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Anti‑neuroinflammatory potential of porcine liver decomposition products in improving behavioral abnormalities: Effects on formalin‑ and LPS‑induced inflammation

  • Authors:
    • Ikuya Sato
    • Tomoji Maeda
    • So Katsuyama
    • Takahiro Kawase
    • Teppei Kaku
    • Toru Takahashi
    • Hisao Haniu
    • Tamotsu Tsukahara
    • Takamitsu Tsukahara
    • Yoshikazu Matsuda
  • View Affiliations / Copyright

    Affiliations: Division of Clinical Pharmacology, Graduate School of Pharmaceutical Science, Nihon Pharmaceutical University, Saitama 362‑0806, Japan, Kyoto Institute of Nutrition and Pathology, Kyoto 610‑0231, Japan, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Matsumoto 390‑8621, Japan, SLC Pharmaceuticals Co., Ltd., Tokyo 107‑6011, Japan
    Copyright: © Sato et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 154
    |
    Published online on: July 18, 2025
       https://doi.org/10.3892/br.2025.2032
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Abstract

Porcine liver decomposition product (PLDP) is a functional food that enhances delayed memory recall and frontal lobe function in humans and exerts antidepressant and anxiolytic effects. In the present study, the previously unexplored anti‑inflammatory effects of PLDP were investigated both in vitro and in vivo. The effects of PLDP on interleukin (IL)‑1β production were examined in lipopolysaccharide (LPS)‑stimulated Raw 264.7 cells and on their transition to an M1 or M2 phenotype. The effects of PLDP administered 30 min before the initiation of a formalin‑induced inflammation‑related behavior were also evaluated. Furthermore, the effects of PLDP on LPS‑induced inflammation related to cytokine production and behavior in vivo were examined. PLDP was orally administered for five consecutive days and 24 h after LPS administration the mice were evaluated in an open field test and plasma cytokine production was measured. PLDP and its lipid fraction, PLDP extracted lipids (PEL) suppressed LPS‑induced IL‑1β production. Flow cytometry revealed that PEL shifted Raw 264.7 cells to the M2 phenotype. Moreover, PEL reduced phase 2 inflammation‑related behavior in formalin‑induced inflammation. In the LPS‑induced inflammation model, PLDP improved the LPS‑attenuated locomotor activity and exploratory behavior and reduced the increased plasma interferon‑γ levels. These results suggest that PLDP exerts anti‑inflammatory effects and shifts macrophages to the M2 phenotype. Furthermore, our results indicate that the lipid components in PLDP, especially phospholipids, could exert considerable central neuroprotective effects.
View Figures

Figure 1

Effects of PLDP and its lipid fraction
PEL on (IL)-1β production in LPS-stimulated Raw 264.7 cells. IL-1β
production induced by LPS stimulation (100 ng/ml) was inhibited by
~95% when PLDP was diluted 1,000-fold from the original solution
and by ~93% when PEL was used at a concentration of 25 µg/ml. Data
are expressed as the mean ± S.E (n=3/group); Cont=LPS; PLDP=PLDP +
LPS (P=0.01); PEL=PEL + LPS (P=0.01). PLDP, porcine liver
decomposition product; PEL, PLDP extracted lipids; IL, interleukin;
LPS, lipopolysaccharide.

Figure 2

PEL activates macrophages and induces
the M2 phenotype. Total phospholipids (PEL) were extracted from
PLDP using the Bligh and Dyer method. Data are expressed as the
mean ± SE (n=3); Control=LPS (100 ng/ml); PEL=PEL (25 µg/ml) + LPS
(100 ng/ml). PLDP, porcine liver decomposition product; PEL, PLDP
extracted lipids; LPS, lipopolysaccharide.

Figure 3

PLDP significantly reduces pain
behaviors during the secondary reaction time in a formalin-induced
acute pain model. PLDP was administered into the footpads of mice
30 min before the irritant formalin was administered. Data are
expressed as the mean ± SE (n=7). PLDP, porcine liver decomposition
product.

Figure 4

Percentage change from day-one
baseline in the mean total distance traveled, number of exploratory
behaviors, number of central entries, and time spent in the central
zone on the second day of the OFT in the LPS-induced inflammation
model. PLDP or saline were orally administered daily for 5 days
prior to LPS administration. The LPS group received saline + LPS,
and the PLDP group received PLDP + LPS. Data are expressed as the
mean ± SE (n=8). OFT, open field test; LPS, lipopolysaccharide;
PLDP, porcine liver decomposition product.

Figure 5

Percentage change from day-one
baseline in plasma cytokine levels on the second day of the
LPS-induced inflammation model. PLDP and saline were orally
administered daily for 5 days prior to LPS administration. The LPS
group received saline + LPS, and the PLDP group received PLDP +
LPS. Data are expressed as the mean ± SE (n=8). LPS,
lipopolysaccharide; PLDP, porcine liver decomposition product.
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Copy and paste a formatted citation
Spandidos Publications style
Sato I, Maeda T, Katsuyama S, Kawase T, Kaku T, Takahashi T, Haniu H, Tsukahara T, Tsukahara T, Matsuda Y, Matsuda Y, et al: Anti‑neuroinflammatory potential of porcine liver decomposition products in improving behavioral abnormalities: Effects on formalin‑ and LPS‑induced inflammation. Biomed Rep 23: 154, 2025.
APA
Sato, I., Maeda, T., Katsuyama, S., Kawase, T., Kaku, T., Takahashi, T. ... Matsuda, Y. (2025). Anti‑neuroinflammatory potential of porcine liver decomposition products in improving behavioral abnormalities: Effects on formalin‑ and LPS‑induced inflammation. Biomedical Reports, 23, 154. https://doi.org/10.3892/br.2025.2032
MLA
Sato, I., Maeda, T., Katsuyama, S., Kawase, T., Kaku, T., Takahashi, T., Haniu, H., Tsukahara, T., Tsukahara, T., Matsuda, Y."Anti‑neuroinflammatory potential of porcine liver decomposition products in improving behavioral abnormalities: Effects on formalin‑ and LPS‑induced inflammation". Biomedical Reports 23.3 (2025): 154.
Chicago
Sato, I., Maeda, T., Katsuyama, S., Kawase, T., Kaku, T., Takahashi, T., Haniu, H., Tsukahara, T., Tsukahara, T., Matsuda, Y."Anti‑neuroinflammatory potential of porcine liver decomposition products in improving behavioral abnormalities: Effects on formalin‑ and LPS‑induced inflammation". Biomedical Reports 23, no. 3 (2025): 154. https://doi.org/10.3892/br.2025.2032
Copy and paste a formatted citation
x
Spandidos Publications style
Sato I, Maeda T, Katsuyama S, Kawase T, Kaku T, Takahashi T, Haniu H, Tsukahara T, Tsukahara T, Matsuda Y, Matsuda Y, et al: Anti‑neuroinflammatory potential of porcine liver decomposition products in improving behavioral abnormalities: Effects on formalin‑ and LPS‑induced inflammation. Biomed Rep 23: 154, 2025.
APA
Sato, I., Maeda, T., Katsuyama, S., Kawase, T., Kaku, T., Takahashi, T. ... Matsuda, Y. (2025). Anti‑neuroinflammatory potential of porcine liver decomposition products in improving behavioral abnormalities: Effects on formalin‑ and LPS‑induced inflammation. Biomedical Reports, 23, 154. https://doi.org/10.3892/br.2025.2032
MLA
Sato, I., Maeda, T., Katsuyama, S., Kawase, T., Kaku, T., Takahashi, T., Haniu, H., Tsukahara, T., Tsukahara, T., Matsuda, Y."Anti‑neuroinflammatory potential of porcine liver decomposition products in improving behavioral abnormalities: Effects on formalin‑ and LPS‑induced inflammation". Biomedical Reports 23.3 (2025): 154.
Chicago
Sato, I., Maeda, T., Katsuyama, S., Kawase, T., Kaku, T., Takahashi, T., Haniu, H., Tsukahara, T., Tsukahara, T., Matsuda, Y."Anti‑neuroinflammatory potential of porcine liver decomposition products in improving behavioral abnormalities: Effects on formalin‑ and LPS‑induced inflammation". Biomedical Reports 23, no. 3 (2025): 154. https://doi.org/10.3892/br.2025.2032
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