A Potential Mechanism of Kidney-Tonifying Herbs Treating Unexplained Recurrent Spontaneous Abortion: Clinical Evidence From the Homogeneity of Embryo Implantation and Tumor Invasion.

Hang Zhou,Linwen Deng,Xin Liao,Yongqing Yao,Yi Yang

doi:10.3389/fphar.2021.775245

Abstract

Background: Kidney-tonifying herbs (KTHs) are widely used to treat unexplained recurrent spontaneous abortion (URSA) based on the theory of traditional Chinese medicine (TCM). However, there is still a lack of systematic evaluation and mechanistic explanation for these treatments. Objective: The purpose of this study was to assess the clinical efficacy, and to investigate the potential mechanisms, of KTH based on TCM for the treatment of URSA. Methods: A systematic literature search was conducted within PubMed, Embase, China Biomedical Literature database, Web of Science (WOS), China National Knowledge Infrastructure (CNKI) database, and the Wanfang database to find articles reporting on the Chinese herbal formula based around KTH for treating URSA, which were published between January 2010 and June 2021. A full bibliometric analysis was carried out; in addition, randomized controlled trial (RCT) articles were selected for systematic evaluation and meta-analysis. The drugs with the highest frequency of KTHs were screened for meta-analysis. Finally, network analysis and molecular docking were used to study the key components and potential pathway of KTHs in the treatment of URSA. Results: The meta-analysis included nine RCTs involving 1,054 subjects. Compared with the control groups, the clinical efficacy of TCM-based KTHs in the treatment of URSA patients significantly improved outcomes. Additionally, a component target pathway network was identified, which included 32 potential blood activating components and 113 main targets. Japonine, sopranol, lysine, and matrine were considered the most important bioactive molecules for KTHs. The key potential therapeutic pathway for URSA was a tumor-related signaling pathway. The target genes for URSA regulated by KTHs were highly similar to tumor biological processes such as the regulation of apoptotic signaling pathways, inflammatory responses, angiogenesis, and epithelial metabolic transition. Conclusion: KTH has great potential for treating URSA. Because the maintenance of pregnancy has a high similarity with tumor invasion, the research relating to tumor mechanisms should also be followed up as it may lead to new ideas and breakthroughs for research into URSA. At the same time, embryonic and decidual cells share a high degree of cellular heterogeneity and spatial structural complexity with tumor cells, and a single cell combined with spatial omics may be the best future approach for validating KTH mechanisms.

Highlights

Recurrent spontaneous abortion (RSA) is challenging to diagnose and treat
Citespace was used for keyword colinear analysis (Figure 2B), and the polar coordinate histogram was calculated according to the count value (Figure 2C)
Analysis from the publications over the past 10 years showed that the research hotspots for traditional Chinese medicine in the treatment of RSA mainly focused on the following key words: recurrent spontaneous abortion, TCM treatment, tonifying kidneys, and promoting blood circulation, Kidney-tonifying herbs (KTHs), integrated traditional Chinese and Western medicine, clinical research, experience of famous doctor, prethrombotic state, progesterone, kidney deficiency and blood stasis, the damage of pre culture, and deficiency of spleen and kidney (Yang et al, 2013; Obstetrics; Subgroup et al, 2019; Cao et al, 2021; Li et al, 2021)

Summary

Introduction

Recurrent spontaneous abortion (RSA) is challenging to diagnose and treat. About 50% of RSAs are still undiagnosed and/or untreated This condition is often referred to as unexplained recurrent spontaneous abortion (URSA) after exclusion of diagnosis and is considered an early spontaneous abortion within the first 12 weeks of pregnancy (Pereza et al, 2017; ESHRE Guideline Group on RPL et al, 2018). It is necessary to study effective treatment methods to reduce pregnancy loss and to help maintain pregnancy in URSA patients (Zhang et al, 2021). The current therapeutic options for URSA mainly include preimplantation genetic screening (PGS), suppression of alloimmunity, and anticoagulant therapy (Rey et al, 2003; Qin et al, 2016; Zhao et al, 2017; Ding et al, 2019; Feng, 2019; Qin et al, 2020; Zhang et al, 2021). Kidney-tonifying herbs (KTHs) are widely used to treat unexplained recurrent spontaneous abortion (URSA) based on the theory of traditional Chinese medicine (TCM). There is still a lack of systematic evaluation and mechanistic explanation for these treatments

Methods

Results

Discussion

Conclusion