Hepatocellular carcinoma (HCC) is the one of the major health problem in the world, is a leading cause of cancer related mortality. NF-kB pathways is considered as the singling pathway which activates the various cellular function including cell expansion, survival, proliferation and vesicular transport and found frequently dysregulated pathway in HCC. Consequently, natural product based inhibitors play a significant role in the NF-kB pathway and extensively scrutinized in the targeting the cancer in recent years. Present study was aimed to scrutinize the effect of 2beta-hydroxybetulinic acid 3beta-oliate (HBO) as NF-kB inhibitors for hepatic cancer.
Swiss albino Wistar rats (48) were divided into four groups. Diethylnitrosamine (DEN) (200 mg/kg) dose was used for induction the HCC in rats and treated with the HBO for 22 weeks. Pro-inflammatory cytokines including IL-6, TNF-α, IL-1β and NF-κB expression were estimated, respectively. Docking analysis was also performed with NF-kB (PDB:1NFK) to explicate imperative structural residues essential for bioactivity.
HBO significantly (p < 0.001) altered the hepatic parameters such as AFP, AST, ALT along with the biochemical and antioxidant parameters. DEN group rats suggest the expansion of hepatic nodules, which was reduced by HBO dose dependently. DEN up-regulated the proinflammatory cytokines including IL-6, TNF-α, IL-1β and NF-κB, which suggest the expansion of hepatic inflammation during cancer and down-regulated by HBO. Whereas, docking research results exhibits that compound HBO was found to be efficient to inhibit NF-kB by binding the ATP pocket through interaction with SER888, GLY705, PRO853, TRP707 and GLY893.
Collectively, we may conclude that HBO has shown excellent activity towards down-regulation of HCC via inhibition of NF-kB pathways supported by molecular docking research analysis. Therefore, HBO could be a potential candidate for hepatic cellular carcinoma.
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All authors have declared no conflicts of interest.