2.1. Inflammatory Pathway-
It has been established that FOXOs are crucial for hepatic metabolism (Fig 3). Inhibiting cell growth, oxidative stress, and the development of apoptogenic signals, which are mediated by the overexpression of Bcl-2-associated X protein (Bax) and FOXO-1 expression and the downregulation of B-cell leukemia/lymphoma 2 protein (Bcl-2), are some of the ways that cyclic isoprenoid (I) inhibits DENA-induced HCC significantly (Abd-Elbaset et al., 2020). βI also reduced the expression of the proliferative marker Ki-67 mRNA and prevented hepatocarcinogenesis. The abnormal pro-inflammatory mediators expressed involving nitric oxide (NO), Prostaglandin E2 (PGE2), as well as Tumor necrosis factor alpha (TNF-α), which are generated by microglial cells, are a hallmark of immunological diseases like AD. Therefore, downregulating pro-inflammatory mediators is a promising method for managing brain inflammatory diseases. Recent research has found that βI has strong anti-proliferative along with anti-cancerous effects. The study also showed that βI suppresses Akt-dependent NF-kB activity as well as dephosphorylates Mitogen-activated protein kinase (MAPKs) to decrease the expressed mediators of pro-inflammation along with their regulatory genes in BV2 microglia that have been activated by LPS (Chen et al., 2010). Both studies demonstrate the anticancer as well as anti-inflammatory characteristics of β-ionone, which further reduce liver injury and AD respectively. Studies have shown that inflammation in the liver results in the onset of AD. The mechanism behind this is not clear and no study has yet implicated the link between them (Kang et al., 2013). Therefore, future studies can be done to confirm the above. Inhibiting the FOXO1 improved lipid-persuaded stress of ER as well as necroptosis, which is one of the protecting Inhibition of FOXO1 in a mouse model of non-alcoholic fatty liver disease has certain characteristics. Mice, however, displayed reduced levels of steatosis when fed a fat-rich diet, and treatment was done with a FOXO1 inhibitor. Intriguingly, postulate that the FOXO1 inhibitor AS1842856 functions by hindering the phosphorylation pathway (Wang et al., 2016). It was seen that AS1842856 specifically inhibits FOXO1 without changing its phosphorylation. Inhibitors were utilized to reduce FOXO1 function in this case as opposed to a gene deletion (Nagashima et al., 2010). Inhibiting FOXO1 prevents the development of ER stress as well as necrosis and also prevents NAFLD. The cause of NASH, or a deteriorating condition known as liver fibrosis, is yet unknown (Ding et al., 2020). ER stress has been found in the postmortem brains of AD-affected people, animals, and also the vitro models, suggesting that ER disruption has a significant part in the development of AD. It was established that ER stress has a significant role in AD etiology. Nearly all of the brain pathology developments linked with AD, involving presenilin1 gene mutation, presenilin2 unusually cut mRNA, formation of β-amyloid, tau phosphorylation, as well as cell death, are allied to ER stress. Additionally, given their roles in the etiology of AD, ER stress and unfolded protein response have potential therapeutic roles (Li et al., 2015). Recent research has revealed that ER stress activates inflammation reactions via several UPR transducers. The most effective pathways include “inositol-requiring enzyme1- Tumor necrosis factor receptor-associated factor-2 (IRE1-TRAF2), Protein kinase RNA- like endoplasmic reticulum kinase- Eukaryotic Initiation Factor 2α (PERK-eIF2α), and GSK-3, activating transcription factor 6 - cAMP-responsive element-binding protein H (ATF6-CREBH)”, also the pathways induced by inflammation of caspase. Some theories explain the connection between ER stress in neurons, inflammation, and the development of pathogenic alterations in AD. From the above-mentioned studies, it was demonstrated that ER stress provides clues for the progression of NAFLD and AD. There are no studies that have implicated the link between ER stress causing NAFLD, which leads to Alzheimer’s and is attenuated by FOXO inhibition (Salminen et al., 2009).