MOLECULES
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2020
·Vol. 25
·期 5
·1082
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IF 3.267
Limin Li,Bin Hao,Yulong Zhang,Shen Ji,Guixin Chou
Militarine, a natural glucosyloxybenzyl 2-isobutylmalate, isolated fromBletilla striata, was reported with a prominent neuroprotective effect recently. The limited information on the metabolism of militarine impedes comprehension of its biological actions and pharmacology. This study aimed to investigate the metabolite profile and the distribution of militarine in vivo, which help to clarify the action mechanism further. A total of 71 metabolites (57 new metabolites) in rats were identified with a systematic method by ultra-high-performance liquid chromatography combined with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). The proposed metabolic pathways of militarine include hydrolyzation, oxidation, glycosylation, esterification, sulfation, glucuronidation and glycine conjugation. Militarine and its metabolites were distributed extensively in the treated rats. Notably, six metabolites of militarine were identified in cerebrospinal fluid (CSF), which were highly consistent with the metabolites after oral administration of gastrodin in rats. Among the metabolites in CSF, five of them were not reported before. It is the first systematic metabolic study of militarine in vivo, which is very helpful for better comprehension of the functions and the central nervous system (CNS) bioactivities of militarine. The findings will also provide an essential reference for the metabolism of other glucosylated benzyl esters of succinic, malic, tartaric and citric acids.Keywords:militarine;metabolite identification;metabolic profiles;UPLC-Q-TOF-MS/MS
研究领域:
药理学
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分析化学
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产品关联
DOI
PubMed
高影响因子
POLYMER JOURNAL
·
2023
·Vol. 55
·期 3
·203-211
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IF 2.8
Shi Zhichun,Wen Jiaxiang,Zhao Yingnan,Wang Jianjun,Li Jun,Zhao Ming,Teraguchi Masahiro,Aoki Toshiki,Kaneko Takashi
A novel substituted phenylacetylene with a pendant betulin derivative group was designed and synthesized successfully, and the chemical structure of the monomer was confirmed by nuclear magnetic resonance spectroscopy (NMR, 1 H, 13 C), high-resolution mass spectrometry (HRMS) and Fourier transform infrared spectroscopy (FTIR). The obtained monomer was further polymerized in an achiral [Rh(nbd)Cl] 2 /triethylamine (TEA) catalytic system, and the resulting polymer exhibited a strong Cotton effect at the main-chain absorption regions in the circular dichroism (CD) spectra. This one-handed helical backbone was induced by the chiral source on the side chain and maintained by the rigid betulin derivative pendant flats. Furthermore, the rigid betulin derivatives also contributed to the porous morphology and perfect thermal stability of the polymer. This study will provide a new method for preparing porous chiral polymers as efficient separation materials to solve practical issues.
研究领域:
材料化学
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有机合成
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高分子科学
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产品关联
DOI
高影响因子
PEST MANAGEMENT SCIENCE
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2025
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IF 3.8
Xiaobo Huang,Nan Hao,Lili Shu,Zhenyang Wei,Jiawei Shi,Yuee Tian,Genqiang Chen,Xinling Yang,Zhiping Che
BACKGROUND The emergence and increasing intensification of insect pest resistance greatly shortens the service life of commercial insecticides. Hence, the continuous development of novel insecticides is extremely necessary. Discovering new insecticide molecules based on natural products with insecticidal activity has been a popular technique and has made outstanding contributions in this field. RESULTS A series of betulin-cinnamic acid-related hybrid compounds was prepared by molecular hybridization through the bridge of acyloxy groups and their chemical structures were unambiguously confirmed. Against A. pisum , compounds 2e , 3a-3e , 3g , 3i , 3j , and 3m showed complete antifeedant activity at 2 mg/mL; compound 5b exhibited 2.7 times the aphicidal activity of the precursor betulin. Against P. xylostella , compound 2l displayed 3.9 times the insecticidal activity of betulin. Meanwhile, some interesting structure–activity relationships were obtained. Furthermore, compound 2l could destroy the ultrastructure of midgut cells and significantly inhibit the activity of α-amylase in P. xylostella larvae. Molecular docking indicated that the lupane skeleton and p -nitrocinnamoyloxy groups played a key role in the binding of compound 2l to α-amylase. CONCLUSION Compounds 5b and 2l could be further optimized structurally as the secondary lead compounds for the discovery of novel insecticide molecules. © 2025 Society of Chemical Industry.
研究领域:
昆虫学
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天然产物化学
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植物保护
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DOI
PubMed
高影响因子
JOURNAL OF LIPOSOME RESEARCH
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2021
·
IF 3.648
Gang Wang,Yu Yang,Du Yi,Lu Yuan,Pei-Hao Yin,Xu Ke,Wang Jun-Jie,Min-Fang Tao
This study aimed to develop polymer Eudragit S100 for preparing pH-responsive liposomes-loaded betulinic acid (pH-BA-LP) to improve the therapeutic index of chemotherapy for colorectal cancer. BA-loaded liposomes were coated with Eudragit S100 by a thin film dispersion and easily scalable pH-driven method. The prepared liposomes were evaluated for size, surface morphology, entrapment efficiency, stability, in vitro drug release, and antitumor activity. In particular, pH-BA-LP showed advantages such as lower size (<100 nm), encapsulation efficiency of 90%, high stability, and stably cumulative release. By detecting the antitumor effects of pH-BA-LP in vivo, it showed that the tumor proliferation and cell migration were significantly inhibited in colorectal cancer. The pH-BA-LP also inhibited tumor growth via the regulation of Akt/TLR-mediated signalling and significantly down-regulated the expression of NFAT1 and NFAT4 proteins. It was found that pH-BA-LP can increase NK cells and CD3+ cells in tumor tissues, and the proportion of CD8+ cells in CD3+ cells was also increased, which proved that pH-BA-LP can play an antitumor effect by enhancing the autoimmunity level in tumor-bearing mice. The positive infiltration rates of CD8 and CD68 were increased and CD163 was relatively decreased by using pH-BA-LP, which proved that pH-BA-LP can regulate the immune infiltration levels in tumor-bearing mice. Therefore, the present work provides an effective method to prepare pH-responsive polymer-coated liposomes for colonic delivery with biologically active compounds.
研究领域:
药学
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肿瘤学
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药理学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
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2022
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IF 8.786
Sun Xiaoxi,Huang Bing,Pan Yuping,Fang Jinhua,Wang Hefeng,Ji Yanru,Ling Yingchen,Guo Pei,Lin Jiangguo,Li Quhuan,Fang Ying,Wu Jianhua
Activation of integrins is crucial for recruitment of flowing leukocytes to inflammatory or injured vascular sites, but their spatiotemporal characteristics are incompletely understood. We discovered that β2-integrin activation over the entire surface of neutrophils on immobilized P-selectin occurred via mitogen-activated protein kinase (MAPK) or non-MAPK signaling with a minute-level timescale in a force-dependent manner. In flow, MAPK signaling required intracellular Ca2+ release to activate integrin within 2 min. Integrin activation via non-MAPK signaling occurred first locally in the vicinity of ligated P-selectin glycoprotein ligand-1 (PSGL-1) within sub-seconds, and then over the entire cell surface within 1 min in an extracellular Ca2+ influx-dependent manner. The transition from a local (but rapid) to global (but slow) activation mode was triggered by ligating the freshly activated integrin. Lipid rafts, moesin, actin, and talin were involved in non-MAPK signaling. Fluid loads had a slight effect on local integrin activation with a second-level timescale, but served as enhancers of global integrin activation.
研究领域:
免疫学
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细胞生物学
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生物物理学
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产品关联
DOI
PubMed
高影响因子
Molecular & Cellular Toxicology
·
2022
·Vol. 19
·期 3
·551-564
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IF 1.718
Cheng Weina,Chen Qihong,Wang Xiaoning,Liu Liu,Li Xiaofei,Duan Cancan,Zhang Jianyong
Background Norcantharidin (NCTD) has multiple antitumor effects. However, NCTD can induce significant hepatotoxicity and the mechanism of hepatotoxicity is not clear for now. Objective This study aimed to explore the hepatotoxicity of NCTD in rat by ultra-performance liquid chromatography (UPLC) quadrupole time-of-flight (Q-TOF)-MS (UPLC/Q-TOF-MS) metabolomics. Results Serum biochemical indices including alanine aminotransferase (ALT) and total bilirubin (T-BIL) were significantly increased. Histopathological and ultrastructure results revealed that hepatocytes were damaged. Furthermore, the metabolomics results showed that 11 metabolites in serum and 8 metabolites in liver were differential metabolites for NCTD hepatotoxicity. Four metabolic pathways including the sphingolipid metabolism, purine metabolism, arachidonic acid metabolism, and glycerophospholipid metabolism were the key metabolic pathways related to NCTD hepatotoxicity. Conclusion The metabolomics analysis in this study reveal new clues on the hepatotoxicity mechanism of NCTD in rats. These findings have potential applications in the toxicity study of NCTD.
研究领域:
药理学
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毒理学
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代谢组学
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DOI
高影响因子
危险品化学品经营许可证（带存储）