Abstract
This work evaluates nano-lipid carrier of ganoderic acid (GA) and molecular docking on various cancer signaling pathways, an attempt to improve the hepatic condition associated with hepatic carcinoma (HCC) induced by diethyl-nitrosamine (DEN) in Wistar rats. Molecular docking mechanism of GA was performed through binding simulation analysis for various cancer signaling pathway, viz., Bcl-2, Pl3K, NF-κB, Akt/PKB, and Stat-3. Double emulsion solvent displacement method was implied for preparation of GA-loaded nano-lipid carrier. GA-NLCs were evaluated for drug loading capacity, entrapment efficiency, particle size, gastric stability, in vitro drug release, cytotoxicity, cellular uptake, and in vivo studies including macroscopical, hepatic injury markers, non-hepatic, biochemical, antioxidant parameters, and histopathological evaluation. HCC was induced by intraperitoneal injection of DEN (200 mg/kg). Both in vivo and molecular docking results were compatible in establishing the alteration in hepatic nodules, hepatic, non-hepatic, and antioxidant parameters, in a significant manner (p < .001) by GA and GA-NLC along with signal alteration of Bcl-2, Pl3K, NF-κB Akt/PKB, and Stat-3 pathway. Histopathological observation confirmed and supported the above result by GA and GA-NLC. On the basis of our results, we can advocate that, GA interferes with various cancer signaling proteins involved in pathogenesis of cancer and was able to cease the progression of disease. Additionally, GA-NLCs proved its chemoprotective effect against the DEN-induced HCC by modulation of hepatic and non-hepatic parameters through various mechanisms.
Highlights
Hepatocellular carcinoma (HCC) is third most common cause of mortality in the world (Lawrence et al, 1995)
Molecular docking of ganoderic acid (GA) performed against RAC-alpha serine/threonine-protein kinase receptor revealed a common binding orientation of GA in the catalytic binding pocket of RAC-alpha serine/threonine-protein kinase receptor (PDBID: 3o96)
From the above experimental discussion, it is concluded that GA is able to interact at various cancer signaling proteins, which play significant role in the pathogenesis of cancer
Summary
Hepatocellular carcinoma (HCC) is third most common cause of mortality in the world (Lawrence et al, 1995). It accounts for 70–85% of primary malignancy of liver and its frequent development is associated with chronic inflammation either due to persistent of hepatitis infection or continues state of fatty liver. As on date several synthetic chemotherapeutic agents/drugs are available, but they are inadequate and have serious adverse effects during treatment regime. There is urgent requirement of effective, well tolerated chemotherapeutic agents in the management of liver cancer that can minimize the mortality and morbidity in patients (Sadek et al, 2018)
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