Kuwanon G protects HT22 cells from advanced glycation end product-induced damage

Abstract

The incidence of diabetic encephalopathy is increasing as the population ages. Evidence suggests that formation and accumulation of advanced glycation end products (AGEs) plays a pivotal role in disease progression, but limited research has been carried out in this area. A previous study demonstrated that Kuwanon G (KWG) had significant anti-oxidative stress and anti-inflammatory properties. As AGEs are oxidative products and inflammation is involved in their generation it is hypothesized that KWG may have effects against AGE-induced neuronal damage. In the present study, mouse hippocampal neuronal cell line HT22 was used. KWG was shown to significantly inhibit AGE-induced cell apoptosis in comparison with a control treatment, as determined by both MTT and flow cytometry. Compared with the AGEs group, expression of pro-apoptotic protein Bax was reduced and expression of anti-apoptotic protein Bcl-2 was increased in the AGEs + KWG group. Both intracellular and extracellular levels of acetylcholine and choline acetyltransferase were significantly elevated after KWG administration in comparison with controls whilethe level of acetylcholinesterase decreased. These changes in protein expression were accompanied by increased levels of superoxide dismutase and glutathione peroxidase synthesis and reduced production of malondialdehyde and reactive oxygen species. Intracellular signaling pathway protein levels were determined by western blot and immunocytochemistry. KWG administration was found to prevent AGE-induced changes to the phosphorylation levels of Akt, IκB-α, glycogen synthase kinase 3 (GSK3)-α and β, p38 MAPK and NF-κB p65 suggesting a potential neuroprotective effect of KWG against AGE-induced damage was via the PI3K/Akt/GSK3αβ signaling pathway. The findings of the present study suggest that KWG may be a potential treatment for diabetic encephalopathy.

Novel Potent Autophagy Inhibitor Ka-003 Inhibits Dengue Virus Replication

“…This study aimed to identify the natural-product-derived compounds and their derivatives exhibiting autophagy inhibitory activity by using phenotypic-based screening. The high-content image analysis screen identified Ka-003, a derivative of methyl cyclohexene (Figure 5), resembling those found in mulberry plants [31][32][33][34][35], as enabling a potent decrease in the number of autophagic vacuoles in cells in a dose-dependent manner (Figures 1 and 2). More importantly, upon the application of the Ka-003 treatment to DENV-infected cells, a dose-dependent decrease in DENV infectious particle production was observed (Figures 3 and 6).…”

“…As mentioned above, Ka-003 is a derivative of methyl cyclohexene that resembles those found in mulberry plants [31][32][33][34][35]. These include kuwanon G, kuwanon H, kuwanon X and mulbenofuran C. Kuwanon G treatment was previously shown to decrease ROS levels in LPS-treated Caco-2 cells, resulting in the reduced production of proinflammatory cytokines, including IL-1β and TNF-α, and increased cell survival [31].…”

AGE-RAGE axis culminates into multiple pathogenic processes: a central road to neurodegeneration

“…Specifically, it was observed that there was upregulation of pentosidine and a concomitant decrease in the anti-oxidant systems including vitamin E ( Lapolla et al, 2007 ). Levels of glutathione peroxidase and SOD were also found to be diminished in in vitro diabetic encephalopathy model, HT22 cells ( Gan et al, 2021 ).…”

Integrative Omic Analysis Reveals the Dynamic Change in Phenylpropanoid Metabolism in Morus alba under Different Stress

“…M. alba is also used as an herb in traditional Chinese medicine. Secondary metabolites of M. alba have been proved to have multiple physiological activities, including antiviral, antibacterial, and anti-inflammatory activities [ 15 , 16 , 17 , 18 , 19 ]. To better illustrate the regulation mode of flavonoid biosynthesis and lignin biosynthesis in M. alba leaves under different stresses, we treated M. alba leaves using two kinds of stress: B. cinerea infection, which is biotic stress, and high-level UV-B radiation, which is abiotic stress.…”