Structural characterization and neuroprotective effect of a polysaccharide from Corydalis yanhusuo
Introduction
Alzheimer's disease (AD) is the most widespread neurodegenerative disorders of the brain, characterized by irreversible loss of cognitive function, progressive deterioration of mental functions including learning and memory, and behavioral changes [1,2]. More than 35 million people across the globe today are affected by dementia, most suffering from AD, and this numbers are expected to 66 million by 2030 [3]. Although much progress has been made in understanding the cause of AD, unfortunately, there is no definitive solution for curing this disorder [4,5]. Currently, the therapeutic approaches conventionally used to maintain cognitive functions of patients consists of two classes of medications, the acetylcholinesterase inhibitors (AChEIs; tacrine, donepezil, rivastigmine, galantamine) and the noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist (memantine), which have been approved by the US FDA for the treatment of AD [6,7]. However, these drugs exhibited mild ameliorating effect on cognitive symptoms, limited duration of their efficacy and some undesired effects, such as diarrhea, vomiting, nausea, and weight loss for AChEIs, and constipation, confusion, dizziness, and headache for memantine, respectively [8]. Due to the complexity of pathology of AD and the limitations of current AD therapeutics, increasing attentions on the development of innovative therapeutics have become urgently. The neuropathological features of AD include the excessive extracellular deposition of amyloid-β (Aβ) protein in senile plaques, hyperphosphorylated tau-containing neurofibrillary tangle, and massive neuronal death [9]. Aβ is a 39–43 amino acid peptide fragment derived from amyloid precursor protein by proteolytic processing with β-secretase and γ-secretase [10]. Experimental data from in vitro and in vivo studies indicated that Aβ can elicit apoptosis in neurons, suggesting a critical role of Aβ in the pathogenesis of AD, though the precise mechanism underlying this Aβ neurotoxicity remains to be fully elucidated [11]. In this regard, therapeutic strategies that address the modulation of Aβ toxicity may foster novel developments for the treatment of AD. Thus, searching for any substances from natural sources that can block Aβ toxicity on a cultured neuronal cell line may provide clinical benefits to control the onset of AD patients.
There is a long history of the use of traditional Chinese medicinal medicine (TCM) in the treatment of neurological disorders and these effects were documented in Chinese herbal books [12], suggesting that TCM may be a valuable resource of alternative and complementary candidates for the treatment of AD. Until now, TCM is still in current use and has been attracted a great deal of attention in recent years. For example, Chinese herbal extracts have been found to be effective in the treatment of age-associated neurodegenerative diseases, including Angelica sinensis [13], Polygonum multiflorum [14], Gastrodia elata [3], Eriobotrya japonica [15], and so on. Corydalis yanhusuo W.T. Wang is a well-known TCM that has been used traditionally to promote blood circulation, reinforce vital energy and relieve pain for a long history [16,17]. Alkaloids are known to be its main pharmacologically active ingredients in C. yanhusuo [18], and modern pharmacological experiments have recently shown that these have extensive biological functions such as antitumor, antinociceptive, antihypertensive, and antimyocardial ischemia [19]. Recently, several lines of evidence demonstrated that C. yanhusuo possessed certain beneficial effect on neurodegenerative patients with cognitive impairment, cerebral circulation insufficiency or dementia [20,21,22]. Up to now, most research on C. yanhusuo has been extensively focused on alkaloid and its derivatives, but few reports has been initiated on the polysaccharide from this plant, except that a water soluble polysaccharide has been isolate and purified from it. Considering its potential benefit on the neurodegenerative disease and no available information about the protective effect of its polysaccharide constituents on nervous system, especially at the cellular level, in this study, we aim to purify another important water-soluble neutral polysaccharide from this plant and observe its effect against Aβ-induced toxicity in PC 12 cells. Furthermore, the underlying molecular signaling pathway involved in the neuroprotective effect of this polysaccharide on Aβ-induced neurotoxicity in PC12 cells was also elucidated.
Section snippets
Materials and chemicals
C. yanhusuo was obtained from a local Traditional Chinese Medicine pharmacy store in Xi'an (China). Lactate dehydrogenase (LDH) kit was obtained from Jiancheng Bioengineering Institute (Nanjing, China). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT), dimethylsulfoxide (DMSO), Aβ25–35, 3,3′-diaminobenzidine, penicillin, streptomycin, T-series dextran (T-2000, T-70, T-40, T-20, and T-10), bovine serum albumin (BSA), monosaccharide standards (glucose, mannose, rhamnose,
Isolation, purification and characteristic of the polysaccharide CYP
The crude polysaccharide CCYP was obtained from the roots of C. yanhusuo after pre-extraction by 95% ethanol, hot water extraction, ethanol precipitation and deproteinization, with a yield (50.12 g) of 5.11% accounting for raw material. This CCYP were purified using DEAE Sepharose Fast Flow column and eluted with 0, 0.25, and 0.5 mol/l NaCl, each giving a corresponding fraction, namely CYP-a, CYP-b, or CYP-c (Fig. 1A). In the present study, we focused on the CYP-a fraction and the other
Conclusion
In summary, our present study demonstrated for the first time that CYP possesses the ability to protect PC12 cells from Aβ (25–35)-induced neurotoxicity, possibly by inhibiting apoptosis via regulation of both the mitochondrial apoptotic pathway and death receptor pathway, which provides new insight into the application of CYP as a promising therapeutic agent for AD. However, our experiments were limited to the cellular model of AD, and further studies on the neuroprotective effects of this
CRediT authorship contribution statement
Yufeng He: Conceptualization, Methodology, Writing - original draft. Wenzhong Xu: Software, Data curation. Yimin Qin: Investigation, Resources.
References (59)
- et al.
Prevention of age-associated dementia
Brain Res. Bull.
(2009) - et al.
Contribution of neural networks to Alzheimer disease’s progression
Brain Res. Bull.
(2009) - et al.
Multiple pathways of apoptosis in PC12 cells CrmA inhibits apoptosis induced by β-amyloid
J. Biol. Chem.
(1999) Alzheimer's disease and oxidative stress: implications for novel therapeutic approaches
Prog. Neurobiol.
(1999)- et al.
Protective effects of Angelica sinensis extract on amyloid β-peptide-induced neurotoxicity
Phytomedicine
(2008) - et al.
Protective effect of Polygonum multiflorum Thunb on amyloid β-peptide 25-35 induced cognitive deficits in mice
J. Ethnopharmacol.
(2006) - et al.
Neuroprotective effects of Eriobotrya japonica against β-amyloid-induced oxidative stress and memory impairment
Food Chem. Toxicol.
(2011) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein binding
Anal. Biochem.
(1976)- et al.
Measurement of uronic acids without interference from neutral sugars
Anal. Biochem.
(1991) - et al.
Water-soluble polysaccharide from the fruiting bodies of Chroogomphis rutilus (Schaeff.: Fr.) OK Miller: isolation, structural features and its scavenging effect on hydroxyl radical
Carbohydr. Polym.
(2010)
Avoiding oxidative degradation during sodium hydroxide/methyl iodide-mediated carbohydrate methylation in dimethyl sulfoxide
Carbohydr. Res.
Quantitative analysis by various GLC response-factor theories for partially methylated and partially ethylated alditol acetates
Carbohydr. Res.
beta-Amyloid-induced dynamin 1 degradation is mediated by N-methyl-d-aspartate receptors in hippocampal neurons
J. Biol. Chem.
Amnesia induced in mice by centrally administered b-amyloid peptides involves cholinergic dysfunction
Brain Res.
Structural analysis of an alkali-extractable and water-soluble polysaccharide (ABP-AW1) from the fruiting bodies of Agaricus blazei Murill
Carbohydr. Polym.
Chemical structure of one low molecular weight and water-soluble polysaccharide (EFP-W1) from the roots of Euphorbia fischeriana
Carbohydr. Polym.
A polysaccharide from dried aerial parts of Agrimonia pilosa: structural characterization and its potential therapeutic activity for steroid-induced necrosis of the femoral head (SANFH)
Carbohydr. Polym.
Protective effects of trans-2,4-dimethoxystibene on cognitive, impairments induced by Abeta (25–35) in hypercholesterolemic rats
Brain Res. Bull.
Activating glucocorticoid receptor-ERK signaling pathway contributes to ginsenoside Rg1 protection against β-amyloid peptide-induced human endothelial cells apoptosis
J. Ethnopharmacol.
Triggering andmodulation of apoptosis by oxidative stress
Free Radic. Biol. Med.
A neuronal model of Alzheimer’sdisease: an insight into the mechanisms of oxidative stress-mediated mitochondrial injury
Neuroscience
Bcl-2 protects against Abeta (25–35)-induced oxidative PC12 cell death by potentiation of antioxidant capacity
Biochem. Biophys. Res. Commun.
17β-Estradiol protects cerebellar granule cells against β-amyloid-induced toxicity via the apoptotic mitochondrial pathway
Neurosci. Lett.
Panax ginseng polysaccharide induces apoptosis by targeting Twist/AKR1C2/NF-1 pathway in human gastric cancer
Carbohydr. Polym.
Rosmanol potently induces apoptosis through both the mitochondrial apoptotic pathway and death receptor pathway in human colon adenocarcinoma COLO 205 cells
Food Chem. Toxicol.
Bryonia dioica aqueous extract induces apoptosis through mitochondrial intrinsic pathway in BL41 Burkitt’s lymphoma cells
J. Ethnopharmacol.
Panax ginseng polysaccharide induces apoptosis by targeting Twist/AKR1C2/NF-1 pathway in human gastric cancer
Int J Biol Macromol.
Protective effects of lycopene against amyloid β-induced neurotoxicity in cultured rat cortical neurons
Neurosci. Lett.
Neurodegenerative diseases: a decade of discoveries paves the way for therapeutic breakthroughs
Nat. Med.
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