The ameliorative effect of bioactive phytochemicals (resveratrol, curcumin and sulforaphan) on environmental chemicals evoked inflammation: toxicogenomic data mining approach

Inflammation is a well-described adaptive response triggered by endogenous and exogenous antigens and different conditions, such as infection and tissue injury. However, wide varieties of physiological and pathological processes are connected with inflammation. We distinguish acute inflammation, which is manifested by cardinal signs of inflammation, and chronic inflammation that can occur in the absence of some of them (Medzhitov, 2008; Khansari et al., 2009). The low-grade systemic chronic inflammation can contribute to emergence of serious pathological conditions such as autoimmunity, neurodegeneration, diabetes, cancer and accelerated aging. Although usually inflammation is not a primary cause, it plays an important role in development of these diseases, and treatment focused on suppression of inflammatory reactions and its consequences in many cases can ameliorate these conditions (Kuprash and Nedospasov, 2016). There is a growing body of evidence demonstrating that environmental chemicals promote different diseases by inducing inflammation (Ghezzi et al., 2018). Conversely to inflammatory-promotive mode of action, resveratrol, curcumin and sulforaphane are powerful phytochemicals known for their antioxidant and anti-inflammatory properties, thus they can be examined as a potential protective combination in the treatment of inflammation (Chen et al., 2018). The aim of this in silico study was to analyze the individual and combined therapeutic effects of resveratrol, curcumin and sulforaphane on the regulation of genes associated with the development of inflammation evoked by environmental chemicals using the toxicogenomic data mining approach.


Introduction
Inflammation is a well-described adaptive response triggered by endogenous and exogenous antigens and different conditions, such as infection and tissue injury. However, wide varieties of physiological and pathological processes are connected with inflammation. We distinguish acute inflammation, which is manifested by cardinal signs of inflammation, and chronic inflammation that can occur in the absence of some of them (Medzhitov, 2008;Khansari et al., 2009).
The low-grade systemic chronic inflammation can contribute to emergence of serious pathological conditions such as autoimmunity, neurodegeneration, diabetes, cancer and accelerated aging. Although usually inflammation is not a primary cause, it plays an important role in development of these diseases, and treatment focused on suppression of inflammatory reactions and its consequences in many cases can ameliorate these conditions (Kuprash and Nedospasov, 2016).
There is a growing body of evidence demonstrating that environmental chemicals promote different diseases by inducing inflammation (Ghezzi et al., 2018).
Conversely to inflammatory-promotive mode of action, resveratrol, curcumin and sulforaphane are powerful phytochemicals known for their antioxidant and anti-inflammatory properties, thus they can be examined as a potential protective combination in the treatment of inflammation (Chen et al., 2018).
The aim of this in silico study was to analyze the individual and combined therapeutic effects of resveratrol, curcumin and sulforaphane on the regulation of genes associated with the development of inflammation evoked by environmental chemicals using the toxicogenomic data mining approach.

Materials and methods
The Comparative Toxicogenomic Database (CTD; http://ctd. mdibl.org) and its tools (Batch Query, MyVenn and Set Analyzer) were used to obtain the information about the interactions of investigated phytochemicals with genes/proteins associated with environmental chemical-linked inflammation. Functions of genes were obtained from the GeneCards: the Human Gene Database (https://www.genecards.org), while GeneMania prediction server (https://genemania.org) revealed detailed gene interactions.

Conclusion
These results confirm both individual and combined anti-inflammatory effect of investigated phytochemicals that could be considered for further in vitro and in vivo investigation in order to clarify the mechanisms of their beneficial effects, especially the different acting manner of their common 26 genes.