EGCG ameliorates high‐fat– and high‐fructose‐induced cognitive defects by regulating the IRS/AKT and ERK/CREB/BDNF signaling pathways in the CNS

Abstract

Obesity, which is caused by an energy imbalance between calorie intake and consumption, has become a major international health burden. Obesity increases the risk of insulin resistance and age-related cognitive decline, accompanied by peripheral inflammation. (-)-Epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, possesses antioxidant, anti-inflammatory, and cardioprotective activities; however, few reports have focused on its potential effect on cognitive disorders. In this study, our goal was to investigate the protective effects of EGCG treatment on insulin resistance and memory impairment induced by a high-fat and high-fructose diet (HFFD). We randomly assigned 3-mo-old C57BL/6J mice to 3 groups with different diets: control group, HFFD group, and HFFD plus EGCG group. Memory loss was assessed by using the Morris water maze test, during which EGCG was observed to prevent HFFD-elicited memory impairment and neuronal loss. Consistent with these results, EGCG attenuated HFFD-induced neuronal damage. Of note, EGCG significantly ameliorated insulin resistance and cognitive disorder by up-regulating the insulin receptor substrate-1 (IRS-1)/AKT and ERK/cAMP response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathways. Long-term HFFD-triggered neuroinflammation was restored by EGCG supplementation by inhibiting the MAPK and NF-κB pathways, as well as the expression of inflammatory mediators, such as TNF-α. EGCG also reversed high glucose and glucosamine-induced insulin resistance in SH-SY5Y neuronal cells by improving the oxidized cellular status and mitochondrial function. To our knowledge, this study is the first to provide compelling evidence that the nutritional compound EGCG has the potential to ameliorate HFFD-triggered learning and memory loss.-Mi, Y., Qi, G., Fan, R., Qiao, Q., Sun, Y., Gao, Y., Liu, X. EGCG ameliorates high-fat- and high-fructose-induced cognitive defects by regulating the IRS/AKT and ERK/CREB/BDNF signaling pathways in the CNS.

Effects of Microbial Metabolites of (−)-Epigallocatechin Gallate on Glucose Uptake in L6 Skeletal Muscle Cell and Glucose Tolerance in ICR Mice

“…39) It was found that EGC-M5 and EGC-M7 had an inhibitive effect on ACE enzyme in vitro and hypotensive effects in vivo. 39) Kiryu et al 40) reported that ACE inhibitors sig- Data are expressed as the mean ± SEM (n = 5).…”

“…These findings indicate that metabolites play a crucial role in metabolic regulation in the body following green tea intake. Yashi et al 41) reported that EGCG administration reversed insulin resistance and neuroinflammation in the brain of C57BL/6J mice fed a long-term high-fat and high-fructose diet (HFFD). Recently, Unno et al 33) discovered that EGC-M5 could significantly prolong neurite length of human neuroblastoma SH-SY5Y cells, and increase the number of these cells significantly.…”

Neural Underpinnings of Obesity: The Role of Oxidative Stress and Inflammation in the Brain

“…As with other polyphenolic compounds, EGCG has been studied for its antioxidant, anti-inflammatory, and anti-obesity effects [ 135 , 136 , 137 ]. When treated with EGCG for 16 weeks, mice placed on a HFD and 10% fructose solution resisted obesity development and displayed better CNS insulin sensitivity than HFD-fed obese control mice [ 138 ]. Further, EGCG attenuated neuroinflammation by lowering TNF-α mRNA and phosphorylation of inflammatory markers p38 and NF-kβ in the brain.…”

Neuroprotective effects of Camellia nitidissima Chi leaf extract in hydrogen peroxide‐treated human neuroblastoma cells and its molecule mechanisms

“…UPLC‐TOF MS/MS analysis demonstrated that the main active compounds of CLE were catechin, quercetin, kaempferol, and their derivatives, which have been evidenced as neuroprotective phytochemicals (Costa, Garrick, Roquè, & Pellacani, 2016; Hussein, Mohamed, & Omar, 2018; Sutcliffe, Winter, Punessen, & Linseman, 2017). Moreover catechin, an essential constituents of tea polyphenol, has been evidenced in upregulation of CREB/BDNF signaling (Ding, Ma, Man, & Lv, 2017; Mi et al., 2017). Therefore, the neuroprotective effect of CNC leaves might be a combined effect of these active compounds.…”