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Objective:Structure-based angiotension converting enzyme 2 (ACE2) and interleukin-6R (IL-6R) were taken as the target proteins to in the investigation of the material basis of Xuanfei Huazhuo prescription in the treatment of coronavirus disease-2019 (COVID-19) by molecular docking. Method:The compounds in Xuanfei Huazhuo prescription were retrieved through TCMSP. Structure-based ACE2 and IL-6R were taken as the target proteins to screen out the compounds with a better activity by molecular docking, and analyze structural properties of these compounds. Furthermore, the potential molecular mechanism of Xuanfei Huazhuo prescription in the treatment of COVID-19 was analyzed by target reverse prediction. Result:There were 312 potentially active compounds in Xuanfei Huazhuo prescription, including 75 highly active compounds and 15 highly active compounds for ACE2. There were 100 eligible active compounds and 3 highly active compounds for IL-6R, most of which belong to flavonoids. The herb-component-target network included 10 herbs, 126 compounds and 130 targets. String analysis showed that PIK3R1, SRC, AKT1, AR and EGFR might be the key targets of Xuanfei Huazhuo prescription. Conclusion:Based on the virtual screening of multi-target molecular docking, the anti-virus and anti-inflammatory material basis of Xuanfei Huazhuo prescription was preliminarily obtained. At the same time, based on the reverse prediction and analysis, potential targets and molecular mechanism of the recipe in the treatment of COVID-19 were explored, so as to provide clues for the multi-angle mining of Xuanfei Huazhuo prescription and its relevant prescriptions and the modernization development of monomer components.
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Objective: To study the effect of small molecule compounds of Hedysari Radix in ntagonizing tumor necrosis factor receptor type 1 (TNFR1) based on molecular docking. Method: The structure of small molecular compound of Hedysari Radix was downloaded from the chemical composition compound library of traditional Chinese medicine, and then optimized to obtain the composition compound library of Hedysari Radix. The three-dimensional structure of the inflammatory target TNFR1 (PDB ID:1TNR) was identified. After hydrotreating and anhydrating, the binding pocket residues were identified according to the literature. According to the defined target structure and binding pocket, the flexible molecular docking was conducted between the composition compound library and the target, and the score (Glide Score) was obtained. Based on the results of molecular docking, the first nine small molecular compounds of Glide Score were selected as candidate components. On this basis, the drug-likeness was analyzed, which involved small molecular compounds that meet the number of hydrogen-bonded receptors, the number of hydrogen-bonded donors, the formula weight, the number of rotatable key and the numerical range of lipo-hydro partition coefficient. Finally, the binding mode was analyzed according to pharmacokinetic parameters and complex structure of composition-target docking. Result: The residue set in the TNFR1 drug-binding pocket were identified as glutamic acid109 (Glu109), lysine 35(Lys35), alanine62 (Ala62), serine 74 (Ser74), lysine75 (Lys75), cysteine76 (Cys76), argnine 77(Arg77), glutamine82 (Gln82), threonine89 (Thr89), asparticacid91 (Asp91), argnine92 (Arg92), aspartic acid93 (Asp93), threonine 94(Thr94), valine95 (Val95), cysteine 96(Cys96), argnine104 (Arg104), tyrosine106 (Tyr106), asparagine110 (Asn110), leucine111 (Leu111), phenylalanine112(Phe112), glutamic acid 131(Glu131) and lysine132 (Lys132). Totally 43 small molecular compounds of Hedysari Radix were obtained. Five small molecular compounds, namely hedysari radix, quercetin, isoliquiritin, naringenin, calycosin and liquiritigenin, were screened by comprehensive factors, like docking scoring. Conclusion: Quercetin, isoliquiritin, naringenin, calycosin and liquiritigenin are the effective anti-inflammatory substances of Hedysari Radix, with a great possibility of becoming TNFR1 antagonists.
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Objective To study the effect of Astragali Lilium Granules on the survival time,CAT,ATP,and pathological changes in mice exposed to sodium nitrite (NaNO2)poisoning.Methods We randomly divided 60 male mice of SPF grade KM into blank group,positive control group,model group and Astragali Lilium Granules low-,medium-and high-dose groups.After 3 days of normal feeding,blank group and model group received intragastric gavage of normal saline,and positive control group was given Rhodiola rosea capsule solution.Astragali Lilium Granules groups received intragastric gavage according to the concentration (1.75,3.5 and 7 mg/kg per day) for 30 days. One hour after the last administration, all groups except the blank control group received intraperitoneal injection of NaNO2(200 mg/kg,injection amount of 0.1 mL/g).We recorded the mice's survival time,observed the pathological changes of brain,lung and heart tissues by HE staining under the microscope.The activity of CAT and the level of ATP in brain tissue were determined by colorimetric analysis.Results Compared with the blank group,the survival time in model group [(9.64±1.60)min,P＜0.05]was significantly lower;in model group,the lung tissue showed extensive pulmonary edema,red cell exudation,emphysema,and local atrophy of the lung;the interstitium of the myocardium was dilated and congested,and the local cells in the epicardium became edematous and denatured;brain cells showed necrosis,cytoplasm condensation,pyknosis,and perinuclear vacuoles.The tissues were loose and the spaces between the vessels and nerve cells widened;the activity of CAT decreased and the content of ATP decreased in lung,heart and brain tissues (P＜0.05).Compared with the model group,the survival time was significantly prolonged in Astragali Lilium Granules low-[(12.78±2.20)min]and medium-dose [(13.22±2.10)min]groups (P＜0.05).Compared with model group,the three dose groups had lessened lung tissue edema and emphysema,cardiac interstitial vascular dilatation and congestion,necrosis and nuclear pyknosis of brain nerve cells;the activity of CAT increased and the content of ATP increased in lung,heart and brain tissues (both P＜0.05).Conclusion Astragali Lilium Granules can improve the toxicity of NaNO2in mice and thus effectively protect against NaNO2-induced anoxic injury.
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Objective To explore the protective effect and possible mechanism of Astragalus immortal prescription (AIP) from hepatic oxidative stress in mice irradiated by X ray.Methods Six to eight weeks old Kunming mice were randomly divided into normal control group,irradiation alone group,positive control group,and low,medium and high dose groups of AIP (10 rats in each group),physiological saline,thymus peptide and different concentration decocta of AIP were given respectively.After continuous gavage for 10 days,the whole body was irradiated with X ray at the dose of 8 Gy at a time,and then continued lavaging for 3 days,with weighing the mice and observing the diet,water intake and general condition.After killing the mice,the liver was take and the liver index was calculated;the morphological changes of the liver tissues were observed and the expressions of superoxide dismutase (SOD),malondiadehyde (MDA),glutathione peroxidase (GSH-Px) and nuclear factor erythroid 2-related factor 2 (Nrf2) in the liver tissues were detected.Results Compared with the normal control group,the weight of mice in model group decreased obviously (P＜0.01);pathological section showed that the liver cells were disordered,the central vein was congested and blocked seriously,the surrounding liver cells were denatured and necrotic;the activity of SOD and GSH-Px in liver tissues decreased,and the content of MDA increased (P＜0.05),the expression of Nrf2 protein increased significantly (P＜0.01).Compared with the radiation alone group,the weight of mice in positive control group and high dose AIP group increased significantly (P＜0.01);pathological section showed that the liver tissue structure was basically normal,the liver cells were radially arranged with the central vein as the center;the activity of SOD and GSH-Px in liver tissues increased,and the content of MDA decreased (P＜0.05),the expression of Nrf2 protein decreased significantly (P＜0.01).Conclusion AIP has protective effect from hepatic oxidative stress in mice irradiated by X ray,and the mechanism may be related to its antioxidant effects.