Effect of dexamethasone on levels of inflammatory factors and EGF mRNA in rabbits suffering from oral ulcers

Purpose: To investigate the therapeutic effect of dexamethasone on rabbits suffering from oral ulcers, and the underlying mechanism(s) of action. Methods: A rabbit model of oral ulcer was established by applying 40 % glacial acetic acid solution to the oral buccal membranes of the animals. Three groups of rabbits were used. Changes in area of the oral ulcer were recorded after dexamethasone administration. Levels of epidermal growth factor (EGF) were assayed using reverse transcription PCR (RT-PCR), while MDA levels and expression levels of IL- 6, IL-8 and TNF-α were determined by enzyme-linked immunosorbent assay (ELISA). Local histopathological changes were examined histologically with the aid of hematoxylin and eosin (H & E) staining. Results: There were reductions in ulcer areas in group C on the 2nd, 4th and 7th days of dexamethasone administration, when compared with group B (p < 0.05). The EGF levels in the buccal mucosa of rabbits in groups B and C were significantly higher than those in group A (p < 0.05), while the highest EGF level was in group C (p < 0.05). The levels of MDA, IL-6, IL-8, and TNF-α significantly increased in groups B and C (p < 0.05). Results from H & E staining showed lower levels of inflammatory cells in group C than in group B, with visible proliferation of fibroblast cells and epithelial cells in group C after dexamethasone administration. Conclusion: Dexamethasone accelerates healing of oral ulcer by regulating EGF levels. This finding provides a new approach to the treatment of oral ulcers.

Qingwei San treats oral ulcer subjected to stomach heat syndrome in db/db mice by targeting TLR4/MyD88/NF-κB pathway

Background Qingwei San (QWS), one of classic Chinese Medicine prescripts, has been widely used to treat stomach heat syndrome which manifests oral ulcer (OU), periodontitis and upper gastrointestinal bleeding for seven hundred years. However, the therapeutic effects of QWS on diabetic OU subjected to stomach heat syndrome are still ambiguous. In the study, we investigated the pharmacological mechanisms. Methods The main components of QWS aqueous extract were analyzed by LC–MS, and potential pathways of QWS targeting OU were predicted by network pharmacology. The db/db mice were administered with the decoction of dried Zingiber officinale Rosc. rhizome combined with NaOH cauterization to establish the model of diabetic OU subjected to stomach heat syndrome. Subsequently, the model mice were treated with QWS, and OU wound healing status were recorded. The pathological changes of gastric tissue and oral mucosa were evaluated using hematoxylin–eosin staining, and the morphology of collagen fibers in oral mucosa was assessed by Masson staining. The levels of thromboxane B2 (TXB2), 6-Keto-prostaglandin F1α (6-keto-PGF1α), interleukin-1 β (IL-1β), IL-2, IL-6, tumor necrosis factor-α (TNF-α), β-endorphin (β-EP) and 5-Hydroxytryptamine (5-HT) were determined by ELISA assay. The protein expressions of Toll-like receptor 4 (TLR4), TNF receptor associated factor 6 (TRAF6), myeloid differentiation factor 88 (MyD88), inhibitor of NF-κB alpha (IκΒα), p-IκΒα and nuclear factor kappa-B (NF-κB) p65 were measured by Western Blotting. Results A total of 183 compounds in QWS were identified by LC–MS, and identified 79 bioactive compounds corresponded to 269 targets and 59 pathways. QWS high-dose treatment significantly reduced the level of TXB2 and the ratio of TXB2/6-keto-PGF1α. Meanwhile, it improved mucosal pathological morphology, and reduced the area of OU and local edema. Simultaneously, the levels of TNF-α, IL-1β, IL-6, IL-2 and 5-HT, and the expressions of TLR4, TRAF6, MyD88, p-IκΒα and NF-κB p65 were decreased. Conclusion QWS treatment facilitates the healing of OU, ameliorates pathological morphologies of gastric and oral mucosa and decreases the levels of pro-inflammatory cytokines in db/db mice subjected to stomach heat syndrome, whose mechanism may be associated with the inhibition of TLR4/MyD88/NF-κB signaling pathway to exert anti-inflammatory effects.

Qingwei San Treats Oral Ulcer Subjected to Stomach Heat Syndrome in db/db Mice by Targeting TLR4/MyD88/NF-κB Pathway

Background Qingwei San (QWS), one of classic Chinese Medicine prescripts, has been widely used to treat stomach heat syndrome which manifests oral ulcer (OU), periodontitis and upper gastrointestinal bleeding for seven hundred years. However, the therapeutic effects of QWS on diabetic OU subjected to stomach heat syndrome are still ambiguous. In the study, we investigate the pharmacological mechanisms. Methods The main components of QWS aqueous extract were analyzed by LC-MS, and potential pathways of QWS targeting OU were predicted by network pharmacology. The db/db mice were administered with the decoction of dried Zingiber officinale Rosc. rhizome combined with NaOH cauterization to establish the model of diabetic OU subjected to stomach heat syndrome. Subsequently, the model mice were treated with QWS, and OU wound healing status were recorded. The pathological changes of gastric tissue and oral mucosa were evaluated using hematoxylin-eosin staining, and the morphology of collagen fibers in oral mucosa was assessed by Masson staining. The levels of thromboxane B 2 (TXB 2 ), 6-Keto-prostaglandin F1α (6-keto-PGF1α), interleukin-1 β (IL-1β), IL-2, IL-6, tumor necrosis factor-α (TNF-α), β-endorphin (β-EP) and 5-Hydroxytryptamine (5-HT) were determined by ELISA assay. The protein expressions of Toll-like receptor 4 (TLR4), TNF receptor associated factor 6 (TRAF6), myeloid differentiation factor 88 (MyD88), inhibitor of NF-κB alpha (IκΒα), p-IκΒα and nuclear factor kappa-B (NF-κB) p65 were measured by Western Blotting. Results A total of 183 compounds in QWS were identified by LC-MS, and identified 79 bioactive compounds corresponded to 269 targets and 59 pathways. QWS high-dose treatment significantly reduced the level of TXB 2 and the ratio of TXB 2 /6-keto-PGF1α. Meanwhile, it improved mucosal pathological morphology, and reduced the area of OU and local edema. Simultaneously, the levels of TNF-α, IL-1β, IL-6, IL-2 and 5-HT, and the expressions of TLR4、TRAF6、MyD88、p-IκΒα and NF-κB p65 were decreased. Conclusion QWS treatment facilitates the healing of OU, ameliorates pathological morphologies of gastric and oral mucosa and decreases the levels of pro-inflammatory cytokines in db/db mice subjected to stomach heat syndrome, whose mechanism may be associated with the inhibition of TLR4/MyD88/NF-κB signaling pathway to exert anti-inflammatory effects.

Associations between psychological wellbeing, depression, general anxiety, perceived social support, tooth brushing frequency and oral ulcers among adults resident in Nigeria during the first wave of the COVID-19 pandemic

Introduction The aims of this study were to determine the associations between psychological wellbeing, and the frequency of tooth brushing and presence of oral ulcers during the COVID-19 pandemic; and to identify the mediating roles of psychological distress (general anxiety and depression) and perceived social support in the paths of observed associations. Methods This cross-sectional study recruited 996 adults in Nigeria between June and August 2020. Data collected through an online survey included outcome variables (decreased frequency of tooth brushing and presence of oral ulcers), explanatory variable (psychological wellbeing), mediators (general anxiety symptoms, depression symptoms and perceived social support) and confounders (age, sex at birth, educational and employment status). Multivariate logistic regression was used to determine the risk indicators for the outcome variables. A path analysis was conducted to identify the indirect effect of mediators on the association between the outcome and explanatory variables. Results Of the 966 respondents, 96 (9.9%) reported decreased tooth-brushing frequency and 129 (13.4%) had oral ulcers during the pandemic. The odds of decreased tooth-brushing during the pandemic decreased as the psychological wellbeing increased (AOR: 0.87; 95% CI: 0.83–0.91; p < 0.001) and as generalized anxiety symptoms increased (AOR: 0.92; 95% CI: 0.86–0.98; p = 0.009). The odds of having an oral ulcer was higher as the generalized anxiety symptoms increased (AOR: 1.15; 95% CI: 01.08–1.21; p < 0.001). Only generalized anxiety (indirect effect: 0.02; 95% CI: 0.01–0.04; P = 0.014) significantly mediated the relationship between wellbeing and tooth-brushing accounting for approximately 12% of the total effect of wellbeing on decreased toothbrushing. Generalized anxiety (indirect effect 0.05; 95% CI: − 0.07–0.03; P < 0.001) also significantly mediated the relationship between wellbeing and presence of oral ulcer accounting for 70% of the total effect of wellbeing on presence of oral ulcer. Depressive symptoms and perceived social support did not significantly mediate the associations between psychological wellbeing, decreased frequency of tooth brushing and the presence of oral ulcers. Conclusion Patients who come into the dental clinic with poor oral hygiene or oral ulcers during the COVID-19 pandemic may benefit from screening for generalized anxiety and psychological wellbeing to identify those who will benefit from interventions for mental health challenges.

The cytotoxicity, anti-inflammation, anti-nociceptive and oral ulcer healing properties of coconut shell liquid smoke

Introduction: Coconut shell liquid smoke (CS-LS) from Cocos nucifera L. has been traditionally used by Indonesians as a natural preservative. Besides that, liquid smoke is also used as a medicine to treat various types of wounds. During the storage, liquid smoke resulting from pyrolysis is still questionable in relation to the oxidation process and changes in its properties and potentials. We observed the physical characteristics, components, toxicity, anti-inflammatory, anti-nociceptive properties, and effect in oral ulcer healing of CS-LS. Methods: Acidity was analyzed using a digital pH meter, density test was analyzed using a pycnometer, and the components were determined using gas chromatography-mass spectrometry (GC-MS). Eight concentrations of CS-LS (1%, 2%, 4%, 6%, 8%, 10%, 12%, and 14%) were tested on baby hamster kidney (BHK21) for the extract toxicity, carrageenan-induced rat paw edema for its anti-inflammatory properties, hot-plate test for its anti-nociceptive, and traumatized labial fornix incisive inferior for its oral ulcer healing. Results: The acidity of CS-LS was 2.296 and the density was 1.0102 g/mL. The major components analyzed were phenol (32.75%), 2-methoxy-phenol (17.45%), and furfural (13.09%). The CS-LS 100% and CS-LS 8% were the optimum concentrations for maintaining the BHK21 and increasing the number of fibroblasts in oral ulcer healing. The CS-LS 100% showed potent anti-nociceptive ability compared to other concentrations (P = 0.001), but not for the anti-inflammation properties. Conclusion: CS-LS is a promising natural herb for oral medicine, especially oral ulcer medicine.