BuShen HuoXue Decoction Promotes Decidual Stromal Cell Proliferation via the PI3K/AKT Pathway in Unexplained Recurrent Spontaneous Abortion.

Xiaoling Feng,Lu Chen,Ling Wang,Wingting Leung,Hans Jürgen Gober,Sha Jiang,Yang Zhang,Wenyi Kang

doi:10.1155/2020/6868470

Abstract

BuShen HuoXue decoction (BSHXD) has been used to treat patients with unexplained recurrent spontaneous abortion (URSA). However, the chemical compounds and mechanism by which BSHXD exerts its therapeutic and systemic effects to promote the proliferation of decidual stromal cells (DSCs) has not been elucidated. This work sought to elucidate the cellular and molecular mechanism of BSHXD in terms of inflammatory factors IL-17A in DSCs in vitro because of the critical roles of inflammation, apoptosis, and immunity in the development and progression of pregnancy loss. Twelve migratory chemical compounds from BSHXD extract were qualitatively analyzed by high-performance liquid chromatography (HPLC). DSCs were collected from normal early pregnancy (NEP) and URSA to determine whether BSHXD affects IL-17A/IL17RA via the PI3K/AKT pathway. Abnormal apoptosis and activated p-AKT were observed in URSA DSCs. RhIL-17 A, LY294002 (a PI3K pathway inhibitor), and BSHXD were individually or simultaneously administered in NEP DSCs, suggesting that BSHXD restored cell proliferation without excessive stimulation and IL-17A promotes proliferation via the PI3K/AKT pathway. Using the same intervention in URSA DSCs, qRT-PCR measured the upregulated mRNA levels of IL-17 A/IL-17RA, PI3K, AKT, p-AKT, PTEN, Bcl-2, and Bcl-xL and downregulated mRNA levels of BAD and ACT1 after treatment with BSHXD. We demonstrated that BSHXD affected IL-17A/IL-17R via PI3K/AKT pathway to promote the proliferative activity of DSCs in URSA. These results provide a new insight to further clarify the relationship between inflammation and apoptosis and the mechanism of imbalance in the dynamic equilibrium between Th17/Treg immune cells at the maternal-fetal interface.

Highlights

Recurrent spontaneous abortion (RSA) refers to consecutive abortions occurring before 20 weeks with the same biological father [1]
We found that decidual stromal cells (DSCs) represent the majority of decidual cells
All procedures involving rats were approved by the animal ethics committee of the Heilongjiang University of Chinese Medicine. e composition of BuShen HuoXue decoction (BSHXD) is listed in Table 1. ese compounds were obtained from the First Affiliated Hospital of Heilongjiang University of Chinese Medicine (Harbin, China)

Summary

Introduction

Recurrent spontaneous abortion (RSA) refers to consecutive abortions occurring before 20 weeks with the same biological father [1]. Up to 50% of RSA cases occur in the absence of common obstetrical and gynecological complications [3] and are referred to as unexplained RSA (URSA). Treatment strategies such as aspirin and low-molecularweight heparin (LMWH) have recently been recommended by practical guidelines for URSA and had provided some curative effects [4]. Targeted drugs such as TNF-α inhibitors and granulocyte colony-stimulating factor (G-CSF) are Evidence-Based Complementary and Alternative Medicine potential drugs for URSA [5]. TCM is currently recognized as a prevalent complementary and alternative treatment for URSA in the Western world [6]

Methods

Results

Conclusion