Frontiers in Pharmacology
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2025
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IF 4.8
Jia-Ming Bai,Tong Li,Xue Di,Jing-Xian Yang,Zhao-Qi Cui,Dong-Yu Min,Yu-Feng Shen,Si-Yu Shan,Ye-Xin Zhang,Yi-Jun Shi,Zhi-Li Xu,De-Qiang Dou,Hong-He Xiao
Introduction: Alzheimer’s disease (AD), the most common form of dementia, currently has no effective cure. Epimedii Folium (EF), a traditional Chinese medicine known as Yin-yang-huo, has demonstrated significant neuroprotective properties.Methods: In this study, neural stem cells overexpressing the APPswe gene (APP-NSCs) were used as an in vitro AD model. The CCK-8, LDH, neurosphere formation, and BrdU incorporation assays were employed to identify the most effective bioactive metabolite of EF in promoting NSC proliferation. Subsequently, JC-1 staining, ATP quantification, and ROS assays were conducted to evaluate the protective effects of Icariside II (ICS II)-identified as the most effective metabolite-on mitochondrial function. APP/PS1 transgenic mice received an oral administration of 10 mg/kg ICS II for 7 weeks. Cognitive function was assessed using the Morris water maze and nest-building tests, while H&E and Nissl staining were used to evaluate brain tissue pathology. Transmission electron microscopy (TEM) examined the ultrastructural integrity of hippocampal neurons, immunofluorescence assessed hippocampal neurogenesis, and Western blotting quantified proteins involved in mitochondrial dynamics. Additionally, Rotenone (Rot), a mitochondrial respiratory chain inhibitor, was applied to disrupt mitochondrial function, allowing an evaluation of whether the neurogenesis-promoting effect of ICS II depends on maintaining mitochondrial structure and function.Results and discussion: The results demonstrated that ICS II exhibited the strongest capacity to promote APP-NSC proliferation (P < 0.01, η2 = 0.845), followed by Icariin and Icaritin. ICS II treatment significantly ameliorated cognitive deficits (P < 0.01, η2 = 0.883), neuronal damage, and impairments in neurogenesis in adult APP/PS1 mice. Moreover, ICS II rescued mitochondrial damage by upregulating fusion proteins (Mfn1 and Mfn2) and downregulating fission proteins (p-Drp1/Drp1 and Mff); however, these protective effects were negated by Rot administration. In conclusion, this study identifies ICS II as one of the most effective metabolites of EF, promoting hippocampal neurogenesis and alleviating mitochondrial dysfunction in APP/PS1 mice, thereby offering promising therapeutic potential for AD.
研究领域:
神经科学
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药理学
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分子生物学
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PubMed
高影响因子
Chemistry Africa-A Journal of the Tunisian Chemical Society
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2025
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IF 2.2
Chen Wang,Zhang Fen,Xu Jianghe,Lai Feifan
Purpose To immobilize snailase on SBA-15 to enhance the efficient conversion of Epimedium wushanense extracts for the preparation of rhamnosyl icariside II. Methods The snailase was covalently coupled to amino and aldehyde modified SBA-15, and the immobilization conditions were optimized. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), N 2 adsorption-desorption analysis, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to characterize the physicochemical properties of immobilized snailase. The optimal enzymatic hydrolysis conditions, enzymatic kinetic parameters, storage stability and reusability of the immobilized snailase were investigated. Results The optimal immobilization conditions were pH 5.0, temperature 30℃, immobilization time 3 h and snailase concentration 10 mg⋅mL − 1 . The immobilized snailase showed a retained activity of 235.8 µmol⋅(h⋅g) −1 and a high enzyme loading capacity of 249.6 mg⋅g − 1 support. The optimum hydrolysis conditions for immobilized snailase were pH 5.5, temperature 50℃, substrate concentration 3.0 mg⋅mL − 1 , and reaction time 6 h. The V max and K m of the immobilized snailase were 3.92 µg⋅min − 1 and 1.18 mmol⋅L − 1 , respectively. Conclusion The immobilized snailase has a high enzyme loading capacity, strong conversion capability, better storage stability and good reusability, making it suitable for the efficient conversion of Epimedium wushanense extracts to produce rhamnosyl icariside II.
研究领域:
酶学
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生物催化
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植物化学
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纳米技术
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生物技术
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高影响因子
CHINESE JOURNAL OF PHYSIOLOGY
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2023
·Vol. 66
·期 6
·437
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IF 1.8
Fan Wenbo,Zhou Jianwu
Parkinson's disease (PD) is recognized as a degenerative and debilitating neurodegenerative disorder. The novel protective role of icariside II (ICS II) as a plant-derived flavonoid compound in neurodegenerative diseases has aroused much attention. Herein, the definite impacts of ICS II on the process of PD and the relevant action mechanism were studied. Human neuroblastoma SK-N-SH cells were challenged with 1-methyl-4-phenylpyridinium ion (MPP + ) to construct the PD cell model. MTT assay and flow cytometry analysis, respectively, appraised cell viability and apoptosis. Caspase 3 Activity Assay examined caspase 3 activity. Corresponding kits examined oxidative stress levels. BODIPY 581/591 C11 assay evaluated lipid reactive oxygen species. Iron Assay Kit assessed iron content. Western blot tested the expression of apoptosis-, ferroptosis- and Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) signaling-associated proteins. Molecular docking verified the binding of ICS II with Keap1. The existing experimental results unveiled that ICS II elevated the viability whereas reduced the apoptosis, oxidative stress, and ferroptosis in MPP + -treated SK-N-SH cells in a concentration-dependent manner. Furthermore, ICS II declined Keap1 expression while raised Nrf2, heme oxygenase 1, and GPX4 expression. In addition, ICS II had a strong binding with Keap1 and Nrf2 inhibitor ML385 partially abolished the suppressive role of ICS II in MPP + -triggered apoptosis, oxidative stress, and ferroptosis in SK-N-SH cells. To summarize, ICS II might inhibit apoptosis, oxidative stress, and ferroptosis in the MPP + -stimulated PD cell model, which might be due to the activation of Keap1/Nrf2/GPX4 signaling.
研究领域:
神经科学
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药理学
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细胞生物学
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分子生物学
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PubMed
高影响因子
MOLECULAR PHARMACEUTICS
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2025
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IF 4.5
Zheng Sun,Zhiyong Li,Teng Hao,Xuecun Liu,Yuanyuan Jiang,Songyuge Ping,Na Dong,Ruiling Guo,Xin Yang,Hui Xu
Hepatocellular carcinoma (HCC) is one of the leading causes of death worldwide, accounting for about 90% of all primary liver malignancies. The emergence of natural antitumor compounds provides a new strategy for the treatment of HCC, but their delivery in vivo has become a major problem. In this study, the copolymer of the natural product glycyrrhetinic acid (AMGA) was prepared and served as a carrier for encapsulation of the natural active ingredient Icariside II (AMGA@ICAII). The results show that AMGA still retains the interaction with GA-R and achieves active targeting by interacting with GA-R. In addition, GA-modification changes the physical chemistry nature of the carrier, providing it with better colloidal stability. AMGA@ICAII significantly inhibited the proliferation of the human hepatoma cell line HepG-2 in vitro compared with other treatment groups. Furthermore, AMGA@ICAII improved the distribution of ICAII in the C57BL/6J mouse Hepa1–6 hepatoma model and showed a significant antitumor effect. This work demonstrated that small molecule target modification in the hydrophobic segment of block copolymer will do benefit to improve the performance of the carrier, while retaining ligand–receptor-mediated targeting properties and providing a reference for the targeted delivery of anticancer agents.
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BIOORGANIC CHEMISTRY
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2022
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IF 5.307
Chuan-Jian Shi,Shi-Ying Li,Chun-Hui Shen,Fei-Fei Pan,Li-Qiang Deng,Wei-Ming Fu,Ji-Yong Wang,Jin-Fang Zhang
Icariside II, a flavonol glycoside, one of the major components of Traditional Chinese Medicine Herba epimedii. In the present study, we found that Icariside II suppressed the proliferation of CRC by inducing cell cycle arrest and apoptosis in vitro and inhibited tumor growth in vivo . The further mechanism investigation showed that Icariside II suppressed the expression of β-catenin and led to the functional inactivation of Wnt/β-catenin signaling. Circβ-catenin was considered as a promising candidate for mediating the tumorigenesis and the activation of Wnt/β-catenin signaling in CRC cells. Furthermore, Icariside II has been proven to suppress the biogenesis of circβ-catenin via epigenetically targeting DNA methyltransferases (DNMTs) to decrease global DNA methylation levels in CRC cells. Taken together, our results indicated that Icariside II suppressed tumorigenesis by epigenetically silencing the activation of circβ-catenin-Wnt/β-catenin axis in colorectal cancer. More importantly, the information gained from this study suggest that Icariside II may have great potential to be developed as a therapeutic drug for CRC patients.
研究领域:
肿瘤学
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药理学
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分子生物学
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表观遗传学
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PubMed
高影响因子
Journal of Materials Chemistry B
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2025
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IF 5.7
Yishun Yang,Yue Ding,Tong Zhang
Icariside II (ICAII), a bioactive compound from Epimedii Folium, exhibits promising anti-tumor activity but faces challenges in clinical application due to poor solubility and low bioavailability. This study developed a novel carrier-free co-delivery system of ICAII and doxorubicin (DOX) through self-assembly into nanofibers. The ICAII combined with DOX nanofibers (ICAII-DOX NFs) and ICAII-DOX/TPGS NFs (with TPGS as a stabilizer) were systematically characterized for their physicochemical properties, including size distribution, morphology, and molecular interactions. The synergistic anti-lung cancer effect of ICAII and DOX was evaluated both in vitro and in vivo. The prepared ICAII-DOX NFs and ICAII-DOX/TPGS NFs showed mean sizes of 127 and 338 nm respectively, with PDI values of 0.2~0.3 and drug loading contents > 48%. FTIR, fluorescence, NMR and X-ray powder diffraction analyses revealed that the formation of ICAII-DOX co-assembly was primarily driven by intermolecular hydrogen bonding between the two molecules. The nanofibers demonstrated controlled drug release profiles (DOX’s cumulative release rate was 65.88% at 48 h, and ICAII’s cumulative release rate was 74.29% at 48 h) and enhanced cellular uptake (1.8-fold more than free DOX group). CCK-8 assay results showed that the IC50 (calculated in term of DOX) of ICAII-DOX mixture, ICAII-DOX NFs and ICAII-DOX/TPGS NFs were 0.67, 0.60 and 0.44 μM on A549 human lung carcinoma cells. In vivo studies using an A549 xenograft mouse model showed improved therapeutic efficacy (the inhibition rates of ICAII-DOX Mixture and ICAII-DOX/TPGS NFs groups were 29.90%) compared to single drug treatment (the inhibition rates of DOX and ICAII groups were 8.70% and 17.72%). This study presents a self-assembled carrier-free co-delivery system, providing a potential strategy for treating lung cancer.
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高影响因子
BIOCHEMICAL PHARMACOLOGY
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2025
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IF 5.6
Jianping Hu,Jinhu Chen,Caili Zhao,Pei Yu,Wenjun Xu,Yong Yin,Lei Yang,Zhenzhen Zhang,Lingyi Kong,Chao Zhang
Osteosarcoma, the most prevalent malignant bone tumor in adolescents, is characterized by its aggressiveness and tendency to metastasize. Despite the advancements in treatment that have improved survival rates for localized cases, metastatic osteosarcoma remains challenging to treat due to the limited efficacy of current therapies and the severe side effects of chemotherapy. Epithelial-mesenchymal transition (EMT) is a key factor in osteosarcoma metastasis, and the miR-194/215 cluster, which is upregulated in osteosarcoma, promotes this process. This study sought to investigate natural compounds that could counteract the miR-194/215 cluster’s effects and inhibit osteosarcoma metastasis. By analyzing miRNA databases and clinical data, a signature gene set for the miR-194/215 cluster was established, and the LINCS database was screened to find natural compounds with antagonistic effects. Icariside II, an active component of Epimedium, was identified as a potential inhibitor and was shown to reduce the migration and invasion of osteosarcoma cells in vitro and lung metastasis in vivo . The study utilized various techniques, including Gene Set Enrichment Analysis (GSEA), Drug Affinity Responsive Target Stability (DARTS), Cellular Thermal Shift Assay (CETSA), molecular docking, and enzyme activity assays, to identify phosphoglycerate kinase 1 (PGK1) as the target protein of Icariside II. It was found that Icariside II competitively inhibits PGK1 by binding to its ADP binding pocket, reducing its activity and thus antagonizing the miR-194/215 cluster’s promotion of EMT in metastatic osteosarcoma. The results suggest that Icariside II could be a promising therapeutic agent for metastatic osteosarcoma, providing new targets and strategies for clinical treatment.
研究领域:
肿瘤学
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分子生物学
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药理学
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天然产物化学
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PubMed
高影响因子
EXPERIMENTAL AND MOLECULAR PATHOLOGY
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2020
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IF 2.28
Chunyan Tian,Fengli Gao,Xing Li,Zhuying Li
Asthma is a chronic inflammatory airway disease. Icariside II has been reported to exert anti-inflammatory effect in multiple human diseases . The present study aimed to investigate the effects and mechanisms of Icariside II on airway inflammation and remodeling in asthma. We established an asthma mouse model with ovalbumin (OVA) immunization. Histological analysis using H&E, PAS and Masson staining showed that administration of Icariside II attenuated OVA-induced airway inflammation and remodeling. Icariside II reduced the numbers of total white blood cells and eosinophils in bronchoalveolar lavage fluid (BALF). The levels of interleukin (IL)-4, IL-5, IL-13 and transforming growth factor (TGF)-β1 in peripheral blood and the expression of α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), eotaxin-1, CC-chemokine receptor-3 (CCR-3), Toll-like receptor (TLR)-2 and TLR-4 were significantly down-regulated in lung tissues of OVA-induced mouse model. These results suggested that Icariside II inhibited eosinophil activation and thus decreased eosinophils-induced airway inflammation and remodeling in asthma. Moreover, Icariside II suppressed TGF-β1-induced cell proliferation , migration, and CTGF expression in airway smooth muscle cells (ASMCs). In both OVA-induced mouse model of asthma and TGF-β1-induced ASMCs, Icariside II decreased IκBα degradation, nuclear translocation of NF-κB p65 and STAT3 phophorylation, indicating an inactivation of NF-κB and STAT3 in the presence of Icariside II. Therefore, we demonstrate that Icariside II attenuates eosinophils-induced airway inflammation and remodeling in asthmatic mice and inhibits TGF-β1-induced cell proliferation and migration in ASMCs via suppressing NF-κB and STAT3 signalings.
研究领域:
免疫学
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药理学
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呼吸医学
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DOI
PubMed
高影响因子
Molecular Medicine Reports
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2020
·Vol. 22
·期 4
·3151-3160
·
IF 2.1
Bing‑Feng Guan,Xiao‑Feng Dai,Qi‑Bin Huang,Di Zhao,Jin‑Long Shi,Cheng Chen,Yan Zhu,Fen Ai
Icariside II (ICAII) is a bioflavonoid compound which has demonstrated anti‑oxidative, anti‑inflammatory and anti‑apoptotic biological activities. However, to the best of our knowledge, whether ICAII can alleviate myocardial ischemia and reperfusion injury (MIRI) remains unknown. The aim of the present study was to determine whether ICAII exerted a protective effect on MIRI and to investigate the potential underlying mechanism of action. A rat MIRI model was established by ligation of the left anterior descending coronary artery for 30 min, followed by a 24 h reperfusion. Pretreatment with ICAII with or without a PI3K/AKT inhibitor was administered at the beginning of reperfusion. Morphological and histological analyses were detected using hematoxylin and eosin staining; the infarct size was measured using Evans blue and 2,3,5‑triphenyltetrazolium chloride staining; and plasma levels of lactate dehydrogenase (LDH) and creatine kinase‑myocardial band (CK‑MB) were analyzed using commercialized assay kits. In addition, the cardiac function was evaluated by echocardiography and the levels of cardiomyocyte apoptosis were determined using a TUNEL staining. The protein expression levels of Bax, Bcl‑2, cleaved caspase‑3, interleukin‑6, tumor necrosis factor‑α, PI3K, phosphorylated (p)‑PI3K, AKT and p‑AKT were analyzed using western blotting analysis. ICAII significantly reduced the infarct size, decreased the release of LDH and CK‑MB and improved the cardiac function induced by IR injury. Moreover, ICAII pretreatment significantly inhibited myocardial apoptosis and the inflammatory response. ICAII also upregulated the expression levels of p‑PI3K and p‑AKT. However, the protective effects of ICAII were abolished by an inhibitor (LY294002) of the PI3K/AKT signaling pathway. In conclusion, the findings of the present study suggested that ICAII may mitigate MIRI by activating the PI3K/AKT signaling pathway.
研究领域:
药理学
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心脏病学
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分子生物学
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PubMed
高影响因子
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