Neurological Effects of Cleistocalyx nervosum var. paniala Berry on Hippocampal Transcriptome, Neuritogenesis, and Synaptogenesis
1
Issued Date
2026-04-10
Resource Type
eISSN
20726643
Scopus ID
2-s2.0-105038125902
Pubmed ID
42075012
Journal Title
Nutrients
Volume
18
Issue
8
Rights Holder(s)
SCOPUS
Bibliographic Citation
Nutrients Vol.18 No.8 (2026)
Suggested Citation
Kanlayaprasit S., Parnich W., Jantheang T., Lertpeerapan P., Panjabud P., Kasitipradit K., Poolcharoen C., Saeliw T., Muangnoi C., Plaingam W., Charoenkiatkul S., Hu V.W., Tencomnao T., Sarachana T., Sukprasansap M. Neurological Effects of Cleistocalyx nervosum var. paniala Berry on Hippocampal Transcriptome, Neuritogenesis, and Synaptogenesis. Nutrients Vol.18 No.8 (2026). doi:10.3390/nu18081200 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/116766
Title
Neurological Effects of Cleistocalyx nervosum var. paniala Berry on Hippocampal Transcriptome, Neuritogenesis, and Synaptogenesis
Corresponding Author(s)
Other Contributor(s)
Abstract
Background/Objectives: Neuritogenesis and synaptogenesis support learning and cognitive function, and hippocampal neurons play central roles in these processes. Cleistocalyx nervosum var. paniala (CNP), a Southeast Asian berry, has reported neuroprotective activities, but its direct effects on hippocampal neurons remain unclear. We investigated whether CNP extract modulates hippocampal neuronal transcriptomes, neuritogenesis, and synaptogenesis. Methods: Primary hippocampal neurons isolated from male and female Wistar rat pups were treated with CNP extract in vitro. Cytotoxicity was assessed to define non-cytotoxic concentrations. Transcriptomic responses were profiled by RNA sequencing and validated by RT-qPCR. Neuritogenesis was quantified by neurite morphology and Sholl analysis. Synaptogenesis was evaluated by synaptic immunocytochemistry. Molecular docking of cyanidin-3-glucoside (C3G) and resveratrol was used to generate mechanistic hypotheses. Results: At 0.1-10 µg/mL, CNP was non-cytotoxic, whereas a 100 µg/mL dose reduced viability; therefore, 10 µg/mL was used in subsequent experiments. Exploratory RNA-seq profiling identified thousands of differentially expressed genes enriched in synapse- and neurite-related pathways, including synaptogenesis signaling, axon guidance, and neuritogenesis. RT-qPCR showed upregulation of Igf1 in males and Glul in females, with sex-dependent modulation of Bdnf and Cask. CNP increased neurite length, branching, and Sholl complexity in both sexes, with a more pronounced effect in males. A male-biased effect was also observed in synapse-related marker colocalization, with increased Syn1-Psd95 colocalization detected in males. Docking suggested plausible interactions of C3G and resveratrol with regulators such as MYC, TP53, and CREB1. Conclusions: CNP extract alters transcriptional networks and enhances neurite outgrowth in primary hippocampal neurons in a sex-dependent manner, with male-biased effects on Syn1-Psd95 colocalization. These findings support further dose-response, mechanistic, and sex-stratified in vivo studies to evaluate its neurobiological potential.