Comparing the pharmacological effects of the prepared folium of Epimedium brevicornu Maxim. and Epimedium sagittatum Maxim. on kidney-Yang deficiency syndrome and liver injury complications.

Yinyanghuo, a famous herb, includes the folium of Epimedium brevicornu Maxim. and Epimedium sagittatum Maxim. It is believed that their processed products, the prepared slices of the folium of Epimedium brevicornu Maxim. (PFEB) and Epimedium sagittatum Maxim. (PFES) have greater efficacy in tonifying kidney Yang to treat kidney-Yang deficiency syndrome (KDS). However, there are few studies comparing the pharmacological effects of PFEB and PFES, and the underlying mechanisms. This study compared their effects on improving hypothalamic-pituitary-adrenal (HPA) axis, immune system and sexual characteristic, as well as repairing liver injury complications in the KDS model mice. Additionally, the mechanisms of the effects relevance to their main components were explored. It was found that PFEB was more effective than PFES in increasing cAMP/cGMP ratio, SOD activity, CRH and ACTH levels, eNOS and testosterone levels, splenic lymphocytes proliferation, while in decreasing MDA content, atrophy of spleen and thymus, splenic lymphocytes apoptosis, and PDE5 level. PFES showed stronger protection than PFEB in decreasing triglyceride and hepatic lipid. The contents of baohuoside I and epimedin A, B were much higher in PFEB, while Epimedin C, Icariin, 2-O″-rhamnosylicaridide II were higher in PFES. Consequently, PFEB exhibits superior efficacy over PFES in tonifying the kidney-Yang by improving the neuroendocrine-immune network, including HPA axis, immune systems, and corpus cavernosum. However, PFES has better recovery effect on mild hepatic lipid caused by KDS. The efficacy difference between PFEB and PFES in kidney-Yang and liver may be attributed to the content variations of baohuoside I.

High-Throughput Sequencing to Investigate the Expression and Potential Role of Differentially Expressed microRNAs in Myocardial Cells after Ischemia-Reperfusion Injury.

BACKGROUND: microRNAs (miRNAs) are closely associated with the pathogenesis of various diseases, but the relationship between miRNAs and myocardial ischemia-reperfusion (I/R) injury remains unclear. Therefore, we aimed to explore the role and function of miRNAs and identify target genes regulating I/R. METHODS: We established a hypoxia/reoxygenation (H/R) model to detect differentially expressed miRNAs using high-throughput sequencing in rat myocardial cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were used to analyze the potential functions and signaling pathways of target genes. RESULTS: We identified 113 differentially expressed miRNAs, comprising 76 and 37 upregulated and downregulated genes, respectively. Database predictions suggested that miR-200a-3p may act through the ferroptosis pathway, and we assessed the expression of miR-200a-3p, iron ions, and ferroptosis markers. The expression of miR-200a-3p significantly increased in the H/R group, along with increased production of reactive oxygen species (ROS) and iron ions. When the expression of miR-200a-3p was inhibited, iron ions and ROS levels decreased significantly. Western blotting showed that transferrin receptor (TFRC) and Acyl-coA synthetase long-chain family member 4 (ACSL4) levels were decreased and Glutathione peroxidase 4 (GPX4) expression was increased. CONCLUSIONS: These findings offer a novel perspective on I/R regulation, and the specific mechanisms underlying the actions of miR-200a-3p merit further investigation.

The pharmacological effects and safety of the raw and prepared folium of Epimedium brevicornu Maxim. on improving kidney-yang deficiency syndrome and sexual dysfunction.

Background: Kidney-Yang deficiency syndrome (KDS) is a group of diseases related to hypothalamic-pituitary-adrenal (HPA) axis and sexual dysfunction. The folium of Epimedium brevicornu Maxim. (FEB) includes raw and prepared slices, named RFEB and PFEB, respectively. PFEB is traditionally believed to be good for tonifying kidney-Yang and improving sexual dysfunction. However, there are few studies comparing the pharmacological effects of RFEB and PFEB, and their underlying mechanisms. In this study, we aimed to compare the effects and safety of RFEB and PFEB on the HPA axis and sexual function. Additionally, the mechanisms of their roles in relation to the neuroendocrine-immune (NEI) network in the KDS model mice were explored. Methods: Male adult C57BL/6 mice were treated with corticosterone to establish a KDS mouse model, and RFEB and PFEB were administered intragastrically. Corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), testosterone levels and oxidative damage indexes were measured. The mRNA and protein levels of CRH and ACTH in hypothalamus and pituitary, endothelial nitric oxide synthase (eNOS) and phosphodiesterase 5 (PDE5) in corpus cavernosum were examined. TNFα, IL-6, NF-κB, eNOS and PDE5 were investigated in mouse corpus cavernosum. Results: Our results showed that PFEB was more effective than RFEB in increasing corticosterone-suppressed ACTH levels, enhancing CRH levels and cAMP/cGMP ratio, and reducing oxidative damage. In vivo, PFEB significantly increased eNOS and inhibited PDE5 expression in corpus cavernosum. PFEB showed stronger protective effect on normal spleen lymphocytes from apoptosis both in vitro and in vivo. Additionally, it noticeably inhibited the levels of inflammatory cytokines in corpus cavernosum. Both RFEB and PFEB were safe and did not cause any clinical signs of toxicity in mice at the dosage of 20 times dosages of that in the Chinese Pharmacopeia. Conclusion: We demonstrated that PFEB was better than RFEB at tonifying the kidney-Yang by comparing their effects on improving the NEI network, which includes the HPA axis, immune system and corpus cavernosum. This study revealed that PFEB could significantly improve the sexual function of KDS mice by regulating the HPA axis and activating the immune system through the NEI network.

A review on the current literature regarding the value of exosome miRNAs in various diseases.

Exosome microRNAs (miRNAs) have great research outlook in clinical therapy and biomarkers, they have been found to have a close to multiple diseases. A growing number of studies have attempted to alleviate or treat diseases through exosomes. It indicates that miRNAs in exosomes have great significance in preventing and controlling diseases in clinical research. We summarise these studies below to better understand their implications.We screened and analyzed more than 100 articles from PubMed, Web of Science, and other databases from 1987 to 2022. Data of the clinical trials are collected from clinicaltrials.gov.In this review, we introduce the source, type, and characteristics of several exosomes, summarising current research on their role in cardiovascular, nervous system disease, tumour, and other diseases. Further, we discuss their mechanism of action and future directions for development of treatments in several diseases, and highlight the significant research value and potential use of exosomes in clinical diagnosis and treatment.An increasing number of researchers have begun to explore the link between exosomal miRNAs and diseases. More exosome therapeutics will be used in future clinical trials, which may bring new hope for the diagnosis and treatment of several diseases.KEY MESSAGESExosomes have unique advantages in molecular transport and cell signal transduction.miRNAs play an essential role in the formation of multiple diseases.Research on the clinical application and potential value of exosomes is growing.

Flavonoids and prenylhydroquinones from the prepared folium of Epimedium sagittatum Maxim. and their inhibition against phosphodiesterase5A.

An effort to identify novel active substances of the prepared folium of Epimedium sagittatum Maxim. (PFES) that was an important herb for male erectile dysfunction (ED) was taken. At present, phosphodiesterase-5A (PDE5A) is the most important target of new drugs for the treatment of ED. Therefore, the inhibition ingredients in PFES were systematically screened for the first time in this study. Eleven compounds, including eight new flavonoids and three prenylhydroquinones were isolated: sagittatosides DN (1-11), and their structures were elucidated by spectra and chemical analyses. Among them, a novel prenylflavonoid with oxyethyl group (1) was obtained and three prenylhydroquinones (9-11) were firstly isolated from Epimedium. All compounds were analyzed for the inhibition against PDE5A by molecular docking, and they all showed significant binding affinity as same as sildenafil. Their inhibitory activities were verified, and the results showed compound 6 had significant inhibition against PDE5A1. The isolation of new flavonoids and prenylhydroquinones with inhibitory activities of PDE5A from PFES implied that this herb might be a good source for the treatment of ED agents finding.

Association between monocyte to high-density lipoprotein ratio and coronary heart disease in US adults in the National Health and Nutrition Examination Surveys 2009-2018.

BACKGROUND: Monocyte to high-density lipoprotein ratio (MHR) is associated with coronary heart disease (CHD) events. The purpose of this study was to analyze the correlation between MHR and CHD in American adults from 2009 to 2018 in the National Health and Nutrition Examination Surveys (NHANES) database. METHODS: A total of 25 862 persons in the NHANES from 2009 to 2018 were included in the cross-sectional analysis. The independent variable was MHR and the outcome variable was CHD. MHR was obtained by dividing the number of monocytes by the high-density lipoprotein concentration, and whether it is CHD is obtained through a questionnaire. Univariate analysis, stratified analysis, and a multivariate linear regression model were used to study the correlation between MHR and CHD. RESULTS: In each multivariate linear regression model, MHR was positively correlated with CHD, and this positive correlation was stable in both men and women [man odds ratio (OR): 1.54; 95% confidence interval (CI), 1.17-2.03; woman OR: 2.21; 95% CI, 1.40-3.50]. Our results show that the association between MHR and CHD was significant until MHR was less than 0.6 (OR: 7.2; 95% CI, 4.0-13.0); however, in cases where MHR was greater than 0.6, the results were negative but not significantly different (OR: 0.6; 95% CI, 0.3-1.2). CONCLUSION: MHR has a clear association with CHD. Our prediction model and validation model show that MHR is highly predictive and robust as a predictor of CHD, therefore it can play an important role in the prediction of CHD.

Association between hypertension and stroke in US adults in the National Health and Nutrition Examination Surveys (NHANES) 2007 to 2018.

BACKGROUND: Hypertension is associated with stroke events. The purpose of this study was to analyze the correlation between hypertension and stroke in American adults from 2007 to 2018 in National health and Nutrition Examination Survey (NHANES) database. METHODS: 28528 individuals in the NHANES from 2007 to 2018 were included in the cross-sectional analysis. The independent variable was blood pressure (BP) and the outcome variable was stroke. Multivariate linear regression model was used to study the correlation between BP and stroke. RESULTS: In each multivariate linear regression model, BP level was positively correlated with stroke, and this positive correlation was stable in both men and women (man OR: 1.36, 95% CI: 0.95 to 1.69; woman OR: 1.45, 95% CI: 1.12 to 1.78). CONCLUSION: Our results show that there is a significant positive correlation between BP and stroke. When the systolic blood pressure (SBP) is about 140 mmHg, the risk of stroke is the lowest; Male patients with diastolic blood pressure (DBP) of about 80 mmHg have a lower risk of stroke.

Isolation, bioassay and 3D-QSAR analysis of 8-isopentenyl flavonoids from Epimedium sagittatum maxim. as PDE5A inhibitors.

BACKGROUND: As known, inhibition of phosphodiesterase 5 (PDE5) has the therapeutic effect on male erectile dysfunction (ED), and the processed folium of Epimedium sagittatum Maxim. (PFES) characterized by 8-isopentenyl flavonoids is a famous herb for treating ED. However, the main flavonoids inhibitory activities, structure-activity relationship (SAR) and signaling pathway have been not systematically studied so that its pharmacodynamic mechanism is unclear. METHODS: We aimed to initially reveal the PFES efficacy mechanism for treating ED. For the first time, 6 main 8-isopentenyl flavonoids (1-6) from PFES were isolated and identified. Then based on HPLC detection, we proposed a novel method to screen inhibitors among them. We further analyze the three-dimensional quantitative structure-activity relationship (3D-QSAR) for those inhibitors. RESULTS: The results were verified by cellular effects of the screened flavonoids. Among 6 compounds, Icariin: (1), 2-O''rhamnosylicaridide II (2) and Baohuoside I (3) were identified with significant activities (IC50 = 8.275, 3.233, 5.473 µM). Then 3D-QSAR studies showed that the replacement of C8 with bulky steric groups as isopentenyl, C3 with positive charge groups and C4' with a hydrogen bond acceptor substituent could increase inhibitory effects. In contrast, the substitution of C7 with bulky steric groups or hydrophilic groups tended to decrease the efficacies. And compounds 1, 2, 3 could increase cGMP level and decrease cytoplasmic Ca2+ of rat corpus cavernosum smooth muscle cells (CCSMCs)by activating PKG. CONCLUSION: 8-isopentenyl flavonoids could be the main pharmacodynamic substances of PFES in the treatment for ED, and some had significant PDE5A1 inhibitory activities so as to activate cGMP/PKG/Ca2+ signaling pathway in CCSMCs, that was related to the substituents at the key sites such as C8, C3, C4' and C7 in the characteristic compounds.

A metabolomics study of the intervention effect of Tartary buckwheat on hyperlipidemia mice.

Tartary buckwheat can improve hyperlipidemia and affect the changes of metabolic pathways to the body. In this study, we use LC/MS to obtain metabolic fingerprints of plasma samples collected from control (LFD), high-fat diet (HFD), Tartary buckwheat protein (BWP), and Tartary buckwheat starch (BWS). Using the metabolic network database, through OPLS-DA, the potential biomarkers and pathways of BWP and BWS intervention in hyperlipidemia mice are initially determined. The results showed that there are 30 metabolites in total, among which linoleic acid, glycerol, phosphatidyl, ethanolamine, and galactose ceramide are the most important differentially expressed metabolites in BWP and BWS plasma samples. These metabolites are involved in eight metabolic pathways, such as linoleic acid metabolism, arachidonic acid metabolism. Tartary buckwheat can alleviate the symptoms of hyperlipidemia in mice by affecting the above-mentioned metabolic pathways. This research has a profound impact on the development of nutritious foods of buckwheat. PRACTICAL APPLICATIONS: Tartary buckwheat, also known as wild buckwheat, is a typical embodiment homology of medicine and food. We have clarified that the protein and starch extracted from tartary buckwheat have the function of reducing blood lipids. It is expected to be applied to functional food materials in the health food market. Also, the effects of tartary buckwheat protein and starch in improving metabolic pathways can be generally applied as a physiological active compound of functional food supplements.

Practicability of Bivalirudin plus Glycoprotein IIb/IIIa Inhibitors in Patients Undergoing Percutaneous Coronary Intervention: A Meta-Analysis.

A variety of antithrombotic drugs are used during percutaneous coronary interventions (PCIs). We aimed to investigate the practicability of the use of bivalirudin and GPIs in patients receiving PCI. We searched 7 of 629 relevant records from PubMed, the Cochrane Library, EMBASE, and Web of Science for randomised controlled trials. There were no significant differences in the rates of major adverse cardiac events (MACE) between bivalirudin plus GPI and heparin (all P  >  .05). Bivalirudin plus planned GPI was similar to bivalirudin monotherapy in terms of the risk of MACE (risk ratio [RR] = 1.07; 95% confidence interval [CI] = .91 - 1.27; P = .55). Bivalirudin plus provisional GPI was associated with lower bleeding risk (RR = .57; 95% CI = .47 - .69; P < .01) compared to using heparin plus GPI. Compared to bivalirudin alone, bivalirudin plus planned GPI evidently increased bleeding risk (RR = 2.20; 95% CI = 1.73 - 2.79; P < .01). Patients receiving bivalirudin or heparin therapy had semblable efficacy endpoints, but those receiving bivalirudin had a significantly lower bleeding risk. For high-risk bleeding patients, bivalirudin plus provisional GPI can have a better antithrombotic effect than heparin, without increasing the bleeding risk.