# Antioxidant Activity of _Panax ginseng_ to Regulate ROS in Various Chronic Diseases
## 4 Pathways Related to Oxidative Stress in Cells  
There are multiple mechanisms involved in the normal cellular process. These mechanisms produce antioxidant enzymes such as SOD, CAT, GPx, HO-1, and G-S-T to inhibit the production of ROS which protect the cell from damage by maintaining antioxidant/oxidation balance [20]. Several pathways including NF-kB, Keap1/Nrf2/ARE, Wnt/\(\beta\)catenin, and PI3k/Akt are the most important for regulating the redox balance. NF-kB is an essential nuclear transcription factor that regulates innate immunity, tumor progression, and inflammatory responses [40]. Excessive ROS production activates NF-kB by activating the MMP [41]. NF-kB is an important factor in the expression of COX-2, iNOS, and cytokines [42]. Cox-2 generates prostaglandin E2 in the cell which causes skin cancer and iNOS produces nitric oxide that leads to inflammation [43]. However, the suppression of NF-kB activity may reduce inflammation and oxidative stress [31]. The Keep1/Nrf2/ARE (kelch-like epoxychloropropane-related protein 1/nuclear factor erythroid2-related factor 2/antioxidant response element) signaling pathway plays a vital role in the improvement in oxidative stress [44]. Nrf2 is an important transcription factor that protects the cell from oxidative stress [45]. In extreme antioxidant stress conditions, Nrf2 dissociates from keap1 and binds with the ARE which down-regulates antioxidant enzyme production, resulting in DNA damage, apoptosis, autophagy, etc. [46]. Furthermore, the Wnt signaling pathway is crucial for numerous basic processes of embryonic development and the homeostasis of normal cells [47]. The Wnt/\(\beta\)-catenin pathway is generally composed of \(\beta\)catenin, glycogen synthase kinase-3 (gsk-3), and casein kinase-1 (CK-1) proteins. In normal physiological conditions, gsk-3\(\beta\) and CK-1 phosphorylate \(\beta\)-catenin, the ligase complex of E3-ubiquitin, specifically targets \(\beta\)-catenin for destruction and ubiquitination. During oxidative stress, \(\beta\)-catenin is not decomposed, leading to the activation of the Wnt/\(\beta\)-catenin pathway [48]. Figure 2: Scavenge and production of reactive oxygen species (ROS). Organic and inorganic constituents can produce, convert, and scavenge ROS. Antioxidant enzymes (SOD, CAT, GPx, and GR) intercept ROS through the chemical reactions. Oxidases convert oxygen to O\({}_{2}\)\({}^{-}\), which is then dismutated to H\({}_{2}\)O\({}_{2}\) via SOD. H\({}_{2}\)O\({}_{2}\) can be converted to H\({}_{2}\)O via CAT or GPx or to hydroxyl radical (-OH) after reaction with Fe\({}^{2+}\). **Abbreviations:** SOD-Superoxide dismutase, CAT-catalase, GPx-glutathione Peroxidase, GR-glutathione reductase. GSH-glutathione. GSSG-glutathione disulfide. O\({}_{2}\)\({}^{\bullet-}\)-superoxide anion. H\({}_{2}\)O\({}_{2}\)-hydrogen peroxide, (HO-)-hydroxyl, ROS-reactive oxygen species. In addition, the PI3k/Akt signaling pathway is also essential in the mechanism of oxidative stress which controls cell proliferation and cell apoptosis [49]. The stimulation of Akt activity helps to regulate apoptosis by enhancing Bcl-2 and reducing Bax and caspase-3 expression. Many researchers have shown that the PI3K/Akt signaling pathway offers antioxidative activity which inhibits apoptosis and mitigates ischemia-reperfusion injury [50]. However, excessive ROS production blocks the PI3k/Akt, resulting in tumorigenesis [51] (Figure 3). Figure 3: The overproduction of ROS causes oxidative damage which dysregulates several signaling pathways. (a) Oxidative stress increases NF-kB, thus increasing the expression of COX-2, iNOS, and pro-inflammatory cytokines that may cause skin cancer and inflammation. However, ginseng Rg1, Rg3, Rb1, and Rh3 increase the antioxidant enzymes (SOD, CAT, GST, and GPx) activity, which suppresses the activation of NF-kB and oxidative stress totrigger skin cancer and inflammation.