The Neuroprotective Effects of Danggui-Shaoyao San on Vascular Cognitive Impairment: Involvement of the Role of the Low-Density Lipoprotein Receptor-Related Protein

Abstract

Effective drugs for treating dementia are still rare. Danggui-Shaoyao San (DSS), a traditional Chinese medicine, has been widely used in oriental countries for the treatment of various gynecological diseases. Many studies reported that DSS could ameliorate cognitive impairment. In this study, we aimed to investigate the underlying mechanism of DSS on vascular cognitive impairment (VCI) rats. Chronic cerebral hypoperfusion (CCH) is one of the main causes of VCI. CCH resulted in a chain of pathological process, including neuroinflammation, neuronal apoptosis, and oxidative stress. The most widely used animal model of VCI is permanent bilateral common carotid artery occlusion in rats. In this research, we determined whether DSS attenuated cognitive impairment by targeting I kappa B kinase (IKK)/nuclear factor of kappa B (NF-jB) signal pathway in VCI rats. Morris water maze and fear conditioning tests results indicated that DSS [7.2 g/(kg$d)] could improve learning and memory ability in VCI rats. We also found DSS significantly elevated the levels of low-density lipoprotein receptor-related protein 1 (LRP1) in the brain of VCI rats and this might indirectly target the IKK/NF-jB signal pathway to exert inhibitory effect on neuroinflammation, neuronal apoptosis, and oxidative stress in VCI rats. The present researches indicated that DSS might attenuate cognitive impairment by targeting IKK/NF-jB signal pathway in VCI rats and DSS might be a promising agent on VCI.

Contribution of blood-brain barrier-related blood-borne factors for Alzheimer’s disease vs. vascular dementia diagnosis: A pilot study

“…Our study focused on Aβ clearance-related proteins and enzymes in AD, which can help discover their potential in the development of AD drugs and provide an optimistic prospect for future therapeutic targets. Furthermore, previous studies found downregulation of LRP1 protein and mRNA expression in VaD rats via the IKK/NF-κB signaling pathway ( Cai et al, 2020 ; Wang et al, 2020 ). Nevertheless, Mercedes et al proposed that serum sLRP1 can serve as a candidate marker to differentiate AD from mixed dementia phenotypes, with a significant increase in sLRP1 serum protein levels in subjects with mixed dementia and relatively normal levels in AD ( Lachén-Montes et al, 2021 ).…”

Pentapeptide WN5 targets the gut microbiota in alleviating Alzheimer’s disease pathologies

“…These improvements were only mild or absent when administered by intraperitoneal injection suggesting that the route of administration could be a critical determinant to the level of efficacy of WN5. Morris water maze and shuttle box tests are standard tests frequently used for the evaluation of cognitive function in aging and neurological conditions [19,20]. Intraperitoneal injection introduces substances of interest directly into the bloodstream but the direct introduction of peptide drugs into the bloodstream may pose allergic reaction challenges [10,21].…”

The effects of Danggui-Shaoyao-San on neuronal degeneration and amyloidosis in mouse and its molecular mechanism for the treatment of Alzheimer’s disease

“…Many studies have demonstrated that RAGE blockade could alleviate amyloidosis and cognitive deficits [32,36,37]. Our previous studies indicated that DSS increases the level of LRP1 and decreases the level of RAGE in a vascular cognitive deficit rat [22]. Therefore, we sought to further investigate whether DSS affects RAGE and LRP1 in APP/PS1 mice.…”

“…Our earlier research demonstrated that DSS effectively alleviates cognitive impairment in APP/PS1 mice [21]. We also found that DSS can enhance the expression of LRP1 in rats with vascular cognitive dysfunction [22]. Although previous studies have proved DSS is effective to reduce the neurotoxicity induced by Aβ, it remains unknown whether DSS is effective to alleviate the Aβ deposition of AD, and if so, what is the molecular mechanism.…”