The Effectiveness and Safety of Bushen Huoxue Decoction on Treating Coronary Heart Disease: A Meta-Analysis

Objective. The aim of this meta-analysis was to systematically evaluate the effectiveness and safety of the traditional Chinese medicine (TCM) formula Bushen Huoxue Decoction (BSHXD) in treating coronary heart disease (CHD). Methods. Randomized controlled trials (RCTS) of BSHXD in treating CHD were searched until March 2020, through six electronic databases: PubMed, Cochrane Library, CNKI, WanFang, SinoMed, and VIP. This study used the Cochrane Risk Test bias tool in the Cochrane Handbook to assess the quality of the methodology. Review Manager (RevMan) 5.3 was used to analyze the results. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria were applied in the classification of evidence quality. Results. Ten RCTs involving 901 patients were finally included in this meta-analysis. It revealed that the effectiveness of BSHXD in treating CHD was significantly better than that of the conventional western medicine (CWM) treatment ( P < 0.00001 ). The effective rate of BSHXD treatment group on ECG was also significantly higher than that of CWM group ( P < 0.00001 ). The low-density lipoprotein cholesterol was decreased in the treatment groups compared with those in the control groups ( P < 0.00001 ). There was also a reduction in frequency and duration of angina pectoris ( P < 0.00001 ). There were no significant differences in TC level ( P = 0.08 ), TG level ( P = 0.86 ), and HDL level ( P = 0.76 ) between the treatment and control groups. Five studies had informed adverse events, including nausea and diarrhea. Conclusion. Our findings laid the foundation to the use of TCM Formula BSHXD in combination with conventional western medicine for treating CHD. However, due to the limitation of the quality of the included researches, in addition to potential reporting bias, the above conclusions still need verification by higher-quality and better-designed studies.

Identification of the Active Constituents and Significant Pathways of Bushen Huoxue Decoction for the Treatment of Recurrent Spontaneous Abortion Based on Network Pharmacology

Background: To explore Bushen Huoxue Decoction (BHD) mechanism in recurrent spontaneous abortion (RSA).Methods: We predicted and screened the action targets of four Traditional Chinese Medicine representatives by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and searched the disease targets of RSA through Drugbank, DisGeNET, and TTD databases. According to the obtained drug targets and disease targets, the "drug target-disease target" interaction network was further analyzed and constructed. The core target of BHD for treating RSA was were imported to establish in STRING. GO and KEGG pathway analysis were conducted with the RStudio (ggplot2). Finally, HTR-8/SVneo cells were selected to establish a cell model of oxidative stress, and the network pharmacologic results of BHD-RSA were verified by cell biology, Western blot and qRT-PCR.Results: A total of 73 active compounds were obtained from 1084 ingredients present in the BHD, and 125 genes were closely related to RSA. According to the "drug target-disease target" interaction network analysis, 26 core targets of BHD for treating RSA were finally selected, and 203 biological processes, 10 molecular functions, and 10 cell components were enriched by GO function enrichment. KEGG pathway enrichment related pathways, a total of 19, are mainly associated with a Neuroactive ligand-receptor interaction pathway. Experimental results show that compared with the oxidative stress cell model of RSA, BHD increases the expression of PTGFR, AGTR1 and OXTR mRNA by upregulating the expression of PTGFR, AGTR1 and OXTR protein, which may interfere with the occurrence and development of RSA through Neuroactive ligand-receptor interaction pathway.Conclusion: Combined with the pathological mechanism of RSA and the absence of specific signaling pathways, we hypothesized that the BHD might play a role in tonifying the kidney, strengthening the bone, promoting blood circulation, and removing blood stasis，it also can virtually relieve the symptoms of RSA, and our network pharmacological analysis lays the foundation for future clinical research.These results may help define the possible roles the BHD plays in RSA through Neuroactive ligand-receptor interaction pathway.

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

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.