Hua-Feng-Dan alleviates LPS-induced neuroinflammation by inhibiting the TLR4/Myd88/NF-κB pathway: Through Integrating Network Pharmacology and Experimental Validation.

BACKGROUND: Neuroinflammation is the pathological basis of many neurological diseases, including neurodegenerative diseases and stroke. Hua-Feng-Dan (HFD) is a well-established traditional Chinese medicine that has been used for centuries to treat stroke and various other brain-related ailments. OBJECTIVE: Our study aims to elucidate the molecular mechanism by which HFD mitigates neuroinflammation by combining network pharmacology and in vitro experiments. METHODS: TCMSP and SymMap databases were used to extract active compounds and their related targets. The neuroinflammation-related targets were obtained from the GeneCards database. The common targets of HFD and neuroinflammation were used to construct a protein-protein interaction (PPI) network. MCODE plug-in was used to find the hub module genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to dissect the hub module genes. The lipopolysaccharide (LPS)-induced BV2 microglial neuroinflammation model was utilized to assess the therapeutic effects of HFD on neuroin- flammation. Western blotting analysis was performed to examine the core target proteins in the TLR4/My- D88/NF-κB signaling pathway, potentially implicated in HFD's therapeutic effects on neuroinflammation. Hoechst 33342 staining and JC-1 staining were employed to evaluate neuronal apoptosis. RESULTS: Through network pharmacology, 73 active compounds were identified, with quercetin, beta-sitos- terol, luteolin, and (-)-Epigallocatechin-3-Gallate recognized as important compounds. Meanwhile, 115 com- mon targets of HFD and neuroinflammation were identified, and 61 targets were selected as the hub targets uti- lizing the MCODE algorithm. The results of in vitro experiments demonstrated that HFD significantly inhibit- ed microglial-mediated neuronal inflammation induced by LPS. Integrating the predictions from network phar- macology with the in vitro experiment results, it was determined that the mechanism of HFD in mitigating neu- roinflammation is closely related to the TLR4/MyD88/NF-κB pathway. Furthermore, HFD demonstrated the capacity to shield neurons from apoptosis by curbing the secretion of pro-inflammatory factors subsequent to microglial activation. CONCLUSION: The findings demonstrated that HFD had an inhibitory effect on LPS-induced neuroinflammation in microglia and elucidated its underlying mechanism. These findings will offer a theoretical foundation for the clinical utilization of HFD in treating neurodegenerative diseases associated with neuroinflammation.

Safety and efficacy of probiotics in the prevention of necrotizing enterocolitis in premature and/or low-birthweight infants: a systematic review and meta-analysis.

Background: Neonatal necrotizing enterocolitis (NEC) is a serious pediatric gastrointestinal disease and a cause of death in neonates, especially in premature infants. The addition of probiotics to the diet can reduce the incidence and severity of neonatal NEC. This meta-analysis explored the preventive effect of probiotics on NEC. Methods: Endnote X9 software was used to search for relevant studies in the Ovid, Embase, PubMed, and Web of Science databases. The search terms were "probiotics" and "necrotizing enterocolitis". After retrieval, screening, and quality evaluation of the studies, Stata 16.0 software was used to analyze the data. Results: A total of 10 studies, which collectively included 3,227 patients, were selected for analysis. Of them, 5 used a multiple-strain probiotics, and 5 used single-strain probiotic. Meta-analysis showed that treatment with probiotics could reduce the incidence of severe NEC [risk ratio (RR) =0.66; 95% confidence interval (CI): (0.50, 0.87); Z=-2.978; P=0.003], reduce mortality in underweight premature children [RR =0.81; 95% CI: (0.70, 0.94); Z=-2.864; P=0.004], and reduce the incidence of feeding intolerance [RR =0.78; 95% CI: (0.67, 0.90); Z=-3.280; P=0.001]. Discussion: The addition of probiotics to the diet of low-birthweight and premature infants can reduce the incidence of severe NEC and reduce related mortality rates.

Enhancement of anti-inflammatory effect of cattle bile by fermentation and its inhibition of neuroinflammation on microglia by inhibiting NLRP3 inflammasome.

As a kind of animal medicine, cattle bile has anti-inflammatory, antipyretic and cholagogic effects. The fermentation process of cattle bile is included in the application of many traditional Chinese medicines. In this study, we fermented cattle bile singly and investigated the impact of fermentation on the anti-inflammatory effect of cattle bile, as well as the mechanism of fermented cattle bile on microglia cells. After high temperature sterilization, cattle bile was fermented with Massa Medicata Fermentata (medicated leaven, Shen Qu). We used ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UHPLC-MS/MS) to analyze the bile acids of cattle bile and fermented cattle bile. The results showed that 3-dehydrocholic acid, 7-ketolithocholic acid, 12-dehydrocholic acid, 12-Ketolithocholic acid, ursodeoxycholic acid and dehydrolithocholic acid increased more significantly than others; glycocholic acid and glycochenodeoxycholic acid decreased more significantly than others. After fermentation, cattle bile significantly reduced the release of NO and inflammatory factors (TNF-α and IL-1ß). Furthermore, the protein expression of TNF-α, IL-1ß and iNOS were decreased. In addition, we found that fermented cattle bile could have an anti-inflammatory effect through attenuating the activation of NLRP3 inflammasome. Thus, fermentation can enhance the anti-inflammatory effect of cattle bile. Fermented cattle bile has an anti-inflammatory effect by inhibiting the NLRP3 inflammasome pathway, which can expand the clinical application of cattle bile and provide new thoughts and methods for the application of cattle bile.

Integrated Analysis of the Mechanisms of Da-Chai-Hu Decoction in Type 2 Diabetes Mellitus by a Network Pharmacology Approach.

BACKGROUND: The incidence of type 2 diabetes mellitus (T2DM) has increased year by year, which not only seriously affects people's quality of life, but also imposes a heavy economic burden on the family, society, and country. Currently, the pathogenesis, diagnosis, and treatment of T2DM are still unclear. Therefore, exploration of a precise multitarget treatment strategy is urgent. Here, we attempt to screen out the active components, effective targets, and functional pathways of therapeutic drugs through network pharmacology with taking advantages of traditional Chinese medicine (TCM) formulas for multitarget holistic treatment of diseases to clarify the potential therapeutic mechanism of TCM formulas and provide a systematic and clear thought for T2DM treatment. METHODS: First, we screened the active components of Da-Chai-Hu Decoction (DCHD) by absorption, distribution, metabolism, excretion, and toxicity (ADME/T) calculation. Second, we predicted and screened the active components of DCHD and its therapeutic targets for T2DM relying on the Traditional Chinese Medicine Systems Pharmacology Analysis Platform (TCMSP database) and Text Mining Tool (GoPubMed database), while using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) to obtain T2DM targets. Third, we constructed a network of the active component-target, target-pathway of DCHD using Cytoscape software (http://cytoscape.org/,ver.3.5.1) and then analyzed gene function, related biological processes, and signal pathways through the DAVID database. RESULTS: We screened 77 active components from 1278 DCHD components and 116 effective targets from 253 ones. After matching the targets of T2DM, we obtained 38 important targets and 7 core targets were selected through further analysis. Through enrichment analysis, we found that these important targets were mainly involved in many biological processes such as oxidative stress, inflammatory reaction, and apoptosis. After analyzing the relevant pathways, the synthetic pathway for the treatment of T2DM was obtained, which provided a diagnosis-treatment idea for DCHD in the treatment of T2DM. CONCLUSIONS: This article reveals the mechanism of DCHD in the treatment of T2DM related to inflammatory response and apoptosis through network pharmacology, which lays a foundation for further elucidation of drugs effective targets.

Clinical study for external Chinese herbal medicine LC09 treating hand-foot skin reaction associated with the antitumor targeted drugs: Protocol for a prospective, randomized, controlled, double-blind, and monocentric clinical trial.

BACKGROUND: Molecular targeted anticancer drugs such as multikinase inhibitors have shown obvious therapeutic advantages in a variety of tumors. The occurrence of hand-foot skin reaction (HFSR) is positively correlated with therapeutic effect, but it is also the most common cause of dose limiting toxicity for this treatment. This can lead to interruption or decrement of the treatment, a reduction in quality of life for patients, as well as potentially leading to secondary infections. As a result, the curative effect of targeted anticancer drugs will be negatively impacted. Currently, there is no certain and effective therapy. External use of Chinese herb medicine LC09 in the early treatment of HFSR has shown positive outcomes, but it is necessary to carry out further clinical research to confirm. OBJECTIVES: The purpose of this study was to investigate the efficacy and safety of topical soaks of Chinese herbal medicine LC09 for HFSR induced by molecular targeted anticancer drugs. METHODS: The trial is a prospective, randomized, controlled, double-blind, monocentric, and interventional study. A total of 66 patients with HFSR will be recruited and randomly assigned to receive either LC09 Granules or placebo. The primary outcomes are the assessment of HFSR grade and pain score. The secondary outcomes are the evaluation of the quality of life, incidence of targeted drug dosage reduction, and incidence of targeted drug withdrawal. DISCUSSION: This prospective, randomized clinical trial will provide valuable data regarding the efficacy and safety of topical soak treatments with LC09 granules for HFSR. Positive results would provide evidence-based complementary therapeutic approach future treatments of HFSR. TRIAL REGISTRATION: Chinese Clinical Trial Registry, http://www.chictr.org.cn, ChiCTR1900023679. Registered on 7 June 2019.