Periodontitis is an inflammatory condition that affects the supporting tissues surrounding the teeth (Kwon et al., 2021). Strongly indicated by numerous epidemiological studies, smoking and poor oral hygiene habits are important factors contributing to periodontitis (Slots, 2013). Additionally, a close association between periodontitis and systemic diseases such as heart disease (Sanz et al., 2020) and diabetes (Kocher et al., 2018) has been documented. According to data from the World Health Organization, almost half of the world’s adult population has suffered from varying degrees of periodontitis, underscoring the widespread prevalence of the condition. Untreated or ineffectively treated periodontitis can potentially escalate to more serious periodontal diseases, even leading to tooth loss (Kassebaum et al., 2017; Worthington et al., 2019). In terms of treatment, plaque control remains the focus of fundamental periodontitis treatment, incorporating mechanical methods of plaque and calculus removal such as scaling, brushing and flossing (Pastagia et al., 2006; Ramseier et al., 2017). At the same time, drug therapy including antibacterial mouthwashes as well as topical or systemic antibiotics remain common (Graziani et al., 2017; Herrera et al., 2022). In addition to traditional mechanical debridement and drug therapy, emerging therapeutic modalities in recent years include immunomodulatory therapy, biofilm disruption therapy, laser therapy, and regenerative therapy (Kinane et al., 2017). However, additional clinical studies are necessary to evaluate the long-term efficacy and safety of these emerging therapeutic strategies. Therefore, the urgent need to accelerate the development of safer, more effective and cost-effective drugs for periodontitis cannot be overstated.
Periodontitis, or gum disease, falls under the category of traditional Chinese medicine (TCM) known as “teeth declaration” and is characterized by different types of syndromes such as exuberant stomach fire, kidney Yin deficiency, qi and blood and Yin deficiency . – Yang deficiency among others (Chen et al., 2019). TCM practices are gaining recognition for the advantage of personalized treatment offered through holistic diagnostic methods and the combined use of medicinal herbs, which provides new opportunities for the treatment of periodontitis (Furquim Dos Santos Cardoso et al., 2021; Surathu and Kurumathur, 2011 ). . In light of the modern lifestyle characterized by sedentary behavior, excessive consumption of rich food and preference for cold drinks, renowned TCM master Minru Liu highlighted the common pathogenesis of periodontitis associated with exuberant stomach fire syndrome, such as the accumulation of moisture toxins -heat, the blockage. due to stasis of blood and consumption of Qi and Yin. Accordingly, basic treatments should revolve around clearing heat, detoxifying, resolving dampness, regulating blood, restoring Qi, and nourishing Yin. Professor Liu innovatively developed a herbal formula known as “Kouqiangjie Formula (KQJF)”, which consists of twelve therapeutic ingredients including Rhizoma Smilacis Glabrae, Polygonati Rhizoma, Taraxaci Herba, Herba Portulacae, Agrimoniae Herba, Plantamenxiuladix, Ch. , Sepiae Endoconcha, Fructus Mume, Radix Glycyrrhizae. KQJF has been involved in clinical use for several years. Its long-term effectiveness is remarkable, with no noticeable adverse effects, especially in the treatment of symptoms such as toothache, chewing pain, dry and foul-smelling mouth, swollen gums and pus. Preliminary clinical trials conducted by our group also confirm these findings (He et al., 2023). However, KQJF, which is a complex TCM formula with a multitude of active ingredients, has a sophisticated flavor profile, many potential therapeutic pathways and targets, leaving its exact mechanism of action still obscured.
UPLC-Q-TOF-MS technology equips researchers with a precise tool for the separation of complex mixtures, offering high-resolution mass spectrometry data and accurate mass-to-charge ratio information (Ou et al., 2020). This mitigates the challenges of compound identification and enables a comprehensive understanding and analysis of the complex ingredients found in TCM or mixed formulas (Wei et al., 2023). On the other hand, network pharmacology presents a holistic view of the multiple components, targets and pathways of drugs, enhancing the in-depth understanding of complex interaction mechanisms within biological systems (Xia et al., 2023; Xing et al., 2023 ). Essentially, the integration of UPLC-Q-TOF-MS technology and network pharmacology greatly increases the efficiency and depth of research on complex components of TCM or mixed types (Liu et al., 2022a). Particularly in understanding the properties of drug compatibility and the complex multi-component and target mechanisms inherent in Chinese medicines (Zhang et al., 2022), this provides researchers with a new strategy to discover more effective and safer drugs.
In light of the aforementioned framework, this study aims to elucidate the potential active ingredients, key targets and underlying mechanisms of the therapeutic activity of KQJF against periodontitis using a mixture of techniques including UPLC-Q-TOF-MS technology, network pharmacology and in vivo animal experiments. Moreover, in vivo experiments will be performed to validate the molecular mechanisms postulated by network pharmacology to position KQJF as a treatment for periodontitis. This will lay a theoretical foundation and provide evidence-based directions for future intensive studies and clinical promotion of KQJF for the treatment of periodontitis.
