Apigenin in freezing medium improves frozen-thawed sperm quality and fertilization competence of Oura-type Tibetan sheep.

Spectroscopic investigation of the competitive-allosteric-synergistic mechanism in the binding of benazepril/apigenin to bovine serum albumin.

Apigenin attenuates LPS-induced corneal inflammation by modulating NF-κB and JNK/ERK signaling pathways.

Ziziphora clinopodioides Lam., a valuable medicinal plant, exhibits significant potential for flavonoid production, which significantly contributes to its therapeutic properties. In the initial phase of this ongoing study, phenolic derivatives were analyzed in 13 populations during two vegetative growth stages under greenhouse conditions. In the next phase, the effects of precursors [phenylalanine (Phe) and naringenin (Nar)], biotic elicitor [yeast extract (YE)], and abiotic elicitors [salicylic acid (SA) and methyl jasmonate (MeJA)] were evaluated on the accumulation of specific flavonoids and phenolic acids in a selected population. Younger plants (2-MO growth stage) exhibited higher phenolic content than older ones (5-MO growth stage). Selected populations (P1, P4, P5, and P10 for shoots; P4, P8, P11, and P13 for roots) were subjected to further LC-MS/MS analysis, revealing that P5 shoots had the highest potential for producing quercetin (QUE), rutin (RUT), and apigenin (API). Treatment with 5 mM Phe resulted in its highest level in 96 h post-treatment, reaching 3.49- and 6.66-fold higher levels than the control, respectively. Nar at concentrations of 0.4- and 0.8-mM enhanced API and QUE production by 1.91- and 3.28-fold, respectively. YE notably increased API and ACA (acacetin) levels, while SA resulted in the highest accumulation of QUE and RUT, highlighting its crucial role in flavonol biosynthesis. YE and Nar significantly enhanced FNSII gene expression, with Nar being the most effective. This makes Nar an effective candidate for increasing flavonoid production in Z. clinopodioides. This finding may have important implications for industries seeking to elevate flavonoid content, particularly the medicinal compound ACA, in plant-based products.

Salt stress constrains plant distribution and productivity, posing challenges to agriculture and ecosystems. Alfalfa (Medicago sativa L.) is one of the most important forages in the world. Seed germination, epigenetic physiology, transcriptome, metabolome, and the common regulatory mechanism of transcriptome and metabolome were investigated in Xizang's first independently bred alfalfa, ZangMu 1 (ZM1, highly salt-resistant type) and ZangMu 2 (ZM2, salt-sensitive type), under the treatments of 0, 100, and 200 mmol L-1 NaCl. The results showed that the salt tolerance of ZM1 was significantly better than that of ZM2. Additionally, the seed germination and physiological indices of both varieties exhibited a trend of low promotion and high inhibition. The joint transcriptome and metabolome analyses revealed that the flavonoid biosynthesis pathway was the core pathway in response to salt stress, and ZM1 enhanced stress tolerance by significantly upregulating more differential genes and metabolites. The levels of five key antioxidant metabolites (naringenin (NAR), apigenin (API), dihydroquercetin (DHQ), galangin (GAL), and epigallocatechin (EGC)) were significantly changed under salt stress, indicating that the free radical scavenging system of the plant was regulated. The expression levels of the core genes (CHI1, FL3H, CYP9B16, CYP75A1, FLS, and LAR) showed a synergistic regulation pattern with the salt tolerance metabolites, and the results of qRT-PCR validation were highly consistent with the transcriptome data. This study systematically analysed the flavonoid metabolic network of salt tolerance in Xizang alfalfa, providing molecular targets and a theoretical basis for the selection and breeding of salt-tolerant varieties.

Apigenin alleviates DFZ-induced cardiac, renal, and intestinal injury in carp by modulating oxidative stress and inflammatory responses.

Methotrexate (METX) is a widely used chemotherapeutic and immunosuppressive agent, frequently employed as a first-line treatment for various malignancies and autoimmune disorders. Despite its clinical efficacy, METX is known to induce cardiotoxicity primarily through mechanisms involving oxidative stress, inflammation, and apoptosis. Apigenin (API), a natural dietary flavonoid, exhibits potent antioxidant and anti-inflammatory properties. The current study evaluated the protective effects of API against METX-induced cardiotoxicity in mice, focusing on the modulation of transforming growth factor-β (TGF-β)/(SMAD2) signaling. Molecular docking was done to investigate the possible inhibition of TGF-β by API and bioinformatic tools were utilized to investigate the correlation between the target proteins. Male Swiss albino mice were randomly distributed to four groups: Group I: a saline group, Group II: a METX control group (20 mg/kg, per week), Group III: METX + API (40 mg/kg, per day) and Group IV: METX + API (80 mg/kg, per day, via oral gavage); the study continued for three weeks. Our findings suggest that API administration significantly mitigated METX cardiotoxicity and serum CK-MB, likely through attenuation of the inflammatory cytokines (NF-κB, IL-1β, TNF-α, and IL-6) and suppression of cardiac TGF-β/SMAD2 signaling. The congruence between bioinformatics and experimental validation findings strongly highlighted API as a promising therapeutic candidate for alleviating METX cardiotoxicity. While the current data reveals key underlying molecular mechanisms for API′s cardioprotective effect, further comprehensive studies across diverse cardiotoxicity models are essential to fully elucidate cardioprotective effect of API.

A stability-indicating RP-HPLC method was developed and validated for the simultaneous quantification of five flavonoids, viz., epigallocatechin gallate (EGCG), silibinin (SL), naringenin (NG), genistein (GT), and apigenin (AG), in herbal extracts. Chromatographic separation was achieved on a C18 column using 0.1 M ammonium acetate and methanol at 40:60% v/v. The method demonstrated acceptable resolution, linearity (r 2: 0.9905–0.9969), precision (<2% RSD), recovery (82.09–99.62%), and sensitivity (LOD: 0.068–1.516 μg/mL; LOQ: 0.20–4.59 μg/mL). The method successfully quantified these flavonoids in the aqueous extracts of Phyllanthus emblica L., Brassica oleracea L., Camellia sinensis (L.). Kuntze, Moringa oleifera L., Syzygium cumini (L.) Skeels, and Allium cepa L. Results revealed that EGCG was the major constituent found in all extracts, whilst AG, GT, and SL were found as minor constituents. The method identified six degradation products with a mass balance of >98%. The method demonstrated acceptable green chemistry by the AGREES and GAPI tools.

Apigenin modulates cell survival pathways and restores olaparib sensitivity in high-grade serous ovarian cancer cells.

Targeting kynurenine pathway and A1 /A2 astrocytes polarization in experimentally induced fibromyalgia: Modulatory role of apigenin on kynurenine/ aryl hydrocarbon receptor signaling.

Yujie recipe attenuates bleomycin-induced pulmonary fibrosis via suppressing NF-κB/NLRP3 signaling in a Nrf2-dependent manner.

The mycotoxin zearalenone (ZEN), commonly found in contaminated food and feed, poses a significant threat to human and animal health, particularly to reproductive function. Mitigating its toxicity represents a critical research priority in food safety. Apigenin (AP) is a naturally occurring dietary flavonoid with phytoestrogenic properties and exhibits diverse pharmacological activities. In this study, we investigated the protective effects of AP against ZEN-induced apoptosis and oxidative stress in Swine Testis (ST) cells and elucidated its underlying mechanisms. The identity of ST cells was verified via RT-PCR and agarose gel electrophoresis. ST cells were treated with 40 μM ZEN and 1 μM and 0.1 μM AP for 24 h. Cell viability was detected via CCK8 and EdU assays, cytotoxicity was evaluated via LDH assay, cell cycle and apoptosis levels were analyzed via flow cytometry, and the mechanism by which AP alleviated the damage caused by ZEN to ST cells was preliminarily revealed using RNA-Seq technology. Further, the expression levels of related genes and proteins were detected by qRT-PCR and Western blot. Our results show that 1 μM or 0.1 μM AP effectively attenuated the cytotoxicity induced by 40 μM ZEN in ST cells, as evidenced by restored cell viability, reduced the LDH level, normalized cell cycle progression, reduced apoptotic rates, and enhanced antioxidant capacity. RNA-Seq analysis was coupled with molecular validation and used to elucidate the mechanisms underlying AP-mediated protection against ZEN-induced cellular injury. It is shown that ZEN suppressed the expression of LRP5, a pivotal gene in the Wnt signaling pathway, along with its downstream effector c-Myc. Conversely, treatment with 1 μM or 0.1 μM AP upregulated the expression of LRP5, iASPP, and TRAF2 at both transcriptional and translational levels. Importantly, the protective effects of AP were abrogated with IWR-1-endo, a specific Wnt pathway inhibitor, confirming pathway dependency. Collectively, our findings show that AP alleviates ZEN-induced oxidative stress and apoptosis in ST cells through the upregulation of LRP5 and subsequent activation of the Wnt signaling pathway. This study provides molecular evidence supporting the potential clinical application of AP as a preventive agent against ZEN-induced reproductive toxicity.

Revealing the polyphenol modulation mechanism for in vitro gastric digestion properties of myofibrillar proteins via noncovalent interaction.

Colorectal cancer (CRC) represented a pervasive manifestation of malignant neoplasia within the digestive tract. Apigenin, exhibiting a multitude of physiological attributes and pharmacological actions, has undergone extensive scrutiny for its antitumor efficacy and benign toxicity profile. Cisplatin (DDP)-centered chemotherapy constituted a pivotal aspect of multidisciplinary therapeutic strategies. Nevertheless, resistance to DDP posed a considerable impediment to the efficacy of CRC chemotherapy. The aim of this investigation was to assess the impact of combining Apigenin with DDP on the proliferation and apoptotic processes of human CRC cells, while also delving into the underlying mechanisms. HCT116 and SW480 were cultivated and subjected to treatment with Apigenin (API) either as a monotherapy or in combination with cisplatin (DDP). Cell viability, proliferation, cycle distribution, apoptosis, migration, invasion and inflammatory factors were assessed. Western blot analysis was performed to detect the protein expression levels of Glut1, HK-2, KRT23, and β-catenin. In comparison to other treatment groups, the combined API and DDP group exhibited a more potent suppressive effect on cellular proliferation, migration, invasion, and glycolysis, while also enhancing apoptotic activity. Additionally, the combined API and DDP treatment group led to a reduction in the expression levels of KRT23, β-catenin, HK-2, and Glut1. Intriguingly, this combined treatment group demonstrated significantly elevated levels of TNF-α, IL-6, and IL-8 compared to the other groups. Notably, the overexpression of KRT23 was capable of reversing the changes induced by the combined API and DDP treatment. In vivo studies further validated that the combined API and DDP treatment suppressed tumor growth by inhibiting the expression of KRT23 and β-catenin. The present findings indicated that the combination of API with DDP has the potential to enhance colorectal cancer therapy through the modulation of the KRT23/Wnt/β-catenin signaling pathway. Our research may offer fresh perspectives and novel molecular therapeutic strategies for the treatment of colorectal cancer.Graphical Supplementary InformationThe online version contains supplementary material available at 10.1007/s12672-025-03942-w.

Alzheimer's Disease (AD) is a neurological disorder characterized by progressive cognitive impairment and memory loss. In vitro artificial membrane permeability assays targeting the blood-brain barrier (BBB), such as the parallel artificial membrane permeability assay (PAMPA), are useful for pre-evaluating the BBB penetration of molecules during the early stages of drug development. Inhibitors of glycogen synthase kinase-3β (GSK-3β), casein kinase-1δ (CK-1δ), and acetylcholinesterase (AChE) exhibit neuroprotective effects, indicating a potential therapeutic approach for AD. This study aimed to assess the ability of 23 phenolic compounds derived from natural sources to penetrate the central nervous system (CNS) and examine their potential neuroprotective effects. Following the prediction of BBB penetration of the compounds by PAMPA, neuroprotective effects of CNS+ compounds were evaluated through in vitro inhibition of GSK-3β, CK-1δ, and AChE. Based on the data obtained, five flavonoids (hispidulin, nepetin, platanoside, apigenin, and kaempferol) and two furanocoumarins (isopimpinellin and bergapten) were predicted to penetrate the CNS. Apigenin (API) and kaempferol (KEM) exhibited the most potent dual inhibitory activity against CK-1δ and GSK-3β. Furthermore, API and KEM did not exhibit cytotoxic effects in SH-SY5Y cells. Molecular modeling studies, including molecular docking, molecular dynamics simulations, and dynophore analysis, were performed to understand the binding mechanism of these most potent compounds to their target enzymes. Overall, the current study offers a rational approach to designing new molecules inspired by natural compounds to treat Alzheimer's Disease.

Intracerebral hemorrhage (ICH), a severe cerebrovascular disorder with high mortality, leads to secondary brain injury (SBI) primarily through neuroinflammation and blood-brain barrier (BBB) disruption. Among the pathological cascades, excessive activation of macrophages and the CCR5/JAK1/STAT1/MMPs signaling pathway play pivotal roles in amplifying neuronal damage. Apigenin (API), a natural flavonoid with anti-inflammatory and neuroprotective properties, has emerged as a promising therapeutic candidate to counteract these processes. In this study, we developed apigenin-loaded PLGA nanoparticles functionalized with DSPE-PEG2000-RVG29 and DSPE-PEG2000-folic acid (RVG/FA-NPs@API) to achieve targeted delivery to inflammatory macrophages and investigated their therapeutic effects against SBI after ICH. In a murine ICH model, API administration significantly improved neurological outcomes, reduced cerebral edema, suppressed neuronal apoptosis, and preserved BBB integrity. Mechanistically, API bound covalently to JAK1 at Cys1052, inhibiting its phosphorylation and subsequently downregulating the CCR5/JAK1/STAT1/MMPs cascade. Furthermore, RVG/FA-NPs@API demonstrated excellent stability, efficient brain-targeting, and superior biocompatibility, achieving enhanced therapeutic efficacy compared with free API. These findings highlight a novel strategy for targeted immunomodulation and provide translational insights into nanoparticle-assisted delivery of natural compounds for the treatment of ICH-induced SBI.Graphical Supplementary InformationThe online version contains supplementary material available at 10.1186/s12951-025-03748-6.

Unraveling the effect of ultrasound-assisted alkali treatment on β-lactoglobulin-flavonoids covalent complex system formation and its potential for lipophilic bioactive compounds delivery.

Apigenin and doxorubicin loaded zeolitic imidazole frameworks for triple-combination therapy of breast cancer.

The work presented here is part of our study series aimed at investigating the countermeasure effectiveness of apigenin (AP) against both early and late effects of heavy silicon (28Si) on the same cohort of exposed male C57BL/6 mice. We previously reported the countermeasure of AP against 28Si-induced early effects of 28Si ions. This section focuses on the protective effects of AP on late effects, specifically on the induction of acute lymphoma/lymphoblastic leukemia. Mice received a diet containing 20 mg/kg body weight of AP for five days before and after total-body irradiation with either 0 or 0.5 Gy of 260 MeV 28Si ions. They were divided into four groups based on AP intake and irradiation status. At one-week after irradiation, six mice from each group were euthanized to assess AP's effectiveness against early inflammation (in the bone marrow and gut tissues) and gut dysbiosis. The remaining mice were monitored until approximately 770 days of age. Incidence rates were analyzed using Chi-Square tests, while survival data were evaluated with Kaplan-Meier plots and log-rank tests, setting significance at p ≤ 0.05. At 770 days, survival rates were 37% for 28Si-exposed mice and 63% for those consuming AP, despite irradiation. There was a 2.57-fold increase in acute lymphoma/lymphoblastic leukemia incidence among 28Si-exposed mice not receiving AP compared to controls and AP-fed mice. Together with our previous report on the countermeasure activity of AP against early effects, these findings suggest that the gut-bone marrow axis plays an important role in 28Si-induced acute lymphoma/lymphoblastic leukemia. Our findings demonstrate that AP is an effective means of tackling the challenges posed by space radiation, and it has the potential to revolutionize protection in this critical area.

Nickel nanoparticles (NiNPs) are extensively used in nanotechnology, electronics, and biomedical fields, raising concerns about their pulmonary toxicity and potential role in inducing lung adenocarcinoma (LUAD). While heavy metals, like arsenic and cadmium, are well-known to drive LUAD through metabolic reprogramming, the molecular mechanism linking NiNPs to LUAD—particularly their impact on fatty acid metabolism (FAM)—remains unclear. This study is the first to explore whether NiNPs promote LUAD progression via the CDK1/STAT3/FASN axis, a key regulator of FAM, and to evaluate the natural compound apigenin (API) as a potential inhibitory agent. When human (A549) and mouse (LLC) LUAD cells were exposed to NiNPs, assessments of cell function and protein expression revealed increased malignant phenotypes, including enhanced proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT), along with activation of the CDK1/STAT3/FASN axis and upregulation of FAM-related markers. Genetic silencing of either CDK1 or FASN reversed the dysregulation of FAM and reduced the malignant characteristics of the cells. Molecular docking analysis confirmed that API binds strongly to CDK1, and further experiments demonstrated that API suppresses NiNP-induced tumor growth both in laboratory cell models and in living organisms, while also blocking the activity of the CDK1/STAT3/FASN axis.