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In traditional Chinese medicine, propolis has been used for treating oral diseases for centuries, widely. Flavonoid extract is the main active ingredient in propolis, which has attracted extensive attention in recent years. The objective and novelty of the current study aims to identify the mechanism of total flavonoid extract of propolis (TFP) for the treatment of periodontitis, and evaluate the therapeutic effect of TFP-loaded liquid crystal hydrogel (TFP-LLC) in rats with periodontitis. In this study, we used lipopolysaccharide-stimulated periodontal ligament stem cells (PDLSCs) to construct in vitro inflammation model, and investigated the anti-inflammatory effect of TFP by expression levels of inflammatory factors. Osteogenic differentiation was assessed using alkaline phosphatase activity and alizarin red staining. Meanwhile, the expression of toll like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), nuclear factor-kappa B (NF- κ B), receptor activator of NF- κ B (RANK) etc, were quantitated to investigate the therapeutic mechanism of TFP. Finally, we constructed TFP-LLC using a self-emulsification method and administered it to rats with periodontitis via periodontal pocket injection to evaluate the therapeutic effects. The therapeutic index, microcomputed tomography (Micro-CT), H&E staining, TRAP staining, and Masson staining were used for this evaluation. TFP reduced the expression of TLR4, MyD88, NF- κ B and inflammatory factor in lipopolysaccharide-stimulated PDLSCs. Meanwhile, TFP simultaneously regulating alkaline phosphatase, RANK, runt-associated transcription factor-2 and matrix metalloproteinase production to accelerate osteogenic differentiation and collagen secretion. In addition, TFP-LLC can stably anchor to the periodontal lesion site and sustainably release TFP. After four weeks of treatment with TFP-LLC, we observed a decrease in the levels of NF- κ B and interleukin-1 β (IL-1β) in the periodontal tissues of rats, as well as a significant reduction in inflammation in HE staining. Similarly, Micro CT results showed that TFP-LLC could significantly inhibit alveolar bone resorption, increase bone mineral density (BMD) and reduce trabecular bone space (Tb.Sp) in rats with periodontitis. Collectively, we have firstly verified the therapeutic effects and mechanisms of TFP in PDLSCs for periodontitis treatment. Our results indicate that TFP perform anti-inflammatory and tissue repair activities through TLR4/MyD88/NF-κB and RANK/NF- κ B pathways in PDLSCs. Meanwhile, for the first time, we employed LLC delivery system to load TFP for periodontitis treatment. The results showed that TFP-LLC could be effectively retained in the periodontal pocket and exerted a crucial role in inflammation resolution and periodontal tissue regeneration. Scheme 1. Schematic diagram of TFP-LLC alleviating periodontitis via PDLSCs-dependent anti-inflammatory and periodontium regeneration mechanism. TFP–LLC was in situ injected into the periodontal pocket to ensure the sustained release of the active TFP ingredients at the periodontal lesion. TFP–LLC suppresses the expression of inflammatory factors and osteoclastogenesis by interfering with TLR4/MyD88/NF-κB and RANK/NF-κB signaling. In addition, TFP–LLC promotes osteogenic differentiation and collagen regeneration in PDLSCs, as demonstrated by the upregulation of ALP and RUNX2 and downregulation of MMP. The TFP–LLC-induced periodontal homeostasis alleviates acute periodontal inflammation and assists in the long-term tissue regeneration of the gingiva, cementum, periodontal ligament, and alveolar bone, thereby demonstrating comprehensive treatment efficacy in periodontitis. [Display omitted] • We demonstrated that TFP exerts an anti-inflammatory pathway through TLR4/MyD88/NF-κB pathway in PDLSCs. • We proved TFP boosting periodontium regeneration via RANK/NF- κ B pathway in PDLSCs. • We prepared lyotropic liquid crystals containing total flavonoid extract of propolis (TFP-LLC). • TFP-LLC was stably anchored to the periodontal lesion site to form a drug reservoir. • TFP-LLC demonstrated excellent periodontal protection in rats with periodontitis. [ABSTRACT FROM AUTHOR]

Herbal formulas have unique efficacy and are of great significance to the theory and practice of Chinese medicine and are therefore gaining increasing attention in research. Painong powder (PNS), composed of Aurantii fructus immaturus (Zhishi in Chinese, ZS), Paeoniae Radix Alba (Baishao in Chinese, BS), and Platycodonis Radix (Jiegeng in Chinese, JG), has remarkable effects on the detoxification and discharge of pus. JG is traditionally used to treat pulmonary carbuncles and is considered a 'medicinal guide'. According to the composition theory of prescriptions, JG is an 'assistant and guide' medicine. The role of JG as an adjuvant has gained increasing attention. The study was designed to prove the efficacy of PNS in ulcerative colitis (UC) and to study the role of JG in PNS via pharmacodynamic, pharmacokinetic, and tissue distribution analyses. For the pharmacodynamic study, the UC rat model was induced using 5% trinitrobenzene sulfonic acid (TNBS). The results of the macroscopic characterization, histological analysis, and cytokine levels, including those of tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and nuclear factor-kappa B (NF-κB), were integrated to evaluate the treatment of UC with PNS. In addition, an LC-MS/MS method was established and validated to analyze the blood pharmacokinetic parameters and tissue distribution of naringin and paeoniflorin. After the administration of high-dose PNS, the UC rats showed amelioration of macroscopic damage at the lesion site. The cytokine levels in the plasma, colon, and lung tissues were also decreased. The pharmacokinetic parameters showed that compared with UC rats administered with PNS-JG, those administered with PNS showed an increase in the AUC, MRT, and T max of naringin and paeoniflorin, and a decrease in their clearance rate. Furthermore, naringin and paeoniflorin had higher concentrations in the colon and lung tissues in the normal and model groups administered with PNS than in those administered with PNS-JG. PNS was shown to have marked therapeutic efficacy against TNBS-induced UC in rats. The effect of JG in PNS was reflected by the differences in the pharmacokinetic parameters and tissue distribution of the active components, providing valuable information for the clinical application of PNS in the treatment of UC. However, knowledge about how JG works as an adjuvant medicine in PNS is still lacking. [Display omitted] • In this study, the efficacy of Painong powder (PNS) in the treatment of ulcerative colitis (UC) was proved by comprehensive macroscopic characterization, histological analysis and cytokine level, including tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6) and nuclear factor- κB (NF-κB). • The LC-MS/MS method was established and validated to analyze the blood pharmacokinetic parameters of naringin and paeoniflorin after treatment with PNS and PNS without JG (PNS-JG). • The established LC-MS/MS method was also applied to analyze the distribution of naringin and paeoniflorin in rat colon and lung tissues following treatment with PNS and PNS-JG. [ABSTRACT FROM AUTHOR]