scholarly journals Network Pharmacology-Based Antioxidant Effect Study of Zhi-Zi-Da-Huang Decoction for Alcoholic Liver Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Li An ◽  
Fang Feng

Zhi-Zi-Da-Huang decoction (ZZDHD), a classic traditional Chinese medicine (TCM) formula, has been used for centuries to treat alcoholic liver disease. Reliable therapeutics of ZZDHD has also been validated in clinical practice. In this study, molecular docking and network analysis were carried out to explore the antioxidative mechanism of ZZDHD as an effective therapeutic approach to treat alcoholic liver disease. Multiple active compounds of ZZDHD were screened based on four key original enzymes (cytochrome P450 2E1, xanthine oxidase, inducible nitric oxide synthase, and cyclooxygenase-2) involved in ethanol-induced oxidative stress damage. A drug-target network was constructed through network pharmacology analysis, which predicted the relationships of active ingredients to the targets. Some results had been verified by the previous experimental pharmacological studies; meanwhile, it was first reported that xanthine oxidase and eriocitrin, neoeriocitrin, isorhoifolin, and poncirin had interactions. The network pharmacology strategy used provided a forceful tool for searching the mechanism of action of TCM formula and novel bioactive ingredients.

1998 ◽  
Vol 94 (6) ◽  
pp. 637-643 ◽  
Author(s):  
A. Sánchez-Rodríguez ◽  
M. Criado ◽  
A. M. Rodríguez-López ◽  
A. Esteller ◽  
A. Martín De Arriba ◽  
...  

1. The synthesis and release of nitric oxide may play a role in the pathogenesis of peripheral vasodilatation and hyperdynamic circulation observed in liver cirrhosis. In this work, we analysed the synthesis of nitric oxide by the lympho-mononuclear cells of peripheral blood from patients with chronic alcoholic and non-alcoholic liver disease and we identified the isoform of nitric oxide synthase involved in the increased nitric oxide synthesis. 2. Patients were classified following clinical and histological criteria in non-alcoholic cirrhotic, alcoholic cirrhotic and non-cirrhotic chronic liver disease. We studied clinical and analytical characteristics, haemodynamic parameters and endotoxin levels in these patients. 3. Cirrhotic patients showed an increase of cardiac output and a decrease of peripheral vascular resistance. These patients had higher levels of plasma endotoxin than those observed in the control group. Nω-Nitro-l-arginine methyl ester (l-NAME)-inhibitable nitrite production from mononuclear lymphocyte cells was higher in patients than in the control group, the highest levels being in non-alcoholic cirrhotic patients, and the lowest levels in patients with non-cirrhotic alcoholic liver disease. 4. Immunocytochemistry studies revealed a positive immunoreactivity for the inducible isoform of nitric oxide synthase in lympho-mononuclear cells that was more evident in non-alcoholic than in alcoholic cirrhotic patients. By Northern blot, inducible nitric oxide synthase mRNA expression was observed only in lympho-mononuclear cells from non-alcoholic cirrhotic patients. 5. Our patients show a correlation between nitric oxide synthesis, endotoxin levels and haemodynamic parameters. 6. These findings indicate that lympho-mononuclear cell stimulation may play a role in elevated nitric oxide production in hepatic cirrhosis. Thus, this increased nitric oxide synthesis could be implicated in the pathogenesis of the haemodynamic disturbances frequently found in cirrhotic patients. This increase seems to be induced, at least in part, by activation of an inducible isoform of nitric oxide synthase.


2020 ◽  
Vol 15 (9) ◽  
pp. 1934578X2095459
Author(s):  
Anping Yang ◽  
Hui Liu ◽  
Fang Liu ◽  
Lixia Fan ◽  
Wanqin Liao ◽  
...  

At present, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread all over the world, and the best way to effectively carry out drug diagnosis and treatment presents difficulties for all medical staff. In China, some traditional Chinese medicines (TCMs) have been successfully applied to the treatment of SARS-CoV-2 and have achieved good clinical results, including the Reyanning mixture. In this study, we systematically analyzed the mechanism of the Reyanning mixture and its effects against SARS-CoV-2 based on the method of network pharmacology. Here, we used the TCM Systems Pharmacology database and employed a similarity algorithm to screen and identify the bioactive ingredients and potential targets of the Reyanning mixture. The GeneCards database was used to predict and screen the disease targets and build the active ingredient target network diagram. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to construct the target signal pathway associations. The STRING tool was used to reconstruct the protein-protein interaction network. As a result, 27 candidate targets, such as tumor necrosis factor, interferon gamma, tumor protein P53, C-reactive protein, and peroxisome proliferator-activated receptor gamma, were identified among the 33 bioactive ingredients of the 4 TCMs in the Reyanning mixture with effects on treating SARS-CoV-2. These targets were significantly enriched in 20 KEGG pathways and associated with 48 diverse GO terms. All of these targets may play a role in inhibiting inflammatory reactions, regulating immune function, and reducing lung injury to achieve the purpose of treating SARS-CoV-2.


2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Jaroslaw Dudka ◽  
Franciszek Burdan ◽  
Agnieszka Korga ◽  
Magdalena Iwan ◽  
Barbara Madej-Czerwonka ◽  
...  

Cytochrome P450 NADPH-reductase (P450R), inducible synthase (iNOS) and xanthine oxidase play an important role in the antracycline-related cardiotoxicity. The expression of P450R and iNOS is regulated by triiodothyronine. The aim of this study was to evaluate the effect of methimazole-induced hypothyreosis on oxidative stress secondary to doxorubicin administration. 48 hours after methimazole giving cessation, rats were exposed to doxorubicin (2.0, 5.0 and 15 mg/kg). Blood and heart were collected 4, 48 and 96 h after the drug administration. Animals exposed exclusively to doxorubicin or untreated ones were also assessed. The hypothyreosis (0.025% of methimazole) significantly increased the doxorubicin effect on the cardiac carbonyl group and they may increase the glutathione level. An insignificant effect of methimazole was noticed in case of the cardiac lipid peroxidation product, the amount of DNA oxidative damages, iNOS and xanthine oxidase-enzymes responsible for red-ox activation of doxorubicin. However, the concentration of P450R was affected by a lower dose of methimazole in rats administered with doxorubicin. Since in rats receiving doxorubicin changes in oxidative stress caused by methimazole were not accompanied by elevation of bioreductive enzymes, it may be concluded that these changes in the oxidative stress were not related to the tested enzymes.


2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Guoqiang Liang ◽  
Lurong Zhang ◽  
Guorong Jiang ◽  
Xuanyi Chen ◽  
Yang Zong ◽  
...  

Diabetic gastroparesis (DGP) is a serious and chronic complication of long-standing diabetes mellitus, which brings a heavy burden to individuals and society. Traditional Chinese medicine (TCM) is considered a complementary and alternative therapy for DGP patients. Huanglian (Coptidis Rhizoma, HL) and Banxia (Pinelliae Rhizoma, BX) combined as herb pair have been frequently used in TCM prescriptions, which can effectively treat DGP in China. In this article, a practical application of TCM network pharmacological approach was used for the research on herb pair HL-BX in the treatment of DGP. Firstly, twenty-seven potential active components of HL-BX were screened from the TCMSP database, and their potential targets were also retrieved. Then, the compound-target network and PPI network were constructed from predicted common targets, and several key targets were found based on the degree of the network. Next, GO and KEGG enrichment analyses were conducted to obtain several significantly enriched terms. Finally, the experimental verification was made. The results demonstrated that network pharmacological approach was a powerful means for identifying bioactive ingredients and mechanisms of action for TCM. Network pharmacology provided an effective strategy for TCM modern research.


2003 ◽  
Vol 284 (2) ◽  
pp. G321-G327 ◽  
Author(s):  
Amin A. Nanji ◽  
Kalle Jokelainen ◽  
George L. Tipoe ◽  
Amir Rahemtulla ◽  
Peter Thomas ◽  
...  

Induction of NF-κB-mediated gene expression has been implicated in the pathogenesis of alcoholic liver disease (ALD). Curcumin, a phenolic antioxidant, inhibits the activation of NF-κB. We determined whether treatment with curcumin would prevent experimental ALD and elucidated the underlying mechanism. Four groups of rats (6 rats/group) were treated by intragastric infusion for 4 wk. One group received fish oil plus ethanol (FE); a second group received fish oil plus dextrose (FD). The third and fourth groups received FE or FD supplemented with 75 mg · kg−1 · day−1of curcumin. Liver samples were analyzed for histopathology, lipid peroxidation, NF-κB binding, TNF-α, IL-12, monocyte chemotactic protein-1, macrophage inflammatory protein-2, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and nitrotyrosine. Rats fed FE developed fatty liver, necrosis, and inflammation, which was accompanied by activation of NF-κB and the induction of cytokines, chemokines, COX-2, iNOS, and nitrotyrosine formation. Treatment with curcumin prevented both the pathological and biochemical changes induced by alcohol. Because endotoxin and the Kupffer cell are implicated in the pathogenesis of ALD, we investigated whether curcumin suppressed the stimulatory effects of endotoxin in isolated Kupffer cells. Curcumin blocked endotoxin-mediated activation of NF-κB and suppressed the expression of cytokines, chemokines, COX-2, and iNOS in Kupffer cells. Thus curcumin prevents experimental ALD, in part by suppressing induction of NF-κB-dependent genes.


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