weeks, and oral PD (10mg/kg/day) was administered at the same time. The liver and intestines were the collected, and the intestines were tested. The expressions of lipid absorption genes (CD36, NPC1L1, and ApoB), the serum total triglyceride (TG) and total cholesterol (TC) levels in the intestines and livers, the fecal free fatty acid (FFA) levels, and the expression of AMPK phosphorylated proteins in the intestines were examined using Western blot analyses. The lipid distribution in the livers, intestines, and fat was detected using Oil Red O and hematoxylin and eosin (H&E) staining. A colon cancer cell line (Caco2) was used to confirm the effect of PD on the cellular lipid uptake in vitro. In addition, serum inflammatory factors and liver enzymes were measured to clarify the impact of PD on the circulation of metabolic syndrome. Leptin-deficient mice (OB) were then used to further explore the improvement of PD on body weight and blood lipids. PD had a very significant therapeutic or preventive effect on metabolic syndrome and fatty liver induced by a high-fat diet. PD improved body weight, insulin sensitivity, and glucose tolerance in mice fed a high-fat diet and also prevented non-alcoholic fatty liver disease, reduced blood lipid levels, and increased fecal lipid excretion. In addition, PD reduced lipid absorption by activating the intestinal AMPK protein, which may have involved the inhibition of the gene expression levels of intestinal lipid absorption genes (CD36, NPC1L1, and ApoB). The combined effect of these factors improved hepatic lipid accumulation and lipid accumulation in adipose tissue. It was further found that PD also improved the body weights and blood lipid levels of leptin-deficient mice (OB) mice. PD had a very strong therapeutic effect on mice under a high-fat diet. PD reduced high-fat diet-induced obesity and non-alcoholic fatty liver disease by inhibiting intestinal fat absorption.

Predictive and therapeutic value of lipoprotein-associated phospholipaseA2 in sarcopenia in chronic obstructive pulmonary disease

BackgroundSarcopenia, characterized by progressive muscle dysfunction, is a common complication of chronic obstructive pulmonary disease (COPD). Our previous study revealed serum Lipoprotein-associated phospholipaseA2 (Lp-PLA2) level significantly increased in COPD and associated with exercise tolerance. This study further investigated the functions and target potential of Lp-PLA2 for sarcopenia in COPD. MethodsThe circulating Lp-PLA2 level/enzyme activity in COPD patients and age-matched healthy volunteers were measured. Clinical parameters on skeletal muscle were measured and their correlations with Lp-PLA2 were analyzed. We explored the involvement of Lp-PLA2 in vivo and treatment effectiveness of darapladib (a specific Lp-PLA2 inhibitor) in CS-induced muscle dysfunction models. ResultsCirculating Lp-PLA2 level/enzyme activity was elevated in COPD patients compared with healthy controls, negatively associated with skeletal muscle mass and function. In CS-induced muscle dysfunction murine models, up-regulated serum Lp-PLA2 level/enzyme activity was verified again. In CS-exposed mouse models, darapladib treatment reversed muscle mass loss and muscle dysfunction, meanwhile rescued upregulation of MuRF1 and atrogin-1, and activation of inflammatory factors, oxidant enzymes and NF-κB signaling. ConclusionsLp-PLA2 could be a potential indicator for sarcopenia in COPD. Darapladib, a Lp-PLA2 inhibitor, can alleviate CS-induced skeletal muscle dysfunction and represents a potential therapeutic for sarcopenia in COPD.