# Evaluation of the safety and functional effects of recombinant humanized type III collagen in food toxicology

**Authors:** Zhiyu Zhang, Wenqing Yang, Jingbo Yang, Xiaobin Lan, Chuanxiu Chen

PMC · DOI: 10.3389/fmed.2026.1765276 · Frontiers in Medicine · 2026-02-12

## TL;DR

This study shows that recombinant humanized type III collagen is safe to eat and has health benefits like reducing inflammation and aging signs.

## Contribution

The study introduces rhCol III as a safe and bioactive ingredient with potential for nutricosmetic applications.

## Key findings

- rhCol III showed no toxic effects in subchronic and genetic toxicity tests.
- rhCol III reduced inflammation, AGEs, oxidative stress, and improved skin barrier markers in zebrafish.
- rhCol III has anti-inflammatory, anti-glycation, antioxidant, and anti-aging properties.

## Abstract

This study aimed to comprehensively assess the edible safety and in vivo bioactivities of recombinant humanized type III collagen (rhCol III). A systematic toxicological evaluation was conducted, including subchronic toxicity tests, bacterial reverse mutation assays, mammalian erythrocyte micronucleus tests, and chromosome aberration tests. Concurrently, efficacy was evaluated using a zebrafish model to investigate multiple biological endpoints. The safety assessment revealed no toxicologically significant abnormalities, confirming a favorable safety profile for long-term oral consumption. In the zebrafish model, rhCol III significantly inhibited the expression of inflammatory factors, reduced the accumulation of advanced glycation end products (AGEs), alleviated oxidative stress damage, and improved molecular indicators associated with skin barrier function. The results demonstrate that rhCol III possesses multifaceted bioactivities, including anti-inflammatory, anti-glycation, antioxidant, and anti-aging properties. This research provides a robust scientific foundation for the development and application of rhCol III in high-value-added oral nutricosmetic products.

## Linked entities

- **Species:** Danio rerio (taxon 7955)

## Full-text entities

- **Genes:** Flg (filaggrin) [NCBI Gene 24641] {aka Pflg}, RENBP (renin binding protein) [NCBI Gene 5973] {aka RBP, RNBP}, glb1 (galactosidase, beta 1) [NCBI Gene 548343] {aka zgc:110823}, Has2 (hyaluronan synthase 2) [NCBI Gene 25694], ELN (elastin) [NCBI Gene 2006] {aka ADCL1, SVAS, WBS, WS}, Alb (albumin) [NCBI Gene 24186] {aka Alb1, Albza}, nfe2l2a (nfe2 like bZIP transcription factor 2a) [NCBI Gene 360149] {aka Nrf2, nfe2l2, wu:fc15g09, wu:fj67e03}, Hyal2 (hyaluronidase 2) [NCBI Gene 64468], Ivl (involucrin) [NCBI Gene 60583], Ggt1 (gamma-glutamyltransferase 1) [NCBI Gene 116568] {aka GGLUT, Ggt, Ggtp}, Cldn1 (claudin 1) [NCBI Gene 65129], AGER (advanced glycosylation end-product specific receptor) [NCBI Gene 177] {aka RAGE, SCARJ1, sRAGE}, Pdlim3 (PDZ and LIM domain 3) [NCBI Gene 114108] {aka Actn2lp, Alp}, Hyal1 (hyaluronidase 1) [NCBI Gene 367166], Has1 (hyaluronan synthase 1) [NCBI Gene 282821], Il1b (interleukin 1 beta) [NCBI Gene 24494] {aka IL-1F2}, IGHE (immunoglobulin heavy constant epsilon) [NCBI Gene 3497] {aka IgE}
- **Diseases:** aneuploidy (MESH:D000782), Occupational (MESH:D009784), dislocation (MESH:D004204), pathological lesions (MESH:D013568), parakeratosis (MESH:D010241), hepatic toxicity (MESH:D056486), cardiac hypertrophy (MESH:D006332), allergic reactions (MESH:D004342), parasitic infections (MESH:D010272), bacterial (MESH:D001424), renal dysfunction (MESH:D007674), toxicity (MESH:D064420), dehydration (MESH:D003681), deaths (MESH:D003643), deficiency in Col III (MESH:D020152), weight gain (MESH:D015430), CML (MESH:D015464), atrophy (MESH:D001284), ocular abnormalities (MESH:D005124), behavioral abnormalities (MESH:D001523), chromosomal aberration (MESH:D002869), CHL (MESH:D008171), poisoning (MESH:D011041), epidermal inflammation (MESH:D007249)
- **Chemicals:** DMSO (MESH:D004121), GLU (MESH:D005947), Cr (MESH:D003404), formaldehyde (MESH:D005557), ROS (MESH:D017382), beta-naphthoflavone (MESH:D019324), PBS (MESH:D007854), lipid (MESH:D008055), melanin (MESH:D008543), pentosidine (MESH:C062187), methylglyoxal (MESH:D011765), Glutathione (MESH:D005978), CO2 (MESH:D002245), 2-Aminofluorene (MESH:C012177), Dacthal (MESH:C007220), Cl- (MESH:D002713), MMS (MESH:D008741), acetoacetic acid (MESH:C016635), X-Gal (MESH:C044888), oil (MESH:D009821), peroxides (MESH:D010545), amino-acid (MESH:D000596), indomethacin (MESH:D007213), coenzyme II (MESH:D009249), Urea (MESH:D014508), K+ (MESH:D011188), TA102 (MESH:C000613803), hydroxyproline (MESH:D006909), Na (MESH:D012964), penicillin (MESH:D010406), glycerol (MESH:D005990), aluminum (MESH:D000535), A0345092 (-), superoxides (MESH:D013481), Hydrogen peroxide (MESH:D006861), cholesterol (MESH:D002784), D-galactose (MESH:D005690), ceramide (MESH:D002518), Cyclophosphamide (MESH:D003520), chloride (MESH:D002712), hyaluronic acid (MESH:D006820), hydroxyl radicals (MESH:D017665), colchicine (MESH:D003078), SDS (MESH:D012967), DCFH-DA (MESH:C029569), 1,8-Dihydroxyanthraquinone (MESH:C004315), water (MESH:D014867), Giemsa (MESH:D001399), AGEs (MESH:D017127), LEU (MESH:D007930), Chloral hydrate (MESH:D002697), sodium phenobarbital (MESH:D010634), methylcellulose (MESH:D008747), Sodium Azide (MESH:D019810), agar (MESH:D000362), ketone (MESH:D007659), TG (MESH:D014280), 2',7'-Dichlorodihydrofluorescein diacetate (MESH:C110400), streptomycin (MESH:D013307), vitamin E (MESH:D014810)
- **Species:** Homo sapiens (human, species) [taxon 9606], Escherichia coli K-12 (strain) [taxon 83333], Rattus norvegicus (brown rat, species) [taxon 10116], Danio rerio (leopard danio, species) [taxon 7955], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** rhCol III — Rattus norvegicus (Rat), Rat malignant mesothelioma, Cancer cell line (CVCL_C7S0), CHL — Cricetulus griseus (Chinese hamster), Spontaneously immortalized cell line (CVCL_0212)

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12936025/full.md

## References

70 references — full list in the complete paper: https://tomesphere.com/paper/PMC12936025/full.md

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Source: https://tomesphere.com/paper/PMC12936025