Bromelain inhibits the inflammation and senescence effect in diabetic periodontitis

Background/purpose: Diabetes mellitus (DM) is a chronic metabolic disorder that affects millions of people worldwide. A growing evidence suggests that hyperglycemia in DM causes a pre-aging and pro-inflammatory condition known as inflammaging, which increases periodontitis susceptibility. Bromelain has been demonstrated to have anti-inflammatory and anti-aging properties in variety of tissues, but its effects on diabetic periodontitis remain unclear. Thus, the aim of this study is to investigate the its Bromelain's impact in diabetic periodontitis in terms of inflammation and senescence activity. Materials and methods: We assessed the wound healing capacity, production of pro-inflammatory cytokines Interleukin (IL)-6 and IL-8 and senescence marker p16 in human gingival fibroblasts (HGFs) in response to Advanced glycation end-products (AGEs) stimulant, with or without Bromelain treatment. The expression of p65, p-ERK, and p-p38 were also examined to elucidate whether Bromelain's anti-inflammaging activity is mediated through NF-κB and MAPK/ERK signaling pathway. Results: Bromelain concentrations ranging from 2.5 to 20 g/mL had no adverse effect on HGF cell proliferation. Bromelain improved wound healing in HGFs with AGEs stimulation. In addition, Bromelain suppressed the production of pro-inflammatory cytokines IL-6 and IL-8 in HGFs elicited by AGEs. Meanwhile, Bromelain treatment also inhibited the senescence activity and expression of p16 in AGEs-stimulated HGFs. Western blot analysis indicated that the upregulation of p-ERK, p-p38 and p65 induced by AGEs were inhibited by Bromelain in HGFs. Conclusion: These data suggest that excessive AGEs in the gingiva may lead to the accumulation of pro-inflammatory cytokines and marked senescence activity. Bromelain application may be helpful in enhancing wound healing by suppressing inflammaging via downregulation of NF-κB and MAPK/ERK signaling pathways in DM individuals with periodontal disease.