Verbascoside Protects Gingival Cells against High Glucose-Induced Oxidative Stress via PKC/HMGB1/RAGE/NFκB Pathway

Impaired wound healing often occurs in patients with diabetes and causes great inconvenience to them. Aside from the presence of prolonged inflammation, the accumulation of oxidative stress is also implicated in the delayed wound healing. In the present study, we tested the effect of verbascoside, a caffeoyl phenylethanoid glycoside, on the improvement of cell viability and wound healing capacity of gingival epithelial cells under high glucose condition. We showed that verbascoside attenuated the high glucose-induced cytotoxicity and impaired healing, which may be associated with the downregulation of oxidative stress. Our results demonstrated that verbascoside increased the activity of the antioxidant enzyme SOD and reduced the oxidative stress indicator, 8-OHdG, as well as apoptosis. Moreover, verbascoside upregulated the PGC1-α and NRF1 expression and promoted mitochondrial biogenesis, which was mediated by suppression of PKC/HMGB1/RAGE/NFκB signaling. Likewise, we showed the inhibitory effect of verbascoside on oxidative stress was via repression of PKC/HMGB1/RAGE/NFκB activation. Also, our data suggested that the PKC-mediated oxidative stress may lead to the elevated production of inflammatory cytokines, IL-6 and IL-1β. Collectively, we demonstrated that verbascoside may be beneficial to ameliorate impaired oral wound healing for diabetic patients.

The Bigger Picture: Why Oral Mucosa Heals Better Than Skin

Wound healing is an essential process to restore tissue integrity after trauma. Large skin wounds such as burns often heal with hypertrophic scarring and contractures, resulting in disfigurements and reduced joint mobility. Such adverse healing outcomes are less common in the oral mucosa, which generally heals faster compared to skin. Several studies have identified differences between oral and skin wound healing. Most of these studies however focus only on a single stage of wound healing or a single cell type. The aim of this review is to provide an extensive overview of wound healing in skin versus oral mucosa during all stages of wound healing and including all cell types and molecules involved in the process and also taking into account environmental specific factors such as exposure to saliva and the microbiome. Next to intrinsic properties of resident cells and differential expression of cytokines and growth factors, multiple external factors have been identified that contribute to oral wound healing. It can be concluded that faster wound closure, the presence of saliva, a more rapid immune response, and increased extracellular matrix remodeling all contribute to the superior wound healing and reduced scar formation in oral mucosa, compared to skin.

Cytocompatibility Properties of an Herbal Compound Solution Support In vitro Wound Healing

The aim of this study was to evaluate the cytocompatibility of an herbal extract compound oral rinse [StellaLife VEGA (SLife)] against relevant human cellular models of oral surgical wound healing. SL was compared to the gold standard for peri-/post-operative oral surgical use, i.e., Chlorhexidine (CHX) and to a commonly utilized essential-oil (EO) based antiseptic rinse. Fibroblasts and primary oral stem cells of the apical papilla (SCAPs) were employed to assess its comparative cytotoxicity to the active comparator antiseptic rinses and its effects on wound healing in vitro. In cytotoxicity assays, multiple timepoints were tested ranging from clinically relevant of 60-s rinsing to protracted challenge of up to 5 min, to determine dose-dependent toxicity. The SLife group consistently demonstrated minimal cytotoxicity as compared to active comparators across experimental timepoints and different cells lines. At concentrations up to 20% v/v SLife-challenged fibroblasts and SCAPs demonstrated no significant toxicity as compared to unstimulated controls (p > 0.05). When assessing wound healing, a scratch wound assay revealed significantly accelerated cell migration for SLife as compared to CHX (p < 0.05). Notably, all active comparator antiseptic rinses affected wound healing responses by significantly reducing total collagen deposition after intermittent “rinsing” intervals that simulated post-surgical oral rinsing. Nonetheless, intermittent as well as continuous challenge of cells with SLife had a positive effect in functional collagen assays. An herbal extract compound-based oral rinse was found to be cytocompatible to cells critical to oral wound healing and to promote fibroblast migration and differentiation, contrary to existing antiseptic rinses that lack selective cytotoxicity.

Retraction Note: Accelerated oral wound healing using a pre-vascularized mucosal cell sheet

Editor's Note: this Article has been retracted; the Retraction Note is available at https://doi.org/10.1038/s41598-021-82919-5.

Frequency of Oral Manifestation in Diabetic Patients in Yazd 2016-2017

Objective: Diabetes Mellitus (DM) is one of the most common endocrine diseases with many systemic complications such as oral manifestations. The present study aimed to compare the oral manifestations frequency in diabetic patients and healthy subjects. Materials and Methods: This cross sectional study was conducted during 2016-17 on subjects came to Yazd Diabetic Research Center. In this study, 181 type 2 diabetic patients (T2DM) and 181 healthy individuals, based on convenient sample method, were included. Two groups were compared for basic information and oral manifestations including candidiasis, oral lichen planus (OLP), periodontitis, xerostomia, delayed oral wound healing, geographic tongue, gingival hyperplasia, fissured tongue, burning mouth and finally at least one of these lesions. Results: The frequency of candidiasis, OLP, periodontitis, delay oral wound healing, geographic tongue, xerostomia and at least one of lesions in diabetics were significantly higher than control group (P-value< 0.001). After regression analysis and adjusting for confounding factors, candidiasis, periodontitis and xerostomia in diabetics were significantly more prevalent than non-DM patients with odds ratio of 15.16 (1.80-127.57), 9.58 (4.68-19.63) and 78.639 (10.05-615.231) respectively. Conclusion: Xerostomia, candidiasis and periodontitis were significantly more prevalent in T2DM than Non-T2DM persons. Therefore, increasing awareness on oral manifestations in this group is recommended for timely diagnosis and referring to an oral medicine.

Evaluation of the In Vitro Oral Wound Healing Effects of Pomegranate (Punica granatum) Rind Extract and Punicalagin, in Combination with Zn (II)

Pomegranate (Punica granatum) is a well-established folklore medicine, demonstrating benefits in treating numerous conditions partly due to its antimicrobial and anti-inflammatory properties. Such desirable medicinal capabilities are attributed to a high hydrolysable tannin content, especially punicalagin. However, few studies have evaluated the abilities of pomegranate to promote oral healing, during situations such as periodontal disease or trauma. Therefore, this study evaluated the antioxidant and in vitro gingival wound healing effects of pomegranate rind extract (PRE) and punicalagin, alone and in combination with Zn (II). In vitro antioxidant activities were studied using DPPH and ABTS assays, with total PRE phenolic content measured by Folin–Ciocalteu assay. PRE, punicalagin and Zn (II) combination effects on human gingival fibroblast viability/proliferation and migration were investigated by MTT assay and scratch wounds, respectively. Punicalagin demonstrated superior antioxidant capacities to PRE, although Zn (II) exerted no additional influences. PRE, punicalagin and Zn (II) reduced gingival fibroblast viability and migration at high concentrations, but retained viability at lower concentrations without Zn (II). Fibroblast speed and distance travelled during migration were also enhanced by punicalagin with Zn (II) at low concentrations. Therefore, punicalagin in combination with Zn (II) may promote certain anti-inflammatory and fibroblast responses to aid oral healing.