Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disease [1]. The main clinical manifestations of SS are dry mouth and dry eyes, with severe cases leading to systemic multi-system damage [2].The pathogenesis of SS is complex and remains unclear. It is generally believed that the disease was related to excessive proliferation of helper T cells and activation of B cells [3].There is no curative drug for SS. The corticosteroids and immunosuppressant are still used in clinical treatment, but these drugs have obvious side effects.

Traditional Chinese medicine may effectively compensate the shortcomings of western medicine, because it has the advantages of multiple targets, multiple pathways and multiple levels [4]. Previous studies have shown that total glucosides of white paeony (TGP) and its main component paeoniflorin (PF) have good anti-inflammatory, antioxidant and immunomodulatory effects, and they have beneficial effects on SS. However, there are few studies on the mechanism of its effects in SS [[5], [6], [7], [8], [9]].

NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome is currently the most characterized inflammasome.It is a multimeric cytoplasmic protein complex composed of NLRP3,ASC and cysteine protease-1 precursor (procaspase-1). After activation of the NLRP3 inflammasome, procaspase-1 is cleaved into caspase-1, which promotes the maturation and release of IL-1β and IL-18. [10,11]. Since the activation of NLRP3 inflammasome involves many complex signaling cascades, the abnormal activation of NLRP3 can be regulated by different mechanisms, such as regulating the upstream signaling of NLRP3 inflammasome to block assembly of the inflammasome [12,13]. Recent reports have shown that activated NLRP3 inflammasome may contribute to the pathogenesis of SS [14].Studies indicated that activating the Nrf2/HO-1 can inhibit the NLRP3 inflammasome [15],and activating the Nrf2/HO-1 pathway can alleviate diseases such as osteoarthritis, rheumatoid arthritis (RA),and lupus nephritis [[16], [17], [18]].

Nuclear factor erythroid-2-related factor 2 (Nrf2) consists of 605 amino acids and is divided into seven highly conserved functional domains, called Neh1 ∼ Neh7, which is a member of the Cap 'n 'collar (CNC) transcription factor family. Nrf2 is a major transcription factor regulating antioxidant responses [19].The heme oxygenase (HO) family has three isomers:HO-1, HO-2 and HO-3, which are important enzymes in heme catabolism. Among them, HO-1 is a cell protective enzyme whose transcription is regulated by Nrf2. Nrf2/HO-1 has important functions such as antioxidant,anti-inflammatory and inhibiting apoptosis, and has become an important signaling pathway for oxidative stress [20,21]. This study aims to explore whether PF inhibits NLRP3 inflammasome activation by regulating the Nrf2/HO-1 pathway to alleviate Sjögren's syndrome.