Berberine Reduces Neurotoxicity Related to Nonalcoholic Steatohepatitis in Rats

Abstract

Berberine is a plant alkaloid that has several pharmacological effects such as antioxidant, antilipidemic, and anti-inflammatory effects. Nonalcoholic steatohepatitis (NASH) triggers different aspects of disorders such as impaired endogenous lipid metabolism, hypercholesterolemia, oxidative stress, and neurotoxicity. In this study, we examined the mechanism by which NASH induces neurotoxicity and the protective effect of berberine against both NASH and its associated neurotoxicity. NASH induced rats showed significant impairments in lipid metabolism with increased serum triglycerides, cholesterol, and low-density lipoprotein (LDL). The NASH induced group also demonstrated a significant oxidative stress which is characterized by increased TBARs level and decreased antioxidant capacity such as GSH and SOD levels. Moreover, the NASH induction was associated with inflammation which was demonstrated by increased TNFα and nitric oxide levels. Hyperglycemia and hyperinsulinemia were observed in the NASH induced group. Also, our results showed a significant increase in the expression of the acetylcholine esterase (AChE) and amyloid beta precursor protein (AβPP). These changes were significantly correlated with decreased insulin degrading enzyme (IDE) and beta-amyloid40 (Aβ 40) and increased beta-amyloid42 (Aβ 42) in the hippocampal region. Daily administration of berberine (50 mg/kg) for three weeks ameliorated oxidative stress, inflammation, hyperlipidemia, hyperglycemia, hyperinsulinemia, and the observed neurotoxicity.

Berberine: Pathways to protect neurons

“…BBR may be a promising multitarget drug to prevent and protect against AD by regulating AD‐associated products such as PP‐2A, APP, amyloid‐β, and tau. For instance, besides normal defense of inflammation and oxidative stress, decreased Aβ 40 and increased Aβ 42 in the hippocampal region were noticed in BBR treated rat model (Ghareeb et al, ). It was reported that BBR improves spatial learning capacity and memory retention in the hippocampus of triple‐transgenic mouse model of AD by promoting autophagic clearance (Aβ clearance) and inhibit Aβ production (Huang et al, ).…”

Insights into the Role and Interdependence of Oxidative Stress and Inflammation in Liver Diseases

“…BBR treatment significantly attenuated hepatic inflammation, lipid peroxides, and fibrosis in NAFLD model, which may be a therapeutic strategy to prevent the progress of hepatic steatosis to NASH [182]. In another study, it was shown that daily administration of BBR at the dose of 50 mg/kg for three weeks relieved oxidative stress, inflammation, hyperglycemia, hyperlipidemia, hyperinsulinemia, and the neurotoxicity related with NASH [183]. Pseudoberberine, a berberine analogue, displayed antioxidant and anti-inflammatory activities in diabetic mice with fatty liver.…”

Berberine chloride ameliorated PI3K/Akt‐p/SIRT‐1/PTEN signaling pathway in insulin resistance syndrome induced in rats

“…Group 5 (Induction treated group) fed HFD for 8 weeks, then orally given BER‐chloride dissolved in 20% of PEG (100 mg/kg Bwt) for 2 weeks. Doses of BER‐chloride and PEG which were used in this protocol referred to other previous studies (El‐Sayed, Ghareeb, Talat, & Sarhan, ; Ghareeb et al, ; Saleh, Attia, & Ghareeb, ).…”