Wyniki wyszukiwania - BazTech

1

Rapid comparison of antitumor chemical constituents and mechanisms between Dendrobium nobile and Dendrobium officinale by UPLC-IT-TOF, network pharmacology and experimental verification

Liu Jie, Li Zhaoyang, Zeng Meiling, Liang Yan, Liang Bing, Ge Qiuping, Zhang Xiaoyan, Zhang Shilin, Zhou Wei

Acta Chromatographica

|

2023

|

Vol. 35, no. 2

123--138

EN

Dendrobium nobile and Dendrobium officinale as the main varieties of traditional Chinese medicine Dendrobium are widely used in clinic. The study aimed to systematically explore chemical constituents and their antitumor effect of D. nobile and D. officinale by ultra-performance liquid chromatography coupled with ion trap time-of-flight mass spectrometry (UPLC-IT-TOF), network pharmacology and cancer cell experiments. D. nobile extract and D. officinale extract could significantly inhibit the proliferation of human lung cancer A549 cells, human liver cancer HepG2 cells and human breast cancer MCF-7 cells in the dose-dependent manner (P < 0.05), the antitumor effect of D. officinale extract was stronger than that of D. nobile extract at the same drug concentration. A total of 40 chemical constituents of D. nobile and D. officinale including phenanthrenes, bibenzyls and other types of compounds had been identified by UPLC-IT-TOF, LCMSsolution and MetID software according to retention times, accurate mass, MSⁿ fragmentation, reference compounds and natural product databases. Phenanthrenes with good antitumor activity were mainly present in D. nobile, bibenzyls were the main compounds of D. officinale. Integrated networks of Herb-Compounds-Targets-Cancer revealed that gigantol, moscatilin, tristin, moscatin and densiflorol B were regarded as key antitumor compounds of D. nobile and D. officinale, D. nobile and D. officinale shared 7 targets accounting for 70% of the antitumor core targets, more than half of their antitumor KEGG pathways were similar. The results of molecular docking and western blotting experiments indicated that the antitumor mechanisms of D. nobile and D. officinale may be through inhibiting PI3K-Akt and HIF-1α signaling pathways.

2

CF–PK–PD analysis of natural hemostatic compounds from Toddalia asiatica (Linn) Lam root bark in rats

Zhang Xiaoyan, Liu Jie, Sun Wenbo, Shen Xiangchun, Gong Xiaojian, Wang Cong, Liang Yan, Zhou Wei

Acta Chromatographica

|

2021

|

Vol. 33, no. 3

261--269

EN

Natural hemostatic compounds from Toddalia asiatica (Linn) Lam (T. asiatica) root bark had been investigated by a novel strategy, chemical fingerprint–pharmacokinetic–pharmacodynamic (CF–PK–PD) for the first time in this study. The extract sample of T. asiatica root bark was subdivided into petroleum ether (PE), ethyl acetate (EA) and n-butanol (n-B) sample by reagent extraction, EA sample showed significant hemostatic activity using prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (FIB) as evaluation indexes from rat plasma of PK experiment in hemorrhagic rat model. CF analysis was adopted to assist us to discover six natural compounds from T. asiatica root bark in actual rat plasma after sample treatment by Ultra Performance Liquid Chromatography-Electrospray Ionization (UPLC-ESI) MS, there were only lomatin and 5-methoxy-8-hydroxy psoralen showing significant hemostatic effect (P < 0.05) mainly through endogenous coagulation pathway and fibrinolytic system. In PK–PD study, six compounds in EA sample exhibited relatively rapid absorption and slow elimination characteristics. The mean Tmax and t1/2β of isopimpinellin and pimpinellin were 1.74 and 0.59 h, 5.31 and 6.89 h in rats. On the basis of Sigmoid–Emax model, PK–PD related curves of FIB in hemorrhagic rat model after treatment of T. asiatica root bark were obtained. Predicted Emax, EC50 and ke0 of FIB under isopimpinellin were 4.87 mg/mL, 1.39 μg/mL and 0.81 1/h; predicted Emax, EC50 and ke0 of FIB under pimpinellin were 4.29 mg/mL, 2.47 μg/mL and 0.77 1/h. In conclusion, hemostatic compounds from T. asiatica root bark had been materialized, there were lomatin, isopimpinellin, pimpinellin and 5-methoxy-8-hydroxy psoralen at least as its main active substances through coagulation pathways and fibrinolytic system. CF–PK–PD method as a promising method was worthy of follow-up opening, application in pharmaceutical research.

3

Antitumor chemical constituents of Toddalia asiatica (Linn) Lam root bark and its rational alternative medicinal parts by multivariate statistical analysis

Luo Cairong, Liu Jie, Liang Yan, Shen Xiangchun, Zhang Xiaoyan, Zhou Wei

Acta Chromatographica

|

2021

|

Vol. 33, no. 2

153--161

EN

Toddalia asiatica (Linn) Lam (T. asiatica) as a traditional Miao medicine was investigated to find rational alternative medicinal parts for T. asiatica root bark and its antitumor chemical constituents by quantitative pharmacognostic microscopy, high performance liquid chromatography (HPLC) fingerprint and multivariate statistical analysis. A bivariate correlation analysis method based on microscopic characteristics and content of chemical constituents was established for the first time, there were some regular discoveries between powder microscopic characteristics and common chromatographic peaks of T. asiatica through quantitative pharmacognostic microscopy, cork cells, calcium oxalate square crystal, brown clump, starch granule and phloem fiber, as powder microscopic characteristics may be placed where the main chemical constitutes were enriched. Scores plot of principal component analysis (PCA) and dendrogram of hierarchical clustering analysis (HCA) showed that 18 T. asiatica samples were distinguished correctly, clustered clearly into two main groups as follows: S01∼S03 (root bark) and S07∼S09 (stem bark) in cluster 1, S04∼S06 and S10∼S18 in cluster 2. Nineteen common peaks were obtained in HPLC fingerprint of T. asiatica, loadings plot of PCA indicated seven compounds played important roles in different part of samples (P10 > P08 > P07 > P14 > P16 > P17 > P19), peaks 04, 06, 07, 08, 10 were identified as hesperidin, 4-methoxycinnamic acid, toddalolactone, isopimpinlline and pimpinellin. MTT assay was used to determine the inhibitory activity of different medicinal parts of T. asiatica on human breast cancer MCF-7 cells, all parts of T. asiatica had different inhibitory effects on MCF-7 cell lines, root and stem barks of T. asiatica showed the best inhibitory activity. The relationship between chemical constituents and the inhibitions on MCF-7 cell had been established, significant antitumor constituents of T. asiatica were identified by correlation analysis, the order of the antitumor effect of the main compounds was P07 (toddalolactone) > P16 > P06 (4-methoxycinnamic acid), P11 > P18 > P10 (pimpinellin) > P08 (isopimpinellin) > P01 > P19 > P14 > P04 (hesperidin) > P17, which were antitumor chemical constituents of T. asiatica root bark. T. asiatica stem bark was the most rational alternative medicinal part for T. asiatica root bark.