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absorption and has low bioavailability. Curcumin gets FLAVONOIDS
[43]
directly conjugated once it is absorbed, and only a small
amount remains as free curcumin. It has been suggested Flavonoids are polyphenols found in vegetables, fruits,
[43]
that its metabolite, curcumin glucuronide, is responsible flowers, tea, wine, stems, and roots. There are seven
[62]
for most of its therapeutically assumed action, however, types of flavonoids: Anthocyanidins, flavanones, flavonols,
[44]
a recent study showed that curcumin glucuronide has a flavones, flavanols, flavononol, and isoflavones. They have
[63]
less potent effect than curcumin itself on HepG2 cells, as been shown to be cardio-protective and hepato-protective
the expression of GSTT1, CAT, IL-8, AREG, and ACOX1 genes and possess anti-viral and anti-cancer activity. [64-66] Flavonoids
was greatly downregulated by curcumin than by curcumin have found to induce apoptosis in HepG2 cells via activation
glucuronide. [43] In addition, curcumin is more rapidly of the mitochondrial pathway, along with the translocation
absorbed than curcumin glucuronide. Curcumin is the of cytochrome c, activation of caspases such as 9, 8, and 3,
[43]
most studied natural product for HCC; it is clearly effective abnormal changes in mitochondrial membrane potential,
in HCC at different molecular mechanisms for inflammation, generation of reactive oxygen species, elevation in
proliferation, and apoptosis, there is a lack of clinical data in intracellular calcium, and upregulated transcription of
humans to confirm the above. endonuclease G and apoptosis inducing factor-related
genes. [67] Flavonoids have also been found to inhibit
RESVERATROL HepG2 cells growth by inhibiting the NF-kB pathway via
blocking tumor necrosis factor-alpha. [68] Administering
Resveratrol (3, 4’, 5-trihydroxy-trans-stilbene) is found in epigallocatechin-3-gallate (EGCG), which is found in green
red wine, berries, grapes, and peanuts. Resveratrol has tea, to HepG2 cells induces their apoptosis by suppressing
[45]
been found to be anti-inflammatory in viral infections, epidermal growth factor receptor/c-Met signaling; therefore,
neurodegenerative diseases, cardiovascular diseases, suppress tumor cell proliferation and invasion. Quercetin,
[69]
ischemia, and cancer. Resveratrol has anti-cancer effects by found in flavonol, has shown to restrain the expression of
suppressing initiation, promotion, and progression of tumor heat shock proteins 27 and 40, which lead to resistance
formation. [46-49] Moreover, it has significant anti-cancer activity to chemotherapy, hence potentiating the effect of the
by inhibiting inflammation and free radicals generation. [50,51] chemotherapeutic agent. Moreover, flavonoids have been
[70]
Resveratrol has been found to hold rat hepatoma Fao cells found to be anti- hepatitis B virus (HBV) and hepatitis B core.
and HepG2 cells in S and G2/M phase and prevent them from EGCG inhibits HBV replication by altering its DNA synthesis.
[71]
engaging in mitotic division. Another study showed that Furthermore, hepatitis C virus is inhibited by catechin that
[52]
cells exposed to resveratrol were held in G1 phase and had interferes with NF-kB and COX-2 pathways. [72]
[53]
an upregulation in Bax and p21 genes. It also decreased
the invasion of cancer cells by downregulating hepatic Like curcumin and resveratrol, flavonoids appear to have
[54]
growth factor. It inhibits vascular endothelial growth factor activity against HCC with different mechanisms, through
[55]
gene expression by inducing hypoxia in HepG2 cells. In different pathways but need to be tested in clinical trial.
another study, HepG2 cells exposed to high concentrations
of resveratrol reaching between 50 and 100 umol/L for more TOTAL ALKALOIDS OF RUBUS ALEAEFOLIOUS POIR
than 48 h were more prone to apoptosis, in a dose-dependent
fashion. In a study that exposed H22 cells to resveratrol R. aleaefolious is a plant used for the management of hepatitis
[56]
[74]
with 5-fluorouracil (FU) vs. 5-FU alone; resveratrol and in China. Hong et al. have reported that components
[73]
5-FU had a greater anti-cancer activity compared to 5-FU of R. aleaefolious, such as butanol and ethylacetate, are
alone. Notas et al. concluded that resveratrol has an hepatoprotective in mice with acute liver injury after exposure
[58]
[57]
anti-proliferative effect against HepG2 cells as well as to carbon tetrachloride. Reports from the literature have
inducing the production of nitric oxide. It has also been discussed the protective and therapeutic role of R. aleaefolious
[73]
shown to downregulate NF-kB, caveolin-1, and MMP-9. [59,60] Poir in carcinogenesis. [75,76] Zhao et al. examined the
Several in vivo studies also support the anti-tumor activity therapeutic effects of total alkaloids in R. aleaefolious
of resveratrol in HCC. Resveratrol was administered to mice Poir (TARAP) on HCC both in vitro and in vivo. TARAP has
that had HCC tumor cells, hepatic tumor growth reduced and been shown to affect HCC growth and induce apoptosis
cell cycle proteins p34cdc2 and cyclin B1’s expression was in HepG2 cells via mitochondrion-mediated apoptosis by
[61]
suppressed. Resveratrol has shown to have both in vivo causing the loss of mitochondrion potential and activation
[73]
and in vitro effect against HCC though different pathways of caspases 9 and 3, apoptosis was dose dependent. Bax
and appear to have a promising potential, yet there is no and Bcl-2 are important proteins involved in the process of
[73]
[77]
clinical data in humans. apoptosis. Bcl-2 is known to be anti-apoptotic, and BAX
Hepatoma Research | Volume 1 | Issue 3 | October 15, 2015 121