NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2022
·Vol. 396
·期 4
·683-692
·
IF 3.195
Huang Hui,Xue Jie,Xie Tao,Xie Mei-Lin
Osthole is a natural coumarin substance that has an inhibitory effect on hepatic cancer, but its radiosensitization effect on hepatoma cells has not been reported. This study aimed to investigate the effect of osthole. Human HCC-LM3 and SK-Hep-1 hepatoma cells were used and treated with or without osthole, irradiation, or their combination; the cell survival, migration, colony formation, DNA damage repair, intracellular lactic acid content, and glycolysis-related glycogen synthase kinase-3β (GSK-3β), p-GSK-3β, AMP-activated protein kinase (AMPK), p-AMPK, mammalian target of rapamycin (mTOR), p-mTOR, glucose transporter-1 (GLUT-1), GLUT-3, and pyruvate kinase isozyme type M2 (PKM2) protein expressions were determined. Compared with the irradiation group, the osthole plus irradiation group could further decrease the survival rate, migration, colony formation, and DNA damage repair of both hepatoma cells, indicating a synergistic effect of the combination treatment. Moreover, the combination of osthole and irradiation could decrease the content of intracellular lactic acid, ratios of intracellular p-GSK-3β/GSK-3β and p-mTOR/mTOR proteins, and expressions of intracellular GLUT-1/3 and PKM2 proteins, and increase the ratio of intracellular p-AMPK/AMPK proteins. Osthole can increase the radiosensitivity of hepatoma cells, and its radiosensitization mechanisms may be related to glycolytic inhibition by attenuating the GSK-3β/AMPK/mTOR pathway.
研究领域:
癌症生物学
·
分子生物学
·
药理学
·
放射生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
·
2021
·
IF 6.543
Lijun Fang,Wei Wang,Jiazheng Chen,Anju Zuo,Hongmei Gao,Tao Yan,Pengqi Wang,Yujia Lu,Ruijuan Lv,Feng Xu,Yuguo Chen,Linmao Lyu
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease characterized by the extensive accumulation of myofibroblasts and collagens. However, the exact mechanism that underlies this condition is unclear. Growing evidence suggests that NADPH oxidases (NOXs), especially NOX4-derived oxidative stress, play an important role in the development of lung fibrosis. Bleomycin (BLM) is a tumor chemotherapeutic agent, which has been widely employed to establish IPF animal models. Osthole (OST) is an active constituent of the fruit of Cnidium ninidium. Here, we used an in vivo mouse model and found that OST suppressed BLM-induced body weight loss, lung injury, pulmonary index increase, fibroblast differentiation, and pulmonary fibrosis. OST also significantly downregulated BLM-induced NOX4 expression and oxidative stress in the lungs. In vitro, OST could inhibit TGF-β1-induced Smad3 phosphorylation, differentiation, proliferation, collagen synthesis, NOX4 expression, and ROS generation in human lung fibroblasts in a concentration-dependent manner. Moreover, NOX4 overexpression could prevent the above effects of OST. We came to the conclusion that OST could significantly attenuate BLM-induced pulmonary fibrosis in mice, via the mechanism that involved downregulating TGF-β1/NOX4-mediated oxidative stress in lung fibroblasts.
研究领域:
药理学
·
呼吸病学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2023
·
IF 4.7
Duo Lai,Delin Wang,Xuehua Shao,Jian Qin,Qingli Zhuang,Hanhong Xu,Weiqiang Xiao
Blue mold induced by Penicillium choerospondiatis is a primary cause of growth and postharvest losses in the fruit of Phyllanthus emblica . There is an urgent need to explore novel and safe fungicides to control this disease. Here, we demonstrated osthole, a natural coumarin compound isolated from Cnidium monnieri , exhibited a strong inhibitory effect on mycelia growth, conidial germination rate and germ tube length of P. choerospondiatis , and effectively suppressed the blue mold development in postharvest fruit of P. emblica . The median effective concentration of osthole was 9.86 mg/L. Osthole treatment resulted in cellular structural disruption, reactive oxygen species (ROS) accumulation, and induced autophagic vacuoles containing cytoplasmic components in fungal cells. Transcriptome analysis revealed that osthole treatment led to the differentially expressed genes mainly enriched in the cell wall synthesis, TCA cycle, glycolysis/ gluconeogenesis , oxidative phosphorylation . Moreover, osthole treatment led to increase genes expression involved in peroxisome , autophagy and endocytosis . Particularly, the autophagy pathway related genes ( PcATG1 , PcATG3 , PcATG15 , PcATG27 , PcYPT7 and PcSEC18 ) were prominently up-regulated by osthole. Summarily, these results revealed the potential antifungal mechanism of osthole against P. choerospondiatis . Osthole has potentials to develop as a natural antifungal agent for controlling blue mold disease in postharvest fruits.
研究领域:
植物病理学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2026
·
IF 5.2
Jian Yang,Mingjuan Xu,Yanzhu Li,Wei Su,Yao Qian,Jun Yi
Knee osteoarthritis (KOA) is a degenerative joint disorder characterized by excessive reactive oxygen species (ROS) accumulation, persistent inflammation, and progressive extracellular matrix (ECM) degradation. However, effective modulation of the pathological redox-inflammatory microenvironment remains challenging due to the poor bioavailability of natural antioxidants and the limited catalytic durability of conventional nanomaterials. In this study, we report a polyethylene glycol (PEG)-assisted coordination assembly strategy to construct an osthole–ceria (OST–CeO 2 ) nanocomposite with synergistic ROS-scavenging and chondroprotective functions. The resulting OST-CeO 2 nanoparticles exhibit a uniform quasi-spherical morphology, a hydrodynamic diameter of 150 nm, a mildly positive surface charge, excellent colloidal stability, and pH/ROS dual-responsive release profiles. In vitro assays confirm that OST-CeO 2 possesses potent concentration-dependent antioxidant activity against diverse radicals including DPPH·, ABTS + ·, and hydrogen peroxide. In IL-1β-stimulated ATDC5 chondrocytes, OST-CeO 2 treatment restores cell viability and significantly suppresses pro-inflammatory cytokines (IL-1β, TNF-α, IL-6). In an H 2 O 2 -induced oxidative stress model, it effectively quenches intracellular ROS, reinstates antioxidant enzyme activities such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), and reduces malondialdehyde (MDA) levels. Furthermore, intra-articular injection of OST-CeO 2 in a destabilization of the medial meniscus (DMM)-induced KOA mouse model significantly attenuates cartilage erosion, lowers Mankin and OARSI histological scores, and improves joint function, with no appreciable toxicity to major organs. Collectively, OST-CeO 2 integrates ceria-mediated catalytic ROS elimination with osthole's inherent antioxidant and anti-inflammatory properties, establishing a dual-functional nano-antioxidant platform that reshapes the redox and inflammatory imbalance in the KOA niche. This study presents a promising nanotherapeutic strategy for cartilage preservation and provides a foundation for designing hybrid systems combining natural bioactive compounds with nanozymes against degenerative joint diseases. Download: Download high-res image (294KB) Download: Download full-size image
✓ 已验证
DOI
高影响因子
Journal of Traditional and Complementary Medicine
·
2025
·
IF 3
Huan Hou,Yaping Yang,Minyan Zhu,Meilin Xie,Yan Zhang,Rong Chen
Background and aim Trastuzumab (TRZ)-induced cardiotoxicity impairs breast cancer patients' quality of life, with no effective prevention currently. Osthole (OST) has been reported to exert cardioprotective effects in certain cardiovascular diseases. The purpose of this study was to investigate the probable mechanisms behind the protective effect of OST against TRZ-induced cardiotoxicity. Experimental procedure Mice were pretreated with OST (50 or 100 mg/kg) for 5 days, followed by TRZ (10 mg/kg, 10 days) to establish a cardiotoxicity model. The protective effects of OST on TRZ-induced cardiotoxicity was assessed via echocardiography, cardiac weight index (CWI), serum myocardial injury markers, H&E, and Masson staining. To explore the mechanisms, SOD/MDA levels, DHE staining (ROS), Nick-End-Labeling (TUNEL) staining (apoptosis), and Western blot were performed with/without 3-methyladenine (autophagy inhibitor) or SB203580 (p38MAPK inhibitor). Results and Conclusion OST pretreatment significantly improved cardiac function, alleviated myocardial damage and fibrosis, and enhanced autophagy (increased LC3II/I, Beclin-1 and decreased p62). Oxidative stress damage was ameliorated by OST, as demonstrated by higher activity of SOD, lower level of MDA and reactive oxygen species (ROS). In addition, OST decreased the ratio of Bax/Bcl-2 and Caspase-3 expression, and reduced apoptosis rate. OST activated p38MAPK (increased p-p38MAPK level) while inhibiting mTOR (decreased p-mTOR level). While these effects were blocked by the autophagy inhibitor 3-MA or p38MAPK inhibitor SB203580. These results indicated that OST has a protective effect on TRZ-induced cardiotoxicity, and its underlying mechanism may be related to enhancing autophagy via the p38MAPK/mTOR signaling pathway, thus reducing oxidative stress and apoptosis.
✓ 已验证
产品关联
DOI
高影响因子
Revista Brasileira de Farmacognosia-Brazilian Journal of Pharmacognosy
·
2023
·
IF 1.6
Huang Mingjun,Wu Fanchang,Zuo Xue,Liu Jinman,Yu Wenqian,Xie Ruiye,Liu Guoqing,Tan Qiwen,Wang Qi,Liang Yong
Plant-based medicines derived from traditional Chinese medicine have garnered widespread attention for their potential in the prevention and treatment of various diseases, offering superior oral bioavailability compared to the use of single drug formulations. Nonetheless, the precise biological mechanisms and interactions between compounds and enzymes remain inadequately understood. This study delves into the inhibitory interactions of quercetin with cytochrome P450 and P-glycoprotein, leading to a synergistic enhancement of osthole bioavailability in rat plasma. The results indicate that quercetin demonstrates concentration-dependent and uncompetitive inhibition of liver microsomal cytochrome P450 proteins 3A, with an observed IC 50 value of 34.17 μM. Additionally, quercetin notably suppresses the expression of P-glycoprotein in the small intestines of rats, resulting in a significant 52.9% reduction ( p < 0.001) and a corresponding downregulation of its associated mRNA Mdr1b level. The administration of quercetin alongside osthole in rats leads to a marked increase of over 80% ( p < 0.001) in osthole blood concentration, as determined by pharmacokinetic analysis, surpassing the effects of pure osthole usage. This multifunctional attribute of quercetin, along with the observed synergistic changes in pharmacokinetics, holds promise for shedding light on the interplay of drug–drug/enzyme interactions in the context of medicinal plants. Graphical abstract
✓ 已验证
产品关联
DOI
高影响因子
TOXICOLOGY IN VITRO
·
2023
·
IF 3.2
Huan Hou,Yaping Yang,Rong Chen,Zhiping Guo
Trastuzumab (TRZ) is a novel targeted anti-tumor agent that significantly improve the survival of patients with human epidermal growth factor receptor (HER2) positive breast cancer. However, its clinical application is limited due to the side effects of cardiotoxicity. Osthole (OST), a coumarin derivative isolated from Cnidium monnieri (L.) Cusson, has previously demonstrated cardioprotective effects. The aim of this study was to observe the protective effect of OST on TRZ-induced cardiomyocytes damage and to explore its potential mechanism. The results showed that OST pretreatment could significantly inhibit TRZ-induced cardiomyocytes damage, markedly increase the ratio of LC3II/I and Beclin-1 protein expression, and reduce the protein expression of p62. OST pretreatment significantly attenuated oxidative stress and apoptosis induced by TRZ, as evidenced by reducing intracellular ROS level, the Bax/Bcl-2 ratio, and Caspase-3 protein expression. Additionally, OST markedly increased the phosphorylation level of p38MAPK and decreased the mTOR phosphorylation level. However, the effects of OST on enhancing autophagy, reducing oxidative stress, apoptosis, and the phosphorylation level of mTOR were reversed after the addition of 3-MA or SB203580. Molecular docking results indicated that OST exerted a good binding ability with the p38MAPK protein. Our findings suggested that OST could protect TRZ-induced cardiomyocytes damage by enhancing autophagy via the p38MAPK/mTOR signaling pathway.
研究领域:
药理学
·
心脏病学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2023
·Vol. 29
·期 1
·21
·
IF 4.6
Xue Wang,Xiaomei Fu,Xiurong Luo,Yiyi Lai,Chuipu Cai,Yanfang Liao,Zhao Dai,Shuhuan Fang,Jiansong Fang
Osthole, a natural coumarin found in various medicinal plants, has been previously reported to have neuroprotective effects. However, the specific mechanism by which Osthole alleviates dysmnesia associated with Alzheimer’s disease (AD) remains unclear. This study aimed to investigate the neuroprotective properties of Osthole against cognitive impairment in rats induced by D-galactose and elucidate its pharmacological mechanism. The rat model was established by subcutaneously injecting D-galactose at a dose of 150 mg/kg/day for 56 days. The effect of Osthole on cognitive impairment was evaluated by behavior and biochemical analysis. Subsequently, a combination of in silico prediction and experimental validation was performed to verify the network-based predictions, using western blot, Nissl staining, and immunofluorescence. The results demonstrate that Osthole could improve memory dysfunction induced by D-galactose in Sprague Dawley male rats. A network proximity-based approach and integrated pathways analysis highlight two key AD-related pathological processes that may be regulated by Osthole, including neuronal apoptosis, i.e., neuroinflammation. Among them, the pro-apoptotic markers (Bax), anti-apoptotic protein (Bcl-2), the microgliosis (Iba-1), Astro-cytosis (GFAP), and inflammatory cytokines (TNF-R1) were evaluated in both hippocampus and cortex. The results indicated that Osthole significantly ameliorated neuronal apoptosis and neuroinflammation in D-galactose-induced cognitive impairment rats. In conclusion, this study sheds light on the pharmacological mechanism of Osthole in mitigating D-galactose-induced memory impairment and identifies Osthole as a potential drug candidate for AD treatment, targeting multiple signaling pathways through network proximity and integrated pathways analysis.Keywords:Alzheimer’s disease;cognitive disorder;Osthole;neuronal apoptosis;neuroinflammation;network proximity
研究领域:
药理学
·
神经科学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2020
·Vol. 24
·期 8
·4439-4451
·
IF 4.486
Hongping Yu,Daoyu Zhu,Pei Liu,Qianhao Yang,Junjie Gao,Yigang Huang,Yixuan Chen,Youshui Gao,Changqing Zhang
Characteristic pathological changes in osteonecrosis of the femoral head (ONFH) include reduced osteogenic differentiation of bone mesenchymal stem cells (BMSCs), impaired osseous circulation and increased intramedullary adipocytes deposition. Osthole is a bioactive derivative from coumarin with a wide range of pharmacotherapeutic effects. The aim of this study was to unveil the potential protective role of osthole in alcohol-induced ONFH. In vitro, ethanol (50 mmol/L) remarkably decreased the proliferation and osteogenic differentiation of BMSCs and impaired the proliferation and tube formation capacity of human umbilical vein endothelial cell (HUVECs), whereas it substantially promoted the adipogenic differentiation of BMSCs. However, osthole could reverse the effects of ethanol on osteogenesis via modulating Wnt/β-catenin pathway, stimulate vasculogenesis and counteract adipogenesis. In vivo, the protective role of osthole was confirmed in the well-constructed rat model of ethanol-induced ONFH, demonstrated by a cascade of radiographical and pathological investigations including micro-CT scanning, haematoxylin-eosin staining, TdT-mediated dUTP nick end labelling, immunohistochemical staining and fluorochrome labelling. Taken together, for the first time, osthole was demonstrated to rescue the ethanol-induced ONFH via promoting bone formation, driving vascularization and retarding adipogenesis.
研究领域:
药理学
·
骨科
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Chinese Medicine
·
2026
·Vol. 21
·期 1
·87
·
IF 7.4
Li Yuan,Han Dongyang,Liu Junjie,Qiao Yuxin,Wei Jiaoxia,Lu Haitao,Yao Li
Background Pulmonary hypertension (PH) is a severe pulmonary vascular disease lacking early diagnostic biomarker and effective therapeutics. Osthole has capability to alleviate pulmonary vascular remodeling targeting by decadienyl-L-carnitin (C10:2) in PH rats. We sought to explore the novel functional mechanism of C10:2 in cell proliferation, apoptosis, extracellular matrix remodeling, and energy biosynthesis of pulmonary vascular remodeling as well as new inventional mechanism of osthole. Methods Animal and cell models of PH were established using monocrotaline (MCT) and platelet-derived growth factor-BB (PDGF-BB). C10:2 biosynthesis was manipulated through the administration of exogenous C10:2 and etomoxir. Markers of pyroptosis and pulmonary vascular remodeling, as well as components of the C10:2/HSP47/NLRP3 axis, were evaluated using western blotting, ELISA, and biochemical assays. Results Osthole inhibited cell pyroptosis and alleviated pulmonary vascular remodeling by suppressing the expression of NLRP3, GSDMD, Caspase-1, IL-1β, IL-18, and C10:2 in PH rats. Additionally, C10:2 levels were positively correlated with the progression of pulmonary vascular remodeling in a time-dependent manner. C10:2, similar to PDGF-BB, promoted the proliferation of pulmonary arterial smooth muscle cells (PASMCs), accelerated extracellular matrix remodeling, inhibited apoptosis, activated AMPKα-1, and increased ROS accumulation, ultimately leading to mitochondrial dysfunction in PASMCs. Osthole attenuated C10:2-induced pulmonary vascular remodeling by downregulating proliferation markers (PCNA, cyclin A, CDK2), modulating apoptosis markers (Caspase-3, Bax, Bcl-2), inhibiting migration-related proteins (MMP2, MMP9, TGF-β), and reducing AMPKα-1 and ROS overaccumulation as well as HSP47 expression. Collectively, our findings reveal a novel role for C10:2 in accelerating pulmonary vascular remodeling by promoting proliferation, apoptosis resistance, extracellular matrix remodeling, and mitochondrial dysfunction through NLRP3 inflammasome activation. Mechanistically, osthole significantly inhibited pyroptosis and mitigated pulmonary vascular remodeling via the C10:2/HSP47/NLRP3 axis. Conclusion Our study identifies a novel function of C10:2 in promoting pyroptosis and accelerating pulmonary vascular remodeling through activation of the HSP47/NLRP3 axis. Furthermore, we demonstrate that osthole effectively inhibits C10:2/HSP47/NLRP3 axis-induced pyroptosis, thereby alleviating pulmonary vascular remodeling. These findings suggest that C10:2 may serve as a potential biomarker for PH diagnosis and provide a foundation for the development of novel anti-PH therapeutic strategies. Graphical
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2013
·
IF 3.463
Xiao-juan Hu,Yang Liu,Xiao-feng Zhou,Qiao-ling Zhu,Yong-yan Bei,Ben-gang You,Chun-ge Zhang,Wei-liang Chen,Zhou-li Wang,Ai-jun Zhu,Xue-nong Zhang,Yu-jiang Fan
Novel amphiphilic chitosan derivatives (N-caprinoyl-N-trimethyl chitosan [CA-TMC]) were synthesized by grafting the hydrophobic moiety caprinoyl (CA) and hydrophilic moiety trimethyl chitosan to prepare carriers with good compatibility for poorly soluble drugs. Based on self-assembly, CA-TMC can form micelles with sizes ranging from 136 nm to 212 nm. The critical aggregation concentration increased from 0.6 mg • L −1 to 88 mg • L −1 with decrease in the degree of CA substitution. Osthole (OST) could be easily encapsulated into the CA-TMC micelles. The highest entrapment efficiency and drug loading of OST-loaded CA-TMC micelles(OST/CA-TMC) were 79.1% and 19.1%, respectively. The antitumor efficacy results show that OST/CA-TMC micelles have significant antitumor activity on Hela and MCF-7 cells, with a 50% of cell growth inhibition (IC50) of 35.8 and 46.7 μg. mL −1 , respectively. Cell apoptosis was the main effect on cell death of Hela and MCF-7 cells after OST administration. The blank micelles did not affect apoptosis or cell death of Hela and MCF-7 cells. The fluorescence imaging results indicated that OST/CA-TMC micelles could be easily uptaken by Hela and MCF-7 cells and could localize in the cell nuclei. These findings suggest that CA-TMC micelles are promising carriers for OST delivery in cancer therapy.
研究领域:
药学
·
生物技术
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Sustainable Food Systems
·
2025
·
IF 3.1
Huifang Liu,Jianmei Yao,Rongxiu Yin,Chiyu Ma,Lulu Li,Wen Yang,Zhiwei Lei
Introduction: Tea gray blight disease is a major leaf disease in tea plants, significantly reducing tea quality and yield. Plants are rich in bioactive compounds that are safe, non-toxic, and biodegradable. In this study, we evaluated the antifungal activities and mechanisms of 11 plant extracts against N. ellipsospora.Methods: This study evaluated the antifungal activity of 11 plant extracts against N. ellipsospora of tea gray blight disease and systematically examined the impacts of osthole and carvacrol on the mycelial morphology, mycelial weight, cell microstructure, membrane permeability, various biochemical substrate levels and related gene expression levels of N. ellipsospora.Results: The results showed that carvacrol and osthole exhibited significant antifungal effects among 11 plant extracts with EC50 values of 24.40 and 9.38 mg/L, respectively. Further research demonstrated that carvacrol and osthole significantly inhibited mycelial growth, reduced lesion areas on tea leaves, and markedly affected mycelial morphology and ultrastructure. Observations of mycelial morphology and ultrastructure revealed that carvacrol and osthole caused shrinkage and distortion of the mycelial surface, damage to cell wall and membrane, and disorganization of cellular organelles. Particularly carvacrol and osthole significantly increased chitinase activity, inhibited β-1,3-glucanase activity, and regulated the expression of genes encoding these enzymes.Discussion: The findings indicated that carvacrol and osthole could inhibit the growth of N. ellipsospora by disrupting the integrity of the cell wall and membrane and interfere with energy metabolism. This study would provide a theoretical basis for the development of novel plant-based fungicides.
研究领域:
植物学
·
微生物学
·
生物化学
·
农业科学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）