ABSTRACT
Background: Pregnancy-induced Hypertension (PIH) is a disease that causes serious maternal and fetal morbidity and mortality. Alisma Orientale (AO) has a long history of use as traditional Chinese medicine therapy for PIH. This study explores its potential mechanism and biosafety based on network pharmacology, network toxicology, molecular docking and molecular dynamics simulation. Methods: Compounds of AO were screened in TCMSP, TCM-ID, TCM@Taiwan, BATMAN, TOXNET and CTD database; PharmMapper and SwissTargetPrediction, GeneCards, DisGeNET and OMIM databases were used to predict the targets of AO anti-PIH. The protein-protein interaction analysis and the KEGG/GO enrichment analysis were applied by STRING and Metascape databases, respectively. Then, we constructed the "herb-compound-target-pathway-disease" map in Cytoscape software to show the core regulatory network. Finally, molecular docking and molecular dynamics simulation were applied to analyze binding affinity and reliability. The same procedure was conducted for network toxicology to illustrate the mechanisms of AO hepatotoxicity and nephrotoxicity. Results: 29 compounds with 78 potential targets associated with the therapeutic effect of AO on PIH, 10 compounds with 117 and 111 targets associated with AO induced hepatotoxicity and nephrotoxicity were obtained, respectively. The PPI network analysis showed that core therapeutic targets were IGF, MAPK1, AKT1 and EGFR, while PPARG and TNF were toxicity-related targets. Besides, GO/KEGG enrichment analysis showed that AO might modulate the PI3K-AKT and MAPK pathways in treating PIH and mainly interfere with the lipid and atherosclerosis pathways to induce liver and kidney injury. The "herb-compound-target-pathway-disease" network showed that triterpenoids were the main therapeutic compounds, such as Alisol B 23-Acetate and Alisol C, while emodin was the main toxic compounds. The results of molecular docking and molecular dynamics simulation also showed good binding affinity between core compounds and targets. Conclusion: This research illustrated the mechanism underlying the therapeutic effects of AO against PIH and AO induced hepato-nephrotoxicity. However, further experimental verification is warranted for optimal use of AO during clinical practice.
ABSTRACT
Background: Osteoarthritis (OA) is a degenerative disease which serious affects patients. Ligusticum chuanxiong (CX) has been shown to have a certain curative effect on osteoarthritis in traditional Chinese medicine therapy. This study is based on network pharmacology and molecular docking technology to explore the potential mechanism of CX. Methods: Components of CX to treat osteoarthritis were screened in the TCMSP database and targets were predicted by the PharmMapper database, the osteoarthritis targets were collected from the GeneCards database, and intersection genes were found to be the possible targets of CX anti-OA. The STRING database and Cytoscape software were utilized for protein-protein interaction analysis and further screening of core targets. The Metascape database was used for KEGG and GO enrichment analyses. Then, the top 10 pathways were selected to construct "drug-compound-target-pathway-disease" network analysis. Finally, molecular docking was used to analyze the binding affinity of seven compounds with core targets and TNF-α. Results: Seven compounds with 253 non-repetitive targets of CX were screened from the TCMSP database and 60 potential intersection targets of CX anti-OA were found. PPI network analysis showed that the core targets were ALB, AKT1, IGF1, CASP3, MAPK1, ANXA5, and MAPK14, while GO and KEGG pathway enrichment analyses showed that the relevant biological processes involved in the treatment of osteoarthritis by CX might include the MAPK cascade and reactive oxygen species metabolic process. The KEGG pathway analysis result was mainly associated with the MAPK signaling pathway and PI3K-AKT signaling pathway. We further docked seven ingredients with MAPK1 and MAPK14 enriched in the MAPK pathway, and TNF-α as the typical inflammatory cytokine. The results also showed good binding affinity, especially FA, which may be the most important component of CX anti-OA. Conclusion: Our research revealed the potential mechanism of CX in the treatment of OA, and our findings can also pave the way for subsequent basic experimental verification and a new research direction.
ABSTRACT
To evaluate the effects of dietary Molybdenum (Mo) or/and Cadmium (Cd) on trace elements and the mRNA expression levels of heat shock proteins (Hsps) and inflammatory cytokines in duck livers. 240 healthy 11-day-old ducks were randomly divided into six groups with 40 ducks in each group, which were treated with Mo or/and Cd at different doses on the basal diet for 120 days. On days 30, 60, 90 and 120, 10 birds in each group were randomly selected and euthanized and then the livers were collected to determine the contents of Mo, Cd, copper (Cu), iron (Fe), zine (Zn), Selenium (Se) and the mRNA expression levels of Hsps, inflammatory cytokines. In addition, liver tissues at 120 days were subjected to histopathological analysis with the optical microscope. The results showed that the mRNA expression of Hsp60, Hsp70, Hsp90, tumor necrosis factor-α (TNF-α), nuclear factor-kappa B (NF-κB), and cyclooxygenase-2 (COX-2) were significantly (P<0.01) upregulated in combination groups; Contents of Cu, Fe, Zn, and Se decreased in combined groups (P<0.05) in the later period of the test while contents of Mo and Cd significantly increased (P<0.01); Furthermore severe hepatocyte diffuse fatty, hepatic cords swelling, hepatic sinusoid disappeared, and inflammatory cells infiltrated around the hepatic central vein were observed in Mo combined with Cd groups. The results indicated that dietary Mo or/and Cd might lead to stress, inflammatory response, tissue damage and disturb homeostasis of trace elements in duck livers. Moreover the two elements showed a possible synergistic relationship. And the high mRNA expression of HSPs and inflammatory cytokines may play a role in the resistance of liver toxicity induced by Mo and Cd.