tumor growth. Many studies have provided evidence for the interference of EGCG
in different metabolic pathways [56]. It selectively inhibits specific enzymes
involved in cancer-developing activities such as DNA methyltransferases and
repairs DNA aberrations [57]. EGCG can induce apoptosis by an ROS-dependent
mechanism [54]. EGCG also induced H 2 O 2 formation in human lung adenocarcinoma (H661) and in Ha-ras gene-transformed human bronchial (21BES) cells, but
exogenously added catalase prevented EGCG-induced cell apoptosis, which
suggests that H 2 O 2 is involved in the apoptotic process provoked by EGCG [58].
Studies suggested that EGCG-mediated ROS production may underlie its ability to
induce endogenous antioxidants, at least in vitro. Treatment of Hepa1c1c7 human
hepatoma cells with EGCG resulted in dose-dependent increases in NADPH:quinone reductase-1 and glutathione gene expression through the electrophile response
element. Liquid chromatography–mass spectrometry (LC–MS) analysis of the cell
culture medium revealed the presence of EGCG-20-glutathione [59].
Silymarin is also reported to be a strong scavenger of free radicals. In
erythrocytes exposed to H 2 O 2 , silymarin increases the activities of anti-oxidant
enzymes like superoxide dismutase, catalase, glutathione peroxidase, glutathione
reductase, and glutathione-S-transferase. Silymarin reduces glutathione depletion
and ROS production [60]. One of the in vivo studies reported dose-dependent
inhibition of malondialdehyde formation in epidermal microsomes and lipid peroxidation caused by 12-O-tetradecanoylphorbol-13-acetate (TPA) and benzoyl peroxide in mouse skin epidermis by silymarin [61]. GSE is also a strong radical
scavenger and studies have reported the antioxidant potential of GSE [62].
2.2 Anti-inflammatory Effect
The anti-inflammatory effects of curcumin are related to the inhibition of transcription factor NF-kB, which regulates and coordinates the expression of various genes
involved in inflammation, cell survival, differentiation, and growth and also
regulates the free-radical scavenging activity of curcumin by decreasing the amount
of oxidative stress that can trigger the inflammatory cascade [14]. Curcumin has
been shown to suppress the activation of NF-kΒ, an inducible transcription factor
that regulates the expression of a host of genes involved in inflammation, cellular
proliferation, and cell survival [13, 63–68]. Genes regulated by NF-kΒ include those
encoding for COX-2, the NF-kΒ inhibitor IkBa, TNF-a, cyclin D1, ICAM-1, c-myc,
Bcl-2, MMP-9, iNOS, and interleukins (including IL-6 and IL-8) [13]. Curcumin
blocked the IkK-mediated phosphorylation and degradation of IkBa, thus NF-kB
remains bound to IkBa in the cytoplasm and is not able to enter the nucleus to
activate transcription [65, 69, 70]. Suppression of NF-kB activity subsequently
downregulated COX-2, iNOS and inflammatory markers [71, 72]. The inflammatory
cytokines are secreted by activated monocytes and macrophages and include
COX-2, lipoxygenase (LOX), iNOS, monocyte chemotactic protein-1 (MCP-1),
monocyte inflammatory protein-1a (MIP-1a), and interleukins (including IL-1,
210
S. Maya et al.
in different metabolic pathways [56]. It selectively inhibits specific enzymes
involved in cancer-developing activities such as DNA methyltransferases and
repairs DNA aberrations [57]. EGCG can induce apoptosis by an ROS-dependent
mechanism [54]. EGCG also induced H 2 O 2 formation in human lung adenocarcinoma (H661) and in Ha-ras gene-transformed human bronchial (21BES) cells, but
exogenously added catalase prevented EGCG-induced cell apoptosis, which
suggests that H 2 O 2 is involved in the apoptotic process provoked by EGCG [58].
Studies suggested that EGCG-mediated ROS production may underlie its ability to
induce endogenous antioxidants, at least in vitro. Treatment of Hepa1c1c7 human
hepatoma cells with EGCG resulted in dose-dependent increases in NADPH:quinone reductase-1 and glutathione gene expression through the electrophile response
element. Liquid chromatography–mass spectrometry (LC–MS) analysis of the cell
culture medium revealed the presence of EGCG-20-glutathione [59].
Silymarin is also reported to be a strong scavenger of free radicals. In
erythrocytes exposed to H 2 O 2 , silymarin increases the activities of anti-oxidant
enzymes like superoxide dismutase, catalase, glutathione peroxidase, glutathione
reductase, and glutathione-S-transferase. Silymarin reduces glutathione depletion
and ROS production [60]. One of the in vivo studies reported dose-dependent
inhibition of malondialdehyde formation in epidermal microsomes and lipid peroxidation caused by 12-O-tetradecanoylphorbol-13-acetate (TPA) and benzoyl peroxide in mouse skin epidermis by silymarin [61]. GSE is also a strong radical
scavenger and studies have reported the antioxidant potential of GSE [62].
2.2 Anti-inflammatory Effect
The anti-inflammatory effects of curcumin are related to the inhibition of transcription factor NF-kB, which regulates and coordinates the expression of various genes
involved in inflammation, cell survival, differentiation, and growth and also
regulates the free-radical scavenging activity of curcumin by decreasing the amount
of oxidative stress that can trigger the inflammatory cascade [14]. Curcumin has
been shown to suppress the activation of NF-kΒ, an inducible transcription factor
that regulates the expression of a host of genes involved in inflammation, cellular
proliferation, and cell survival [13, 63–68]. Genes regulated by NF-kΒ include those
encoding for COX-2, the NF-kΒ inhibitor IkBa, TNF-a, cyclin D1, ICAM-1, c-myc,
Bcl-2, MMP-9, iNOS, and interleukins (including IL-6 and IL-8) [13]. Curcumin
blocked the IkK-mediated phosphorylation and degradation of IkBa, thus NF-kB
remains bound to IkBa in the cytoplasm and is not able to enter the nucleus to
activate transcription [65, 69, 70]. Suppression of NF-kB activity subsequently
downregulated COX-2, iNOS and inflammatory markers [71, 72]. The inflammatory
cytokines are secreted by activated monocytes and macrophages and include
COX-2, lipoxygenase (LOX), iNOS, monocyte chemotactic protein-1 (MCP-1),
monocyte inflammatory protein-1a (MIP-1a), and interleukins (including IL-1,
210
S. Maya et al.