Development of a comprehensive method combining UHPLC-CAD fingerprint, multi-components quantitative analysis for quality evaluation of Zishen Yutai Pills: A step towards quality control of Chinese patent medicine

Cao, Jiliang; Lei, Ting; Wu, Sijia; Li, Hongyi; Deng, Yun; Lin, Ruizhen; Ning, Na; Geng, Chunxian; Wang, Shengpeng; Wu, Xu; Wang, Ying

doi:10.1016/j.jpba.2020.113570

Cited by 30 publications

(30 citation statements)

References 24 publications

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“…Recent studies with ZSYT pills identi ed improvements in clinical symptoms of hormone disorders and an increase in the FSH and luteinizing hormone (LH) levels in the treatment group compared to the controls, indicating the clinical potential of ZSYT in treating POF (11,12). Although the methanol extracts of ZSYT pills were analyzed previously in vitro via UHPLC-Q-TOF-MS (13), the active components in vivo and their pharmacological targets in treating POF have not been elucidated. Our study indicates synergistic effects of ZSYT components and suggests their pharmacological mechanisms in treating POF.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of Action of Zishen Yutai pills in Treating Premature Ovarian Failure Determined by Integrating UHPLC-Q-TOF-MS and Network Pharmacology Analysis

Dang

Zhang

Su³

et al. 2022

Preprint

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Background: Zishen Yutai (ZSYT) pill, a patent Chinese medicine, has been widely used in the treatment of infertility, abortion, and adjunctive treatment of in vitro fertilization (IVF) for decades. Recently, the results of clinical observations showed that premature ovarian failure (POF) patients exhibited improved expression of steroids and clinical symptoms associated with hormone disorders after treatment with ZSYT pills. However, the pharmacological mechanism of action of these pills remains unclear.Methods: The components of ZSYT found in blood circulation were identified via ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) technique in the serum of POF mice after oral administration of ZSYT pills. The potential targets of components were screened using Traditional Chinese Medicine Systems Pharmacology Database, Traditional Chinese Medicine Database@Taiwan, Drugbank Database, PubChem, HIT, Pharmapper, and SwissTargetPrediction. The target genes associated with POF were collected from Online Mendelian Inheritance in Man Database, PharmGkb, Genecards, therapeutic target database, and Genetic Association Database. The overlapping genes between the potential targets of ZSYT components and the target genes associated with POF were clarified via protein-protein interaction (PPI), pathway, and network analysis.Results: Nineteen components in ZSYT pills were detected in the serum of POF mice after oral administration. A total of 695 ZSYT-related targets was screened, and 344 POF-related targets were collected. From the results of ZSYT-POF PPI analysis, CYP19A1, AKR1C3, ESR1, AR, and SRD5A2 were identified as key targets via network analysis, indicating their core role in the treatment of POF with ZSYT pills. Moreover, the pathway enrichment results suggested that ZSYT pills treat POF primarily by regulating neuroactive ligand-receptor interaction, steroid hormone biosynthesis, and ovarian steroidogenesis.Conclusions: We demonstrated that regulation of neuroactive ligand-receptor interaction, steroid hormone biosynthesis, and ovarian steroidogenesis are very likely to be therapeutic mechanism of ZSYT pills in treating POF. Our study suggests that combining the analysis of ZSYT pills components in blood in vivo in the POF models and network pharmacology prediction may offer a tool to characterize the mechanism of ZSYT pills in the POF.

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Section: Introductionmentioning

confidence: 99%

Mechanisms of Action of Zishen Yutai pills in Treating Premature Ovarian Failure Determined by Integrating UHPLC-Q-TOF-MS and Network Pharmacology Analysis

Dang

Zhang

Su³

et al. 2022

Preprint

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“…Traditional Chinese medicine is an important complementary therapy in the IVF-ET ( Smith et al, 2010 ). Zishen Yutai Pills (ZYP) is a safe and well quality-controlled TCM preparation with promising effects in many fields of reproduction, including prevention of miscarriage, increase of pregnancy rate ( Zhu et al, 2002 ; Gao et al, 2015b ; Ma et al, 2018 ; Cao et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…), and Amomi Fructus (the dried fruit of Amomum villosum Lour.) ( Cao et al, 2020 ). The formula of ZYP is listed as shown in Table 1 , including detailed formula and the amounts of raw materials contained in the daily dose.…”

Section: Introductionmentioning

confidence: 99%

“…In another report, ultrahigh performance liquid chromatography coupled with charged aerosol detector (UPLC-CAD) fingerprint and multi-components quantitative analysis was developed and validated for quality evaluation of ZYP. Fifty-two characteristic peaks were selected to evaluate the similarities among different batches of ZYP ( Cao et al, 2020 ). Both methods could be the proof of the stability of ZYP, due to the consistency in both contents of components and fingerprint chromatogram.…”

Section: Introductionmentioning

confidence: 99%

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Metabonomics Study on the Infertility Treated With Zishen Yutai Pills Combined With In Vitro Fertilization-embryo Transfer

Ning²,

Wei

et al. 2021

Front. Pharmacol.

Self Cite

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Zishen Yutai Pills (ZYP) is a safe and well quality-controlled TCM preparation with promising effects in many fields of reproduction, including prevention of miscarriage, increase of pregnancy rate during in vitro fertilization-embryo transfer (IVF-ET). The plasma of patients was collected from a clinical trial, namely, “Effect of Traditional Chinese Medicine vs placebo on live births among women undergoing in vitro fertilization, a multi-center randomized controlled trial.” Plasma samples were analyzed with metabonomics method. UPLC-MS technology was used to establish the plasma metabolic fingerprint. Multivariate statistical analysis was applied for comparing the differences of plasma metabolites between ZYP group and placebo group, 44 potential metabolites were screen out and identified. Pathway analysis was conducted with database mining. Compared with placebo, chemicals were found to be significantly down-regulated on HCG trigger day and 14 days after embryo transplantation, including trihexosylceramide (d18:1/26:1), glucosylceramide(d18:1/26:0), TG(22:6/15:0/22:6), TG(22:4/20:4/18:4). Compared with placebo, some chemicals were found to be significantly up-regulated on HCG trigger day and 14 days after embryo transplantation, i.e., PIP3(16:0/16:1), PIP2(18:1/18:1), tauroursodeoxycholic acid, L-asparagine, L-glutamic acid, kynurenic acid, 11-deoxycorticosterone, melatonin glucuronide, hydroxytyrosol. These metabolites were highly enriched in pathways including sphingolipid metabolism, alanine, aspartic acid and glutamic acid metabolism, aminoacyl tRNA biosynthesis, taurine and hypotaurine metabolism. This study revealed metabolic differences between subjects administered with ZYP and placebo. Relating metabolites were identified and pathways were enriched, providing basis on the exploration on the underlying mechanisms of ZYP combined with IVF-ET in the treatment of infertility.

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“…Previous experimental studies and clinical experiences have suggested that compound Chinese medicine have significant clinical efficacy [7]. ZSYTP is a well-known compound Chinese medicine that is widely used for treating reproductive disorders [8,9]. ZSYTP can effectively relieve the clinical symptoms caused by low estrogen through lowering serum follicle-stimulating hormone (FSH) levels and elevating serum estrogen levels [10,11].…”

Section: Introductionmentioning

confidence: 99%

Network Pharmacology Approach for Predicting Targets of Zishen Yutai Pills on Premature Ovarian Insufficiency

Feng

Chai

Chen

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Background and Purpose. Premature ovarian insufficiency (POI) is a serious reproductive disease in females that is characterized by menstrual and ovulation disorders and infertility. The clinical efficacy of complementary and alternative medicine (CAM) has been reported in POI, including compound Chinese medicine. Zishen Yutai Pills (ZSYTP), a well-known patented Chinese medicine, has been widely used for treating POI; however, the pharmacological mechanism and molecular targets of ZSYTP remain unknown. Here, we systematically elucidated the pharmacological mechanism of ZSYTP on POI using a network pharmacology approach and further validated our findings with molecular docking. Methods. A comprehensive strategy based on several Chinese herb databases and chemical compound databases was established to screen active compounds of ZSYTP and predict target genes. For network pharmacological analysis, network construction and gene enrichment analysis were conducted and further verified by molecular docking. Results. A total of 476 target genes of ZSYTP were obtained from 205 active compounds. 13 herbs of ZSYTP overlapped on 8 active compounds based on the compound-target-disease network (C-T network). 20 biological processes and 9 pathways were strongly connected to the targets of ZSYTP in treating POI, including negative regulation of gene expression, mRNA metabolic process, hypoxia-inducible factor 1 (HIF-1) signaling pathway, and gluconeogenesis. Finally, molecular docking was visualized. Conclusion. Intriguingly, the signal pathways and biological processes uncovered in this study implicate inflamm-aging and glucose metabolism as potential pathological mechanisms of POI. The therapeutic effect of ZSYTP could be mediated by regulating glucose metabolism and HIF-1 signal pathway. Collectively, this study sheds light on the therapeutic potential of ZSYTP on POI.

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Development of a comprehensive method combining UHPLC-CAD fingerprint, multi-components quantitative analysis for quality evaluation of Zishen Yutai Pills: A step towards quality control of Chinese patent medicine

Cited by 30 publications

References 24 publications

Mechanisms of Action of Zishen Yutai pills in Treating Premature Ovarian Failure Determined by Integrating UHPLC-Q-TOF-MS and Network Pharmacology Analysis

Mechanisms of Action of Zishen Yutai pills in Treating Premature Ovarian Failure Determined by Integrating UHPLC-Q-TOF-MS and Network Pharmacology Analysis

Metabonomics Study on the Infertility Treated With Zishen Yutai Pills Combined With In Vitro Fertilization-embryo Transfer

Network Pharmacology Approach for Predicting Targets of Zishen Yutai Pills on Premature Ovarian Insufficiency

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