Search Results (2,107)

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

The deterioration of uterine calcium transport capacity induced by aging is a common problem for late-laying period hens, causing decline in eggshell quality. This study aimed to investigate the effects and possible regulatory mechanisms of dietary puerarin (PU) on calcium transport and eggshell quality in aged hens. Two hundred eighty-eight Hubbard Efficiency Plus broiler breeder hens (50-week-old) were randomly allocated to three dietary treatments containing 0, 40, or 200 mg/kg puerarin (PU), with 8 replicates of 12 birds each, for an 8-week trial. The results demonstrated that dietary PU ameliorated the eggshell thickness and strength, which in turn reduced the broken egg rate (p < 0.05). Histological analysis showed that PU improved uterus morphology and increased epithelium height in the uterus (p < 0.05). Antioxidative capacity was significantly improved via upregulation of Nrf2, HO-1, and GPX1 mRNA expression in the uterus (p < 0.05), along with enhanced total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-PX) activity, and decreased levels of the oxidative stress marker malondialdehyde (MDA) (p < 0.05). Meanwhile, PU treatment reduced the apoptotic index of the uterus, followed by a significant decrease in expression of pro-apoptotic genes Caspase3 and BAX and the rate of BAX/BCL-2. Additionally, calcium content in serum and uterus, as well as the activity of Ca²⁺-ATPase in the duodenum and uterus, were increased by dietary PU (p < 0.05). The genes involved in calcium transport including ERα, KCNA1, CABP-28K, and OPN in the uterus were upregulated by PU supplementation (p < 0.05). The 16S rRNA gene sequencing revealed that dietary PU supplementation could reverse the age-related decline in the relative abundance of Bacteroidota within the uterus (p < 0.05). Overall, dietary PU can improve eggshell quality and calcium transport through enhanced antioxidative defenses and mitigation of age-related uterine degeneration. Full article

With the acceleration of the pace of life, increased stress levels, and changes in lifestyle factors such as diet and exercise, the incidence of diseases such as cancer and immunodeficiency has been on the rise, which is closely associated with the impaired antioxidant capacity of the body. Polypeptides and polysaccharides derived from edible fungi demonstrate significant strong antioxidant activity and immunomodulatory effects. Auricularia auricula, the second most cultivated mushroom in China, is not only nutritionally rich but also offers considerable health benefits. In particular, its polysaccharides have been widely recognized for their immunomodulatory activities, while its abundant protein content holds great promise as a raw material for developing immunomodulatory peptides. To meet the demand for high-value utilization of Auricularia auricula resources, this study developed a key technology for the stepwise extraction of polypeptides (AAPP1) and polysaccharides (AAPS3) using a composite enzymatic hydrolysis process. Their antioxidant and immunomodulatory effects were assessed using cyclophosphamide (CTX)-induced immune-suppressed mice. The results showed that both AAPP1 and AAPS3 significantly reversed CTX-induced decreases in thymus and spleen indices (p < 0.05); upregulated serum levels of cytokines (e.g., IL-4, TNF-α) and immunoglobulins (e.g., IgA, IgG); enhanced the activities of hepatic antioxidant enzymes SOD and CAT (p < 0.05); and reduced the content of MDA, a marker of oxidative damage. Intestinal microbiota analysis revealed that these compounds restored CTX-induced reductions in microbial α-diversity, increased the abundance of beneficial bacteria (Paramuribaculum, Prevotella; p < 0.05), decreased the proportion of pro-inflammatory Duncaniella, and reshaped the balance of the Bacteroidota/Firmicutes phyla. This study represents the first instance of synergistic extraction of polypeptides and polysaccharides from Auricularia auricula using a single process. It demonstrates their immune-enhancing effects through multiple mechanisms, including “antioxidation-immune organ repair-intestinal microbiota regulation.” The findings offer a theoretical and technical foundation for the deep processing of Auricularia auricula and the development of functional foods. Full article

Eriobotrya japonica (Thunb.) Lindl. leaves are rich in polyphenolic compounds, yet their toxicological effects in aquatic models remain poorly understood. This study evaluated the impact of a hydroethanolic E. japonica leaf extract on zebrafish embryos through the use of morphological, behavioral, and biochemical parameters. The 96 h LC₅₀ was determined as 189.8 ± 4.5 mg/L, classifying the extract as practically non-toxic, according to OECD guidelines. Thereby, embryos were exposed for 90 h to 75 and 150 mg/L concentrations of the E. japonica leaf extract. While no significant effects were noted at the lowest concentration of 150 mg/L, significant developmental effects were observed, including reduced survival, delayed hatching, underdevelopment of the swim bladder, and retention of the yolk sac. These malformations were accompanied by marked behavioral impairments. Biochemical analysis revealed a concentration-dependent increase in superoxide dismutase (SOD) and catalase (CAT) activity, suggesting the activation of antioxidant defenses, despite no significant change in reactive oxygen species (ROS) levels. This indicates a potential compensatory redox response to a pro-oxidant signal. Additionally, the acetylcholinesterase (AChE) activity was significantly reduced at the highest concentration, which may have contributed to the observed neurobehavioral changes. While AChE inhibition is commonly associated with neurotoxicity, it is also a known therapeutic target in neurodegenerative diseases, suggesting concentration-dependent dual effects. In summary, the E. japonica leaf extract induced concentration-dependent developmental and behavioral effects in zebrafish embryos, while activating antioxidant responses without triggering oxidative damage. These findings highlight the extract’s potential bioactivity and underscore the need for further studies to explore its safety and therapeutic relevance. 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

Background: The majority of parotid gland tumors are benign, e.g., pleomorphic adenoma (PA) and Warthin’s tumor (WT). From a biomedical point of view, oxidative stress is of significant importance due to its established association with the initiation and progression of various types of cancer, including parotid gland cancers. This study aimed to assess whether blood prooxidant–antioxidant markers could aid in diagnosing and guiding surgery for recurrent malignancies after parotid tumor treatment. Methods: We examined patients (n = 20) diagnosed with WT (n = 14) and PA (n = 6) using histopathological verification and computed tomography (CT) who qualified for surgical treatment. Blood samples were taken before the surgery and again 10 days later for biochemical analysis. The activities of the antioxidant enzymes (SOD, CAT and GPx), the non-enzymatic antioxidants (GSH and UA) and oxidative stress markers (MDA and TOS) were determined in the blood. The activities of CK and LDH and the concentrations of Cor and TAS were measured in the serum. Hb and Ht were determined in whole blood. Results: The patients’ SOD, CAT, and GPx activities after surgery did not differ significantly from their preoperative levels. However, following surgery, their serum TOS levels were significantly elevated in all the patients compared to baseline. In contrast, the plasma MDA concentrations were markedly reduced after surgery. Similarly, the GSH concentrations showed a significant decrease postoperatively. No significant changes were observed in the CK and LDH activities, TAS concentrations, or levels of Hb, Ht and Cor following surgery. Conclusions: The surgical removal of salivary gland tumors did not result in a reduction in oxidative stress at 10 days after surgery. Therefore, further studies are needed to determine the effectiveness of endogenous defense mechanisms in counteracting the oxidative stress induced by salivary gland tumors. Full article

Volatile organic compounds (VOCs) are highly volatile chemicals in natural and anthropogenic environments, significantly affecting indoor air quality. Major sources of indoor VOCs include emissions from building materials, furnishings, and consumer products. Natural wood products release VOCs, including terpenes and aldehydes, which exert diverse health effects ranging from mild respiratory irritation to severe outcomes, such as formaldehyde-induced carcinogenicity. The temporal dynamics of VOC emissions were investigated, and the toxicological and physiological effects of the VOCs emitted by two types of natural wood, Korean Red Pine (Pinus densiflora) and Japanese Cypress (Chamaecyparis obtusa), were evaluated. Using female C57BL/6 mice as an animal model, the exposure setups included phytoncides, formaldehyde, and intact wood samples over short- and long-term durations. The exposure effects were assessed using oxidative stress markers, antioxidant enzyme activity, hepatic and renal biomarkers, and inflammatory cytokine profiles. Long-term exposure to Korean Red Pine and Japanese Cypress wood VOCs did not induce significant pathological changes. Japanese Cypress exhibited more distinct benefits, including enhanced oxidative stress mitigation, reduced systemic toxicity, and lower pro-inflammatory cytokine levels compared to the negative control group, attributable to its more favorable VOC emission profile. These findings highlight the potential health and environmental benefits of natural wood VOCs and offer valuable insights for optimizing timber use, improving indoor air quality, and informing public health policies. 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

Background: This study presents an innovative approach to cardiovascular disease (CVD) risk prediction based on a comprehensive analysis of clinical, immunological and biochemical markers using mathematical modelling and machine learning methods. Baseline data include indices of humoral and cellular immunity (CD59, CD16, IL-10, CD14, CD19, CD8, CD4, etc.), cytokines and markers of cardiovascular disease, inflammatory markers (TNF, GM-CSF, CRP), growth and angiogenesis factors (VEGF, PGF), proteins involved in apoptosis and cytotoxicity (perforin, CD95), as well as indices of liver function, kidney function, oxidative stress and heart failure (albumin, cystatin C, N-terminal pro B-type natriuretic peptide (NT-proBNP), superoxide dismutase (SOD), C-reactive protein (CRP), cholinesterase (ChE), cholesterol, and glomerular filtration rate (GFR)). Clinical and behavioural risk factors were also considered: arterial hypertension (AH), previous myocardial infarction (PICS), aortocoronary bypass surgery (CABG) and/or stenting, coronary heart disease (CHD), atrial fibrillation (AF), atrioventricular block (AB block), and diabetes mellitus (DM), as well as lifestyle (smoking, alcohol consumption, physical activity level), education, and body mass index (BMI). Methods: The study included 52 patients aged 65 years and older. Based on the clinical, biochemical and immunological data obtained, a model for predicting the risk of premature cardiovascular aging was developed using mathematical modelling and machine learning methods. The aim of the study was to develop a predictive model allowing for the early detection of predisposition to the development of CVDs and their complications. Numerical methods of mathematical modelling, including Runge–Kutta, Adams–Bashforth and backward-directed Euler methods, were used to solve the prediction problem, which made it possible to describe the dynamics of changes in biomarkers and patients’ condition over time with high accuracy. Results: HLA-DR (50%), CD14 (41%) and CD16 (38%) showed the highest association with aging processes. BMI was correlated with placental growth factor (37%). The glomerular filtration rate was positively associated with physical activity (47%), whereas SOD activity was negatively correlated with it (48%), reflecting a decline in antioxidant defence. Conclusions: The obtained results allow for improving the accuracy of cardiovascular risk prediction, and form personalised recommendations for the prevention and correction of its development. 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

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