COSMETICS & PERSONAL CARE
‣ These bacteria are also responsible for the bad smell related to halitosis . AHE was investigated by quantifying , in gingiva probing samples , the six most important bacterial species indicative for periodontitis , periimplantitis and halitosis before and after application . After 24 hours of contact time a base toothpaste with 5 % AHE was shown to be 99 % effective against P . gingivalis ( Figure 1 ). AHE showed excellent anti-bacterial activity against P . gingivalis and can therefore be applied to prevent periodontal diseases and halitosis .
Reinforcing epithelial barrier
Epithelial cells are connected to each other by specialised transmembrane molecular complexes , among them cell-cell junctions comprising tight junctions , adherens junctions , gap junctions and desmosomes . They provide the first line of defence in the oral mucosa . P . gingivalis impairs the oral epithelial barrier partly through targeting grainy-head-like 2 , an epithelial-specific transcription factor which regulates the expression of the junction proteins . 5 E-cadherins are components of adherens junctions . These structures ensure intercellular adhesion amongst epithelial cells . They regulate a diverse range of other cellular processes , such as cell shape , division , growth , apoptosis , wound healing and barrier function .
Figure 4 - LPS-induced inflammatory responses in monocytes by AHE
AHE was found to activate E-Cad B1 expression by 57 % and E-Cad-B2 by 25 % in cultured HaCaT cells , hence counteracting the invasive properties of P . gingivalis . It therefore enhances the oral mucosa barrier , thus preventing injuries and penetration of noxious substances that can impair oral health and responsible for nonoral systemic diseases .
Cell senescence
A recent study shows that P . gingivalis induces premature senescence in dendritic cells by direct cellular invasion , leading to disruption of immune homeostasis in periodontitis . 6 Cellular senescence is an irreversible growth arrest evoked by various stimuli , including oxidative , epigenetic , and genotoxic stresses , telomere damage and oncogene activation . 10 During the senescence process , senescent cells secrete senescenceassociated phenotype factors , including cytokines , proteases , growth factors and MMPs , that preclude senescent cell clearance by the immune system , a process orchestrated by age-related immune system remodelling . 4 , 11 The accumulation of senescent cells plays a causal role in driving ageing and chronic diseases , while their clearance delays and reduces the ageing phenotype in several tissues of premature and naturally aged models . Defence against infection , improvement of wound healing and regenerative capability of tissues are also crucial parameters in preventing premature gingival ageing and bacteria invasion . Gingival fibroblasts are the primary cell type present in periodontal connective tissue . They maintain gingival tissue integrity by regulating collagen and proteoglycan metabolism . In response to P . gingivalis LPS , gingival fibroblasts produce several proinflammatory cytokines , such as IL-6 and IL-8 , which mediates periodontitis . 12 AHE may therefore act through various potential mechanisms involving gingival fibroblasts and senescent cells that play important roles in the pathogenesis of periodontitis and gingival ageing . Using SA β-gal , a common biomarker of cellular senescence , we showed that 1 %, 2 % and 5 % AHE was able to clear the SA β-gal positive cells , by 8 %, 14 and 21 % respectively , demonstrating that it exhibits significant dose-dependent senolytic properties ( Figure 2 ). AHE can therefore be used to prevent premature ageing and consequently to preserve the wound healing and regenerative properties of gums .
Wound healing & regeneration
Previously , we had demonstrated the senolytic effects of AHE , suggesting its ability to maintain the self-renewal of cells , essential for regeneration and wound healing of tissues . Wound healing and regenerative capacity are key properties for a healthy oral mucosa . After injury to the periodontal tissues , a sequentially phased healing response is initiated that enables wound closure and partial restoration of tissue structure and function . Fibroblasts , which synthesise and organise the collagen fibres linking alveolar bone and gingiva to the cementum covering the tooth root , play a critical role during periodontal wound healing . 13 Importantly , the regeneration of connective tissues involves different cellular activities driven by fibroblast populations . These include the
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36 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981