scholarly journals Pro- and Anti-Inflammatory Cytokine Expression Levels in Macrophages; An Approach to Develop Indazolpyridin-methanones as Novel Inflammation Medication

Author(s):  
Manikandan Alagumuthu ◽  
Vanshika Srivastava ◽  
Manisha Shah ◽  
Sivakumar Arumugam ◽  
Mohandoss Sonaimuthu ◽  
...  

Background: Macrophages play a serious part in the instigation, upkeep, and resolution of inflammation. They are activated or deactivated during inflammation progression. Activation signals include cytokines (IF-γ, granulocyte-monocyte colonystimulating factor (GM-CSF), and TNF-α), extracellular matrix proteins, and other chemical mediators. Activated macrophages are deactivated by anti-inflammatory cytokines (IL- 10 and TGF-β (transforming growth factor-beta) and cytokine antagonists that are mainly produced by macrophages. Based on this, the present study aimed to develop novel (E)- Benzylidene-indazolpyridin methanones (Cpd-1-10) as effective anti-inflammatory agents by analyzing pro- and anti-inflammatory cytokine levels in macrophages. Objectives: To determine the anti-inflammatory effect of indazolpyridin-methanones by examining pro- and anti-inflammatory interleukin levels in J77A.1 macrophages. Methods: Expression of cytokines such as TNF-α, IL-1β, IL-6 and IL-10 serum levels measured by ELISA method. Anti-cancer and cytotoxicity studies were carried out by MTT assay. COX-2 seems to be associated with cancers and atypical developments in the duodenal tract. So, a competitive ELISA based COX-2 inhibition assay was done. To validate the inhibitory potentials and to get more insight into the interaction of COX-2 with Cpd1-10, molecular docking was performed. Results: Briefly, the COX-2 inhibitory relative activity was found to be in between the range of 80-92% (Diclofenac showed 84%, IC50 0.95 μM). Conclusion: Cytotoxicity effect of the compounds against breast cancer cell lines found excellent and an extended anticancer study ensured that these compounds are also alternative therapeutic agents against breast cancer. Among all the tested cancer cell lines, the anti- cancer effect on breast cancer was exceptional for the most active compounds Cpd5 and Cpd9.

Oncotarget ◽  
2017 ◽  
Vol 8 (60) ◽  
pp. 101461-101474 ◽  
Author(s):  
Yung-Lung Chang ◽  
Yu-Juei Hsu ◽  
Ying Chen ◽  
Yi-Wen Wang ◽  
Shih-Ming Huang

2010 ◽  
Vol 163 (2) ◽  
pp. 235-243 ◽  
Author(s):  
Balraj Singh ◽  
LaTashia R. Irving ◽  
Karen Tai ◽  
Anthony Lucci

2013 ◽  
Vol 850-851 ◽  
pp. 1291-1294
Author(s):  
Xiu Rui Han ◽  
Xian Chao Li ◽  
Hong Zong Si ◽  
Cui Zhu Ge ◽  
Hua Gao ◽  
...  

Using the GEP,the QSAR model for anti-cancer activity of 38 compounds in 5 cancer cell lines was establish. These compounds are a novel class of anticarcinogen named tricyclic 5:7:5-fused diimidazo [4, 5-d:4, 5-f ][1, diazepines. The carcinoma cell lines involved in this research are A549 lung cancer, MCF-7 breast cancer, MDA-MB-231 breast cancer, OVCAR-3 ovarian cancer and PC-3 prostate cancer. Accuracies of these models in training group and test group are over 90%, showing perfect predictive ability. This QSAR model will be great valuable in providing guidance for future designing and synthesizing of anticancer drugs.


2015 ◽  
Vol 37 (7) ◽  
pp. 1355-1359 ◽  
Author(s):  
Shahedeh Shahbazian ◽  
Azim Akbarzadeh ◽  
Sepideh Torabi ◽  
Mansour Omidi

2021 ◽  
Vol 25 (06) ◽  
pp. 1161-1172
Author(s):  
Sang Koo Park

Rheum emodi Wall. ex Meissn is a popular medicinal herb having wide application in traditional medicine for treating of several diseases. The present study was aimed to identify and isolate phytochemicals present in ethyl acetate extract fraction of R. emodi and to evaluate the anticancer and anti-inflammatory activities of water/organic solvent fractions and isolated compounds of R. emodi rhizome extracts. Based on the structure, flavonoid compound i.e., Myricitrin (sym. Myricetin 3- rhamnoside), myricetin 3-galloylrhamnoside and myricetin were identified to be present in ethyl acetate extract. The molecular weight of compound 1 cannot be identified; while compound 5 remained unknown as there was not enough evidence to propose its structure. The isolated compounds and different solvent fractions were tested for their anticancer and antiinflammatory activities. Among Myricetins derivatives, particularly unknown compounds significantly induced the apoptosis and restrained the proliferation of cancer cell lines (A549 and MCF-7) and inhibited the LPS induced NO production (proinflammatory mediator), IL-6 activity, IL-1β and TNF-α (cytokines) activity in RAW 264.7 macrophages in a dose dependent manner and was effective even at lower concentration (50 µg/mL). Similarly, the higher concentration of aqueous and solvent fractions exhibited strong cytotoxic and anti-inflammatory activities. However, water and dichloromethane fractions were most effective in inhibiting the anticancer activities in A549 and MCF-7 cancer cell lines, respectively. At lower concentration (50 and 100 µg/mL), highest inhibition activity for NO, IL-6 and IL-1β was noted with ethyl acetate fractions and n-Hexane fractions; while water and n-Butanol (fractions) strongly inhibited the TNF-α activity at lower (100 µg/mL) and high (200 µg/mL) concentration, respectively. In conclusion, the isolated compounds from R. emodi rhizome extracts and its rhizome solvent fractions exhibit strong anti-cancer and anti-inflammatory activities and can be used to develop chemotherapeutics and anti-inflammation drugs. © 2021 Friends Science Publishers


2019 ◽  
Vol 46 (2) ◽  
pp. 2187-2196 ◽  
Author(s):  
Nael Abutaha ◽  
Fahd A. Nasr ◽  
Al-Zahrani Mohammed ◽  
AbdelHabib Semlali ◽  
Fahd A. Al-Mekhlafi ◽  
...  

2021 ◽  
Vol 35 (1) ◽  
pp. 853-861
Author(s):  
Rumiana Tzoneva ◽  
Veselina Uzunova ◽  
Tihomira Stoyanova ◽  
Borislava Borisova ◽  
Albena Momchilova ◽  
...  

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