Ferulic acid interventions ameliorate NDEA-CCl4-induced hepatocellular carcinoma via Nrf2 and p53 upregulation and Akt/PKB-NF-κB-TNF-α pathway downregulation in male Wistar rats.

Hepatocellular carcinoma is a prevalent form of liver cancer that is life threatening. Many chemically synthesized anti-cancer drugs have various degrees of side effects. Hence, this study investigated the effect of FEAC interventions on NDEA-CCl4-induced HCAR in male Wistar rats. HCAR was induced by intraperitoneal administration of 200 mg/kg of NDEA and 0.5 mL/kg CCl4 (as a promoter of HCAR). Following the induction of HCAR, rats were treated differently with two different doses (25 and 50 mg/kg) of FEAC. HCAR induction was confirmed by the significant elevation of serum levels of ALT, AST, and α-FP. Also elevated significantly were liver levels of Akt/PKB, NF-κB, TNF-α, MDA, GSH, and activities of GST, SOD, and CAT, while levels of liver p53 and Nrf2 were significantly lowered compared with normal rats. Treatment interventions with both 25 and 50 mg/kg of FEAC against the DEN-CCl4-induced HCAR gave comparable effects, marked by a significant reduction in the levels of serum ALT, AST and α-FP, as well as liver levels of MDA, GSH, Akt/PKB, NF-κB, TNF-α, GST, SOD, and CAT, while levels of liver p53 and Nrf2 were significantly elevated compared with normal rats. Put together and judging by the outcomes of this study, FEAC being a potent antioxidant may also be potent against chemical-induced HCAR via upregulation of p53 and Nrf2, as well as downregulation of the Akt/PKB-NF-κB pathway in rats.

Computational and Preclinical Prediction of the Antimicrobial Properties of an Agent Isolated from Monodora myristica: A Novel DNA Gyrase Inhibitor.

The African nutmeg (Monodora myristica) is a medically useful plant. We, herein, aimed to critically examine whether bioactive compounds identified in the extracted oil of Monodora myristica could act as antimicrobial agents. To this end, we employed the Schrödinger platform as the computational tool to screen bioactive compounds identified in the oil of Monodora myristica. Our lead compound displayed the highest potency when compared with levofloxacin based on its binding affinity. The hit molecule was further subjected to an Absorption, Distribution, Metabolism, Excretion (ADME) prediction, and a Molecular Dynamics (MD) simulation was carried out on molecules with PubChem IDs 529885 and 175002 and on three standards (levofloxacin, cephalexin, and novobiocin). The MD analysis results demonstrated that two molecules are highly compact when compared to the native protein; thereby, this suggests that they could affect the protein on a structural and a functional level. The employed computational approach demonstrates that conformational changes occur in DNA gyrase after the binding of inhibitors; thereby, this resulted in structural and functional changes. These findings expand our knowledge on the inhibition of bacterial DNA gyrase and could pave the way for the discovery of new drugs for the treatment of multi-resistant bacterial infections.