WVSPLAGRT (H2) and
IGFLIIWV (H3) are two transepithelial transported
intestinal peptides obtained from the hydrolysis of hempseed protein
with pepsin, which exert antioxidant activity in HepG2 cells. Notably,
both peptides reduce the H
2
O
2
-induced reactive
oxygen species, lipid peroxidation, and nitric oxide (NO) production
levels in HepG2 cells via the modulation of the nuclear factor erythroid
2-related factor 2 and the inducible nitric oxide synthase (iNOS)
pathways, respectively. Due to the close link between inflammation
and oxidative stress and with the objective of fostering the multifunctional
behavior of bioactive peptides, in this study, the molecular characterization
of the anti-inflammatory and immunomodulatory properties of H2 and
H3 was carried out in HepG2 cells. In fact, both peptides were shown
to modulate the production of pro (IFN-γ: −33.0 ±
6.7% H2,
p
= 0.011; −13.1 ± 2.0% H3,
p
= <0.0001; TNF: −17.6 ± 1.7% H2,
p
= 0.0004; −20.3 ± 1.7% H3,
p
= <0.0001; and IL-6: −15.1 ± 6.5% H3,
p
= 0.010)- and anti (IL-10: +9.6 ± 3.1% H2,
p
= 0.010; +26.0 ± 2.3% H3,
p
= < 0.0001)-inflammatory
cytokines and NO (−9.0 ± 0.7% H2,
p
=
<0.0001; −7.2 ± 1.8% H3,
p
= <0.0001)
through regulation of the NF-κB and iNOS pathways, respectively,
in HepG2 cells stimulated by lipopolysaccharides.