Bisdemethoxycurcumin inhibits oxidative stress and antagonizes Alzheimer's disease by up‐regulating SIRT1

Abstract

Introduction Alzheimer's disease (AD) is a progressive neurodegenerative disease. It can lead to progressive cognitive impairment, memory loss, and behavioral alterations. So far, the exact cellular and molecular mechanisms underlying this disorder remain unclear. And there are no effective treatments to prevent, halt, or reverse AD. In recent years, Chinese traditional medicine has become a new force in the treatment of AD, and the typical representatives of natural herbal ingredients are curcumin and its derivatives. Bisdemethoxycurcumin (BDMC), which is a classical derivative of curcumin, was found to have neuroprotective effects against a cell model of Alzheimer's disease (AD) in our previous studies. This study investigated the intrinsic mechanism of BDMC against AD in animal models. Methods In this study, BDMC was injected into the lateral ventricles of normal C57BL/6 mice, APP/PS mice, and APP/PS mice treated with EX527 (the inhibitor of SIRT1). Y maze and Morris water maze were used to test the learning and memory ability of mice. Nissl staining was used to observe the morphological changes of neurons. Immunofluorescence staining was used to detect Aβ deposition in mice. The activities of GSH and SOD were determined to observe the levels of oxidative stress in mice. And Western blot analyses were used to detect content of SIRT1 in mice. Results In the APP/PS mice, after BDMC intervention, their cognitive function improved, oxidative stress adjusted, the number of neurons increased, Aβ deposition decreased, and the level of SIRT1 expression increased. However, when SIRT1 is inhibited, BDMC on the improvement in the learning and memory ability and the improvement on oxidative stress in APP/PS1 mice were reversed. Conclusion Our findings demonstrated that in the AD mice, BDMC has antagonistic effect on AD. And an intermediate step in the antagonism effect is caused by SIRT1 upregulation, which leading to decreased oxidative stress. Based on these, we concluded that BDMC injection into the lateral ventricle can act against AD by upregulating SIRT1 to antioxidative stress.

Bisdemethoxycurcumin Protects Small Intestine from Lipopolysaccharide‐Induced Mitochondrial Dysfunction via Activating Mitochondrial Antioxidant Systems and Mitochondrial Biogenesis in Broiler Chickens

“…Impaired mitochondrial morphology has been implicated in increased electron leak from the mitochondrial respiratory chain and loss of mitochondrial membrane potential, which is the initial stage of mitochondrial dysfunction [ 37 ]. Bisdemethoxycurcumin has been widely used to suppress the burst of ROS and counteract oxidant stress in various diseases [ 26 , 28 , 38 ]. In our study, increased ROS levels and decreased mitochondrial membrane potential induced by LPS were partially rectified by dietary bisdemethoxycurcumin treatment.…”

Curcumae Radix Extract Reduces Beta-Amyloid (Αβ) and Tau Protein Through Increased Mitochondrial Respiration

“…Our previous study con rmed the components of Curcumae Radix extract, such as curcumin, demethoxycurcumin, and bisdemethoxycurcumin [12]. Curcumin suppresses breast cancer [20], demethoxycurcumin has neuroprotective effects [21], and bis-demethoxycurcumin inhibits Alzheimer's disease by suppressing oxidative stress [22]. In neurodegenerative diseases involving mitochondrial dysfunction, demethoxycurcumin, which is a natural derivative of curcumin, exerts neuroprotective activity [21].…”

Comparative Phosphoproteomics of Neuro-2a Cells under Insulin Resistance Reveals New Molecular Signatures of Alzheimer’s Disease

“…It is known that Aβ oligomers temporarily inhibit AMPK and cause metabolic dysfunction in hippocampal neurons in the early AD brain [83]. In addition, AMPK alleviates AD by activating sirtuin 1, whose expression is reduced with impairment of spatial learning and memory [84,85]. Previous studies have confirmed the association between integrin or AMPK and neurodegenerative disease, and our results showed changes in the integrin and AMPK pathways in insulin resistance-induced neuronal cells, suggesting the possibility that metabolic disease may induce AD.…”