Pterostilbene attenuates the proliferation and differentiation of TNF‑α‑treated human periodontal ligament stem cells

Abstract

Periodontitis is a common chronic inflammatory oral disease. The objective of periodontal treatment is to control infection whilst regenerating damaged periodontal tissue. The present study aimed to determine the potential effects of pterostilbene (PTE), a representative stilbene compound, on the proliferation and differentiation of human periodontal ligament stem cells (hPDLSCs). Different concentrations (1, 5, 10 and 20 µM) of PTE were applied to hPDLSCs, after which Cell Counting Kit-8 and western blotting assays were performed to examine the protein levels of Ki67, PCNA, p-IκBα, IκBα, Bcl-2, Bax, cleaved caspase3. The effect of PTE on the release of inflammatory factors, including IL-1β, IL-6 and IL-10 was assessed by RT-qPCR. The apoptosis of TNF-α-induced hPDLSCs was evaluated by TUNEL assay and western blotting. Additionally, the role of PTE in hPDLSC mineralization was evaluated using alizarin red staining. The expression levels of mineralization indices, including RUNX2 and ALP were subsequently determined using western blotting. Subsequently, the target of PTE was predicted using TargetNet database and AutoDock v4.2 software and verified using western blotting. The results of the present study revealed that PTE promoted the proliferation of hPDLSCs in a concentration-dependent manner. Furthermore, PTE treatment decreased the release of inflammatory factors and alleviated the apoptosis of TNF-α-induced hPDLSCs. PTE was also demonstrated to promote the formation of mineral nodules in TNF-α-induced hPDLSCs. The Targetnet database, along with molecular docking, indicated that histone deacetylases (HDACs) were the probable targets of PTE upstream of regulating periodontitis. The results of western blotting implied that TNF-α significantly increased expression levels of HDAC2, 4, 6 and 8, whilst PTE treatment markedly decreased HDAC4, 6 and 8 expression in a concentration-dependent manner compared with the TNF-α group, which further confirmed these conclusions. In summary, results of the present study revealed that PTE promoted TNF-α-induced hPDLSC proliferation and differentiation, whilst alleviating inflammation and apoptosis. PTE also inhibited the expression of HDACs, which may be involved in the mechanism of periodontitis.

Potential Chemopreventive Role of Pterostilbene in Its Modulation of the Apoptosis Pathway

“…Pterostilbene is capable of regulating the proliferation and differentiation of human periodontal ligament stem cells (hPDLSCs). Moreover, pterostilbene exerts an anti-inflammation effect to protect against TNF-α induced damage on hPDLSCs by reducing the levels of pro-inflammatory mediators of IL-6 and IL-1β and preventing the activation of NF-κβ (p65) [107].…”

Pterostilbene in the treatment of inflammatory and oncological diseases

“…PTS mitigates inflammation by decreasing inflammatory indicators, notably tumor necrosis factor-alpha (TNF-α), and obstructing NF-κB activation, a primary orchestrator of inflammation ( Lin et al, 2016 ; Liu et al, 2019 ). By suppressing the production of TNF-α, PTS can effectively reduce the extent of the inflammatory response ( Yi et al, 2022 ). By inhibiting the activation of NF-κB, PTS prevents this sequence of events and reduces the inflammatory response ( Zhang et al, 2023 ).…”

Modulation of atherosclerosis‐related signaling pathways by Chinese herbal extracts: Recent evidence and perspectives

“…Emodin, an anthraquinone compound found in traditional Chinese medicines such as rhubarb, huzhang, and cassia seeds, prevents the activation of key signaling molecules in the TLR/My D88/NF‐κB signaling pathway (Chen, Feng, et al, 2020), diminishes the extent of aortic lesions, and reduces lipid and macrophage accumulation within plaques. Pterostilbene, derived from the leguminous plant Pterocarpus marsupium, lowers the phosphorylation level of the NF‐κB signaling pathway by decreasing TLR5 expression, downregulates inflammatory cytokines (Yi et al, 2022), and alleviates iliac arterial endothelial damage, macrophage infiltration, and apoptosis in the vascular wall through the Nrf2‐mediated TLR4/MyD88/NF‐κB pathway (Xiong et al, 2020). Ligustilide curtails TNF‐α‐induced ROS production and NF‐κB pathway activation, inhibits VSMC migration, and reduces the expression of migration‐associated proteins such as MMP‐2, p‐JNK, and JNK (Choi et al, 2018; Li, Long, et al, 2022).…”