Chuanzhitongluo capsule ameliorates microcirculatory dysfunction in rats: Efficacy evaluation and metabolic profiles

Background: Ischemic stroke is a leading cause of mortality and disability worldwide. Microcirculatory dysfunction is the foremost hindrance for a good clinical prognosis in ischemic stroke patients. Clinical researches show that Chuanzhitongluo capsule (CZTL) has a curative effect during the recove...

Full description

Bibliographic Details
Main Authors: Yuanfang Sun, Guoliang Cheng, Lijing Du, Yu Gan, Bing Li, Shikai Yan, Mingguo Shao, Huizi Jin, Shasha Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-10-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2022.1011333/full
_version_ 1797996566910337024
author Yuanfang Sun
Yuanfang Sun
Yuanfang Sun
Guoliang Cheng
Guoliang Cheng
Lijing Du
Lijing Du
Lijing Du
Yu Gan
Yu Gan
Bing Li
Bing Li
Shikai Yan
Shikai Yan
Shikai Yan
Mingguo Shao
Huizi Jin
Huizi Jin
Shasha Li
Shasha Li
author_facet Yuanfang Sun
Yuanfang Sun
Yuanfang Sun
Guoliang Cheng
Guoliang Cheng
Lijing Du
Lijing Du
Lijing Du
Yu Gan
Yu Gan
Bing Li
Bing Li
Shikai Yan
Shikai Yan
Shikai Yan
Mingguo Shao
Huizi Jin
Huizi Jin
Shasha Li
Shasha Li
author_sort Yuanfang Sun
collection DOAJ
description Background: Ischemic stroke is a leading cause of mortality and disability worldwide. Microcirculatory dysfunction is the foremost hindrance for a good clinical prognosis in ischemic stroke patients. Clinical researches show that Chuanzhitongluo capsule (CZTL) has a curative effect during the recovery period of ischemic stroke, which contributes to a good prognosis. However, it is not known whether CZTL treats ischemic stroke by ameliorating microcirculation dysfunction.Objective: In this study, we investigated the influence of CZTL on microcirculation and its underlying mechanism.Methods: A rat model of acute microcirculatory dysfunction was established by stimuli of adrenaline and ice water. The microcirculatory damage in model rats and the efficacy of CZTL were assessed by detecting laser speckle contrast imaging, coagulation function, hemorheology, vasomotor factor and microcirculation function. The potential mechanism of CZTL action was explored by the untargeted metabolomic analysis based on ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry.Results: Laser speckle contrast imaging showed that model rats suffered low perfusion in ears, feet and tails, and CZTL treatment increased microcirculatory blood flow. Coagulation function detection results showed that CZTL diminished the reduction of thrombin time, prothrombin time, activated partial thromboplastin time and the elevated fibrinogen level caused by acute microcirculatory dysfunction. Furthermore, CZTL could recover the increased blood viscosity as well as the abnormal vasomotor and microcirculation function in rats with acute microcirculatory dysfunction. Metabolomics analysis indicated that CZTL might regulate sphingolipid metabolism and arachidonic acid metabolism to exert protective effects on microcirculation.Conclusion: These results elucidated that CZTL was highly effective against microcirculatory dysfunction and its potential mechanisms related with the modulation of sphingolipid and arachidonic acid metabolic pathways. The present study provided a new perspective on the clinical application of CZTL, and it contribute to explore novel therapeutic drug against microcirculatory dysfunction.
first_indexed 2024-04-11T10:19:23Z
format Article
id doaj.art-5532ff7ed14d4d2ba7c3406631ae0e2c
institution Directory Open Access Journal
issn 1663-9812
language English
last_indexed 2024-04-11T10:19:23Z
publishDate 2022-10-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Pharmacology
spelling doaj.art-5532ff7ed14d4d2ba7c3406631ae0e2c2022-12-22T04:29:49ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-10-011310.3389/fphar.2022.10113331011333Chuanzhitongluo capsule ameliorates microcirculatory dysfunction in rats: Efficacy evaluation and metabolic profilesYuanfang Sun0Yuanfang Sun1Yuanfang Sun2Guoliang Cheng3Guoliang Cheng4Lijing Du5Lijing Du6Lijing Du7Yu Gan8Yu Gan9Bing Li10Bing Li11Shikai Yan12Shikai Yan13Shikai Yan14Mingguo Shao15Huizi Jin16Huizi Jin17Shasha Li18Shasha Li19The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, ChinaSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai, ChinaState Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaState Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co.,Ltd, Linyi, ChinaSchool of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaThe Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, ChinaSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai, ChinaState Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, ChinaState Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai, ChinaState Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co.,Ltd, Linyi, ChinaThe Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, ChinaSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai, ChinaState Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co.,Ltd, Linyi, ChinaState Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co.,Ltd, Linyi, ChinaSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai, ChinaState Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co.,Ltd, Linyi, ChinaThe Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, ChinaState Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaBackground: Ischemic stroke is a leading cause of mortality and disability worldwide. Microcirculatory dysfunction is the foremost hindrance for a good clinical prognosis in ischemic stroke patients. Clinical researches show that Chuanzhitongluo capsule (CZTL) has a curative effect during the recovery period of ischemic stroke, which contributes to a good prognosis. However, it is not known whether CZTL treats ischemic stroke by ameliorating microcirculation dysfunction.Objective: In this study, we investigated the influence of CZTL on microcirculation and its underlying mechanism.Methods: A rat model of acute microcirculatory dysfunction was established by stimuli of adrenaline and ice water. The microcirculatory damage in model rats and the efficacy of CZTL were assessed by detecting laser speckle contrast imaging, coagulation function, hemorheology, vasomotor factor and microcirculation function. The potential mechanism of CZTL action was explored by the untargeted metabolomic analysis based on ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry.Results: Laser speckle contrast imaging showed that model rats suffered low perfusion in ears, feet and tails, and CZTL treatment increased microcirculatory blood flow. Coagulation function detection results showed that CZTL diminished the reduction of thrombin time, prothrombin time, activated partial thromboplastin time and the elevated fibrinogen level caused by acute microcirculatory dysfunction. Furthermore, CZTL could recover the increased blood viscosity as well as the abnormal vasomotor and microcirculation function in rats with acute microcirculatory dysfunction. Metabolomics analysis indicated that CZTL might regulate sphingolipid metabolism and arachidonic acid metabolism to exert protective effects on microcirculation.Conclusion: These results elucidated that CZTL was highly effective against microcirculatory dysfunction and its potential mechanisms related with the modulation of sphingolipid and arachidonic acid metabolic pathways. The present study provided a new perspective on the clinical application of CZTL, and it contribute to explore novel therapeutic drug against microcirculatory dysfunction.https://www.frontiersin.org/articles/10.3389/fphar.2022.1011333/fullchuanzhitongluo capsulemicrocirculatory dysfunctionlaser speckle contrast imagingefficacy outcomemechanism exploration
spellingShingle Yuanfang Sun
Yuanfang Sun
Yuanfang Sun
Guoliang Cheng
Guoliang Cheng
Lijing Du
Lijing Du
Lijing Du
Yu Gan
Yu Gan
Bing Li
Bing Li
Shikai Yan
Shikai Yan
Shikai Yan
Mingguo Shao
Huizi Jin
Huizi Jin
Shasha Li
Shasha Li
Chuanzhitongluo capsule ameliorates microcirculatory dysfunction in rats: Efficacy evaluation and metabolic profiles
Frontiers in Pharmacology
chuanzhitongluo capsule
microcirculatory dysfunction
laser speckle contrast imaging
efficacy outcome
mechanism exploration
title Chuanzhitongluo capsule ameliorates microcirculatory dysfunction in rats: Efficacy evaluation and metabolic profiles
title_full Chuanzhitongluo capsule ameliorates microcirculatory dysfunction in rats: Efficacy evaluation and metabolic profiles
title_fullStr Chuanzhitongluo capsule ameliorates microcirculatory dysfunction in rats: Efficacy evaluation and metabolic profiles
title_full_unstemmed Chuanzhitongluo capsule ameliorates microcirculatory dysfunction in rats: Efficacy evaluation and metabolic profiles
title_short Chuanzhitongluo capsule ameliorates microcirculatory dysfunction in rats: Efficacy evaluation and metabolic profiles
title_sort chuanzhitongluo capsule ameliorates microcirculatory dysfunction in rats efficacy evaluation and metabolic profiles
topic chuanzhitongluo capsule
microcirculatory dysfunction
laser speckle contrast imaging
efficacy outcome
mechanism exploration
url https://www.frontiersin.org/articles/10.3389/fphar.2022.1011333/full
work_keys_str_mv AT yuanfangsun chuanzhitongluocapsuleamelioratesmicrocirculatorydysfunctioninratsefficacyevaluationandmetabolicprofiles
AT yuanfangsun chuanzhitongluocapsuleamelioratesmicrocirculatorydysfunctioninratsefficacyevaluationandmetabolicprofiles
AT yuanfangsun chuanzhitongluocapsuleamelioratesmicrocirculatorydysfunctioninratsefficacyevaluationandmetabolicprofiles
AT guoliangcheng chuanzhitongluocapsuleamelioratesmicrocirculatorydysfunctioninratsefficacyevaluationandmetabolicprofiles
AT guoliangcheng chuanzhitongluocapsuleamelioratesmicrocirculatorydysfunctioninratsefficacyevaluationandmetabolicprofiles
AT lijingdu chuanzhitongluocapsuleamelioratesmicrocirculatorydysfunctioninratsefficacyevaluationandmetabolicprofiles
AT lijingdu chuanzhitongluocapsuleamelioratesmicrocirculatorydysfunctioninratsefficacyevaluationandmetabolicprofiles
AT lijingdu chuanzhitongluocapsuleamelioratesmicrocirculatorydysfunctioninratsefficacyevaluationandmetabolicprofiles
AT yugan chuanzhitongluocapsuleamelioratesmicrocirculatorydysfunctioninratsefficacyevaluationandmetabolicprofiles
AT yugan chuanzhitongluocapsuleamelioratesmicrocirculatorydysfunctioninratsefficacyevaluationandmetabolicprofiles
AT bingli chuanzhitongluocapsuleamelioratesmicrocirculatorydysfunctioninratsefficacyevaluationandmetabolicprofiles
AT bingli chuanzhitongluocapsuleamelioratesmicrocirculatorydysfunctioninratsefficacyevaluationandmetabolicprofiles
AT shikaiyan chuanzhitongluocapsuleamelioratesmicrocirculatorydysfunctioninratsefficacyevaluationandmetabolicprofiles
AT shikaiyan chuanzhitongluocapsuleamelioratesmicrocirculatorydysfunctioninratsefficacyevaluationandmetabolicprofiles
AT shikaiyan chuanzhitongluocapsuleamelioratesmicrocirculatorydysfunctioninratsefficacyevaluationandmetabolicprofiles
AT mingguoshao chuanzhitongluocapsuleamelioratesmicrocirculatorydysfunctioninratsefficacyevaluationandmetabolicprofiles
AT huizijin chuanzhitongluocapsuleamelioratesmicrocirculatorydysfunctioninratsefficacyevaluationandmetabolicprofiles
AT huizijin chuanzhitongluocapsuleamelioratesmicrocirculatorydysfunctioninratsefficacyevaluationandmetabolicprofiles
AT shashali chuanzhitongluocapsuleamelioratesmicrocirculatorydysfunctioninratsefficacyevaluationandmetabolicprofiles
AT shashali chuanzhitongluocapsuleamelioratesmicrocirculatorydysfunctioninratsefficacyevaluationandmetabolicprofiles