EUROPEAN JOURNAL OF PHARMACOLOGY
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2019
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IF 3.17
Yasi Mo,Yong Wu,Xin Li,Hui Rao,Xianxiang Tian,Danni Wu,Zhenpeng Qiu,Guohua Zheng,Junjie Hu
Hepatocellular carcinoma (HCC) is one of the most common fatal malignancies worldwide. Inhibition of the lipogenic enzymes involved in hepatic de novo lipogenesis can both effectively restrain proliferation of HCC cells in vitro and reduce the risk of hepatocarcinogenesis in vivo . Although a natural coumarin derivative osthole shows efficacy in suppressing cell proliferation and inducing apoptosis in cultured hepatoma cells and HCC xenograft tumors, the molecular mechanism by which osthole delays hepatocellular malignant transformation during lipogenesis-driven hepatocarcinogenesis remains unknown. Here, we evaluate the efficacy of osthole in a rapid HCC mouse model featuring excessive levels of hepatic steatosis established via hydrodynamic transfection of activated forms of AKT and c-Met proto-oncogenes. Moreover, human hepatoma cell lines were employed for in vitro assessment. Hematoxylin and eosin staining , immunoblotting and immunohistochemistry were applied for mechanistic investigations. The results revealed that if osthole was administered in the early stage of AKT/c-Met-driven HCC, it led to disease stabilization. Moreover, osthole alleviated hepatic steatosis in the AKT/c-Met mice. Further evidence at the molecular level suggested that osthole reduced the expression of phosphor-extracellular signal-regulated kinase 1/2 (ERK1/2), proliferating cell nuclear antigen (PCNA) and Ki67 in livers of the AKT/c-Met mice. Mechanically, osthole efficiently repressed the phospho-AKT (Thr308) / ribosomal protein S6 (RPS6) / fatty acid synthase (FASN) signaling both in mice and in vitro . Altogether, this study suggests that osthole exerts its antilipogenic and antiproliferative efficacy by suppressing the AKT/FASN axis and ERK phosphorylation, which contributes to its capacity to delay hepatocarcinogenesis.
研究领域:
癌症研究
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分子生物学
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药理学
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肝病学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2022
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IF 5.895
Ruige Yang,Zhiyan Liu,Meiyue Han,Liping Cui,Yong Guo
To discover novel natural-product-based insecticide candidates, herein, a variety of osthole-derived N-benzoylthioureas were synthesized and assessed for their insecticidal activities against three insect pests. An insecticidal assay showed that most of the target osthole-derived N-benzoylthioureas displayed a more potent and broad-spectrum insecticidal effect than the parent osthole after the introduction of N-benzoylthioureas on the C-3′ position of osthole. Compound B24 displayed the most potent growth inhibitory (GI) effect on Mythimna separata Walker, with a final corrected mortality rate of 82.1% when treated with a concentration of 1 mg/mL, which was 1.64- and 1.53-fold higher in comparison to osthole and the botanical insecticide toosendanin, respectively. Compounds B22, B23, and B25 displayed a more promising aphicidal effect on Myzus persicae Sulzer, and their LD50 values were 0.015, 0.017, and 0.019 μg/larvae, respectively, superior to the commercially available insecticide rotenone (0.024 μg/larvae). Derivatives B19, B20, B23, and B25 displayed more potent larvicidal activity against Plutella xylostella Linnaeus, with LC50 values of 0.22, 0.26, 0.15, and 0.30 mg/mL, respectively, exceeding that of rotenone (0.37 mg/mL). Furthermore, both compounds B19 and B23 against P. xylostella were found to be more effective than rotenone in a control efficacy assay under greenhouse conditions. The structure–activity relationship (SAR) suggested that osthole-derived N-benzoylthioureas are more active in most cases when the R group is an electron-withdrawing group than when it is an electron-donating group, especially for halogenated groups. Additionally, the potent compounds B19 and B23 possessed good selectivity and were less toxic to non-target organisms. This study suggests that these osthole-derived N-benzoylthioureas could be further studied in depth as eco-friendly natural product pesticides in crop protection.
研究领域:
昆虫学
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有机化学
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农药科学
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DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
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2024
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IF 2.3
Shu-Hang Li,Meng-Ying Li,Tao-Tao Yuan,Guo-Wei Wang,Jian-Bin Zeng,Zhimian Shi,Jian-Hang Liu,Jun-Cheng Su
Osthole (also known as Osthol) is the main anti-inflammatory coumarin found in Cnidium monnieri and severs as the exclusive quality-controlled component according the Chinese Pharmacopoeia. However, its underlying anti-inflammatory mechanism remains unknown. In this study, we demonstrated that Osthole treatment significantly inhibited the generation of TNF-α, but not IL-6 in the classical LPS-stimulated RAW264.7 macrophage model. In addition, LPS induced the activation of both MAPK and NF-κB signalling pathways, of which the former was dose-dependently restrained by Osthole via suppressing the phosphorylation of JNK and P38 proteins, while the phosphorylation of IκB and P65 proteins remained unaffected. Interestingly, Osthole dose-dependently up-regulated the expression of the key cholinergic anti-inflammatory pathway regulator α7nAChR, and the TNF-α inhibition effect of Osthole was also significantly alleviated by the treatment of α7nAChR antagonist methylbetaine. These results demonstrate that Osthole may regulate TNF-α by promoting the expression of α7nAChR, thereby activate the vagus nerve-dependent cholinergic anti-inflammatory pathway.
研究领域:
药理学
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免疫学
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分子生物学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
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2021
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IF 5.34
Zheng Niu,Min Fu,Yuan Li,Huanhuan Ren,Xuanyu Zhang,Li Yao
Background Pulmonary vascular remodeling is the key pathological feature of pulmonary arterial hypertension (PAH) characterized by a pattern of lipid-related insulin resistance(IR), hormonal derangements and metabolic reprogramming. Our previous studies have demonstrated osthole as natural coumarin compound derived from traditional Chinese medicine is a promising agent for the treatment of pulmonary vascular remodeling in PAH. Purpose The present study sought to delineate lipid metabolic modulatory mechanism of osthole against pulmonary vascular remodeling by employing an interdisciplinary strategy. Methods Rat model with PAH induced with MCT and PASMCs proliferation model induced with PDGF-BB were established in this study. Serum and lung tissues were used to lipid-related IR, hormone related indexes, pulmonary vascular remodeling analysis. Then, lipid metabolic gene, key enzymes , metabolites and cell proliferation indexes were examined to investigate metabolic regulatory mechanism in vivo and vitro model of PAH. Results Osthole significantly showed improvement of lipid-related IR and hormone dysregulation in rats with PAH evidenced by elevating testosterone, androgen receptor and cyclic guanosine monophosphate (cGMP), inhibiting phosphodiesterase-5(PDE-5), modulating lipid-related IR indexes total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), triglyceride (TG)/HDL-C ratio. Additionally, osthole limited key metabolic gene and enzymes to inhibit accumulation of decadienyl-l-carnitine in lipid metabolism , thus to promote oxidative phosphorylation and ATP production through inhibition of miRNA-22–3p, fatty acid translocase (CD36), fatty acid synthase (FAS), phospholipase A2 (PLA2), carnitine palmitoyltransferase 1A (CPT1A), hexokinase 2 (HK2), activation of metabolic switch isocitrate dehydrogenase 3α (IDH3α), NADH dehydrogenase 1 (ND1). We found for the first time miRNA-22–3p modulated PASMCs proliferation and vascular remodeling by regulating lipid metabolism reprogramming. Those modifications uncovered therapeutic mechanism of osthole against pulmonary vascular remodeling. Conclusion Our findings revealed the function of miRNA-22–3p in PASMCs and demonstrated a novel mechanism that miRNA-22–3p as a regulator can be targeted by osthole to greatly restore dysregulated lipid metabolism thus to alleviate pulmonary vascular remodeling in PAH, which provides novel insight into the potential therapeutic target for PAH, further highlights the development potential of osthole derived new drug against PAH.
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DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR LIQUIDS
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2021
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IF 6.165
Tianxiang Yin,Jieyu Wu,Jing Yuan,Xiaoyong Wang
Recently, a new type of drug delivery system termed therapeutic deep eutectic solvent (THEDES) was developed to increase the solubility and/or permeation ability of drugs, where an active pharmaceutical ingredient (API) was included as the component in the eutectic system. In this work, we designed a new THEDES based on two well-known active pharmaceutical ingredients (APIs), osthole and paeonol. The macroscopic properties and the microscopic structures were investigated by various techniques. The THEDES has been proven to retain the bioactivities of pure APIs and shows better solubility than pure APIs in water. Furthermore, an O/W microemulsion formulation was constructed with THEDES as the oil phase and TX-100 and 1,2-propanediol serving as the surfactant and the co-surfactant respectively, which showed good stability and an average size of 50 nm. The permeation behavior of the THEDES was compared to that of pure APIs in gel form, and the results suggested that the THEDES had a better permeation ability than pure APIs at the same concentrations. Hence, a multifunctional drug delivery system with great simplicity and convenience was demonstrated herein, showing great potential application in the transdermal delivery systems.
研究领域:
药剂学
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药物递送系统
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药物化学
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DOI
高影响因子
Chinese Journal of Natural Medicines
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2020
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IF 2.014
Li YAO,Yu-Xia YANG,Hui CAO,Huan-Huan REN,Zheng NIU,Ling SHI
Osthole is observed to have the capacity to treat pulmonary arterial hypertension (PAH) in rats, but molecular mechanism is still unknown. The present study aims to discover therapeutic targets and explore therapeutic mechanism of osthole against PAH from metabolic perspective. A rat model with PAH was successfully established with MCT, following osthole administration, then untargeted metabolomics assay was performed using UPLC-Q-TOF-MS to identify differential metabolites and associated metabolic pathways, at last mechanism investigation was done by qRT-PCR, Western blot and ELISA. Differential metabolites characterized in rats with PAH were mostly assigned to sphingolipid metabolism, synthesis of unsaturated fatty acids, glycolysis, nucleotide metabolism, steroid hormone biosynthesis. Furthermore, osthole reversed high level of S1P by modulating metabolic enzyme Sphk1 in rats with PAH. In addition, osthole inhibited the expression of Sphk1 by downregulating microRNA-21, phosphorylation of Akt, phosphorylation of mTOR in vivo and in vitro . These results demonstrated that metabolomics is a promising approach to discover potential drug target for PAH treatment. Importantly, our findings further elucidated therapeutic mechanism of osthole, a natural product, having a role of metabolic regulator to potentially treat PAH by targeting inhibition of Sphk1/S1P via microRNA-21-PI3K/Akt/mTOR signal pathway. Altogether, this discovery paves a critical foundation for enabling osthole to be a candidate compound to treat PAH.
研究领域:
药理学
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心血管疾病
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代谢紊乱
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产品关联
DOI
PubMed
高影响因子
Oncology Letters
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2021
·Vol. 22
·期 4
·1-9
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IF 2.967
Xing-Hua Zhou,Jian Kang,Zhen-Dong Zhong,Yue Cheng
Endoplasmic reticulum stress (ERS) and autophagy are important pathways, which induce apoptosis of tumor cells. Osthole has been demonstrated to exert anticancer effects via the induction of apoptosis in several human colon cancer lines, but the mechanism underlying its involvement in the induction of ERS and autophagy in the human HT‑29 colorectal cancer cell line remains unknown. The present study aimed to identify the possible signaling pathways involved in osthole‑induced apoptosis of HT29 cells. Methodologically, colony formation and Cell Counting Kit‑8 assays were used to assess cell proliferation and viability, respectively, while flow cytometry was performed to investigate apoptosis. Signaling pathways, including apoptosis, autophagy and ERS, were also investigated in the HT‑29 cell line using western blot analysis. The results demonstrated that osthole inhibited cellular proliferation and viability in a dose‑dependent manner. In addition, osthole induced the expression level of proteins associated with mitochondria‑mediated cell apoptosis, autophagy and ERS. The association between autophagy and ERS in osthole‑induced apoptosis in the HT‑29 cell line was further clarified. Inhibiting cell autophagy with the inhibitor, 3‑methyladenine, suppressed osthole‑induced cell apoptosis and enhanced osthole‑induced ERS. By contrast, alleviating ERS with the inhibitor, 4‑phenylbutyric acid attenuated osthole‑induced cell apoptosis and autophagy. In conclusion, osthole could significantly suppress the proliferation and viability of the HT‑29 colorectal cancer cell line and induce cell apoptosis via autophagy and ERS. Furthermore, ERS may play a more important role in osthole‑induced cell apoptosis.
研究领域:
肿瘤学
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细胞生物学
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药理学
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DOI
PubMed
高影响因子
Coatings
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2026
·Vol. 16
·期 4
·499
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IF 3.4
Yue Fan,Shiyu Jin,Yumeng Dong,Feiyang Wang,Junyan Yao,Juyi Yang,Lu Zhang,Shuyi Wang,Cheng Wang,Jing Bai,Feng Xue,Chenglin Chu,Junqing Ma,Yanbin Zhao,Paul K. Chu
HighlightsA PCL/nanocapsule coating was developed on Mg alloy by spin-coating.Pluronic F127 modified nanocapsules enabled ultrasound-triggered drug release.The coating enhanced corrosion resistance and enabled self-healing at 50 °C.The coating showed antibacterial effect and promoted osteogenic differentiation.Magnesium alloys exhibit promising application prospects in medical orthopedic implants. However, their practical applications are limited by rapid corrosion, suboptimal osseointegration, and implant-related infections. Although conventional drug-eluting polymer coatings can provide various biological functions, the uncontrolled drug release often compromises long-term therapeutic efficacy. In this study, a self-healing Mg-poly(ε-caprolactone) (PCL)@OHF coating is designed and prepared on WE43 Mg by spin coating to achieve ultrasound-triggered release of osthole. OHF consists of osthole-loaded hollow mesoporous silica nanoparticles (HMSs) modified with Pluronic F127. Drug release studies show that the nanocapsules respond to ultrasound stimulation, with the cumulative release increasing from 39.94% to 75.93% after 7 days. Furthermore, the coating demonstrates intrinsic self-healing capacity upon thermal treatment at 50 °C. Electrochemical and immersion tests reveal that the composite coating provides good barrier protection for the WE43 Mg alloy, evidenced by a decrease in corrosion current density from 2.04 × 10−6to 5.94 × 10−7A/cm2. In vitro biological assays confirm the antibacterial efficacy againstStaphylococcus aureusandEscherichia coli, as well as the ability to promote osteogenic differentiation. The results reveal a surface modification strategy that combines self-healing, anticorrosion, and on-demand drug release, offering a promising approach for advanced orthopedic implants.
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DOI
高影响因子
Chinese Herbal Medicines
·
2024
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IF 4.7
Shuang He,Xiaoling Liang,Weixiong Chen,Yangji Nima,Yi Li,Zihui Gu,Siyue Lai,Fei Zhong,Caixiong Qiu,Yuying Mo,Jiajun Tang,Guanyi Wu
Objective This study aims to elucidate the therapeutic potential of osthole for the treatment of atopic dermatitis (AD), focusing on its ability to alleviate chronic pruritus (CP) and the underlying molecular mechanisms. Methods In this study, we investigated the anti-inflammatory effects of osthole in both a 2,4-dichloronitrobenzene (DNCB)-induced AD mouse model and tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) stimulated human immortalized epidermal (HaCaT) cells. The anti-itch effect of osthole was specifically assessed in the AD mouse model. Using methods such as hematoxylin and eosin (HE) staining, enzyme-linked immunosorbent assay (ELISA), western blot (WB), quantitative real-time PCR (qRT-PCR), and immunofluorescence staining. Results Osthole improved skin damage and clinical dermatitis scores, reduced scratching bouts, and decreased epidermal thickness in AD-like mice. It also reduced the levels of interleukin (IL)-31 and IL-31 receptor A (IL-31 RA) in both skin tissues and HaCaT cells. Furthermore, Osthole suppressed the protein expression levels of phosphor-p65 (p-p65) and phosphor-inhibitor of nuclear factor kappa-Bα (p-IκBα). Meanwhile, it increased the protein expression levels of peroxisome proliferator-activated receptor α (PPARα) and PPARγ in HaCaT cells. Conclusion These findings indicated that osthole effectively inhibited CP in AD by activating PPARα, PPARγ, repressing the NF-κB signaling pathway, as well as the expression of IL-31 and IL-31 RA.
研究领域:
药理学
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免疫学
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皮肤病学
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DOI
高影响因子
Oxidative Medicine and Cellular Longevity
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2021
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IF 6.543
Yilei Song,Xiangyu Wang,Xingrong Wang,Jianze Wang,Qiulian Hao,Jifu Hao,Xueqin Hou
Osthole (OST) is a natural coumarin compound that exerts multiple pharmacologic effects. However, the poor water solubility and the low oral absorption of OST limit its clinical application for the treatment of neurologic diseases. A suitable preparation needs to be tailored to evade these unfavourable properties of OST. In this study, an OST nanoemulsion (OST-NE) was fabricated according to the pseudoternary phase diagram method, which was generally used to optimize the prescription in light of the solubility of OST in surfactants and cosurfactants. The final composition of OST-NE was 3.6% of ethyl oleate as oil phase, 11.4% of the surfactant (polyethylene glycol ester of 15-hydroxystearic acid: polyoxyethylene 35 castor ), 3% of polyethylene glycol 400 as cosurfactant, and 82% of the aqueous phase. The pharmacokinetic study of OST-NE showed that the brain-targeting coefficient of OST was larger by the nasal route than that by the intravenous route. Moreover, OST-NE inhibited cell death, decreased the apoptosis-related proteins (Bax and caspase-3), and enhanced the activity of antioxidant enzymes (superoxide dismutase and glutathione) in L-glutamate-induced SH-SY5Y cells. OST-NE improved the spatial memory ability, increased the acetylcholine content in the cerebral cortex, and decreased the activity of acetylcholinesterase in the hippocampus of Alzheimer’s disease model mice. In conclusion, this study indicates that the bioavailability of OST was improved by using the OST-NE via the nasal route. A low dose of OST-NE maintained the neuroprotective effects of OST, such as inhibiting apoptosis and oxidative stress and regulating the cholinergic system. Therefore, OST-NE can be used as a possible alternative to improve its bioavailability in the prevention and treatment of Alzheimer’s disease.
研究领域:
药剂学
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神经科学
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药理学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
CELLULAR & MOLECULAR BIOLOGY LETTERS
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2018
·Vol. 23
·期 1
·1-11
·
IF 1.291
Xu Renguo,Liu Zhen,Hou Jiande,Huang Tao,Yang Ming
Background Osthole is a natural product that has multiple bioactive functions and has been reported to exert potent immunosuppressive effects. However, the therapeutic effect of osthole on arthritis has not been explored. In the present study, a collagen-induced arthritis rat model, IL-1β-stimulated SW982 cells, and RA-like fibroblast-like synoviocytes (FLS) were employed to investigate the effect and possible mechanism of osthole on arthritis in vivo and in vitro.Results 20 and 40 mg/kg osthole significantly alleviated collagen-induced arthritic symptoms based on histopathology and clinical arthritis scores, and improved erosion using HE staining. 20 and 40 mg/kg osthole decreased the level of IL-1β, TNF-α and IL-6 in rats and ameliorated oxidative stress in serum evaluated using ELISA kits. In addition, treatment with 50 and 100 μM osthole for 48 h inhibited 10 ng/ml IL-1β-stimulated proliferation and migration of SW982, and significantly inhibited the expression of matrix metalloproteinases, such as MMP-1, MMP-3 and MMP-13, as detected by western blot. 50 and 100 μM osthole also blocked the generation of IL-6 and TNF-α in IL-1β-stimulated SW982 cells. The NF-κB and MAPK pathways were also inhibited by osthole in IL-1β-treated SW982 cells.Conclusion These results collectively demonstrated that osthole improves collagen-induced arthritis in a rat model and IL-1β-treated SW982 cells through inhibiting inflammation and cellular stress in vivo and in vitro, and osthole might be a promising therapeutic agent for RA.
研究领域:
药理学
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免疫学
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风湿病学
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产品关联
DOI
PubMed
高影响因子
NANO
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2020
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IF 1.566
Ning Wang,Xuefang Yang,Haojiang Wang,Liping Xie,Weihua Jia,Wei Bian,Martin M. F. Choi
A fluorescence probe has been synthesized for the detection of osthole using the nitrogen-doped carbon dots (NCDs) as shown in Fig. 1. The NCDs were fully characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), x-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR). Under the optimal experimental conditions, the NCDs fluorescence probe was highly selective and sensitive to osthole. The linear response range for osthole was 5.0–75 μ M with a detection limit of 38 nM. The mechanism of the interaction of osthole and NCDs was discussed. The fluorescence probe has been applied to the analysis of biological samples. The as-synthesized NCDs with high fluorescence intensity, low toxicity and good biocompatibility were applied to cell imaging.
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高影响因子
危险品化学品经营许可证（带存储）