Search Results (492)

This study aimed to optimize the extraction and purification of TSG-enriched Polygonum multiflorum extract and evaluate its therapeutic potential against androgenetic alopecia. P. multiflorum Thunb. has long been used in traditional Chinese medicine to promote hair growth and preserve hair pigmentation. Microwave-assisted extraction (MAE) was optimized to obtain a 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside (TSG)-enriched P. multiflorum extract (PME). The crude extract was further purified by medium-pressure liquid chromatography and semipreparative high-performance liquid chromatography. Phytochemical profiling by HPLC demonstrated a 3.75-fold increase in TSG content, from 22,770.0 ± 815 ppm to 85,387.5 ± 192 ppm, and the identity of the enriched TSG was confirmed by LC–MS and ¹H NMR spectroscopy. PME exhibited potent dose-dependent inhibition of 5α-reductase activity, reaching 92.7% inhibition at 1 μg/mL, comparable to that of finasteride. In a testosterone (TES)-induced androgenetic alopecia (AGA) mouse model, PME markedly accelerated hair regrowth and increased both the number and size of hair follicles. Mechanistically, PME suppressed the conversion of TES to dihydrotestosterone (DHT) through 5α-reductase inhibition and promoted GSK3β inactivation, β-catenin stabilization, and nuclear translocation, indicating activation of the Wnt/β-catenin signaling pathway. Consequently, the expression of hair growth-related proteins, including Ki67 (1.98-fold), epidermal growth factor (EGF, 1.54-fold), insulin-like growth factor-1 (IGF-1, 1.21-fold), and vascular endothelial growth factor (VEGF, 1.34-fold), was significantly upregulated. These findings demonstrate, for the first time, that TSG-enriched PME obtained through optimized MAE and chromatographic purification promotes hair regeneration through a dual mechanism involving 5α-reductase inhibition and Wnt/β-catenin activation, highlighting its potential as a natural therapeutic candidate for androgenetic alopecia. Full article

Gemcitabine-based chemotherapy has long served as a standard treatment for urothelial carcinoma (UC), particularly in perioperative and metastatic settings. However, therapeutic efficacy is frequently limited by intrinsic or acquired resistance. Gemcitabine functions as a prodrug whose activity depends on coordinated processes involving cellular uptake, intracellular activation, metabolic inactivation, and nucleotide metabolism. Increasing evidence suggests that resistance in UC is mediated by multiple interconnected mechanisms beyond alterations in gemcitabine transport, activation, and inactivation alone. Key molecular determinants include human equilibrative nucleoside transporter 1 (hENT1), deoxycytidine kinase (dCK), cytidine deaminase (CDA), and ribonucleotide reductase regulatory subunit M1 (RRM1), which is involved in nucleotide pool maintenance and DNA synthesis. In addition, replication stress responses, apoptosis evasion pathways, and tumor microenvironment-associated factors also contribute to gemcitabine resistance. Stress-adaptive pathways involving Y-box binding protein 1 (YB-1), hypoxia-inducible factor-1 alpha (HIF-1α), and autophagy-related mechanisms may further promote survival under chemotherapy-induced stress conditions. In addition, extracellular mucin-associated mechanisms may alter intratumoral drug accessibility and contribute to resistance. In this review, we summarize UC-specific evidence regarding gemcitabine resistance and discuss how these pathways collectively shape an integrated resistant phenotype. Full article

Microplastic exposure is an emerging environmental risk factor for cardiovascular health; however, whether cardiovascular alterations can be detected after exposure cessation remains unclear. This study investigated subclinical cardiovascular alterations following repeated oral exposure to polystyrene microplastics (PSMPs), with particular emphasis on redox imbalance and mitochondrial function in delayed cardiovascular alterations. Male Sprague-Dawley rats were administered 0.5 μm PSMPs via oral gavage at varying dosages of 5 or 20 mg/kg every 5 days for 70 days, followed by a 35-day exposure-free period. Repeated exposure to PSMPs did not affect body or organ weights but altered cardiac serum biochemical markers. Cardiac tissue exhibited elevated NADPH oxidase 4 (NOX4) expression and decreased superoxide dismutase 1 (SOD1), SOD2, and catalase (CAT) activities, whereas malondialdehyde (MDA) levels remained unchanged, indicating a state of chronic, low-level oxidative stress. Mitochondrial respiratory chain activities, including nicotinamide adenine dinucleotide cytochrome c reductase (NCCR) and succinate cytochrome c reductase (SCCR), were significantly reduced. Ultrastructural analysis revealed mitochondrial swelling and cristae disruption. In parallel, mitochondrial biogenesis-related proteins, including peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), nuclear respiratory factor 1 (NRF-1), and mitochondrial transcription factor A (TFAM), were downregulated, while mitophagy markers, including PTEN-induced kinase 1 (PINK1), Parkin RBR E3 ubiquitin protein ligase (Parkin), microtubule-associated protein 1 light chain 3 (LC3), and sequestosome 1 (p62), were upregulated. Notably, most significant alterations were primarily observed in the high-dose group. Furthermore, the aorta showed increased oxidative stress markers without overt structural remodeling. These findings suggest that repeated exposure to PSMP is associated with subclinical cardiac redox–mitochondrial dysregulation, potentially involving redox imbalance, impaired mitochondrial respiratory chain activity, reduced mitochondrial biogenesis, and altered mitochondrial quality-control markers. Full article

Background/Objectives: American trypanosomiasis, caused by Trypanosoma cruzi, remains a major public health challenge due to the limited efficacy and adverse effects associated with current treatments. Octyl gallate (OG), a semi-synthetic derivative of gallic acid, has demonstrated promising biological activities, including antiparasitic effects. Methods: The in vitro trypanocidal activity of OG was evaluated against T. cruzi. Mechanism of action studies included the inhibition of the trypanothione reductase enzyme and flow cytometry assays to measure cell death pathways (propidium iodide uptake). Additionally, the immunomodulatory potential of the compound was investigated by assessing cytokine production and innate immune responses. Results: In this study, the trypanocidal activity of OG against different evolutionary forms of T. cruzi was investigated. Using MTT-based viability assays, OG exhibited significant activity against epimastigotes (IC50 = 5.92 ± 0.47 µM), trypomastigotes (EC50 = 3.20 ± 0.14 µM), and intracellular amastigotes (EC50 = 4.07 ± 0.72 µM). The compound also demonstrated favorable selectivity indices, particularly against trypomastigotes and amastigotes, indicating selective toxicity toward the parasite compared to mammalian host cells. In infected macrophages, OG increased TNF-α and IL-12 production while reducing IL-10 and IL-6 levels, in addition to stimulating reactive oxygen species (ROS) and nitric oxide (NO) production, suggesting an immunomodulatory effect that contributes to parasite control. Molecular docking analyses revealed a favorable interaction between OG and trypanothione reductase (TR), while biochemical assays demonstrated reduced NADPH consumption, indicating interference with TR activity. Ultrastructural analysis revealed severe morphological alterations, including membrane disruption, cytoplasmic disorganization, mitochondrial swelling, and features consistent with apoptosis-like cell death. Conclusions: Collectively, these findings demonstrate that OG exhibits potent and selective trypanocidal activity associated with immunomodulatory effects, ultrastructural damage, and disruption of parasite redox metabolism through TR inhibition, supporting its potential as a candidate for future preclinical studies against Chagas disease. Full article

Metabolic and cardiometabolic diseases are closely associated with mitochondrial dysfunction and redox imbalance. Ubiquinol–cytochrome c reductase core protein 2 (UQCRC2), a non-catalytic structural core subunit of mitochondrial respiratory chain Complex III, is increasingly recognized as a regulator of Complex III integrity, electron transfer, oxidative phosphorylation, and mitochondrial redox homeostasis. Under metabolic stress, reduced expression or functional impairment of UQCRC2 may promote electron leakage, mitochondrial reactive oxygen species (mtROS) generation, lipid peroxidation, impaired antioxidant defense, and disrupted glucose–lipid metabolism. These alterations may contribute to insulin resistance (IR), metabolic dysfunction-associated steatotic liver disease (MASLD), obesity, and cardiovascular disease (CVD). This review summarizes current evidence linking UQCRC2 dysfunction to mitochondrial bioenergetic failure, oxidative stress, inflammatory signaling, and cardiometabolic injury. We further discuss redox-regulatory pathways, including Nrf2, AMPK–SIRT1–PGC-1α, glutathione metabolism, and mitophagy, as well as pharmacological agents and natural compounds that may modulate UQCRC2-related mitochondrial responses. Collectively, these findings highlight UQCRC2 as a redox-sensitive mitochondrial node linking Complex III dysfunction to cardiometabolic injury and targeted redox-based interventions. Full article

Current treatment options for hair loss remain limited. Therefore, this study compared a botanical extract derived from multiple plants with the pharmaceutical agent minoxidil for topical application. The evaluated parameters included inflammatory cytokines (IL-1β, IL-6, TNF-α), growth factors (TGF-β, VEGF, KGF), and 5α-reductase type II (SRD5A2) expression in the human keratinocyte cell line HaCaT, as measured by ELISA. Both the botanical extract and minoxidil reduced IL-6 levels by 21% and 35%, and TNF-α levels by 13% and 35%, respectively. Treatment with the botanical extract and minoxidil increased VEGF expression by 50% and 85%, and KGF by 16% and 31%, respectively, while reducing SRD5A2 expression by 21% and 28%, respectively. Overall, the results of this in vitro study suggest that the botanical extract exhibits a response pattern similar to that of minoxidil, characterized by the suppression of pro-inflammatory cytokines and SRD5A2, along with enhanced expression of growth factors VEGF and KGF in HaCaT cells. These results provide a promising basis for further in vivo studies. Full article

Dietary factors, including the consumption of isoflavones-rich foods of plant origin, may contribute to the reduced incidence of prostate cancer. Isoflavones, natural phytoestrogens often found in legumes, can modulate estrogen and androgen receptor signaling. This study aimed to evaluate the biological potential of isoflavone-rich extracts obtained from twelve species from the Fabaceae family, targeting prostate cancer cell viability, proliferation, inflammatory markers, prostate-specific antigen secretion, and 5α-reductase activity. The tested extracts showed moderate cytotoxic activity against prostate cancer cell lines, apart from highly susceptible PC3 cells, and only weak toxicity to normal prostate epithelial cells. Significant antiproliferative activity was observed, especially for Cytisus scoparius, Ononis arvensis, and Genista tinctoria, while most extracts reduced prostate-specific antigen (PSA) secretion in normal prostate cells. Furthermore, the extracts showed anti-inflammatory properties by reducing the pro-inflammatory cytokine interleukin 6 (IL-6) and improving cytokine balance indices. Multivariate analyses revealed correlations between total isoflavone content and antiproliferative activity. Full article

Background/Objectives: 5α-Reductase inhibitors (5ARIs) are commonly used to treat and prevent androgenic alopecia and benign prostatic hyperplasia. Despite their well-established effectiveness, they are associated with adverse drug reactions (ADRs), highlighting the need for continuous safety assessment. This study aimed to analyze the ADRs associated with finasteride and dutasteride, both as monotherapy and in combination therapy. Methods: A retrospective analysis of ADRs associated with finasteride and dutasteride reported to EudraVigilance between 1 January 2005 and 27 March 2023 was performed. A total of 7777 reports were selected, and various variables were examined, including the temporal evolution of ADR reports, reporter profile, and the age group of the affected population. ADRs were categorized based on their seriousness and outcome, with particular focus on the most common reactions and their alignment with the Summary of Product Characteristics (SmPC). Results: The most affected age group, excluding the “Not Specified” category, was “18–64 years.” Overall, finasteride was the most reported. The majority of reported ADRs were classified as “Serious,” with a predominant outcome of “Persists without recovery,” and a significant proportion of these ADRs were not listed in the respective 5ARI SmPCs. Among the ADRs classified as “Serious,” the most frequently reported seriousness criterion was “Clinically important”. Conclusions: The results emphasize how crucial it is to continuously monitor these drugs in order to prevent and mitigate ADRs, ensure population safety, and promote public health. Additionally, more research is required to determine whether the ADRs not included in the SmPC could be new warning signs. Full article

To address the lack of a comprehensive quality control system for Ganoderma lucidum, we developed an integrated evaluation strategy across four varieties and three growth stages. This system integrates the targeted screening of anti-benign prostatic hyperplasia (BPH) triterpenoids acting on 5α-reductase type 2 (SRD5A2) with a chemical consistency assessment utilizing systematic quantitative fingerprint method (SQFM) and chemometrics. UPLC-Q-TOF-MS/MS identified 85 triterpenoids in the samples. An orthogonal partial least squares (OPLS) regression was utilized to screen seven chromatographic peaks that positively correlated with SRD5A2 inhibitory activity. Three principal bioactives were structurally identified as ganoderic acids DM and B, and ganoderenic acid A, which demonstrated significant in vitro SRD5A2 inhibition rates of 61.16 ± 1.87%, 36.41 ± 1.10%, and 41.82 ± 2.09%, respectively. Molecular dynamics simulations and averaged weak interaction analysis revealed that these compounds exert potent enzyme inhibition via hydrogen bonds and hydrophobic interactions with distinct SRD5A2 amino acid residues. The SQFM-chemometrics quality system confirmed ten samples reached Grade 6 or above, identifying the H3 variety at the initial stage as possessing the highest active ingredient content and optimal overall quality. This integrated framework enables rapid bioactive discovery and robust standardization for G. lucidum-based functional foods, thereby facilitating their industrial development. Full article

Statins are commonly used cholesterol-lowering drugs, but their effects on astrocyte oxidative metabolism are poorly understood. To investigate this, rat astrocytes were exposed to 200 nM atorvastatin or simvastatin for 6 days and then assessed for changes in coenzyme Q (CoQ) homeostasis, mitochondrial function, and energy metabolism. Both statins comparably decreased cellular CoQ9 and CoQ10 levels (~35%), with greater losses of their reduced antioxidant forms (60–75%). Lower intracellular and mitochondrial levels of reactive oxygen species (ROS) were accompanied by the upregulation of nuclear factor erythroid 2-related factor 2 (NRF2)-dependent antioxidant pathways (superoxide dismutase 1 and glutathione reductase) and metabolic stress response factors, including hypoxia-inducible factor 1-alpha (HIF1α) and brain-derived neurotrophic factor (BDNF). Both statins promoted glycolytic reprogramming, mitochondrial fission, and biogenesis while impairing oxidative phosphorylation, as evidenced by reduced ATP-linked respiration, increased proton leak, and lower ATP levels. These findings suggest that statin-treated astrocytes adapt by prioritizing redox homeostasis over ATP production. CoQ10 supplementation increased cellular CoQ10 levels and restored ATP levels without further decreasing ROS, suggesting that its primary benefit is bioenergetic support, not additional antioxidant protection. Overall, statin-induced CoQ deficiency induces adaptive metabolic remodeling of astrocytes, while CoQ10 supplementation may help maintain energy metabolism under these conditions. Full article

Candida albicans is an opportunistic fungal pathogen of clinical relevance, and plant-derived antifungal agents have attracted interest because of rising resistance to conventional drugs. This study aimed to characterize the chemical composition of Mespilodaphne quixos (Lam.) Rohwer essential oil (EO) by GC/MS, evaluate its in vitro antifungal activity against C. albicans, model its concentration-dependent response using one-factor quadratic polynomial modeling, and investigate the interactions of its constituents with selected fungal targets using molecular docking. Freshly collected leaves were subjected to steam distillation, then the EO was characterized using GC/MS. Antifungal activity was determined using the Kirby–Bauer disk diffusion method. A one-factor quadratic polynomial model was fitted to describe the inhibition halo diameter as a function of EO concentration. Moreover, 22 identified compounds were docked against 14-α-demethylase, Δ(14)-sterol reductase, and exo-β-(1,3)-glucanase. The EO was mainly composed of (E)-cinnamaldehyde (47.2%), caryophyllene (10.8%), and α-humulene (5.37%). The EO reached an inhibitory capacity of 87.3% relative to ketoconazole. The quadratic model showed good predictive performance. Molecular docking revealed favorable affinities for several sesquiterpenes present in M. quixos essential oil: α-copaene showed the best interaction profile against 14-α-demethylase and Δ(14)-sterol reductase, whereas α-guaiene and spathulenol performed best against exo-β-(1,3)-glucanase. These findings provide preliminary in vitro and in silico evidence supporting the antifungal activity of M. quixos EO. Full article

Intestinal oxidative imbalance, inflammatory activation, and microbial dysbiosis are increasingly recognized as major factors affecting the health status of intensively cultured largemouth bass (Micropterus salmoides). Chlorogenic acid (CGA) is a plant-derived polyphenolic compound that is well known for its antioxidant and anti-inflammatory properties. Although its inclusion as a dietary supplement in aquafeeds has garnered increasing interest, its effects on intestinal health in largemouth bass under normal rearing conditions remain largely unknown. Hence, the present investigation was designed to elucidate how incrementally elevated dietary CGA concentrations modulate oxidative capacity, inflammatory gene expression, mucosal histological features, and enteric microbiota structure in juvenile largemouth bass. In this study, largemouth bass were fed diets containing 0, 200, 400, or 600 mg/kg CGA for 70 days, and we evaluated intestinal antioxidant capacity, inflammation-related transcriptional responses, histomorphology, and gut microbiota were assessed. The results demonstrated that CGA supplementation significantly raised intestinal total antioxidant capacity as well as the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, while substantially decreasing malondialdehyde levels (p < 0.05). The transcription levels of cat, gsh-px, gst, sod, nrf2, and ucp2 were markedly upregulated, whereas keap1 expression was downregulated (p < 0.05). CGA supplementation also reduced the transcription levels of several proinflammatory genes, including il-1β, il-6, il-8, tnf-α, nf-κb, p50, map3k, jak2, as well as stat3, while significantly elevating il-10 expression, in the 200 and 400 mg/kg groups, tgf-β expression was also lowered (p < 0.05). Histological examination revealed that CGA supplementation influenced intestinal morphology in a dose-dependent manner; the most consistent improvements in villus length, villus width, and muscularis thickness occurred at the 400 mg/kg level, whereas the 600 mg/kg level showed weaker effects in several parameters compared with the control. Furthermore, 16S rRNA sequencing indicated that CGA altered microbial diversity, community structure, and predicted functional profiles in the intestine. In summary, dietary CGA supplementation was associated with enhanced intestinal antioxidant capacity, modified inflammation-related transcriptional responses, changes in intestinal morphology, and shifts in the gut microbial community of largemouth bass. Within the tested dose range, the 400 mg/kg group exhibited relatively favorable responses in several measured indicators under the present experimental conditions. Full article

Background/Objectives: Cardiovascular diseases (CVDs) and cancer remain major global health challenges and are among the leading causes of mortality worldwide, including in Kuwait. Medicinal plants are important sources of bioactive compounds with therapeutic potential. This study aimed to identify the phytochemical constituents of Curcuma longa L. root extract and evaluate their potential cardioprotective and anticancer activities using integrated computational approaches. Methods: Phytochemical profiling of Curcuma longa root extract was performed using gas chromatography–mass spectrometry (GC–MS). The identified compounds were evaluated through molecular docking against selected cardiovascular- and cancer-related targets, including HMG-CoA reductase, phosphoinositide 3-kinase (PI3K), cyclin-dependent kinase 6 (CDK6), and HER2 kinase receptors. Protein–ligand interactions were analyzed to determine binding stability. Biological activity prediction and pharmacokinetic properties were assessed using PASS prediction and SwissADME tools, while density functional theory (DFT) calculations were conducted to investigate electronic and quantum chemical characteristics associated with ligand reactivity. Results: GC–MS analysis identified seventeen phytochemical constituents with retention times ranging from 7.57 to 32.70 min. The major compounds detected were 2-oxo-cyclooctaneacetic acid (30.88%), curlone (20.99%), and tumerone (13.85%). Molecular docking revealed favorable binding affinities for α-curcumene, caryophyllene, bergamotene, cyclohexene derivatives, tumerone, curlone, and (6R,7R)-bisabolone against the selected targets, with interaction profiles comparable to reference drugs. PASS and SwissADME analyses indicated promising biological activities, acceptable drug-likeness, and favorable pharmacokinetic properties. DFT analysis demonstrated that curlone and tumerone possessed stable electronic configurations and favorable reactivity profiles. Conclusions: The findings suggest that bioactive compounds from Curcuma longa may serve as promising lead candidates for the development of cardioprotective and anticancer agents. However, further experimental validation through in vitro and in vivo studies is required to confirm these computational predictions. Full article

Background and Objectives: Benign prostatic hyperplasia (BPH) is a progressive, androgen-dependent condition driven by dihydrotestosterone (DHT). 5α-reductase inhibitors (5-ARIs), including finasteride and dutasteride, target this pathway and provide disease-modifying effects. Materials and Methods: This narrative review summarizes evidence from randomized trials, meta-analyses, and observational studies evaluating the efficacy, timing, and safety of 5-ARIs in the management of LUTS due to BPH. Results: 5-ARI therapy reduces prostate volume by 18–28% and serum PSA by approximately 50% within 6–12 months. Landmark trials (MTOPS, CombAT) demonstrate significant reductions in acute urinary retention (AUR) and BPH-related surgery (>50% RR reduction). Combination therapy with α-blockers provides superior symptom control and greater prevention of clinical progression, particularly in men with prostate volume ≥ 30–40 mL or PSA ≥ 1.5 ng/mL. Early initiation of combination therapy improves long-term outcomes, while α-blocker withdrawal may be feasible in selected patients. Adverse events are mainly sexual, with emerging data suggesting a possible association with depression. Conclusions: 5-ARIs are central to BPH management, offering sustained clinical benefits and prevention of progression. Optimal outcomes depend on appropriate patient selection, early treatment in high-risk individuals, and individualized long-term strategies. Full article

Hydrogen sulfide (H₂S) functions as a pivotal gaseous signaling molecule in plants, yet its role in promoting crop yield remains elusive. Here, we demonstrate that sodium hydrosulfide (NaHS) application, a donor of hydrogen sulfide (H₂S), significantly accelerates growth, promotes flowering, and enhances grain yield in rice (Oryza sativa L.). Optimal NaHS treatment increased plant height, root length, and biomass accumulation, concomitant with elevated sucrose, starch, chlorophyll contents, and nitrate reductase activity. Integrated transcriptomic and proteomic analyses revealed that NaHS reprograms key biological pathways, including photosynthesis, carbon metabolism, lipid metabolism, the hormone signal transduction pathway, and reactive oxygen species (ROS) homeostasis. NaHS also remodels fatty acid metabolism, significantly increasing unsaturated fatty acids, linoleic acid (C18:2n6c), and α-linolenic acid (C18:3n3)—the latter serving as the direct precursor for JA biosynthesis—thereby fueling jasmonic acid (JA) biosynthesis. NaHS treatment also induced ROS accumulation while simultaneously activating antioxidant enzymes, maintaining redox homeostasis, and promoting cell proliferation in root meristems. Transmission electron microscopy revealed that NaHS enlarges peroxisomes and increases chloroplast oil body number, linking organellar dynamics to enhanced JA synthesis and ROS signaling. Collectively, our findings establish NaHS as a novel chemical regulator that coordinates JA and ROS signaling to boost rice growth, flowering, and grain yield, offering a promising strategy to improve crop productivity. Full article