Antidepressant-like and neuroprotective effects of pine needle extracts: evidence from behavioral, transcriptomic, and biochemical studies

Authors

  • Hisako Iwahashi Ogawa Degree Programs in Life and Earth Sciences, Graduate School of Science and Technology, University of Tsukuba, Tsukuba, Ibaraki, 305-8572, Japan; Arakawa Chemical Industries, Ltd.,1-3-7, Hiranomachi, Chuo-ku, Osaka,541-0046, Japan https://orcid.org/0009-0007-7611-330X
  • Eiji Yasaka Arakawa Chemical Industries, Ltd.,1-3-7, Hiranomachi, Chuo-ku, Osaka, 541-0046, Japan https://orcid.org/0009-0004-8222-1938
  • Shinji Kondo Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba, Ibaraki 305-8572 Japan https://orcid.org/0000-0002-9097-6394
  • Farhana Ferdousi Degree Programs in Life and Earth Sciences, Graduate School of Science and Technology, University of Tsukuba, Tsukuba, Ibaraki, 305-8572, Japan; Institute of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan; Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba, Ibaraki 305-8572 Japan https://orcid.org/0000-0003-2816-9118
  • Nakajima Mitsutoshi Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba, Ibaraki 305-8572 Japan; Open Innovation Laboratory for Food and Medicinal Resource Engineering (FoodMed-OIL), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, 305-0821, Japan; MED R&D Co. Ltd., Tsukuba, Ibaraki, 305-8572, Japan https://orcid.org/0000-0002-3453-2481
  • Hiroko Isoda Institute of Life and Environmental Sciences, University of Tsukuba, Japan1-1-1 Tennodai, Tsukuba City, Ibaraki 305-8572, Japan. E-mail: isoda.hiroko.ga@u.tsukuba.ac.jp; Degree Programs in Life and Earth Sciences, Graduate School of Science and Technology, University of Tsukuba, Tsukuba, Ibaraki, 305-8572, Japan; Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba, Ibaraki 305-8572 Japan; Open Innovation Laboratory for Food and Medicinal Resource Engineering (FoodMed-OIL), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, 305-0821, Japan; MED R&D Co. Ltd., Tsukuba, Ibaraki, 305-8572, Japan https://orcid.org/0000-0002-1399-9541

DOI:

https://doi.org/10.17179/excli2025-8720

Keywords:

depression, transcriptomics, neuroinflammation, tail suspension test, neuroprotection, apelin

Abstract

Neuroinflammation is a key characteristic associated with neurological disorders, particularly depression and anxiety. This study aims to evaluate the neuroprotective and antidepressant-like effects of pine needle (PN) extracts in an LPS-induced neuroinflammation mouse model. Following seven days of oral administration of PN, the tail suspension test demonstrated a significant reduction in immobility time in PN-treated mice compared to LPS controls, surpassing the effect of the standard antidepressant bupropion. To elucidate the underlying mechanisms, we conducted a whole-genome microarray analysis. This analysis highlighted pathways related to neuroprotection, synaptic plasticity, and pro-inflammatory cytokine regulation, with a notable enrichment in the Apelin signaling pathway. Quantitative PCR analysis revealed that PN treatment increased the levels of Apelin and its receptor while decreasing proinflammatory cytokines Tnfa and IL1b in the hippocampus. ELISA further demonstrated elevated levels of key neurotransmitters, including dopamine and noradrenaline, in the mouse hippocampus. Additionally, we performed GC/MS analysis to identify bioactive compounds in PN, revealing D-Pinitol and Shikimic acid as major constituents. Importantly, catechol exhibited significant neuroprotective effects, and similar protective effects were also noted in the mixed compositions. The MTT assay showed that PN and its compounds significantly improved cell metabolic activity against dexamethasone-induced cytotoxicity. In conclusion, our findings highlight the potential of PN as a natural therapeutic agent for depressive symptoms, promoting neuroprotection, enhancing neurotransmitter levels, and modulating inflammatory responses.

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Published

2025-10-17

How to Cite

Iwahashi Ogawa, H., Yasaka, E., Kondo, S., Ferdousi, F., Mitsutoshi, N., & Isoda, H. (2025). Antidepressant-like and neuroprotective effects of pine needle extracts: evidence from behavioral, transcriptomic, and biochemical studies. EXCLI Journal, 24, 1372–1396. https://doi.org/10.17179/excli2025-8720

Issue

Vol. 24 (2025)

Section

Original articles

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Copyright (c) 2025 Hisako Iwahashi Ogawa, Eiji Yasaka, Shinji Kondo, Farhana Ferdousi, Nakajima Mitsutoshi, Hiroko Isoda

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