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. 2024 Nov 15:19:11941-11956.
doi: 10.2147/IJN.S483091. eCollection 2024.

Therapeutic Potential of Ginger Exosome-Like Nanoparticles for Alleviating Periodontitis-Induced Tissue Damage

Qingpeng Xie #  1   2 , Jiawen Gu #  1   2 , Yujia Sun  3 , Jinjia Hong  1   2 , Jia Wang  1   2 , Na Li  1   2 , Yuan Zhang  1   2 , Meixian Liu  1   2 , Xiaoxuan Zhang  1   2 , Xiangyu Zhao  1   2 , Xiaohang Chen  1   2 , Xing Wang  1   2
Affiliations

Therapeutic Potential of Ginger Exosome-Like Nanoparticles for Alleviating Periodontitis-Induced Tissue Damage

Qingpeng Xie et al. Int J Nanomedicine. .

Abstract

Purpose: Periodontitis is a chronic inflammatory oral disease that causes defects in periodontal tissue. Conventional therapies are limited, and often lead to high recurrence rates. The emerging concept of medicinal food homology has shed light on the potential of ginger as a therapeutic adjuvant for periodontitis, given its antioxidant and anti-inflammatory properties. However, fresh ginger exhibits poor stability and bioavailability. Ginger exosome-like nanoparticles (GELNs), a derivative of ginger, have not been reported to exert therapeutic effects in periodontitis. This study aimed to explore the therapeutic effects of GELNs on tissue damage caused by periodontitis and their underlying mechanisms of action.

Methods: The GELNs composition was analyzed using a widely targeted metabolome. Stability was assessed using nanoparticle tracking analysis (NTA) and zeta potential measurements, flavor was evaluated using an electronic nose, and membrane penetration was studied using confocal microscopy. A periodontitis model was established in SD rats, periodontal clinical indicators were monitored, and histological changes were assessed using H&E and TRAP staining. Co-culture experiments investigate the antioxidant and reparative abilities of GELNs on periodontal ligament fibroblasts (PDLFs) in inflammatory environment. NF-κB protein expression was examined by immunofluorescence and immunohistochemistry.

Results: The findings revealed that GELNs demonstrated good stability in different environments and mitigated the pungent taste of the raw ginger. In vivo experiments showed that GELNs improved periodontal clinical parameters and pathology compared with ginger juice. In vitro data suggested that GELNs enhanced the proliferation and migration of PDLFs while reducing the reactive oxygen species (ROS) levels by inhibiting the NF-κB signaling pathway in an inflammatory setting.

Conclusion: This study is the first to demonstrate that GELNs have a potential therapeutic effect on periodontitis. GELNs can alleviate oxidative stress (OS) and inflammatory reactions by inhibiting the NF-κB signaling pathway. These findings provide a promising method for the treatment of periodontitis by regulating an unbalanced OS state.

Keywords: ginger exosome-like nanoparticles; oxidative stress; periodontal ligament fibroblasts; periodontitis; tissue repair.

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Conflict of interest statement

The authors declare that they have no competing interests in this work.

Figures

None
Graphical abstract
Figure 1
Figure 1
Isolation and characterization of GELNs. (A) Schematic representation of the method used to isolate and purify GELNs from ginger. (B) Transmission electron microscopy of GELNs, bar: 500 nm. (C) Concentration of GELNs determined by NTA measurement. (D) zeta potential of GELNs. (E) Electronic nose technology detect the flavour differences between GELNs and ginger juice. (F) Widely targeted metabolome analysis the compounds contained in GELNs. (G) Stability of GELNs in different pH environments.
Figure 2
Figure 2
Cellular uptake of GELNs. Representative fluorescence microscope images of cellular uptake of GELNs at 1 and 10 μg/mL. Scale bars: 50μm. *, ** and *** indicate difference for p<0.05, p<0.01 and p<0.001 in comparison to the cells treated with cell culture media as negative control, respectively, n=3.
Figure 3
Figure 3
The histological analysis of periodontal tissues in four rat periodontitis models. (A-D) H&E staining of periodontal tissues around the maxillary first molar after 2 weeks treatment of GELNs, scale bar: 500 µm. The I-IV indicate magnification of black rectangle, sacle bar: 100 µm. (E-H) TRAP staining for osteoclast, scale bar: 500 µm. The white arrows in (V-VIII) indicate TRAP-positive (stained red) cells, scale bar: 100 µm.
Figure 4
Figure 4
The proliferation, migration and antioxidant effect of GELNs on PDLFs. (A) Cell scratch test result of GELNs intervened PDLFs after 12 and 48h, scale bar: 1 mm. (B)The effect of GELNs on PDLFs invasion after 24h, scale bar: 100 µm. (C) Detection of intracellular ROS levels by DCFH-DA, scale bar: 200 µm. (D) EdU effects on proliferation of PDLFs, scale bar: 50 µm. (E) Quantitation of the migration results. (F) The number of invading cells are presented as percent of invading cells. (G) Quantitative measurements the relative fluorescence intensity. (H) Quantitative measurements the proliferation of EdU-labeled PDLFs. *, **,*** and **** indicate difference for p<0.05, p<0.01, p<0.001 and p<0.0001 in comparison to Ctrl, respectively. #, ##,###and #### indicate difference for p<0.05, p<0.01, p<0.001 and p<0.0001 in comparison to LPS, respectively. n=3.
Figure 5
Figure 5
The antioxidant mechanism of GELNs. (A) The nuclear translocation of p-p65, scale bar: 50μm. (B) Immunohistochemical images of NF-κB from different groups, scale bar: 100μm (left of Figure 5B). The right side is a magnification of the black box on the left (scale bar:50μm). The NF-κB positive cells are marked with black arrows. (C-E) CAT, T-AOC, MDA activity. Data are shown as the mean±SD, n=3. *, **,*** and **** indicate difference for p<0.05, p<0.01, p<0.001 and p<0.0001 in comparison to Ctrl, respectively. # and ## indicate difference for p<0.05, p<0.01 in comparison to Perio, respectively.
Figure 6
Figure 6
In vitro and in vivo biosafety evaluation of GELNs. (A) Viabilities of PDLFs after incubation with GELNs at different concentrations for 6h,12h,24h, n=3.* indicate difference for p<0.05 in comparison to 6h. (B) Hemolysis test under different concentrations of GELNs and ginger juice by using blood of rats, n=3. (C) H&E staining of main organs slices from four group rats, scale bar:100 μm. (D) The organs coefficients, n=3.
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Grants and funding

This work was supported by the National Natural Science Foundation of China (82071155, 82271023, 82301052), Basic Research Program of Shanxi Province (Distinguished Young Scholars)(202203021223006), Traditional Chinese Medicine Administration Research of Shanxi (2024ZYYC073), Graduate Education Innovation Project of Shanxi Province (2023SJ139), Health Commission of Shanxi Province (No. 2022XM14), and the Natural Science Foundation of Shanxi Province (202203021222266, 202203021212368, 202303021212132, 202303021212131, 202403021212211).