Cleistocalyx nervosum var. paniala seed extracts exhibit sigma-1 antagonist sensitive neuroprotective effects in PC12 cells and protect C. elegans from stress via the SKN-1/NRF-2 pathway

Abstract

BACKGROUND: Cleistocalyx nervosum var. paniala (C. nervosum) is a plant that produces berries that are popular as a health food in Thailand. In previous studies we have identified C. nervosum fruit extracts to have anti-aging and anti-stress properties in C.elegans OBJECTIVE: Evaluate the neuroprotective properties of C. nervosum seed extracts and investigate the mechanisms behind their neuroprotective properties. METHODS: PC-12 cells were differentiated using NGF and treated with amyloid-β (Aβ) (25–35) creating a model of neurodegeneration, in which C. nervosum seed extracts were tested for neuroprotective properties. Cell viability was measured after 24 hours of using the MTT assay. We also measured the lifespan and “health span” of various C.elegans mutants and the wild type. RESULTS: C. nervosum seed extract protects PC12 cells from Aβ (25–35) toxicity, as well as potentiating NGF induced neurite outgrowth in the same cell line potentially under the control of the sigma-1 receptor. C. nervosum seed extracts have anti-aging properties in C. elegans, causing a significant increase in lifespan of Aβ expressing C. elegans and wild type worms. This appears to be regulated by SKN-1/NRF-2, possibly via the sigma-1 receptor. The DAF-16 pathway is also involved in the lifespan extension of C. elegans. CONCLUSIONS: C. nervousum has been often used as a functional food. We have shown its neuroprotective properties which are sensitive to sigma-1 receptor antagonism in PC12 cells, and involve the SKN-1/NRF-2 and DAF-16 pathway in C.elegans. Further research into the active compounds may lead to future drugs for preventing or treating neurodegenerative disease.

DAF-16 and SKN-1 mediate Anti-aging and Neuroprotective efficacies of “thai ginseng” Kaempferia parviflora Rhizome extract in Caenorhabditis elegans

“…The obtained images were processed using Image J and fluorescence intensity was denoted in arbitrary units (AU) [13].…”

“…C. elegans have been used to study the antiaging, stress resistance and neuroprotective effects of various traditional medicinal plants including, Cleistocalyx nervosum [13,14], Lignosus rhinoceros [15], Bacopa monnieri [16], Caesalpinia mimosoides [17] and Diplocyclos palmatus [18]. In the present study, the anti-aging and neuroprotective effects of KP and its active constituent DMF has been analyzed using C. elegans model.…”

Effect of Thai medicinal plants Acanthus ebracteatus Vahl. Carthamus tinctorius L. and Streblus asper Lour. on neurite outgrowth activity in Neuro-2A cells

“…Many studies with herbal extracts have identified increased neurite outgrowth 10 as a potential feature of the herb's neuroprotective properties. 11,12 Thai medicinal herb Streblus asper Lour. (SA) Has previously been shown to protect against photoaging and provide neuroprotection in C.elegans.…”

Anti-neuroinflammatory effects of Cleistocalyx nervosum var. paniala berry-seed extract in BV-2 microglial cells via inhibition of MAPKs/NF-κB signaling pathway

“…Interestingly, the pulp extract of CN also exerted an anti-aging effect by increasing the life span of Caenorhabditis elegans model and neuroprotective effects in glutamate-induced oxidative stress in mouse hippocampal cell line (HT-22) ( Nantacharoen et al., 2022 ; Prasanth et al., 2019 ; Sukprasansap et al., 2017 ). However, the seed of this fruit, which is classified as a waste by-product of agricultural food production has not yet been investigated for its medicinal properties, despite its neuroprotective effects having been demonstrated ( Brimson et al., 2021 ). Furthermore, resveratrol (RESV), a natural compound found in several berry fruits, is regarded as the NF-κB signaling inhibitor ( Kadri et al., 2019 ; Ma et al., 2015 ; Pap et al., 2021 ).…”