EUROPEAN JOURNAL OF PHARMACOLOGY
·
2024
·
IF 4.2
Li-ying Guo,Ting Wang,Hou-xu Ma,Shihao Chen,Zhi-yong Chang,Fei Li
Alzheimer's disease (AD) and osteoporosis (OP) are both serious degenerative diseases, with the potential for concurrent occurrence in clinical settings, and they share certain pathological correlations. Osthole (OST) and notopterol (NOT) are the main active ingredients in traditional Chinese medicine, Angelica pubescens and Notopterygium incisum , respectively, and they exhibit neuroprotective and osteoprotective effects. However, whether the combination of OST and NOT produces a synergistic effect against AD and/or OP remains unclear. The aim of this study was to investigate whether the combination of OST and NOT could produce synergistic anti-AD and/or OP effects using the previously constructed zebrafish AD/OP comorbidity model. Active compounds with anti-AD and OP effects were screened from Angelica pubescens and Notopterygium incisum through network pharmacology, identifying OST and NOT, respectively. Then, the AlCl 3 -induced (Aluminum chloride, AlCl 3 ) AD combined with OP zebrafish model, in conjunction with the Chou-Talalay synergy evaluation model, was employed to assess whether the OST and NOT combination produced synergistic effects against AD and/or OP. Furthermore, a CuSO 4 -induced (Copper sulfate, CuSO 4 ) inflammation zebrafish model was used to investigate whether the combination of OST and NOT produced synergistic anti-inflammatory effects, thereby resulting in synergistic anti-AD and/or OP effects. The results demonstrated that the OST-NOT combined treatment produced a synergistic anti-AD and OP effect. Moreover, the combined treatment of OST and NOT significantly inhibited nitric oxide (NO) and reactive oxygen species (ROS) release more effectively than OST or NOT alone, indicating a synergistic anti-inflammatory effect of the OST and NOT combined treatment.
研究领域:
药理学
·
神经科学
·
骨骼生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2025
·
IF 6.8
Ting Xu,Zihan Xue,Xinhui Li,Miaomiao Zhang,Ruige Yang,Shangshang Qin,Yong Guo
Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of hospital- and community-acquired infections, necessitating the development of novel antibacterials. Here, we designed and synthesized 30 osthole derivatives with pyridinium quaternary ammonium moieties. In vitro bioassay showed that compounds 8u and 8ac exhibited potent antibacterial activity against S. aureus ATCC 29213 and ten clinical MRSA isolates (MIC = 0.5–1 μg/mL), with low hemolytic activity, rapid bactericidal effects, and minimal resistance induction. In MRSA-infected mouse models of skin abscesses and sepsis, 8u and 8ac also displayed excellent antibacterial effects and safety, which were comparable to vancomycin. Mechanistic studies revealed that 8u and 8ac selectively target bacterial membranes via binding to phosphatidylglycerol (PG), increasing intracellular reactive oxygen species (ROS), inducing content leakage, and ultimately causing bacterial death. These findings suggest 8u and 8ac as promising novel lead candidates for anti-MRSA drug development.
研究领域:
药理学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2018
·
IF 2.831
Nani Wang,Xuping Wang,Yang Zhang,Qiaoyan Zhang,Pingcui Xu,Hailiang Xin,Renjie Wu,Dan Shou,Luping Qin
Osthole is a derivative of coumnarin, which has been used to treat several diseases, including osteoporosis. To investigate the metabolite profile of osthole in osteoporosis rats was utilized to understand its underlying mechanisms of its anti-osteoporosis effect. In this study, plasma samples were collected from normal and osteoporosis rats after oral administration of osthole and analyzed to identify the metabolites of osthole by high performance liquid chromatography quadrupole time-of-flight mass spectrometry. By comparing the molecular weight and MS fragmentation of the metabolites with those of parent drug and reference standards, a total of 36 metabolites in plasma were identified. Demethylation, hydroxylation, hydroxymethylene loss and reduction, and subsequent glucuronidation, methylation and sulfation were the major metabolic pathways of osthole in both normal and osteoporosis rats. A specific hydration metabolic pathway was found in osteoporosis rats. These results provided a meaningful basis for studying the underlying mechanism of the anti-osteoporosis effect of osthole.
研究领域:
药理学
·
代谢组学
✓ 已验证
DOI
PubMed
高影响因子
NEUROPHARMACOLOGY
·
2025
·
IF 4.6
Yanman Liu,Jimei Zhang,Wenjuan Li,Qingwen Qu,Zhengxing Shan,Chunwei Liu,Ke Jiao,Xueqin Hou
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive dysfunction that is closely associated with cholinergic system damage. Estrogen deficiency is a well-established risk factor for AD in women. Osthole (OST), a phytoestrogen with mild, bidirectional regulatory properties, has been proposed as a potential estrogen replacement. This study aimed to investigate the mechanisms by which OST ameliorates cognitive impairment. Cognitive deficits were induced in female Sprague-Dawley rats by bilateral ovariectomy (OVX), and OST was subsequently administered by oral gavage. Behavioral tests revealed that OST significantly improved learning and memory and reduced anxiety-like and depression-like behaviors in OVX rats. H&E staining and Nissl staining demonstrated that OST reversed neuronal damage in the hippocampus and cortex. Western blotting, ELISA, and immunofluorescence staining indicated that OST treatment restored the estrogen–cholinergic–NGF axis: E 2 , ERα, and ERβ expression were upregulated; Ach, ChAT, NGF, and TrkA levels were increased, whereas AChE activity was decreased. Moreover, OST inhibited neuronal apoptosis by elevating Bcl-2 and reducing Bax expression, enhanced the expression of markers of synaptic plasticity (PSD95, SYN, and BDNF), and modulated neurotransmitter release (GABA and E). Collectively, these multi-target effects identify OST as a promising candidate for treating AD in women.
研究领域:
神经科学
·
药理学
·
内分泌学
·
阿尔茨海默病研究
·
天然产物
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACOLOGICAL SCIENCES
·
2018
·
IF 2.575
Botao Wang,Xin Zheng,Jing Liu,Zhen Zhang,Chongyang Qiu,Lei Yang,Lanqiu Zhang,Qi Zhang,Hongwei Gao,Ximo Wang
Pancreatic cancer has remained a major cause of cancer-related deaths. A hallmark of pancreatic cancer is extensive stromal reactions, resulting in a unique tumor microenvironment, especially the involvement of macrophages. These tumor-educated cells limit the efficacy of chemotherapy. Therefore, it is necessary to identify an effective treatment strategy. In this study, we aimed to explore the anti-tumor and immunomodulatory effects of osthole on pancreatic cancer. We found that osthole suppressed Panc 02 cell migration and proliferation and induced apoptosis as shown in vitro. Osthole also attenuated the development of pancreatic cancer in mice by inhibiting tumor-infiltrating M2 macrophages in our study. Additionally, osthole inhibited the polarization of primary bone marrow cells into M2 macrophages and inhibited the expression of MRC1 , CCL22 and TGF-β in the M2 polarization process in vitro. Detection of the related signaling pathways revealed that osthole exerted immunomodulatory effects on M2 macrophages by down-regulating p-STAT6 and the p-ERK1/2-C/EBP β axis. These results indicated that osthole has effective anti-tumor and immunomodulatory effects on pancreatic cancer.
研究领域:
肿瘤学
·
免疫学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2021
·
IF 4.36
Jin-man Liu,Jun-mei Chen,Ming-jun Lin,Fan-chang Wu,Cui-ru Ma,Xue Zuo,Wen-qian Yu,Ming-jun Huang,Jian-song Fang,Wei-rong Li,Qi Wang,Yong Liang
Ethnopharmacological relevance With the features of multiple-components and targets as well as multifunction, traditional Chinese medicine (TCM) has been widely used in the prevention and treatment of various diseases for a long time. During the application of TCM, the researches about bioavailability enhancement of the bioactive constituents in formula are flourishing. Bushen-Yizhi formula (BSYZ), a TCM prescription with osthole (OST) as one of the main bioactive ingredients, have been widely used to treat kidney deficiency, mental retardation and Alzheimer's disease . However, the underlying biological mechanism and compound-enzyme interaction mediated bioavailability enhancement of OST are still not clearly illuminated. Aim of the study The aim of this study is to explore the material basis and molecular mechanism from BSYZ in the bioavailability enhancement of OST. Screening the potential CYP3A4 inhibitors using theoretical prediction and then verifying them in vitro , and pharmacokinetics study of OST in rat plasma under co-administrated of screened CYP3A4 inhibitors and BSYZ were also scarcely reported. Materials and methods Screening of CYP3A4 inhibitors from BSYZ was performed with molecular docking simulation from systems pharmacology database. The screened compounds were verified by using P450-Glo Screening Systems. A multiple reaction monitoring (MRM) mass spectrometry method was established for OST quantification. Male Sprague-Dawley rats divided into four groups and six rats in each group were employed in the pharmacokinetics study of OST. The administrated conditions were group I, OST (20 mg/kg); group II, BSYZ (containing OST 1 mg/mL, at the dose of 20 mg/kg OST in BSYZ); group III, co-administration of ketoconazole (Ket, 75 mg/kg) and OST (20 mg/kg); group IV, co-administration of CYP3A4 inhibitor (10 mg/kg) and OST (20 mg/kg). They were determined by using HPLC-MS/MS (MRM) and statistical analysis was performed using student’s t-test with p < 0.05 as the level of significance. Results 21 potential CYP3A4 inhibitors were screened from BSYZ compounds library. From the results of verification in vitro , we found 4 compounds with better CYP3A4 inhibition efficiency including Oleic acid , 1,2,3,4,6-O-Pentagalloylglucose, Rutin , and Schisantherin B. Under further verification, Schisantherin B exhibited the best inhibitory effect on CYP3A4 (IC 50 = 0.339 μM), and even better than the clinically used drug (Ket) at the concentration of 5 μM. In the study of pharmacokinetics, the area under the curve (AUC, ng/L*h) of OST after oral administration of BSYZ, Ket and Schisantherin B (2196.23 ± 581.33, 462.90 ± 92.30 and 1053.03 ± 263.62, respectively) were significantly higher than that of pure OST treatment (227.89 ± 107.90, p < 0.01). Conclusions Schisantherin B, a profoundly effective CYP3A4 inhibitor screened from BSYZ antagonized the metabolism of CYP3A4 on OST via activity inhibition, therefore significantly enhanced the bioavailability of OST in rat plasma. The results of this study will be helpful to explain the rationality of the compatibility in TCM formula, and also to develop new TCM formula with more reasonable drug compatibility.
研究领域:
民族药理学
·
药物代谢
·
系统药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Fanchang Wu,Mingjun Huang,Xue Zuo,Ruiye Xie,Jinman Liu,Junyu Ke,Weirong Li,Qi Wang,Yong Liang
Alzheimer’s disease (AD) poses a significant threat to the global elderly population. Traditional Chinese medicine (TCM) has been widely utilized in the treatment of AD. Osthole, a bioactive ingredient classified as an “emperor” in many TCM formulas, has been demonstrated to effectively alleviate AD symptoms. However, its low bioavailability in the brain has limited its clinical application. This study aimed to increase the intracerebral bioavailability of osthole by using borneol as a “courier,” based on the classical “Emperor–Minister–Assistant–Courier” model, and to investigate the enhanced pharmacological performance of osthole on AD. Results indicated that a suitable in situ thermosensitive gel matrix for intranasal administration mixed with osthole and borneol consists of P407 at 20%, P188 at 7%, and PEG300 at 6%. The concentration of osthole in the cerebrospinal fluid increased almost tenfold after intranasal administration of osthole/borneol compared to oral administration. Mechanisms showed that borneol as a “courier” opened up intercellular space and loosened the tight junctions of the nasal mucosa by suppressing ZO-1 and occludin expression, thereby expediting the nose-to-brain route and guiding osthole as “emperor” to its target in the brain. Osthole assisted by borneol demonstrated significantly improved efficiency in suppressing cleaved caspase-3 expression, increasing the Bcl-2/Bax ratio, improving T-SOD and catalase expression, reducing malondialdehyde levels, inhibiting neuron apoptosis, and decreasing Aβ levels by inhibiting BACE1 expression to alleviate cognitive impairment in APP/PS1 mice compared to osthole alone. Overall, our study demonstrated that the intracerebral bioavailability of osthole profoundly improved with intranasal administration of osthole/borneol and provided a wider application of TCM for AD treatment with higher intracerebral bioavailability.
研究领域:
药理学
·
神经科学
·
传统中药
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
STRAHLENTHERAPIE UND ONKOLOGIE
·
2023
·
IF 3.1
Huang Hui,Xue Jie,Xie Mei-Lin,Xie Tao
Purpose Osthole possesses anti-tumor activities. However, whether osthole can have a radiosensitization effect on hepatic cancer remains unclear. Here, an HCC-LM3 cells-inoculated subcutaneous transplanted tumor was adopted to explore the effect of osthole. Methods The tumor-bearing mice were treated with 100 mg/kg osthole for 12 days, 4 Gy irradiation twice, or their combination. The tumor volume and weight, lactic acid content, glycolytic enzyme activities, and protein expression of glycogen synthase kinase 3β (GSK-3β), p‑GSK-3β, mammalian target of rapamycin (mTOR), p‑mTOR, AMP-activated protein kinase (AMPK), p‑AMPK, glucose transporter 1/3, and pyruvate kinase M2 were determined. The GSK-3β-overexpressed HCC-LM3 or SK-Hep‑1 cell models were also adopted to verify the effects of osthole on expression of these proteins. Results The tumor volume and weight, lactic acid content, and glycolytic enzyme activities in tumor tissues were lower in the osthole + radiation group than in the radiation group. Moreover, osthole could reverse the radiation-induced increments of p‑GSK-3β/GSK-3β and p‑mTOR/mTOR protein ratios and the expression of glucose transporter 1/3 and pyruvate kinase M2 proteins in tumor tissues, and increase the protein ratio of p‑AMPK/AMPK. The effects of osthole on these glycolysis-related proteins were also observed in GSK-3β-overexpressed HCC-LM3 or SK-Hep‑1 cell models. Conclusion Osthole has a radiosensitizing effect on subcutaneous transplanted hepatocellular carcinoma, and its mechanism may be related to inhibition of GSK-3β/AMPK/mTOR pathway-controlled glycolysis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INDUSTRIAL CROPS AND PRODUCTS
·
2024
·
IF 5.6
Hongli Zhang,Yawen Zhang,Yikun Wang,Xiaowen Wang,Fanrong Zhao,Xu Jing,Jiajun Han
Osthole, a compound found in Cnidum monnieri (L.) Cuss has various pharmacological activities. Ultrasound-assisted extraction of osthole was conducted using natural deep eutectic solvents (NADESs) combined with switchable hydrophilicity solvents (SHSs), and the feasibility of repeated use of recycled extractants was evaluated. NADES (xylose-levulinic acid) was used as an extraction solvent for the green extraction of osthole from Cnidum monnieri (L.) Cuss. Osthole in NADES was finally enriched in heptanoic acid, and due to the heptanoic acid convertibility, osthole can be easily and rapidly isolated and recovered. By adjusting the pH to alkaline, hydrophobic heptanoic acid was switched into a hydrophilic solution to precipitate the osthole. The recovery of osthole was over 90 %, with a yield of 8.35 mg g –1 . After five reuses of recycled NADES to extract new Cnidum monnieri (L.) Cuss powder, the change in osthole yield was non-significant. This novel, eco-friendly, and sustainable extraction method offers a new idea for developing bioactive substances in medicinal plants.
研究领域:
植物化学
·
药用植物学
·
环境科学
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Chun-ge Zhang,Qiao-ling Zhu,Yi Zhou,Yang Liu,Wei-liang Chen,Zhi-Qiang Yuan,Shu-di Yang,Xiao-feng Zhou,Ai-jun Zhu,Xue-nong Zhang,Yong Jin
N-Succinyl-chitosan (NSC) was synthesized and NSC nanoparticles (NPs) with loaded osthole (Ost) (Ost/NSC-NPs) were prepared by emulsion solvent diffusion. Subsequently, low-density lipoprotein (LDL)-mediated NSC-NPs with loaded Ost (Ost/LDL-NSC-NPs) were obtained by coupling LDL with Ost/NSC-NPs through amide linkage. The average particle size of Ost/NSC-NPs was approximately 145 nm, the entrapment efficiency was 78.28%±2.06%, and the drug-loading amount was 18.09%±0.17%. The release of Ost from Ost/NSC-NPs in vitro showed a more evident sustained effect than the native material. The half maximal inhibitory concentration of Ost/LDL-NSC-NPs was only 16.23% that of the free Ost at 24 hours in HepG2 cells. Ost inhibited HepG2 cell proliferation by arresting cells in the synthesis phase of the cell cycle and by triggering apoptosis. Cellular uptake and subcellular localization in vitro and near-infrared fluorescence real-time imaging in vivo showed that Ost/LDL-NSC-NPs had high targeting efficacy. Therefore, LDL-NSC-NPs are a promising system for targeted Ost delivery to liver tumor.
研究领域:
药理学
·
药物递送
·
癌症研究
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2026
·
IF 11.3
Yinlan Xu,Jie Dong,Hejun Liu,Jinmei Zheng,Haonan Guo,Yue Chen,Jialin Wang,Weidong Wu
Network pharmacology and docking identified key compounds and targets. • Osthole and matrine were key bioactives against lead-exposed NSCLC. • Core targets and pathways in lead-driven NSCLC were identified. • In vitro assays confirmed inhibition of NSCLC progression. Background Non-small cell lung cancer (NSCLC) is the predominant subtype of lung malignancy. Accumulating epidemiological evidence demonstrates that environmental lead (Pb) exposure as a critical driver of its initiation and progression. Purpose This study integrated network pharmacology, molecular docking, and in vitro assays to investigate the oncogenic effects of low-concentration Pb on A549 cells and explore the potential therapeutic mechanisms of osthole and matrine. Study design and methods Network pharmacology identified key potential signaling pathways, and molecular docking screened genes with higher binding affinity to the target. MTT assay was used to determine CC 50 , maximum safe concentration (MNTC) and cellular proliferative capacity of Pb, matrine and osthole. Scratch test and Matrigel invasion test detected A549 cell migration and invasion; flow cytometry detected apoptosis, ∆Ψm, ROS and cell cycle. qRT-PCR and Western blot measured gene expression levels. Results Network pharmacology analysis showed that the shared targets of osthole, Pb and NSCLC were mainly enriched in the PI3K/AKT and apoptosis pathways, while matrine, Pb, and NSCLC targets were primarily enriched in cancer metabolism, key hub genes included CDK2, CASP9, IKBKB, PDPK1 and MDM2. Molecular docking demonstrated that osthole showed strong binding to HSD11B1 and CDK2, while matrine exhibited high affinity for DRD4 and CDK2. Considering the essential functions of CDK2 in G1 phase transition, PDPK1, IKBKB, and CASP9 in cell survival, inflammatory signaling, and mitochondrial apoptosis, and MDM2 in p53-mediated cell cycle regulation, phenotypic validation experiments were conducted. Pb exposure significantly enhanced malignant characteristics of A549 cells, including increased migratory and invasive abilities, decreased apoptosis, and a significant reduction in mitochondrial membrane potential. At the molecular level, Pb exposure disrupted cellular homeostasis, as reflected by altered expression of SIRT-1, NRF-1, TGF-β1, Smad, STAT3, STAT1, and mtTFA. Treatment with osthole or matrine effectively reversed all lead-induced abnormalities. Conclusion Taken together, osthole or matrine exerts anti-cancer effects against Pb- promoted NSCLC progression by restoring disrupted cellular homeostasis through modulating cell cycle progression, inhibiting Pb-induced mitochondrial dysfunction and stress-related signaling imbalance. Download: Download high-res image (130KB) Download: Download full-size image
✓ 已验证
DOI
PubMed
高影响因子
BRITISH JOURNAL OF NUTRITION
·
2026
·
IF 3.1
Xin Yu,Renzhi Liu,Futao Jing,Zhengxu Chen,Mingxiang Lu,Yaobing Li,Luqing Pan
Dietary plant-derived bioactive compounds for enhancing physiological health are becoming a prevalent strategy for antibiotic alternatives. Our study revealed the effects and underlying mechanism of Osthole (OST) and OST-Tetramethylpyrazine (TMP) compound in Litopenaeus vannamei based on network pharmacology, molecular docking and a 42-day feeding trial verification. The results illustrated that OST and OST-TMP compound significantly improved the survival rate (SR), weight gain rate (WGR), specific growth rate (SGR) and feed conversion ratio (FCR), strengthening the growth performance of L. vannamei. Meanwhile, combining the predictive results from network pharmacology and molecular docking, we propose that OST and TMP synergistically enhance the antioxidant defense capacity of shrimp through the synergistic Nrf2 signaling pathway, thereby enhancing the expression of total antioxidant capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Furthermore, OST-TMP exhibited a significant increase of the immune response in hemocyte and intestine of shrimp, increasing the expression of antimicrobial peptide and lysozyme, and suppressing the inflammatory factors, via the synergistic (NF-κB) and complementary targets predicted by network pharmacology. Additionally, gut microbiota composition of L. vannamei was improved, and the dominant genera were correlated with intestinal immune in the compound groups. For the first time, we elucidated the mechanism of plant-derived bioactive compounds mediating physiological health in aquatic animals via a new strategy of network pharmacology-molecular docking-experimental verification, and identified the optimal addition amount of OST-TMP in shrimp (150 mg/kg TMP + 20 mg/kg OST), providing a technical safeguard for the animal health and the safety of aquatic products.
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）