Royal jelly fermented by honeybee queen (Apis mellifera)-derived Lactobacillus panisapium M1 enhances macrophage phagocytosis through the TLR2/MAPK/SR signaling pathway
Abstract Background Royal jelly (RJ) has traditionally been used to maintain health, and its fatty acids (10-hydroxy decanoic acid and 10-hydroxy-2-decenoic acid) are reported to have immunomodulatory effects. We recently developed fermented RJ (fRJ) by fermenting RJ with honeybee queen (Apis mellif...
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BMC
2025-07-01
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| Series: | BMC Complementary Medicine and Therapies |
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| Online Access: | https://doi.org/10.1186/s12906-025-04976-x |
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| author | Shuhei Nonobe Hideto Okamoto Takashi Ito Hayate Itatani Ayanori Yamaki Nobuaki Okumura |
| author_facet | Shuhei Nonobe Hideto Okamoto Takashi Ito Hayate Itatani Ayanori Yamaki Nobuaki Okumura |
| author_sort | Shuhei Nonobe |
| collection | DOAJ |
| description | Abstract Background Royal jelly (RJ) has traditionally been used to maintain health, and its fatty acids (10-hydroxy decanoic acid and 10-hydroxy-2-decenoic acid) are reported to have immunomodulatory effects. We recently developed fermented RJ (fRJ) by fermenting RJ with honeybee queen (Apis mellifera)-derived lactic acid bacterium, Lactobacillus panisapium M1. fRJ increased the 10-hydroxy decanoic acid content five-fold and facilitated macrophage phagocytosis. In this study, we explored the components involved in the fRJ-induced enhancement of macrophage phagocytosis and assessed the biological mechanisms of these components. Methods The effects of fRJ on the phagocytosis of negatively charged carboxylate-modified latex beads, zymosan, IgG-coated beads, and apoptotic cells, Toll-like receptor 2 (TLR2) and phagocytic receptor expression, and p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) phosphorylation were assessed in the murine macrophage cell line J774.1. To explore the mechanisms of fRJ-induced macrophage phagocytosis, we used TLR2, mitogen-activated protein kinases (MAPKs), cluster of differentiation 36 (CD36), scavenger receptor inhibitors, and small interfering RNA. Phagocytosis was assessed using fluorescence microscopy or flow cytometry, whereas mRNA, protein, and cell surface antigen expression was assessed using quantitative polymerase chain reaction, western blotting, and flow cytometry, respectively. Results fRJ enhanced macrophage phagocytosis of carboxylate-modified latex beads and apoptotic cells. Additionally, L. panisapium M1 enhanced macrophage phagocytosis. Moreover, the assessment of lactic acid bacteria-mediated signaling pathways revealed that fRJ enhanced TLR2 expression, promoted p38 and JNK phosphorylation, and facilitated activator protein-1 nuclear translocation. However, fRJ-induced macrophage phagocytosis was reduced by the presence of inhibitors targeting TLR2, p38, and JNK. fRJ facilitated the gene expression of scavenger receptors, including Msr1 and Cd36, and this upregulation was suppressed by TLR2 inhibition. Surprisingly, fRJ-induced augmentation of macrophage phagocytosis was not suppressed by CD36 inhibition. However, it was significantly attenuated by the broad-spectrum scavenger receptor inhibitor polyinosinic acid. Conclusions The results indicate that fRJ enhances macrophage phagocytosis through TLR2/MAPK/SR, and L. panisapium M1 primarily contributes to immune function. |
| format | Article |
| id | doaj-art-bd9a9ff7f75c4f5795e6cdbe33e6f57f |
| institution | Kabale University |
| issn | 2662-7671 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Complementary Medicine and Therapies |
| spelling | doaj-art-bd9a9ff7f75c4f5795e6cdbe33e6f57f2025-08-20T03:37:23ZengBMCBMC Complementary Medicine and Therapies2662-76712025-07-0125111210.1186/s12906-025-04976-xRoyal jelly fermented by honeybee queen (Apis mellifera)-derived Lactobacillus panisapium M1 enhances macrophage phagocytosis through the TLR2/MAPK/SR signaling pathwayShuhei Nonobe0Hideto Okamoto1Takashi Ito2Hayate Itatani3Ayanori Yamaki4Nobuaki Okumura5Institute for Bee Products & Health Science, Yamada Bee Company, IncInstitute for Bee Products & Health Science, Yamada Bee Company, IncInstitute for Bee Products & Health Science, Yamada Bee Company, IncInstitute for Bee Products & Health Science, Yamada Bee Company, IncInstitute for Bee Products & Health Science, Yamada Bee Company, IncInstitute for Bee Products & Health Science, Yamada Bee Company, IncAbstract Background Royal jelly (RJ) has traditionally been used to maintain health, and its fatty acids (10-hydroxy decanoic acid and 10-hydroxy-2-decenoic acid) are reported to have immunomodulatory effects. We recently developed fermented RJ (fRJ) by fermenting RJ with honeybee queen (Apis mellifera)-derived lactic acid bacterium, Lactobacillus panisapium M1. fRJ increased the 10-hydroxy decanoic acid content five-fold and facilitated macrophage phagocytosis. In this study, we explored the components involved in the fRJ-induced enhancement of macrophage phagocytosis and assessed the biological mechanisms of these components. Methods The effects of fRJ on the phagocytosis of negatively charged carboxylate-modified latex beads, zymosan, IgG-coated beads, and apoptotic cells, Toll-like receptor 2 (TLR2) and phagocytic receptor expression, and p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) phosphorylation were assessed in the murine macrophage cell line J774.1. To explore the mechanisms of fRJ-induced macrophage phagocytosis, we used TLR2, mitogen-activated protein kinases (MAPKs), cluster of differentiation 36 (CD36), scavenger receptor inhibitors, and small interfering RNA. Phagocytosis was assessed using fluorescence microscopy or flow cytometry, whereas mRNA, protein, and cell surface antigen expression was assessed using quantitative polymerase chain reaction, western blotting, and flow cytometry, respectively. Results fRJ enhanced macrophage phagocytosis of carboxylate-modified latex beads and apoptotic cells. Additionally, L. panisapium M1 enhanced macrophage phagocytosis. Moreover, the assessment of lactic acid bacteria-mediated signaling pathways revealed that fRJ enhanced TLR2 expression, promoted p38 and JNK phosphorylation, and facilitated activator protein-1 nuclear translocation. However, fRJ-induced macrophage phagocytosis was reduced by the presence of inhibitors targeting TLR2, p38, and JNK. fRJ facilitated the gene expression of scavenger receptors, including Msr1 and Cd36, and this upregulation was suppressed by TLR2 inhibition. Surprisingly, fRJ-induced augmentation of macrophage phagocytosis was not suppressed by CD36 inhibition. However, it was significantly attenuated by the broad-spectrum scavenger receptor inhibitor polyinosinic acid. Conclusions The results indicate that fRJ enhances macrophage phagocytosis through TLR2/MAPK/SR, and L. panisapium M1 primarily contributes to immune function.https://doi.org/10.1186/s12906-025-04976-xRoyal Jelly (RJ)Fermented RJ (fRJ)Macrophage phagocytosisLactic acid bacteriumLactobacillus panisapium M1Phagocytic receptors |
| spellingShingle | Shuhei Nonobe Hideto Okamoto Takashi Ito Hayate Itatani Ayanori Yamaki Nobuaki Okumura Royal jelly fermented by honeybee queen (Apis mellifera)-derived Lactobacillus panisapium M1 enhances macrophage phagocytosis through the TLR2/MAPK/SR signaling pathway BMC Complementary Medicine and Therapies Royal Jelly (RJ) Fermented RJ (fRJ) Macrophage phagocytosis Lactic acid bacterium Lactobacillus panisapium M1 Phagocytic receptors |
| title | Royal jelly fermented by honeybee queen (Apis mellifera)-derived Lactobacillus panisapium M1 enhances macrophage phagocytosis through the TLR2/MAPK/SR signaling pathway |
| title_full | Royal jelly fermented by honeybee queen (Apis mellifera)-derived Lactobacillus panisapium M1 enhances macrophage phagocytosis through the TLR2/MAPK/SR signaling pathway |
| title_fullStr | Royal jelly fermented by honeybee queen (Apis mellifera)-derived Lactobacillus panisapium M1 enhances macrophage phagocytosis through the TLR2/MAPK/SR signaling pathway |
| title_full_unstemmed | Royal jelly fermented by honeybee queen (Apis mellifera)-derived Lactobacillus panisapium M1 enhances macrophage phagocytosis through the TLR2/MAPK/SR signaling pathway |
| title_short | Royal jelly fermented by honeybee queen (Apis mellifera)-derived Lactobacillus panisapium M1 enhances macrophage phagocytosis through the TLR2/MAPK/SR signaling pathway |
| title_sort | royal jelly fermented by honeybee queen apis mellifera derived lactobacillus panisapium m1 enhances macrophage phagocytosis through the tlr2 mapk sr signaling pathway |
| topic | Royal Jelly (RJ) Fermented RJ (fRJ) Macrophage phagocytosis Lactic acid bacterium Lactobacillus panisapium M1 Phagocytic receptors |
| url | https://doi.org/10.1186/s12906-025-04976-x |
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