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

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

Identyfikatory

DOI

10.1556/1326.2020.00800

• Języki publikacji: EN

Abstrakty

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 T^max and t^1/2β of isopimpinellin and pimpinellin were 1.74 and 0.59 h, 5.31 and 6.89 h in rats. On the basis of Sigmoid–E^max model, PK–PD related curves of FIB in hemorrhagic rat model after treatment of T. asiatica root bark were obtained. Predicted E^max, EC⁵⁰ and k^e0 of FIB under isopimpinellin were 4.87 mg/mL, 1.39 μg/mL and 0.81 1/h; predicted E^max, EC⁵⁰ and k^e0 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.

Słowa kluczowe

EN

Toddalia asiatica (Linn) Lam; CF–PK–PD; LC-MS; pharmacokinetics; pharmacodynamics; hemostatic activity

• Wydawca: University of Silesia in Katowice ; Akademiai Kiado
• Czasopismo: Acta Chromatographica
• Rocznik: 2021
• Tom: Vol. 33, no. 3
• Strony: 261--269
• Opis fizyczny: Bibliogr. 15 poz., rys., tab.

Twórcy

autor

Zhang Xiaoyan

• School of Basic Medical Sciences, Guizhou Medical University, Guiyang, Guizhou, 550025, China

autor

Liu Jie

• School of Basic Medical Sciences, Guizhou Medical University, Guiyang, Guizhou, 550025, China
• School of Pharmacy, Guizhou Medical University, Guiyang, Guizhou, 550025, China

autor

Sun Wenbo

• School of Pharmacy, Guizhou Medical University, Guiyang, Guizhou, 550025, China

autor

Shen Xiangchun

• School of Pharmacy, Guizhou Medical University, Guiyang, Guizhou, 550025, China

autor

Gong Xiaojian

• Research Center for Quality Control of Natural Medicine, Guizhou Normal University, Guiyang, Guizhou, 550001, China

autor

Wang Cong

• School of Pharmacy, Guizhou Medical University, Guiyang, Guizhou, 550025, China

autor

Liang Yan

• School of Pharmacy, Guizhou Medical University, Guiyang, Guizhou, 550025, China

• https://orcid.org/0000-0002-3458-6818

autor

Zhou Wei

• School of Pharmacy, Guizhou Medical University, Guiyang, Guizhou, 550025, China

• https://orcid.org/0000-0002-4123-2276

Bibliografia

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