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Identifying the underlying mechanisms and exploring effective therapies for intracerebral hemorrhage (ICH) are urgently needed. Here, we aim to elucidate the potential roles and underlying mechanisms of Buyang Huanwu decoction (BYHWD) in ICH. In the first set of experiments, rats were randomly divided into five groups: Sham, ICH, ICH + sodium oxamate (OXA), ICH + BYHWD, and ICH + BYHWD + OXA. The lactate level around the hematoma was evaluated. PCNA+/vWF+ nuclei were observed. Additionally, an online bioinformatics analysis tool was used to predict the BYHWD druggable targets related to angiogenesis. Then, we validated these predictions. In the second set, exogenous sodium L-lactate (Lac) was infused into the intact brains of rats. Rats were randomly divided into three groups: Sham, Lac, and Lac + YC-1. The numbers of PCNA+/vWF+ nuclei and the expression of HIF-1α and VEGF were evaluated. In the first set of experiments, compared with the ICH group, the BYHWD group exhibited significantly increased numbers of PCNA+/vWF+ nuclei, and neurological dysfunction was markedly improved. Bioinformatics analysis revealed that the improvements caused by BYHWD indicated a role for the HIF-1α pathway. The HIF-1α and VEGF protein levels were upregulated after BYHWD administration. Moreover, we verified that lactate was involved in the predicted mechanisms. In the second set, lactate facilitated angiogenesis and HIF-1α and VEGF expression. Co-infusion with a HIF-1α inhibitor, YC-1, significantly inhibited these effects. Our data suggest that the pharmacological effects of BYHWD involve lactate-induced angiogenesis, these data may provide new evidence for its use in ICH. [ABSTRACT FROM AUTHOR]

Background. Infertility affects approximately 15% of couples around the world, and male factors are accounted for 40–50%. Oligoasthenozoospermia is the most common reason for male infertility. Unfortunately, effective drug therapy is still lacking except for assisted reproductive technology (ART). Previous researchers found that Wuzi Ershen decoction (WZESD) can increase sperm count, enhance sperm vitality, and improve semen quality. However, the pharmacological mechanisms remain unclear. Methods. In this study, we screened compounds and predicted the targets of WZESD based on the TCMSP and BATMAN-TCM database combined with literature searching in the PubMed database. We obtained proteins related to oligoasthenozoospermia through GeneCards and submitted them to STRING to obtain the protein-protein interaction (PPI) network. Potential targets of WZESD were mapped to the network, and the hub targets were screened by topology. We used online platform Metascape and Enrichr for GO and KEGG enrichment analyses. AutoDock Vina was utilized for further verification of the binding mode between compounds and targets. Results. Totally, 276 bioactive compounds were obtained and targeted 681 proteins. 446 oligoasthenozoospermia disease-specific proteins were acquired, and further bioinformatics analysis found that they were mainly involved in the formation of gametes, meiosis, and sperm differentiation. Protein interaction network analysis revealed that target proteins of WZESD were associated with oligoasthenozoospermia disease-specific proteins. The 79 targets of disease-specific proteins, which were anchored by WZESD, mainly participate in the cellular response to the organic cyclic compound, regulation of the apoptotic process, nitricoxide biosynthetic and metabolic process, oxidative stress, and protein phosphorylation regulation, which are the causes for oligoasthenozoospermia. Molecular docking simulation further validated that bioactive compounds originated from WZESD with targeted proteins showed high binding efficiency. Conclusions. This study uncovers the therapeutic mechanisms of WZESD for oligoasthenozoospermia treatment from the perspective of network pharmacology and may provide a valuable reference for further experimental research studies and clinical applications. [ABSTRACT FROM AUTHOR]

As a bioactive absorbed compound of rhubarb, Rhein is applied for the treatment of brain injury. However, the underlying pharmacological mechanisms remain unclear. In this study, we aimed to explore antineuroinflammatory functions and underlying mechanisms of Rhein in vitro. BV2 microglia cells were chosen and irritated by LPS. The influence of Rhein on cell viability was determined using MTT assay. We finely gauged the proinflammatory cytokines of TNF-α and IL-1β through tests of immunofluorescence staining, ELISA, RT-qPCR, and western blot. Additionally, mediators including IL-6, IL-12, iNOS, and IL-10 were surveyed by ELISA. Furthermore, protein levels of the underlying signaling pathways (PI3K/Akt, p38, ERK1/2, and TLR4/NF-κB) were tested adopting western blot. We found that Rhein reduced the secretion of pivotal indicators including TNF-α and IL-1β, effectively restraining their mRNA and protein expression in LPS-activated BV2 microglial cells. Besides, Rhein treatment demoted the production of IL-6, IL-12, and iNOS and promoted the excretion of IL-10. Subsequent mechanistic experiments revealed that Rhein obviously downregulated the phosphorylation levels of PI3K, Akt, p38, and ERK1/2 and simultaneously upregulated the PTEN expression. In addition, Rhein antagonized the increase of TLR4, p-IκBα, and NF-κB. In summary, Rhein suppresses neuroinflammation via multiple signaling pathways (PI3K/Akt, p38, ERK1/2, and TLR4/NF-κB) in LPS-stimulated BV2 microglia cells. This study highlights a natural agent for prevention and treatment of neuroinflammation. [ABSTRACT FROM AUTHOR]

Objectives. Xuefu Zhuyu decoction (XFZYD), a traditional Chinese medicine (TCM) formula, has been demonstrated to be effective for the treatment of traumatic brain injury (TBI). However, the underlying pharmacological mechanisms remain unclear. This study aims to explore the potential action mechanisms of XFZYD in the treatment of TBI and to elucidate the combination principle of this herbal formula. Methods. A network pharmacology approach including ADME (absorption, distribution, metabolism, and excretion) evaluation, target prediction, known therapeutic targets collection, network construction, and molecule docking was used in this study. Results. A total of 119 bioactive ingredients from XFZYD were predicted to act on 47 TBI associated specific proteins which intervened in several crucial pathological processes including apoptosis, inflammation, antioxidant, and axon genesis. Almost each of the bioactive ingredients targeted more than one protein. The molecular docking simulation showed that 91 pairs of chemical components and candidate targets had strong binding efficiencies. The “Jun”, “Chen”, and “Zuo-Shi” herbs from XFZYD triggered their specific targets regulation, respectively. Conclusion. Our work successfully illuminates the “multicompounds, multitargets” therapeutic action of XFZYD in the treatment of TBI by network pharmacology with molecule docking method. The present work may provide valuable evidence for further clinical application of XFZYD as therapeutic strategy for TBI treatment. [ABSTRACT FROM AUTHOR]

Introduction. Chinese medicine syndrome diagnosis is the key requisite in the treatment of male infertility with traditional Chinese medicine (TCM). Kidney-Yang deficiency syndrome (KYDS) is the critical Chinese medicine syndrome of male infertility. To explore the modernized mechanisms of KYDS in male infertility, this study aims to investigate the metabolomics of males with KYDS. Methods. The gas chromatography-mass spectrometry method was applied to analyze the plasma samples of 67 infertile males with KYDS compared with 55 age-matched healthy controls. The chemometric methods including principal component and partial least squares-discriminate analyses were employed to identify the potential biochemical patterns. With the help of the variable importance for the projection and receiver operating characteristic curve analyses, the potential biomarkers were extracted to define the clinical utility. Simultaneously the high-quality KEGG metabolic pathways database was used to identify the related metabolic pathways. Results. The metabolomics profiles of infertile males with KYDS including 10 potential biomarkers and six metabolic pathways were identified. They precisely distinguished infertile males with KYDS from healthy controls. Conclusions. These potential biomarkers and pathways suggest the substantial basis of infertile males with KYDS. The metabolomics profiles highlight the modernized mechanisms of infertile males with KYDS. [ABSTRACT FROM AUTHOR]