Modulation of an aqueous extract of Chinese medicine prescription Anzi Heji (安子合剂) on ratio of CD4+CD25+FOXP3+ regulatory T cells in anticardiolipin antibody-positive patients with threatened abortion

Lu, Qibin; Zhu, Shiyun

doi:10.1007/s11655-015-2444-3

Cited by 5 publications

(9 citation statements)

References 20 publications

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“…Formation, uterine settlement, nutrition, and embryo development can significantly affect the local decidual tissues and induce increased levels of CD4 + CD25 + Treg cells. These, however, seldomly enter the peripheral circulation, where there are insufficient corresponding antigens or receptors to interact with CD4 + CD25 + Treg ( 12 ).…”

Section: Discussionmentioning

confidence: 99%

Correlation between unexplained recurrent spontaneous abortion with CD4+CD25+ regulatory T-cell and killer cell immunoglobulin-like receptor levels

Quan

Yang

2017

Experimental and Therapeutic Medicine

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The present study investigated the correlation between unexplained recurrent spontaneous abortion (URSA) with CD4+CD25+ regulatory T-cell (Treg) and killer cell immunoglobulin-like receptor (KIR)-2DL1 levels. A total of 76 URSA patients were enrolled (35 without pregnancy, Group A, and 41 with early abortion, Group B). Additionally, 30 patients who received a regular abortion as planned (Group C) and 30 healthy volunteers (Group D) were selected. Peripheral venous blood and fresh decidual tissue samples were obtained from all the patients, and flow cytometry was performed to detect CD4+CD25+Treg and Foxp3 transcription factor levels. mRNA and protein KIR-2DL1 expression levels were assayed using quantitative PCR and western blot analysis, respectively. No statistically significant differences in peripheral venous blood CD4+CD25+Treg/CD4+ and Foxp3+/CD4+CD25+Treg cell proportions were found among the groups (P>0.05). However, the decidual tissues of Group C presented significantly higher levels of both cell types versus other groups (P<0.05). No statistically significant differences were found in comparisons among Groups A, B, and D (P>0.05). In peripheral venous blood, mRNA and protein KIR-2DL1 expression levels in Group C were significantly higher than those in the other three groups (P<0.05), but again, there were no statistically significant differences among Groups A, B, and D (P>0.05). In decidual tissues, KIR-2DL1 levels were significantly higher in Group C relative to Groups A, B, and D (P<0.05). Decreased CD4+CD25+Treg counts and KIR-2DL1 expression levels were closely associated with the onset of URSA. CD4+CD25+Tregs mainly exert their effects on decidual tissues, while KIR-2DL1 can act on peripheral venous blood and decidual tissues. These may present new targets for early intervention in URSA.

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Section: Discussionmentioning

confidence: 99%

Correlation between unexplained recurrent spontaneous abortion with CD4+CD25+ regulatory T-cell and killer cell immunoglobulin-like receptor levels

Quan

Yang

2017

Experimental and Therapeutic Medicine

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“…9 Our previous study showed that AZHJ could significantly reduce the serum ACA content in model mice and improve the proliferation activity of trophoblast cells, markedly ameliorate the clinical symptoms of ACA-positive pregnant women at risk of spontaneous abortion and improve pregnancy hormones levels. 10 AZHJ could also regulate peripheral blood and maternal–fetal interface Treg cells, and effectively increase the proportion of peripheral blood Treg cells in patients with ACA-positive abortion. 10,11 However, the therapeutic mechanism of AZHJ is not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Anzi Heji Downregulates DNMT1 to Improve Anticardiolipin Antibody (ACA)-Positive Abortion by Regulating JAK/STAT Pathway

2022

Natural Product Communications

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Anzi Heji (AZHJ) is a traditional Chinese medicine compound prepared for long-term treatment of Anticardiolipin Antibody (ACA)-positive abortion, with small side effects and definite curative effect. Abortion was reported to be related to DNMT1, a methylation transferase regulated by JAK2 pathway, so this study aimed to explore whether AZHJ treated ACA-positive abortion by regulating the DNMT1. Cell proliferation estimation employed Cell counting kit-8 (CCK-8) and flow cytometry. Human β2-glycoprotein I (GPI) was used as an inducer to establish ACA-positive mice model. Western blot was applied to examine the expressions of DNMT1, FOXP3, IL-6, and JAK/STAT3 pathway-related proteins. ACA titers and IL-6 levels in peripheral blood were tested by enzyme-linked immunosorbent assay (ELISA). Placental tissue damage was assessed by hematoxylin and eosin (H&E) staining. Based on the findings from experiments, AZHJ could significantly inhibit apoptosis and regulate the proliferation activity of HTR-8/SVneo cells. AZHJ treatment reduced the expression levels of DNMT1, FOXP3, IL-6, and JAK/STAT3 signaling pathways-related proteins in HTR-8/SVneo cells and maternal–fetal interface (uterine decidua and placenta), and the titer of serum ACA was also significantly decreased. In addition, AZHJ effectively alleviated placental tissue damage caused by ACA-positive abortion compared with model group. To sum up, AZHJ may play a therapeutic role by inhibiting DNMT1 activation through Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, and then promoting FOXP3 expression in maternal–fetal interface of pregnant mice, thereby improving immune tolerance at the maternal–fetal interface, preventing and treating ACA-positive abortion.

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“…Extracts from traditional Chinese medicine herbs or other herbs have been used to prevent abortion due to their various abilities to regulate immune responses [ 5 – 7 ]. Anzi Heji (AZHJ) is an approved prescription at Jiangsu Province Hospital of Traditional Chinese Medicine, China (approval no.…”

Section: Introductionmentioning

confidence: 99%

“…It has been used to prevent spontaneous abortion (especially in ACA-positive cases) for many years. It has no toxic side effects [ 7 ]. The main components of AZHJ are Cuscuta chinensis , sangjisheng, ramie root, Dipsacus asperata , Salvia miltiorrhiza , Atractylodes macrocephala , Scutellaria baicalensis , radix Pseudostellariae, and roasted Glycyrrhizae.…”

Section: Introductionmentioning

confidence: 99%

Proteomic Analysis of Differentially Expressed Proteins in the Placenta of Anticardiolipin Antibody‐ (ACA‐) Positive Pregnant Mice after Anzi Heji Treatment

Xie

2020

Evidence-Based Complementary and Alternative Medicine

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Anzi Heji (AZHJ) has been used to treat anticardiolipin antibody- (ACA-) positive pregnant women at risk of spontaneous abortion for many years. The aim of this study was to investigate the protective mechanism of AZHJ in a mouse model of ACA-positive pregnancy at risk of spontaneous abortion using label-free quantitative proteomics. Mice were divided into three groups: normal pregnant mice (control group), ACA-positive pregnant mice administered normal saline (model group), and ACA-positive pregnant mice administered AZHJ (AZHJ group). The model was established by injecting β 2 -glycoprotein I (GPI) into mice for 18 days. The DEPs and their functions were analyzed by label-free quantitative proteomic and bioinformatic analyses. The levels of IL-6, IL-10, ACA, and TNF- α in the serum and placentas of the mice were measured by enzyme-linked immunosorbent assays (ELISAs). Proteomic data were validated by western blot analysis. The abnormal serum and placental levels of IL-6, ACA, and TNF- α in the model group were reversed by AZHJ. There were 39 upregulated and 10 downregulated DEPs in the AZHJ group relative to the model group. Bioinformatic analysis revealed that the DEPs were mainly involved in nucleic acid binding, signal conduction, and posttranslational modification. The placental levels of T-cell immunoglobulin mucin 3 (Tim-3) and Toll-like receptor 4 (TLR4) expression and AKT phosphorylation in the three groups were consistent with the proteomic findings. Tim-3/AKT signaling is involved in maternal-fetal immune tolerance, while TLR4 is associated with inflammatory responses. Collectively, these results indicate that AZHJ may exert its protective effect in ACA-positive pregnant mice by regulating the maternal-fetal immune tolerance and inflammatory response.

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Modulation of an aqueous extract of Chinese medicine prescription Anzi Heji (安子合剂) on ratio of CD4+CD25+FOXP3+ regulatory T cells in anticardiolipin antibody-positive patients with threatened abortion

Abstract: AZHJ can regulate the immune function of pregnant women by increasing number of CD4CD25FOXP3 Tregs.

Cited by 5 publications

References 20 publications

Correlation between unexplained recurrent spontaneous abortion with CD4+CD25+ regulatory T-cell and killer cell immunoglobulin-like receptor levels

Correlation between unexplained recurrent spontaneous abortion with CD4+CD25+ regulatory T-cell and killer cell immunoglobulin-like receptor levels

Anzi Heji Downregulates DNMT1 to Improve Anticardiolipin Antibody (ACA)-Positive Abortion by Regulating JAK/STAT Pathway

Proteomic Analysis of Differentially Expressed Proteins in the Placenta of Anticardiolipin Antibody‐ (ACA‐) Positive Pregnant Mice after Anzi Heji Treatment

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