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Efficacy of Traditional Chinese Medicine Tonifying Kidney (Bushen) and Activating Blood (Huoxue) Prescription for Premature Ovarian Insufficiency: A Systematic Review and Meta-Analysis.

ABSTRACT: Objective:We carried out this systematic review and meta-analysis to evaluate the effectiveness of TKABP on POI. Methods:The following eight databases were searched from the establishment to September 30, 2019, for randomized controlled trials (RCTs): PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), the Chinese BioMedical database (CBM), Chinese Scientific Journal Database (VIP), and the Wanfang database. The quality of evidence was estimated by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Results:Twenty-three RCTs involving 1712 patients with POI were included. Compared to hormone therapy (HT) groups, TKABP groups showed a significantly higher total effective rate (RR: 1.10; 95% CI: 1.04-1.17; P < 0.01, I 2?=?32%). In addition, TKABP groups revealed a better improvement in terms of serum follicle-stimulating hormone (FSH) levels, serum estradiol (E2) levels, peak systolic velocity (PSV) of ovarian stromal blood, and Kupperman index (KI) score. However, serum luteinizing hormone (LH) levels and ovarian volume (OV) showed no significant statistical difference. Subgroup analyses showed that herbal paste and 3?months of treatment duration had a greater effect on the improvement of hormone levels. Besides, the occurrence of related adverse events in TKABP groups was lower than that in HT groups. Conclusions:Our review suggests that TKABP appears to be an effective and safe measure for patients with POI, and the herbal paste may be superior. However, the methodological quality of included RCTs was unsatisfactory, and it is necessary to verify its effectiveness with furthermore standardized researches of rigorous design.

SUBMITTER: Li HF

PROVIDER: S-EPMC7191427 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Efficacy of Traditional Chinese Medicine Tonifying Kidney (Bushen) and Activating Blood (Huoxue) Prescription for Premature Ovarian Insufficiency: A Systematic Review and Meta-Analysis.

Li Hui-Fang HF Shen Qi-Hong QH Chen Wen-Jun WJ Chen Wei-Min WM Feng Zhang-Feng ZF Yu Li-Ying LY

Evidence-based complementary and alternative medicine : eCAM 20200421

<h4>Objective</h4>We carried out this systematic review and meta-analysis to evaluate the effectiveness of TKABP on POI.<h4>Methods</h4>The following eight databases were searched from the establishment to September 30, 2019, for randomized controlled trials (RCTs): PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), the Chinese BioMedical database (CBM), Chinese Scientific Journal Database (VIP), and the Wanfang database. The quality of evidence was ...[more]

PMID: 32382277

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Project description:IntroductionPremature ovarian insufficiency (POI) seriously affects the quality of life, endocrine function, and fertility of women of childbearing age. Currently, hormone replacement therapy for POI has some limitations, either with low efficacies or high side effects. Bushen Huoxue (BSHX) plays an important role in alleviating clinical symptoms and improving health status of POI patients. This placebo-controlled, randomized, double-blind, and multicenter clinical trial protocol aims to evaluate the effectiveness and safety of BSHX in women with POI.Methods and designWe plan to recruit 150 women with POI from four participating hospitals in China. Participants will be randomized in a 1:1 to receive oral BSHX or BSHX placebo. All participants will be treated for 3 months and will be followed up for another 3 month. The primary outcome is questionnaire scores based on the changes in the total symptoms, which is the Chinese version of the Menopause-Specific Quality of Life (CMS) (Nie G, Yang H, Liu J, Zhao C, Wang X, Menopause 24(5):546-554, 2017). CMS will be measured before the intervention, at 3 months and 6 months after randomization for all participants. The other measurements include serum sex hormone levels, anti-Müllerian hormone (AMH) levels, ovarian peak systolic velocity (PSV; cm/s), and antral follicle count (AFC). In this study, the regulatory effects of traditional Chinese medicine on hormones were evaluated by the changes of serum sex hormone levels, which include serum estradiol (E2), luteinizing hormone (LH), and follicle-stimulating hormone (FSH). These indicators will be measured before intervention and at 3 months after randomization.Ethics and disseminationThis study was approved by the Research Ethics Committee of Jiangsu Province Hospital on Integration of Chinese and Western Medicine (2019LWKY014). All participants will provide written informed consent prior to randomization. The results of this research will be presented to academic conferences and peer-reviewed journals.Trial registrationChiCTR1900028451. Registered on 22 December 2019, https://www.chictr.org.cn/index.aspx .

Project description:BackgroundDuring the fresh cycles of in vitro fertilization and embryo transfer, a disturbance in the reproductive endocrine environment following controlled ovarian hyperstimulation (COH) is closely related to compromised endometrial receptivity. This is a major disadvantage for women during pregnancy. Based on the theory of traditional Chinese medicine, Bushen Huoxue recipe (BSHXR) has been indicated to facilitate embryo implantation.MethodsThe COH model (Kunming breed) was induced by injecting mice with pregnant mare serum gonadotrophin (0.4 IU/g) and human chorionic gonadotropin (1 IU/g), followed by treatment with BSHXR at three different concentrations (5.7, 11.4, and 22.8 g/kg), Bushen recipe (BSR) (5.7 g/kg), and Huoxue recipe (HXR) (5.7 g/kg). After successful mating, the pregnancy rate and implantation sites were examined on embryo day 8 (ED8), and the weight ratio of endometrium was calculated on ED4 midnight. Serum estrogen, progesterone, and endometrial PGE2 levels were measured using enzyme-linked immunosorbent assay. The endometrial microvasculature was evaluated using CD31 immunostaining. The protein and mRNA levels of the angiogenic factors in the endometrium were evaluated using western blot, immunohistochemistry, and polymerase chain reaction.ResultsIn the COH group, the pregnancy rate and implantation sites were significantly decreased, and abnormal serum hormone levels and impaired endometrial vascular development were observed. After BSHXR treatment, the supraphysiological serum progesterone level in COH mice was restored to normalcy. Moreover, the abnormal expression of the endometrial pro-angiogenic factors, including HIF1α, COX2-PGE2 pathway, and the down-stream factors, namely, MMP2, MMP9, TIMP2, and FGF2 after subjecting mice to COH was significantly improved after BSHXR treatment.ConclusionBSHXR could improve embryo implantation by regulating hormonal balance and modulating endometrial angiogenesis in mice, without inducing any side effects in normal pregnancy.

Project description:BackgroundPremature ovarian insufficiency (POI) patients are predisposed to metabolic disturbances, including in lipid metabolism and glucose metabolism, and metabolic disorders appear to be a prerequisite of the typical long-term complications of POI, such as cardiovascular diseases or osteoporosis. However, the metabolic changes underlying the development of POI and its subsequent complications are incompletely understood, and there are few studies characterizing the disturbed metabolome in POI patients. The aim of this study was to characterize the plasma metabolome in POI by using ultrahigh-performance liquid chromatography-mass spectrometry (UHPLC-MS/MS) metabolomics and to evaluate whether these disturbances identified in the plasma metabolome relate to ovarian reserve and have diagnostic value in POI.MethodsThis observational study recruited 30 POI patients and 30 age- and body mass index (BMI)-matched controls in the Center for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, from January 2018 to October 2020. Fasting venous blood was collected at 9:00 am on days 2-4 of the menstrual cycle and centrifuged for analysis. An untargeted quantitative metabolomic analysis was performed using UHPLC-MS/MS.ResultsOur study identified 48 upregulated and 21 downregulated positive metabolites, and 13 upregulated and 48 downregulated negative metabolites in the plasma of POI patients. The differentially regulated metabolites were involved in pathways such as caffeine metabolism and ubiquinone and other terpenoid-quinone biosynthesis. Six metabolites with an AUC value > 0.8, including arachidonoyl amide, 3-hydroxy-3-methylbutanoic acid, dihexyl nonanedioate, 18-HETE, cystine, and PG (16:0/18:1), were correlated with ovarian reserve and thus have the potential to be diagnostic biomarkers of POI.ConclusionThis UHPLC-MS/MS untargeted metabolomics study revealed differentially expressed metabolites in the plasma of patients with POI. The differential metabolites may not only be involved in the aetiology of POI but also contribute to its major complications. These findings offer a panoramic view of the plasma metabolite changes caused by POI, which may provide useful diagnostic and therapeutic clues for POI disease.

Project description:ObjectiveThis study aimed to explore the mechanism of the Bushen Huoxue Formula (BHF) in treating diminished ovarian reserve (DOR) through the use of metabolomics and integrated network pharmacology.MethodsThe study involved 24 non-pregnant female Sprague-Dawley rats, divided into four groups of six rats each: control, model, BHF, and DHEA (n = 6 per group). The model group was induced with DOR by administering Tripterygium glycosides orally [50 mg (kg·d)-1] for 14 days. Subsequently, BHF and Dehydroepiandrosterone (DHEA) treatments were given to the respective groups. Ovarian reserve function was assessed by measuring anti-Müllerian hormone (AMH), estradiol (E2), and follicle-stimulating hormone (FSH) levels and conducting hematoxylin-eosin staining. In addition, UHPLC-QTOF-MS analysis was performed to identify differential metabolites and pathways in DOR rats treated with BHF. In this study, LC-MS was utilized to identify the active ingredients of BHF, while network pharmacology was employed to investigate the correlations between BHF-related genes and DOR-related genes. An integrated analysis of metabonomics and network pharmacology was conducted to elucidate the mechanisms underlying the efficacy of BHF in treating DOR.ResultsThe model group exhibited a poor general condition and a significant decrease in the number of primordial, primary, and secondary follicles (P < 0.05) when compared to the control group. However, BHF intervention resulted in an increase in the number of primordial, primary, and secondary follicles (P < 0.05), along with elevated levels of AMH and E2 (P < 0.05), and a decrease in FSH levels (P < 0.05) in DOR rats. The modeling process identified eleven classes of metabolites, including cholesterol esters (CE), diacylglycerols (DAG), hexosylceramides (HCER), lysophosphatidylcholines (LPC), phosphatidylcholines (PC), phosphatidylethanolamines (PE), sphingomyelins (SM), ceramides (CER), free fatty acids (FFA), triacylglycerols (TAG), and lysophosphatidylethanolamines (LPE). The study found that PC, CE, DAG, and TAG are important metabolites in the treatment of DOR with BHF. LC-MS analysis showed that there were 183 active ingredients in ESI(+) mode and 51 in ESI(-) mode. Network pharmacology analysis identified 285 potential genes associated with BHF treatment for DOR in ESI(+) mode and 177 in ESI(-) mode. The combined analysis indicated that linoleic acid metabolism is the primary pathway in treating DOR with BHF.ConclusionBHF was found to improve ovarian function in rats with DOR induced by Tripterygium glycosides. The study identified key metabolites such as phosphatidylcholine (PC), cholesteryl ester (CE), diacylglycerol (DAG), triacylglycerol (TAG), and the linoleic acid metabolism pathway, which were crucial in improving ovarian function in DOR rats treated with BHF.

Project description:Hypertension is the most common chronic disease. A large amount of evidence showed that traditional Chinese medicine (TCM) method of tonifying kidney (TK) combined with routine treatment is more effective and safer in the treatment of hypertension. This study integrated meta-analysis, data mining, and network pharmacology to explore the efficacy and potential mechanisms of TK in the treatment of hypertension. Meta-analysis was performed to explore the efficacy and safety of TK combined with routine treatment in the treatment of hypertension. Data mining was used to screen the core herbs of the TK. Network pharmacology was used to predict the antihypertensive mechanism of TK core herbs. A total of 18 studies with 2,024 patients were included in this study. Meta-analysis showed that TK combined with routine treatment was superior to routine treatment alone in lowering blood pressure (systolic and diastolic blood pressures), lowering blood lipids (total cholesterol, triglyceride, low-density lipoprotein cholesterol), improving vascular endothelial functions (nitric oxide, endothelin) and TCM symptoms (headache dizziness, soreness, and weakness of waist and knees). In addition, TK was safe and has no obvious adverse reactions. Data mining showed that the core herbs of TK were Eucommia ulmoides Oliv. (Duzhong), Vitex negundo L. (Huangjing), Taxillus chinensis (DC.) Danser (Sangjisheng), Ligustrum lucidum W.T.Aiton (Nuzhenzi), Astragalus mongholicus Bunge (Huangqi), Rehmannia glutinosa (Gaertn.) DC. (Shudihuang). Network pharmacology predicted that core herbs antihypertensive components were oleanolic acid, ursolic acid, and civetone, and the antihypertensive targets were NOS3, NOS2, MMP9, TNF, PTGS2, HMOX1. In addition, the antihypertensive targets were enriched in cGMP-PKG signaling pathway, calcium signaling pathway, aldosterone-regulated sodium reabsorption, HIF-1 signaling pathway. In conclusion, TK combined with routine treatment for hypertension is effective and safe. The mechanism of TK may be related to GMP-PKG signaling pathway, calcium signaling pathway, aldosterone-regulated sodium reabsorption. On the premise of syndrome differentiation and treatment, it is promising to treat hypertension with TK.Systematic review registration[https://www.crd.york.ac.uk/prospero/], identifier [CRD42022358276].

Project description:Premature ovarian insufficiency (POI) is defined as a primary ovarian defect characterized by absent menarche (primary amenorrhea) or premature depletion of ovarian follicles before the age of 40 (secondary amenorrhea) with hypergonadotropism and hypoestrogenism. Premature ovarian insufficiency has few known genetic causes but in familial cases a genetic link is often suspected. A large consanguineous family with three female affected with POI was investigated. All samples including 3 affected and 5 unaffecd underwent whole genome SNP genotyping using Affymetric Axiom_GW_Hu_SNP array. Linkage analysis was carried out using HomozygosityMapper and Allegro softwares.Linkage analysis mapped the disease phenotype to long arm of chromosome 20. Sequence data analysis of potential candidate genes failed to detect any pathogenic variant. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from peripheral blood samples. DNA of eight individuals including three affected subjects was used for homozygosity mapping. Genotyping was performed using the Affymetrix Axiom_GW_Hu_SNP array. Briefly, 250 ng genomic DNA was digested with Digestion Master Mix containing 2 µl NE buffer 2 (10X), 0.5 µl BSA (100X; 10 mg/ml) and 1 µl Nsp1. Digested DNA sample was ligated to Nsp1 adaptor using T4 DNA ligase and amplified by 2 µl of TITANIUM Taq DNA polymerase (50X) and 100 µM PCR primer. PCR products were purified on a Clean-Up plate (Clontech Lab, Madison, USA) and eluted by RB buffer. Purified PCR products were fragmented using Fragmentation Reagent (0.05U/µl DNase 1) for 35 minutes at 37°C followed by labeling of fragmented samples with Labeling Master Mix (30 mM GeneChip DNA Labeling Reagent, 30 U/µl Terminal Deoxynucleotidyl Transferase) for 4 hours at 37°C. Labeled samples were hybridized to Axiom_GW_Hu_SNP array by mixing the sample with Hybridization Master Mix, denatured on thermoblock and loaded on to Array. Array was then placed in a hybridization oven (GeneChip Hybridization Oven 640, USA) for 16-18 hours. After hybridization, array was washed and stained on an automated Fluidic Station 450 followed by scanning on GeneChip Scanner 3000 7G using GeneChip Operating Software (GCOS).

Dataset Information

Efficacy of Traditional Chinese Medicine Tonifying Kidney (Bushen) and Activating Blood (Huoxue) Prescription for Premature Ovarian Insufficiency: A Systematic Review and Meta-Analysis.

Publications

Efficacy of Traditional Chinese Medicine Tonifying Kidney (Bushen) and Activating Blood (Huoxue) Prescription for Premature Ovarian Insufficiency: A Systematic Review and Meta-Analysis.

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