Search Results (1,847)

Proteomic profiling using ultrafast chromatography–mass spectrometry provides valuable insights into plant responses to abiotic factors by linking molecular changes with physiological outcomes. Nanopriming, a novel approach involving the treatment of seeds with nanoparticles, has demonstrated potential for enhancing plant metabolism and productivity. However, the molecular mechanisms underlying nanoparticle-induced effects remain poorly understood. In this study, we investigated the impact of gold nanoparticle (Au-NP) seed priming on the proteome of wheat (Triticum aestivum L.) seedlings. Differentially regulated proteins (DRPs) were identified, revealing a pronounced reorganization of the photosynthetic apparatus (PSA). Both the light-dependent reactions and the Calvin cycle were affected, with significant upregulation of chloroplast-associated protein complexes, including PsbC (CP43), chlorophyll a/b-binding proteins, Photosystem I subunits (PsaA and PsaB), and the γ-subunit of ATP synthase. The large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCo) exhibited over a threefold increase in expression in Au-NP-treated seedlings. The proteomic changes in the large subunit RuBisCo L were corroborated by transcriptomic data. Importantly, the proteomic changes were supported by physiological and biochemical analyses, ultrastructural modifications in chloroplasts, and increased photosynthetic activity. Our findings suggest that Au-NP nanopriming triggers coordinated molecular responses, enhancing the functional activity of the PSA. Identified DRPs may serve as potential biomarkers for further elucidation of nanopriming mechanisms and for the development of precision strategies to improve crop productivity. Full article

Background/Objectives: Chemotherapy-induced neuropathic pain (CINP) represents a critical challenge in oncology, emerging as a common and debilitating side effect of widely used chemotherapeutic agents, such as paclitaxel (PTX). Current therapeutic interventions and preventive strategies for CINP are largely insufficient, as they fail to address the underlying peripheral nerve damage, highlighting an urgent need for the development of new drugs. This study aimed to investigate the dual-function effects on normal cell protection and tumor suppression of BMX-001, a redox-active manganese metalloporphyrin that has demonstrated antioxidant and anti-inflammatory properties, which offers potential in protecting central nervous system tissues and treating CINP. Methods: This study assessed BMX-001’s different roles in protecting normal cells while acting as a pro-oxidant and pro-inflammatory molecule in cancer cells in vitro. We also evaluated its neuroprotective effect in preclinical PTX-induced CINP models in vivo. Results: Our results showed significant reductions in mechanical and cold allodynia, decreased pro-inflammatory cytokine levels, and restored antioxidant capacity in peripheral nerves and dorsal root ganglia (DRGs) following BMX-001 treatment. Conclusions: Overall, our study highlights the therapeutic potential of BMX-001 to mitigate CINP and enhance anticancer efficiency. Its dual-selective mechanism supports the future clinical investigation of BMX-001 as a novel adjunct to chemotherapeutic regimens. Full article

Ozone (O₃) occurs in nature as a chemical compound made of three oxygen atoms. It is an unstable, highly oxidative gas that rapidly decomposes into oxygen. The therapeutic use of O₃ dates back to the beginning of the 20th century and is currently based on the application of low doses, inducing a moderate oxidative stress that stimulates the antioxidant cellular defenses without causing cell damage. Low O₃ doses also induce anti-inflammatory and regenerative effects, and their anticancer potential is under investigation. In addition, the oxidative properties of O₃ make it an excellent antibacterial, antimycotic, and antiviral agent. Thanks to these properties, O₃ is currently widely used in several medical fields. However, its chemical instability represents an application limit, and ozonated oil is the only stabilized form of medical O₃. In recent years, novel O₃ formulations have been proposed for their sustained and more efficient administration, based on nanotechnology. This review offers an overview of the nanocarriers designed for the delivery of medical O₃, and of their therapeutic applications. The reviewed articles demonstrate that research is active and productive, though it is a rather new entry in the nanotechnological field. Liposomes, nanobubbles, nanoconstructed hydrogels, polymeric nanoparticles, and niosomes were designed to deliver O₃ and have been proven to exert antiseptic, anticancer, and pro-regenerative effects when administered in vitro and in vivo. Improving the therapeutic administration of O₃ through nanocarriers is a just-started challenge, and multiple prospects may be foreseen. Full article

Background: Acute mountain sickness (AMS) is a prevalent and potentially life-threatening condition caused by rapid exposure to high-altitude hypoxia, affecting pulmonary and neurological functions. Tongqiao Jiuxin Oil (TQ), a traditional Chinese medicine formula composed of aromatic and resinous ingredients such as sandalwood, agarwood, frankincense, borneol, and musk, has been widely used in the treatment of cardiovascular and cerebrovascular disorders. Clinical observations suggest its potential efficacy against AMS, yet its pharmacological mechanisms remain poorly understood. Methods: The chemical profile of TQ was characterized using UHPLC-Q-Exactive Orbitrap HRMS. Network pharmacology was applied to predict the potential targets and pathways involved in AMS. A rat model of AMS was established by exposing animals to hypobaric hypoxia (~10% oxygen), simulating an altitude of approximately 5500 m. TQ was administered at varying doses. Physiological indices, oxidative stress markers (MDA, SOD, GSH), histopathological changes, and the expression of hypoxia- and apoptosis-related proteins (HIF-1α, VEGFA, EPO, Bax, Bcl-2, Caspase-3) in lung and brain tissues were assessed. Results: A total of 774 chemical constituents were identified from TQ. Network pharmacology predicted the involvement of multiple targets and pathways. TQ significantly improved arterial oxygenation and reduced histopathological damage in both lung and brain tissues. It enhanced antioxidant activity by elevating SOD and GSH levels and reducing MDA content. Mechanistically, TQ downregulated the expression of HIF-1α, VEGFA, EPO, and pro-apoptotic markers (Bax/Bcl-2 ratio, Caspase-3), while upregulated Bcl-2, the anti-apoptotic protein expression. Conclusions: TQ exerts protective effects against AMS-induced tissue injury by improving oxygen homeostasis, alleviating oxidative stress, and modulating hypoxia-related and apoptotic signaling pathways. This study provides pharmacological evidence supporting the potential of TQ as a promising candidate for AMS intervention, as well as the modern research method for multi-component traditional Chinese medicine. Full article

Disruption of the intestinal epithelial barrier is a key driver of gut-derived inflammation in various disorders, yet strategies to preserve or restore barrier integrity remain limited. To address this, we evaluated a four-strain Bifidobacterium mixture—selected for complementary anti-inflammatory potency and industrial scalability—in lipopolysaccharide (LPS)-challenged RAW 264.7 macrophages and a Caco-2/THP-1 transwell co-culture model. Pretreatment with the probiotic blend reduced nitric oxide (NO) release in a dose-dependent manner by 25.9–48.3% and significantly down-regulated the pro-inflammatory markers in macrophages. In the co-culture system, the formulation decreased these markers, increased transepithelial electrical resistance (TEER) by up to 31% at 10⁵ colony-forming unit (CFU)/mL after 48 h, and preserved the membrane localization of tight junction (TJ) proteins. Adhesion to Caco-2 cells (≈ 6%) matched that of the benchmark probiotic Lacticaseibacillus rhamnosus GG, suggesting direct epithelial engagement. These in vitro findings demonstrate that this probiotic mixture can attenuate LPS-driven inflammation and reinforce epithelial architecture, providing a mechanistic basis for its further evaluation in animal models and clinical studies of intestinal inflammatory disorders. Full article

Natural compounds, particularly flavonoids, have emerged as promising anticancer agents due to their various biological activities and no or negligible toxicity towards healthy tissues. Among these, isorhamnetin, a methylated flavonoid, has gained significant attention for its potential to target multiple cancer hallmarks. This review comprehensively explores the mechanisms by which isorhamnetin exerts its anticancer effects, including cell cycle regulation, apoptosis, suppression of metastasis and angiogenesis, and modulation of oxidative stress and inflammation. Notably, isorhamnetin arrests cancer cell proliferation by regulating cyclins, and CDKs induce apoptosis via caspase activation and mitochondrial dysfunction. It inhibits metastatic progression by downregulating MMPs, VEGF, and epithelial–mesenchymal transition (EMT) markers. Furthermore, its antioxidant and anti-inflammatory properties mitigate reactive oxygen species (ROS) and pro-inflammatory cytokines, restricting cancer progression and modulating tumor microenvironments. Combining isorhamnetin with other treatments was also discussed to overcome multidrug resistance. Importantly, this review integrates the recent literature (2022–2024) and highlights isorhamnetin’s roles in modulating cancer-specific signaling pathways, immune evasion, tumor microenvironment dynamics, and combination therapies. We also discuss nanoformulation-based strategies that significantly enhance isorhamnetin’s delivery and bioavailability. This positions isorhamnetin as a promising adjunct in modern oncology, capable of improving therapeutic outcomes when used alone or in synergy with conventional treatments. The future perspectives and potential research directions were also summarized. By consolidating current knowledge and identifying critical research gaps, this review positions Isorhamnetin as a potent and versatile candidate in modern oncology, offering a pathway toward safer and more effective cancer treatment strategies. Full article

Knowing the superior biochemical defense mechanisms of sessile organisms, it is not hard to believe the cure for any human sickness might be hidden in nature—we “just” have to identify it and make it safely available in the right dose to our organs and cells that are in need. For decades, green tea catechins (GTCs) have been a case in point. Because of their low redox potential and favorable positioning of hydroxyl groups, these flavonoid representatives (namely, catechin—C, epicatechin—EC, epicatechin gallate—ECG, epigallocatechin—EGC, epigallocatechin gallate—EGCG) are among the most potent plant-derived (and not only) antioxidants. The proven anti-inflammatory, neuroprotective, antimicrobial, and anticarcinogenic properties of these phytochemicals further contribute to their favorable pharmacological profile. Doubtlessly, GTCs hold the potential to “cope” with the majority of today‘s socially significant diseases, yet their mass use in clinical practice is still limited. Several factors related to the compounds’ membrane penetrability, chemical stability, and solubility overall determine their low bioavailability. Moreover, the antioxidant-to-pro-oxidant transitioning behavior of GTCs is highly conditional and, to a certain degree, unpredictable. The nanoparticulate delivery systems represent a logical approach to overcoming one or more of these therapeutic challenges. This review particularly focuses on the lipid-based nanotechnologies known to be a leading choice when it comes to drug permeation enhancement and not drug release modification nor drug stabilization solely. It is our goal to present the privileges of encapsulating green tea catechins in either vesicular or particulate lipid carriers with respect to the increasingly popular trends of advanced phytotherapy and functional nutrition. Full article

Atopic dermatitis (AD) is a common chronic inflammatory skin disorder characterized by immune dysregulation and skin barrier impairment. This study evaluated the anti-inflammatory and immunomodulatory effects of Camellia japonica extract in a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model using SKH-1 hairless mice. Topical application of Camellia japonica extract for four weeks significantly alleviated AD-like symptoms by reducing epidermal thickness, mast cell infiltration, and overall skin inflammation. Hematological analysis revealed a marked decrease in total white blood cell (WBC) and neutrophil counts. Furthermore, the Camellia japonica extract significantly decreased oxidative stress, as evidenced by reduced serum reactive oxygen species (ROS) and nitric oxide (NO) levels, while enhancing the activity of antioxidant enzymes such as catalase. Importantly, allergic response markers including serum immunoglobulin E (IgE), histamine, and thymic stromal lymphopoietin (TSLP), were also downregulated. At the molecular level, Camellia japonica extract suppressed the expression of key pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and T helper 2 (Th2)-type cytokines such as IL-4 and IL-5, while slightly upregulating the anti-inflammatory cytokine IL-10. Collectively, these findings suggest that Camellia japonica extract effectively modulates immune responses, suppresses allergic responses, attenuates oxidative stress, and promotes skin barrier recovery. Therefore, application of Camellia japonica extract holds the promising effect as a natural therapeutic agent for the prevention and treatment of AD-like skin conditions. 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

Chronic high-fat diet (HFD) feeding in male rats causes significant metabolic as well as inflammatory disturbances, including obesity, insulin resistance, dyslipidemia, liver and kidney dysfunction, oxidative stress, and hypothalamic dysregulation. This study assessed the therapeutic effects of chlorogenic acid (CGA), a natural polyphenol, administered at 10 mg and 100 mg/kg/day for the last 4 weeks of a 12-week HFD protocol. Both CGA doses reduced body weight gain, abdominal circumference, and visceral fat accumulation, with the higher dose showing greater efficacy. CGA improved metabolic parameters by lowering fasting glucose and insulin and enhancing lipid profiles. CGA suppressed orexigenic genes (Agrp, NPY) and upregulated anorexigenic genes (POMC, CARTPT), suggesting appetite regulation in the hypothalamus. In abdominal white adipose tissue (WAT), CGA boosted antioxidant defenses (SOD, CAT, GPx, HO-1), reduced lipid peroxidation (MDA), and suppressed pro-inflammatory cytokines including TNF-α, IFN-γ, and IL-1β, while increasing the anti-inflammatory cytokine IL-10. CGA modulated inflammatory signaling via upregulation of miR-146a and inhibition of IRAK1, TRAF6, and NF-κB. It also reduced apoptosis by downregulating p53, Bax, and Caspase-3, and restoring Bcl-2. These findings demonstrate that short-term CGA administration effectively reverses multiple HFD-induced impairments, highlighting its potential as an effective therapeutic for obesity-related metabolic disorders. Full article

Parishin C (PaC) is an active ingredient in Gastrodia elata Bl. that has neuroprotective effects. However, research on its role in oxidative stress and neuroinflammation is still limited. This study used LPS–stimulated HT22 cells to investigate the antioxidant properties of PaC. Through the co–culture system of HT22 and BV2 cells, the effect of PaC on neuroinflammation was explored. The current results indicated that PaC can inhibit the levels of reactive oxygen species and peroxides in LPS–stimulated HT22 cells and increase the levels of antioxidant factors. Meanwhile, PaC can also inhibit neuronal ferroptosis and the levels of pro–inflammatory cytokines in BV2 cells. Importantly, the antioxidant and anti–inflammatory effects of PaC are achieved by activating the Nrf2 signaling pathway. The WB and IF results indicated that PaC can promote nuclear translocation of Nrf2, activate downstream antioxidant factors, and thereby regulate inflammatory responses. Inhibition of Nrf2 can significantly inhibit the regulation of PaC on the Nrf2 signaling pathway. These results indicated that PaC can activate the Nrf2 signaling pathway to inhibit oxidative stress and inflammation. Full article

Tuberaria lignosa (Sweet) Samp. (Cistaceae) is a herbaceous species native to southwestern Europe, traditionally used to treat wounds, ulcers, and inflammatory or infectious skin conditions. This study aimed to characterize the phytochemical profile of its aqueous leaf extract and evaluate its skin-related in vitro biological activities. The phenolic composition was determined using UHPLC-HRMS/MS, HPLC-DAD, and quantitative colorimetric assays. Antioxidant activity was assessed against synthetic free radicals, reactive oxygen and nitrogen species, transition metals, and pro-oxidant enzymes. Enzymatic inhibition of tyrosinase, hyaluronidase, collagenase, and elastase were evaluated using in vitro assays. Cytocompatibility was tested on human keratinocytes and NIH/3T3 fibroblasts using MTT and resazurin assays, respectively, while wound healing was evaluated on NIH/3T3 fibroblasts using the scratch assay. Antifungal activity was investigated against several Candida and dermatophyte species, while antibiofilm activity was tested against Epidermophyton floccosum. The extract was found to be rich in phenolic compounds, accounting for nearly 45% of its dry weight. These included flavonoids, phenolic acids, and proanthocyanidins, with ellagitannins (punicalagin) being the predominant group. The extract demonstrated potent antioxidant, anti-tyrosinase, anti-collagenase, anti-elastase, and antidermatophytic activities, including fungistatic, fungicidal, and antibiofilm effects. These findings highlight the potential of T. lignosa as a valuable and underexplored source of bioactive phenolic compounds with strong potential for the development of innovative approaches for skin care and therapy. Full article

Oxysterols such as 7-ketocholesterol (7KCh) contribute to the pathogenesis of autoimmune and chronic inflammatory diseases by inducing oxidative stress and promoting pro-inflammatory immune cell activation. Dendritic cells (DCs) play a central role in maintaining immune tolerance, and their dysregulation is a key driver of autoimmunity. Targeting DCs by using natural compounds offers a promising strategy to restore redox balance and suppress aberrant immune responses. This study investigated the immunomodulatory and antioxidant properties of Lupeol, a natural triterpenoid, in human monocyte-derived DCs exposed to 7KCh. Flow cytometry and cytokine profiling demonstrated that Lupeol preserved the immature, tolerogenic phenotype of DCs by promoting a dose-dependent increase in the anti-inflammatory cytokine IL-10. Lupeol also inhibited the 7KCh-induced upregulation of maturation markers (CD83, CD86) and suppressed the release of pro-inflammatory cytokines IL-1β and IL-12p70. Functionally, Lupeol-treated DCs directed T cell polarization toward an anti-inflammatory and regulatory profile while dampening the inflammatory responses triggered by 7KCh. This immunoregulatory effect was further supported by the decreased secretion of the pro-inflammatory cytokines IL-1β and IL-12p70 in DC culture supernatants. Mechanistic analyses using immunofluorescence showed that Lupeol alone significantly increased nuclear NRF2 levels and upregulated HO-1 expression. Western blot analysis further confirmed Lupeol’s ability to activate the KEAP1-NRF2 signaling pathway, as evidenced by increased expression of NRF2 and its downstream target, NQO1. The use of ML385, a selective NRF2 inhibitor, in ROS and cytokine assays supported the involvement of NRF2 in mediating the Lupeol antioxidant and anti-inflammatory effects in DCs. Notably, the oxidative burden induced by 7KCh limited the full activation of NRF2 signaling triggered by Lupeol. Furthermore, docking and MM/PBSA analyses revealed the specific interactions of Lupeol with the kelch domain of KEAP1. These findings suggest that Lupeol may serve as a promising orally available immunomodulatory agent capable of promoting tolerogenic DCs, offering potential applications in autoimmune and other chronic inflammatory diseases. Full article

Phosphodiesterase type 5 (PDE5) inhibitors, including sildenafil, tadalafil, and vardenafil, are primarily prescribed for erectile dysfunction and pulmonary hypertension. Emerging evidence suggests they may also modulate inflammatory pathways and improve vascular function, but their effects on inflammatory biomarkers in humans remain incompletely defined. A systematic review and meta-analysis were conducted to evaluate the impact of PDE5 inhibitors on inflammatory and endothelial markers in adult humans. Randomized controlled trials comparing PDE5 inhibition to placebo were identified through electronic database searches. Outcomes included pro-inflammatory markers (TNF-α, IL-6, IL-8, CRP, VCAM-1, ICAM-1, P-selectin) and anti-inflammatory or signalling markers (IL-10, NO, cGMP), assessed at short-term (≤1 week), intermediate-term (4–6 weeks), or long-term (≥12 weeks) follow-up. Risk of bias was assessed using the Cochrane RoB 2 tool. A total of 20 studies comprising 1549 participants were included. Meta-analyses showed no significant short-term effects of PDE5 inhibition on TNF-α, IL-6, or CRP. Long-term treatment was associated with reduced IL-6 (SMD = −0.64, p = 0.002) and P-selectin (SMD = −0.57, p = 0.02), and increased cGMP (SMD = 0.87, p = 0.0003). Effects on IL-10 and nitric oxide were inconsistent across studies. Most trials had low risk of bias. PDE5 inhibitors may exert anti-inflammatory effects in long-term use by reducing vascular inflammation and enhancing cGMP signalling. These findings support further investigation of PDE5 in chronic inflammatory conditions. Full article

Gingival inflammation compromises the integrity of the gingival epithelium and the underlying tissues, highlighting the need for adjuvant therapies with immunomodulatory and healing properties. Casearia sylvestris, a medicinal plant known as guaçatonga, is traditionally used to treat inflammatory lesions. This study aimed to investigate the effects of C. sylvestris on the synthesis of pro- and anti-inflammatory, proteolytic, and antioxidant molecules and on wound healing in epithelial cells. A human telomerase-immortalized gingival keratinocyte cell line (TIGKs) was used, and cells were exposed to Escherichia coli lipopolysaccharide (LPS) in the presence and absence of C. sylvestris extract, its diterpene-concentrated fraction, and its clerodane diterpene casearin J for 24 h and 48 h. Gene expression and protein synthesis were analyzed by RT-qPCR and ELISA, respectively. Nitric oxide (NO) and NF-κB activation were analyzed by Griess reaction and immunofluorescence, respectively. Additionally, cell viability was evaluated by alamarBlue^® assay, and an automated scratch assay was used for wound healing. LPS significantly increased the expression of cytokines (TNF-α, IL-1β, IL-6, IL-8, IL-10, IL-17), proteases (MMP-1 and MMP-13), iNOS as well as NO synthesis, and triggered NF-κB nuclear translocation. It also reduced IL-4 expression, cell viability, and cellular wound repopulation. Treatment with C. sylvestris derivatives significantly abrogated all aforementioned LPS-induced effects by 80–100%. Furthermore, even at higher concentrations, C. sylvestris did not affect cell viability, thus proving the safety of its derivatives. C. sylvestris exerts anti-inflammatory, antiproteolytic, and antioxidant effects on gingival keratinocytes, highlighting its potential as a valuable adjunct in the prevention and treatment of periodontal diseases. Full article