# Novel bioprocessing strategies and evaluation models for walnut meal bioactives

**Authors:** Fengling Tan, Yachun Chen, Bing Qi, Siting Li, Zhou Chen, Aijin Ma, Yingmin Jia

PMC · DOI: 10.1016/j.fochx.2026.103670 · Food Chemistry: X · 2026-02-20

## TL;DR

This paper reviews new methods to extract and evaluate health-promoting compounds from walnut meal using sustainable processing and human-like models.

## Contribution

The paper introduces an integrated framework combining green processing and human biomimetic evaluation for walnut meal bioactives.

## Key findings

- Mixed-strain solid-state fermentation improves bioactive compound availability.
- Organoid models provide accurate human-relevant assessments of walnut bioactives.
- Multi-organ chips evaluate systemic health benefits of walnut-derived compounds.

## Abstract

This review addresses the challenges in valorizing walnut meal, a by-product of walnut oil extraction, by outlining its key bioactive constituents—proteins/active peptides, polysaccharides, and phenolic compounds—and their health benefits. It examines emerging green processing strategies, including mixed-strain solid-state fermentation, microbe-enzyme synergistic fermentation, and integrated multi-technology approaches. The article also discusses the evolution of efficacy assessment from conventional cellular and animal models toward human biomimetic platforms such as organoids and organs-on-chips, which offer more physiologically relevant models for elucidating functional mechanisms. In contrast to existing reviews focusing on isolated components or conventional techniques, this work constructs an integrated framework spanning from “green synergistic processing” to “human biomimetic evaluation.” It aims to accelerate the translation of walnut-derived bioactive compounds into functional foods and pharmaceuticals, promoting comprehensive, high-value utilization of walnut resources.

•Novel processing strategies enhance yield and sustainability of bioactives.•Mixed-strain SSF and enzyme synergy enhances component bioavailability.•Organoid models enable precise human-relevant bioactivity evaluation.•Multi-organ chips holistically assess systemic health benefits of bioactives.

Novel processing strategies enhance yield and sustainability of bioactives.

Mixed-strain SSF and enzyme synergy enhances component bioavailability.

Organoid models enable precise human-relevant bioactivity evaluation.

Multi-organ chips holistically assess systemic health benefits of bioactives.

## Full-text entities

- **Genes:** MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, CREB1 (cAMP responsive element binding protein 1) [NCBI Gene 1385] {aka CREB, CREB-1}, SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, Nos2 (nitric oxide synthase 2, inducible) [NCBI Gene 18126] {aka MAC-NOS, NOS-II, Nos-2, Nos2a, i-NOS, iNOS}, DPP4 (dipeptidyl peptidase 4) [NCBI Gene 1803] {aka ADABP, ADCP2, CD26, DPPIV, TP103}, CAT (catalase) [NCBI Gene 847], ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, C1qa (complement component 1, q subcomponent, alpha polypeptide) [NCBI Gene 12259] {aka Adic, C1q}, SLC15A1 (solute carrier family 15 member 1) [NCBI Gene 6564] {aka HPECT1, HPEPT1, PEPT1}, ACHE (acetylcholinesterase (Yt blood group)) [NCBI Gene 43] {aka ACEE, ARACHE, N-ACHE, YT}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, BDNF (brain derived neurotrophic factor) [NCBI Gene 627] {aka ANON2, BULN2}, MMP1 (matrix metallopeptidase 1) [NCBI Gene 4312] {aka CLG}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, GDNF (glial cell derived neurotrophic factor) [NCBI Gene 2668] {aka ATF, ATF1, ATF2, HFB1-GDNF, HSCR3}
- **Diseases:** nerve damage (MESH:D000080902), colorectal cancer (MESH:D015179), death (MESH:D003643), insulin resistance (MESH:D007333), vascular injury (MESH:D057772), cytotoxicity (MESH:D064420), colitis (MESH:D003092), cardiovascular diseases (MESH:D002318), dementia (MESH:D003704), constipation (MESH:D003248), liver injury (MESH:D017093), liver damage (MESH:D056486), depression (MESH:D003866), type 2 diabetes (MESH:D003924), neuronal loss (MESH:D009410), chronic diseases (MESH:D002908), motor dysfunction (MESH:D000068079), glioblastoma (MESH:D005909), cognitive and emotional disorders (MESH:D003072), Parkinson 's disease (MESH:D010300), metabolic syndrome (MESH:D024821), hyperuricemic (MESH:C537696), disease (MESH:D004194), neurodegenerative diseases (MESH:D019636), inflammatory (MESH:D007249), anxiety (MESH:D001007), neuroinflammation (MESH:D000090862), diabetic (MESH:D003920), cancer (MESH:D009369), Alzheimer 's disease (MESH:D000544), neurotoxicity (MESH:D020258), inflammatory damage (MESH:D018746), obesity (MESH:D009765), liver steatosis (MESH:D005234), gluconeogenesis disorders (MESH:D009358), metabolic disease (MESH:D008659)
- **Chemicals:** proanthocyanidin (MESH:C013221), polyunsaturated fatty acids (MESH:D005231), PTZ (MESH:D010433), curcumin (MESH:D003474), H2O2 (MESH:D006861), naphthoquinone (MESH:D009285), DJF-W (-), oil (MESH:D009821), urolithin A (MESH:C026423), arginine (MESH:D001120), ochratoxin A (MESH:C025589), galacturonic acid (MESH:C007819), tannin (MESH:D013634), phenols (MESH:D010636), proanthocyanidins (MESH:D044945), amino acid (MESH:D000596), scopolamine (MESH:D012601), rhamnose (MESH:D012210), xylose (MESH:D014994), arabinose (MESH:D001089), lipopolysaccharide (MESH:D008070), lipid (MESH:D008055), Rot (MESH:D012402), fructose (MESH:D005632), bisphenol AF (MESH:C583074), protocatechuic acid (MESH:C009091), polyphenol (MESH:D059808), 5-HT (MESH:D012701), glucose (MESH:D005947), flavonoids (MESH:D005419), ellagic acid (MESH:D004610), alcohol (MESH:D000438), ammonia (MESH:D000641), gallic acid (MESH:D005707), sugar (MESH:D000073893), n-hexane (MESH:C026385), mannose (MESH:D008358), carbon (MESH:D002244), ciprofloxacin (MESH:D002939), uric acid (MESH:D014527), nitrogen (MESH:D009584), DA (MESH:C025953), polysaccharide (MESH:D011134), peptides (MESH:D010455), phenolic acids (MESH:C017616), Th (MESH:C026166), phenol (MESH:D019800), water (MESH:D014867), hydroxyl (MESH:D017665), blood glucose (MESH:D001786), Val-Tyr (MESH:C414029), galactose (MESH:D005690), ethanol (MESH:D000431), alkaloids (MESH:D000470), 4-hydroxybenzoic acid (MESH:C038193), GABA (MESH:D005680), silver (MESH:D012834), epicatechin gallate (MESH:C062669)
- **Species:** Danio rerio (leopard danio, species) [taxon 7955], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Staphylococcus aureus (species) [taxon 1280], Juglans regia (English walnut, species) [taxon 51240], Drosophila melanogaster (fruit fly, species) [taxon 7227], Bacillus subtilis (species) [taxon 1423], Mus musculus (house mouse, species) [taxon 10090], Caenorhabditis elegans (species) [taxon 6239], Juglans nigra (black walnut, species) [taxon 16719], C. elegans [taxon 328850]
- **Cell lines:** PC-12 — Rattus norvegicus (Rat), Rat adrenal gland pheochromocytoma, Cancer cell line (CVCL_0481), Caco-2 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0025), MDA-MB231 — Homo sapiens (Human), Breast adenocarcinoma, Cancer cell line (CVCL_0062), HT22 — Mus musculus (Mouse), Transformed cell line (CVCL_0321), 3 T3 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0594), SH-SY5Y — Homo sapiens (Human), Neuroblastoma, Cancer cell line (CVCL_0019), HT-29 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0320), L1 — Drosophila melanogaster (Fruit fly), Spontaneously immortalized cell line (CVCL_Z786), A549 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_0023), T47D-KBluc — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_K229), RAW264.7 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0493), A172 — Homo sapiens (Human), Glioblastoma, Cancer cell line (CVCL_0131), MCF-7 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0031)

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12938866/full.md

## References

91 references — full list in the complete paper: https://tomesphere.com/paper/PMC12938866/full.md

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Source: https://tomesphere.com/paper/PMC12938866