Sorbus alnifolia protects dopaminergic neurodegeneration in Caenorhabditis elegans

Abstract

ContextThe twigs of Sorbus alnifolia (Sieb. et Zucc.) K. Koch (Rosaceae) have been used to treat neurological disorders as a traditional medicine in Korea. However, there are limited data describing the efficacy of S. alnifolia in Parkinson’s disease (PD).ObjectiveThis study was conducted to identify the protective effects of the methanol extracts of S. alnifolia (MESA) on the dopaminergic (DA) neurodegeneration in Caenorhabditis elegans.Materials and methodsTo test the neuroprotective action of MESA, viability assay was performed after 48 h exposure to 1-methyl-4-phenylpyridine (MMP+) in PC12 cells and C. elegans (400 μM and 2 mM of MMP+, respectively). Fluorescence intensity was quantified using transgenic mutants such as BZ555 (Pdat-1::GFP) and and UA57 (Pdat-1::GFP and Pdat-1::CAT-2) to determine MESA’s effects on DA neurodegeneration in C. elegans. Aggregation of α-synuclein was observed using NL5901 strain (unc-54p::α-synuclein::YFP). MESA’s protective effects on the DA neuronal functions were examined by food-sensing assay. Lifespan assay was conducted to test the effects of MESA on the longevity.ResultsMESA restored MPP+-induced loss of viability in both PC12 cells and C. elegans (85.8% and 54.9%, respectively). In C. elegans, MESA provided protection against chemically and genetically-induced DA neurodegeneration, respectively. Moreover, food-sensing functions were increased 58.4% by MESA in the DA neuron degraded worms. MESA also prolonged the average lifespan by 25.6%. However, MESA failed to alter α-synuclein aggregation.Discussion and conclusionsThese results revealed that MESA protects DA neurodegeneration and recovers diminished DA neuronal functions, thereby can be a valuable candidate for the treatment of PD.

The Sorbus spp.—Underutilised Plants for Foods and Nutraceuticals: Review on Polyphenolic Phytochemicals and Antioxidant Potential

“…It is evident that among phytochemicals and other nutrients, polyphenolic compounds and ascorbic acid may be considered as the most valuable health beneficial constituents, which have been reported in various anatomical parts of Sorbus spp. The polyphenolics, which may influence the colour and flavour, have demonstrated antioxidant [54,81], antidiabetic [11,82] anti-hyperlipidemic [83], anti-inflammatory [84], antimicrobial [85], anticancer [86,87] antiviral [67], antifungal [79], antitumoral [88], anti-periodontal [89], and anti-osteoarthritis [90] effects, as well as vasoprotective [84], neuroprotective [26,91,92], cardioprotective [36], hepatoprotective [7], properties and COX-2 (cyclooxygenase-2) inhibitory [93] activities. Many of these activities are correlated to antioxidant capacity of bioactive compounds, which at cellular level may neutralize excessive reactive oxygen species, and thereby protect important biomolecules in the conditions of oxidative stress, which can cause cellular injury and development of chronic diseases.…”

“…Moreover, methanol extract of S. alnifolia plant increased food-sensing functions in the dopaminergic neuron degraded worms by 58.4% hereby prolonging the average lifespan by 25.6%. Therefore, the extract of S. alnifolia can be a useful candidate for the treatment of Parkinson's disease [26].…”

The Potential Use of Plant Natural Products and Plant Extracts with Antioxidant Properties for the Prevention/Treatment of Neurodegenerative Diseases: In Vitro, In Vivo and Clinical Trials

“…In this study, the MPP + -mediated oxidative damage led to neurotoxicity. The viability of neurons was improved by pre-treatment with the methanol extract of Sorbus alnifolia for 2 h [58]. The same group also studied the effect of the extract in MPP + C. elegans models of PD, which are detailed later.…”

“…In a PD model induced by the treatment of C. elegans with MPP + , the extract of Korean mountain ash ( Sorbus alnifolia ) restored viability of the worms after 30 min pre-treatment prior to MPP + addition. Using the transgenic strain BZ555 ((egIs1, Pdat-1::GFP) expressing GFP in the 8 dopaminergic (DAergic) neuron of hermaphrodite C. elegans , observations also showed that the extract protected DAergic neurons from MPP + (environmental) induced neuronal loss [58]. The same was true for the genetic PD model UA57 (Pdat-1::GFP and Pdat-1::CAT-2), where the overexpression of tyrosine hydroxylase led to DAergic neurodegeneration.…”

“…Further studies into the phenotypical induced behavioral dysfunction induced by MPP + (basal slowing response) demonstrated the extracts’ activity in reducing the phenotypical dysfunction. In addition, the extract increases the overall life span in N2 (wild type) animals [58].…”