Quercetin promotes autophagy to alleviate cigarette smoke‐related periodontitis

Abstract

Background and ObjectivesCigarette smoking has been reported as an independent risk factor for periodontitis. Tobacco toxins affect periodontal tissue not only locally but also systemically, leading to the deterioration and recurrence of periodontitis. However, the mechanism of cigarette smoke‐related periodontitis (CSRP) is unclear and thus lacks targeted treatment strategies. Quercetin, a plant‐derived polyphenolic flavonoid, has been reported to have therapeutic effects on periodontitis due to its documented antioxidant activity. This study aimed to evaluate the effects of quercetin on CSRP and elucidated the underlying mechanism.MethodsThe cigarette smoke‐related ligature‐induced periodontitis mouse model was established by intraperitoneal injection of cigarette smoke extract (CSE) and silk ligation of bilateral maxillary second molars. Quercetin was adopted by gavage as a therapeutic strategy. Micro‐computed tomography was used to evaluate the alveolar bone resorption. Immunohistochemistry detected the oxidative stress and autophagy markers in vivo. Cell viability was determined by Cell Counting Kit‐8, and oxidative stress levels were tested by 2,7‐dichlorodihydrofluorescein diacetate probe and lipid peroxidation malondialdehyde assay kit. Alkaline phosphatase and alizarin red staining were used to determine osteogenic differentiation. Network pharmacology analysis, molecular docking, and western blot were utilized to elucidate the underlying molecular mechanism.ResultsAlveolar bone resorption was exacerbated and oxidative stress products were accumulated during CSE exposure in vivo. Oxidative stress damage induced by CSE caused inhibition of osteogenic differentiation in vitro. Quercetin effectively protected the osteogenic differentiation of human periodontal ligament cells (hPDLCs) and periodontal tissue by upregulating the expression of Beclin‐1 thus to promote autophagy and reduce oxidative stress damage.ConclusionOur results established a role of oxidative stress damage and autophagy dysfunction in the mechanism of CSE‐induced destruction of periodontal tissue and hPDLCs, and provided a potential application value of quercetin to ameliorate CSRP.

Quercetin in the Prevention of Induced Periodontal Disease in Animal Models: A Systematic Review and Meta-Analysis

“…Quercetin ameliorated cigarette smoke related periodontal tissue destruction in mice by reducing oxidative stress damage and autophagy dysfunction [ 6 , 51 ].…”

“…Quercetin might be an option; in an in vivo mouse model it reduced the viability and resulted in cell death of senescent cells [47]. Quercetin ameliorated cigarette smoke related periodontal tissue destruction in mice by reducing oxidative stress damage and autophagy dysfunction [6,51].…”

“…Sundaram et al [52] found that quercetin was able to regulate the expression of various chromatin modifiers and reduce the activity of DNA methyltransferases, histone Quercetin ameliorated cigarette smoke related periodontal tissue destruction in mice by reducing oxidative stress damage and autophagy dysfunction [6,51].…”

Association of Dietary Flavonoid Intake with Serum Cotinine Levels in the General Adult Population

“…Concerning total flavonoids, a negative linear association was observed when intake remained below 99.61 mg/day. (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)40-59, or ≥60), sex (male or female), and race/ethnicity (Mexican American, Other Hispanic, Non-Hispanic White, Non-Hispanic Black, or Other), education level (below high school, high school, or above high school), family poverty income ratio (≤1.0, 1.1-3.0, or >3.0), drinking status (nondrinker, low-to-moderate drinker, or heavy drinker), energy intake levels (in quartiles), BMI (<25.0, 25.0-29.9, or >29.9), and supplement use (yes or no); Model 2 was adjusted as model 1 plus smoking status (never smoker, former smoker, or current smoker).…”

“…The dietary flavonoid intake with the largest weight in the serum cotinine levels was anthocyanidins (32.30%), followed by Isoflavones (26.80%), flavones (19.50%), flavanones (18.80%), and flavan-3-ols (2.49%), and the detailed weight of each dietary flavonoid intake is presented in Figure 2. (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59), or ≥60), sex (male or female), and race/ethnicity (Mexican American, Other Hispanic, Non-Hispanic White, Non-Hispanic Black, or Other), education level (below high school, high school, or above high school), family PIR (≤1.0, 1.1-3.0, or >3.0), drinking status (nondrinker, low-to-moderate drinker, or heavy drinker), energy intake levels (in quartiles), BMI (<25.0, 25.0-29.9, or >29.9), supplement use (yes or no), and smoking status (never smoker, former smoker, or current smoker).…”