Search Results (5,066)

Cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from Cannabis sativa L., has emerged as a promising multifunctional agent in dermatology and cosmetic science. The review provides an updated synthesis of CBD’s topical therapeutic potential, challenges, and evolving regulatory frameworks. CBD exhibits diverse biological effects, including anti-inflammatory, antioxidant, antibacterial, analgesic, lipostatic, antiproliferative, moisturising, and anti-ageing properties through interactions with the skin’s endocannabinoid system (ECS), modulating CB1, CB2, TRPV channels, and PPARs. Preclinical and clinical evidence support its efficacy in managing acne, psoriasis (including scalp psoriasis), atopic and seborrheic dermatitis, and allergic contact dermatitis. CBD also relieves pruritus through neuroimmune modulation and promotes wound healing in conditions such as pyoderma gangrenosum and epidermolysis bullosa. In hair disorders such as androgenetic alopecia, it aids follicular regeneration. CBD shows promise in managing skin cancers (melanoma, squamous cell carcinoma, Kaposi sarcoma) and pigmentation disorders such as melasma and vitiligo. It enhances skin rejuvenation by reducing oxidative stress and boosting collagen and hydration. However, there are challenges regarding CBD’s physicochemical stability, skin penetration, and regulatory standardisation. As consumer demand for natural, multifunctional skincare grows, further research is essential to validate its long-term safety, efficacy, and optimal formulation strategies. Full article

Excessive alcohol consumption is associated with various health complications, including liver damage and systemic inflammation. Probiotic interventions have emerged as promising strategies to mitigate alcohol-induced harm, yet their mechanisms of action remain incompletely understood. This randomized, double-blind, placebo-controlled clinical trial aimed to evaluate the protective effects of Weizmannia coagulans BC179 in chronic alcohol consumers. Seventy participants with a history of long-term alcohol intake were randomly assigned to receive either BC179 (3 g/day, 1 × 10¹⁰ CFU) or a placebo for a 30-day intervention period. Following alcohol ingestion, dynamic monitoring of blood alcohol concentration (BAC), inflammatory and oxidative stress biomarkers, and serum metabolomic profiles was conducted. BC179 supplementation significantly reduced BAC and enhanced the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), while decreasing levels of alkaline phosphatase (ALP), high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Conversely, the anti-inflammatory cytokine interleukin-10 (IL-10), superoxide dismutase (SOD), and glutathione (GSH) were significantly upregulated. Levels of cytochrome P4502E1 (CYP2E1) and malondialdehyde (MDA) were also markedly reduced. Metabolomic analysis revealed significant modulation of taurine and hypotaurine metabolism, as well as downregulation of caffeine-related pathways. Collectively, these findings indicate that W. coagulans BC179 alleviates alcohol-induced discomfort by enhancing alcohol metabolism, attenuating inflammation, reducing oxidative stress, and modulating key metabolic pathways. This probiotic strain may represent a promising adjunctive strategy for managing alcohol-related health issues. Full article

Isoegomaketone [(E)-1-(furan-3-yl)-4-methylpent-2-en-1-one; 1] is abundant in the essential oil of Perilla species and exhibits various biological activities, such as anticancer and anti-inflammatory effects. In order to discover compounds with reduced toxicity or enhanced biological activity through structural modification of natural product-derived components, isoegomaketone was irradiated with an electron beam at five different doses, and (±)-8-methoxy-perilla ketone (2) was obtained with the highest yield of 3.8% (w/w) at 80 kGy. Its structure was identified by one-dimensional and two-dimensional nuclear magnetic resonance spectroscopy and high-resolution chemical ionization mass spectrometry. Compound 2 inhibited nitric oxide production and inducible nitric oxide synthase mRNA expression in a dose-dependent manner in lipopolysaccharide-stimulated RAW 264.7 cells. It also dose-dependently suppressed the mRNA expression of pro-inflammatory mediators such as IL-1β, IFN-β, and MCP-1, while having no significant effect on IL-6 mRNA levels. Furthermore, ELISA analysis demonstrated that 2 reduced MCP-1 protein expression but did not affect the protein level of TNF-α or IL-6. This study provides a reference for the structural analysis of compounds related to 2 by presenting NMR data acquired with chloroform-d, and is the first to report the anti-inflammatory properties of 2. Full article

Background and Objectives: Kumazasa extract (KZExt) is a food product obtained by steam extraction of Kumazasa (Sasa senanensis and Sasa kurilensis) leaves under high temperature and pressure. It contains abundant polyphenols, including trans-p-coumaric acid and ferulic acid, as well as xylooligosaccharides. In this study, we investigated the antibacterial, anti-viral, and anti-inflammatory effects of KZExt in vitro and in vivo. Materials and Methods: The anti-oxidant, antibacterial, and anti-viral effects of KZExt were assessed in vitro. Anti-oxidant activity was evaluated based on the scavenging of •OH, •O₂⁻ and ¹O₂. Antibacterial effects were assessed by determining the minimum inhibitory concentration (MIC) using a microdilution method. Anti-influenza activity was measured via plaque formation in MDCK cells. Anti-inflammatory effects were assessed by measuring interleukin (IL)-1β inhibition in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. In vivo, KZExt was administered once (30 min before) in a formalin-induced inflammation model to evaluate pain-related behavior. In the LPS-induced inflammation model, KZExt was administered for five days before LPS injection. Behavioral changes and cytokine levels were assessed 24 h later via the open field test and cytokine quantification. Results: In vitro, KZExt showed antibacterial, anti-influenza, and anti-oxidant effects, and suppressed LPS-induced IL-1β production. In vivo, it significantly reduced the second phase of formalin-induced pain behavior. In the LPS model, although behavioral changes were unaffected, KZExt suppressed IL-6 and interferon-γ production. Conclusions: The antibacterial, anti-viral, and anti-inflammatory effects of KZExt were confirmed in vitro and in vivo. Notably, the anti-inflammatory effect suggests potential immunomodulatory activity. These findings indicate that KZExt may help suppress smoldering inflammation and inflammation associated with various diseases through its combined antibacterial, anti-viral, and immunomodulatory actions. Full article

Aortic stenosis (AS) and atherosclerosis are progressive cardiovascular conditions that frequently coexist and share multiple clinical and molecular features. Medical therapies have shown effectiveness in preventing and treating atherosclerosis and its consequences. For AS, effective pharmacological therapies remain limited. Understanding the shared risk factors and mechanisms between the two conditions may provide opportunities for therapeutic repositioning in AS. We performed a narrative review focusing on studies published from 2005 to 2025. Inclusion criteria encompassed clinical trials, experimental models, and molecular studies addressing overlapping risk factors, pathological pathways, and treatment approaches for AS and atherosclerosis. AS and atherosclerosis share key risk factors, including age, hypertension, hyperlipidemia, and diabetes. Molecular mechanisms, such as chronic inflammation, endothelial dysfunction, oxidative stress, lipid accumulation, and calcific remodeling, are common to both. Pathways involving the renin-angiotensin system, Notch signaling, and osteogenic mediators contribute to disease progression. Several drug classes, notably proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, lipoprotein(a) (Lp(a)) lowering therapies, anti-inflammatory agents, and immunomodulators, show potential for repositioning in AS management. The substantial overlap in risk factors and molecular mechanisms between AS and atherosclerosis supports a rationale for therapeutic repositioning. Targeting shared pathways could lead to innovative strategies for slowing AS progression and improving patient outcomes. Full article

Background/Objectives: Recently, concerns about age-related conditions, such as sarcopenia and chronic inflammation, have increased owing to the global acceleration of population aging. Notably, these conditions are interrelated and further exacerbate functional decline in older adults. Therefore, this study aimed to evaluate the efficacy of a novel bioactive compound, DuoX (a mixture of the postbiotic beLP1 and Cichorium intybus L.), in alleviating muscle wasting and chronic inflammation. Specifically, the mixture consisted of inulin-rich C. intybus L. root extract, known for its anti-inflammatory effects, and beLP1, a postbiotic previously shown to exert anti-sarcopenic effects. Methods: To assess the multifunctional effects of the DuoX, dexamethasone-induced sarcopenia models (C2C12 myotubes and an in vivo rat model) and a lipopolysaccharide-stimulated RAW 264.7 macrophage inflammation model were established. Results: Pretreatment with DuoX prevented the dexamethasone-induced reduction in myotube diameter and effectively inhibited muscle degradation by downregulating the expression of atrogin-1 caused by dexamethasone treatment. In rats with DEX-induced sarcopenia, DuoX prevented muscle weight loss, grip strength reduction, and the upregulation of atrogin-1 expression in vivo. In lipopolysaccharide-stimulated RAW 264.7 macrophages, DuoX significantly reduced nitric oxide production and cyclooxygenase-2 protein expression and suppressed p38 and ERK phosphorylation in the MAPK signaling pathway, thereby alleviating inflammatory responses. Conclusions: DuoX holds promise as a dual-functional candidate with both anti-sarcopenic and anti-inflammatory properties. Further preclinical and clinical studies are required to validate its therapeutic efficacy and safety in humans, which may contribute to the development of preventive strategies for healthy aging. Full article

Bovine endometritis can be caused by Escherichia coli (E. coli), from which the lipopolysaccharide (LPS) triggers TLR4/NF-κB-mediated inflammation and reactive oxygen species (ROS) overproduction, resulting in impaired reproductive performance. While NADPH oxidase (NOX) is a critical source of ROS generation, its role in bovine endometrial epithelial cells (BEEC) and modulation by selenium remains unexplored. In this study, primary BEEC was challenged by LPS to assess NOX2/4 expression kinetics. Inhibitors of NOX and NF-κB were applied to observe the role of NOX-derived ROS in BEEC inflammation and in selenomethionine (SeMet)-modulated anti-inflammation. ROS levels were measured by flow cytometry. The changes in inflammatory cytokines, and the proteins related to NOX4 and NF-κB, were analyzed via qPCR and Western blot. As a result, the inhibition of NOX decreased LPS-induced proinflammatory cytokine expression, ROS accumulation, NOX4 level, and the phosphorylation of NF-κB P65 and IκBα. Conversely, the suppression of NF-κB downregulated the levels of ROS and NOX4. Cotreatment with SeMet and a NOX inhibitor further suppressed the inflammatory response, ROS level, and NF-κB pathway activation compared to individual treatment, but had no additive effect on the NOX4 protein level. In conclusion, the NOX4/ROS/NF-κB axis forms a proinflammatory feedback loop in LPS-stimulated BEEC. SeMet mitigates oxidative stress and inflammation partially through NOX4 inhibition. Full article

The renin-angiotensin system (RAS) has evolved from being considered solely a peripheral endocrine system for cardiovascular control to being recognized as a complex molecular network with important functions in the central nervous system (CNS) and peripheral nervous system (PNS). Here we examine the organization, mechanisms of action, and clinical implications of cerebral RAS in physiological conditions and in various neurological pathologies. The cerebral RAS operates autonomously, synthesizing its main components locally due to restrictions imposed by the blood–brain barrier. The key elements of the system are (pro)renin; (pro)renin receptor (PRR); angiotensinogen; angiotensin-converting enzyme types 1 and 2 (ACE1 and ACE2); angiotensin I (AngI), angiotensin II (AngII), angiotensin III (AngIII), angiotensin IV (AngIV), angiotensin A (AngA), and angiotensin 1-7 (Ang(1-7)) peptides; RAS-regulating aminopeptidases; and AT1 (AT1R), AT2 (AT2R), AT4 (AT4R/IRAP), and Mas (MasR) receptors. More recently, alamandine and its MrgD receptor have been included. They are distributed in specific brain regions such as the hypothalamus, hippocampus, cerebral cortex, and brainstem. The system is organized into two opposing axes: the classical axis (renin/ACE1/AngII/AT1R) with vasoconstrictive, proinflammatory, and prooxidative effects, and the alternative axes AngII/AT2R, AngIV/AT4R/IRAP, ACE2/Ang(1-7)/MasR and alamandine/MrgD receptor, with vasodilatory, anti-inflammatory, and neuroprotective properties. This functional duality allows us to understand its role in neurological physiopathology. RAS dysregulation is implicated in multiple neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and neuropsychiatric disorders such as depression and anxiety. In brain aging, an imbalance toward hyperactivation of the renin/ACE1/AngII/AT1R axis is observed, contributing to cognitive impairment and neuroinflammation. Epidemiological studies and clinical trials have shown that pharmacological modulation of the RAS using ACE inhibitors (ACEIs) and AT1R antagonists (ARA-II) not only controls blood pressure but also offers neuroprotective benefits, reducing the incidence of cognitive decline and dementia. These effects are attributed to direct mechanisms on the CNS, including reduction of oxidative stress, decreased neuroinflammation, and improved cerebral blood flow. Full article

Photoaging is a multifactorial and progressive skin aging process primarily triggered by prolonged exposure to ultraviolet (UV) radiation. This condition leads to both structural and functional impairments in the skin, including the formation of wrinkles, loss of elasticity, pigmentation irregularities, and an elevated risk of skin malignancies. At the core of photoaging is the accumulation of reactive oxygen species (ROS), which generate oxidative stress, initiate chronic inflammation, cause DNA damage, and accelerate the breakdown of the extracellular matrix—largely through the activity of matrix metalloproteinases (MMPs). The review provides a comprehensive analysis of various natural substances, including antioxidants, anti-inflammatory agents, photoprotective compounds, and emerging regenerative treatments, based on in vitro and in vivo research. Special emphasis is placed on natural substances, including polyphenols, cannabinoids, carotenoids, retinoids, and vitamins, highlighting their potential in preventing and treating photoaging. This review aims to present a detailed, evidence-based overview of photoaging mechanisms and innovative approaches to mitigate its effects. Full article

Objectives: Animal studies have demonstrated that mesenchymal stem cell-conditioned medium (MSC-CM) possesses various therapeutic effects, including anti-inflammatory and anti-fibrotic properties. This study investigated the efficacy and safety of administering MSC-CM as a treatment for patients with generalized fatigue. Methods: The MSC-CM used in this study was derived from human adipose tissue and umbilical cord-derived mesenchymal stem cells cultured in a medium free of animal-derived components to avoid the risk of infection. This MSC-CM has recently been shown to possess anti-inflammatory effects and has been reported to be safe for human administration. With the expectation of alleviating fatigue symptoms through its anti-inflammatory effects, it was administered to patients intravenously and by inhalation. Safety and changes in subjective symptoms were evaluated, and blood biomarkers related to inflammation and oxidative stress were measured. Results: In this trial involving 19 patients experiencing fatigue, no serious side effects were observed following MSC-CM administration. Nearly half of the patients reported symptom improvement after a single dose, and some exhibited signs of reduced inflammation. Conclusions: This report presents the first investigation of systemic MSC-CM treatment for generalized fatigue, paving the way for more targeted studies on dosage and treatment frequency. These findings offer new hope and possibilities for treating fatigue, providing valuable insights into the clinical application of MSC-CM. Full article

Diabetes is increasingly recognized as a chronic inflammatory disease marked by systemic metabolic disturbances, with endothelial dysfunction playing a central role in its complications. Hyperglycemia, a hallmark of diabetes, drives endothelial damage by inducing excessive reactive oxygen species (ROS) production, particularly hydrogen peroxide (H₂O₂). This oxidative stress impairs endothelial cells, which are vital for vascular health, leading to severe complications such as diabetic nephropathy, retinopathy, and coronary artery disease—major causes of morbidity and mortality in diabetic patients. Recent studies have highlighted the therapeutic potential of placenta-derived mesenchymal stem cells (pMSCs), in mitigating these complications. pMSCs exhibit anti-inflammatory, antioxidant, and tissue-repair properties, showing promise in reversing endothelial damage in laboratory settings. To explore their efficacy in a more physiologically relevant context, we used a streptozotocin (STZ)-induced diabetic mouse model, which mimics type 1 diabetes by destroying pancreatic beta cells and causing hyperglycemia. pMSCs were administered via intra-peritoneal injections, and their effects on endothelial injury and tissue damage were assessed. Metabolic tests, including glucose tolerance tests (GTTs) and insulin tolerance tests (ITTs) revealed that pMSCs did not restore metabolic homeostasis or improve glucose regulation. However, histopathological kidney, heart, and eye tissue analyses demonstrated significant protective effects. pMSCs preserved glomerular structure in the kidneys, protected cardiac blood vessels, and maintained retinal integrity, suggesting their potential to address diabetes-related tissue injuries. Although these findings underscore the therapeutic potential of pMSCs for diabetic complications, further research is needed to optimize dosing, elucidate molecular mechanisms, and evaluate long-term safety and efficacy. Combining pMSCs with other therapies may enhance their benefits, paving the way for future clinical applications. Full article

Taxifolin is a natural flavonoid found in a variety of plants, including Siberian larch (Larix sibirica) and milk thistle (Silybum marianum), that has attracted attention for its multifaceted pharmacological properties, including cardioprotective effects. Through its antioxidant and anti-inflammatory activities, taxifolin has shown significant therapeutic potential in cardiovascular diseases such as atherosclerosis, myocardial ischemia, and diabetic cardiomyopathy. This review highlights the cardioprotective effects of taxifolin in preclinical models of atherosclerosis, ischemia/reperfusion injury, and diabetic cardiomyopathy. Taxifolin contributes to its cardioprotective effects through key mechanisms such as modulation of pathways such as PI3K/AKT and JAK2/STAT3, inhibition of NADPH oxidase, and modulation of nitric oxide production. Recent studies have shown that taxifolin can affect glucose metabolism by modulating sodium–glucose transporter (SGLT) expression, potentially enhancing the cardioprotective effects of SGLT2 inhibitors. Given the emerging role of SGLT2 inhibitors in the management of cardiovascular disease, further investigation of the interaction of this pathway with taxifolin may provide new therapeutic insights. Although taxifolin has multifaceted potential in the prevention and treatment of cardiovascular disease, further studies are needed to better understand its mechanisms and validate its efficacy in different disease stages. This review aims to provide a rationale for the clinical application of taxifolin-based cardiovascular therapies and suggest directions for future research. Full article

Type 2 diabetes is a multifactorial disease characterized by chronic hyperglycemia, insulin resistance, oxidative stress, inflammation, and dyslipidemia, factors that contribute to the development of long-term complications. In this context, the 2-aminobenzothiazole scaffold has emerged as a promising candidate due to its broad spectrum of biological properties. In this study, we performed a multidisciplinary evaluation of benzothiazole derivatives (5a–d, 8a–d, 11a–d, and 12c–d), starting with the in silico prediction of their properties, along with molecular docking against aldose reductase (ALR2) and peroxisome proliferator-activated receptor gamma (PPAR-γ). All compounds complied with the main rules of pharmacological similarity and optimal affinity, highlighting 8d (ΔG = −8.39 kcal/mol for ALR2 and −7.77 kcal/mol for PPAR-γ). Selected compounds from families C and D were synthesized in moderate yields (~60%) and showed low acute oral toxicity (LD₅₀ > 1250 mg/Kg). Compounds 8c and 8d inhibited ALR2 at concentrations below 10 µM. In vivo studies using a streptozotocin-induced diabetic rat model with a high-fat diet revealed that compound 8d produced sustained antihyperglycemic effects and reduced insulin resistance, dyslipidemia, and polydipsia, without inducing hepatotoxicity or displaying intrinsic antioxidant or anti-inflammatory activity. These findings suggest that 8d is a promising candidate for further development in diabetes-related therapeutic strategies. Full article

The pregnane X receptor (PXR), a ligand-activated nuclear receptor, plays a central role in regulating the metabolism of both endogenous substances and xenobiotics. In recent years, increasing evidence has highlighted its involvement in chronic diseases, particularly metabolic disorders and cancer. PXR modulates drug-metabolizing enzymes, transporters, inflammatory factors, lipid metabolism, and immune-related pathways, contributing to the maintenance of hepatic–intestinal barrier homeostasis, energy metabolism, and inflammatory responses. Specifically, in type 2 diabetes mellitus (T2DM), PXR influences disease progression by regulating glucose metabolism and insulin sensitivity. In obesity, it affects adipogenesis and inflammatory processes. In atherosclerosis (AS), PXR exerts protective effects through cholesterol metabolism and anti-inflammatory actions. In metabolic dysfunction-associated steatotic liver disease (MASLD), it is closely associated with lipid synthesis, oxidative stress, and gut microbiota balance. Moreover, PXR plays dual roles in various cancers, including hepatocellular carcinoma, colorectal cancer, and breast cancer. Currently, PXR-targeted strategies, such as small molecule agonists and antagonists, represent promising therapeutic avenues for treating metabolic diseases and cancer. This review comprehensively summarizes the structural features, signaling pathways, and gene regulatory functions of PXR, as well as its role in metabolic diseases and cancer, providing insights into its therapeutic potential and future drug development challenges. Full article

Ovarian aging is characterized by a gradual decline in both reproductive and endocrine functions, ultimately culminating in the cessation of ovarian activity around the age of 50, when most women experience natural menopause. The decline begins early, as follicular attrition is initiated in utero and continues throughout childhood and reproductive life. Most follicles undergo atresia without progressing through substantial stages of growth. With increasing age, a pronounced reduction occurs in the population of resting follicles within the ovarian reserve, accompanied by a decline in the size of growing follicular cohorts. Around the age of 38, the rate of follicular depletion accelerates, sometimes resulting in diminished ovarian reserve (DOR). The subsequent menopausal transition involves complex, irregular hormonal dynamics, manifesting as increasingly erratic menstrual patterns, primarily driven by fluctuations in circulating estrogens and a rising incidence of anovulatory cycles. In parallel with the progressive depletion of the follicular pool, the serum concentrations of anti-Müllerian hormone (AMH) decline gradually, while reductions in inhibin B levels become more apparent during the late reproductive years. The concomitant decline in both inhibin B and estrogen levels leads to a compensatory rise in circulating follicle-stimulating hormone (FSH) concentrations. Together, these endocrine changes, alongside the eventual exhaustion of the follicular reserve, converge in the onset of menopause, which is defined by the absence of menstruation for twelve consecutive months. The mechanisms contributing to ovarian aging are complex and multifactorial, involving both the oocyte and the somatic cells within the follicular microenvironment. Oxidative stress is thought to play a central role in the age-related decline in oocyte quality, primarily through its harmful effects on mitochondrial DNA integrity and broader aspects of cellular function. Although granulosa cells appear to be relatively more resilient, they are not exempt from age-associated damage, which may impair their hormonal activity and, given their close functional relationship with the oocyte, negatively influence oocyte competence. In addition, histological changes in the ovarian stroma, such as fibrosis and heightened inflammatory responses, are believed to further contribute to the progressive deterioration of ovarian function. A deeper understanding of the biological processes driving ovarian aging has facilitated the development of experimental interventions aimed at extending ovarian functionality. Among these are the autologous transfer of mitochondria and stem cell-based therapies, including the use of exosome-producing cells. Additional approaches involve targeting longevity pathways, such as those modulated by caloric restriction, or employing pharmacological agents with geroprotective properties. While these strategies are supported by compelling experimental data, robust clinical evidence in humans remains limited. Full article