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Aim To investigate the sites and mechanisms of action of Ginseng-Rhodiola rosea in the treat ment of myocardial ischemia-reperfusion injury ( MI-RI) via using network pharmacology approach, molecu¬lar docking techniques and experimental studies. Methods The active ingredients and targets of Gin¬seng-Rhodiola rosea were screened through the TCMSP database and literature supplementation, and the GEN-EC ARDS ,DISGENET and DRUGBANK databases were searched to obtain the targets of MIRI. Functional pro¬tein interaction networks (PPIs) and the STRING database were used to screen out core targets. The DAVID database was also selected for gene ontology functional analysis ( GO) and KEGG signaling pathway enrich¬ment analysis. Lastly, the preliminary validation was performed with the help of molecular docking techniques and experimental studies. Results Forty-three active ingredients and 348 potential targets of Ginseng-Rhodiola were obtained, and targets such as IL-6 , TNF-α and VEGFA were found to be closely related to MIRI, mainly involving TNF, PDK-Akt, HIF-1 and other signaling pathways.The molecular docking results showed that soysterol, ginsenoside rh2 and rhodioloside had good binding effects and high matching with IL-6, TNF-α,Caspase-3,VEGFA,MAPK1 and other targets, among which the best binding was between Caspase-3 and ginsenoside rh2. The results of the experimental study further showed that Ginseng-Rhodiola rosea could improve myocardial tissue necrosis after myocardial ischemia-reperfusion , reduce myocardial cell edema and vascular congestion, and decrease the expression levels of TNF-α and IL-6 in MIRI rats. Conclusions Ginseng-Rhodiola may modulate multiple targets such as IL-6,TNF-α, Caspase-3, VEGFA and MAPK1 through dousterol, ginsenoside rh2 and rhodiol glycosides to inhibit inflammatory response and oxidative stress, reduce cardiomyocyte damage and exert therapeutic effects on MIRI.
ABSTRACT
Objective To investigate the correlation between the CT perfusion and microvessel density (MVD),expression of vascular endothelial growth factor(VEGF)in neoplasm of head and neck.Methods Eighty-eight lesions of head and neck were scanned by spiral CT.The largest axial surface of the mass was searched on unenhanced imaging,and at this level the dynamic contrast enhanced scan series was acquired.Time-density curves (TDC)were created from circular or oval regions of the interest drawn over the mass,target artery by Toshiba Xpress/SX spiral CT with perfusion functional software.The parameters were measured including:peak height (PH ),peak time (PT ),mean transit time (MTT), contrast enhancement ratio(RPH),and perfusion flow (PF).Histopathological slides of 35 masses were carefully prepared for the anti-CD34 and VEGF immunohistochemical staining and tumor microvessel density and calculation of VEGF expression scores.The parameters of CT perfusion were correlatively study with MVD and VEGF.Results(1)The TDC of CT perfusion imaging could be classified into 3 types.The TDC of 53/77 (68.9% )malignant tumors presented the type with rapid ascending and rapid descending after injecting contrast.The TDC of 6/9 malignant lymphomas showed low platform curve。(2)The PF median of thyroid carcinoma was 82.2(41.0,183.4)ml?min~(-1)?100 g~(-1).There was significantly difference in the parameters of CT perfusion among thyroid carcinoma and squamaous cell cancer (Median 23.8 (7.0, 108.4)ml?min~(-1)?100 g~(-1))and lymphomas (Median 24.5(13.2,78.6)ml?min~(-1)?100 g~(-1)).(3) MVD in benign tumors was (44.7?3.4),and in malignant tumors,it is (49.6?14.8 ).There was no significantly difference in MVD between benign and malignant tumors.High VEGF expression was found in 15 malignant tumors and 1 benign tumors,low VEGF expression was found in 9 malignant tumors and 10 benign tumors.(4)There were no significantly difference in VEGF expression and MVD.There was good correlation between MVD (M 40.0 )and PH (M 26.9 ),RPH (M 14.5 ),PF (M 46.8 )(r = 0.35,45.49, 0.41 ).There was correlation between VEGF(M 4.0)and MTT(M 16.7 )(r = -0.41 ).Conclusion The TDC and CT perfusion could be helpful to differentiate benign from malignant tumors. CT peffusion in neoplasm of head and neck is correlated with MVD and VEGF,and may reflect MVD and expression of VEGF.