Search Results (76)

Ecology and adaptive differentiation of Epimedium are central to understanding both its taxonomic complexity and medicinal value. In this study, we integrate transcriptomic and plastid data from four natural populations of E. brevicornu (HZ, QLH, TS, WD) to reconstruct their phylogenetic relationships, estimate divergence times, and identify candidate genes associated with local adaptation. Nuclear gene-based phylogenies provide higher resolution and greater topological consistency than plastid data, underscoring the utility of nuclear data in lineages affected by hybridization and incomplete lineage sorting. Molecular dating indicated that major intraspecific divergence occurred during the mid-Quaternary (0.61–0.45 Ma), coinciding with climatic oscillations and montane isolation. Population structure showed strong correlations with temperature and precipitation gradients, suggesting environmentally driven selection. Signatures of positive selection and accelerated evolutionary rates revealed population-specific enrichment of genes involved in stress response, protein modification, signaling, and carbohydrate metabolism—key pathways linked to high-elevation adaptation. Protein–protein interaction networks further indicated a two-tier adaptation mechanism: ancestral network rewiring combined with population co-evolution of interacting genes. Together, these findings advance our understanding of alpine plant adaptation and provide candidate genes for further functional and breeding studies in Epimedium. Full article

Icariin (ICA) is a bioactive flavonoid compound extracted from Epimedium plants. In recent years, it has attracted significant research interest in the field of bone tissue repair due to its pharmacological effects via multiple targets and pathways. Studies have shown that ICA promotes the osteogenic differentiation of mesenchymal stem cells (MSCs) and enhances bone matrix formation by regulating signaling pathways such as Akt and Wnt/β-catenin. It concurrently inhibits osteoclast activity to maintain the balance of bone remodeling, thereby simultaneously stimulating new bone regeneration and suppressing bone resorption. At the same time, ICA exerts potent anti-inflammatory and antioxidant effects and promotes angiogenesis, improving the local microenvironment of bone injury and significantly facilitating the regeneration of bone and cartilage tissues. Additionally, ICA exhibits notable protective effects in multiple organ systems including the cardiovascular, hepatic, renal, and nervous systems. Specifically, ICA reduces cardiomyocyte apoptosis and fibrosis to preserve cardiac function, improves hepatic metabolic function and alleviates oxidative stress, attenuates renal inflammation and fibrosis, and—through neuroprotective actions—reduces neuroinflammation and promotes neuronal survival. These multi-organ effects help optimize the systemic environment for bone healing. However, ICA faces significant pharmacokinetic challenges. It has low oral bioavailability (due to poor absorption and extensive first-pass metabolism) as well as a short half-life. Consequently, maintaining effective drug concentrations in vivo is difficult, which limits its therapeutic efficacy and impedes clinical translation. To fully realize its regenerative potential, advanced drug delivery strategies (e.g., nanocarrier-based delivery systems) are being explored to enhance ICA’s bioavailability and prolong its duration of action. Overall, ICA’s multi-modal actions on bone cells, the immune microenvironment, and systemic factors make it a promising multi-target agent for bone regeneration. Addressing its pharmacokinetic limitations through optimized delivery and conducting further clinical studies will be crucial to realize its full therapeutic potential. This review provides a comprehensive overview of recent advances and challenges in translating ICA’s benefits into orthopedic therapy. Full article

Healing large bone defects remains challenging. Gelatin scaffolds are biocompatible and biodegradable, but lack osteoinductive activity. Plant-derived exosomes carry miRNAs, growth factors, and proteins that modulate osteogenesis, but free exosomes suffer from poor stability, limited targeting, and low bioavailability in vivo. We developed a 3D GelMA hydrogel loaded with Epimedium-derived exosomes (“GelMA@Exo”) to improve exosome retention, stability, and sustained release. Its effects on MC3T3-E1 preosteoblasts—including proliferation, osteogenic differentiation, migration, and senescence—were evaluated via in vitro assays. Angiogenic potential was assessed using HUVECs. Underlying mechanisms were examined at transcriptomic and protein levels to elucidate GelMA@Exo’s therapeutic osteogenesis actions. GelMA@Exo exhibited sustained exosome release, enhancing exosome retention and cellular uptake. In vitro, GelMA@Exo markedly boosted MC3T3-E1 proliferation, migration, and mineralized nodule formation, while reducing senescence markers and promoting angiogenesis in HUVECs. Mechanistically, GelMA@Exo upregulated key osteogenic markers (RUNX2, TGF-β1, Osterix, COL1A1, ALPL) and activated the PI3K/Akt pathway. Transcriptomic data confirmed global upregulation of osteogenesis-related genes and bone-regeneration pathways. This study presents a GelMA hydrogel functionalized with plant-derived exosomes, which synergistically provides osteoinductive stimuli and structural support. The GelMA@Exo platform offers a versatile strategy for localized delivery of natural bioactive molecules and a promising approach for bone tissue engineering. Our findings provide strong experimental evidence for the translational potential of plant-derived exosomes in regenerative medicine. Full article

Chemotherapy-induced renal encephalopathy (RE) is a disease characterized by cognitive impairment of the brain caused by impaired kidney function for which there is no definitive treatment. Icariin (ICA), the main active component of Epimedium, has a good nervous system protection and anti-neuroinflammation effect, but its effect on the brain injury caused by renal insufficiency as a result of chemotherapy remains unclear. In this study, we demonstrated that 100 mg/kg ICA can not only successfully interface with serotonin and regulate hormone levels but also ameliorates kidney damage and cognitive impairment in cyclophosphamide (CTX)-induced RE mouse models and inhibits inflammation, oxidation, and apoptosis by regulating NF-κB, keap1-Nrf2, and apoptosis pathways. In order to further study the protective effect of ICA on RE, we used CTX-induced HT22 and HEK293 cell injury models, and the ICA intervention showed that ICA could prevent apoptosis by regulating the expression of the apoptosis-related proteins caspase-3, Bcl-2, Bax and BDNF. Overall, our study provides a basis for further investigation of the therapeutic potential of ICA in the treatment of neurodegenerative diseases in the context of renal dysfunction, and further studies are needed at a later stage to fully elucidate the underlying molecular mechanisms. Full article

The optimal parameters for the microwave-assisted extraction of Epimedium brevicornum Maxim. were determined by using response surface methodology (RSM), increasing the extraction of flavonoids by 1.79 times. The resulting extract facilitated the green synthesis of zinc oxide nanoparticles (ZnONPs) with a wurtzite structure through a reaction with zinc nitrate. These ZnONPs were then incorporated into polycaprolactone (PCL) by using an electrospinning technique to produce nanofibers. The incorporation of ZnONPs resulted in an increase in Young’s modulus, biodegradation rate, and swelling ratio while decreasing the diameter and water contact angle of the nanofibers, thereby improving the hydrophilicity of PCL. ZnO demonstrates excellent biocompatibility with periodontal ligament stem cells (PDLSCs), increasing cell proliferation and enhancing alkaline phosphatase activity by 56.9% (p < 0.05). Additionally, mineralization deposition increased by 119% (p < 0.01) in the presence of 1% ZnO and showed a concentration-dependent response. After inducing PDLSC cultures with PCL–1% ZnO for 21 days, the protein expression levels of Runx2 and OCN increased by 50% (p < 0.05) and 30% (p < 0.001), respectively. Additionally, Col-1, Runx2, BSP, and OCN gene expression levels increased by 2.18, 1.88, 1.8, and 1.7 times, respectively. This study confirms that biosynthesized ZnONPs improve the physical properties of PCL nanofibers and effectively induce the osteogenic differentiation of PDLSCs. Full article

The prevalence of erectile dysfunction (ED) among the male population worldwide has significant ramifications for their quality of life and psychological well-being. This narrative review explores both conventional treatments, such as pharmacotherapy and surgery, and emerging approaches, including regenerative therapies, dietary interventions, physiotherapy, and vacuum erection devices (VEDs). Unlike prior reviews, this study emphasises unconventional therapies and their role in comprehensive ED management. A systematic literature review was conducted using PubMed, Embase, and Medline, including studies published up to 2024. Keywords such as “ED”, “pharmacotherapy”, “shock wave therapy”, “regenerative medicine”, and “dietary interventions” were used to identify relevant studies. Eligible studies examined treatment efficacy, mechanisms, and patient outcomes. Phosphodiesterase type 5 (PDE5i) inhibitors remain the primary treatment, demonstrating effectiveness across diverse populations. Regenerative therapies, including stem cells and platelet-rich plasma (PRP), show promise, but require further validation. Surgical interventions, particularly penile prostheses, provide high patient and partner satisfaction. Non-invasive methods, including physiotherapy and dietary changes like adoption of the Mediterranean diet, improve vascular health and erectile function. The efficacy of VEDs as standalone or adjunct treatments has been demonstrated, enhancing outcomes in prosthetic surgery. A multimodal, personalised approach is essential for optimising ED treatment. Despite promising advancements, gaps remain in terms of long-term data, standardised protocols, and partner-centred outcomes. Future research should focus on large-scale, multi-centre trials and synergistic treatment approaches to improve therapeutic outcomes and patient satisfaction. Full article

This study employs the Biomod2 model, along with 22 bioclimatic variables, to predict the geographic distribution of the medicinal plant Epimedium acuminatum Franch. for the current period and three future timeframes (2050s, 2070s, and 2090s). Ultimately, 11 key environmental variables were identified as critical for assessing the habitat suitability of the medicinal plant. These include the annual mean temperature (Bio 1), isothermally (Bio 3), temperature seasonality (Bio 4), maximum temperature of the warmest month (Bio 5), minimum temperature of the coldest month (Bio 6), mean temperature of the driest quarter (Bio 9), mean temperature of the coldest quarter (Bio 11), precipitation of the driest quarter (Bio 17), elevation (Elev), aspect, and slope. The results indicate that the current high suitability areas are primarily distributed across Yunnan, Chongqing, Sichuan, Hunan, Guangxi, and Hubei provinces. In the future, the extent of high suitability areas is expected to increase. This study aims to provide a theoretical reference for the conservation of E. acuminatum genetic resources from a geographic distribution perspective. Full article

Epimedium Folium (EF) is a traditional Chinese herbal medicine, and its primary bioactive ingredients, such as icariin, are flavonoid glycosides. A rare EF flavonoid, baohuoside I, exhibits superior bioactivities and enhanced bioavailability compared to its metabolic precursor icariin. The biotransformation of icariin to baohuoside I can be effectively and specifically achieved by β-glucosidases. In this study, 33 candidate full-length β-glucosidase genes were screened from a previously built carbohydrate active enzyme (CAZyme) gene dataset derived from cow fecal microbiota. Thirteen of them exhibited β-glucosidase activity, with DCF-bgl-26 and DCF-bgl-27 showing relatively high expression levels and β-glucosidase activity. The maximum β-glucosidase activity of DCF-bgl-26 and DCF-bgl-27 was achieved at 45 °C and pH 6.0, with DCF-bgl-26 demonstrating better thermostability and pH tolerance compared to DCF-bgl-27. The activities of DCF-bgl-26 and DCF-bgl-27 were 123.2 U/mg protein and 157.9 U/mg protein, respectively, both of which are higher than those of many bacterial β-glucosidases. Structure analysis suggested that both β-glucosidases possess canonical (β/α)₈-TIM barrel fold structure of GH1 family β-glucosidases. Thin-layer chromatography results showed that both enzymes could efficiently convert icariin to baohuoside I in 30 min, indicating they have potential application in the production of high value rare baohuoside I. Full article

Epimedium is used in traditional Chinese medicine. Epimedium polysaccharides have a variety of physiological properties. This study compared three different processes for the extraction of polysaccharides from Epimedium spp., including ultrasonic, aqueous enzymatic, and microwave extraction, to optimize the extraction conditions and determine the optimal extraction method. The optimal parameters for each method were analyzed. The results showed that the optimal process for ultrasonic extraction was an ultrasonic power of 250 W, an extraction time of 60 min, a temperature of 50 °C, and a solid–liquid ratio of 1:35. The optimal conditions for the aqueous enzymatic method were a papain concentration of 70 U/mL, extraction time of 70 min, a temperature of 50 °C, and a material-to-liquid ratio of 1:30, while those for microwave extraction were a microwave power of 650 W, an extraction time of 50 min, a temperature of 40 °C, and a material-to-liquid ratio of 1:25. The polysaccharide yields were 4.85%, 4.72%, and 3.98% for the three methods, respectively, indicating that ultrasonic extraction resulted in the highest yield of polysaccharides from Epimedium brevicornum. After purification with DEAE-cellulose, the polysaccharide yields were 4.13%, 3.67%, and 3.12%, respectively. A comprehensive comparison demonstrated the superiority of the ultrasonic extraction method in terms of both extraction yield and purification efficiency. Characterization of the extracted Epimedium polysaccharides showed the presence of five monosaccharides, i.e., glucose, galactose, mannose, galacturonic acid, and rhamnose, and a number average molecular weight Mn of 1.65 × 10⁵ Da and weight average molecular weight Mw of 6.61 × 10⁵ Da. These results provide a scientific basis for the in-depth study and application of Epimedium polysaccharides. Full article

In this study, four previously undescribed flavonoids, named epimesatines P (1), Q (2), R (3), and S (4), were isolated from the aerial parts of Epimedium sagittatum Maxim. Their structures and absolute configurations were confirmed via spectroscopic analyses, quantum chemical electronic circular dichroism (ECD) calculations, Mo₂(OAc)₄–induced ECD, and Rh₂(OCOCF₃)₄–induced ECD experiments. Epimesatines Q and R were characterized by the presence of furan rings. A cytotoxicity assay demonstrated that epimesatines P–S exhibited significant inhibitory effects on the viability of MCF-7 human breast cancer cells, with IC₅₀ values ranging from 1.27 to 50.3 μM. Notably, epimesatines Q and R exhibited superior efficacy against MCF-7 cells compared to epimesatines P and S, suggesting that the presence of furan rings may enhance their activity against MCF-7 cells. Specifically, epimesatine Q displayed a more potent inhibitory effect at 1.27 μM compared to a positive control, docetaxel, which had an IC₅₀ of 2.13 μM, highlighting its potential as a therapeutic agent for breast cancer. Importantly, none of the tested compounds exhibited obvious toxicity toward MCF-10A human breast epithelial cells. Furthermore, compounds 1, 3, and 4 were found to significantly inhibit the expression of sphingosine kinase 1 (Sphk1) in MCF-7 cells. Full article

Degeneration and death of dopaminergic neurons in the substantia nigra of the midbrain are the main pathological changes in Parkinson’s disease (PD); however, the mechanism underlying the selective vulnerability of specific neuronal populations in PD remains unclear. Here, we used single-cell RNA sequencing to identify seven cell clusters, including oligodendrocytes, neurons, astrocytes, oligodendrocyte progenitor cells, microglia, synapse-rich cells (SRCs), and endothelial cells, in the substantia nigra of a rotenone-induced rat model of PD based on marker genes and functional definitions. We found that SRCs were a previously unidentified cell subtype, and the tight interactions between SRCs and other cell populations can be improved by icaritin, which is a flavonoid extracted from Epimedium sagittatum Maxim. and exerts anti-neuroinflammatory, antioxidant, and immune-improving effects in PD. We also demonstrated that icaritin bound with transcription factors of SRCs, and icaritin application modulated synaptic characterization of SRCs, neuroinflammation, oxidative stress, and survival of dopaminergic neurons, and improved abnormal energy metabolism, amino acid metabolism, and phospholipase D metabolism of astrocytes in the substantia nigra of rats with PD. Moreover, icaritin supplementation also promotes the recovery of the physiological homeostasis of the other cell clusters to delay the pathogenesis of PD. These data uncovered previously unknown cellular diversity in a rat model of Parkinson’s disease and provide insights into the promising therapeutic potential of icaritin in PD. Full article

Icaritin (ICT), a natural compound extracted from the dried leaves of the genus Epimedium, possesses antitumor and immunomodulatory properties. However, the mechanisms through which ICT modulates pyroptosis and immune response in hepatocellular carcinoma (HCC) remain unclear. This study demonstrated that ICT exhibits pyroptosis-inducing and anti-hepatocarcinoma effects. Specifically, the caspase1-GSDMD and caspase3-GSDME pathways were found to be involved in ICT-triggered pyroptosis. Furthermore, ICT promoted pyroptosis in co-cultivation of HepG2 cells and macrophages, regulating the release of inflammatory cytokines and the transformation of macrophages into a proinflammatory phenotype. In the Hepa1-6+Luc liver cancer model, ICT treatment significantly increased the expression of cleaved-caspase1, cleaved-caspase3, and granzyme B, modulated cytokine secretion, and stimulated CD8⁺ T cell infiltration, resulting in a reduction in tumor growth. In conclusion, the findings in this research suggested that ICT may modulate cell pyroptosis in HCC and subsequently regulate the immune microenvironment of the tumor. These observations may expand the understanding of the pharmacological mechanism of ICT, as well as the therapy of liver cancer. Full article

Epimedium brevicornu Maxim. is a herbal plant with various therapeutic effects, and its aboveground tissues contain flavonol compounds such as icaritin that can be used to produce new drugs for the treatment of advanced liver cancer. Previous studies have shown that ultraviolet-B (UV-B, 280–315 nm) stress can increase the levels of flavonoid substances in plants. In the current study, we observed the microstructure of E. brevicornu leaves after 0, 5, 10, 15, and 20 d of UV-B radiation (60 μw·cm⁻²) and quality formation mechanism of E. brevicornu leaves after 0, 10, and 20 d of UV-B radiation by LC‒ESI‒MS/MS. The contents of flavonols such as icariside I, wushanicaritin, icaritin, and kumatakenin were significantly upregulated after 10 d of radiation. The results indicated that UV-B radiation for 10 d inhibited the morphological development of E. brevicornu but increased the content of active medicinal components, providing a positive strategy for epimedium quality improvement. Full article

Osteoporosis is a global health challenge characterized by bone loss and microstructure deterioration, which urgently requires the development of safer and more effective treatments due to the significant adverse effects and limitations of existing drugs for long-term treatment. Traditional Chinese medicine, like Epimedium, offers fewer side effects and has been used to treat osteoporosis, yet its active compounds and pharmacological mechanisms remain unclear. In this study, 65 potential active compounds, 258 potential target proteins, and 488 pathways of Epimedium were identified through network pharmacology analysis. Further network analysis and review of the literature identified six potential active compounds and HIF-1α for subsequent experimental validation. In vitro experiments confirmed that 2″-O-RhamnosylIcariside II is the most effective compound among the six potential active compounds. It can promote osteoblast differentiation, bind with HIF-1α, and inhibit both HIF-1α gene and protein expression, as well as enhance COL1A1 protein expression under hypoxic conditions. In vivo experiments demonstrated its ability to improve bone microstructures and reduce bone loss by decreasing bone marrow adipose tissue, enhancing bone formation, and suppressing HIF-1α protein expression. This study is the first to describe the therapeutic effects of 2-O-RhamnosylIcariside II on osteoporosis, which was done, specifically, through a mechanism that targets and inhibits HIF-1α. This study provides a scientific basis for the clinical application of Epimedium and offers a new candidate drug for the treatment of osteoporosis. Additionally, it provides new evidence supporting HIF-1α as a therapeutic target for osteoporosis. Full article

Epimedium koreanum is a perennial herb of the Berberidaceae family, which is a traditional tonic in Chinese medicine. Seed germination of E. koreanum is difficult. Dormancy is an intrinsic factor that affects seed germination. Elucidating the molecular mechanism of seed dormancy and the lifting process of E. koreanum is of great significance for the breeding, conservation, and utilization of E. koreanum. Previous studies have concluded that E. koreanum seed dormancy breakage requires warm-temperature stratification followed by low-temperature stratification treatments. Therefore, we performed transcriptome sequencing using freshly harvested, untreated seeds (NS), seeds that developed a cotyledonary embryo after 90 d of constant-temperature stratification at 15 °C (CS), and seeds that broke dormancy by 90 d of stratification at 15 °C and 60 d of stratification at 5 °C (ND) in order to find the responsive genes and regulatory genes that regulate dormancy. A total of 92,867 genes with differential expression were identified. GO enrichment analysis highlighted redox processes, as well as structural components of the nucleus and ribosomes. KEGG enrichment analysis revealed a significant enrichment of phytohormone signaling pathways, which play a crucial role in seed dormancy release. Additionally, protein–protein interactions (PPIs) were predicted with starch and sucrose metabolic pathways. This study introduces a novel concept for a more profound comprehension of the molecular regulatory mechanism of E. koreanum and lays a theoretical foundation for the screening of E. koreanum candidate genes. Full article