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Osteoporosis is a global health challenge characterized by bone loss and microstructure deterioration, which urgently requires the development of safer and more effective treatments due to the significant adverse effects and limitations of existing drugs for long-term treatment. Traditional Chinese medicine, like Epimedium, offers fewer side effects and has been used to treat osteoporosis, yet its active compounds and pharmacological mechanisms remain unclear. In this study, 65 potential active compounds, 258 potential target proteins, and 488 pathways of Epimedium were identified through network pharmacology analysis. Further network analysis and review of the literature identified six potential active compounds and HIF-1α for subsequent experimental validation. In vitro experiments confirmed that 2″-O-RhamnosylIcariside II is the most effective compound among the six potential active compounds. It can promote osteoblast differentiation, bind with HIF-1α, and inhibit both HIF-1α gene and protein expression, as well as enhance COL1A1 protein expression under hypoxic conditions. In vivo experiments demonstrated its ability to improve bone microstructures and reduce bone loss by decreasing bone marrow adipose tissue, enhancing bone formation, and suppressing HIF-1α protein expression. This study is the first to describe the therapeutic effects of 2-O-RhamnosylIcariside II on osteoporosis, which was done, specifically, through a mechanism that targets and inhibits HIF-1α. This study provides a scientific basis for the clinical application of Epimedium and offers a new candidate drug for the treatment of osteoporosis. Additionally, it provides new evidence supporting HIF-1α as a therapeutic target for osteoporosis. [ABSTRACT FROM AUTHOR]

Background: Myocardial infarction (MI) poses a global public health challenge, often associated with elevated mortality rates and a grim prognosis. A crucial aspect of the inflammatory injury and healing process post-MI involves the dynamic differentiation of macrophages. A promising strategy to alleviate myocardial damage after MI is by modulating the inflammatory response and orchestrating the shift from pro-inflammatory (M1) to anti-inflammatory (M2) macrophages, aiming to achieve a reduced M1/M2 ratio. Nuanxinkang (NXK), a simplified herbal decoction, has demonstrated noteworthy cardioprotective, inflammation-regulating, and myocardial energy metabolism-regulating properties. Methods: In this study, we constructed an MI model by ligating coronary arteries to investigate the efficacy of NXK in improving ventricular remodeling and cardiac function. Mice were administered NXK (1.65 g/kg/d) or an equivalent volume of regular saline via gavage for 28 consecutive days, commencing the day after surgery. Then, we conducted echocardiography to assess the cardiac function, Masson staining to illustrate the extent of myocardial fibrosis, TUNEL staining to reveal myocardial apoptosis, and flow cytometry to analyze the polarization of M1 and M2 macrophages in the hearts. Besides, a lipopolysaccharide (LPS)-induced pro-inflammatory macrophage (M1) polarization model was implemented in RAW264.7 cells to elucidate the underlying mechanism of NXK in regulating macrophage polarization. RAW264.7 cells were pre-treated with or without NXK-containing serum. Oxidative stress was detected by MitoSox staining, followed by Seahorse energy metabolism assay to evaluate alterations in mitochondrial metabolic patterns and ATP production. Both In vivo and in vitro, HIF-1α and PDK1 were detected by fluorescent quantitative PCR and Western blotting. Results: In vivo, MI mice exhibited a decline in cardiac function, adverse ventricular remodeling, and an increase in glycolysis, coupled with M1-dominant polarization mediated by the HIF-1α/PDK1 axis. Notably, robust responses were evident with high-dose NXK treatment (1.65 g/kg/day), leading to a significant enhancement in cardiac function, inhibition of cardiac remodeling, and partial suppression of macrophage glycolysis and the inflammatory phenotype in MI mice. This effect was achieved through the modulation of the HIF-1α/PDK1 axis. In vitro, elevated levels of mitochondrial ROS production and glycolysis were observed in LPS-induced macrophages. Conversely, treatment with NXK notably reduced the oxidative stress damage induced by LPS and enhanced oxidative phosphorylation (OXPHOS). Furthermore, NXK demonstrated the ability to modify the energy metabolism and inflammatory characteristics of macrophages by modulating the HIF-1α/PDK1 axis. The influence of NXK on this axis was partially counteracted by the HIF-1α agonist DMOG. And NXK downregulated PDK1 expression, curtailed glycolysis, and reversed LPS-induced M1 polarization in macrophages, similar to the PDK1 inhibitor DCA. Conclusion: In conclusion, NXK protects against MI-induced cardiac remodeling by inducing metabolic reprogramming and phenotypic differentiation of macrophages, achieved through the modulation of the HIF-1α/PDK1 axis. This provides a novel and promising strategy for the treatment of MI. Highlights: Balancing the coordination between M1 and M2 macrophages emerges as a promising therapeutic strategy for addressing myocardial infarction. Metabolic reprogramming plays a crucial role in the activation and differentiation of macrophages. NXK formulation intricately regulates macrophage polarization through the HIF-1α/PDK1 axis within a metabolic-inflammatory network. [ABSTRACT FROM AUTHOR]

Background: Chelidonium majus is a well-known traditional Chinese medicine, and has been reported of the effect in relieving cough and asthma. However, the mechanism of action is still unknown. Methods: Asthmatic SD rats were first sensitized and established through ovalbumin (OVA) motivation. Subsequently, Hematoxylin and eosin (H&E) staining, Masson's trichrome (Masson) staining, Periodic acid-Schiff (PAS) staining and inflammatory cytokines assay of interleukin (IL)-4, IL-6, IL-17 were implemented to evaluate the protective effects of Chelidonium majus on asthma. Then, the effects of Chelidonium majus and their molecular mechanisms of action on asthma were detected based on the integration of transcriptomics and metabolomics analyses. Results: After administration with Chelidonium majus, the histological injuries of inflammation, collagen deposition and mucus secretion in lungs were attenuated and the serum inflammatory cytokines perturbations were also converted. Furthermore, integrated analysis revealed that after Chelidonium majus treatment, 7 different expression genes (DEGs) (Alox15, P4ha1, Pla2g16, Pde3a, Nme1, Entpd8 and Adcy9) and 9 metabolic biomarkers (ADP, Xanthosine, Hypoxanthine, Inosine, prostaglandin E2 (PGE2), prostaglandin F2a (PGF2a), phosphatidylserine, Creatine and LysoPC (10:0)) were discovered to be connected with the enrichment metabolic pathways, including Purine metabolism, Arachidonic acid metabolism, Arginine and proline metabolism and Glycerophospholipid metabolism. The obtained metabolic biomarkers and DEGs were mainly related to energy metabolism and inflammation, and may be potential therapeutic targets. Conclusion: Chelidonium majus relieved OVA-induced asthma in rats by regulating the Alox15, P4ha1, Pla2g16, Pde3a, Nme1, Entpd8 and Adcy9 genes expression to restore the disorders in energy metabolism and inflammation. [ABSTRACT FROM AUTHOR]

This meta‐analysis was conducted to evaluate the efficacy and safety of the addition of Traditional Chinese Medicine (TCMs) to capecitabine‐based regimens for colorectal cancer (CRC) in term of tumor. The eight electronic databases including Cochrane Library, PubMed, Web of Science (WOS), Excerpt Medica Database (Embase), Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Journals (CQVIP), and Wanfang Database were systematically searched for eligible studies from their inception to March 2021. Thirty‐nine randomized controlled trials were involved in this study, and all the data were analyzed by Review Manager 5.3 (Nordic Cochran Centre, Copenhagen, Denmark) and R 4.0.5 software. The meta‐analyses suggested that TCMs in combination with capecitabine‐based regimens increased objective response rate (ORR) in the palliative treatment of CRC (risk ratio [RR], 1.35 [1.17, 1.55], I2 = 0%), disease control rate (DCR) (RR, 1.22 [1.12, 1.32], I2 = 3%), and quality of life (QOL) (RR, 1.71 [1.44, 2.03], I2 = 0%), with decreased risks of myelosuppression, anemia, thrombocytopenia, liver/renal dysfunction, neurotoxicity, nausea/vomiting, neutropenia, diarrhea, leukopenia, improved the peripheral lymphocyte, reduced the expression of tumor markers, and related factors. Further sensitivity analysis of specific plant‐based TCMs found that dangshen, fuling, and gancao had significantly higher contributions to the results of the RR. The results show that capecitabine‐based chemotherapy combined with TCM in the treatment of CRC increases the efficiency of ORR and DCR, reduces chemotherapeutic agents‐associated adverse reactions, and improves their life quality as compared with chemotherapy alone, but further randomized and large sample of studies are needed. [ABSTRACT FROM AUTHOR]

Xinyang tablet (XYT) has been used for heart failure (HF) for over twenty years in clinical practice, but the underlying molecular mechanism remains poorly understood. In the present study, we aimed to explore the protective effects of XYT in HF in vivo and in vitro. Transverse aortic constriction was performed in vivo to establish a mouse model of cardiac pressure overload. Echocardiography, tissue staining, and real-time quantitative PCR (qPCR) were examined to evaluate the protective effects of XYT on cardiac function and structure. Adenosine 5′-triphosphate production, reactive oxygen species staining, and measurement of malondialdehyde and superoxide dismutase was used to detect mitochondrial damage. Mitochondrial ultrastructure was observed by transmission electron microscope. Immunofluorescence staining, qPCR, and Western blotting were performed to evaluate the effect of XYT on the mitochondrial unfolded protein response and mitophagy, and to identify its potential pharmacological mechanism. In vitro , HL-1 cells and neonatal mouse cardiomyocytes were stimulated with Angiotensin II to establish the cell model. Western blotting, qPCR, immunofluorescence staining, and flow cytometry were utilized to determine the effects of XYT on cardiomyocytes. HL-1 cells overexpressing receptor-interacting serum/three-protein kinase 3 (RIPK3) were generated by transfection of RIPK3-overexpressing lentiviral vectors. Cells were then co-treated with XYT to determine the molecular mechanisms. In the present study, XYT was found to exerta protective effect on cardiac function and structure in the pressure overload mice. And it was also found XYT reduced mitochondrial damage by enhancing mitochondrial unfolded protein response and restoring mitophagy. Further studies showed that XYT achieved its cardioprotective role through regulating the RIPK3/FUN14 domain containing 1 (FUNDC1) signaling. Moreover, the overexpression of RIPK3 successfully reversed the XYT-induced protective effects and significantly attenuated the positive effects on the mitochondrial unfolded protein response and mitophagy. Our findings indicated that XYT prevented pressure overload-induced HF through regulating the RIPK3/FUNDC1-mediated mitochondrial unfolded protein response and mitophagy. The information gained from this study provides a potential strategy for attenuating mitochondrial damage in the context of pressure overload-induced heart failure using XYT. [Display omitted] • XYT reduces cardiac dysfunction in TAC mice. • XYT reduces AngII-induced cardiomyocyte injury. • RIPK3/FUNDC1-mediated UPRmt and mitophagy is an important pathway for the efficacy of XYT. [ABSTRACT FROM AUTHOR]

Traditional Chinese medicine (TCM) has played an indispensable role in clinical diagnosis and treatment. Based on a patient's symptom phenotypes, computation-based prescription recommendation methods can recommend personalized TCM prescription using machine learning and artificial intelligence technologies. However, owing to the complexity and individuation of a patient's clinical phenotypes, current prescription recommendation methods cannot obtain good performance. Meanwhile, it is very difficult to conduct effective representation for unrecorded symptom terms in an existing knowledge base. In this study, we proposed a subnetwork-based symptom term mapping method (SSTM) and constructed a SSTM-based TCM prescription recommendation method (termed TCMPR). Our SSTM can extract the subnetwork structure between symptoms from a knowledge network to effectively represent the embedding features of clinical symptom terms (especially the unrecorded terms). The experimental results showed that our method performs better than state-of-the-art methods. In addition, the comprehensive experiments of TCMPR with different hyperparameters (i.e., feature embedding, feature dimension, subnetwork filter threshold, and feature fusion) demonstrate that our method has high performance on TCM prescription recommendation and potentially promote clinical diagnosis and treatment of TCM precision medicine. [ABSTRACT FROM AUTHOR]

Atherosclerosis is the pathological basis of cardiovascular and cerebrovascular diseases. Nelumbo nucifera Gaertn. leaves are edible, an effective traditional Chinese medicine in the treatment of atherosclerosis, but its mechanisms of action remain unclear. In this study, we employed network pharmacology and molecular docking approaches to explore it, and preliminarily verify it through animal experiments. Firstly, we obtained the active ingredients of N. nucifera leaves and their potential targets in several databases. Comparing with the atherosclerosis drug targets, we acquired their common targets by Venny 2.1.0 software, with which, a protein–protein interaction (PPI) network was then constructed. Then, we performed enrichment analysis of GO functions and KEGG pathways by Metascape. Molecular docking was also carried out between the active ingredients and their core targets to test their binding activity. Lastly, animal experiments with Apoe-/- mice were performed to initially verify the efficacy of N. nucifera leaves in treating atherosclerosis. As a result, a total of 16 major active ingredients of N. nucifera leaves and 219 potential targets were identified, and 11 core targets were obtained from the PPI network. The molecular docking results showed stronger binding activity of these core targets with the major active ingredients. The animal experiments indicated that N. nucifera leaves could effectively improve atherosclerosis by lowering the levels of lipids and inflammatory factors. Accordingly, our present study provided experimental foundation for the underlying mechanisms and clinical application in treating atherosclerosis via N. nucifera leaves. Further work still needs to be performed to verify them in future experiments. [ABSTRACT FROM AUTHOR]

Modified Tabusen-2 decoction (MTBD) is traditional Chinese Mongolia medicine, mainly used to treat osteoporosis. However, the precise material basis of this prescription is not yet fully elucidated. Herein, we establish an HPLC-Q-Exactive MS/MS spectrometer method with four-step characteristic ion filtering (FSCIF) strategy to quickly and effectively identify the structural features of MTBD and determine the representative compounds content. The FSCIF strategy included database establishment, characteristic ions summarization, neutral loss fragments screening, and secondary mass spectrum fragment matching four steps. By using this strategy, a total of 143 compounds were unambiguously or tentatively annotated, including 5 compounds which were first reported in MTBD. Nineteen representative components were simultaneously quantified with the HPLC-Q-Exactive MS/MS spectrometer, and it is suitable for eight batches of MTBD. Methodology analysis showed that the assay method had good repeatability, accuracy, and stability. The method established above was successfully applied to assess the quality of MTBD extracts. Collectively, our findings enhance our molecular understanding of the MTBD formulation and will allow us to control its quality in a better way. At the same time, this study can promote the development and utilization of ethnic medicine. [ABSTRACT FROM AUTHOR]

Interstitial lung disease (ILD) is a chronic lung dysfunction disease with a poor prognosis and poor recovery. The clinically used therapeutic drugs, such as glucocorticoids and immunosuppressants, have no significant therapeutic effect and are accompanied with severe side effects. In recent years, considerable progress has been made in exploring and applying natural herb components for treating ILD. Traditional Chinese Medicine (TCM) possesses innate, non-toxic characteristics and offers advantages in preventing and treating pulmonary ailments. However, a comprehensive study of TCM on ILD therapy has not yet been reviewed. This review aimed to provide a comprehensive summary of the monomer components, total extracts, and prescriptions of TCM for ILD therapy, elucidating their molecular mechanisms to serve as a reference in treating ILD. The literature information was searched in the PubMed, Web of Science databases. The search keywords included 'interstitial lung disease', 'lung fibrosis' or 'pulmonary fibrosis', and 'traditional Chinese medicine', 'traditional herbal medicine', or 'herb medicine'. The active components of single herbs, such as alkaloids, flavonoids, terpenoids, phenols, and quinones, have potential therapeutic effects on ILD. The active extracts and prescriptions were also summarized and analyzed. The herbs, Glycyrrhiza uralensis Fisch. (Gancao), Astragalus membranaceus Fisch. Bunge. (Huangqi) and Angelicasinensis (Oliv.) Diels (Danggui), play significant roles in the treatment of ILD. The mechanisms involve the inhibition of inflammatory factor release, anti-oxidative injury, and interference with collagen production, etc. This review examines the therapeutic potential of TCM for ILD and elucidates its molecular mechanisms, demonstrating that mitigating inflammation and oxidative stress, modulating the immune system, and promoting tissue repair are efficacious strategies for ILD therapy. The depth research will yield both theoretical and practical implications. [Display omitted] • The active components derived from TCM have potential therapeutic effects against ILD. • The total extract from TCM is effective for the treatment of ILD. • The therapeutic mechanisms of TCM for ILD include anti-inflammatory, antioxidant and immunomodulatory effects. [ABSTRACT FROM AUTHOR]

Cybister chinensis Motschulsky belongs to the family Dytiscidae. As a traditional Chinese medicine, the insect is called Longshi in the folk and is commonly used to treat enuresis in children and frequent urination in the elderly. Inflammation is involved in chronic kidney disease. The previous study proved ethanol extract of C. chinensis exhibited anti-inflammation effects in the Doxorubicin-induced kidney disease. However, the material basis and their possible mechanism of the insect were still unclear. Thus, we aimed to separate the active compounds of the ethanol extract from C. chinensis and to investigate their possible mechanism of anti-inflammation by network pharmacology and molecular docking. The insect was extracted with 75% ethanol to produce ethanol extracts and then were extracted by petroleum ether, ethyl acetate and n-butanol respectively. Silica gel column chromatography and preparative HPLC were applied to separate the compounds of the extract. The compounds were characterized and identified by NMR and mass. The compound associated genes were collected by BATMAN-TCM database and the inflammation associated genes were obtained through DigSee database. The protein-protein interaction (PPI) network was carried out via Search Tool for the Retrieval of Interacting Genes/Protein (STRING) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) target pathway analysis was performed in Database for Annotation, Visualization and Integrated Discovery (DAVID). The possible mechanism of compounds against inflammation was investigated by molecular docking. Finally, the anti-inflammatory effect of the representative compound was verified by the LPS-induced Raw 264.7 cell inflammatory model. TNF- α , IL-1 β and IL-6 of the cell supernatants were analyzed via using ELISA kits and the key proteins in JAK2/STAT3 signaling pathway were verified via the Western blot assays. Among crude extracts from C. chinensis , ethyl acetate extract showed the obvious anti-inflammatory effects. Nine compounds were isolated from ethyl acetate extract of Cybister chinensis for the first time, including benzoic acid (1), hydroxytyrosol (2), protocatechualdehyde (3), N -[2-(4-hydroxyphenyl)ethyl]acetamide (4), (2 E)-3-phenylprop-2-enoic acid (5), 3-phenylpropionic acid (6), methyl 3,4-dihydroxybenzoate (7), 1,4-diphenyl butane-2,3-diol (8) and p - N , N -dimethylaminobenzaldehyde (9). After searching in the database, 1079 compound associated genes and 467 inflammation associated genes were found. The 137 common targets covered 77 signaling pathways, in which HIF-1 signaling pathway, TNF signaling pathway, influenza A, PI3K/Akt signaling pathway, NOD-like receptor signaling pathway, MAPK signaling pathway, Toll-like receptor signaling pathway and Jak-STAT signaling pathway were important for inflammation. Molecular docking studies showed compound 1, 4, 5, 6, 7 and 8 were the potential inhibitors of JAK2 protein. In addition, the in vitro test showed compound 5 reduced the expression of tumor necrosis factor (TNF)- α , interleukin (IL)-6 and IL-1 β in lipopolysaccharide (LPS)-stimulated RAW264.7 cells in a dose-dependent manner. Furthermore, it was found that compound 5 inhibited the expression of p-JAK2 and p-STAT3 in LPS-induced RAW264.7 cells in a dose-dependent manner. Based on the network pharmacology and molecular docking, the study suggested that C. chinensis could relieve the inflammation based on the multi-compounds and multi-pathways, which provided the foundation for the medicinal application of C. chinensis. [Display omitted] [ABSTRACT FROM AUTHOR]