ABSTRACT
Objective: The Huanghuai (HH), which is made from the dried roots of Scutellaria baicalensis (Huangqin in Chinese) and the dried flowers and buds of Sophora japonica (Huaihua in Chinese), is a traditional Chinese formula used to treat dysfunctional uterine bleeding (DUB) (Benglou in Chinese) and proven to treat hemostasis effectively in our previous study. Network pharmacology and molecule docking were performed to study the underlying mechanism of Huanghuai (HH), and pharmacodynamic experiments were conducted to verify its curative effect. Methods: TCMSP, UniProt, GeneCards, STRING, DAVID databases, and Cytoscape 3.7.2 were utilized for the construction of a compound-target-pathway network. Docking the potential effective components with potential targets. The HPLC analysis of the potential effective components was performed. In vivo, the hot plate test model was used to study the analgesic activity, the egg white was used to study the swollen reaction in the sole in mice, and the hemostasis effect was studied by the capillary method, tail-breaking method and abortion uterus test. Results: The results showed that six compounds (acacetin, beta-sitosterol, wogonin, baicalein, kaempferol and quercetin) and four potential targets (PTGS2, AKT1, TP53 and TNF) in the compound-target-pathway network were the potential material basis for HH to treat DUB. It can be seen that the binding energy of the acacetin, wogonin, baicalein, beta-sitosterol, kaempferol and quercetin in HH docked with the receptor proteins PTGS2, AKT1, TP53, and TNF were far less than −5.0 kJ/mol, which means the molecules have low conformational energy, stable structure and high binding activity. And the result of HPLC analysis showed that acacetin, wogonin, baicalein, kaempferol and quercetin were the potential effective components of the hemostasis mechanism of HH, beta-sitosterol was removed due to low content. In vivo testing of the potential effective components, it revealed that the group of potential effective components identified by HPLC could increase the pain threshold, inhibit the swelling hind paws of mice induced by egg white, reduce the bleeding time and clotting time, reduce uterine bleeding, decrease the uterine weight, increase the content of Ca and ET-1, and reduce the content of NO in uterine homogenate tissue, and decrease of E
ABSTRACT
Objective: To explore the potential material basis of Kangbingdu Granules for the treatment of coronavirus disease 2019 (COVID-19) through network pharmacology and molecular docking technology. Methods: The chemical constituents and action targets of Isatidis Radix, Forsythiae Fructus, Gypsum Fibrosum, Anemarrhenae Rhizoma, Phragmitis Rhizoma, Rehmanniae Radix Praeparata, Pogostemon cablin, Acoritataninowii Rhizoma and Curcumae Radix in Kangbingdu Granules were searched by TCMSP. The gene corresponding to the target was searched by UniProt database, and Cytoscape 3.6.1 was used to build a medicinal material-compound-target (gene) network. DAVID was used to perform gene ontology (GO) function enrichment analysis and KEGG pathway enrichment analysis to predict its mechanism. Molecular docking of the top 15 components was carried out in the medicinal material-compound-target network with SARS-CoV-2 3CL hydrolase, and molecular docking with bicuculline, luteolin, quercetin and angiotensin-converting enzyme II (ACE2) was performed. Results: The medicinal material-compound-target (gene) network contained eight medicinal materials, 75 compounds and 255 targets. GO function enrichment analysis revealed 161 GO items (P < 0.05), including 65 biological process (BP) items, 36 cell composition (CC) items, and 60 molecular function (MF) items. KEGG pathway enrichment screened 131 signaling pathways (P < 0.05). The results of molecular docking showed that the core active compounds such as bicuculline, luteolin, and quercetin in the Kangbingdu Granules had similar affinities with those recommended by COVID-19. Conclusion: The active compounds in Kangbingdu Granules can interact with angiotensin-converting enzyme II (ACE2) via targets PTGS2, HSP90AB1, and PTGS1 to regulate multiple signaling pathways, thereby exerting therapeutic effects on COVID-19.