Investigating the multi-target therapeutic mechanism of Guihuang formula on Chronic Prostatitis.

Purpose Shiliao Decoction (SLD) was developed for treatment and prevention of cancer-associated malnutrition (CAM) in China. In this study, we aim to discover SLD’s active compounds and demonstrate the mechanisms of SLD that combat CAM through network pharmacology and molecular docking techniques. Methods All components of SLD were retrieved from the pharmacology database of Traditional Chinese Medicine Systems Pharmacology (TCMSP). The GeneCards database and the Online Mendelian Inheritance in Man database (OMIM) were used to identify gene encoding target compounds, and Cytoscape was used to construct the drug compound–target network. The network of target protein-protein interactions (PPI) was constructed using the STRING database, while gene ontology (GO) functional terms and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways associated with potential targets were analyzed using a program in R language (version 4.2.0). Core genes linked with survival and the tumor microenvironment were analyzed using the Kaplan–Meier plotter and TIMER 2.0 databases, respectively. Protein expression and transcriptome expression levels of core gene were viewed using the Human Protein Atlas (HPA) and the Cancer Genome Atlas (TCGA). A component-target-pathway (C-T-P) network was created using Cytoscape, and Autodock Vina software was used to verify the molecular docking of SLD components and key targets. Results The assembled compound–target network primarily contained 134 compounds and 147 targets of the SLD associated with JUN, TP53, MAPK3, MAPK1, MAPK14, STAT3, AKT1, HSP90AA1, FOS, and MYC, which were identified as core targets by the PPI network. KEGG pathway analysis revealed pathways involved in lipid and atherosclerosis, the PI3K/Akt signaling pathway, and immune-related pathways among others. JUN is expressed at different levels in normal and cancerous tissues, it is closely associated with the recruitment of different immune cells and has been shown to have a significant impact on prognosis. The C-T-P network suggests that the active component of SLD is capable of regulating target genes affecting these related pathways. Finally, the reliability of the core targets was evaluated using molecular docking technology. Conclusion This study revealed insights into SLD’s active components, potential targets, and possible molecular mechanisms, thereby demonstrating a potential method for examining the scientific basis and therapeutic mechanisms of TCM formulae.

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Network pharmacology and molecular docking analysis reveal insights into the molecular mechanism of shiliao decoction in the treatment of cancer-associated malnutrition

Background. The traditional Chinese medicines Astragalus and Angelica are often combined to treat male infertility, but the specific therapeutic mechanism is not clear. Therefore, this study applies a network pharmacology approach to investigate the possible mechanism of action of the drug pair Astragalus-Angelica (PAA) in the treatment of male infertility. Methods. Relevant targets for PAA treatment of male infertility are obtained through databases. Protein-protein interactions (PPIs) are constructed through STRING database and screen core targets, and an enrichment analysis is conducted through the Metascape platform. Finally, molecular docking experiments were carried out to evaluate the affinity between the target protein and the ligand of PAA. Results. The active ingredients of 112 PAA, 980 corresponding targets, and 374 effective targets of PAA for the treatment of male infertility were obtained, which are related to PI3K-Akt signaling pathway, HIF-1 signaling pathway, AGE-RAGE signaling pathway, IL-17 signaling pathway, and thyroid hormone signaling pathway. Conclusion. In this study, using a network pharmacology method, we preliminarily analyzed the effective components and action targets of the PAA. We also explored the possible mechanism of action of PAA in treating male infertility. They also lay a foundation for expanding the clinical application of PAA and provide new ideas and directions for further research on the mechanisms of action of the PAA and its components for male infertility treatment.

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Network Pharmacology-Based Strategy to Investigate Pharmacological Mechanisms of the Drug Pair Astragalus-Angelica for Treatment of Male Infertility.

The modern clinical use of hallucinogens. What can we learn from the natural product research?

The largest solid organ of the male genitalia, the prostate gland, is comprised of a variety of cells such as prostate epithelial cells, smooth muscle cells, fibroblasts, and endothelial cells. Prostate diseases, especially prostate cancer and prostatitis, are often accompanied by acute/chronic inflammatory responses or even cell death. Pyroptosis, a cell death distinct from necrosis and apoptosis, which mediate inflammation may be closely associated with the development of prostate disease. Pyroptosis is characterized by inflammasome activation via pattern recognition receptors (PRR) upon recognition of external stimuli, which is manifested downstream by translocation of gasdermin (GSDM) protein to the membrane to form pores and release of inflammatory factors interleukin (IL)-1β and IL-18, a process that is Caspase-dependent. Over the past number of years, many studies have investigated the role of inflammation in prostate disease and have suggested that pyroptosis may be an important driver. Understanding the precise mechanism is of major consequence for the development of targeted therapeutic strategies. This review summarizes the molecular mechanisms, regulation, and cellular effects of pyroptosis briefly and then discuss the current pyroptosis studies in prostate disease research and the inspiration for us. 

Relationship between pyroptosis-mediated inflammation and the pathogenesis of prostate disease

Erectile dysfunction (ED) is one of the most common sexual dysfunctions in men. The prevalence of ED has been increasing in recent years, which has critically affected male reproductive health and quality of life. According to various guidelines, phosphodiesterase-5 inhibitors are the most commonly recommended drugs for treating ED. However, many patients turn to alternative therapies because of adverse reactions, such as headache, and the poor efficacy of these drugs. Acupuncture is a long-established treatment in traditional Chinese medicine (TCM) and has been approved by the World Health Organization for improving penile erection as well as other discomforts in patients. However, previous systematic reviews have not discussed the characteristics and the related mechanisms of acupuncture treatment. Therefore, this study focuses on summarizing the characteristics and advantages of TCM in acupuncture treatment for ED based on relevant literature and on predicting and analyzing the related mechanisms.

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The Efficacy of Acupuncture on Patients with Erectile Dysfunction: A Review

To observe the efficacy and safety of Guihuang Formula (GHF) in treating patients with type III prostatitis and Chinese medicine syndrome of dampness-heat and blood stasis.Sixty-six patients diagnosed with type III prostatitis with dampness-heat and blood stasis syndrome were randomly divided into the treatment group (GHF) and the control group (tamsulosin) using a random number table, with 33 cases each group. The treatment group received GHF twice a day, and the control group received tamsulosin 0.2 mg once daily before bedtime. Patients in both groups received treatment for 6 weeks and was followed up for 2 weeks. The outcomes included the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score, Chinese Medicine Symptoms Score (CMSS), expressed prostatic secretions (EPS) and adverse events (AEs).After treatment, the NIH-CPSI total score and domain scores of pain discomfort, urination and quality of life decreased significantly from the baseline in both groups (P<0.05). The CMSS score decreased in both groups (P<0.05). The WBC count decreased and lecithin body count increased in both groups (P<0.05). GHF showed a more obvious advantage in reducing the pain discomfort and quality of life domain scores of NIH-CPSI, reducing the CMSS score, increasing the improvement rate of the WBC and lecithin body counts, compared with the control group (P<0.05). There were no significant differences in decreasing urination domain score of NIH-CPSI between two groups (P>0.05). In addition, no serious AEs were observed.GHF is effective in treating type III prostatitis patients with dampness-heat and blood stasis syndrome without serious AEs. (Registration No. ChiCTR1900026966). 

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Efficacy and Safety of Guihuang Formula in Treating Type III Prostatitis Patients with Dampness-Heat and Blood Stasis Syndrome: A Randomized Controlled Trial

Objective: The objective is to study the network pharmacology of Qixiong formula (QXF) and explore the mechanism of QXF in the treatment of oligoasthenospermia. Materials and Methods: Using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), a Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-traditional Chinese medicine), and an encyclopaedia of traditional Chinese medicine (ETCM) databases as well as data from relevant studies, the effective components and targets of QXF were obtained. Genes associated with oligospermia were screened using GeneCards, OMIM, DisGeNet, DrugBank, and GAD databases. The intersection target was obtained by mapping the target to the gene, and the protein interaction network was created using the STRING database to screen the core target of QXF in the treatment of oligospermia. The intersection target was enriched using gene ontology (GO) and the Kyoto Encyclopedia of genes and genomes (KEGG) pathway analysis with the DAVID database. The network of the disease drug target pathway was drawn using Cytoscape software. Results: Overall, 536 active components of QXF and 40 core targets for the treatment of oligoasthenozoospermia were obtained. The analysis of GO and KEGG showed that QXF is mainly involved in oxidative stress, cell motility, nutritional response, and other biological processes. Through the regulation of FOXO, p53, PI3K/Akt, MAPK, mammalian target of rapamycin, Foxo, Wnt, and other signaling pathways, QXF played a role in the treatment of oligoasthenospermia. Conclusion: QXF has multi-component, multi-target, and multi-channel characteristics, providing a new way to study the mechanism of QXF in the treatment of oligoasthenospermia.

Sheng-Jing Liu

Papers

Investigating the multi-target therapeutic mechanism of Guihuang formula on Chronic Prostatitis.

The Efficacy of Acupuncture on Patients with Erectile Dysfunction: A Review

Efficacy and Safety of Guihuang Formula in Treating Type III Prostatitis Patients with Dampness-Heat and Blood Stasis Syndrome: A Randomized Controlled Trial

Network pharmacology-based study of chinese herbal qixiong formula in treating oligoasthenospermia

Network Pharmacology-Based Strategy to Investigate Pharmacological Mechanisms of the Drug Pair Astragalus-Angelica for Treatment of Male Infertility.