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Inhibitory effect of parthenolide on peripheral nerve degeneration

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Abstract

Traumatic axonal damage disrupts connections between neurons, leading to the loss of motor and sensory functions. Although damaged peripheral nerves can regenerate, recovery depends on the variety and severity of nerve damage. Thus, many phytochemicals have been studied for their ability to reduce peripheral nerve degeneration, and among them, Parthenolide (PTL), which is extracted from Feverfew has effects against production of free radicals, inflammation, and apoptosis. Thus, we conducted a study to investigate whether PTL has an inhibitory effect on peripheral nerve degeneration during peripheral nerve damage. To verify the effect of PTL on peripheral nerve degeneration process, a morphological comparison of peripheral nerves with and without PTL was performed. PTL significantly reduced the quantity of fragmented ovoid formations at 3DIV (days in vitro). Immunostaining for MBP revealed that the ratio of intact myelin sheaths increased significantly in sciatic nerve with PTL compared with absence of PTL at 3DIV. Furthermore, nerve fibers in the presence of PTL maintained the continuity of Neurofilament (NF) compared to those without at 3DIV. Immunostaining for LAMP1 and p75 NTR showed that the expression of LAMP1 and p75 NTR decreased in the nerve after PTL addition at 3DIV. Lastly, immunostaining for anti-Ki67 revealed that PTL inhibited Ki67 expression at 3DIV compared to without PTL. These results confirm that PTL inhibits peripheral nerve degenerative processes. PTL may be a good applicant to inhibit peripheral nerve degeneration. Our study examined the effect of Parthenolide in preventing degeneration of peripheral nerves by inhibiting the breakdown of peripheral axons and myelin, also inhibiting Schwann cell trans-dedifferentiation and proliferation.

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Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NO. 2022R1F1A1072918)

Institutional Review Board Statement

The animal study protocol was approved by the Institutional Review Board of Kyung Hee University Medical Center Medical Science Research Institute Animal Laboratory (KHMC-IACUC 2021-108).

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Authors and Affiliations

  1. Department of Otorhinolaryngology, Head and Neck Surgery, Kyung Hee University School of Medicine, Kyung Hee University Medical Center, Seoul, 02447, Korea

    Jung Min Kim, Seung Geun Yeo & Sang Hoon Kim

  2. Clinical Research Institute, Kyung Hee Medical Center, Seou, 02447, Korea

    Jae Sun Choi

  3. Department of Anatomy and Neurobiology, College of Medicines, Kyung Hee University, Seoul, 02447, Korea

    Junyang Jung

  4. Department of Otohinolaryngology - H & N Surgery, School of Medicine, KyungHee University, #1 Hoegi-Dong, Dongdaemun-Gu, Seoul, 130-702, Korea

    Sang Hoon Kim

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  1. Jung Min Kim
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Contributions

Conceptualization, SHK; methodology,JSC; software, JSC; validation, SGY; formal analysis, JSC; investigation, JJ; resources, JMK; data curation, JSC; writing—original draft preparation, JMK; writing—review and editing, SHK; visualization, JSC; supervision, JJ and SGY; project administration, SHK; funding acquisition, SHK All authors have read and agreed to the published version of the manuscript.

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Correspondence to Sang Hoon Kim.

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Kim, J.M., Choi, J.S., Jung, J. et al. Inhibitory effect of parthenolide on peripheral nerve degeneration. Anat Sci Int 98, 529–539 (2023). https://doi.org/10.1007/s12565-023-00718-6

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