# Study of the Cytotoxic and Wound Healing Activity of Polysaccharides from Bovistella utriformis

**Authors:** Aya Maaloul, Piedad Valverde-Guillén, Casimiro Cárdenas-García, Claudia Pérez Manríquez, Marisel Araya-Rojas, Manuel Marí-Beffa, Victor Fajardo, Roberto T. Abdala Díaz

PMC · DOI: 10.3390/molecules31040653 · Molecules · 2026-02-13

## TL;DR

This study shows that polysaccharides from Bovistella utriformis are safe and promote wound healing and tissue regeneration in both lab and animal models.

## Contribution

The study introduces B. utriformis polysaccharides as novel bioactive compounds with wound-healing and regenerative potential.

## Key findings

- PsBU showed no cytotoxicity and increased cell viability at higher concentrations.
- PsBU promoted wound closure in vitro and enhanced zebrafish fin regeneration in vivo.
- Proteomic analysis revealed upregulation of proteins involved in tissue repair and cell cycle regulation.

## Abstract

Bovistella utriformis (Bull.) Demoulin & Rebriev is a cosmopolitan puffball mushroom traditionally recognized for its anti-inflammatory and wound-healing properties. This study aimed to evaluate the cytotoxic profile, regenerative potential, and molecular effects of polysaccharides extracted from B. utriformis (PsBU) using complementary in vitro and in vivo approaches. Thermogravimetric analysis revealed good thermal stability up to 300 °C with 26.91% residual mass at 800 °C. Human HaCaT keratinocytes were used to assess cell viability, proliferation, and cell-cycle distribution through MTT assays and flow cytometry, while wound-healing activity was examined using in vitro scratch assays. PsBU exhibited no cytotoxic effects across concentrations from 19.53 to 10,000 µg mL−1, with cell viability remaining above 68%. At 5000 and 10,000 µg mL−1, viability increased to 130% and 126%, respectively. The optimal in vitro wound-healing effect was observed at 500 µg mL−1, achieving 40% wound closure at 32 h. Label-free quantitative proteomic analysis by UHPLC-HRMS identified 83 differentially expressed proteins, including upregulation of tissue repair-related factors such as plasminogen and FHL2, alongside modulation of cell-cycle regulation and mRNA transport pathways. In vivo zebrafish caudal fin regeneration assays demonstrated maximal regenerative activity at 200 µg mL−1 (p < 0.001 vs. control). Overall, these findings demonstrate that B. utriformis polysaccharides are safe bioactive compounds that promote key biological processes involved in tissue regeneration, supporting their potential application as natural wound-healing agents.

## Linked entities

- **Proteins:** LOC125948914 (serine protease snake-like), FHL2 (four and a half LIM domains 2)
- **Species:** Bovistella utriformis (taxon 2493946), Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** il1b (interleukin 1, beta) [NCBI Gene 405770] {aka il1-b, zgc:111873}, plg (plasminogen) [NCBI Gene 322691] {aka wu:fb70e09}, CCNK (cyclin K) [NCBI Gene 8812] {aka CPR4, IDDHDF}, vaspa (vasodilator stimulated phosphoprotein a) [NCBI Gene 555805] {aka vasp, zgc:162320}, DYNLRB1 (dynein light chain roadblock-type 1) [NCBI Gene 83658] {aka BITH, BLP, DNCL2A, DNLC2A, ROBLD1}, NDC1 (NDC1 transmembrane nucleoporin) [NCBI Gene 55706] {aka NEDAPA, NET3, TMEM48}, KIFC1 (kinesin family member C1) [NCBI Gene 3833] {aka HSET, KNSL2}, ZFR (zinc finger RNA binding protein) [NCBI Gene 51663] {aka SPG71, ZFR1}, RPL19 (ribosomal protein L19) [NCBI Gene 6143] {aka L19, eL19}, RGPD2 (RANBP2 like and GRIP domain containing 2) [NCBI Gene 729857] {aka NUP358, RANBP2L2, RGP2, ranBP2-like 2}, RPS13 (ribosomal protein S13) [NCBI Gene 6207] {aka S13, uS15}, MRPS10 (mitochondrial ribosomal protein S10) [NCBI Gene 55173] {aka MRP-S10, PNAS-122, S10mt, uS10m}, VASP (vasodilator stimulated phosphoprotein) [NCBI Gene 7408], NUP85 (nucleoporin 85) [NCBI Gene 79902] {aka FROUNT, NPHS17, Nup75}, MYL12B (myosin light chain 12B) [NCBI Gene 103910] {aka MLC-B, MRLC2}, RPL7 (ribosomal protein L7) [NCBI Gene 6129] {aka L7, humL7-1, uL30}, il6 (interleukin 6 (interferon, beta 2)) [NCBI Gene 100885851], BUB1B (BUB1 mitotic checkpoint serine/threonine kinase B) [NCBI Gene 701] {aka BUB1beta, BUBR1, Bub1A, MAD3L, MVA1, SSK1}, Nup85 (nucleoporin 85) [NCBI Gene 445007] {aka Pcnt1, frount}, Ndc1 (NDC1 transmembrane nucleoporin) [NCBI Gene 72787] {aka 2810475A17Rik, Tmem48, sks}, Nup210 (nucleoporin 210) [NCBI Gene 54563] {aka 9830001L10, Pom210, gp190, gp210}, FHL2 (four and a half LIM domains 2) [NCBI Gene 2274] {aka AAG11, DRAL, FHL-2, SLIM-3, SLIM3}, Bub1b (BUB1B, mitotic checkpoint serine/threonine kinase) [NCBI Gene 12236] {aka BUBR1}, SRSF3 (serine and arginine rich splicing factor 3) [NCBI Gene 6428] {aka SFRS3, SRp20}, YWHAH (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta) [NCBI Gene 7533] {aka YWHA1}, U2AF1 (U2 small nuclear RNA auxiliary factor 1) [NCBI Gene 7307] {aka FP793, RN, RNU2AF1, U2AF35, U2AFBP}, tnfa (tumor necrosis factor a (TNF superfamily, member 2)) [NCBI Gene 405785], PLG (plasminogen) [NCBI Gene 5340] {aka HAE4}, NUP210 (nucleoporin 210) [NCBI Gene 23225] {aka GP210, POM210}, Bub1 (BUB1, mitotic checkpoint serine/threonine kinase) [NCBI Gene 12235] {aka Bub1a, D2Xrf87}, ITPR3 (inositol 1,4,5-trisphosphate receptor type 3) [NCBI Gene 3710] {aka CMT1J, IMD132, IMD133, IP3R, IP3R-3, IP3R3}, RNASE1 (ribonuclease A family member 1, pancreatic) [NCBI Gene 6035] {aka RAC1, RIB1, RNS1}
- **Diseases:** aneuploidy (MESH:D000782), Cytotoxic (MESH:D064420), weight loss (MESH:D015431), tumorigenesis (MESH:D063646), cancer (MESH:D009369), osteoporotic (MESH:D058866), injury to (MESH:D014947), inflammation (MESH:D007249)
- **Chemicals:** hydrogen (MESH:D006859), ulvan (MESH:C571831), PBS (MESH:D007854), beta-glucan (MESH:D047071), tricaine (MESH:C003636), saponins (MESH:D012503), glucose (MESH:D005947), flavonoids (MESH:D005419), CO2 (MESH:D002245), L-glutamine (MESH:D005973), BCA (MESH:C047117), 2-methoxyestradiol (MESH:D000077584), ABTS (MESH:C002502), MTT (MESH:C070243), amphotericin B. (MESH:D000666), carbohydrate (MESH:D002241), phenols (MESH:D010636), S (MESH:D013455), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MESH:C022616), NO (MESH:D009614), DTG (-), PI (MESH:D011419), penicillin (MESH:D010406), alkaloids (MESH:D000470), dithiothreitol (MESH:D004229), galactose (MESH:D005690), ethanol (MESH:D000431), nitric oxide (MESH:D009569), water (MESH:D014867), iodoacetamide (MESH:D007460), alumina (MESH:D000537), PVPP (MESH:C077842), nitrogen (MESH:D009584), Polysaccharide (MESH:D011134), CO (MESH:D002248), C (MESH:D002244), streptomycin (MESH:D013307), polyacrylamide (MESH:C016679), polymer (MESH:D011108), DPPH (MESH:C004931), mannose (MESH:D008358), formazan (MESH:D005562), P (MESH:D010758)
- **Species:** Limnospira maxima (species) [taxon 129910], PX clade (clade) [taxon 569578], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Lentinula edodes (shiitake mushroom, species) [taxon 5353], Calvatia utriformis [taxon 258083], Danio rerio (leopard danio, species) [taxon 7955], Ganoderma lucidum (species) [taxon 5315], Mus musculus (house mouse, species) [taxon 10090], Trametes versicolor (turkey-tail fungus, species) [taxon 5325], Ulva rigida (species) [taxon 75689], Coriolus (genus) [taxon 5326], Agaricus bisporus (common mushroom, species) [taxon 5341]
- **Cell lines:** HACAT — Homo sapiens (Human), Spontaneously immortalized cell line (CVCL_0038)

## Full text

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## Figures

10 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12943274/full.md

## References

66 references — full list in the complete paper: https://tomesphere.com/paper/PMC12943274/full.md

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Source: https://tomesphere.com/paper/PMC12943274