The effects of C-glycosylation of luteolin on its antioxidant, anti-Alzheimer’s disease, anti-diabetic, and anti-inflammatory activities

Abstract

To investigate the effect of C-glycosylation at different positions of luteolin, the structure-activity relationships of luteolin and a pair of isomeric C-glycosylated derivatives orientin and isoorientin, were evaluated. We investigated the effects of C-glycosylation on the antioxidant, anti-Alzheimer's disease (AD), anti-diabetic and anti-inflammatory effects of luteolin and its two C-glycosides via in vitro assays of peroxynitrite (ONOO(-)), total reactive oxygen species (ROS), nitric oxide (NO), 1,1-diphenyl-2-picrylhydraxyl (DPPH), aldose reductase, protein tyrosine phosphatase 1B (PTP1B), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor cleaving enzyme 1 (BACE1), and cellular assays of NO production and inducible nitric oxide synthase (iNOS)/cyclooxygenase-2 expression in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Of the three compounds, isoorientin showed the highest scavenging activity against DPPH, NO, and ONOO(-), while luteolin was the most potent inhibitor of ROS generation. In addition, luteolin showed the most potent anti-AD activity as determined by its inhibition of AChE, BChE, and BACE1. With respect to anti-diabetic effects, luteolin exerted the strongest inhibitory activity against PTP1B and rat lens aldose reductase. Luteolin also inhibited NO production and iNOS protein expression in LPS-stimulated macrophages, while orientin and isoorientin were inactive at the same concentrations. The effects of C-glycosylation at different positions of luteolin may be closely linked to the intensity and modulation of antioxidant, anti-AD, anti-diabetic, and anti-inflammatory effects of luteolin and its C-glycosylated derivatives.

Maysin and Its Flavonoid Derivative from Centipedegrass Attenuates Amyloid Plaques by Inducting Humoral Immune Response with Th2 Skewed Cytokine Response in the Tg (APPswe, PS1dE9) Alzheimer’s Mouse Model

“…The natural flavonoid compounds, named the EA-CG extract, which contained five phytochemicals that are the major constituents of Maysin (i.e., Luteolin, Isoorientin, Rhamnosylisoorientin, Derhamnosylmaysin, and Maysin) in which those are may represents a potential anti-BACE1 phytochemicals as non-pharmacological alternatives or diet regimen that could prevent AD-like pathological symptoms by reducing soluble β-amyloid production and inhibiting amyloid plaque formation [20]. Compelling evidence support the premise likely effectiveness of natural flavonoids as Anti-AD in which one of flavonoid compound, Luteolin (include c-glycosylated derivatives) or Isoorientin, have shown its efficacy to prevent anti-Diabetic, anti-diabetic using diet induce cognitive deficit in obesity C57Bl/6 mice [35, 20] Liu et al reported that Luteolin exerted anti-AD effect such as impairment of spatial learning and memory capabilities, dysfunction of microvascular function, the intervene regional cerebral blood flow, result from Aβ (25–35) derived production of reactive oxygen species (ROS) using i.c.v. injection of aggregated Aβ (25–35) peptide in Male Kunming mice [36].…”

Modifications of dietary flavonoids towards improved bioactivity: An update on structure–activity relationship

“…Orientin and isoorientin with 3 0 -OH group showed activities against HMGB1 and its receptors while vitexin and isovitexin without 3 0 -OH group showed no effect, indicating that the existence of 3 0 -OH group of flavone plays a pivotal role in anti-inflammatory activities (Yoo et al 2014). Furthermore, orientin with 8-C-glucoside was more active than isoorientin with 6-C-glucoside in anti-inflammatory activities both in vitro and in vivo (Choi et al 2014;Yoo et al 2014). Orientin, which has been used as an anti-inflammatory herb in China, regulates the key molecules involved in inflammation.…”

Glucose‐mediated protein glycation: Contribution of methanolic extract of Ceratonia siliqua L. in protection and in vitro potential inhibition of acetylcholinesterase

“…Several studies have been focused on the link between diabetes mellitus (DM) and AD. In fact, insulin plays a major role in learning and memory processes, is also involved in neuromodulatory and neuroendocrine responses, as a consequence, the modification in the insulin pathway observed in diabetic patients is currently thought to be associated with cognitive impairment and dementia (Choi, Nurul Islam, Yousof Ali, Myeong Kim, et al, ). Moreover, several lines of evidence have demonstrated an increase in AChE activity in brains of diabetic rats (Sanchez‐Chavez & Salceda, ; Schmatz et al, ).…”