@article {1061, title = {KRAS G12C as a Target of Naringenin for Inducing Cell Death in NCI-H23 Cells}, journal = {Pharmacognosy Research}, volume = {14}, year = {2022}, month = {July 2022}, pages = {256-262}, type = {Original Article}, chapter = {256}, abstract = {

Background: Naringenin (NGN) is a commonly available flavonoid in the citrus fruits. We have previously shown that NGN is cytotoxic to the non-small cell lung cancer (NSCLC) cell line NCI-H23 (H23). Objectives: To check whether NGN could bind to the Kirsten rat sarcoma (KRAS) G12C mutant and cause its inhibition to promote apoptosis in H23 cells. Materials and Methods: NGN was docked with mutant KRAS protein followed by molecular dynamics simulation. HDOCK was used to analyse the influence of NGN on the KRAS and PI3K proteinprotein docking. We checked the ultramorphological structure of the cells. A 2D-QSAR study was carried out to predict the activity of NGN. Results: We observed that NGN bound stably to the mutant KRAS. NGN showed steady RMSF and RMSD values, good structural stability, and favourable MM/PBSA values. NGN interfered in the binding of KRAS and PI3K. NGN treated cells showed hallmarks of apoptotic cell death. The predictive pIC50 value was found to be 7.39 for NGN against KRAS. NGN cleared all the drug filters. Conclusion: We conclude that NGN could bind to the mutant KRAS potentially inhibiting KRAS. That affects the PI3K/Akt pathway activation leading to apoptosis in the NCI-H23 cells.

}, keywords = {Apoptosis, Docking, KRAS, naringenin, NSCLC, QSAR}, doi = {10.5530/pres.14.3.37}, author = {Abani Kumar Patar and Lakhon Kma and Jitul Barman and Shekhar Ghosh and Taranga Jyoti Baruah} } @article {950, title = {Combined effects of p-coumaric acid and naringenin against doxorubicin-induced cardiotoxicity in rats}, journal = {Pharmacognosy Research}, volume = {3}, year = {2011}, month = {September 2011}, pages = {214-219}, type = {Original Article}, chapter = {214}, abstract = {

Background: Doxorubicin (DOX) is the most active cytotoxic agents having efficacy in malignancies either alone or combined with other cytocidal agents. The clinical usefulness of the anthracycline drug has been precluded by cardiac toxicity. Many therapeutic interventions have been attempted to improve the therapeutic benefits of the drug. This study is based on the possible protective effects of combination of p-coumaric acid (PC) and naringenin (NR) on DOX induced cardiac toxicity in male Swiss albino rats. Methods: Total nine groups of Swiss albino rats were used, Group I (vehicle control) receive saline solution daily and Group II (disease control) receive saline solution daily up to 29 th day and at 30 th day a single dose of DOX (15 mg/kg i.p.) is given. PC alone (100 mg/kg/day p.o.) and (200 mg/kg/day p.o.) also NR alone (15 mg/kg/day) orally administer for 30 days. Similarly a standard drug Vit. E (100 mg/kg/day) administers alone for 30 days. Group PC/DOX and PC and NR/DOX receive PC (200 mg/kg/day) and combine PC (200 mg/kg/day). Results: Doxorubicin induced marked biochemical alterations characteristic of cardiac toxicity including increase in MDA level and decrease SOD, CAT \& GSH level but prior administration of combination of PC \& NR ahead of doxorubicin challenge ameliorated all these biochemical markers. Conclusion: The study proves the beneficial effects of combination of PC and NR in protecting animal against DOX induced cardiotoxicity.

}, keywords = {Antioxidents, cardiotoxicity, doxorubicine, naringenin, p-coumaric acid}, doi = {10.4103/0974-8490.85012}, author = {Shruti S Shiromwar and Vijay R Chidrawar} }