Hempseed (Cannabis sativa) Peptides WVSPLAGRT and IGFLIIWV Exert Anti-inflammatory Activity in the LPS-Stimulated Human Hepatic Cell Line

Abstract

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.

Integrated Evaluation of the Multifunctional DPP-IV and ACE Inhibitory Effect of Soybean and Pea Protein Hydrolysates

“…Legumes, pseudocereals, and hempseed are among the plant foods which can be considered good sources of bioactive peptides [3][4][5][6].…”

Identification of Bioactive Peptides from a Laminaria digitata Protein Hydrolysate Using In Silico and In Vitro Methods to Identify Angiotensin-1-Converting Enzyme (ACE-1) Inhibitory Peptides

“…A search of the BIOPEP database ( , accessed on 10 December 2022) [ 46 ] determined the novelty of the peptides identified and shown in Table 1 . Of the ten peptides analyzed and listed in Table 2 , their amino acid sequences were not identified in previously published papers concerning seaweed proteins and bioactive peptides [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ].…”

“…The anti-inflammatory peptide sequence IGF also results from the GI digestion of SEFIGFPIK. This tripeptide is found in the pepsin hydrolysis of hempseed protein [ 42 ]. The peptide GNK that is cleaved from sequenced peptide GDFGNKDGKLTF is found in the Arietin peptide-A known as Fibrinogen interaction inhibitor.…”

Peptides and protein hydrolysates exhibiting anti-inflammatory activity: sources, structural features and modulation mechanisms

“…Interestingly, only peptide IGFLIIWV showed the ability to reduced IL-6 levels up to 15.1%. 126 Moreover, treatment with a combination of enzymes other than pepsin, specifically Viscozyme and pancreatin, generated neuroprotective short peptides GVYY, APTLW and LPF from walnut, as well as Neutrase treatment, gave better results regarding the inhibition of NO production by anti-inflammatory peptides from Lychee seeds such as RPLVTHK, in comparison with Alcalase and Flavourzyme hydrolysates. 127,128 3.1.3.…”