Moringa oleifera Lam. leaf extract safely inhibits periodontitis by regulating the expression of p38α/MAPK14-OPG/RANKL
Graphical Abstract
Introduction
Periodontitis is a chronic inflammatory disease related to some other chronic diseases, such as cancer (Michaud et al., 2018). It greatly affects human health, especially in children and young adults. In later stages, the disease leads to the destruction of supporting tissues and the loss of teeth through alveolar bone resorption (Carvalho-Filho et al., 2016). Porphyromonas gingivalis (P. gingivalis) is a pathogen causing periodontitis, the lipopolysaccharide (LPS) of P. gingivalis promotes the production of proinflammatory factors that upregulate RANKL—an osteoclast differentiating factor that causes bone loss—and that OPG is a decoy receptor of RANKL, the OPG/RANKL ratio has extensively been used as an index of bone formation and resorption (Pinto et al., 2020). Furthermore, previous studies have reported that p38α MAPK signaling is associated with osteogenesis and the expression of inflammatory cytokines in periodontitis (Sabbieti et al., 2010, Schwab et al., 2018). In this study, the roles and interaction between p38α MAPK signaling and OPG/RANKL in periodontitis were investigated.
At present, the use of natural compounds for periodontitis treatment is favored due to their harmless nature and antimicrobial activities (Chu, Ma, Sun, Xu, & Zhang, 2020). Moringa oleifera Lam. (MO), a fast-growing tree of the Moringacea family, is widely distributed in many countries. This tree is rich in proteins, vitamins, antioxidants, and phenolic acids (Kou, Li, Olayanju, Drake, & Chen, 2018), and its leaf extract exhibits inhibitory effects against some chronic diseases, especially inflammatory diseases, including ulcerative colitis (Kim et al., 2017) and arthritis (Saleem, Saleem, Akhtar, & Shahzad, 2020). Despite the established medicinal effects of MO leaf extract (MOL), its activity against periodontitis remains unknown.
Network pharmacology is a multidisciplinary methodology that relies on “syndrome differentiation” in evaluating multitarget herbal medicines that tend to be more effective than the commonly known single-target drugs. Herein, network pharmacology analysis and molecular docking (Saenkham et al., 2020) were used to explore the potential effect of MOL against periodontitis and to elucidate the underlying mechanism. Furthermore, these results were verified by in vivo and in vitro experiments.
Section snippets
Preparation of fractions
MO PKM1 leaves (CATAS-056) were identified and provided by the Chinese Academy of Tropical Agricultural Sciences (Zhanjiang, Guangdong, China) in November 2017. A voucher specimen of these leaves had been deposited in the Academy herbarium. Dried MO leaf powder (1000 g, water content <8%) was extracted in water (liquid/solid ratio of 20:1 v/m, mL/g) at 60 °C for 1 h. Subsequently, the supernatant was collected, and the residue was re-extracted twice. The combined supernatant was concentrated
Characterization of the chemical constituents in MOL
UPLC-ESI-MS/MS (Solarbio Biotechnology Co. Ltd., Shanghai, China) was used to identify the phenol compounds in MOL based on retention time and response values. Considering that the response values of the test compounds were higher in the negative ion mode than in the positive ion mode, only the former was used for the identification of these compounds. In total, 88 phenolics were detected, and they were all eluted at a retention time between 3 and 32 min (Fig. 1). These data confirmed that
Conclusion
We reported data in support of the hypothesis that MOL provides anti-periodontitis activity highly likely by regulating the p38α/MAPK14-OPG/RANKL pathway. Our findings showed that MOL not only altered the expression of inflammatory cytokines but also significantly reduced alveolar bone resorption in vivo and in vitro. As such, MOL can be used to clinically treat periodontitis, a chronic inflammatory disease that is associated with some other chronic diseases. It is worth noting that network
Funding
This study was financially supported by the Natural Science Foundation of China (Grant No. 81960200) and Distinguished Young Scholars of Jiangxi Province (Grant No. 20171BCB23090).
CRediT authorship contributions statement
The statement is accurate and agreed by all authors. Sang Long: Conceptualization, Methodology, Software, Jie Zhang: Methodology, Supervision, Funding acquisition, Fang Wang: Visualization, Writing – original draft, Writing - review & editing.
Author contributions
MOL was extracted by FW. The applications of MOL in vivo and in vitro were investigated by SL. The manuscript was written and reviewed by FW. All of the experiments were supervised by JZ. All of the authors contributed to the article and approved the submitted version.
Acknowledgments
We gratefully acknowledge the identification and provision of MO by the Chinese Academy of Tropical Agricultural Sciences (Zhanjiang, Guangdong, China).
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These authors contributed equally to this study and share first authorship.