ABSTRACT
BACKGROUND: The P2X7 receptor (P2X7R) is known to play a significant role in regulating various pathological processes associated with immune regulation, neuroprotection, and inflammatory responses. It has emerged as a potential target for the treatment of diseases. In addition to chemically synthesized small molecule compounds, natural products have gained attention as an important source for discovering compounds that act on the P2X7R. PURPOSE: To explore the research progress made in the field of natural product-derived compounds that act on the P2X7R. METHODS: The methods employed in this review involved conducting a thorough search of databases, include PubMed, Web of Science and WIKTROP, to identify studies on natural product-derived compounds that interact with P2X7R. The selected studies were then analyzed to categorize the compounds based on their action on the receptor and to evaluate their therapeutic applications, chemical properties, and pharmacological actions. RESULTS: The natural product-derived compounds acting on P2X7R can be classified into three categories: P2X7R antagonists, compounds inhibiting P2X7R expression, and compounds regulating the signaling pathway associated with P2X7R. Moreover, highlight the therapeutic applications, chemical properties and pharmacological actions of these compounds, and indicate areas that require further in-depth study. Finally, discuss the challenges of the natural products-derived compounds exploration, although utilizing compounds from natural products for new drug research offers unique advantages, problems related to solubility, content, and extraction processes still exist. CONCLUSION: The detailed information in this review will facilitate further development of P2X7R antagonists and potential therapeutic strategies for P2X7R-associated disorders.
Subject(s)
Biological Products , Purinergic P2X Receptor Antagonists , Receptors, Purinergic P2X7 , Receptors, Purinergic P2X7/metabolism , Biological Products/pharmacology , Biological Products/chemistry , Humans , Purinergic P2X Receptor Antagonists/pharmacology , Purinergic P2X Receptor Antagonists/chemistry , Signal Transduction/drug effects , AnimalsABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Sinomenii Caulis (SC) is a well-konwn traditional Chinese medicine used for treatment of rheumatoid arthritis (RA), dermatophytosis and paralysis. Patients with RA are usually secondary to osteoporosis, but the potential protective effect of SC on osteoporosis (OP) is seldom reported and its possible action mechanism is little known. AIM: The purpose of this study was to demonstrate the anti-osteoporosis effects of SC extract and alkaloids in prednisolone (Pre)-induced OP of zebrafish, and then to explore the potential mechanism of SC on system level by network pharmacology. METHODS: Firstly, zebrafish OP model was established to investigate the anti-osteoporosis effect of SC. Secondly, the targets of SC and OP from multiple databases were collected, and Compound-Target-Pathway network based on protein-protein interaction (PPI) was constructed. Moreover, gene enrichment and annotation were performed via the DAVID server. Finally, the reliability of the network pharmacology prediction results in Pre-induced OP of zebrafish was verified by qRT-PCR. RESULTS: The results indicated that SC extract and alkaloids have remarkable ability to promote bone formation of cranial bones and reduce TRAP contents in Pre-induced OP of zebrafish. 32 OP-related ingredients in SC and 77 OP-related targets were screened from multiple databases, and 15 OP-related pathways were enriched by the KEGG database. Further experimental validation indicated that SC extract and alkaloids could regulate the expression of MAPK14, CASP3, CXCL8, IL-1ß, IL6, PTGS2, TNF-α, ESR1, and MMP9 for treatment of OP. CONCLUSION: In summary, we conducted an integrative analysis to provide convincing evidence that SC may partially alleviate OP by inhibiting pro-inflammatory cytokines and regulating of RANK/RANKL/OPG system.
Subject(s)
Bone Density Conservation Agents/pharmacology , Bone Remodeling/drug effects , Bone and Bones/drug effects , Drugs, Chinese Herbal/pharmacology , Systems Biology , Zebrafish Proteins/metabolism , Animals , Anti-Inflammatory Agents/pharmacology , Bone Remodeling/genetics , Bone and Bones/metabolism , Bone and Bones/physiopathology , Cytokines/genetics , Cytokines/metabolism , Databases, Protein , Disease Models, Animal , Gene Expression Regulation , Gene Regulatory Networks , Inflammation Mediators/metabolism , Osteoporosis/chemically induced , Osteoporosis/genetics , Osteoporosis/metabolism , Osteoporosis/physiopathology , Osteoprotegerin/genetics , Osteoprotegerin/metabolism , Prednisolone , Protein Interaction Maps , RANK Ligand/genetics , RANK Ligand/metabolism , Receptor Activator of Nuclear Factor-kappa B/genetics , Receptor Activator of Nuclear Factor-kappa B/metabolism , Signal Transduction , Zebrafish , Zebrafish Proteins/geneticsABSTRACT
Obesity is one of the main causes of human cardiovascular and cerebrovascular diseases. Baicalin, a bioactive flavonoid isolated from the herbal medicine Scutellaria baicalensis Georgi, is reported to ameliorate obesity and hyperlipidemia. However, its mechanism remains unclear. Here, we used network pharmacology to explore the potential mechanism of baicalin on a system level. First, we predicted the targets of baicalin and diseases, and then protein-protein interaction (PPI) networks were constructed. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment was performed via the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server. Lastly, we confirmed the results of the network analysis by palmitic acid (PA) treated human hepatoma cells (HepG2) in vitro. The results indicated that 37 targets related to obesity treated by baicalin were predicted by network pharmacology, and top 10 related pathways were extracted by the KEGG database. Baicalin treatment could reduce triglyceride (TG) contents and lipid droplet accumulation in PA-treated HepG2 cells. The anti-obesity effects of baicalin might be due to the up-regulation of solute carrier family 2 member 1 (SLC2A1) and down-regulation of tumor necrosis factor (TNF), nuclear factor kappa B subunit 1 (NFKB1), sterol regulatory element binding transcription factor 1 (SREBF1), peroxisome proliferator activated receptor gamma and caspase 3 (CASP3). Our results indicated that baicalin may regulate key inflammatory markers, adipogenesis process, and apoptosis for treatment of obesity.
Subject(s)
Anti-Obesity Agents/pharmacology , Flavonoids/pharmacology , Hyperlipidemias/drug therapy , Hypolipidemic Agents/pharmacology , Obesity/drug therapy , Plant Extracts/pharmacology , Amino Acid Sequence , Caspase 3/genetics , Caspase 3/metabolism , Drug Discovery , Gene Expression Regulation , Glucose Transporter Type 1/genetics , Glucose Transporter Type 1/metabolism , Hep G2 Cells , Herbal Medicine , Humans , Models, Molecular , Molecular Structure , NF-kappa B p50 Subunit/genetics , NF-kappa B p50 Subunit/metabolism , Protein Binding , Protein Conformation , Scutellaria baicalensis , Signal Transduction , Sterol Regulatory Element Binding Protein 1/genetics , Sterol Regulatory Element Binding Protein 1/metabolism , Structure-Activity Relationship , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolismABSTRACT
The study is aimed to develop a rapid and efficient supercritical fluid chromatography coupled with diode-array detection (SFC-DAD) method for simultaneous quantification of six flavonoids in Citri Reticulatae Pericarpium (CRP). The chromatographic parameters including stationary phase, mobile phase composition, back pressure, temperature and flow rate, were systematically optimized with single-factor test. The results indicated that the six compounds were baseline separated on an Agilent Zorbax RX-SIL column using gradient elution within 10â¯min. The optimized mobile phase was constituted of carbon dioxide (CO2) and methanol. And the parameters were set as follows: backpressure, 95â¯bar; temperature, 45⯰C; flow rate, 0.8â¯mL/min. The optimized method showed satisfactory retention and resolution for the analytes. The method was validated to demonstrate its selectivity, linearity, precision, accuracy and robustness. Thus, the verified SFC method was successfully applied to quantification of flavonoids present in CRP samples. The results indicated that SFC has the potential to become an excellent alternative for the analysis of flavonoids in herbal medicines, owning to its intrinsic features like high efficiency, separation speed and eco-friendly characteristics.