Ethyl acetate extract of Gastrodia elata protects Caenorhabditis elegans from oxidative stress and amyloid β peptide toxicity

Abstract

Gastrodia elata Blume is a traditional Chinese medicine with a long history, which has numerous pharmacological activities, such as anti-inflammation, anti-oxidation and protection of nerves. The present study investigated the regulatory effect of ethyl acetate extract of Gastrodia elata (EEGE) on the β-amyloid (Aβ) toxicity of Caenorhabditis elegans (C. elegans). First, the main components of EEGE were analyzed using high-performance liquid chromatography, and the total phenols, total flavonoids and total antioxidant capacity of EEGE were determined. Next, the regulation effect of EEGE on Aβ-induced toxicity of C. elegans was evaluated through experiments on nematode paralysis, lifespan, oxidative and heat stress, locomotor ability, reproductive ability, reactive oxygen species (ROS) level, Aβ aggregation test, malondialdehyde (MDA) level, catalase (CAT) activity and superoxide dismutase (SOD) activity. Finally, the mechanism of EEGE was elucidated using RNA sequencing (RNA-Seq) and the expression levels of related genes were verified using quantitative PCR. The present study revealed that the main components of EEGE included phosphorylated (p)-hydroxybenzyl alcohol, p-hydroxybenzaldehyde and 4,4'-dihydroxydiphenylmethane, possessing strong in vitro free radical scavenging and reducing abilities. In addition, after the intervention of EEGE, the paralysis of nematodes could be delayed, the survival time of the nematodes was prolonged, the survival rate of the nematodes under stress (high temperature and oxidation) conditions was improved, the activity capacity and reproductive capacity of the nematodes were improved, the activities of SOD and CAT were improved and the levels of ROS and MDA were reduced. Notably, EEGE directly inhibited Aβ plaque aggregation in nematodes. RNA-Seq analysis showed that EEGE regulated metabolism and longevity-related genes, and these genes were regulated by the insulin/IGF-1 signaling (IIS) pathway. Therefore, the present study hypothesized that the regulatory mechanism of EEGE was significantly related to the IIS pathway. The present research results demonstrated that the protective effect of EEGE on transgenic C. elegans was to reduce Aβ protein aggregation, improve the in vivo antioxidant level, effectively remove free radicals and to regulate the expression of genes related to IIS pathway, thereby reducing Aβ-induced toxicity and delaying nematode paralysis.

P-hydroxybenzaldehyde protects Caenorhabditis elegans from oxidative stress and β-amyloid toxicity

“…In our previous study, we found that the EEGE site had the best anti-AD activity of Gastrodia elata , and had good ex vivo and in vivo antioxidant activity, as well as anti-Aβ toxicity, which could improve the symptoms of the C. elegans AD model. The drug could modulate the insulin pathway of Caenorhabditis elegans , indicating that it could be used in the treatment of neurodegenerative disorders, such as AD ( Shi X. et al, 2023 ). Meanwhile, we isolated p -hydroxy benzaldehyde ( p -HBA), the main active ingredient with a relatively high content, from the EEGE site, as one of the main phenolic components of Gastrodia elata , which has been shown in modern studies to have neurorestorative effect on the peri-infarct cortical microenvironment after cerebral ischemia and reperfusion in rats ( Yuan et al, 2022 ).…”

4,4′-methylenediphenol reduces Aβ-induced toxicity in a Caenorhabditis elegans model of Alzheimer’s disease

“…Additionally, Gastrodia elata has greater efficacy and is more widely used than other TCMs with similar effects (e.g., Ginseng , Astragalus membranaceus ), and has recently been applied for the treatment of AD and other related diseases in the clinic ( Lu et al, 2023 ). Meanwhile, studies have shown that the ethyl acetate extract of Gastrodia elata (EEGE) has both neuroprotective and cerebral protective effect, and can improve the symptoms of AD in a nematode model of the condition by mitigating Aβ toxicity and oxidative stress ( Shi et al, 2023b ). In our preliminary study, we isolated a major component of EEGE, 4,4′-methylenediphenol, which is a bisphenol derivative with antioxidant activity ( Yi-Ming et al, 1993 ; Tang et al, 2016 ).…”