**10. RES as an attenuator of risk factors and conditions associated with PD**

It has been well-established that PD is associated, to varying degrees, with a collection of modifiable risk factors as well as a myriad of systemic inflammationmediated diseases [24, 99]. Hence, studies examining the effect of RES on PD in combination with purported comorbidity, and/or risk factor, could contribute to the argument regarding the breadth of its benefits.

Studies employing the integration of RA, DM, cigarette smoking, or osteoporosis (OP) into the induced-PD model have demonstrated that RES may assist in the mitigation of the periodontal damage contributed by associated risk factors and concomitant conditions. For example, with cigarette smoking added to the animal

#### *Evaluation of Trans-Resveratrol as a Treatment for Periodontitis DOI: http://dx.doi.org/10.5772/intechopen.101477*

model, it was found that RES decreased both alveolar bone loss and oxidative stress [100, 101]. Additionally, using a ligature-induced PD model, RES was found to reduce alveolar bone loss and attenuate hyperglycemia in diabetic mice [102, 103].

Another study, which employed an induced-PD and RA animal model, determined immunoenzymatically, that both Ibuprofen and RES reduced the tissue levels of anticyclic citrullinated peptide antibody (ACCPA) by 99 and 72%, respectively (p < 0.05), and RES alone, was reported to reduce serum rheumatoid factor (RF) (p < 0.05) [101].

Interestingly, the results of a study that used an induced-PD model which concurrently induced osteoporosis (OP) by ovariectomising the rats, suggested that RES may reduce alveolar bone loss in oestrogen-deficient rats via the attenuation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, making NADPH oxidase a potential drug target for RES [104].

Also of note, an extensive *in vitro* study showed the potential for RES to address *Pg*-related disease, with a particular focus on the prevention of Alzheimer's disease. Using a human *in vitro* model for neuroinflammation, Bahar and Singarao demonstrated that RES successfully modulated the ROS and deregulated inflammation. A total of 96 genes were analysed in *Pg* LPS-induced human neuroblastoma cells via qPCR followed by pathway analysis. In this way, RES was found to diminish NF-κB, neuroinflammatory acute phase pathways [105].
