# Potential of Laurel (_Laurus mobilis_ L.) Leaf Polyphenols for Modulation of Body Composition
## 4 Influence of Laurel Leaf Polypphenols on Body Composition  
Physiological intracellular redox homeostasis is a balance between the levels of prooxidants (ROS and RNS) and their elimination by antioxidants [31]. This balance is disrupted by the increased production of free radicals during physiological processes (aging and hormonal changes) and pathological events paired with the reduced production of endogenous antioxidants resulting in a state of oxidative stress and enhanced inflammation [32], which results in modified transcriptional activity, cellular signaling pathways, reduced mitochondrial function, altered protein formation and decreased cellular metabolism linked to different human disorders [31; 33]. Oxidative stress and inflammation can be considered some of the main contributors to age-related changes in bones, skeletal muscle and adipose tissue. For example, it has been shown that oxidative stress and inflammation lead to an imbalance between osteoclast and osteoblast activity in bones by interfering with complex molecular pathways [20; 22], which can lead to metabolic bone diseases and contribute to pathogenesis of the skeletal system. In skeletal muscle, chronic low-grade inflammation disrupts the muscle protein metabolism, leading to a progressive loss of skeletal muscle mass [24], while oxidative stress has been connected with the inability of aged satellite cells to maintain the homeostatic activity of skeletal muscle [21]. Adipose tissue is severely affected by inflammation and oxidative stress, which has been shown to affect cellular aspects of adipocyte differentiation [25; 34] and the endocrine and metabolic functions of the adipose tissue [25]. For this reason, the antioxidant and anti-inflammatory activity of polyphenols through their involvement in different signaling pathways in the human body represent the most likely mechanisms by which the polyphenols alleviate age-related changes in body composition.  
Several antioxidant mechanisms of polyphenols have been proposed. First, polyphenols can directly scavenge ROS due to the hydroxyl groups in their structure, the number and position of which, paired with substitution pattern and glycosylation, determine the strength of antioxidant activity [35]. The second possible mechanism is the upregulation of endogenous antioxidant and oxidase enzyme activity (SOD1 in the cytosol and SOD2 in the mitochondria) [35]. Polypphenols may also enhance cellular antioxidant activity through the regulation of the Nrf-mediated pathways included in the regulation of genes responsible for cell survival, metabolism, and adipocyte differentiation (e.g., FoxO1), as well as detoxifying enzymes such as SOD, GSH, NQO1, GST and HO-1 by binding to AREs in the gene promoter regions of the enzymes [36; 37]. There is also emerging evidence that the polyphenols counteract ROS through regulation of microRNAs (endogenous non-coding short RNAs) that regulate various biological pathways [35]. The main molecular mechanisms related to the anti-inflammatory activity of polyphenols include: (a) the inhibition of proinflammatory enzymes (COX-2, LOX, iNOS) through the activation of PPARy; (b) the inhibition of mitogen-activated protein kinases (MAPK), phosphoinositide 3-kinase (PI3K), and tyrosine  
Figure 3: Chemical structure of apigenin and its glycosides detected in laurel leaves (adapted from [13]).  
kinases (NF-\(\kappa\)B); (c) activation of endogenous antioxidant enzymes; and (d) modulation of cell survival genes [38]. A general overview of the polyphenols' molecular targets related to their antioxidant and anti-inflammatory activity is shown in Figure 4, while the specific effects of laurel leaf polyphenols are discussed further in the text.