Search Results (1,235)

Swertiamarin (SW), a natural iridoid glycoside primarily isolated from the genus Swertia, Gentianaceae family, has been extensively utilized in traditional medicine systems, including Ayurveda, Traditional Chinese Medicine, and Tibetan medicine, for treating fever, diabetes, liver disorders, and inflammatory conditions. Pharmacokinetic studies reveal that SW exhibits rapid absorption but demonstrates low oral bioavailability due to the first-pass effect. Pharmacological studies have demonstrated that SW possesses a wide range of pharmacological activities, including antioxidant, anti-inflammatory, anti-tumor, anti-diabetic, and neuroprotective activities. Our analysis demonstrates that SW exerts remarkable therapeutic potential across multiple pathological conditions through coordinated modulation of key signaling cascades, including Nrf2/HO-1, NF-κB, MAPK, PI3K/Akt, and PPAR pathways. This comprehensive review systematically consolidates current knowledge on SW’s pharmacokinetic characteristics, toxicity, diverse biological activities, and underlying molecular mechanisms based on extensive preclinical evidence, establishing a scientific foundation for future drug development strategies and potential clinical applications of the potential natural lead compound. Full article

Chamaecyparis obtusa (Siebold & Zucc.) Endl. (C. obtusa) is an evergreen conifer native to temperate regions such as South Korea and Japan, traditionally used for its anti-inflammatory properties. However, the molecular mechanisms underlying the anti-inflammatory effects of C. obtusa bark extracts remain poorly understood. In this study, I compared the biological activities of C. obtusa bark extracts prepared using boiling water (COWB) and 70% ethanol (COEB), and investigated their anti-inflammatory mechanisms in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. COEB significantly suppressed both mRNA and protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), along with decreased production of their respective inflammatory mediators, nitric oxide (NO) and prostaglandin E₂ (PGE₂). Additionally, COEB selectively downregulated interleukin (IL)-1β expression, without affecting tumor necrosis factor-α (TNF-α), and unexpectedly upregulated IL-6. Notably, COEB did not inhibit the LPS-induced activation of major inflammatory signaling pathways, including mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB), and Janus kinase/signal transducer and activator of transcription (JAK/STAT). These findings suggest that COEB exerts anti-inflammatory effects by modulating key inflammatory mediators independently of canonical signaling pathways and may offer a novel therapeutic strategy for controlling inflammation. Full article

Psoriasis is a chronic inflammatory skin disorder involving oxidative stress and immune dysregulation. Given the limitations and adverse effects of conventional therapies, interest in natural treatments with anti-oxidant and immunomodulatory properties is increasing. This study aimed to comprehensively evaluate the therapeutic potential of Galium verum extract in an imiquimod-induced rat model of psoriasis. The extract was chemically characterized by HPLC and evaluated for anti-oxidant activity using DPPH, ABTS, and FRAP assays. Molecular docking studies targeted psoriasis-related proteins (IL-17, IL-22, IL-23, JAK2, MAPK2, NF-κB, STAT3), revealing strong binding affinities for rutin and quercetin, the extract’s dominant bioactives. In vivo, 18 Wistar albino male rats were divided into control (CTRL), psoriasis (PSORI), and psoriasis treated with Galium verum (PSORI + GV) groups. A seven-day topical application of 5% imiquimod cream was used for the induction of psoriasis. The PSORI + GV group received 250 mg/kg Galium verum extract orally for 7 days. Morphometric and redox analyses were performed. Histological and morphometric analyses showed reduced epidermal thickness, inflammation, and collagen content. Redox analysis revealed lowered oxidative stress biomarkers and enhanced anti-oxidant defenses. These findings suggest that Galium verum extract exerts anti-psoriatic effects through antioxidative and immunomodulatory mechanisms, supporting its potential as a natural adjunct therapy for psoriasis. Full article

Gaultherin [methyl salicylate 2-O-β-D-xylopyranosyl-(1→6)-β-D-glucopyranoside] is a natural salicylate found in some plant species belonging primarily to the Ericaceae and Rosaceae families. Biological studies conducted since the beginning of the 21st century have suggested the potential use of gaultherin in treating various diseases related to inflammation and oxidative stress, including rheumatoid arthritis, sciatica, neuralgia, and muscular pain. The accumulated results indicated a targeted range of biological effects, particularly anti-inflammatory, antipyretic, and anti-rheumatic properties associated with reduced adverse outcomes. The molecular mechanisms involve the influence on several signalling pathways, including NF-κB, MAPK, and potentially AMPK, as well as the inhibition of critical pro-inflammatory enzymes, such as COX-2. This inhibition is achieved without affecting the COX-1 isoform, thereby preventing side effects such as bleeding ulcers or intracranial haemorrhage. This overview summarises the current knowledge about pharmacokinetics, molecular mechanisms, pharmacology, and biocompatibility of gaultherin. Additionally, four methods for isolating gaultherin from plant material and its distribution within the plant kingdom were the focal points of review and discussion. The paper also describes significant differences between synthetic aspirin and natural gaultherin in their biological potential and side effects, resulting from their different mechanisms of action. As a prodrug of salicylic acid, gaultherin releases salicylic acid gradually through enzymatic hydrolysis in the gastrointestinal tract. This controlled release minimises direct gastric irritation and accounts for its superior gastrointestinal safety profile compared to aspirin. Unlike aspirin, which irreversibly inhibits COX-1 and can lead to serious side effects with chronic use, gaultherin selectively inhibits COX-2 while sparing COX-1. These properties position gaultherin as a compelling natural alternative for patients requiring long-term anti-inflammatory therapy with reduced risk of gastrointestinal or bleeding complications. Full article

Tea is one of the most consumed beverages in the world, belonging to the category of compounds known as tannins and flavonoids. One of the polyphenols found in large amounts in green tea leaves (Camellia sinensis) is epigallocatechin-3-O-gallate (EGCG). Though EGCG has shown some pharmacological effects, to date, it has not been utilised as a therapeutic agent. This is attributed to the fact that EGCG lacks adequate stability, and it is known to degrade through epimerization or auto-oxidation processes, especially when it is exposed to light, temperature fluctuations, some pH values, or the presence of oxygen. Consuming green tea with EGCG can alleviate the effects of bone diseases, such as osteoporosis, and support faster bone regeneration in the case of fractures. Therefore, this review focuses on the current state of research, highlighting the effects of EGCG on bone biology, such as enhancing osteoblast differentiation, promoting bone mineralisation, improving bone microarchitecture, and inhibiting osteoclastogenesis through the modulation of the RANK/RANKL/OPG pathway. Additionally, EGCG exerts antioxidant, anti-inflammatory, and dose-dependent effects on bone cells. It also downregulates inflammatory markers (TNF-α, IL-1β, and COX-2) and reduces oxidative stress via the inhibition of reactive oxygen species generation and the activation of protective signalling pathways (e.g., MAPK and NF-κB). Studies in animal models confirm that EGCG supplementation leads to increased bone mass and strength. These findings collectively support the further exploration of EGCG as an adjunct in the treatment and prevention of metabolic bone diseases. The authors aim to present the relationship between EGCG and bone health, highlighting issues for future research and clinical applications. Full article

The developmental processes of microglia follow a general pattern, from immature amoeboid (activated) cells to fully ramified (inactivated) surveilling microglia. However, little is known about the mechanisms controlling the transition of microglia from an activated to an inactivated state during brain development. Due to the complexity of microenvironmentally dynamic changes during neuronal differentiation, interactions between developing nerve cells and microglia might be involved in this process. Extracellular vesicles (EVs) are cell-released particles that serve as mediators of cellular crosstalk and regulation. Using neural progenitor cells (NPCs) and a long-term neuron culture system, we found that EVs derived from NPCs or developing neurons possessed differential capacity on the induction of microglial activation. The exposure of microglia to NPC- or immature neuron (DIV7)-derived EVs resulted in the higher expression of protein and mRNA of multiple inflammatory cytokines (e.g., TNF-α, IL-1β, and IL-6), when compared with mature neuron-derived EVs. Exploration of the intracellular signaling pathways revealed that MAPK signaling, IκBα phosphorylation/degradation, and NF-κB p65 nuclear translocation were strongly induced in microglia treated with NPC- or immature neuron-derived EVs. Using a pharmacological approach, we further demonstrate that Toll-like receptor (TLR) 7-mediated activation of NF-κB and MAPK signaling cascades contribute to EV-elicited microglial activation. Additionally, the application of conditioned media derived from microglia treated with NPC- or immature neuron-derived EVs is found to promote the survival of late-developing dopaminergic neurons. Thus, our results highlight a novel mechanism used by NPCs and developing neurons to modulate the developmental phases and functions of microglia through EV secretion. Full article

Konjac glucomannan (KGM) is a natural polysaccharide polymer. It is degraded by gut microbiota-derived β-mannanase into small-molecule nutrients, which exert diverse physiological regulatory effects. As a prebiotic, KGM modulates gut microbiota composition. It selectively fosters the proliferation of beneficial commensals and suppresses potential pathogens, thereby alleviating microbiota-related disorders. Moreover, microbiota fermentation of KGM produces metabolites. Short-chain fatty acids (SCFAs) are particularly notable among these metabolites. They exert multifaceted beneficial effects, including metabolic regulation, intestinal barrier strengthening, and neuroprotective functions. These effects are mediated through inhibition of inflammatory pathways (e.g., NF-κB, MAPK), modulation of lipid metabolism genes (e.g., CD36), and regulation of neurotransmitters (e.g., GABA, 5-HT). This highlights KGM’s therapeutic potential for metabolic, inflammatory, and neurodegenerative diseases. Current clinical use is limited by dose-dependent adverse effects and interindividual response variability, which stem from different microbial communities. This necessitates personalized dosage strategies. Despite these limitations, KGM as a prebiotic polysaccharide exhibits multifaceted bioactivity. Current evidence suggests its potential to synergistically modulate metabolic pathways, gut microbiota composition, immune cell signaling, and neuroendocrine interactions. This highlights its promise for developing novel therapeutic interventions. Full article

Naturally occurring prostaglandin E₂ (PGE₂) influences cytokine production regulation in bovine neutrophils exposed to Staphylococcus aureus Rosenbach. Here, we employed bovine neutrophils as the primary experimental system, and administered specific inhibitors targeting various receptors, which were subsequently exposed to S. aureus. Cytokine expression levels in dairy cow neutrophils induced by S. aureus via the endogenous PGE₂-EP2/4 receptor pathway were investigated, and its effects on P38, extracellular signal-regulated kinase (ERK), P65 activation, and phagocytic function in Staphylococcus aureus Rosenbach-induced dairy cow neutrophils, were examined. Blocking cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) enzymes substantially decreased PGE₂ production and release in S. aureus-exposed bovine neutrophils. Cytokine output showed significant reduction compared to that in SA113-infected controls. Phosphorylation of P38, ERK, and P65 signaling molecules was depressed in the infected group. Pharmacological interference with EP2/EP4 receptors similarly diminished cytokine secretion and phosphorylation patterns of P38, ERK, and P65, with preserved cellular phagocytic function. During S. aureus infection of bovine neutrophils, COX-2 and mPGES-1 participated in controlling PGE₂ biosynthesis, and internally produced PGE₂ molecules triggered NF-κB and MAPK inflammatory pathways via EP2/EP4 receptor activation, later adjusting the equilibrium between cytokine types that promote or suppress inflammation. This signaling mechanism coordinated inflammatory phases through receptor-mediated processes. Full article

This study aimed to evaluate whether probiotic administration could protect against cognitive impairments in a scopolamine-induced cognitive impairment mice model. Male C57BL/6 mice (8 weeks of age) were injected with scopolamine hydrobromide to induce memory impairments. The experimental groups were additionally supplemented with 10⁹ colony-forming units (CFU)/day probiotics containing Lactobacillus helveticus CNU395 or L. paracasei CNU396. Behavioral test results and histopathological evaluations showed that the spatial memory ability and pathological tissue abnormalities of the mice in the CNU395 and CNU396 groups significantly improved compared with those in the disease group. CNU395 and CNU396 mitigated scopolamine-induced neuroinflammation by reducing the expression of pro-inflammatory cytokines (IL-6, IL-8, IL-10, and TNF-α) and the NLRP3 inflammasome, through the inhibition of MAPK and NF-κB inflammatory pathways. Additionally, the CNU395 and CNU396 groups showed decreased levels of Iba-1 and Bax, alongside increased levels of BDNF and Bcl-2, relative to the disease group. Therefore, CNU395 or CNU396 supplementation might help prevent the onset of cognitive deficits and neuroinflammation. Full article

The immunomodulatory polysaccharide CPP-3a, purified from Chlorella pyrenoidosa, was investigated for its effects on RAW264.7 macrophages and underlying mechanisms, revealing that CPP-3a significantly enhanced phagocytic capacity and nitric oxide production while upregulating pro-inflammatory cytokines TNF-α and IL-6 and elevating the co-stimulatory molecule CD86, collectively driving robust M1 polarization. Mechanistically, TLR4-, TLR2-specific inhibitors, and TLR4-knockout cells confirmed TLR4 as the primary receptor for CPP-3a, with TLR2 playing a secondary role in cytokine modulation. CPP-3a activated NF-κB and p38 MAPK signaling pathways via the MyD88-dependent pathway, evidenced by phosphorylation of NF-κB/p65 with its nuclear translocation and increased phosphorylation of p38 MAPK, with these signaling activations further validated by specific pathway inhibitors that abolished M1 polarization phenotypes. Collectively, CPP-3a emerges as a potent TLR4-targeted immunomodulator with adjuvant potential for inflammatory and infectious diseases. Full article

Atherosclerosis (AS), a progressive inflammatory disease of coronary arteries, the aorta, and the internal carotid artery, is considered one of the main contributors to cardiovascular disorders. Blood flow is restricted by accumulating lipid-rich macrophages (foam cells), calcium, fibrin, and cellular debris into plaques on the intima of arterial walls. Butyrate maintains gut barrier integrity and modulates immune responses. Butyrate regulates G-protein-coupled receptor (GPCR) signaling and activates nuclear factor kappa-B (NF-κB), activator protein-1 (AP-1), and interferon regulatory factors (IFRs) involved in the production of proinflammatory cytokines. Depending on the inflammatory stimuli, butyrate may also inactivate NF-κB, resulting in the suppression of proinflammatory cytokines and the stimulation of anti-inflammatory cytokines. Butyrate modulates mitogen-activated protein kinase (MAPK) to promote or suppress macrophage inflammation, muscle cell growth, apoptosis, and the uptake of oxidized low-density lipoprotein (ox-LDL) in macrophages. Activation of the peroxisome proliferator-activated receptor γ (PPARγ) pathway plays a role in lipid metabolism, inflammation, and cell differentiation. Butyrate inhibits interferon γ (IFN-γ) signaling and suppresses NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) involved in inflammation and scar tissue formation. The dual role of butyrate in AS is discussed by addressing the interactions between butyrate, intestinal epithelial cells (IECs), endothelial cells (ECs) of the main arteries, and immune cells. Signals generated from these interactions may be applied in the diagnosis and intervention of AS. Reporters to detect early AS is suggested. This narrative review covers the most recent findings published in PubMed and Crossref databases. Full article

Sanguisorba tenuifolia is a wild plant of the genus Sanguisorba officinalis. This study aimed to investigate the regulatory effect of the dichloromethane fraction of Sanguisorba tenuifolia on LPS-induced inflammatory responses in RAW264.7 cells, thereby providing a new scientific basis for the medicinal development of Sanguisorba tenuifolia. Initially, we used 75% ethanol to crudely extract the roots of Sanguisorba tenuifolia, followed by fractional extraction using dichloromethane (CH₂Cl₂), ethyl acetate (EtOAc), butanol (BuOH), and distilled water (DW) as solvents. By measuring the inhibitory effects of each fractionated extract on NO production, we determined that the SCE (Dichloromethane fraction of Sanguisorba tenuifolia) exhibited the most potent anti-inflammatory activity, leading to its progression to the next experimental stage. Subsequently, we evaluated the effects of SCE on cell viability and LPS-induced inflammatory cytokine secretion in RAW264.7 cells. A rat model of reflux esophagitis was also used to validate the in vivo anti-inflammatory effects of SCE. Additionally, we utilized UPLC/MS-MS to identify and analyze the active components of SCE. The results indicated that SCE could effectively inhibit LPS-induced cellular inflammation by modulating the p38/ERK/MAPK and NF-κB signaling pathways, and also reduced the damage of the esophageal mucosa in rats with reflux esophagitis. UPLC/MS-MS analysis of SCE identified 423 compounds, including 12 active ingredients such as triterpenoids, phenols, and steroids. This discovery not only provides scientific support for the potential of Sanguisorba tenuifolia as an anti-inflammatory agent but also lays the groundwork for the development of new therapeutics for the treatment of inflammatory diseases. Full article

Background/Objectives: The integration of natural compounds in cancer research marked a crucial shift in the modern medical landscape, through a growing acknowledgment of their potential as efficient, less toxic, and cost-effective alternatives to contemporary chemotherapeutics. Liquiritigenin (LIQ) is a compound obtained from different plants, the most important being the Glycyrrhiza species, commonly known as licorice. Methods: This review compiles findings from previously published preclinical studies and experimental research articles focusing on LIQ’s pharmacological effects, with particular attention to its anticancer potential. The relevant literature was identified using established scientific databases and selected based on relevance to cancer biology and LIQ-associated signaling pathways. Results: LIQ demonstrates anti-oxidant, anti-inflammatory, and anti-proliferative effects. It exerts its potential anticancer activities by inducing apoptosis, preventing cell proliferation, and modulating various signaling pathways such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), phosphoinositide 3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK), and so on. Conclusions: LIQ represents a promising natural agent for cancer therapy, with evidence supporting its multifunctional role in targeting tumor growth and survival mechanisms. By providing a detailed analysis of LIQ, this review aims to highlight its therapeutic efficacy across various cancer types and emphasize its importance as a promising compound in cancer research. In addition, this review seeks to bridge the gap between traditional medicine and modern pharmacology and paves the way for LIQ’s clinical application in cancer therapy. Full article

Plant secondary metabolites possess significant antioxidant and anti-inflammatory properties, but their complex polypharmacological mechanisms remain poorly understood. Network pharmacology has emerged as a powerful systems-level approach for investigating multi-target interactions of natural products. This review systematically analyzes network pharmacology applications in elucidating the antioxidant and anti-inflammatory mechanisms of plant metabolites, evaluating concordance between computational predictions and experimental validation. A comprehensive literature search was conducted across major databases (2015–2025), focusing on network pharmacology studies with experimental validation. Analysis revealed remarkable convergence toward common molecular mechanisms, despite diverse chemical structures. For antioxidant activities, the Nrf2/KEAP1/ARE pathway emerged as the most frequently validated mechanism, along with PI3K/AKT, MAPK, and NF-κB signaling. Anti-inflammatory mechanisms consistently involved NF-κB, MAPK, and PI3K/AKT pathways. Key targets, including AKT1, TNF-α, COX-2, NFKB1, and RELA, were repeatedly identified. Flavonoids, phenolic acids, and terpenoids dominated as bioactive compounds. Molecular docking studies supported predicted interactions, with experimental validation showing good concordance for pathway modulation and cytokine regulation. Network pharmacology provides a valuable framework for investigating the complex bioactivities of plant metabolites. The convergence toward common regulatory hubs suggests that natural compounds achieve protective effects by modulating central nodes that integrate redox balance and inflammatory responses. Despite limitations, including database dependency, integrating network pharmacology with experimental validation accelerates mechanistic understanding in natural-product drug discovery. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disease stemming from genetic susceptibility and environmental factors. It is characterized by immune dysregulation, increased mast cell activity, elevated levels of immunoglobulin E (IgE), and excessive proinflammatory mediator expression. These factors contribute to hallmark symptoms such as pruritus, erythema, and skin barrier dysfunction. In this study, we investigated the antioxidant and anti-inflammatory effects of Taraxacum mongolicum (WTM) water extract, as well as its skin barrier regulation and immune functions in AD. In the present study, we explored the therapeutic efficacy and underlying mechanisms of WTM in a BALB/c mouse model of AD induced by 2,4-dinitrochlorobenzene (DNCB). Mice were administered WTM orally or topically for 14 consecutive days. The results demonstrated that WTM treatment significantly alleviated clinical severity, showing reductions in skin lesion scores, epidermal thickness, mast cell infiltration, and scratching behavior, compared to the DNCB-treated group. Mechanistically, WTM reduced serum levels of IgE and proinflammatory cytokines (IL-4, IL-6, IL-1β, TNF-α, and IL-31) while suppressing the expression of the JAK/STAT/TSLP signaling pathway in skin tissues. Furthermore, WTM inhibited the TLR4/NF-κB and MAPK pathways and enhanced antioxidant defense by elevating superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) activities. These findings indicate that WTM attenuates DNCB-induced AD progression in mice, likely through the dual modulation of inflammatory signaling and oxidative stress. These findings suggest that WTM may modulate the immune response and alleviate AD symptoms by inhibiting the TLR4/NF-κB, MAPK, and JAK/STAT/TSLP pathways. Full article