MICROCHEMICAL JOURNAL
·
2020
·
IF 3.594
Yaping Duan,Congmin Liu,Xiaowen Dou,Liu Wu,Hao Liu,Linan Shan,Shihai Yang,Jiaoyang Luo,Meihua Yang
Triptolide is a characteristic chemical component and quality marker of Tripterygium wilfordii Hook. F., a widely used traditional Chinese medicine with various pharmacological activities. Triptolide-14-succinate is a derivative of triptolide that can be combined with bovine serum albumin and ovalbumin to form an immunogen and coating antigen. Monoclonal antibody specific to triptolide-14-succinate conjugated with ovalbumin was produced and named mAb 2D10 1H8. An indirect competitive enzyme-linked immunosorbent assay (icELISA) was established by using mAb 2D10 1H8. The 50% inhibition concentration and working range of triptolide for the icELISA were 0.28 and 0.09–0.87 μg mL −1 , (based on 20–80% binding inhibition of mAb 2D10 1H8 to triptolide, R 2 = 0.9997, y = -0.571Logx + 0.246), respectively. The icELISA displayed crossreactivity values of 48.6, 20.5, 3.27, and < 1.00% for triptonide, triptophenolide, tripterifordin, and other analogs of triptolide, respectively. The average recovery of triptolide from the Tripterygium wilfordii samples as determined by icELISA ranged from 90.05 to 106.6%. Triptolide was detected in 38 batches of Tripterygium wilfordii samples by icELISA, which was validated by ultra-fast liquid chromatography combined with electrospray ionization tandem-mass spectrometry. In conclusion, the icELISA method established in the present study is applicable for rapid authentication of Tripterygium wilfordii and related products.
研究领域:
中药学
·
免疫学
·
分析化学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2020
·
IF 4.845
Shiping Zhu,Chunhua Luo,Weifeng Feng,Yan Li,Mujuan Zhu,Shengyun Sun,Xingwang Zhang
Arthritis remains the notion of a hard-to-treat disease that raises an area of unmet clinical need. The phytomedicine tripterine (Tri) and trace element selenium (Se) have been shown to be of anti-inflammatory activity. This study was devoted to develop nanomedicine containing Tri and Se used for fighting against arthritis via a coordination mechanism. Se-deposited Tri phytosomes (Se@Tri-PTs) were prepared by a melting-hydration/ in situ reduction technique and characterized by particle size, ζ potential , morphology, and entrapment efficiency ( EE ). The resultant Se@Tri-PTs were 126 nm around in particle size with an EE of 98.85%. Se@Tri-PTs exhibited a sustained drug release both in 0.1 M HCl and pH 6.8 PBS compared with Se-free phytosomes (Tri-PTs). The in vivo antiarthritic test demonstrated that Se@Tri-PTs could result in significant resolution of arthritis and decline of inflammatory factors. Phytosomes primely facilitated the transepithelial transport of Tri, while Se enhanced the antiarthritic efficacy of the phytomedicine synergistically. The present work provides a proof-of-concept for the combined therapy of arthritis using Tri and Se in the form of nanoparticles .
研究领域:
药理学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Yan Zhou,Tian Wen,Shan Yang,Binru Meng,Jing Wei,Jing Zhang,Lun Wang,Xiaofei Shen
Ethnopharmacological relevance Cichorium intybus is a traditional medicinal herb for hepatitis treatment in China and Europe. Sesquiterpene lactones are the main active ingredients in C. intybus . However, their structure-activity relationship (SAR) and molecular mechanisms of anti-inflammatory and hepatoprotective effects require further elucidation. Aim of the study To identify new sesquiterpene lactones from C. intybus , and further evaluate their anti-inflammatory effects, SAR, and mechanisms of anti-inflammatory and hepatoprotective properties. Methods Identification of sesquiterpene lactones from C. intybus using chromatographic fractionation, NMR, and mass spectrometry. The repression of inflammation was evaluated in RAW264.7 macrophages incubated with LPS. Western blotting was employed to investigate the anti-inflammatory mechanisms. The hepatoprotective effect was measured in LPS/D-galactosamine (D-GalN)-induced acute hepatitis in mice. Results We identified 3 new sesquiterpene lactones and 15 known analogues from C. intybus . SAR analysis showed that the α-methylene-γ-lactone moiety was essential for their anti-inflammatory properties. Furthermore, 8-deoxylactucin was identified as the most potent anti-inflammatory component in LPS-induced RAW264.7 macrophages by reduction of nitric oxide production via inhibiting iNOS expression, and suppression of IL-1β, IL-6, and TNF-α expression. Mechanistically, 8-deoxylactucin not only blocked LPS-induced IKKα/β phosphorylation, IκBα phosphorylation and degradation, and NF-κB nuclear accumulation, but also enhanced NRF2 expression and nuclear translocation, HO-1 and NQO1 expression, and reduced ROS generation in vitro . In vivo , 8-deoxylactucin mitigated LPS/D-GalN-induced acute hepatitis, which manifested as reduction in inflammatory infiltration, live injury, serum levels of AST and ALT, and production of pro-inflammatory cytokines and 4-hydroxynonenal. Conclusion 8-Deoxylactucin, the sesquiterpene lactone isolated from C. intybus , exerted anti-inflammatory and hepatoprotective effects by blocking NF-κB activation and enhancing NRF2 activation.
研究领域:
药理学
·
植物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Horticultural Plant Journal
·
2017
·Vol. 3
·期 4
·165-171
·
IF 0
Yanhui ZHANG,Peiying LIU,Qianqian KONG,Shiyan XING,Xiaojing LIU,Limin SUN
Flavonoids and terpene trilactones, especially, ginkgo flavonglycosides, ginkgolides and bilobalides in leaves of ginkgo trees, need to be studied for effective application of these active components with high medical and health-care values. This study was aimed to provide scientific bases for genealogies selection and harvest season confirmation for Ginkgo biloba . A high-performance liquid chromatographic method (HPLC-ELSD) was developed to determine the contents of terpene trilactone and flavonoid of 36 ancient G. biloba genealogies from 19 provinces in China. The study indicated that the content gradually increased from April to August, and thereafter declined. Analysis of variance indicated that the contents of terpene trilactone, flavonoids, and their respective components had significant difference among 36 genealogies. The cluster analysis showed that No. 72 (Xing'an, Guangxi), No. 58 (Youyang, Chongqing), No. 82 (Rugao, Jiangsu), No. 123 (Huixian, Gansu), No. 99 (Dujun, Guizhou), No. 10 (Tai'an, Shandong) and No. 133 (Mentougou, Beijing) genealogies have higher content of terpene trilactone and flavonoid. These results can help us to select superior variety containing high content of terpene trilactone and flavonoid.
研究领域:
植物化学
·
药用植物学
·
天然产物化学
·
林木遗传育种
·
药物代谢
✓ 已验证
DOI
Polymers
·
2024
·Vol. 16
·期 24
·3485
·
IF 4.7
Meizhen Yin,Xinying Zhang,Tongguang Zhang,Zhiqiang Bao,Zhihui He
The present study aimed to explore an ideal delivery system for triptolide (TPL) by utilizing the thin-film hydration method to prepare drug-loaded, folate-modified mixed pluronic micelles (FA–F-127/F-68–TPL). Scanning electron microscopy and atomic force microscopy showed that the drug-loaded micelles had a spherical shape with a small particle size, with an average of 30.7 nm. Cell viability experiments showed that FA–F-127/F-68–TPL significantly reduced HepG2 cell viability, exhibiting strong cytotoxicity. Its cytotoxicity was markedly enhanced compared with bare TPL. Nile red (Nr) was used as a model drug to prepare FA–F-127/F-68–Nr to further validate its tumor-targeting and cellular uptake capability. After coincubation with HepG2 cells, a multifunctional microplate reader showed that intracellular fluorescence intensity significantly increased, indicating that FA–F-127/F-68–Nr could more effectively enter the cells. A nude mouse model of subcutaneous hepatocellular carcinoma was constructed. Following tail vein injection of FA–F-127/F-68–Nr, the fluorescence imaging system showed that FA–F127/F-68–Nr could significantly target tumor tissue, and even if entering the small-sized tumor was challenging, it could be excreted through urine. Nude mice with subcutaneous hepatocellular carcinoma were treated with tail vein injections of FA–F-127/F-68–TPL (45 µg/kg) every other day for 21 days. The results showed that the growth of the transplanted tumors was significantly slowed, with no significant difference compared with bare TPL. In summary, the FA–F-127/F-68–TPL exhibits the advantages of low cost, excellent biological properties, active/passive targeting capabilities, notable cytotoxicity against liver cancer cells, and significant inhibition of transplanted hepatocellular carcinoma growth. Significantly, the FA–F-127/F-68–TPL, despite challenges in targeting tumors with an insignificant EPR effect, can be efficiently excreted via the kidneys, thereby preventing the release of the drug during prolonged circulation and potential damage to normal tissues. Therefore, FA–F-127/F-68–TPL represents a promising antitumor drug delivery system.
研究领域:
药剂学
·
肿瘤学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2025
·
IF 5.1
Yuling Deng,Meifang Jiang,Qing Liu,Jun Wang,Yi Tao
Ginkgo ester (GBE50) is a well-known botanical drug derived from crude material Ginkgo Folium . Nonetheless, a swift and nondestructive method for full quality inspection on Ginkgo Folium is still lacking. Herein, an interpretable deep learning embedded hyperspectral imaging methodology was established to control the quality of Ginkgo Folium . Hyperspectral images were collected from 102 batches of Ginkgo Folium ranging from 389.8 nm to 1048.2 nm. The contents of three flavonol glycosides and four terpene lactones in Ginkgo Folium were unambiguously determined by well-validated high-performance liquid chromatography (HPLC) and ultra-high performance liquid chromatography-triple quadrupole-mass spectrometry (UHPLC-TQ-MS) methods, whilst the moisture content measured through a moisture meter. In order to realize the real-time full quality inspection, competitive adapative reweighted sampling-partial least squares regression (CARS-PLSR) and seven deep learning algorithms (ResNet50, AlexNet, GoogLeNet, DenseNet121, ResNeXt50, Inception-V4 and Inception-ResNet-V2) were attempted to establish a robust quantitative calibration model embedded hyperspectral imager. As a result, DenseNet121 algorithm showed the most excellent predictive performance. The R p 2 values of quercetin, kaempferol, isorhamnetin, bilobalide, ginkgolide A, ginkgolide B, ginkgolide C, and moisture were determined to be 0.9969, 0.9913, 0.9965, 0.9988, 0.9951, 0.9952, 0.9988 and 0.9981, respectively, and the RMSEP values were 0.0084, 0.0094, 0.0103, 0.0053, 0.0056, 0.0099, 0.0084 and 0.0050, respectively. Grad-CAM was used to unlock the blackbox of DenseNet121model and interpret the model. It’s believed that the established DenseNet121 embedded hyperspectral imager can rapidly and nondestructive determine the eight quality attributes and provide a tool for full quality inspection on Ginkgo Folium .
研究领域:
植物学
·
药物分析
·
质量控制
✓ 已验证
产品关联
DOI
高影响因子
ACS Biomaterials Science & Engineering
·
2019
·
IF 4.511
Caili Huang,Tao Zeng,Jiawen Li,Lishan Tan,Xiulong Deng,Yanchao Pan,Qi Chen,Aiqing Li,Jianqiang Hu
Triptolide (TP) has been widely used in clinical medicine; however, it has created a dilemma due to its toxicity and nonspecificity. Here, we reported a biocompatible and high-efficiency renal-targeting nanoplatform for renal ischemia/reperfusion injury (IRI) therapy, in which the toxic drug of TP was encapsulated into folate (FA)-modified Pluronic F127/P123 nanoparticles (FPNPs). The TP-loaded FPNPs (TP-FPNPs) had good stability and could effectively reduce the cytotoxicity of TP. Compared with the Pluronic nanoparticles (PNPs) group, cellular uptake ability of FPNPs significantly improved because of folate receptor-mediated endocytosis effect. Ex vivo organ imaging and pharmacokinetic results indicated that FPNPs possessed high kidney selectivity and long retention time. The therapeutic effect of TP-FPNPs on renal IRI was more superior to that of free TP, such as lower acute tubular injury index (2.9-fold), renal function indexes of serum creatinine (4.3-fold), urea nitrogen (2.0-fold), and Western blotting (2.4-fold). Systemic toxicity assay suggested that TP-FPNPs had much lower nephrotoxicity, hepatotoxicity, and genital system toxicity than free TP. Thus, renal-targeting FPNPs will be a potential delivery platform of hydrophobic drugs for treatment of renal diseases.
研究领域:
药学
·
纳米医学
·
肾脏病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Applied Materials Today
·
2024
·
IF 7.2
Huahui Zeng,Man Li,Zhirong Wang,Tianqi Wang,Zhenqiang Zhang,Xiangxiang Wu
M1 macrophages play a crucial role in the development of rheumatoid arthritis (RA), which can produce various inflammation cytokines, and reactive oxygen species (ROS). Disulfide bonds as reduction-responsive linkages have been extensively employed in the drug delivery systems. However, disulfide bonds are rarely reported in the development of the oxidation-responsive drug carriers. Herein, we designed and synthetized novel oxidation-responsive drug carriers based on disulfide bonds, and further developed nanoparticles (FA-TP@NPs) by self-assembly for the RA treatment. FA-TP@NPs was decorated with folic acid and loaded with triptolide (TP), a potent anti-inflammation Chinese medicine, to target and enter M1 macrophages through the folate receptor on the cytomembrane for simultaneous repolarization of the M2 macrophage and elimination of the M1 macrophage. As expected, FA-TP@NPs exhibited an oxidation-responsive TP release via disulfide-bond oxidation and ester-bond hydrolysis in the presence of intracellular ROS, which accumulated preferentially in inflamed joints. FA-TP@NPs exerted a potent anti-arthritic effect with high biosafety in CIA mice, as evidenced by repolarizing M2 macrophages, inducing M1 macrophage apoptosis, and reducing TNF-α, IL-6, and IL-1β expression. This work shows that FA-TP@NPs give a deep insight into disulfide bond-based oxidation-responsive drug delivery systems, and provide a potential platform for RA treatment.
研究领域:
药学
·
免疫学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2015
·
IF 3.65
Wan Li,Tianpeng Zhang,Yanghuan Ye,Xingwang Zhang,Baojian Wu
Chemotherapy via the oral route remains a considerable challenge due to poor water-solubility and permeability of anticancer agents . This study aimed to construct lipid nanoparticles using broccoli-derived lipids for oral delivery of tripterine (Tri), a natural anticancer candidate, and to enhance its oral bioavailability. Tri-loaded broccoli lipid nanoparticles (Tri-BLNs) were prepared by a solvent-diffusion method. The resulting Tri-BLNs were 75 ± 10 nm in particle size with entrapment efficiency over 98%. In vitro release study indicated that Tri was almost not released from Tri-BLNs (<2%), whereas the lipolytic experiment showed that Tri-BLNs possessed a relatively strong anti-enzymatic degradation ability to Tri-CLNs (Tri-loaded common lipid nanoparticles). In situ single-pass intestinal perfusion manifested that the effective permeability of Tri-BLNs were significantly higher than that of Tri-CLNs. Further, Tri-BLNs exhibited more efficient cellular uptake in MDCK-II cells as evidenced by flow cytometry and confocal microscopy . The relative bioavailability of Tri-BLNs and Tri-CLNs was 494.13% and 281.95% compared with Tri suspensions, respectively. Depending on the ability in enhancement of biomembrane permeability, broccoli-derived lipids as an alternative source should be useful to construct lipid nanoparticles for bettering oral delivery of drugs with low bioavailability.
研究领域:
药剂学
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES
·
2025
·
IF 1.2
Jinhao Li,Yuanyuan Wang,Juan Du,Huanhuan Meng,Yingchao Wang,Xingchu Gong
A high-performance liquid chromatography-mass spectrometry (HPLC-MS) method was developed to quantify protocatechuic acid (PA), p-hydroxybenzoic acid (PHA), quercetin (QR), kaempferol (KP), isorhamnetin (ISO), Ginkgolide A (GA), Ginkgolide B (GB), Ginkgolide C (GC) and Bilobalide (BB) in Ginkgo biloba leaf concentrate based on (AQbD) concept. The response values of each compound were selected as the critical method attributes (CMAs).A risk assessment and Plackett–Burman design approach was performed to screen the critical method parameters (CMPs) . Box–Behnken designed experiments were were conducted to explore the relationship between the CMPs and the CMAs,and a stepwise regression method was used to build quantitative models . The method operable design region (MODR) was established and verified . The final method used an Agilent Infinitylab Poroshell 120 column (4.6 mm × 100 mm, 2.7 μm). The Mobile phase A was 0.1% formic acid-water and the mobile B was 0.1% formic acid-methanol. The flow rate was 0.66 mL/min. The column temperature was 30 °C. The gradient elution ratio was: 0–15 min, 0–35%B; 15–30 min, 35–80%B; 30–41 min, 95–95%B. The nebulizer pressure was 50 psi and the capillary voltage was 2000 V. The gas temperature was 325 °C. The fragmentor voltage of PA, PHA, BB and GA was 90 eV. The fragmentor voltage of GB and GC was 100 eV. The fragmentor voltage of QR, KP and ISO was 140 eV. The method has passed the methodology verification and can be used for the determination of flavonoid glycosides, terpenoid lactones and organic acids in Ginkgo biloba leaves concentrate.
研究领域:
药学
·
分析化学
✓ 已验证
DOI
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2021
·Vol. 35
·期 7
·e5093
·
IF 1.902
Wei Wu,Rui Cheng,Zhenzhou Jiang,Luyong Zhang,Xin Huang
A rapid and specific UPLC–MS/MS method with a total run time of 3.5 min was developed for the determination of pravastatin, fexofenadine, rosuvastatin, and methotrexate in rat primary hepatocytes. After protein precipitation with 70% acetonitrile (containing 30% H 2 O), these four analytes were separated under gradient conditions with a mobile phase consisting of 0.03% acetic acid (v/v) and methanol at a flow rate of 0.50 mL/min. The linearity, recovery, matrix effect, accuracy, precision, and stability of the method were well validated. We evaluated drug–drug interactions based on these four compounds in freshly suspended hepatocytes. The hepatic uptake of pravastatin, fexofenadine, rosuvastatin, and methotrexate at 4°C was significantly lower than that at 37°C, and the hepatocytes were saturable with increased substrate concentration and culture time, suggesting that the rat primary hepatocyte model was successfully established. Triptolide showed a significant inhibitory effect on the hepatic uptake of these four compounds. In conclusion, this method was successfully employed for the quantification of pravastatin, fexofenadine, rosuvastatin, and methotrexate and was used to verify the rat primary hepatocyte model for Oatp1, Oatp2, Oatp4, and Oat2 transporter studies. Then, we applied this model to explore the effect of triptolide on these four transporters.
研究领域:
药理学
·
分析化学
·
肝脏病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2022
·
IF 5.714
Shaomin Liu,Qiufang Chen,Liang Yan,Yuehong Ren,Jun Fan,Xingwang Zhang,Shiping Zhu
Inflammation mediates a variety of physiological and pathological events, prompting an importance of inflammation management for prevention and treatment of inflammatory diseases. This study formulated tripterine (Tri) into selenized phytosomes in an attempt to attenuate its cytotoxicity and potentiate its inflammation-regulating effect with selenium. Tri-loaded phytosomes (Tri-PTs) with selenium modification were prepared by a melting-hydration followed by in situ reduction technique. Then, selenized Tri-PTs ( [email protected] ) were characterized by particle size, entrapment efficiency, and transmission electron microscope. The in vitro drug release and cellular uptake were performed to examine the formulation performance of [email protected] The cytotoxicity and anti-inflammatory efficacy through inhibiting NLRP3 inflammasome activation and pyroptosis were appreciated in murine J774A.1 macrophage cell line, respectively. The resultant [email protected] presented a particle size of 125 nm around. [email protected] exhibited attenuated cytotoxicity and improved cellular uptake in macrophages compared with free Tri or Tri-PTs. Also, [email protected] inhibited the releases of caspase-1p20 and mature IL-1β, resulting in restriction of NLRP3 inflammasome activation that inhibits the formation of GSDMD-NT whereby to initiate pyroptosis. Altogether, our findings suggest that [email protected] can inhibit inflammatory response by regulating the NLRP3/caspase-1 pathway, which in turn reduces pyroptosis via suppressing the cleavage of GSDMD.
研究领域:
药剂学
·
免疫学
·
炎症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）