Phytochemical Analysis Using UPLC-MS/MS Combined with Network Pharmacology Methods to Explore the Biomarkers for the Quality Control of Lingguizhugan Decoction.

Baolin Li,Yongben Ma,Jingnan Hu,Fengxia Wang,Yu Feng,Shuaishuai Fan,Xinguo Wang,Liying Niu,Nahla S Abdel Azim

doi:10.1155/2021/7849032

Abstract

As a classic TCM prescription, LGZG has been widely used in clinical prevention and treatment of heart failure, nonalcoholic fatty liver, and hyperlipidemia. However, there are few studies on chemical components in recent years, and the basis of quality evaluation is not sufficient. This study was to find the active ingredients of the Lingguizhugan decoction using UPLC-MS/MS and network pharmacology. By comparing the retention time and MS dates of the reference and self-building database, the cleavage rules of chemical composition whose mass errors are less than 1 ppm(FL less than 3 ppm) are analyzed. On this basis, a network pharmacology method was used to find biomarkers for quantitative analysis. The results show that 149 compounds were preliminaries identified or inferred, including 63 flavonoids, 30 triterpenes, 22 phenylpropanoids, 13 organic acids, 6 lactones, 5 alkaloids, 4 anthraquinones, and 6 other compounds. According to the network pharmacology results, 20 chemical constituents were selected as the biomarkers, which were determined simultaneously for the first time, including poricoic acid A, poricoic acid B, glycyrrhizic acid, glycyrrhetinic acid, liquiritin, isoliquiritin, liquiritigenin, isoliquiritin apioside, cinnamic acid, caffeic acid, neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, isochlorogenic acid A, B, and C, atractylenolide I, II, and III, and coumarin. The methodological results show that the linearity, stability, precision, repeatability, and recovery of the method are satisfactory. Therefore, a comprehensive quality assessment system for LGZG was established on the basis of a systematic study of chemical substances and network pharmacology, which provided an important reference for the foundation of pharmacological action and its mechanics.

Highlights

Lingguizhugan decoction (LGZG), coming from Zhang Zhongjing’s Synopsis of Preions of the Golden Chamber, has already been listed as the first batch of “ e Catalogue of ancient classical prescription” by the National Administration of Traditional Chinese Medicine (TCM) in 2018
Combined with the present stage of research, most of the studies on LGZG have been restricted to the main research index of licorice-related components, while the related components in other herbal medicines are rarely involved, or the overall quality evaluation indexes are not comprehensive, or the range of mass error is excessive, which results in a limited accuracy [12, 13]
The 149 components of LGZG were preliminarily identified or inferred by UPLC-Q/ TOF-MS, including flavonoids, triterpenoids, phenylpropanoids, organic acids, quinones, and other types of components. en, a total of 20 biomarkers were screened by network pharmacological screening based on the presumed chemical composition

Summary

Introduction

Lingguizhugan decoction (LGZG), coming from Zhang Zhongjing’s Synopsis of Preions of the Golden Chamber, has already been listed as the first batch of “ e Catalogue of ancient classical prescription” by the National Administration of Traditional Chinese Medicine (TCM) in 2018. LGZG is prepared by four different herbal medicines, namely Fuling (the dry sclerotia of Poria cocos (Schw.), FL), Guizhi (the dry twigs of Cinnamomum cassia Presl, GZ), Baizhu (the dry rhizome of Atractylodes macrocephala Koidz, BZ), and Gancao (the dry root and rhizome of Glycyrrhiza uralensis Fisch., Glycyrrhiza inflata Bat. Or Glycyrrhiza glabra L., GC). Combined with the present stage of research, most of the studies on LGZG have been restricted to the main research index of licorice-related components, while the related components in other herbal medicines are rarely involved, or the overall quality evaluation indexes are not comprehensive, or the range of mass error is excessive, which results in a limited accuracy [12, 13]. Considering that licorice is only used as a guide medicine in the prescription, the comprehensiveness and objectivity of the method cannot be guaranteed

Methods

Results

Conclusion