Integrative transcriptomics and proteomics analyses to reveal the therapeutic effect and mechanism of Buxue Yimu Pills in medical-induced incomplete abortion rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Medical abortions using mifepristone and misoprostol have been approved in many countries for early pregnancy loss. Despite its high success rate, this medication regimen can result in incomplete abortion, which is responsible for endometrial damage, prolonged uterine bleeding, abdominal pain, etc. Buxue Yimu Pills (BYP) is a famous Chinese medicine prescription that is widely used in the field of gynecology and obstetrics for treating patients with postpartum complications. However, the therapeutic effect and mechanism of BYP remain to be explored. AIM OF THE STUDY: This study aimed to clarify the therapeutic effect and mechanism of action of BYP in postpartum complications using mifepristone and misoprostol-induced incomplete abortion in rats. MATERIALS AND METHODS: Experimental medical-induced incomplete abortion model rats were constructed using mifepristone and misoprostol, and further treated with saline or BYP by intragastric administration. Detailed information regarding the changes in mRNA and protein levels in the uterine tissues of rats regulated by BYP was illustrated by RNA sequencing (RNA-seq) analysis and quantitative proteomics analysis. The differentially expressed genes and proteins were further subjected to Gene Ontology (GO) and pathway enrichment analyses and further verified using quantitative Real-time PCR (qRT-PCR) analysis and western blot assay. RESULTS: BYP administration markedly alleviated the increase in serum prostaglandin F2α (PGF2α) and expression of PGF2α receptor (PGF2αR) in uterine tissues and inhibited the decrease in serum chorionic gonadotrophin (CG). Compared with the model group, 674 genes were upregulated and 344 genes were downregulated by BYP administration; 108 proteins were upregulated and 48 proteins were downregulated by BYP administration. qRT-PCR analysis of the uterine tissues showed that BYP treatment reversed the variation tendency of genes, including Mmp7, Mmp14, Timp2, Col6a4, Jak2, Wnt7a, and Mylk compared with the model group. Western blot analysis showed that BYP administration affected PKCδ, Collagen VI, MMP7, TIMP2, MLCK, and p-MLC protein levels. CONCLUSION: BYP administration facilitated uterine recovery in medical-induced incomplete abortion rats, and this therapeutic effect involved various targets and biological processes, including the TIMP2/MMP7 and MLCK/p-MLC signaling pathways, etc.

Buxue Yimu Pills improve angiogenesis and blood flow in experimental zebrafish and rat models.

ETHNOPHARMACOLOGICAL RELEVANCE: Buxue Yimu Pills (BYP) is a well-known traditional Chinese medicine prescription which is clinical used in gynecology and obstetrics, and is documented to exhibit therapeutic potential to defective angiogenesis and impaired blood flow. AIM OF THE STUDY: This study aimed to investigate the effects and biological mechanisms of BYP in improvement of defective angiogenesis and impaired blood flow which represent major health issues associated with various diseases including postpartum or abortion complications. MATERIALS AND METHODS: In this study, VEGFR tyrosine kinase inhibitor II (VRI) was used to establish blood vessel loss model in Tg(fli-1a:EGFP) zebrafish embryos. Blood vessel loss was calculated, and quantitative real-time PCR (qRT-PCR) assay was performed to detect gene expression. Mifepristone and misoprostol were applied to construct a medical-induced incomplete abortion rats model. Whole blood viscosity indexes, hemorheology and coagulation function of the rats were investigated. Immunohistochemistry analysis was used for evaluation of the uterine tissues. RESULTS: BYP treatment significantly promoted angiogenesis as evidenced by the restoration of VRI-induced blood vessel loss in zebrafish embryos. BYP treatment effectively reversed VRI-induced down-regulation of the VEGFRs (Kdr, Kdrl and Flt1). Furthermore, BYP administration significantly suppressed the increase of whole blood viscosity indexes, and remarkably shortened the levels of prothrombin time and activated partial thromboplastin time in the medical-induced incomplete abortion rats, indicating the improvement of hemorheology and coagulation function. Immunohistochemistry analysis suggested that BYP administration increased the expression level of VEGFR2 in uterus tissues of the rats. CONCLUSION: BYP exhibits therapeutic effects in promoting angiogenesis and blood circulation, and mitigating blood stasis, supporting its clinical application for postpartum or abortion complications.

Updates and advances on pharmacological properties of Taraxacum mongolicum Hand.-Mazz and its potential applications.

As a well-recognized dietary and medicinal plant, Taraxacum mongolicum Hand.-Mazz (TMHM) has been used for making wines, candies, energy drinks, and other functional foods. The TMHM contains a diverse range of active phytoconstituents, including flavonoids, triterpenoids, phenolic acids, sesquiterpene lactones, pigments, coumarins and sterols. Recent pharmacological evidence has revealed multiple biological effects of TMHM, including anti-inflammatory, antioxidant, antibacterial, and gastric-protective effects, which contribute to the ameliorative effects of TMHM on inflammation-associated diseases, constipation, gastric disorders, empyrosis, hyperlipidemia, and swollen carbuncles. Although recent advances have highlighted the potential of TMHM to be applied in the clinical practice, food, and nutraceutical industry, the mechanistic understanding and systematic information on TMHM are still scarce. Here, in this timeline review, we have attempted to compile literary documents on pharmacological potential of TMHM concerning its chemical composition, biological activities, toxicity, and pharmacokinetics to promote further researches on clinical and therapeutic potential of TMHM and its food/nutraceutical applications.

Towards a better understanding of Fagopyrum dibotrys: a systematic review.

Fagopyrum dibotrys (F. dibotrys) (D.Don) H.Hara is a well-known edible herbal medicine in Asian countries. It has been widely used for the treatment of lung diseases, swelling, etc., and is also an important part of many Chinese medicine prescriptions. At present, more than 100 compounds have been isolated and identified from F. dibotrys, and these compounds can be primarily divided into flavonoids, phenols, terpenes, steroids, and fatty acids. Flavonoids and phenolic compounds are considered to be the main active ingredients of F. dibotrys. Previous pharmacological studies have shown that F. dibotrys possesses anti-inflammatory, anti-cancer, anti-oxidant, anti-bacterial, and anti-diabetic activities. Additional studies on functional genes have led to a better understanding of the metabolic pathways and regulatory factors related with the flavonoid active ingredients in F. dibotrys. In this paper, we systemically reviewed the research advances on the phytochemistry and pharmacology of F. dibotrys, as well as the functional genes related to the synthesis of active ingredients, aiming to promote the development and utilization of F. dibotrys.

Semi-Mechanism-Based Pharmacodynamic Model for the Anti-Inflammatory Effect of Baicalein in LPS-Stimulated RAW264.7 Macrophages.

Monitoring of the inhibition of TNF-α, IL-6, iNOS, and NO is used to effectively evaluate anti-inflammatory drugs. Baicalein was found to have good anti-inflammatory activities, but its detailed cellular pharmacodynamic events have not been expatiated by any other study. The inflammatory mediators, including TNF-α, IL-6, iNOS, and NO production in RAW264.7 macrophage induced by LPS, were measured. It was found that these data showed a sequential pattern on time and based on these points a cellular pharmacodynamic model was developed and tested. TNF-α and IL-6 were quantified by ELISA, NO was detected by Griess and iNOS expression was measured by Western blot. The pharmacodynamic model was developed using a NLME modeling program Monolix® 2016R1.The results showed that baicalein quickly suppressed release of TNF-α in a concentration-dependent manner, and consequently causing the diminution of IL-6 and iNOS/NO. The pharmacodynamic model simulation successfully described the experimental data, supporting the hypothesis that IL-6 and iNOS /NO release after LPS stimulation is mediated by TNF-α rather than LPS directly. The pharmacodynamic model allowed a well understanding of the cellular pharmacodynamic mechanism of baicalein in the treatment of inflammatory diseases.