Chronic heart failure (CHF) is a key part of cardiovascular continuum. Under the guidance of the theory of vessel-collateral doctrine, the present study proposes therapeutic benefits of Qili Qiangxin (QLQX) capsules, an innovative Chinese medicine, on chronic heart failure. The studies show that multiple targets of the drug on CHF, including enhancing myocardial systole, promoting urine excretion, inhibiting excessive activation of the neuroendocrine system, preventing ventricular remodeling by inhibiting inflammatory response, myocardial fibrosis, apoptosis and autophagy, enhancing myocardial energy metabolism, promoting angiogenesis, and improving endothelial function. Investigation on the effects and mechanism of the drug is beneficial to the treatment of chronic heart failure (CHF) through multiple targets and/or signaling pathways. Meanwhile, it provides new insights to further understand other refractory diseases in the cardiovascular continuum, and it also has an important theoretical and practical significance in enhancing prevention and therapeutic effect of traditional Chinese medicine for these diseases.

To explore the new indications and key mechanism of Bazi Bushen capsule (BZBS) by network pharmacology and in vitro experiment. The ingredients library of BZBS was constructed by retrieving multiple TCM databases. The potential target profiles of the components were predicted by target prediction algorithms based on different principles, and validated by using known activity data. The target spectrum of BZBS with high reliability was screened by considering the source of the targets and the node degree in compound-target (C-T) network. Subsequently, new indications for BZBS were predicted by disease ontology (DO) enrichment analysis and initially validated by GO and KEGG pathway enrichment analysis. Furthermore, the target sets of BZBS acting on AD signaling pathway were identified by intersection analysis. Based on STRING database, the PPI network of target was constructed and their node degree was calculated. Two Alzheimer's disease (AD) cell models, BV-2 and SH-SY5Y, were used to preliminarily verify the anti-AD efficacy and mechanism of BZBS in vitro. In total, 1499 non-repeated ingredients were obtained from 16 herbs in BZBS formula, and 1320 BZBS targets with high confidence were predicted. Disease enrichment results strongly suggested that BZBS formula has the potential to be used in the treatment of AD. GO and KEGG enrichment results provide a preliminary verification of this point. Among them, 113 functional targets of BZBS belong to AD pathway. A PPI network containing 113 functional targets and 1051 edges for the treatment of AD was constructed. In vitro experiments showed that BZBS could significantly reduce the release of TNF-α and IL-6 and the expression of COX-2 and PSEN1 in Aβ_25-35-induced BV-2 cells, which may be related to the regulation of ERK_1/2/NF-κB signaling pathway. BZBS reduced the apoptosis rate of Aβ_25-35 induced SH-SY5Y cells, significantly increased mitochondrial membrane potential, reduced the expression of Caspase3 active fragment and PSEN1, and increased the expression of IDE. This may be related to the regulation of GSK-3β/β-catenin signaling pathway. BZBS formula has a potential use in the treatment of AD, which is achieved through regulation of ERK_1/2, NF-κB signaling pathways, and GSK-3β/β-catenin signaling pathway. Furthermore, the network pharmacology technology is a feasible drug repurposing strategy to reposition new clinical use of approved TCM and explore the mechanism of action. The study lays a foundation for the subsequent in-depth study of BZBS in the treatment of AD and provides a basis for its application in the clinical treatment of AD.

Growing evidence shows that the neuroendocrine immunomodulation (NIM) network plays an important role in maintaining and modulating body function and the homeostasis of the internal environment. The disequilibrium of NIM in the body is closely associated with many diseases. In the present study, we first collected a core dataset of NIM signaling molecules based on our knowledge and obtained 611 NIM signaling molecules. Then, we built a NIM molecular network based on the MetaCore database and analyzed the signaling transduction characteristics of the core network. We found that the endocrine system played a pivotal role in the bridge between the nervous and immune systems and the signaling transduction between the three systems was not homogeneous. Finally, employing the forest algorithm, we identified the molecular hub playing an important role in the pathogenesis of rheumatoid arthritis (RA) and Alzheimer’s disease (AD), based on the NIM molecular network constructed by us. The results showed that GSK3B, SMARCA4, PSMD7, HNF4A, PGR, RXRA, and ESRRA might be the key molecules for RA, while RARA, STAT3, STAT1, and PSMD14 might be the key molecules for AD. The molecular hub may be a potentially druggable target for these two complex diseases based on the literature. This study suggests that the NIM molecular network in this paper combined with the forest algorithm might provide a useful tool for predicting drug targets and understanding the pathogenesis of diseases. Therefore, the NIM molecular network and the corresponding online tool will not only enhance research on complex diseases and system biology, but also promote the communication of valuable clinical experience between modern medicine and Traditional Chinese Medicine (TCM).

Recent studies indicate existence of beige adipocytes in adults. Upon activation, beige adipocytes burn energy for thermogenesis and contribute to regulation of energy balance. In this study, we have analyzed whether Jinlida granules (JLD) could activate beige adipocytes. JLD suspended in 0.5% carboxymethyl cellulose (CMC) was gavage fed to db/db mice at a daily dose of 3.8 g/kg. After 10 weeks, body weight, biochemical, and histological analyses were performed. In situ hybridization, immunofluorescence, and western blotting were conducted to test beige adipocyte activation in mice. X9 cells were induced with induction medium and maintenance medium containing 400 μg/mL of JLD. After completion of induction, cells were analyzed by Nile red staining, time polymerase chain reaction (PCR), western blotting, and immunofluorescence to understand the effect of JLD on the activation of beige adipocytes. A molecular docking method was used to preliminarily identify compounds in JLD, which hold the potential activation effect on uncoupling protein 1 (UCP1). JLD treatment significantly improved obesity in db/db mice. Biochemical results showed that JLD reduced blood glucose (GLU), triglyceride (TG), and low‐density lipoprotein cholesterol (LDL) levels as well as liver aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in mice. Hematoxylin and eosin staining (H&E) showed that JLD reduced hepatocyte ballooning changes in the liver. Immunofluorescence showed that JLD increased the expression of the thermogenic protein, UCP1, in the beige adipose tissue of mice. JLD also increased the expression of UCP1 and inhibited the expression of miR‐27a in X9 cells. Molecular docking results showed that epmedin B, epmedin C, icariin, puerarin, and salvianolic acid B had potential activation effects on UCP1. The results suggest that JLD may activate beige adipocytes by inhibiting miR‐27a expression, thereby promoting thermogenesis in beige adipocytes. This study provides a new pharmacological basis for the clinical use of JLD.

Lianhua Qingke (LHQK) has been utilized as a complementary therapy for respiratory diseases like tracheobronchitis and acute exacerbations of COPD in China. However, its therapeutic efficacy and underlying mechanisms for COPD remain elusive. This study aimed to elucidate the mechanisms underlying the effects of LHQK on COPD, focusing on its anti-senescence properties. The therapeutic effects of LHQK were assessed by chronic cigarette smoke exposure induced COPD mice model. Lung function, histopathology investigation, cytokines detection and bio-molecular analysis were conducted to assess the impact of LHQK on pulmonary inflammation, mucin secretion, and cellular senescence of cigarette smoke (CS)-induced COPD mice. A comprehensive analysis identified a total of 41 compounds as the key compounds of LHQK. Oral administration of LHQK markedly reversed the decline in pulmonary function, suppressed inflammation and mucus secretion, mitigated emphysema, and histopathology damage in lungs of COPD mice. In addition, LHQK attenuated secretory phenotype associated with cellular senescence in pulmonary and circulatory, and reduced the senescence-associated markers levels, such as SA-β-gal, miR-125a-5p, p21, p27 and p53. Network pharmacology and molecular assays indicated that LHQK enhanced Sp1 and SIRT1 expression, resulting to repression of HIF-1α, finally alleviating cellular senescence in COPD mice. LHQK demonstrates potential as a complementary therapy for COPD, attenuating CS-triggered emphysema and pulmonary inflammation by targeting cellular senescence processes and modulation of Sp1/SIRT1/HIF-1α pathway.

Three new chromone glycosides, named 2-methyl-5-hydroxyl-4-chromone-7-O-β-D-glucuronide (1), 2-ethyl-5-hydroxyl-4-chromone-7-O-β-D-glucuronide (2) and 1-acetyl-3-C-β-D-glucopyranosyl-5-methyl-phloroglucinyl-6-O-β-D-glucopyranoside (6), together with eight known compounds were isolated from the water extract of Dryopteris crassirhizoma Nakai，and the water extract preparation process is consistent with Lianhua Qingwen capsule. All the chemical structures of new compounds were characterized by 1D and 2D NMR spectra as well as high resolution mass and IR spectra. The chemical structures of known compounds were characterized by NMR spectra along with comparison of their spectroscopic data with those reported in the literature. The binding ability of these compounds to 3CL hydrolase of SARS-COV-2 was evaluated by molecular docking. The results showed that the chromone glycosides with glucuronic acid fragment had good docking effect with 3CL hydrolase and this indicated the chromone glucuronides could be further studied as potential antiviral compounds.