Targeting BuChE-inflammatory Pathway by SK0506 to Manage Type 2 Diabetes and Alzheimer Disease

Abstract

Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) affect a large percent of the population worldwide. Experimental studies have revealed that T2DM and AD share several molecular processes that underlie their respective degenerative pathology. Based on this information, we quantified TNF-α, IL-6 levels, serum glucose, serum triglyceride, hepatic triglyceride, serum AST, serum ALT and butyrylcholinesterase (BuChE) in various rat tissues. HFD was fed to rats resulting in increased body weight, fasting blood glucose, IL-6, TNF-α levels, hepatic triglyceride, serum AST, serum ALT and BuChE. SK0506 treatment significantly prevented weight gain induced by HFD feeding. SK0506, but not Rosiglitazone, significantly reduced serum and hepatic triglycerides levels. Treatment with SK0506 also ameliorated elevated levels of both inflammatory markers (TNF-α and IL-6) and serum liver enzymes (ALT and AST) significantly in HFD fed rats. BuChE activity also reduced in skeletal muscle and adipose tissues of rats treated by SK0506. In conclusion, current study has opened new potential avenues towards research for management of T2DM and AD by Chinese herbal extracts, ‘‘SK0506’’.

Plasma Cholinesterase Activity in Alzheimer's Disease

“…This is based on observations that LMD and DM are associated with pChE [3,4] and that AD is positively related to pChE [5] because pChE metabolizes ACh and causes inflammatory hyperactivation [17]. The preliminary results of our current study also suggest that the effectiveness of Riv was related to pChE downregulation.…”

“…Dyslipidemia or lipid metabolic disorder (LMD) and diabetes mellitus (DM) are also positively related to pChE activity [3,4]. AD is also thought to be related to LMD and DM [5].…”

Status of Acetylcholinesterase and Butyrylcholinesterase in Alzheimer's Disease and Type 2 Diabetes Mellitus

“…SK0506 has been used as anti-diabetic testing agent in animal studies. In one study, SK0506 treatment resulted in lowering of BuChE activity in adipose tissues and skeletal muscle of rats and also significantly lowered the levels of hepatic and serum triglycerides and inflammatory markers (interleukin-6 and TNF-α) in rats fed with high fat diet [49]. Likewise, in a separate study on rodent model of the metabolic syndrome induced by high-fat fed diet, SK0506 was found to significantly enhance glycogen synthesis and glucose uptake in adipose tissues during hyperinsulinemic clamp [50].…”

Effects of extremely low frequency electromagnetic field (ELF-EMF) on catalase, cytochrome P450 and nitric oxide synthase in erythro-leukemic cells

“…Graphs were plotted using prism software (version 4, GraphPad, San Diego, CA) as described in [22,23] and specific kinetic constants were obtained by the regression analysis (linear and several different nonlinear forms) computed by this packages.…”