Search Results (1,081)

Background/Objectives: Sexual dysfunction is a prevalent and multifactorial condition affecting a large proportion of the global population, with limited therapeutic options beyond pharmacological approaches primarily targeting erectile dysfunction. This has increased interest in botanical supplements for sexual health, although mechanistic evidence and clear links between phytochemical composition and biological activity remain scarce. The present study provides an integrative evaluation of a commercial Turnera diffusa extract (Liboost^®) formulated to support sexual health by combining detailed phytochemical characterization with targeted in vitro mechanistic assays. Methods: The extract was characterized by HPLC-DAD-HRMS, enabling the identification and semi-quantification of its major constituents. A total of 49 compounds were detected, predominantly flavonoids, including luteolin- and apigenin-derived glycosides, flavonols, methoxyflavones, flavanones, and coumaroyl derivatives, with a total quantified flavonoid content of 15.9 mg·g⁻¹. Biological activity was evaluated in human cell models without cytotoxic effects at the tested concentrations. Results: Liboost^® significantly reduced PDE5 expression, inhibited aromatase activity, and moderately increased nitric oxide production. These complementary effects suggest a multi-target modulation of pathways involved in sexual function, integrating vascular, endocrine, and nitrergic mechanisms. Conclusions: Although limited to in vitro models, the findings provide mechanistic support for the biological activity of T. diffusa extracts and highlight the importance of linking phytochemical composition with functional evidence when evaluating botanical supplements. Full article

The genus Cirsium (family Asteraceae, subfamily Carduoideae) comprises more than 200 species distributed throughout the temperate regions of the Northern Hemisphere. In recent years, particular scientific interest has focused on Cirsium arvense (L.) Scop. (creeping thistle) and Cirsium vulgare (Savi) Ten. (spear thistle). These species are notable for their high content of secondary metabolites and broad biological activity. However, the available data on their phytochemical composition and biological potential remain fragmented. This information is methodologically diverse and scattered across different scientific disciplines, underscoring the need for systematic analysis. In this study, a comprehensive literature review was conducted. Sources included PubMed, Scopus, Web of Science, Google Scholar, and other online databases. The focus was on phytochemical composition and pharmacological activity. Both species contain a wide range of secondary metabolites. These include phenolic acids (chlorogenic, caffeic, and ferulic acids), flavonoids (luteolin, apigenin, kaempferol, quercetin), triterpenoids (lupeol, taraxerol), and phytosterols. C. vulgare generally has higher levels of chlorogenic acid and flavonoid glycosides. In contrast, C. arvense has a greater abundance of triterpenes and steroidal compounds. Pharmacological studies show antioxidant, antimicrobial, hepatoprotective, anti-inflammatory, and cytotoxic activities for both species. Overall, the available data indicate that C. arvense and C. vulgare are promising sources of biologically active compounds with diverse pharmacological potential. Although there are some limitations regarding standardization and the depth of preclinical and clinical validation, the obtained results confirm their relevance for further pharmacological and phytochemical research. Full article

Tumor microenvironments, particularly hypoxia and inflammation, heavily influence colorectal cancer (CRC) pathogenesis by altering polyamine metabolism. Identifying natural compounds targeting these vulnerabilities remains critical. Integrating untargeted metabolomics, network pharmacology, and a human endogenous metabolite library screen, we identified apigenin (API) as a potent anti-CRC candidate. API significantly inhibited the proliferation, migration, and invasion of RKO and HCT116 cells in vitro and suppressed xenograft tumor growth in vivo. Crucially, high-throughput screening revealed that polyamines rescued CRC cells from API-induced cytotoxicity. Mechanistically, API exerts its effects by dismantling a newly identified HIF-1α/SMOX positive feedback loop. In CRC, HIF-1α transcriptionally activates spermine oxidase (SMOX), while SMOX-driven polyamine metabolism fuels the TLR4/MyD88 inflammatory cascade to continuously stabilize HIF-1α. API acts as a “circuit breaker” for this axis, significantly reducing the spermidine/spermine ratio and downregulating inflammatory signaling. Ultimately, API effectively remodels polyamine metabolism and suppresses CRC progression by disrupting the HIF-1α/SMOX and TLR4/MyD88 pathways, offering a novel metabolic mechanism for API in CRC therapy. Full article

Allergic rhinitis (AR) and allergic asthma are chronic airway inflammatory diseases characterized by three phases: sensitization, acute exacerbation, and chronic remodeling. While conventional antiallergic drugs provide symptomatic relief, they often face limitations including drug resistance, side effects, and inability to reverse chronic airway remodeling. Natural products have emerged as promising therapeutic alternatives due to their multi-target effects and safety profiles. This review systematically summarizes natural small molecules targeting distinct pathological mechanisms across the three phases of AR and asthma, introducing a chronopharmacological perspective for stage-specific therapeutic strategies. During sensitization, flavonoids (quercetin, luteolin, apigenin, baicalin) and polyphenols (curcumin, resveratrol) target the epithelial–dendritic cell axis by suppressing alarmin release and blocking dendritic cell maturation. In acute exacerbation, flavonoids (hispidulin, quercetin) and isoquinoline alkaloids (coptisine) exhibit rapid intervention through mast cell stabilization and neurogenic inflammation suppression. In chronic remodeling, stilbenes (resveratrol) and flavones (baicalin, baicalein) reverse established structural changes through TGF-β1/Smad, PTEN/PI3K/AKT, and PDGF-BB/PDGFR-β pathways. Mapping natural compounds to specific disease stages provides a molecular basis for precision medicine approaches. Full article

Eutectic solvents have become a viable choice to create innovative pharmaceutical technologies within the framework of the green chemistry approach. Despite the growing applicative interest, a general gap remains in the pharmaceutical sector regarding thorough and systematic research of their properties and useful applications. In this work, eutectic solvents have been prepared from choline chloride and polyols (sorbitol, xylitol, mannitol, and isomalt) at different molar ratios (1:1, 2:3, and 3:2), characterised, and used for the solubility enhancement of poorly water-soluble drugs (ibuprofen and naproxen) as well as the potential drug candidate apigenin. The interactions between the eutectic solvent components were investigated by DSC, FTIR, and refractive index methods. In all eutectic solvents, the water content detected by Karl Fischer titration and loss on drying was less than 3%. Solubility studies, carried out using the shake-flask method, showed significant solubility enhancement of the following: ibuprofen: ~152-fold increase, naproxen: ~144-fold increase, and apigenin: ~188-fold increase. These findings highlighted the great potential of eutectic solvents as solubility enhancers in the development of novel and more effective drug delivery systems. Full article

Background: Apigenin, as a flavonoid, can be protective against oxidative damage in hypoxic events due to its antioxidant properties. Here, we have investigated the neuroprotective effects of apigenin in an ex vivo model of ischemic damage, using cerebellar slices from postnatal day (P)8–12 reporter mice to identify oligodendrocytes (SOX10-EGFP) and astrocytes (GFAP-EGFP). Methods: Apigenin (10 and 20 μM) was administered preventively at 60 min prior to and during inducing ischemic damage by oxygen and glucose deprivation (OGD); controls were maintained with glucose and normoxia (OGN). Results: OGD induced a marked retraction of oligodendroglial processes without reducing the oligodendrocyte number. This structural disruption was prevented by apigenin; notably, 10 μM apigenin blocked process retraction, whereas 20 μM did not, indicating a dose-dependent effect on the oligodendroglial morphology. Consistent with this, MBP and NF70 immunofluorescence analyses of axonal myelination demonstrated that OGD caused a significant loss of myelin sheaths, and this was prevented by pre-treatment with apigenin. In addition, apigenin prevented astrocyte reactivity induced by OGD, as assessed by increased GFAP-EGFP expression and decreased expression of glutamine synthetase. Moreover, immunofluorescence for calbindin indicated that apigenin protected Purkinje neurons from ischemic damage. Conclusions: These results demonstrate that apigenin is neuroprotective in ischemia and this is associated with modulation of astrocyte reactivity and maintenance of oligodendrocyte and myelin integrity. Full article

Cancer ranks as one of the top causes of death worldwide, and the World Health Organisation (WHO) estimates an increase of up to 55% in cases over the next 15 years, reaching 300 million cases worldwide. Current approaches to the treatment of cancer, such as chemotherapy and radiation therapy, have been used with continuous significant advancements. However, these conventional methods have harmful side effects that can last a lifetime. Today, there is growing interest in developing alternative cancer therapies from natural products or complementary medicine. One of the natural sources that has shown promise as an anticancer agent is honey, which has long been applied as a complementary medicine, and its beneficial health effects on various diseases in both animal and human models have been widely studied. Malaysian honey, such as Tualang, pineapple, Gelam, Kelulut, and Acacia, possesses a rich composition of phytochemicals, including polyphenols and flavonoids, which are reported to have promising anticancer properties. Examples of the phytochemicals highlighted in this review are phenolic acid, syringic acid, salicylic acid, p-coumaric acid, gallic acid, benzoic acid, caffeic acid, chrysin and its derivatives, kaempferol, fisetin, catechin, apigenin, quercetin, acacetin, pinocembrin, pinobanksin, hesperetin, naringenin, vitexin, isoorientin, xanthohumol, and galangin. This review highlights the anticancer mechanisms and molecular pathways of the phytochemicals found in Malaysian honey, focusing on their antioxidant effects, induction of mitochondrial-mediated apoptosis, inhibition of angiogenesis and metastasis, and suppression of cancer cell proliferation. The findings of various studies published in the past five years are collated to understand their mechanisms of action. Full article

Salvia transsylvanica, an endemic Romanian sage, remains understudied despite co-occurrence with validated medicinal Salvia species. In this study, leaves and flowers were harvested weekly during flowering (May and June) and subjected to classical hydroethanolic extraction, HPLC–DAD–ESI/MSⁿ profiling, in vitro antioxidant assays (ABTS, DPPH, FRAP), and enzyme-inhibitory screening, with multivariate analysis correlating compositional patterns with bioactivity. Rosmarinic acid dominated the phenolic profile (68.6 mg/g maximum in week 4), alongside salvianolic acids (salvianolic acid K isomers) and flavonoid glycosides (luteolin, apigenin, and hispidulin hexosides). Leaf extracts displayed higher ABTS/DPPH scavenging (higher phenolic acid content), while flowers showed superior FRAP and α-glucosidase inhibition (IC₅₀ 84–143 μg/mL, higher flavonoids), with maximal values being identified during week 4. S. transsylvanica offers complementary antioxidant profiles to commercial sages, warranting future in vivo validation for therapeutic applications. Full article

Ginkgetin (GK) is a naturally occurring biflavonoid predominantly isolated from Ginkgo biloba and has attracted increasing attention because of its broad pharmacological activities. Structurally, GK belongs to the 3′-8″-linked biflavone subclass, which distinguishes it from other biflavonoids like amentoflavone (the parent compound of this subclass) and its monomeric counterparts such as apigenin. This unique C-C linked dimeric architecture confers distinct molecular planarity and lipophilicity, contributing to its enhanced membrane permeability and multitarget engagement capabilities. GK has been shown to exert pleiotropic biological effects in preclinical studies, including anti-inflammatory, antioxidant, antifibrotic, anticancer, neuroprotective, cardioprotective, metabolic regulatory and antibacterial activities. Mechanistically, preclinical evidence indicates that GK functions as a multitarget modulator of key signaling pathways involved in oxidative stress, inflammation, cell death and tissue remodeling, such as nuclear factor erythroid 2–related factor 2/heme oxygenase-1 (Nrf2/HO-1), nuclear factor kappa-B(NF-κB), Janus kinase/signal transducer and activator of transcription(JAK/STAT), mitogen-activated protein kinases(MAPKs), AMP-activated protein kinase/mechanistic target of rapamycin(AMPK/mTOR), phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) and cyclic GMP-AMP synthase–stimulator of interferon genes(cGAS–STING). Notably, GK has been observed to display context-dependent regulation of cell fate decisions, including apoptosis, autophagy and ferroptosis, thereby enabling the selective elimination of pathological cells while preserving normal tissue function. Preclinical studies further demonstrate that GK exhibits therapeutic potential across diverse disease systems, including cancer, metabolic disorders, cardiovascular diseases, neurological disorders and musculoskeletal diseases. In addition, emerging evidence highlights its antibacterial and antivirulence properties through the inhibition of biofilm formation and quorum sensing. It is crucial to note, however, that this promising profile is predominantly derived from preclinical studies, and clinical evidence in humans remains to be established. Despite these promising findings, the clinical translation of GK remains limited by challenges related to pharmacokinetics, bioavailability and druggability. This review systematically summarizes the chemical characteristics, pharmacological activities and molecular mechanisms of GK, with an emphasis on its multitarget actions and therapeutic potential across disease systems, and discusses current limitations and future perspectives to facilitate the rational development of GK-based interventions. Full article

Periodontitis is a chronic inflammatory disease marked by the progressive destruction of periodontal tissues, where conventional therapies often fail to maintain adequate drug levels at the target site. This study reports the development and characterization of a thermosensitive gel containing nanostructured lipid carriers (NLC) for controlled local periodontal delivery. Apigenin (AP)-loaded NLC were prepared using AP as active agent and clove essential oil (CEO) as liquid lipid subsequently incorporated into Poloxamer 407 (5–15% w/w) hydrogels. The formulations were evaluated in relation to particle size, morphology, thermal and rheological behavior, mucoadhesion, in vitro release, antibacterial activity, and stability. Optimized nanoscale NLC showed a high entrapment efficiency, and uniform morphology. Raman analysis confirmed successful AP incorporation and homogeneous distribution in the gel without incompatibility. NLC-loaded gels exhibited sol–gel transition at physiological temperature with improved viscoelasticity and enhanced mucoadhesion. The drug release was sustained for 48 h and followed the Korsmeyer–Peppas model, indicating diffusion-based and anomalous transport. The antibacterial assessment demonstrated the pronounced inhibitory activity of the NLC formulations against key periodontal pathogens, with the formulation-dependent modulation of antimicrobial efficacy observed following the gel incorporation. Stability studies showed preserved nanoparticle structure and uniform dispersion. Overall, the thermoresponsive NLC-hydrogel system offers a promising strategy for prolonged, localized periodontal therapy. Full article

The nuclear factor erythroid 2–related factor 2 (NRF2) is a master transcription factor that orchestrates cellular defense against oxidative and electrophilic stress. Dysregulation of the KEAP1–NRF2–ARE pathway has been implicated in several dermatological disorders, including vitiligo, psoriasis, atopic dermatitis, photoaging, and radiation dermatitis. This review summarizes recent advances in the understanding of NRF2 activation mechanisms and highlights pharmacological and natural compounds with potential dermatological applications. A comprehensive analysis of natural, semisynthetic, and synthetic NRF2 modulators is provided, describing their chemical structures, synthetic approaches, mechanisms of action, preclinical and clinical evidence, and therapeutic relevance for skin disorders. Multiple classes of NRF2 activators, including isothiocyanates such as sulforaphane, triterpenoids such as omaveloxolone, flavonoids including baicalein and apigenin, alkaloids such as berberine, glycosides like afzelin and paeoniflorin, stilbenoids such as tapinarof, and α,β-unsaturated fumaric acid esters such as dimethyl fumarate, have demonstrated antioxidant, anti-inflammatory, and cytoprotective effects in keratinocytes and melanocytes. Some of these agents, particularly dimethyl fumarate and tapinarof, have advanced to clinical development or commercialization, whereas others remain at the preclinical stage but show encouraging results in animal models and cell culture systems. Overall, pharmacological activation of NRF2 represents a promising therapeutic strategy to counteract oxidative stress–driven skin damage and inflammation; however, continued translational and clinical research is required to optimize formulations, dosing regimens, and safety profiles for integration into dermatological practice. Full article

Idesia polycarpa is a multipurpose tree species valued for both fruit production and timber and is often referred to as a “beautiful oil reservoir on trees”. However, research has largely focused on fruits, whereas the metabolic composition and potential value of other tissues, such as leaves and shoot tips, remain insufficiently characterized. Here, we employed UPLC–MS/MS-based untargeted metabolomics to compare metabolite profiles and functional components between the leaves and shoot tips of I. polycarpa. In total, 378 differential metabolites were identified, with 105 significantly upregulated in leaves and 273 significantly upregulated in shoot tips. Among these, 32 metabolites were detected exclusively in shoot tips, and 22 were unique to leaves. Leaves were enriched in secondary metabolites, particularly flavonoids and phenolic acids, with scutellarin and catechol as representative compounds. In contrast, shoot tips exhibited higher levels of primary metabolites, including nucleotides and their derivatives as well as amino acids, with catechin and epicatechin being representative compounds. In addition, targeted metabolomics was performed to quantify 53 flavonoids in leaves; scutellarin (2088.1350 μg/g) and apigenin-7-O-glucuronide (1020.9085 μg/g) showed the highest concentrations. Collectively, these results reveal tissue-specific metabolic characteristics in I. polycarpa and provide a data basis for future functional studies and the comprehensive utilization of leaves and shoot tips. Full article

Mulberry, a plant highly valued for medicinal–edible features, was fermented with Lactobacillus plantarum M3 to enhance its bioactive profile. This study conducted a comprehensive evaluation of the antioxidant activity of fermented mulberry juice (FMJ) and identified key metabolites through an integrated approach involving non-targeted metabolomics, network pharmacology, RT-qPCR, and molecular docking. Under optimized conditions (28 °C, pH 5.5, 12°Bx initial sugar content, 48 h and 5% inoculum), fermentation significantly bolstered the antioxidant capacity of MJ. Specifically, superoxide dismutase (SOD) activity increased from 62.41 ± 0.11 to 84.99 ± 0.07 U/mL, while total phenolic content (TPC) surged from 1108.98 ± 2.90 to 2494.17 ± 7.05 mg GAE/L; DPPH radical scavenging activities were improved by 63.09%. Non-targeted metabolomics identified 195 secondary metabolites, primarily comprising alkaloids, flavonoids, and phenolic acids. Among these, protocatechuic acid, Albanin A, and apigenin exhibited significant dynamic shifts, indicating that they may play a pivotal role in regulating antioxidant capacity. Integrated network pharmacology, RT-qPCR validation, and molecular docking further elucidated that Albanin A and Moracin Q likely drive these enhanced antioxidant effects by activating the Nrf2 pathway, suppressing the NF-κB pathway, and upregulating SOD1 expression. These findings provide a theoretical basis for the development of high-potency functional mulberry products. Full article

The sustainability of egg production in the poultry industry is frequently challenged by the progressive decline in ovarian function as laying chickens age. A primary driver of this reproductive transition is the functional deterioration of small white follicles (SWFs), which constitute the vital pre-hierarchical follicular reserve necessary for sustained egg production. However, the molecular mechanisms underlying age-associated SWF atresia remain poorly understood. In this study, we investigated the protective efficacy of apigenin (AP), a natural bioactive flavonoid, in mitigating follicular senescence by targeting calcium ion (Ca²⁺)-mediated endoplasmic reticulum stress (ERS) in D-galactose (D-gal)-induced SWFs and in naturally aged chickens. Our results revealed that AP treatment effectively rebalanced the D-gal-induced disruption of cell proliferation and survival. Molecular analysis of SWFs revealed that AP treatment promoted the coordinated restoration of transcriptional profiles of key Ca²⁺-handling genes, effectively counteracting the age-related disruption of ionic regulation. In addition, AP suppressed the aberrant upregulation of IP₃R and modulated the expression of other key Ca²⁺-regulatory genes, including CACNA1C, CACNA1D, CAMKII, MCU, and ATP2B1. This restoration of intracellular Ca²⁺ homeostasis was associated with attenuation of the ERS response, as evidenced by the decreased levels of GRP78 and CHOP, and the suppression of Caspase-3-mediated apoptotic signaling. The biological relevance of these findings was further validated in vivo using naturally aged chickens. Dietary supplementation with AP significantly enhanced pre-hierarchical follicle recruitment in aged laying chickens, and improved egg production and eggshell quality in aged laying chickens. Collectively, these findings indicate that AP can modulate ERS signaling in laying chickens by maintaining intracellular Ca²⁺ homeostasis, thereby enhancing laying performance. These results highlight AP as a promising nutritional intervention to enhance reproductive performance and extend productive longevity in poultry. Full article