2. Academic Validation
  3. Chemical basis for the disparate neuroprotective effects of the anthocyanins, callistephin and kuromanin, against nitrosative stress

Chemical basis for the disparate neuroprotective effects of the anthocyanins, callistephin and kuromanin, against nitrosative stress

  • Free Radic Biol Med. 2017 Feb:103:23-34. doi: 10.1016/j.freeradbiomed.2016.12.012.
Aimee N Winter 1,  Erika K Ross 1,  Sonia Khatter 1,  Keith Miller 2,  Daniel A Linseman 3
Affiliations

Affiliations

  • 1 Department of Biological Sciences, University of Denver, Denver CO 80208, United States.
  • 2 Department of Chemistry and Biochemistry, University of Denver, Denver CO 80208, United States.
  • 3 Department of Biological Sciences, University of Denver, Denver CO 80208, United States; Eleanor Roosevelt Institute, University of Denver, Denver CO 80208, United States; Knoebel Institute for Healthy Aging, University of Denver, Denver CO 80208, United States. Electronic address: [email protected].
PMID: 27986528 DOI: 10.1016/j.freeradbiomed.2016.12.012
Abstract

Oxidative and nitrosative stress are major factors in neuronal cell death underlying neurodegenerative disease. Thus, supplementation of antioxidant defenses may be an effective therapeutic strategy for diseases such as amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease. In this regard, treatment with nutraceutical antioxidants has garnered increasing attention; however, the differential neuroprotective effects of structurally similar nutraceuticals, which may affect their suitability as therapeutic agents, has not been directly examined. In this study we compare the ability of two anthocyanins, callistephin (pelargonidin-3-O-glucoside) and kuromanin (cyanidin-3-O-glucoside) to protect cerebellar granule neurons from damage induced by either oxidative or nitrosative stress. These anthocyanins differ by the presence of a single hydroxyl group on the B-ring of kuromanin, forming a catechol moiety. While both compounds protected neurons from oxidative stress induced by glutamate excitotoxicity, a stark contrast was observed under conditions of nitrosative stress. Only kuromanin displayed the capacity to defend neurons from nitric oxide (NO)-induced Apoptosis. This protective effect was blocked by addition of Cu, Zn-superoxide dismutase, indicating that the neuroprotective mechanism is superoxide dependent. Based on these observations, we suggest a unique mechanism by which slight structural variances, specifically the absence or presence of a catechol moiety, lend kuromanin the unique ability to generate superoxide, which acts as a scavenger of NO. These findings indicate that kuromanin and compounds that share similar chemical characteristics may be more effective therapeutic agents for treating neurodegenerative diseases than callistephin and related (non-catechol) compounds.

Keywords

Anthocyanins; Excitotoxicity; Neurodegeneration; Neuroprotection; Nitric Oxide; Nitrosative stress.

Figures
Products