Volume 20, Nº 2 (2024)

Introduction:In this study, core drugs of clinical postmenopausal osteoporosis were retrieved using data mining, the drug molecular action target was predicted through network pharmacology, the key nodes of interaction were identified by combining postmenopausal osteoporosis-related targets, and the pharmacological mechanism of Traditional Chinese Medicine (TCM) against postmenopausal osteoporosis and other action mechanisms was explored.

Methods:TCMISS V2.5 was used to collect TCM prescriptions of postmenopausal osteoporosis from databases, including Zhiwang, Wanfang, PubMed, etc., for selecting the highest confidence drugs. TCMSP and SwissTargetPrediction databases were selected to screen the main active ingredients of the highest confidence drugs and their targets. Relevant targets for postmenopausal osteoporosis were retrieved from GeneCards and GEO databases, PPI network diagrams construction and selection of core nodes in the network, GO and KEGG enrichment analysis, and molecular docking validation.

Results:Correlation analysis identified core drug pairs as 'Corni Fructus-Epimedii Folium- Rehmanniae Radix Praeparata' (SZY-YYH-SDH). After TCMSP co-screening and de-weighting, 36 major active ingredients and 305 potential targets were selected. PPI network graph was built from the 153 disease targets and 24 TCM disease intersection targets obtained. GO, KEGG enrichment results showed that the intersectional targets were enriched in the PI3K-Akt signalling pathway, etc. The target organs were mainly distributed in the thyroid, liver, CD33+_Myeloid, etc. Molecular docking results showed that the core active ingredients of the 'SZY-YYH-SDH' were able to bind to the pair core nodes and PTEN and EGFR.

Conclusion:The results showed that 'SZY-YYH-SDH' can provide the basis for clinical application and treat postmenopausal osteoporosis through multi-component, multi-pathway, and multitarget effects.

Background:Polygonum cuspidatum (PC), a widely used Chinese herbal medicine (CHM), plays an important role in treating various diseases including osteoarthritis (OA). Yet, the multicomponent and multitarget characteristics of PC make deciphering the pharmacological mechanisms difficult.

Objective:The purpose of this study is to identify the core molecular mechanisms of PC against OA.

Methods:The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to search for the active ingredients of PC. GeneCards was then screened to establish relevant databases for OA. A visual interactive network diagram of the relationship between the active ingredient, action target, and disease was built using Uniprot. Finally, we used STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) database to explain the interaction network of proteins and to further analyze the relationships between related proteins.

Results:PC was screened for nine potentially effective active compounds that can be used to treat OA: 6,8-Dihydroxy-7-methoxyxanthone, rhein, physovenine, beta-sitosterol, picralinal, quercetin, luteolin, catechin, and resveratrol. Using GeneCards database and TCMSP database, we obtained 149 OA-related genes after taking the intersection of OA and PC targets. Moreover, eight core target proteins were calculated by CytoNCA plugin, which is used for network centrality analysis. The enrichment analysis of the common target genes shared by PC and OA unraveled the main biological processes, such as responses to lipopolysaccharide, chemical stress, and reactive oxygen species. Previous research has demonstrated that signaling pathways related to apoptosis, inflammation, and cartilage protection are involved with those core target genes we found, like TNF and PI3K-Akt signaling pathways. The results bring that PC similarly has the potential to treat OA.

Conclusion:The main purpose of this study is to screen the active ingredients and most important target molecules of PC in treating OA. This was achieved using bioinformatic tools and databases to investigate molecular docking technology. The findings provide a theoretical foundation and potential new treatment plan for OA using PC.

Introduction:The enteric protozoa, Giardia duodenalis (G. duodenalis), consists of eight distinct assemblages (A-H) with identical morphological characteristics and a direct life cycle. Successful axenic cultivation of this parasite is an important preliminary step for biological, drug resistance and phylogenetic studies. Moreover, G. duodenalis exhibits great genetic and biotypic diversity.

Aim:The current study aimed to evaluate in vitro culture and multilocus genotyping of G. duodenalis trophozoites obtained from human fecal samples in southwest Iran.

Methods:Thirty human fecal specimens containing G. duodenalis cysts were collected from Ahvaz city (southwest of Iran). The purification of cysts was carried out by the sucrose flotation technique. The cysts were inoculated in a modified TYI-S-33 medium and was daily monitored for the development and viability of trophozoites. After extracting DNA, gdh, bg and tpi genes were evaluated using molecular techniques (the semi-nested PCR for gdh gene and the nested PCR for tpi and bg genes). Eventually, the amplified fragments were sequenced and then, the phylogenetic tree was drawn.

Results:Of 30, the trophozoites were encysted from five samples. All three genes were detected in two cases of five samples using molecular techniques. The multilocus phylogenetic analysis demonstrated that all the two samples belonged to assemblage A and sub-assemblage AІІ.

Conclusion:Our findings indicated the presence of different numbers of trophozoites with variable development and survival rates in modified TYI-S-33 medium. Furthermore, the multilocus genotyping showed that these trophozoites belonged to assemblage A and sub-assemblage AІІ.

Background:HongTeng Decoction (HTD) is a traditional Chinese medicine that is widely used to treat bacterial infections and chronic inflammation. However, its pharmacological mechanism is not clear. Here, network pharmacology and experimental verification were applied to investigate the drug targets and potential mechanisms of HTD in inflammation treatment.

Methods:The active ingredients of HTD were collected from the multi-source databases and clarified by Q Exactive Orbitrap analysis in the treatment of inflammation. Then, molecular docking technology was used to explore the binding ability of key active ingredients and targets in HTD. In vitro experiments, the inflammatory factors and MAPK signaling pathways are detected to verify the anti-inflammatory effect of HTD on the RAW264.7 cells. Finally, the anti-inflammatory effect of HTD was evaluated in LPS induced mice model.

Result:A total of 236 active compounds and 492 targets of HTD were obtained through database screening, and 954 potential targets of inflammation were identified. Finally, 164 possible targets of HTD acting on inflammation were obtained. The PPI analysis and KEGG enrichment analyses showed that the targets of HTD in inflammation were mostly related to the MAPK signaling pathway, the IL-17 signaling pathway, and the TNF signaling pathway. By integrating the results of the network analysis, the core targets of HTD in inflammation mainly include MAPK3, TNF, MMP9, IL6, EGFR, and NFKBIA. The molecular docking results indicated solid binding activity between MAPK3-naringenin and MAPK3-paeonol. It has been shown that HTD could inhibit the levels of inflammatory factors, IL6 and TNF-α, as well as the splenic index in the LPS-stimulated mice. Moreover, HTD could regulate protein expression levels of p-JNK1/2, and p-ERK1/2, which reflects the inhibitory effect of HTD on the MAPKS signaling pathway.

Conclusion:Our study is expected to provide the pharmacological mechanisms by which HTD may be a promising anti-inflammatory drug for future clinical trials.