Terpenoids from Azadirachta indica are potent inhibitors of Akt: Validation of the anticancer potentials in hepatocellular carcinoma in male Wistar rats

• Published in: Journal of food biochemistry 2021-01, Vol.45 (1), p.e13559-n/a
• Main Authors: Akinloye, Oluseyi A., Akinloye, Dorcas I., Lawal, Mariam A., Shittu, Mujidat T., Metibemu, Damilohun S.
• Format: Article
• Language: English
• Subjects: Akt; Azadirachta indica; hepatocellular carcinoma; lupeol; terpenoids
• ISSN: 0145-8884; 1745-4514
• DOI: 10.1111/jfbc.13559

Hepatocellular carcinoma (HCC) is the commonest primary malignancy with poor patient prognosis and a high mortality rate. In this study, phytochemicals characterized from Azadirachta indica were screened against the catalytic site of Akt, and the anticancer potentials of the extracted leads (terpenoids) were determined in hepatocellular carcinoma in male Wistar rats. The lead compounds are terpenoids; hence, the extraction of terpenoids from A. indica. Gas chromatography‐mass spectrometry (GCMS) was employed for the characterization of the extract. Diethylnitrosamine (DEN)‐induced hepatocellular carcinoma in male Wistar rats were treated with the terpenoids extract. The hit, lupeol demonstrates inhibition of Akt and is a potential drug candidate. The terpenoids extract downregulate Akt mRNA and demonstrated anti‐Akt downstream signaling effects; anti‐inflammatory, anti‐angiogenesis, pro‐apoptotic, and cell cycle arrest, it also demonstrated cellular regeneration, hepatoprotection, antioxidant potentials, and cellular repairs in hepatocellular carcinoma in male Wistar rats. Practical applications Hepatocellular Carcinoma (HCC) is the most common primary malignancy with poor patient prognosis and a high mortality rate. Akt, a serine/threonine kinase is at the crossroad of cell survival, the progression of the cell cycle, cell signaling, cell growth, cell division, and inactivation of pro‐apoptotic factors. The inhibition of Akt is an effective therapeutic strategy against HCC. In this study, terpenoids from Azadirachta indica are potent inhibitors of Akt and hitherto demonstrate anticancer potentials. A. indica leaves are readily available globally and more also it is readily cultivated in African and Asia, continents with the highest prevalence of HCC. A. indica terpenoids extract demonstrate anti‐HCC potentials and hence should be exploited in this regard. Screening of terpenoids from Azadirachta indica against the Akt showed they are potent inhibitors of the protein. The screening revealed lupeol, a triterpenoid as the lead compound. Lupeol demonstrate surpassing inhibitory potential on Akt 2 than ipatasertib in in‐silico studies Terpenoids extract downregulate Akt mRNA and demonstrated anti‐Akt downstream signaling effects; anti‐inflammatory, anti‐angiogenesis, pro‐apoptotic, and cell cycle arrest. It also demonstrated cellular regeneration, hepatoprotection, antioxidant potentials, and cellular repairs in hepatocellular carcinoma in male Wistar rats.