Unraveling the multitarget mechanisms of aloe emodin against periodontitis: a synergy of network pharmacology and experimental validation
5 affiliations
- 1Department of Stomatology, Gongli Hospital of Shanghai Pudong New Area
- 2Department of Oral Mucosal Diseases, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine
- 3Shanghai Jiao Tong University School of Medicine
- 4Department of Stomatology, Oromaxillofacial Head and Neck Surgery, Huashan Hospital, Fudan University
- 5College of Basic Medical Science, Yunnan University of Chinese Medicine
Abstract
Background: Chronic periodontitis is a prevalent inflammatory disease that leads to destruction of periodontal tissues, resulting in tooth loss. While mechanical debridement and adjunctive antibiotics are commonly used, their therapeutic efficacy is limited by anatomical complexity and concerns over antibiotic resistance and side effects. Aloe-emodin (AE), a naturally occurring anthraquinone compound, exhibits significant anti-inflammatory and antimicrobial effects. However, its mechanisms in periodontitis remain unclear.
Methods: A network pharmacology approach was employed to identify potential targets of AE in periodontitis. The effects of AE on the viability, proliferation, migration, osteogenic differentiation, and inflammatory responses of mouse periodontal ligament stem cells (mPDLSCs) were assessed CCK8, qPCR and ELISA. In vivo , the alveolar bone of mouse periodontitis model was repaired and evaluated by micro-CT and histological analysis.
Results: Network pharmacology analysis identified 179 overlapping targets between AE and periodontitis, with key hubs including TNF, AKT1, EGFR, TP53, and MMP9. These targets were predominantly enriched in the MAPK, PI3K-AKT, NF-κB, and TNF signaling pathways. In vitro , AE significantly enhanced the proliferation, migration, and osteogenic differentiation of mPDLSCs while markedly suppressing LPS-induced expression. In vivo , AE dose-dependently reduced alveolar bone loss, improved trabecular microarchitecture, increased bone mineral density, and enhanced collagen organization in the periodontitis model.
Conclusion: AE is a pleiotropic natural compound that reprograms the inflammatory-osteolytic microenvironment of periodontitis and promotes alveolar bone regeneration through multi-target pathway modulation.
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BibTeX
@article{zhang2026unraveling,
title = {{Unraveling the multitarget mechanisms of aloe emodin against periodontitis: a synergy of network pharmacology and experimental validation}},
author = {Yifan Zhang and Huijing Ma and Shengxiang Zhang and Debao Jing and Hao Liang and Yufeng Wang and Zhengrui Li and Huijiao Yan},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1944429},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1944429/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Unraveling the multitarget mechanisms of aloe emodin against periodontitis: a synergy of network pharmacology and experimental validation
AU - Yifan Zhang
AU - Huijing Ma
AU - Shengxiang Zhang
AU - Debao Jing
AU - Hao Liang
AU - Yufeng Wang
AU - Zhengrui Li
AU - Huijiao Yan
PY - 2026
DA - 2026/10/20
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1944429
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1944429/full
AB - Background: Chronic periodontitis is a prevalent inflammatory disease that leads to destruction of periodontal tissues, resulting in tooth loss. While mechanical debridement and adjunctive antibiotics are commonly used, their therapeutic efficacy is limited by anatomical complexity and concerns over antibiotic resistance and side effects. Aloe-emodin (AE), a naturally occurring anthraquinone compound, exhibits significant anti-inflammatory and antimicrobial effects. However, its mechanisms in periodontitis remain unclear. Methods: A network pharmacology approach was employed to identify potential targets of AE in periodontitis. The effects of AE on the viability, proliferation, migration, osteogenic differentiation, and inflammatory responses of mouse periodontal ligament stem cells (mPDLSCs) were assessed CCK8, qPCR and ELISA. In vivo , the alveolar bone of mouse periodontitis model was repaired and evaluated by micro-CT and histological analysis. Results: Network pharmacology analysis identified 179 overlapping targets between AE and periodontitis, with key hubs including TNF, AKT1, EGFR, TP53, and MMP9. These targets were predominantly enriched in the MAPK, PI3K-AKT, NF-κB, and TNF signaling pathways. In vitro , AE significantly enhanced the proliferation, migration, and osteogenic differentiation of mPDLSCs while markedly suppressing LPS-induced expression. In vivo , AE dose-dependently reduced alveolar bone loss, improved trabecular microarchitecture, increased bone mineral density, and enhanced collagen organization in the periodontitis model. Conclusion: AE is a pleiotropic natural compound that reprograms the inflammatory-osteolytic microenvironment of periodontitis and promotes alveolar bone regeneration through multi-target pathway modulation.
SN - 1663-9812
ER -