# Multilevel Assessment of the Antioxidant Potential of Two Edible Insects Following In Vitro Simulated Gastrointestinal Digestion

**Authors:** Eleni Dalaka, Demeter Lorentha S. Gidari, Constantin S. Filintas, Violetta Bantola, Nickolas G. Kavallieratos, Georgios Theodorou

PMC · DOI: 10.3390/antiox15020262 · Antioxidants · 2026-02-19

## TL;DR

This study shows that digestion increases the antioxidant activity of two edible insects, with each species affecting different genes in immune cells.

## Contribution

The study provides a multilevel assessment of how digestion affects antioxidant activity and gene expression in edible insects.

## Key findings

- Digested insect samples showed higher antioxidant capacity than undigested ones.
- A. diaperinus digestion products increased expression of antioxidant-related genes like Nrf2 and SOD1.
- T. molitor digestion products mainly affected NFKB1 and RELA genes.

## Abstract

In recent years, insect-derived peptides have attracted attention for their potential biological activities, particularly antioxidant properties. This study assessed the antioxidant activity of two widely consumed edible insects, T. molitor and A. diaperinus larvae, using cell-free and cell-based approaches. Whole lyophilized larvae, digestion products from the oral, gastric, and intestinal phases, as well as the <3 kDa permeate fraction (D-P3) derived from the intestinal digestion phase, were evaluated using biochemical antioxidant assays. Overall, digested samples exhibited higher antioxidant capacity than their undigested counterparts. At the cellular level, treatment of LPS-stimulated, PMA-differentiated THP-1 macrophages with A. diaperinus D-P3 was associated with increased mRNA expression of genes related to antioxidant defense, including NFE2-like bZIP transcription factor 2 (NFE2L2, also known as Nrf2), glutathione-disulfide reductase (GSR), superoxide dismutase 1 (SOD1), and catalase (CAT), whereas T. molitor D-P3 preferentially modulated nuclear factor kappa B p50 subunit (NFKB1) and nuclear factor kappa B p65 subunit (RELA). Overall, these findings indicate that gastrointestinal digestion enhances the bioaccessibility of antioxidant components in both edible insect species while revealing species-specific transcriptional responses under in vitro inflammatory conditions. This multilevel assessment provides mechanistic insight into the antioxidant-related biological activity of digestion-derived insect peptides and supports their further investigation as functional ingredients in food and feed systems.

## Linked entities

- **Genes:** NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780], GSR (glutathione-disulfide reductase) [NCBI Gene 2936], SOD1 (superoxide dismutase 1) [NCBI Gene 6647], CAT (catalase) [NCBI Gene 847], NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790], RELA (RELA proto-oncogene, NF-kB subunit) [NCBI Gene 5970]
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Prdx6-ps2 (peroxiredoxin 6 pseudogene 2) [NCBI Gene 384001] {aka Aop2-rs2, GPx*, Prdx6-rs2}, Cat (catalase) [NCBI Gene 12359] {aka 2210418N07, Cas-1, Cas1, Cs-1}, Nfe2l2 (nuclear factor, erythroid derived 2, like 2) [NCBI Gene 18024] {aka Nrf2}, Nqo1 (NAD(P)H dehydrogenase, quinone 1) [NCBI Gene 18104] {aka Dia4, Dtd, Nmo-1, Nmo1, Nmor1, Ox-1}, Keap1 (kelch-like ECH-associated protein 1) [NCBI Gene 50868] {aka INRF2, mKIAA0132}, Sod1 (superoxide dismutase 1, soluble) [NCBI Gene 20655] {aka B430204E11Rik, Cu/Zn-SOD, CuZnSOD, Ipo-1, Ipo1, SODC}, Hmox1 (heme oxygenase 1) [NCBI Gene 15368] {aka D8Wsu38e, HO-1, HO1, Hemox, Hmox, Hsp32}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, Sod2 (superoxide dismutase 2, mitochondrial) [NCBI Gene 20656] {aka MnSOD, Sod-2}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}
- **Diseases:** malnutrition (MESH:D044342), cytotoxic (MESH:D064420), inflammation (MESH:D007249), injury to (MESH:D014947)
- **Chemicals:** K3Fe (CN)6 (MESH:C028033), ADFW (-), H2O2 (MESH:D006861), bile salts (MESH:D001647), thiols (MESH:D013438), AA (MESH:D000596), MTT (MESH:C070243), TCA (MESH:D014238), selenium (MESH:D012643), Carbohydrate (MESH:D002241), polyphenols (MESH:D059808), TPTZ (MESH:C002849), glutathione (MESH:D005978), CO2 (MESH:D002245), lipid (MESH:D008055), 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (MESH:C002502), LPS (MESH:D008070), PBS (MESH:D007854), hydrogen (MESH:D006859), Na2S2O8 (MESH:C024625), ROS (MESH:D017382), ferricyanide (MESH:C007931), metal (MESH:D008670), fat (MESH:D005223), Trolox (MESH:C010643), oligopeptides (MESH:D009842), chitosan (MESH:D048271), P (MESH:D010758), nitrogen (MESH:D009584), FeCl3 (MESH:C024555), Chitin (MESH:D002686), DPPH (MESH:C004931), water (MESH:D014867), Ascorbic acid (MESH:D001205)
- **Species:** Danio rerio (leopard danio, species) [taxon 7955], Protaetia brevitarsis (species) [taxon 348688], Homo sapiens (human, species) [taxon 9606], Solanum tuberosum (potatoes, species) [taxon 4113], Tenebrio molitor (yellow mealworm, species) [taxon 7067], Hermetia illucens (black soldier fly, species) [taxon 343691], Malus domestica (apple, species) [taxon 3750], Tenebrionidae (darkling beetles, family) [taxon 7065], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Zophobas atratus (giant mealworm beetle, species) [taxon 7074], Alphitobius diaperinus (lesser mealworm, species) [taxon 27448], Galleria mellonella (greater wax moth, species) [taxon 7137]
- **Cell lines:** THP-1 — Homo sapiens (Human), Childhood acute monocytic leukemia, Cancer cell line (CVCL_0006), Caco-2 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0025), BL-D-P3 — Mus musculus (Mouse), Hybridoma (CVCL_G241), AML12 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0140), L-929 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_AR58)

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12938569/full.md

## References

76 references — full list in the complete paper: https://tomesphere.com/paper/PMC12938569/full.md

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Source: https://tomesphere.com/paper/PMC12938569