Search Results (743)

Cannabis sativa L. is a phytochemically rich plant with therapeutic potential across various clinical domains, including pain, inflammation, and neurological disorders. Among its constituents, terpenes are gaining recognition for their capacity to modulate the pathophysiological processes underlying chronic pain syndromes. Traditionally valued for their aromatic qualities, terpenes such as myrcene, β-caryophyllene (BCP), limonene, pinene, linalool, and humulene have demonstrated a broad spectrum of biological activities. Beyond their observable analgesic, anti-inflammatory, and anxiolytic outcomes, these compounds exert their actions through distinct molecular mechanisms. These include the activation of cannabinoid receptor type 2 (CB₂), the modulation of transient receptor potential (TRP) and adenosine receptors, and the inhibition of pro-inflammatory signalling pathways such as Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Cyclooxygenase-2 (COX-2). This narrative review synthesizes the current preclinical and emerging clinical data on terpene-mediated analgesia, highlighting both monoterpenes and sesquiterpenes, and discusses their potential for synergistic interaction with cannabinoids, the so-called entourage effect. Although preclinical findings are promising, clinical translation is limited by methodological variability, the lack of standardized formulations, and insufficient pharmacokinetic characterization. Further human studies are essential to clarify their therapeutic potential. Full article

Young leaves of reed (Phragmites communis) have been reported to exhibit antioxidant effects; however, their anti-inflammatory properties have not yet been investigated. In this study, we evaluated the effects of young reed leaf extract (PCE) on LPS-induced inflammation in RAW 264.7 cells and elucidated the underlying molecular mechanisms. Our results demonstrate that PCE significantly inhibited the production of nitric oxide (NO) by approximately 45% at 100 μg/mL (p < 0.01) and pro-inflammatory cytokines such as IL-6, TNF-α, and GM-CSF by 40–60% (p < 0.01) in LPS-stimulated RAW 264.7 macrophages, without cytotoxicity up to 100 μg/mL. PCE also downregulated the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and upregulated heme oxygenase-1 (HO-1) expression by approximately 2-fold at 100 μg/mL (p < 0.05). Mechanistically, these effects were associated with the inhibition of IκBα phosphorylation/degradation, IKKα/β phosphorylation, and AP-1 activation via the suppression of JNK and ERK signaling pathways, as well as the inhibition of STAT1/3 phosphorylation. Collectively, our findings suggest that PCE exerts anti-inflammatory effects by modulating the IκB, AP-1, and STAT1/3 signaling pathways, thereby suppressing inflammatory mediator production and enhancing antioxidant defense mechanisms in LPS-treated macrophages. Full article

Atopic dermatitis (AD) is a chronic, multifactorial inflammatory skin disease characterized by persistent pruritus, immune system dysregulation, and an increased expression of cyclooxygenase-2 (COX-2), an enzyme that plays a central role in the production of prostaglandins and the promotion of inflammatory responses. In this study, we employed a comprehensive computational pipeline to identify phytocompounds capable of inhibiting COX-2 activity, offering an alternative to traditional non-steroidal anti-inflammatory drugs. The African and Traditional Chinese Medicine natural product databases were subjected to molecular screening, which identified six top compounds, namely, Tophit1 (−16.528 kcal/mol), Tophit2 (−10.879 kcal/mol), Tophit3 (−9.760 kcal/mol), Tophit4 (−9.752 kcal/mol), Tophit5 (−8.742 kcal/mol), and Tophit6 (−8.098 kcal/mol), with stronger binding affinities to COX-2 than the control drug rofecoxib (−7.305 kcal/mol). Molecular dynamics simulations over 200 ns, combined with MM/GBSA binding free energy calculations, consistently identified Tophit1 and Tophit2 as the most stable complexes, exhibiting exceptional structural integrity and a strong binding affinity to the target protein. ADMET profiling via SwissADME and pkCSM validated the drug-likeness, oral bioavailability, and safety of the lead compounds, with no Lipinski rule violations and favorable pharmacokinetic and toxicity profiles. These findings underscore the therapeutic potential of the selected phytocompounds as novel COX-2 inhibitors for the management of atopic-prone skin and warrant further experimental validation. Full article

Terpenes represent a structurally diverse class of natural compounds with increasing scientific interest due to their potential anti-inflammatory properties. This study investigates the in silico binding behavior of six plant-derived terpenes—α-pinene, β-pinene, menthol, camphor, limonene, and linalool—against four key enzymes in the arachidonic acid (AA) metabolic pathway: cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), and phospholipase A2 (PLA₂). AA serves as a reference for binding energy comparison. Blind rigid-body molecular docking is performed using AutoDock 4.2 and the Lamarckian Genetic Algorithm, with 100 runs per ligand–enzyme pair and the energy-based selection of optimal poses. The analysis includes binding energy (ΔG), inhibition constants (Ki), root-mean-square deviation (RMSD), and residue-level interactions. Several terpenes exhibit favorable binding energies and inhibition constants across the evaluated enzymes. For COX-1 and COX-2, menthol and camphor show low Ki values, indicating stable binding. Menthol and limonene also show the strongest affinities for PLA₂, exceeding AA. The focus is on compounds with potential to modulate arachidonic acid metabolism. In this context, β-pinene engages the catalytic site of PLA₂, linalool forms multiple contacts within key regions of 5-LOX, and menthol, α-pinene, and β-pinene align with functionally important regions in both COX isoforms. These targeted interactions suggest that the highlighted compounds may selectively interfere with enzymatic activity in inflammation-related pathways. By modulating key steps in AA metabolism, these terpenes may influence the biosynthesis of pro-inflammatory mediators, offering a promising avenue for the development of safer, plant-derived anti-inflammatory agents. The findings lay the groundwork for further experimental validation and the structure-based optimization of terpene-derived modulators. Full article

Glioblastoma (GBM) is the most aggressive form of malignant gliomas, with the eicosanoid-synthesizing enzyme cyclooxygenase-2 (COX-2) playing a pivotal role in its progression via the COX-2/prostaglandin E2/4 axis. COX-2 upregulations in tumor cells induces a pro-inflammatory tumor microenvironment (TME), affecting the behavior of invading bone marrow-derived macrophages (Mϕ) and brain-resident microglia (MG) through unclear autocrine and paracrine mechanisms. Using CRISPR/Cas9 technology, we generated COX-2 knockout U87 glioblastoma cells. In spheroids and in vivo xenografts, this resulted in a significant inhibition of tumorigenic properties, while not observed in standard adherent monolayer culture. Here, the knockout induced a G1 cell cycle arrest in adherent cells, accompanied by increased ROS, mitochondrial activity, and cytochrome c-mediated apoptosis. In spheroids and xenograft models, COX-2 knockout led to notable growth delays and increased cell death, characterized by features of both apoptosis and autophagy. Interestingly, these effects were partially reversed in subcutaneous xenografts after co-culture with Mϕ, while co-culture with MG enhanced the growth-suppressive effects. In an orthotopic model, COX-2 knockout tumors displayed reduced proliferation (fewer Ki-67 positive cells), increased numbers of GFAP-positive astrocytes, and signs of membrane blebbing. These findings highlight the potential of COX-2 knockout and suppression as a therapeutic strategy in GBM, particularly when combined with suppression of infiltrating macrophages and stabilization of resident microglia populations to enhance anti-tumor effects. Full article

Clinacanthus nutans (Burm.f.) Lindau is a Southeast Asian medicinal plant traditionally used for treating skin inflammation and infections. This study evaluated its wound-healing potential through anti-inflammatory, cytoprotective, and antiviral mechanisms. HPLC-DAD analysis identified schaftoside as the major flavonoid in the 95% ethanolic leaf extract. In the lipopolysaccharide (LPS)-stimulated murine macrophage cell line (RAW 264.7), both C. nutans extract (5 and 50 μg/mL) and its flavonoid schaftoside (5 and 20 μg/mL) significantly downregulated the expression of pro-inflammatory genes, including cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and prostaglandin E₂ (PGE₂), under both pre-treatment and post-treatment conditions. ELISA confirmed dose-dependent inhibition of human COX-2 enzymatic activity, reaching up to 99.3% with the extract and 86.9% with schaftoside. In the endothelial cell models (CCL-209), the extract exhibited low cytotoxicity and effectively protected cells from LPS-induced apoptosis, preserving vascular integrity critical to tissue regeneration. Antiviral assays demonstrated suppression of HSV-2 replication, particularly during early infection, which may help prevent infection-related delays in wound healing. Collectively, these findings suggest that C. nutans and schaftoside promote wound repair by attenuating inflammatory responses, supporting endothelial survival, and controlling viral reactivation. These multifunctional properties highlight their potential as natural therapeutic agents for enhancing wound-healing outcomes. Full article

Background/Objectives: Degenerative arthritis is a chronic inflammatory disease marked by tissue degradation and vascular fibrosis. Macrophages play a central role in the inflammatory response by releasing mediators such as nitric oxide (NO), interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), and prostaglandin E2 (PGE2). This study aimed to investigate the anti-inflammatory potential of BTEX-K, a formulation of dried red ginseng combined with alpha-galactosidase, in lipopolysaccharide (LPS)-stimulated cells. Methods: LPS-treated immune cells were used to assess the anti-inflammatory effects of BTEX-K. The levels of NO, IL-6, TNF-α, and PGE2 were measured following BTEX-K treatment. The protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was evaluated. Cytotoxicity assays were conducted to determine whether the observed effects were due to cell viability loss. The involvement of MAPK signaling and NF-κB pathway modulation was examined by analyzing JNK phosphorylation, IκB degradation, and PPAR-γ expression. Results: BTEX-K significantly reduced the production of NO, IL-6, TNF-α, and PGE2 in LPS-treated cells without inducing cytotoxicity. The protein expression levels of iNOS and COX-2 were also suppressed. Furthermore, BTEX-K inhibited the LPS-induced phosphorylation of JNK in the MAPK pathway. It restored IκB levels and suppressed NF-κB activation by preventing the downregulation of PPAR-γ. Conclusions: BTEX-K demonstrates notable anti-inflammatory effects by inhibiting key inflammatory mediators and signaling pathways in immune cells. These findings support its therapeutic potential in mitigating inflammation-related symptoms, including pain, swelling, and redness, commonly seen in degenerative arthritis. Full article

Meloxicam (MLX), a member of the non-steroidal anti-inflammatory drugs (NSAIDs), is a preferential inhibitor of cyclooxygenase-2 (COX-2) responsible for the synthesis of pro-inflammatory prostaglandins. MLX, due to its inhibition of the COX-2 enzyme, which is overexpressed in many cancers, including melanoma, leading to rapid growth, angiogenesis, and metastasis, represents a potentially important compound with anticancer activity. This study aimed to investigate the potential anticancer activity of meloxicam against amelanotic C32 and melanotic COLO 829 melanoma cell lines. The objective was achieved by assessing cell metabolic activity using the WST-1 assay and analyzing mitochondrial potential, levels of reduced thiols, annexin, and caspases 3/7, 8, and 9 by imaging cytometry, as well as assessing reactive oxygen species (ROS) levels using the H₂DCFDA probe. The amelanotic melanoma C32 was more sensitive to MLX exposure, thus exhibiting antiproliferative effects, a disruption of redox homeostasis, a reduction in mitochondrial potential, and an induction of apoptosis. The results provide robust molecular evidence supporting the pharmacological effects of MLX, highlighting its potential as a valuable agent for in vivo melanoma treatment. Full article

This study aimed to evaluate the anti-inflammatory properties of Carthamus caeruleus L. root juice (CRJ), which is used in the traditional medicine of Algeria. The product was characterized by colorimetric assays (total polyphenols, flavonoids, and tannins) and by RP-HPLC-DAD analysis. Experiments were conducted in vitro to assess the ability of CRJ to stabilize human erythrocyte membranes under various stress conditions and inhibit albumin denaturation, a process linked to inflammation. An in silico study was also performed to investigate the inhibitory effects on cyclooxygenase-2 (COX-2) and assess the phenolic constituents with the highest activity. Moderate levels of polyphenols, flavonoids, and tannins were assessed; among these, 22 compounds were identified via chromatographic analysis. While present at low concentrations, some of these compounds, including myricetin, luteolin, and quercetin, are known to exhibit bioactivity at micromolar levels. CRJ provided erythrocyte membranes with notable protection against disruption caused by hypotonic NaCl solutions (protection levels of 90.51%, 87.46%, and 76.87% at NaCl concentrations of 0.7%, 0.5%, and 0.3%, respectively), heat stress (81.54%), and oxidative damage from HClO (75.43%). Additionally, a protection of 61.5% was observed against albumin denaturation. Docking analysis indicated favorable COX-2 binding for myricetin, luteolin, and quercetin. In conclusion, the root juice derived from C. caeruleus demonstrated potential anti-inflammatory activity in vitro and in silico. However, further studies, including in vivo investigations, are necessary to confirm efficacy and fully elucidate the mechanisms of action. Full article

This study investigates the anti-inflammatory effects of the marine diterpene glycosides pseudopterosin A-D (PsA-D) in mitigating nickel sulfate (NiSO₄)-induced skin sensitization. In dermal dendritic cell (DDC) surrogates, PsA-D pre-treatment significantly reduced NiSO₄-induced upregulation of key activation surface markers, cluster of differentiation (CD)54 (~1.2-fold), and CD86 (~1.6-fold). Additionally, PsA-D inhibited the NiSO₄-induced activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway by suppressing inhibitor of kappa B alpha (IκBα) degradation. Furthermore, PsA-D suppressed inflammatory responses by inhibiting the NiSO₄-induced secretion of pro-inflammatory cytokines, including interleukin (IL)-8 (~6.8-fold), IL-6 (~2.2-fold), and IL-1β (~5.3-fold). In a full-thickness human skin model incorporating DDC surrogates, topical application of PsA-D effectively attenuated NiSO₄-induced mRNA expression of IL-8 (~2.1-fold), IL-6 (~2.6-fold), and IL-1β (~2.2-fold), along with the key inflammatory mediators cyclooxygenase-2 (COX-2) (~3.5-fold) and NOD-like receptor family pyrin domain-containing 3 (NLRP3) (~2.1-fold). Overall, PsA-D demonstrated comparable efficacy to dexamethasone, a benchmark corticosteroid, providing a promising therapeutic alternative to corticosteroids for the treatment of skin sensitization and allergic contact dermatitis. However, to maximize PsA-D’s therapeutic potential, future studies on optimizing the bioavailability and formulation of PsA-D are required. Full article

Background/Objectives: Oats and oat bran are rich in dietary fiber, polyphenols and other phytochemicals. Methods: In this study, we evaluated the phytochemical content and established LPS-induced RAW 264.7 macrophage inflammation and DSS-induced Caco-2 cell inflammation models to investigate the anti-inflammatory activities of oat and oat bran polyphenols and their molecular mechanisms. Results: The results showed that oat and oat bran polyphenols (free and bound polyphenols) enhanced phagocytosis, decreased the expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), reduced the production of NO and ROS, increased the mitochondrial membrane potential, and reduced the inflammatory cytokines (TNF-α, IL-1β, and IL-6) at the gene level in the RAW 264.7 macrophage inflammation model induced by LPS expression, thus demonstrating strong anti-inflammatory activity. In Caco-2 cells, oat and oat bran polyphenols pretreatment attenuated the DSS-induced decrease in trans-epithelial electron resistance value, increased tight junction protein expression, and reduced cell permeability in Caco-2 cell monolayers, which in turn reduced inflammatory damage in the organism. Conclusions: In summary, the present study not only reveals the mechanism by which oat and oat bran polyphenols inhibit macrophage inflammation and impairment of intestinal barrier function at defined concentration in vitro, but also highlights potential for oat bran as a functional food. Full article

The pathogenesis of inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn’s disease, remains incompletely understood. Amomum villosum Lour. (Zingiberaceae) is a traditional herbal medicine used across Asia to treat digestive and inflammatory disorders. This study investigated the therapeutic effects of a water extract derived from the fruits of AV (referred to as AVE) in a mouse model of colitis induced by dextran sulfate sodium (DSS). The protective effects of AVE were evaluated by monitoring changes in body weight and colon length, as well as histological and molecular markers of inflammation. Neutrophil infiltration and levels of inflammatory cytokines in colon tissue and serum were assessed, and the integrity of the intestinal epithelial barrier was examined via Western blot analysis. Treatment with AVE significantly alleviated DSS-induced colitis, as evidenced by improved body weight, longer colon length, and reduced inflammatory responses. AVE administration restored tight junction protein expression (zonula occludens-1 [ZO-1] and occludin), suppressed phosphorylation of mitogen-activated protein kinases—specifically, extracellular signal-regulated kinase (ERK) and p38—and inhibited the expression of inflammatory mediators including tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX-2), interleukin (IL)-6, IL-1β, and myeloperoxidase (MPO) activity. These findings suggest that oral AVE treatment effectively protects against experimental colitis by modulating inflammatory signaling and preserving epithelial barrier integrity. Further studies are warranted to explore the clinical potential and safety of AVE in the management of IBD. Full article

Celery (Apium graveolens L.), one of the numerous members of the Apiaceae family, has been traditionally used as food and medicine due to its nutraceutical properties. Nevertheless, understanding the neuroprotective effects of this species requires evaluation through different mechanisms relevant to Alzheimer’s disease (AD) treatment. This study explored the neuroprotective potential of ethanolic extracts of celery leaves. Liquid chromatography and mass spectrometry-based metabolomics analysis of the extract revealed the existence of a diverse array of secondary metabolites, including phenolic acids, hydroxycinnamic acid, flavonoids, flavonoid O-glycosides, flavonol, glycosides, and isoflavones. Celery extract protects human neuroblastoma SH-SY5Y cells against 15 µM amyloid-beta (Aβ_1–42) toxicity, enhancing their vitality from 67% to 81.74% at 100 µg/mL. The extract inhibited the enzymes associated with AD, including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), glycogen synthase kinase 3 beta (GSK3β), cyclooxygenase 1 (COX-1), and cyclooxygenase 2 (COX-2) with IC₅₀ values of 21.84, 61.27, 45.94, 34.1, and 52.2 µg/mL, respectively. In conclusion, celery leaf extract components may be potential therapeutic candidates for AD prevention and treatment. Full article

The present study investigates the anti-skin-aging properties and bioactive compounds of the aerial parts of Astragalus membranaceus, which are typically discarded as agricultural waste. Liquid chromatography–mass spectrometry analysis identified flavonoid glycosides as the major constituents of the aerial parts of A. membranaceus extract. Two principal flavonoids, astraflavonoid A (1) and astraside C (2), were isolated using repetitive chromatography. Compounds 1 and 2 demonstrated antioxidative properties, reducing reactive oxygen species and matrix metalloproteinase-1 levels in human dermal fibroblasts upon stimulation with TNF-α. Specifically, astraside C (2) inhibited the expression of pro-inflammatory cytokines interleukin-6 and interleukin-8, whereas astraflavonoid A (1) did not affect their expression. Additionally, the expression of inflammatory mediators such as nuclear factor kappa B and cyclooxygenase-2 (COX-2) was increased by 1, whereas it was suppressed by 2. Furthermore, in silico molecular docking experiments confirmed that compound 2 effectively binds to COX-2. These findings suggest that the aerial parts of A. membranaceus contain bioactive flavonol glycosides with promising anti-skin-aging properties, offering valuable use as agricultural byproducts. Full article

Background/Objectives: Essential oils are increasingly recognized for their therapeutic potential, yet Ammoides verticillata essential oil (AVEO) remains relatively unexplored, particularly for its anti-inflammatory and analgesic properties. This study aimed to profile AVEO’s chemical composition and evaluate its antioxidant, anti-inflammatory, and analgesic effects, with a focus on its novel pharmacological actions. Methods: The chemical composition of AVEO was determined using GC-MS analysis, and antioxidant capacity was assessed through in vitro assays. Furthermore, the anti-inflammatory potential was investigated using a carrageenan-induced paw edema model in rats, complemented by the inhibition assays of cyclooxygenase (COX) enzymes. The analgesic effects were evaluated through acetic acid-induced writhing and tail immersion tests. Additionally, a computational study was performed to explore the binding affinity of AVEO’s major constituents to COX-2. Results: GC-MS analysis revealed a rich monoterpene profile dominated by carvacrol (32.51%). It was found that AVEO exhibited significant antioxidant activity. Similarly, in vivo, AVEO showed significant anti-inflammatory effects, achieving a percentage inhibition of 52.23% at 200 mg/kg, comparable to diclofenac, along with potent COX-2 inhibition observed (IC₅₀ = 1.51 ± 0.20, SI = 5.56). Moreover, analgesic tests demonstrated dose-dependent pain relief, in which the dose of 200 mg/kg significantly prolonged tail latency to 14.00 ± 1.45 s and markedly reduced abdominal constriction to 21.17 ± 1.62. Computational analysis further corroborated the high binding affinity of carvacrol and thymol with COX-2 (−7.381 and −6.939 Kcal/mol, respectively). Conclusions: These findings underscore AVEO’s potential as a promising therapeutic agent for managing inflammation and pain. Full article