ABSTRACT
BACKGROUND: Yisui Qinghuang powder (YSQHP) is an effective traditional Chinese medicinal formulation used for the treatment of myelodysplastic syndromes (MDS). However, its pharmacological mechanism of action is unclear. MATERIALS AND METHODS: In this study, the active compounds of YSQHP were screened using the traditional Chinese medicine systems pharmacology (TCMSP) and HerDing databases, and the putative target genes of YSQHP were predicted using the STITCH and DrugBank databases. Then, we further screened the correlative biotargets of YSQHP and MDS. Finally, the compound-target-disease (C-T-D) network was conducted using Cytoscape, while GO and KEGG analyses were conducted using R software. Furthermore, DDI-CPI, a web molecular docking analysis tool, was used to verify potential targets and pathways. Finally, binding site analysis was performed to identify core targets using MOE software. RESULTS: Our results identified 19 active compounds and 273 putative target genes of YSQHP. The findings of the C-T-D network revealed that Rb1, CASP3, BCL2, and MAPK3 showed the most number of interactions, whereas indirubin, tryptanthrin, G-Rg1, G-Rb1, and G-Rh2 showed the most number of potential targets. The GO analysis showed that 17 proteins were related with STPK activity, PUP ligase binding, and kinase regulator activity. The KEGG analysis showed that PI3K/AKT, apoptosis, and the p53 pathways were the main pathways involved. DDI-CPI identified the top 25 proteins related with PI3K/AKT, apoptosis, and the p53 pathways. CASP8, GSK3B, PRKCA, and VEGFR2 were identified as the correlative biotargets of DDI-CPI and PPI, and their binding sites were found to be indirubin, G-Rh2, and G-Rf. CONCLUSION: Taken together, our results revealed that YSQHP likely exerts its antitumor effects by binding to CASP8, GSK3B, PRKCA, and VEGFR2 and by regulating the apoptosis, p53, and PI3K/AKT pathways.
ABSTRACT
OBJECTIVE: To explore the expression of pulmonary surfactant in rats with paraquat-induced acute lung injury. METHODS: A total of 36 SD rats were randomly divided into the control group (n=6) and paraquat group at 6, 12, 24, 48, 72 h five time points, each time points 6 rats. All of the rats were injected with paraquat (80 mg/kg) for once. The specimens were collected at 0 h (instant) after paraquat intoxication in the control group, and at the corresponding point in time in the paraquat each time point groups. The pathology changes of lung tissue were observed by HE staining, thiobarbituric acid method was used to detect malondialdehyde (MDA) level, and Western blot method was used to analyze the relative expression of surfactant protein (SP)-A and SP-D in bronchoalveolar lavage fluid (BALF) with time. RESULTS: As compared to control, the levels of MDA in BALF were significantly higher at 6, 24, 48 h after paraquat intoxication ((4.19 ± 0.12), (3.33 ± 0.08), (3.52 ± 0.08) vs (2.82 ± 0.15) nmol/mg, all P<0.01), no significantly different at 12, 72 h ((2.76 ± 0.13), (2.79 ± 0.10) nmol/mg, both P>0.05); the relative expression of SP-A in BALF were significantly higher at 6 h after paraquat intoxication (1.32 ± 0.19 vs 1.00 ± 0.19, P<0.01), lower at 24, 48 h (0.43 ± 0.07, 0.67 ± 0.08, both P<0.01), and no significantly different at 12, 72 h (0.98 ± 0.15, 0.79 ± 0.18, both P>0.05); the relative expression of SP-D in BALF were significantly higher at 6, 12 h after paraquat intoxication (1.54 ± 0.33, 1.64 ± 0.37 vs 1.00 ± 0.23, both P<0.01), no significantly different at 24, 48 h (1.07 ± 0.19, 0.97 ± 0.15, both P>0.05), and reached the peak at 72 h (2.15 ± 0.26, P<0.01); the expression of MDA, SP-A and SP-D were characterized by the state of fluctuation with increased first, reduced after, and finally increased. CONCLUSION: The expression of SP-A, SP-D increase at the early stage of the paraquat-induced acute lung injury in rat, which can reflect the degree of lung injury.