Quercetin ameliorates salivary gland apoptosis and inflammation in primary Sjögren's syndrome through regulation of the leptin/OB‐R signaling

Abstract Dry mouth is the main manifestation of Sjögren syndrome (SS). Quercetin has been reported to alleviate radiation‐induced salivary gland damage, yet the effect of quercetin on SS‐caused salivary gland damage remains unclear. This study aimed to investigate the effects of quercetin on SS‐induced salivary gland damage and the mechanism underlying its therapeutic potential in SS. Here, NOD/Ltj mice were used to spontaneously mimic SS‐induced salivary gland inflammation in vivo and salivary gland epithelial cells (SGECs) were stimulated by interferon‐γ (IFN‐γ) to mimic cell inflammation in vitro. Results showed that quercetin significantly reduced loss of saliva flow, salivary gland damage, cell apoptosis, and inflammatory response in NOD/Ltj mice. Quercetin treatment also significantly reduced the increased serum leptin (LP) levels in NOD/Ltj mice. Furthermore, quercetin blocked the increases in the expression of obesity receptor (OB‐R) and its downstream Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling in the salivary glands. In vitro experiments confirmed that quercetin could protect SGECs from IFN‐γ‐induced cell apoptosis and inflammation through the LP/OB‐R‐activated JAK2/STAT3 signaling. Hence, quercetin might protect against SS‐induced salivary gland damage by relieving cell apoptosis and inflammation by inhibiting the LP/OB‐R signaling, providing a new perspective for treating SS‐induced dry mouth.