# Rakkyo (Allium chinense)-Derived Fructan Stimulates Collagen and Hyaluronan Synthesis in Human Dermal Fibroblasts

**Authors:** Kei Tsukui, Aiko Sano, Kazumi Kamioki, Kiwamu Dohgomori, Shin-ichi Kawaguchi, Yoshihiro Tokudome

PMC · DOI: 10.3390/nu18040649 · Nutrients · 2026-02-16

## TL;DR

A fructan from rakkyo (Allium chinense) boosts collagen and hyaluronan production in human skin cells, suggesting potential for skin health.

## Contribution

Demonstrates that rakkyo-derived fructan directly stimulates extracellular matrix synthesis in dermal fibroblasts.

## Key findings

- Rakkyo fructan increased viable cell numbers and upregulated COL1A1 and HAS2 gene expression.
- Treatment led to 3.8-fold and 1.3-fold increases in type I collagen and hyaluronic acid production.
- Lysyl oxidase mRNA was upregulated, indicating enhanced collagen cross-linking.

## Abstract

Background: Fructans are fructose-based polysaccharides with diverse biological activities; however, their direct activity on skin cells remains unresolved. This study investigated the biological activity of fructan extracted from rakkyo (Allium chinense) (RF) and examined its effects on extracellular matrix (ECM) metabolism, particularly collagen and hyaluronan synthesis, in human dermal fibroblasts. Methods: RF was prepared from fresh rakkyo bulbs by aqueous extraction, alkaline clarification, and membrane filtration. The average molecular weight and structural characteristics of RF were analyzed using size-exclusion chromatography and 13C NMR spectroscopy. Normal human dermal fibroblasts (NHDFs) were treated with RF by culturing cells in RF-supplemented medium (0.1–1.0 mg/mL). Cell viability and viable cell number were evaluated using the thiazolyl blue tetrazolium bromide and trypan blue exclusion assays, respectively. Expression of ECM-related genes was analyzed by qRT-PCR, and collagen and hyaluronan production were quantified by Sirius Red staining and ELISA. Results: RF had an average molecular weight of approximately 11,500 Da and consisted of nearly equal proportions of inulin- and levan-type fructans. RF (≤1 mg/mL) increased the number of viable cells and markedly upregulated collagen, type I, alpha 1 (COL1A1) and hyaluronic acid synthase 2 (HAS2) expression while downregulating Hyal1 expression. After 9 days of treatment, the cumulative production of type I collagen and hyaluronic acid increased by 3.8- and 1.3-fold, respectively, as compared with controls. Upregulation of lysyl oxidase (LOX) mRNA suggested enhanced collagen cross-linking, whereas MMP-1 showed only modest induction. Conclusions: Rakkyo-derived fructan directly stimulates collagen and hyaluronan synthesis in dermal fibroblasts, likely through regulation of ECM-related genes. These results suggest that rakkyo-derived fructan modulates ECM-related readouts in NHDFs under controlled in vitro conditions. Further validation in more complex skin models and in vivo studies is necessary.

## Linked entities

- **Genes:** COL1A1 (collagen type I alpha 1 chain) [NCBI Gene 1277], HAS2 (hyaluronan synthase 2) [NCBI Gene 3037], HYAL1 (hyaluronidase 1) [NCBI Gene 3373], LOX (lysyl oxidase) [NCBI Gene 4015], MMP1 (matrix metallopeptidase 1) [NCBI Gene 4312]
- **Species:** Allium chinense (taxon 130426), Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** HAS3 (hyaluronan synthase 3) [NCBI Gene 3038], CD44 (CD44 molecule (IN blood group)) [NCBI Gene 960] {aka CDW44, CSPG8, ECM-III, ECMR-III, H-CAM, HCELL}, FN1 (fibronectin 1) [NCBI Gene 2335] {aka CIG, ED-B, FINC, FN, FNZ, GFND}, HYAL1 (hyaluronidase 1) [NCBI Gene 3373] {aka HYAL-1, LUCA1, MPS9, NAT6}, HAS1 (hyaluronan synthase 1) [NCBI Gene 3036] {aka HAS}, HAS2 (hyaluronan synthase 2) [NCBI Gene 3037], HYAL2 (hyaluronidase 2) [NCBI Gene 8692] {aka LUCA2, MCCS}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, COL1A1 (collagen type I alpha 1 chain) [NCBI Gene 1277] {aka CAFYD, EDSARTH1, EDSC, OI1, OI2, OI3}, ELN (elastin) [NCBI Gene 2006] {aka ADCL1, SVAS, WBS, WS}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, MMP1 (matrix metallopeptidase 1) [NCBI Gene 4312] {aka CLG}, BCL2A1 (BCL2 related protein A1) [NCBI Gene 597] {aka ACC-1, ACC-2, ACC1, ACC2, BCL2L5, BFL1}, GPHA2 (glycoprotein hormone subunit alpha 2) [NCBI Gene 170589] {aka A2, GPA2, ZSIG51}, CDKN2A (cyclin dependent kinase inhibitor 2A) [NCBI Gene 1029] {aka ARF, CAI2, CDK4I, CDKN2, CMM2, INK4}, LIPA (lipase A, lysosomal acid type) [NCBI Gene 3988] {aka CESD, LAL}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, LOX (lysyl oxidase) [NCBI Gene 4015] {aka AAT10}, H3P16 (H3 histone pseudogene 16) [NCBI Gene 644914] {aka H3.6, H3F3AP6, p21}
- **Diseases:** fibrosis (MESH:D005355), injury to (MESH:D014947), cytotoxic (MESH:D064420), Type I COL (MESH:D006969), atopic dermatitis (MESH:D003876), type I and type III COL (MESH:C564921)
- **Chemicals:** trypan blue (MESH:D014343), chondroitin sulfate (MESH:D002809), proline (MESH:D011392), dextrans (MESH:D003911), Thiazolyl blue tetrazolium bromide (MESH:C022616), DMEM (-), D-glucuronic acid (MESH:D020723), hydroxyproline (MESH:D006909), Levan (MESH:C072599), mucopolysaccharides (MESH:D006025), sugars (MESH:D000073893), phosphate (MESH:D010710), pyridinoline (MESH:C015484), MTT (MESH:C070243), Polysaccharides (MESH:D011134), calcium hydroxide (MESH:D002126), fucoidan (MESH:C007789), V.C (MESH:C098534), polymers (MESH:D011108), N-acetyl-D-glucosamine (MESH:D000117), Fructan (MESH:D005630), acetonitrile (MESH:C032159), monosaccharide (MESH:D009005), fructose (MESH:D005632), D2O (MESH:D017666), water (MESH:D014867), TB (MESH:D013725), disaccharide (MESH:D004187), Bouin's solution (MESH:C026239), Vitamin C (MESH:D001205), isopropyl alcohol (MESH:D019840), inulin (MESH:D007444), HCl (MESH:D006851), lysine (MESH:D008239), PBS (MESH:D007854), beta-glucans (MESH:D047071), NaOH (MESH:D012972), 13C (MESH:C000615229), HA (MESH:D006820), reactive oxygen species (MESH:D017382), glucosamine (MESH:D005944), Lev (MESH:D007978)
- **Species:** Allium chinense (species) [taxon 130426], Hepatovirus A (no rank) [taxon 12092], Helianthus tuberosus (Jerusalem artichoke, species) [taxon 4233], Bacillus subtilis (species) [taxon 1423], Rattus norvegicus (brown rat, species) [taxon 10116], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Homo sapiens (human, species) [taxon 9606], Halomonas (genus) [taxon 2745], Cichorium intybus (chicory, species) [taxon 13427], Allium cepa (onion, species) [taxon 4679], Allium sativum (garlic, species) [taxon 4682]
- **Cell lines:** HA — Homo sapiens (Human), Neuroblastoma, Cancer cell line (CVCL_D044)

## Full text

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## Figures

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## References

39 references — full list in the complete paper: https://tomesphere.com/paper/PMC12942774/full.md

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Source: https://tomesphere.com/paper/PMC12942774