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Yuusuke Tashiro, Ryo Sakai, Tomoko Hirose-Sugiura, Yukio Kato, Hirotaka Matsuo, Tappei Takada, Hiroshi Suzuki, Toshiaki Makino
(1) Background: Crude drugs used in traditional Japanese Kampo medicine or folk medicine are major sources of new chemical entities for drug discovery. We screened the inhibitory potential of these crude drugs against urate transporter 1 (URAT1) to discover new drugs for hyperuricemia. (2) Methods: We prepared the MeOH extracts of 107 different crude drugs, and screened their inhibitory effects on URAT1 by measuring the uptake of uric acid by HEK293/PDZK1 cells transiently transfected with URAT1. (3) Results: We found that the extract of the dried mature fruit of Cnidium monnieri inhibited urate uptake via URAT1...
November 1, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Wen-Bo Zhou, Xin-Xin Zhang, Yun Cai, Wu Sun, Hao Li
Tamoxifen (TMX) is an antiestrogen drug that is used in the treatment and prevention of all stages of estrogen-dependent breast cancer. Adverse effects of TMX include hepatotoxicity. In this study, we investigated the therapeutic effects of osthole, isolated from medicinal plants especially Fructus Cnidii, on TMX-induced acute liver injury in mice. Mice were injected with osthole (100 mg/kg, ip) or vehicle, followed by TMX (90 mg/kg, ip) 24 h later. We showed that a single injection of TMX-induced liver injury and oxidative stress...
October 12, 2018: Acta Pharmacologica Sinica
Gui-Jie Li, Hou-Jiu Wu, Yu Wang, Wei-Lun Hung, Russell L Rouseff
A synergistic combination of analytical techniques was developed for the simultaneous determination of the three most biologically active chemical families in citrus juices: methoxylated flavones, coumarins, and furanocoumarins. No rapid methodology has been available to determine them together. A solid phase extraction concentrated these groups and a ternary reverse phase HPLC gradient completely resolved them from other juice components. Two coumarins, isomeranzin and osthole, were identified in a sweet orange (C...
January 15, 2019: Food Chemistry
Fei Yao, Lurong Zhang, Guorong Jiang, Min Liu, Guoqiang Liang, Qin Yuan
Osthole has been demonstrated to have antitumor activity. Previous studies by our group indicated that osthole effectively inhibited tumor growth in hepatocellular carcinoma (HCC) through the induction of apoptosis and enhancement of antitumor immune responses in mice. The importance of angiogenesis in the proliferation, invasion and metastasis of tumor cells in HCC is well established. The present study aimed to investigate the effects of osthole on angiogenesis in an orthotopic mouse model of HCC. Orthotopic HCC in mice was established, and osthole at 61, 122 and 244 mg/kg was administered intraperitoneally once daily to the tumor-bearing mice for 14 consecutive days...
October 2018: Oncology Letters
Huilong Yuan, Shuai Ouyang, Runan Yang, Shunhua Li, Yingxin Gong, Lifang Zou, Tianyu Jia, Shanhong Zhao, Bing Wu, Zhihua Yi, Hui Liu, Liran Shi, Lin Li, Yun Gao, Guilin Li, Hong Xu, Shuangmei Liu, Chunping Zhang, Shangdong Liang
Diabetes mellitus (DM) is considered the primary cause of neuropathic pain. Osthole (7-methoxy-8[3-methylpent 2-enyl]coumarin) is a component extracted from Cnidium monnieri (L.) cusson plant seeds and has anti-inflammatory and anti-oxidative properties. The aim of the present study was to investigate the effects of osthole on diabetic neuropathic pain (DNP) involving the P2X4 receptor on satellite glial cells (SGCs) in the dorsal root ganglia (DRG) of type 2 diabetic rats. These data showed that the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) in DM rats were lower than those in control rats...
September 2018: Brain Research Bulletin
You-Jiang Yu, Ji-Lin Ye, Jian-Ming Peng, Ai-Lian Wu, Dong-Yan Wang, Yan-Qing Liu
OBJECTIVE: To explore the effects of Osthole on apoptosis of HL-60 cells induced by tumor necrosis factor related apoptosis inducing ligand (TRAIL) and its possible mechanism. METHODS: The proliferative inhibition of HL-60 cells treated with different concentrations of Osthole, TRAIL alone and Osthole combined with TRAIL was measured by MTT assay. The HL-60 cells were treated with Osthole, TRAIL alone and Osthole combined with TRAIL at the concentration<IC50 value, i...
August 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Xiao-Ying Sun, Li-Lan Sun, Hang Qi, Qin Gao, Gong-Xin Wang, Ning-Ning Wei, KeWei Wang
Coumarin osthole is a dominant bioactive ingredient of the natural Cnidium monnieri plant commonly used for traditional Chinese herbal medicines for therapies and treatments including antipruritus and antidermatitis. However, the molecular mechanism underlying the action of osthole remains unclear. In this study, we report that osthole exerts an antipruritic effect through selective inhibition of Ca2+ -permeable and thermosensitive transient receptor potential vanilloid 3 (TRPV3) cation channels that are primarily expressed in the keratinocytes of the skin...
October 2018: Molecular Pharmacology
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...
July 2018: Journal of Pharmacological Sciences
Yiyi Jin, Jianchang Qian, Xin Ju, Xiaodong Bao, Li Li, Suqing Zheng, Xiong Chen, Zhongxiang Xiao, Xuemei Chen, Weiwei Zhu, Weixin Li, Wencan Wu, Guang Liang
Inflammation is a key factor in the pathogenesis of ALI. Therefore, suppression of inflammatory response could be a potential strategy to treat LPS-induced lung injury. Osthole, a natural coumarin extract, has been reported to protect against acute kidney injury through an anti-inflammatory mechanism, but its effect on ALI is poorly understood. In this study, we investigated whether osthole ameliorates inflammatory sepsis-related ALI. Results from in vitro studies indicated that osthole treatment inhibited the LPS-induced inflammatory response in mouse peritoneal macrophages through blocking the nuclear translocation of NF- κ B...
2018: Mediators of Inflammation
Dingkang Chen, Zhiyun Du, Zhirong Lin, Ping Su, Hanyi Huang, Zhirong Ou, Wanyi Pan, Shiya Huang, Kun Zhang, Xi Zheng, Li Lin, Lanyue Zhang
Angelica pubescens, a plant of the family Umbelliferae, has been widely used as traditional Chinese medicine for the treatment of many diseases. However, there has been minimal modern research focused on the pharmacological activity of oils extracted from Angelica pubescens, in particular, the potential anti-photoaging effects. Therefore, in the present study, we analyzed the chemical composition of Angelica pubescens oil (AO) and evaluated its bioactivity against photoaging in ultraviolet (UV) -B radiation-induced hairless mice...
October 2018: Chemistry & Biodiversity
Yilin Che, Juan Li, Zongjuan Li, Jing Li, Shuai Wang, Ying Yan, Kun Zou, Lijuan Zou
Osthole (7‑methoxy‑8‑isopentenoxycoumarin) is an O‑methylated coumarin, originally extracted from Chinese herbal medicine. It has been demonstrated that osthole has antitumor effects in various cancer cells in vitro. The present study assessed the effects of osthole on the regulation of cervical cancer cell viability, apoptosis, and radiation sensitization. HeLa, SiHa, C‑33A and CaSki cervical cancer cell lines were cultured and treated with osthole and/or irradiation and then subjected to 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑-diphenyl‑tetrazolium bromide cell viability, colony formation, apoptosis, acridine orange/ethidium bromide fluorescence staining, wound‑healing, Transwell migration and invasion, immunofluorescence, Comet and western blot assays...
August 2018: Oncology Reports
Yingjia Yao, Xicai Liang, Yue Shi, Ying Lin, Jingxian Yang
In our previous study, we found that osthole could promote the ability of proliferation and differentiation in normal neural stem cells (NSCs) under normal condition. Then, we used tert-butyl hydroperoxide (t-BHP) to establish the model of senescence NSCs to detect the effects of osthole. Interestingly, the immunofluorescence results showed that osthole (100 μM) could enhance the ability of proliferation and differentiation, and CCK-8 assay results showed that osthole could also enhance the cell viabilities...
August 2018: Cellular Reprogramming
Qi Zhao, Jia-Le Zhang, Fei Li
LC-MS-based metabolomics could have a major impact in the study of natural products, especially in its metabolism, toxicity and activity. This review highlights recent applications of metabolomics approach in the study of metabolites and toxicity of natural products, and the understanding of their effects on various diseases. Metabolomics has been employed to study the in vitro and in vivo metabolism of natural compounds, such as osthole, dehydrodiisoeugenol, and myrislignan. The pharmacological effects of natural compounds and extracts were determined using metabolomics technology combined with diseases models in animal, including osthole and nutmeg extracts...
August 2018: Natural Products and Bioprospecting
Dongfeng Zhao, Qiang Wang, Yongjian Zhao, Hao Zhang, Nannan Sha, Dezhi Tang, Shufen Liu, Sheng Lu, Qi Shi, Yan Zhang, Yufeng Dong, Yongjun Wang, Bing Shu
OBJECTIVE: This study was to determine the bone protective effects and underlying mechanisms of Osthole (OT) in ovariectomized (OVX) mice. We found that the inhibitory effects of OT on receptor activator of nuclear factor kappa-B ligand (RANKL)-activated osteoclastogenesis are responsible for its bone protective effects in OVX mice. METHODS: Eight-week-old mice were ovariectomized and OT (10 mg/kg/d) was intraperitoneally administrated to OVX mice 7 days after the surgery and were sacrificed at the end of the 3 months...
June 25, 2018: Menopause: the Journal of the North American Menopause Society
Xingxing Dai, Ran Wang, Zhimin Wu, Shujuan Guo, Chang Yang, Lina Ma, Liping Chen, Xinyuan Shi, Yanjiang Qiao
Borneol (BO) and menthol (MEN) are two widely used natural permeation enhancers in the transdermal drug delivery system. In previous studies, their permeation enhancement effects and mechanisms of action on the hydrophobic drug osthole (logP = 3.8) and hydrophilic drug 5-fluorouracil (logP = -0.9) have been studied. In this study, ligustrazine (LTZ), whose logP is 1.3, was used as a model drug to provide a comprehensive understanding of the influence of its logP on the permeation-enhancing effects of BO and MEN...
November 2018: Chemical Biology & Drug Design
Jin-Cheng Liu, Lei Zhou, Feng Wang, Zong-Qi Cheng, Chen Rong
The present study was designed to elucidate whether the mechanism by which osthole decreases collagenI/III contents and their ratio is regulating the TGF-β/Smad signaling pathway in TGF-β1-overexpressed mouse cardiac fibroblasts (CFs). These CFs were cultured and treated with different concentrations of osthole. Our results showed that the TGF-β1 expression in the CFs transfected with that the recombinant expression plasmids pcDNA3.1(+)-TGF-β1 was significantly enhanced. After the CFs were treated with 1...
May 2018: Chinese Journal of Natural Medicines
Chaojie Sun, Yun Gui, Rongfeng Hu, Jiayi Chen, Bin Wang, Yuxing Guo, Wenjie Lu, Xiangjiang Nie, Qiang Shen, Song Gao, Wenyou Fang
The study was performed aiming to enhance the solubility and oral bioavailability of poorly water-soluble drug osthole by formulating solid self-microemulsifying drug delivery system (S-SMEDDS) via spherical crystallization technique. Firstly, the liquid self-microemulsifying drug delivery system (L-SMEDDS) of osthole was formulated with castor oil, Cremophor RH40, and 1,2-propylene glycol after screening various lipids and emulsifiers. The type and amount of polymeric materials, good solvents, bridging agents, and poor solvents in S-SMEDDS formulations were further determined by single-factor study...
July 2018: AAPS PharmSciTech
Weiling Chen, Jiajia Li, Zhenping Sun, Chunyu Wu, Jiao Ma, Jianyi Wang, Sheng Liu, Xianghui Han
ETHNOPHARMACOLOGICAL RELEVANCE: Wenshen Zhuanggu Formula (WSZG) is a traditional Chinese medicine (TCM) prescription used in clinics for adjuvant treatment of breast cancer bone metastases in Longhua Hospital in China. WSZG has been reported to decrease the risk of bone metastases and alleviate the severity of bone lesions in a breast cancer xenograft model. AIM OF THE STUDY: The present study aimed at investigating the pharmacokinetic behaviors of six coumarins in normal and breast cancer bone-metastatic mice following oral administration of WSZG extract...
October 5, 2018: Journal of Ethnopharmacology
Jing-Jing Zhu, Jian-Guo Jiang
Coumarins are fused benzene and pyrone ring systems with a wide spectrum of bioactivities, including antitumor, anti-inflammation, antiviral, and antibacterial effects. In this paper, the current development of coumarin-based drugs is introduced, and their structure-activity relationship is discussed by reviewing the relevant literature published in the past 20 years. Coumarin molecules can be customized by the target site to prevent systemic side effects by virtue of structural modification. The ortho-phenolic hydroxyl on the benzene ring has remarkable antioxidant and antitumor activities...
May 11, 2018: Molecular Nutrition & Food Research
Renguo Xu, Zhen Liu, Jiande Hou, Tao Huang, Ming Yang
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...
2018: Cellular & Molecular Biology Letters
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