Search Results (1,996)

Background/Objectives: The therapeutic properties of edible flowers are widely used to improve human health. The phenolic compounds present in edible flowers, such as phenols and flavonoids, among others, play an important role as effective antioxidant compounds against diseases related to oxidative stress. These compounds exhibit biological activities such as anti-ulcerogenic, antimicrobial, neuroprotective, anti-cancer, and anti-inflammatory properties. The objective of this study was to evaluate the in vivo anti-inflammatory activity of hydroethanolic extracts of four Mexican cacti flowers. Methods: A hydroethanolic extract was obtained via maceration for each cactus flower and evaluated using a model of edema induced in mouse ears by 12-O-tetradecanoylphorbol-13-acetate (TPA) as a guide for the anti-inflammatory activity. Compounds in cacti flower extracts were quantified by HPLC. Results: All of the hydroalcoholic flower extracts showed an anti-inflammatory effect. The greatest effect of inhibition of auricular edema (61.2 ± 4.23%) was observed in the group of mice treated with the Cardon extract at a dose of 3 mg/ear. This effect can be attributed to the main compounds detected by HPLC in the extract such as p-coumaric acid, catechin, kaempferol, and quercetin. These compounds are involved in the inhibition of pro-inflammatory mediators and enzymes such as cyclooxygenases and lipoxygenases. Conclusions: This preliminary evidence supports further preclinical evaluation of the Cardon flower. Full article

Previous research has demonstrated that the transient bilateral common carotid artery occlusion and reperfusion (BCCAO/R) effectively models early brain inflammation resulting from sudden hypoperfusion and subsequent reperfusion. According to studies showing that diet and nutrition strongly influence brain neuroplasticity, in this study we evaluated whether kaempferol (KAM), a dietary flavonoid, offers neuroprotection in a rat BCCAO/R model. Adult Wistar rats were gavage fed a single dose of KAM (40 mg) six hours before surgery. Comprehensive lipidomic and molecular analyses were conducted on samples from the frontal and temporal-occipital cortices, as well as the plasma. In the frontal cortex, KAM elevated anti-inflammatory N-acylethanolamines palmitoylethanolamide (PEA), oleoylethanolamide (OEA), and docosahexaenoylethanolamide (DHAEA) and reduced oxidized arachidonic acid metabolites. KAM also downregulated cyclooxygenase- 2 (COX-2) protein and selectively decreased the endocannabinoid 2-arachidonoylglycerol (2-AG), showing a shift in AA metabolism. These molecular changes correlated with increased levels of peroxisome proliferator-activated receptor alpha (PPARα) and cannabinoid receptors CB1R and CB2R, supporting activation of both nuclear and membrane-bound anti-inflammatory pathways. No significant changes were observed in the temporal-occipital cortex. In plasma, DHAEA levels increased similarly to those in the cortex. However, rises in PEA and OEA were detected only in sham-operated KAM-treated animals, suggesting possible central redistribution under hypoperfusion/reperfusion stress. In summary, these findings demonstrate that KAM exerts dual anti-inflammatory effects by inhibiting COX-2-mediated prostanoid synthesis and promoting PPARα-driven lipid signaling. This dual mechanism highlights the potential of KAM as a dietary intervention to reduce neuroinflammation associated with hypoperfusion–reperfusion challenges. Full article

Osteoarthritis (OA) is a degenerative joint disorder characterized by progressive articular cartilage degradation, leading to pain, stiffness, and impaired mobility. This study investigated the anti-osteoarthritic effects of Lindera obtusiloba (LO) leaf extract in primary cultured chondrocytes and a mouse model of destabilization of the medial meniscus (DMM)-induced OA. Mouse primary chondrocytes were treated with IL-1β and various concentrations of LO leaf extract (50–150 μg/mL), and analyzed by RT-PCR, Western blotting, and ELISA. For the in vivo experiments, male C57BL/6 mice underwent DMM surgery and were administered LO leaf extract (50–200 mg/kg/day) for eight weeks, followed by micro-CT, histological, and immunohistochemical analyses. LO leaf extract exhibited no cytotoxicity in chondrocytes. In interleukin-1β-induced inflammatory chondrocytes, LO leaf extract significantly suppressed the expression of OA-associated catabolic factors, including cyclooxygenase-2 (Cox-2), matrix metalloproteinases (MMP3 and MMP13), and phosphorylated nuclear factor-kappa B (NF-κB). It also reduced the production of destructive mediators, such as prostaglandin E₂ (PGE₂) and collagenase, in a dose-dependent manner. In vivo, LO leaf extract-treated mice demonstrated significant reductions in articular cartilage degradation, subchondral bone sclerosis, and the expression of catabolic and inflammatory mediators. Additionally, LO leaf extract administration significantly decreased systemic pro-inflammatory cytokine levels in DMM-induced mice. Collectively, these findings indicate that LO leaf extract attenuates OA progression by suppressing both local and systemic inflammatory responses, supporting its potential as a natural therapeutic agent for the prevention and treatment of OA. Full article

Fluoride is a widespread environmental toxin that disrupts metabolic and endocrine functions, but its impact on pancreatic inflammation and hormone secretion remains unclear. This study examined how chronic fluoride exposure affects pancreatic inflammation and secretory function in rats. Pregnant Wistar rats received sodium fluoride (NaF) at 50 mg/L in drinking water during gestation and lactation. Male offspring continued exposure until 3 months old. Controls received fluoride-free water. Pancreatic tissue and serum were collected. Fluoride levels were measured potentiometrically. Eicosanoids were quantified by SPE and HPLC. Serum insulin, glucagon, and somatostatin were measured by ELISA. Histological and biochemical markers of inflammation and oxidative stress were assessed. Fluoride exposure did not lead to significant accumulation in the pancreas or serum. However, fluoride-exposed rats exhibited a significant decrease in serum insulin and somatostatin concentrations, while glucagon levels remained unchanged. Additionally, the pancreas of fluoride-treated animals showed markedly elevated levels of pro-inflammatory eicosanoids, including prostaglandin E2, leukotrienes A4 and B4, and HETE/HODE derivatives, indicating activation of cyclooxygenase and lipoxygenase pathways. Sustained low-dose fluoride exposure induced pancreatic inflammation and disrupted endocrine homeostasis in rats. These findings suggest that chronic fluoride intake may impair insulin secretion and promote pre-diabetic alterations, warranting further research. Full article

Background: Pathological pregnancy is associated with various complications that may affect the health of both the mother and her offspring. In recent years, lipid metabolites such as hydroxyeicosatetraenoic (HETE) fatty acids and hydroxyoctadecadienoic (HODE) fatty acids have gained increasing interest as potential biomarkers of pathological processes in pregnancy. The aims of the present study were to investigate changes in HETE and HODE levels during pathological pregnancy and to assess their potential role in the development and monitoring of pregnancy complications. Attempts were made to determine associations in cross-sectional studies and relationships in longitudinal ones. Methods: In this study, a liquid chromatograph (HPLC) was used to separate the eicosanoids. The study group consisted of 72 Caucasian women, divided into a control group (n = 51) and a group with non-physiological pregnancy (n = 21). Results: The study results show that the levels of the tested metabolites of the cyclooxygenase (COX) and lipoxygenase (LOX) pathways increased as pregnancy progressed. Women with non-physiological courses of pregnancy who developed gestational diabetes and/or preeclampsia were characterized by dysregulation of the inflammatory signaling processes involving eicosanoids. Conclusions: Carbohydrate abnormalities during pregnancy were mainly associated with increased synthesis of 5-oxoETE and the use of 5-HETE in the control group but were not visible in the diabetic group. HODE acids probably do not play a significant role in pathological pregnancy. The relatively small size of the pathological group and the wide range of gestational age mean that the tests should be standardized and carried out on a larger scale. Full article

Various therapeutic approaches have been explored to speed up wound healing, with angiogenesis being a crucial factor in this process and skin repair. This study shows that a polysaccharide extracted from the red alga Osmundea pinnatifida (PSOP) can promote angiogenesis and accelerate healing. The structural properties of PSOP were investigated using various techniques, including scanning electron microscopy, X-ray diffraction, Fourier–transform infrared spectroscopy, ultraviolet–-visible spectroscopy, and high-performance liquid chromatography coupled with a refractive index detector. Additionally, the in vitro antioxidant activity of PSOP was evaluated using the reducing power assay, total antioxidant capacity measurement, and DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging tests. The PSOP extract exhibited significant pro-angiogenic effects in the avian chorioallantoic membrane model. Furthermore, the efficacy of PSOP-based hydrogels for wound healing was assessed in vivo using an excision wound model in Wistar rats. The results indicated accelerated wound healing, increased collagen deposition, and enhanced tissue regeneration. Computational studies suggest that the observed wound healing and pro-angiogenic effects may be attributed to the affinity of the PSOP units for cyclooxygenase-2 and vascular endothelial growth factor. These findings support the potential use of PSOP as a bioactive agent in wound care. Full article

Osteoarthritis (OA) is primarily a degenerative disease triggered by joint inflammation and oxidative stress. While Aster glehni is an edible and traditionally medicinal herb, the beneficial effect of A. glehni on OA progression remains unknown. This study aimed to investigate the effect of A. glehni extract (AGE) and its primary biological compound—3,5-dicaffeoylquinic acid (3,5-DCQA)—on inflammation and oxidative stress in chondrocytes. AGE effectively inhibited the expression of interleukin (IL)-6, cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-1, and MMP-13 in chondrocytes stimulated by IL-1β for 24 h. In contrast, 3,5-DCQA did not inhibit IL-6, COX-2, and MMP expressions under the same conditions. However, when chondrocytes were stimulated by IL-1β for a short duration (6 h), 3,5-DCQA suppressed IL-6, COX-2, and MMP expressions. The inhibition of IL-6, COX-2, and MMP expressions by AGE was associated with the p38 kinase and nuclear factor-κB signaling pathways, but not ERK and JNK signaling pathways. Furthermore, AGE prevented cell apoptosis and reduced intracellular reactive oxygen species levels in chondrocytes induced by hydrogen peroxide (H₂O₂). AGE restored the decreased superoxide dismutase 1 and catalase mRNA expressions caused by H₂O₂. Collectively, AGE may protect against cartilage deterioration by inhibiting inflammation and oxidative stress, making it a promising therapeutic agent for alleviating OA. Full article

There is an urgent need to develop new anti-inflammatory compounds due to the versatility of their applications and the side effects associated with currently used nonsteroidal anti-inflammatory drugs (NSAIDs). Compounds containing the 1,2-benzothiazine 1,1-dioxide moiety in their structure have demonstrated a broad range of pharmacological activities, among which the anti-inflammatory effect is the most well-documented. Numerous in vivo studies have confirmed the effectiveness of these compounds in alleviating pain and inflammation. In turn, in vitro studies have shown that 1,2-benzothiazine derivatives exhibit anti-inflammatory activity not only through the classical mechanism involving the inhibition of cyclooxygenase (COX) but also through modern, more complex mechanisms. These innovative mechanisms include inhibition of microsomal prostaglandin E₂ synthase-1 (mPGES-1) or 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), suppression of pro-inflammatory cytokines, and modulation of kinase activity involved in inflammatory processes. Importantly, many studies have shown that some new 1,2-benzothiazine 1,1-dioxide derivatives exhibit even stronger anti-inflammatory activity than traditional NSAIDs, making them promising candidates for new drugs targeting inflammation-related diseases. This paper presents a review of 1,2-benzothiazine 1,1-dioxide derivatives investigated for their anti-inflammatory activity in both in vivo and in vitro models, taking into account their various mechanisms of action and potential directions for further research. Full article

Chronic inflammation driven by Cyclooxygenase-2 (COX-2) overexpression plays a key role in lung cancer (LC) progression, making it a critical therapeutic target. This study explores thymoquinone (TQ), a potent bioactive phytochemical derived from Nigella sativa, known for its anti-inflammatory and anti-cancer effects, focusing on its ability to suppress lipopolysaccharide (LPS)-induced COX-2 expression via microRNA hsa-miR-199a-3p modulation in LC cells. Using A549 and SHP-77 LC cells, we tested the effect of TQ under LPS stimulation and miRNA inhibition. Advanced techniques like TaqMan qPCR, luciferase reporter gene constructs, and anti-miRNA transfection confirmed that miR-199a-3p directly silences COX-2. Western blot and ELISA assays revealed that TQ dramatically reduces COX-2 protein and PGE2 levels by boosting miRNA-199a-3p. Importantly, TQ also blocked MAPK (p38, JNK, ERK) and NF-κB activation, even when miR-199a-3p was suppressed, proving its multi-targeted action beyond miRNA regulation. These findings reveal a novel anti-inflammatory mechanism, where TQ curbs COX-2-driven inflammation by enhancing miR-199a-3p, simultaneously shutting down pro-cancer MAPK/NF-κB signaling pathways. Given the strong link between chronic inflammation and LC aggressiveness, this study positions TQ as a promising therapeutic candidate, especially for inflammation-mediated lung cancer progression. Its dual ability to modulate miRNA and key signaling cascades makes it a compelling option for future LC treatment strategies. Full article

The development of dressing materials mainly protects the wound, prevents infection, and assists in wound healing. Apart from the most common gauze on the market, different dressing materials can accelerate wound healing. Bacterial cellulose (BC) dressings have had many related studies and applications so far, and other natural or artificial compounds that are beneficial to tissue repair may also be added during the manufacturing process. This study compared the wound healing efficacies of BC dry membrane developed by our team, gauze, commercially available “Tegaderm^TM Hydrocolloid Dressing”, and “AQUACEL^® EXTRA Hydrofiber Dressing”. This study used rats as experimental animals and injured them by scalding. Moreover, Staphylococcus aureus was used to infect wounds to compare the effects on wound healing. We first used NIH-3T3 cells for an in vitro model to confirm that the BC membrane is not harmful to cells. In the animal experiment, wounds were created by scalding and then treated with different dressing materials and doses of S. aureus. After 10 days of treatment, the wound recovery in the BC membrane and AQUACEL^® groups was the most obvious, including angiogenesis in the dermal layer and regeneration of the epidermis layer. Especially without S. aureus infection, inflammatory markers such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression levels were reduced to those of healthy tissue. In conclusion, we confirmed that the BC dry membrane can accelerate wound healing. In the future, it may provide high-efficiency and less expensive options in the dressing market. Full article

Colorectal cancer (CRC) remains a major contributor to global cancer-related mortality, with rising incidence observed in several regions, including Saudi Arabia. This review compiles and critically analyzes recent preclinical research from Saudi-based institutions that investigates the anti-CRC potential of natural and synthetic compounds. Numerous natural products such as Nigella sativa, Moringa oleifera, Curcuma longa, and marine-derived metabolites have demonstrated cytotoxic effects through pathways involving apoptosis induction, reactive oxygen species (ROS) generation, and inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and cyclooxygenase-2 (COX-2). In parallel, synthetic and semi-synthetic agents, including C4–G4 (semi-synthetic hybrids designed from flavonoids and benzoxazole scaffolds that act as dual epidermal growth factor receptor (EGFR)/COX-2 inhibitors)), oxazole derivatives, and camptothecin-based nanocarriers, exhibit promising anti-tumor activity via molecular targeting of cyclin-dependent kinase 8 (CDK8), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), and β-catenin pathways. Selected in vivo studies primarily utilizing xenograft and chemically induced rodent models have shown reductions in tumor volume and modulation of apoptotic and inflammatory biomarkers. Additionally, green-synthesized metallic nanoparticles (NPs) and polyethylene glycol (PEG)-modified carriers have been investigated to improve bioavailability and tumor targeting of lead compounds. While these findings are encouraging, the majority remain in preclinical phases. Limitations such as poor solubility, lack of pharmacokinetic data, and absence of clinical trials impede translational progress. This review highlights the need for standardized evaluation protocols, mechanistic validation, and region-specific clinical studies to assess efficacy and safety. Given Saudi Arabia’s rich biodiversity and growing research capacity under national strategies like Vision 2030, the country is well-positioned to contribute meaningfully to CRC drug discovery. By integrating bioactive natural products, rationally designed synthetics, and advanced delivery platforms, a pipeline of innovative CRC therapeutics tailored to local and global contexts may be realized. Full article

The genus Lavandula represents one of the most valuable aromatic and medicinal plants, holding significant economic importance in the pharmaceutical, food, perfumery, and cosmetics industries. Among them, L. multifida is a traditionally used medicinal plant in the Mediterranean region. This work provides a comprehensive review of L. multifida, focusing on its traditional uses, phytochemistry, and pharmacological properties. Unlike conventional lavenders, its essential oil is dominated by phenolic monoterpenes, principally carvacrol, alongside significant concentrations of β-bisabolene, 1,8-cineole, and camphor. This distinct phytochemical profile is further complemented by a rich range of non-volatile constituents, including flavonoids, phenolic acids, and triterpenoids. Pharmacological investigations have validated its broad-spectrum antimicrobial activity, demonstrating efficacy against multidrug-resistant bacterial strains and fungal pathogens through mechanisms such as membrane disruption, metabolic interference, and quorum sensing inhibition. Furthermore, the species exhibits significant antioxidant and anti-inflammatory properties, mediated primarily through radical scavenging, cyclooxygenase inhibition, and cytokine modulation. Owing to its distinct chemistry, specific traditional uses for respiratory and digestive ailments, limited endemic habitat, and underexplored status, L. multifida presents a promising candidate for future research with high potential for novel drug discovery, particularly in antiparasitic and respiratory therapies. This review concludes by identifying key research priorities for L. multifida, including a detailed analysis of its non-volatile compounds, mechanistic elucidation, toxicological assessments, and standardization of extracts. Addressing these gaps is essential to validate its traditional applications and advance its development into evidence-based phytomedicines, adjuvant therapies, and natural agrochemicals. Full article

Background and Objective: Cerebral cavernous malformation (CCM) is a vascular disorder causing seizures, neurological deficits, and hemorrhagic stroke. It can be sporadic or inherited via CCM1, CCM2, or CCM3 gene mutations. Inflammation is broadly recognized as a promoter of cerebral vascular malformations. This study explores inflammatory mechanisms and differences behind CCM-related hemorrhage and epilepsy. Material and Methods: The study group comprised 28 patients, ten patients with CCM-related epilepsy, and 18 patients who clinically presented with a cerebral hemorrhage at diagnosis. All patients underwent microsurgical resection of the CCMs. Formaldehyde-fixed, paraffin-embedded tissue samples were immunohistochemically stained using a monoclonal antibody against Cyclooxygenase 2 (COX-2) (Dako, Santa Clara, CA; Clone: CX-294) and NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) (ABCAM, Cambridge, MA, USA; ab214185). MRI and clinical data were correlated with immunohistochemical findings, and the analysis was conducted utilizing the Trainable Weka Segmentation algorithm. Results: Median CCM volume was 1.68 cm³ (IQR: 0.85–3.07 cm³). There were significantly more NLRP3-positive cells (32.56% to 91.98%; mean: 65.82%, median: 68.34%; SD: ±17.70%), compared to COX-2-positive cells (1.82% to 79.69%; mean: 45.87%, median: 49.06%; SD: ±22.56%). No correlation was shown between the volume of CCMs and a hemorrhage event (p = 0.13, 95% CI: 0.99–1.02). Symptomatic brain hemorrhage showed a significantly increased inflammatory enzyme upregulation from both COX-2 (p < 0.001) and NLRP3 (p = 0.009) versus patients with symptomatic CCM-related epilepsy at first diagnosis. Conclusions: Inflammatory processes in CCMs seem to be driven by broad and multiple pathways because both COX-2 and NLRP3-driven inflammatory pathways are consistently activated. As a novelty, this study showed that patients with symptomatic hemorrhage showed upregulated inflammatory enzyme activity compared to patients with CCM-related epilepsy. No direct links between NLRP3, COX-2 expression, and radiological, pathological, or preexisting patient conditions were found. Full article

Snack bars are convenient, ready-to-eat foods with various natural ingredients and may serve as functional foods, offering bioactive phytochemicals. In this study, tomato-based snack bars enriched in plant proteins were evaluated for their antioxidant, antidiabetic, anti-obesity, and anti-inflammatory properties by in vitro test, comparing different protein sources (pea and RuBisCO) and drying methods (microwave vacuum and oven). The rubisco bars exhibited the highest levels of polyphenols (10.12 ± 0.27 mg GAE/g) and flavonoids (5.65 ± 0.47 mg CE/g), and demonstrated superior antioxidant capacity in DPPH, ORAC, and FRAP assays, particularly when microwaved. Rubisco bars also exhibited better inhibition activity of dipeptidyl-peptidase IV and pancreatic lipase, suggesting potential antidiabetic and anti-obesity effects. In contrast, pea bars displayed notable anti-inflammatory effects by reducing tumor necrosis factor (TNF)-α-induced cyclooxygenase-2 (COX-2) expression in intestinal cells. Both protein types were digestible, though rubisco bars released more peptides during simulated gastrointestinal digestion. While these in vitro findings provide insights into the functional potential of tomato-based snack bars, further studies, including in vivo investigations, are required to confirm their health-promoting effects and to evaluate physiologically relevant doses. Overall, these findings highlight the potential of tomato-based snack bars as sustainable, nutrient-rich functional foods with potential health-promoting properties. Full article

Background: Blast-induced spinal cord injuries (bSCI) account for 75% of all combat-related spinal trauma and are associated with long-term functional impairments. However, limited studies have evaluated the neuropathological outcomes in the spinal cord following blast exposure. Objectives In this study, we aimed to determine the acute and sub-acute neuropathological changes in the spinal cord of ferrets after blast exposure. Methods: An advanced blast simulator was used to expose ferrets to tightly coupled repeated blasts. The Catwalk XT system was used to detect gait performances in ferrets at 24 h and 1 month post-blast exposure. After euthanasia, the cervical spinal cord samples were collected at 24 h or 1 month post-blast. A quantitative real-time polymerase chain reaction was performed to evaluate changes in the gene expression of multiple Toll-like Receptors (TLR), Cyclooxygenase (COX-1 and COX-2) enzymes and cytokines. Western blotting was performed to investigate markers of axonal injury (Phosphorylated-Tau, pTau; Phosphorylated Neurofilament Heavy Chain, pNFH; and Neurofilament Light Chain present in degenerating neurons, NFL-degen) and neuroinflammation (Glial Fibrillary Acidic Protein, GFAP; and Ionized Calcium Binding Adaptor Molecule, Iba-1). Results: Blast exposure significantly affected the gait performances in ferrets, especially at 24 h post-blast. Multiple TLRs, COX-2, Interleukin-1-beta (IL-1β), Interleukin-6 (IL-6), and Tumor Necrosis Factor-α (TNF-α) were significantly upregulated in the spinal cord at 24 h after blast exposure. Although only TLR3 was significantly upregulated at 1 month, non-significant increases in TLR1 and TLR2 were observed in the spinal cord at 1 month post-blast. Phosphorylation of Tau at serine (Ser396 and Ser404) and threonine (Thr205) increased in the spinal cord at 24 h and 1 month post-blast exposure. The increased expression of pNFH and NFL-degen proteins was evident at both time points. The expression of GFAP, but not Iba-1, significantly increased at 24 h and 1 month following blast exposure. Conclusions: Our results indicate that blast exposure causes acute and sub-acute neuroinflammation and associated axonal injury in the cervical spinal cord. These data further suggest that inhibition of TLRs and/or COX-2 enzyme might offer protection against blast-induced injuries to the spinal cord. Full article