Qualitative and quantitative analyses of chemical constituents in vitro and in vivo and systematic evaluation of the pharmacological effects of Tibetan medicine Zhixue Zhentong capsules

Introduction: Zhixue Zhentong capsules (ZXZTCs) are a Tibetan medicine preparation solely composed of Lamiophlomis rotata (Benth.) Kudo. L. rotata is the only species of the genus Laniophlomis (family Lamiaceae) that has medicinal constituents derived from the grass or root and rhizome. L. rotata is...

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Main Authors: Yinglian Song, Yan Liang, Rong Zeng, Ran Li, You Zhou, Sheng Huang, Xiaoli Li, Ning Zhang, Min Xu, Kaipeng Xiong, Ke Fu, Huixuan Ye, Lei Wu, Shaopeng Yu, Wanyue Chen, Ce Tang, Miao Jiang, Zhang Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-07-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2023.1204947/full
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author Yinglian Song
Yinglian Song
Yan Liang
Yan Liang
Rong Zeng
Ran Li
Ran Li
You Zhou
You Zhou
Sheng Huang
Xiaoli Li
Xiaoli Li
Ning Zhang
Min Xu
Min Xu
Kaipeng Xiong
Ke Fu
Ke Fu
Huixuan Ye
Lei Wu
Lei Wu
Shaopeng Yu
Shaopeng Yu
Wanyue Chen
Wanyue Chen
Ce Tang
Miao Jiang
Miao Jiang
Zhang Wang
Zhang Wang
author_facet Yinglian Song
Yinglian Song
Yan Liang
Yan Liang
Rong Zeng
Ran Li
Ran Li
You Zhou
You Zhou
Sheng Huang
Xiaoli Li
Xiaoli Li
Ning Zhang
Min Xu
Min Xu
Kaipeng Xiong
Ke Fu
Ke Fu
Huixuan Ye
Lei Wu
Lei Wu
Shaopeng Yu
Shaopeng Yu
Wanyue Chen
Wanyue Chen
Ce Tang
Miao Jiang
Miao Jiang
Zhang Wang
Zhang Wang
author_sort Yinglian Song
collection DOAJ
description Introduction: Zhixue Zhentong capsules (ZXZTCs) are a Tibetan medicine preparation solely composed of Lamiophlomis rotata (Benth.) Kudo. L. rotata is the only species of the genus Laniophlomis (family Lamiaceae) that has medicinal constituents derived from the grass or root and rhizome. L. rotata is one of the most extensively used folk medicines by Tibetan, Mongolian, Naxi, and other ethnic groups in China and has been listed as a first-class endangered Tibetan medicine. The biological effects of the plant include hemostasis, analgesia, and the removal of blood stasis and swelling.Purpose: This study aimed to profile the overall metabolites of ZXZTCs and those entering the blood. Moreover, the contents of six metabolites were measured and the hemostatic, analgesic, and anti-inflammatory effects of ZXZTCs were explored.Methods: Ultra-performance liquid chromatography–tandem quadrupole time-of-flight high-resolution mass spectrometry (UPLC-Q-TOF-MS) was employed for qualitative analysis of the metabolites of ZXZTCs and those entering the blood. Six metabolites of ZXZTCs were quantitatively determined via high-performance liquid chromatography The hemostatic, analgesic, and anti-inflammatory effects of ZXZTCs were evaluated in various animal models.Results: A total of 36 metabolites of ZXZTCs were identified, including 13 iridoid glycosides, 9 flavonoids, 9 phenylethanol glycosides, 4 phenylpropanoids, and 1 other metabolite. Overall, 11 metabolites of ZXZTCs entered the blood of normal rats. Quantitative analysis of the six main metabolites, shanzhiside methyl ester, chlorogenic acid, 8-O-acetyl shanzhiside methyl ester, forsythin B, luteoloside, and verbascoside, was extensively performed. ZXZTCs exerted hemostatic effects by reducing platelet aggregation and thrombosis and shortening bleeding time. Additionally, ZXZTCs clearly had an analgesic effect, as observed through the prolongation of the latency of writhing, reduction in writhing, and increase in the pain threshold of experimental rats. Furthermore, significant anti-inflammatory effects of ZXZTCs were observed, including a reduction in capillary permeability, the inhibition of foot swelling, and a reduction in the proliferation of granulation tissue.Conclusion: Speculative identification of the overall metabolites of ZXZTCs and those entering the blood can provide a foundation for determining its biologically active constituents. The established method is simple and reproducible and can help improve the quality control level of ZXZTCs as a medicinal product. Evaluating the hemostatic, analgesic, and anti-inflammatory activities of ZXZTCs can help reveal its mechanism.
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spelling doaj.art-59fed5ab3894494a91edb8fd0a5b28b32023-07-17T23:24:19ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-07-011410.3389/fphar.2023.12049471204947Qualitative and quantitative analyses of chemical constituents in vitro and in vivo and systematic evaluation of the pharmacological effects of Tibetan medicine Zhixue Zhentong capsulesYinglian Song0Yinglian Song1Yan Liang2Yan Liang3Rong Zeng4Ran Li5Ran Li6You Zhou7You Zhou8Sheng Huang9Xiaoli Li10Xiaoli Li11Ning Zhang12Min Xu13Min Xu14Kaipeng Xiong15Ke Fu16Ke Fu17Huixuan Ye18Lei Wu19Lei Wu20Shaopeng Yu21Shaopeng Yu22Wanyue Chen23Wanyue Chen24Ce Tang25Miao Jiang26Miao Jiang27Zhang Wang28Zhang Wang29College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaCollege of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaChengdu Jiuzhitang Jinding Pharmaceutical Company Limited, Chengdu, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaCollege of Ethnomedicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaCollege of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaJiuzhitang Company Limited, Changsha, ChinaCollege of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaChengdu Jiuzhitang Jinding Pharmaceutical Company Limited, Chengdu, ChinaCollege of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaChengdu Jiuzhitang Jinding Pharmaceutical Company Limited, Chengdu, ChinaCollege of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaJiuzhitang Company Limited, Changsha, ChinaCollege of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaCollege of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaCollege of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaCollege of Ethnomedicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaCollege of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaCollege of Ethnomedicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaIntroduction: Zhixue Zhentong capsules (ZXZTCs) are a Tibetan medicine preparation solely composed of Lamiophlomis rotata (Benth.) Kudo. L. rotata is the only species of the genus Laniophlomis (family Lamiaceae) that has medicinal constituents derived from the grass or root and rhizome. L. rotata is one of the most extensively used folk medicines by Tibetan, Mongolian, Naxi, and other ethnic groups in China and has been listed as a first-class endangered Tibetan medicine. The biological effects of the plant include hemostasis, analgesia, and the removal of blood stasis and swelling.Purpose: This study aimed to profile the overall metabolites of ZXZTCs and those entering the blood. Moreover, the contents of six metabolites were measured and the hemostatic, analgesic, and anti-inflammatory effects of ZXZTCs were explored.Methods: Ultra-performance liquid chromatography–tandem quadrupole time-of-flight high-resolution mass spectrometry (UPLC-Q-TOF-MS) was employed for qualitative analysis of the metabolites of ZXZTCs and those entering the blood. Six metabolites of ZXZTCs were quantitatively determined via high-performance liquid chromatography The hemostatic, analgesic, and anti-inflammatory effects of ZXZTCs were evaluated in various animal models.Results: A total of 36 metabolites of ZXZTCs were identified, including 13 iridoid glycosides, 9 flavonoids, 9 phenylethanol glycosides, 4 phenylpropanoids, and 1 other metabolite. Overall, 11 metabolites of ZXZTCs entered the blood of normal rats. Quantitative analysis of the six main metabolites, shanzhiside methyl ester, chlorogenic acid, 8-O-acetyl shanzhiside methyl ester, forsythin B, luteoloside, and verbascoside, was extensively performed. ZXZTCs exerted hemostatic effects by reducing platelet aggregation and thrombosis and shortening bleeding time. Additionally, ZXZTCs clearly had an analgesic effect, as observed through the prolongation of the latency of writhing, reduction in writhing, and increase in the pain threshold of experimental rats. Furthermore, significant anti-inflammatory effects of ZXZTCs were observed, including a reduction in capillary permeability, the inhibition of foot swelling, and a reduction in the proliferation of granulation tissue.Conclusion: Speculative identification of the overall metabolites of ZXZTCs and those entering the blood can provide a foundation for determining its biologically active constituents. The established method is simple and reproducible and can help improve the quality control level of ZXZTCs as a medicinal product. Evaluating the hemostatic, analgesic, and anti-inflammatory activities of ZXZTCs can help reveal its mechanism.https://www.frontiersin.org/articles/10.3389/fphar.2023.1204947/fullLamiophlomis rotata (Benth.) KudoUPLC-Q-TOF-MSmetabolites entered in the bloodHPLCcontent determinationhemostasis
spellingShingle Yinglian Song
Yinglian Song
Yan Liang
Yan Liang
Rong Zeng
Ran Li
Ran Li
You Zhou
You Zhou
Sheng Huang
Xiaoli Li
Xiaoli Li
Ning Zhang
Min Xu
Min Xu
Kaipeng Xiong
Ke Fu
Ke Fu
Huixuan Ye
Lei Wu
Lei Wu
Shaopeng Yu
Shaopeng Yu
Wanyue Chen
Wanyue Chen
Ce Tang
Miao Jiang
Miao Jiang
Zhang Wang
Zhang Wang
Qualitative and quantitative analyses of chemical constituents in vitro and in vivo and systematic evaluation of the pharmacological effects of Tibetan medicine Zhixue Zhentong capsules
Frontiers in Pharmacology
Lamiophlomis rotata (Benth.) Kudo
UPLC-Q-TOF-MS
metabolites entered in the blood
HPLC
content determination
hemostasis
title Qualitative and quantitative analyses of chemical constituents in vitro and in vivo and systematic evaluation of the pharmacological effects of Tibetan medicine Zhixue Zhentong capsules
title_full Qualitative and quantitative analyses of chemical constituents in vitro and in vivo and systematic evaluation of the pharmacological effects of Tibetan medicine Zhixue Zhentong capsules
title_fullStr Qualitative and quantitative analyses of chemical constituents in vitro and in vivo and systematic evaluation of the pharmacological effects of Tibetan medicine Zhixue Zhentong capsules
title_full_unstemmed Qualitative and quantitative analyses of chemical constituents in vitro and in vivo and systematic evaluation of the pharmacological effects of Tibetan medicine Zhixue Zhentong capsules
title_short Qualitative and quantitative analyses of chemical constituents in vitro and in vivo and systematic evaluation of the pharmacological effects of Tibetan medicine Zhixue Zhentong capsules
title_sort qualitative and quantitative analyses of chemical constituents in vitro and in vivo and systematic evaluation of the pharmacological effects of tibetan medicine zhixue zhentong capsules
topic Lamiophlomis rotata (Benth.) Kudo
UPLC-Q-TOF-MS
metabolites entered in the blood
HPLC
content determination
hemostasis
url https://www.frontiersin.org/articles/10.3389/fphar.2023.1204947/full
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