Forskolin Effect on FOXO1 Expression and Relationship of FOXO1 Activation to Oxidative Stress: From Molecular to Therapeutic Strategy

Abstract

Background: Reactive Oxygen Species (ROS) production has been established as an essential contributor in the development cardiotoxicity. The increase of ROS production simultaneously leads to the inhibition of anti-oxidant systems. Forkhead transcription factor O1 (FOXO1) plays an important role in regulating metabolism and oxidant stress. Clozapine was used to induce cardiotoxicity. Forskolin the well-known anti-oxidant and anti-inflammatory agent was used to modulate the effect on both FOXO1 gene and its target gene catalase and to what extent it may protect against clozapine-induced cardiotoxicity. Methods:The animals were classified into: control group, forskolin group; forskolin was administered for 8 weeks; clozapine group, and forskolin + clozapine group; forskolin was pre-administered for 5 weeks then continued along with clozapine for the last 3 weeks. RT-qPCR and gel electrophoresis were done. We analyzed the relation between FoxO1 gene and oxidative stress.Results: These effects are achieved by the ability of Forskolin to modulate the expression of Foxo-1 and catalase, the levels of CKMB, troponin I, GST, MDA, and TNF-α, Caspase-3 were decreased, histopathological changes were improved. Forskolin reduce cardiomyocytes damage, and improve cardiac function by decreasing oxidative stress. Conclusion:Forkolin with its biological activities and anti-oxidative effects control cardiotoxicity induced by ROS in addition to its anti-inflammatory activity. This may be considered as therapy in cardiac problems management.

The Therapeutic Potential of the Labdane Diterpenoid Forskolin

“…Forskolin is synthesized by diterpene synthases via the substrate protonation at the 14,15-double bond of the initial precursor geranyl geranyl diphosphate ( Figure 1b) [22]. Forskolin contains some unique functional elements, notably the tetrahydropyran-derived heterocyclic ring [23].…”

Periplaneta americana peptide decreases apoptosis of pig‐ovary granulosa cells induced by H2O2 through FoxO1

“…NO and MDA are important indicators for evaluating oxidative stress in the body (Luo et al, 2018;Wang et al, 2019) As a member of the FoxO family, FoxO1 activity is regulated by oxidative stress (Sania et al, 2018). It can regulate many targets, such as genes involved in apoptosis and autophagy, and anti-oxidative enzymes (Murtaza et al, 2017;Wang et al, 2016).…”