A computational insights of Ocimum basilicum flavonoid and essential oils interaction in the targeting Keap1/SIRT1/NFKB signaling pathway

Abstract

Type 2 diabetes mellitus (T2DM) is a metabolic disorder that has a negative relationship with male reproduction. The imbalance between endogenous antioxidants and inflammatory mediators would initiate inflammation development, further accelerating tissue aging. This study aimed to investigate the flavonoids and essential oils from Ocimum basilicum involved in Keap1/SIRT1/NFκB. O. basilicum compounds used were flavonoid (apigenin, rutin, and quercetin) and essential oils (α-bergamotene, α-cadinol, methyl cinnamate, and methyl eugenol), which were then evaluated for toxicity by Protox II and pharmacokinetic properties by ADMET. The protein network was built by STRING. The molecular docking was performed by PyRx on NFκB, SIRT1, and Nrf2. The result demonstrated that apigenin, rutin, α-bergamotene, α-cadinol, and methyl cinnamate have low toxicity. The pharmacokinetics study showed that O. basilicum was primarily absorbed in the human intestine. The protein network analysis revealed that NFκB and Nrf2 were involved in inflammatory response, regulation of stress response, and insulin resistance pathways. SIRT1 and Nrf2 have pivotal roles in insulin resistance-induced gonadal disease. Rutin has the strongest binding affinity for Keap1 (4IQK), whereas α-bergamotene and α-cadinol have the strongest binding affinity for NFκB (3DO7) and SIRT1 (4I5I), respectively. The flavonoid contents might be beneficial to activate Nrf2, whereas the essential oils of O. basilicum inhibit NFκB and activate SIRT1. These preliminary findings suggested that O. basilicum bioactive compounds might provide a promising candidate for restoring the imbalance in T2DM through the Keap1/SIRT1/NFκB signaling pathways.