Frontiers in Pharmacology
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2025
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IF 4.8
Yan Liu,Feng Qi,Lun-Jian Xiang,Zhu-Jun Yi,Sheng-Wei Li
Background: Donation after circulatory death (DCD) livers are limited by mandatory warm ischemia and are more susceptible to ischemia‒reperfusion injury (IRI). Inflammation and oxidative stress play key roles in the development of hepatic IRI, and Rutaecarpine (Rut) has anti-inflammatory and anti-oxidative stress effects. The aim of this study was to investigate whether Rut can alleviate hepatic IRI in liver transplantation (LT) and to explore the underlying mechanisms.Methods: Rat DCD LT and oxygen-glucose deprivation/reoxygenation (OGD/R) cell models were established to clarify the effect of Rut on hepatic IRI. The key molecules involved in the hepatoprotective effects of Rut were identified through joint analysis of data from LT patients and drug targets. The target was further validated by in silico, in vivo and in vitro experiments.Results: Rut significantly alleviated liver dysfunction, pathological injury, and apoptosis and improved the survival rate of the rats subjected to LT. In addition, Rut significantly inhibited inflammatory response and oxidative stress. Rut also had similar effects on OGD/R-induced hepatocyte injury. Mechanistically, bioinformatics analysis and in vivo and in vitro experiments revealed that PDE4B may be a key target by which Rut exerts its protective effect, and molecular docking and cellular thermal shift assay confirmed this result. The function of PDE4B was studied via gene intervention technology, and the results showed that PDE4B can aggravate hepatic IRI. Furthermore, PDE4B overexpression abrogated the protective effect of Rut on the liver in LT.Conclusion: Rut alleviates hepatic IRI by targeting PDE4B to inhibit inflammation and oxidative stress. These findings highlight the potential of Rut as a drug candidate for the treatment of patients undergoing LT.
研究领域:
药理学
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移植学
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肝病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
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2016
·Vol. 134
·期 7
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IF 1.866
Jie-Ping Fan,Dan-Dan Liao,Yan-Long Xie,Bing Zheng,Jia-Xin Yu,Ya-Hui Cao,Xue-Hong Zhang,Hai-Long Peng
A composite material (MIP@Fe 3 O 4 @GO) based on molecular imprinted polymer (MIP), superparamagnetic Fe 3 O 4 particles and graphene oxide (GO) was prepared by the chemical coprecipitation method, and used to simultaneously separate and enrich two alkaloids (evodiamine and rutaecarpine) in the extract of Evodiae fructus . The as-prepared MIP@Fe 3 O 4 @GO was characterized by Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), and vibrating sample magnetometer (VSM). The adsorption kinetics, isotherms, competitive adsorption, and reusability of MIP@Fe 3 O 4 @GO were also investigated. The results revealed that MIP@Fe 3 O 4 @GO was sensitive to the magnetic field and could be easily separated using an external magnet; MIP@Fe 3 O 4 @GO showed good recognition selectivity, as well as simultaneous enrichment and separation abilities for evodiamine and rutaecarpine in the extract of E. fructus with satisfactory recoveries. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134 , 44465.
研究领域:
材料科学
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药物分析
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中药学
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产品关联
DOI
高影响因子
BIOCHEMICAL PHARMACOLOGY
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2020
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IF 4.96
Xue-qi Liu,Juan Jin,Zeng Li,Ling Jiang,Yu-hang Dong,Yu-ting Cai,Ming-fei Wu,Jia-nan Wang,Tao-tao Ma,Jia-gen Wen,Ming-ming Liu,Jun Li,Yong-gui Wu,Xiao-ming Meng
Acute kidney injury (AKI), characterized by a rapid decline in renal function, is triggered by an acute inflammatory response that leads to kidney damage . An effective treatment for AKI is lacking. Using in vitro and in vivo AKI models, our laboratory has identified a series of anti-inflammatory molecules and their derivatives. In the current study, we identified the protective role of rutaecarpine (Ru) on renal tubules. We obtained a series of 3-aromatic sulphonamide-substituted Ru derivatives exhibiting enhanced renoprotective and anti-inflammatory function. We identified Compound-6c(Cpd-6c) as having the best activity and examined its protective effect against cisplatin nephropathy both in vivo and in vitro in cisplatin-stimulated tubular epithelial cells (TECs). Our results showed that Cpd-6c restored renal function more effectively than Ru, as evidenced by reduced blood urea nitrogen and serum creatinine levels in mice. Cpd-6c alleviated tubular injury, as shown by PAS staining and molecular analysis of kidney injury molecule-1 (KIM-1), with both prevention and treatment protocols in cisplatin-treated mice. Moreover, Cpd-6c decreased kidney inflammation , oxidative stress and programmed cell death . These results have also been confirmed in cisplatin-treated TECs. Using web-prediction algorithms, molecular docking, and cellular thermal shift assay (CETSA), we identified phosphodiesterase 4B (PDE4B) as a Cpd-6c target. In addition, we firstly found that PDE4B was up-regulated significantly in the serum of AKI patients. After identifying the function of PDE4B in cisplatin-treated tubular epithelial cells by siRNA transfection or PDE4 inhibitor rolipram , we showed that Cpd-6c treatment did not protect against cisplatin-induced injury in PDE4B knockdown TECs, thus indicating that Cpd-6c exerts its renoprotective and anti-oxidative effects via the PDE4B-dependent pathway. Collectively, Cpd-6c might serve as a potential therapeutic agent for AKI and PDE4B may be highly involved in the initiation and progression of AKI.
研究领域:
药理学
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肾病学
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分子生物学
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炎症研究
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药物开发
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2024
·
IF 6.9
Juan Chen,Zi-yun Hu,Yu Ma,Shan Jiang,Jiu-yu Yin,Yu-kai Wang,Yong-gui Wu,Xue-qi Liu
Diabetic nephropathy (DN) is one of the serious microvascular complications of diabetes mellitus. During the progression of DN, the proliferation of glomerular mesangial cells (GMCs) leads to the deposition of excessive extracellular matrix (ECM) in the mesangial region, eventually resulting in glomerulosclerosis. Rutaecarpine (Rut), an alkaloid found in the traditional Chinese medicinal herb Fructus Evodiae ( Euodia rutaecarpa (Juss.) Benth.), has many biological activities. However, its mechanism of action in DN remains unknown. This study used db/db mice and high glucose (HG)-treated mouse mesangial cells (SV40 MES-13) to evaluate the protective effects of Rut and underlying mechanisms on GMCs in DN. We found that Rut alleviated urinary albumin and renal function and significantly relieved renal pathological damage. In addition, Rut decreased the ECM production, and renal inflammation and suppressed the activation of TGF-β1/Smad3 and NF-κB signaling pathways in vitro and in vivo. Protein kinase CK2α (CK2α) was identified as the target of Rut by target prediction, molecular docking, and cellular thermal shift assay (CETSA), and surface plasmon resonance (SPR). Furthermore, Rut could not continue to play a protective role in HG-treated SV40 cells after silencing CK2α. In summary, this study is the first to find that Rut can suppress ECM production and inflammation in HG-treated SV40 cells by inhibiting the activation of TGF-β1/Smad3 and NF-κB signaling pathways and targeting CK2α. Thus, Rut can potentially become a novel treatment option for DN.
研究领域:
药理学
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肾病学
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分子生物学
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糖尿病
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
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2019
·
IF 3.858
Yikun Liu,Wei Zhou,Zhenkun Mao,Zilin Chen
Evodiae Fructus is used as a traditional Chinese medicine for the treatment of several kinds of diseases with its bioactive constituents. In this study, a capillary electrochromatography-mass spectrometry (CEC-MS) method was developed to determine three bioactive compounds including evodiamine, rutaecarpine and limonin in Evodiae Fructus fruit. Home-developed monolithic columns with methyl-vinylimidazole functionalized organic polymer monolilth as stationary phases were used in CEC-MS with excellent separation selectivity and high efficiency. The CEC-MS methods provided 4–16 folds improvement of LODs when compared with CEC-UV method. The conditions, which could affect separation efficiency and detection sensitivity, were optimized. Under optimum conditions, baseline separation with high detection sensitivity was obtained. The method showed good linearity (R 2 >0.99) of 0.8–160 μg mL −1 with low limits of detection of 0.15-0.31 μg mL −1 . Relative standard deviations of migration time and relative peak areas were <13.89%. Recoveries of evodiamine, rutaecarpine and limonin in Evodiae Fructus fruit were tested and calculated, which ranged from 102% to 113%. Finally, the three bioactive compounds in Evodiae Fructus herb samples from different regions were analyzed and studied. It has been demonstrated that the developed method has great potential for quality control of Evodiae Fructus herb.
研究领域:
中药分析
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分析化学
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药学
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DOI
高影响因子
Journal of Cancer
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2022
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IF 4.478
Shixin Chan,Rui Sun,Xucan Tu,Manyu Guo,Qianqian Yuan,Zhen Yu,Zhenglin Wang,Shaocheng Hong,Wei Han,Bingbing Zou,Zeng Li,Huabing Zhang,Wei Chen
Colorectal cancer (CRC) is a malignant disease that is a serious threat to human health. Rutaecarpine (RUT) is an important bioactive alkaloid of Evodia rutaecarpa. According to previous studies, RUT suppressed the proliferation of several human tumors. However, its role in colorectal tumorigenesis remained unknown. The aim of the present study was to determine the functions of RUT in CRC. Here, we have demonstrated that RUT inhibited the proliferation, migration and invasion of CRC cells in vitro . Further, RUT was found to induce the apoptosis of CRC cells. Mechanistically, RUT decreased the phosphorylation levels of NF-κB and STAT3. Moreover, treatment with RUT upregulated the expression of cleaved-Caspase3 and downregulated the expression of Bcl-2 in CRC. In addition, our findings suggested that RUT inhibited the growth and lung metastasis of CRC Cells in vivo . Based on immunofluorescence analysis, the expression of Ki67 was downregulated while that of cleaved-Caspase3 was upregulated in RUT-treated tumors compared with control-treated tumors. Taken together, our findings indicate that RUT can inhibit the proliferation and migration of CRC cells, and induce the apoptosis of CRC cells by inactivating NF-κB/STAT3 signaling. Our study highlights the potential clinical application of RUT for the treatment of CRC.
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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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2023
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IF 4.8
Zhen Yu,Shixin Chan,Xu Wang,Rui Sun,Ming Wang,Zhenglin Wang,Xiaomin Zuo,Jiajie Chen,Huabing Zhang,Wei Chen
Purpose To evaluate the effect of 5-fluorouracil (5-FU) combined with rutaecarpine (RUT) on the antiproliferative, anti-migratory, and apoptosis-promoting ability of colorectal cancer (CRC) cells and explore the underlying mechanism.Methods The antiproliferative effects of RUT and 5-FU on CRC cells were evaluated using MTT and colony formation assays. Anti-migration was assessed by cell scratch and transwell tests. The synergistic effect of RUT and 5-FU was assessed by isobologram and combination index analysis using CompuSyn software. The effects of RUT and 5-FU on cell apoptosis were detected by flow cytometry. Differences in protein expression levels with or without RUT and/or 5-FU treatment were assessed by Western blot. Moreover, a mouse xenograft model of CRC was established to investigate the antitumor effect of RUT and 5-FU in vivo, and Ki67 and cleaved caspase-3 expression was detected by immunofluorescence.Results In this study, we found that 5-FU combined with RUT can inhibit the proliferative, migratory, and antiapoptotic abilities of CRC cells to a significantly greater extent than either RUT or 5-FU alone both in vivo and in vitro. Western blot analysis showed that the level of signal transducer and activator of transcription 3 (STAT3) phosphorylation in CRC cells was significantly reduced after combination therapy compared with that seen with the respective monotherapies. In addition, combination therapy influenced the STAT3 signaling pathway, namely, it inhibited the expression of c-Myc, CDK4, and Bcl-2 while enhancing that of the proapoptotic protein cleaved caspase-3. Immunofluorescence staining further showed that the expression of Ki67 and cleaved caspase-3 was significantly downregulated and upregulated, respectively, in tumor tissues of mice treated with combination therapy compared with that observed with 5-FU treatment alone.Conclusion Combined therapy with 5-FU and RUT exerted a superior curative effect in CRC than treatment with either single drug alone and has potential as a novel therapeutic modality for the treatment of CRC.
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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细胞生物学
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产品关联
DOI
PubMed
高影响因子
XENOBIOTICA
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2021
·
IF 1.908
Xian-Mei Song,Bing-Jie Li,Yan-Yan Zhang,Wen-Jing Ge,She-Feng Zhang,Wei-Feng Cui,Geng-Sheng Li,Rui-Feng Liang
Diabetes mellitus is a chronic metabolic disorder with multiple complications, patients who receive metformin may have a simultaneous intake of herbal medicine containing rutaecarpine due to cardiovascular protection and hypolipidemic effects of rutaecarpine. There might be drug interactions between metformin and rutaecarpine. This study aimed to investigate the effects of rutaecarpine on the pharmacodynamics and pharmacokinetics of metformin in diabetic rats.The diabetic rat model was induced with high-fat diet and low dose streptozotocin. Metformin with or without rutaecarpine was administered by oral gavage for 42 days. Pharmacodynamics and pharmacokinetics parameters were evaluated.The pharmacodynamics results revealed that co-administration of rutaecarpine with metformin resulted in a remarkable reduction of serum glucose and lipid profiles in diabetic rats compared to metformin treated alone. The pharmacokinetics results showed that co-treatments of rutaecarpine with metformin did not affect the systemic exposure and renal distribution of metformin, but increased metformin concentration in liver. Furthermore, rutaecarpine increased Oct1-mediated metformin uptake into hepatocytes by upregulation of Oct1 expression in the liver.The above data indicate that rutaecarpine enhanced the anti-diabetic effect of metformin, which may be associated with the increased hepatic distribution of metformin through up-regulation of Oct1 in response to rutaecarpine.
研究领域:
药理学
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内分泌学
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糖尿病研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2019
·
IF 2.983
Baofang Zhang,Zilin Chen
A simple and valid method for rapid screening of cathepsin B inhibitors from traditional Chinese medicines (TCMs) was established by the combination of immobilized enzyme microreactor (IMER) and capillary electrophoresis. Cathepsin B was immobilized on the inner surface of the capillary by glutaraldehyde method. The separation of substrate and product could be finished by baseline within 3 min. The activity of the immobilized cathepsin B remained approximately 90% after 50 runs. The quantification and statistical analysis of the product peak area was used to evaluate the catalytic activity of cathepsin B. The value of Michaelis-Menten constant of cathepsin B was 0.85 mM. The half-maximal inhibitory concentration (IC 50 ) of L -trans-Epoxysuccinyl-leucylamido(4-guanidino)butane (E-64) was measured as 36.08 nM, which indicated that the cathepsin B reactor was successfully developed and was feasible for inhibitorscreening. The raised method was then applied to discover the inhibitory potential of 17 standard compounds from traditional Chinese medicines. Five natural products, including kaempferol, rutaecarpine, evodiamine, theophylline, lycobetaine showed potential inhibition for cathepsin B. Additionally, molecular docking study was investigated for supporting the interaction between enzyme and inhibitors.
研究领域:
药理学
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生物化学
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药物化学
·
酶学
✓ 已验证
DOI
PubMed
高影响因子
Biochimica et Biophysica Acta-Gene Regulatory Mechanisms
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2015
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IF 6.332
Lushan Yu,Zhangting Wang,Minmin Huang,Yingying Li,Kui Zeng,Jinxiu Lei,Haihong Hu,Baian Chen,Jing Lu,Wen Xie,Su Zeng
The constitutive androstane receptor (CAR) is a key sensor in xenobiotic detoxification and endobiotic metabolism. Increasing evidence suggests that CAR also plays a role in energy metabolism by suppressing the hepatic gluconeogenesis and lipogenesis . In this study, we investigated the effects of two evodia alkaloids, rutaecarpine ( Rut ) and evodiamine ( Evo ), on gluconeogenesis and lipogenesis through their activation of the human CAR (hCAR). We found that both Rut and Evo exhibited anti-lipogenic and anti-gluconeogenic effects in the hyperlipidemic HepG2 cells. Both compounds can potently activate hCAR, and treatment of cells with hCAR antagonists reversed the anti-lipogenic and anti-gluconeogenic effects of Rut and Evo . The anti-gluconeogenic effect of Rut and Evo was due to the CAR-mediated inhibition of the recruitment of forkhead box O1 (FoxO1) and hepatocyte nuclear factor 4α (HNF4α) onto the phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) gene promoters. In vivo, we showed that treatment of mice with Rut improved glucose tolerance in a CAR-dependent manner. Our results suggest that the evodia alkaloids Rut and Evo may have a therapeutic potential for the treatment of hyperglycemia and type 2 diabetes. This article is part of a Special Issue entitled: Xenobiotic nuclear receptors : New Tricks for An Old Dog, edited by Dr. Wen Xie.
研究领域:
药理学
·
内分泌学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
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