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Promotion of neurite outgrowth by 3,5,7,3ʹ,4ʹ-pentamethoxyflavone is mediated through ERK signaling pathway in Neuro2a cells

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Abstract

In this study, the effects of 3,5,7,3ʹ,4ʹ-pentamethoxyflavone (KP1), a major bioactive ingredient isolated from the Kaempferia parviflora rhizomes, on a neurite outgrowth in Neuro2a cells and its mechanism have been investigated. KP1 increased concentration-dependently the percentage of neurite-bearing cells. KP1 showed a remarkable capability to elicit neurite outgrowth in Neuro2a cells, as evidenced by morphological alterations and immunostaining using anti-class III β-tubulin and anti-NeuN antibodies. KP1 also displayed a higher neurogenic activity than retinoic acid (RA), a promoter of neurite outgrowth in Neuro2a cells. KP1 treatment caused significant elevation in phosphorylation of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38 MAPK) and glycogen synthase kinase-3β (GSK-3β). However, KP1-triggered neurite outgrowth was markedly inhibited by treatment with the ERK inhibitor U0126, whereas p38 MAPK inhibitor SB203580 and GSK-3β inhibitor SB216763 did not influence KP1-induced neurite outgrowth. These results demonstrate that KP1 elicits neurite outgrowth and triggers cell differentiation of Neuro2a cells through ERK signal pathway.

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Acknowledgements

We thank Dr. Hyung-In Moon (SKEDERM Cosmetic R&D Center, Seoul, Republic of Korea) for providing the detailed methods on extraction and purification of KP1 from Kaempferia parviflora rhizomes. This work was supported by the Dong-A University research fund.

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  1. Shin-Ji Park and So-Young An contributed equally to this work.

Authors and Affiliations

  1. Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan, 604-714, South Korea

    Shin-Ji Park, So-Young An, Yeon Jin An, Kyoung-Sook Kim, Hyunju Kim, Jong Hyun Cho & Young-Choon Lee

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Contributions

Conceived and designed the experiments: Shin-Ji Park, So-Young An, Kyoung Sook Kim, Jong Hyun Cho, Young-Choon. Performed the experiments: Shin-Ji Park, So-Young An, Yeon Jin An. Analyzed the data: Shin-Ji Park, So-Young An, Yeon Jin An, Kyoung Sook Kim, Jong Hyun Cho, Young-Choon. Contributed reagents/materials/analysis tools: Kyoung Sook Kim, Hyun-Ju Kim, Jong Hyun Cho. Wrote the paper: Shin-Ji Park, So-Young An, Jong Hyun Cho, Young-Choon Lee.

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Correspondence to Jong Hyun Cho or Young-Choon Lee.

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Park, SJ., An, SY., An, Y.J. et al. Promotion of neurite outgrowth by 3,5,7,3ʹ,4ʹ-pentamethoxyflavone is mediated through ERK signaling pathway in Neuro2a cells. J Nat Med 78, 599–607 (2024). https://doi.org/10.1007/s11418-024-01809-y

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