# Ulvan and Ulva oligosaccharides from Ulva sp. attenuate osteoarthritis in a high-fat diet and ligamentous meniscal injury-induced rat model

**Authors:** Sabri Sudirman, Yi-Chia Lin, Yi-Yuh Hwang, Jerrell Felim, Hsiang-Ping Kuo, Deng-Fwu Hwang, Zwe-Ling Kong

PMC · DOI: 10.1186/s40643-026-01012-9 · Bioresources and Bioprocessing · 2026-02-28

## TL;DR

This study shows that compounds from seaweed can reduce osteoarthritis symptoms in rats by lowering inflammation and cartilage damage.

## Contribution

The study demonstrates the protective effects of Ulva-derived ulvan and oligosaccharides in an osteoarthritis rat model.

## Key findings

- Ulvan and Ulva oligosaccharides reduced inflammation and cartilage degradation in OA rats.
- Treatments lowered triglycerides, cholesterol, and pro-inflammatory markers in OA rats.
- Ulva hydrolysate showed higher sugar and sulfated group content than the original extract.

## Abstract

Osteoarthritis (OA) is a chronic joint disease. It is marked by the progressive deterioration of subchondral bone, articular cartilage, and synovium, with obesity acting as a significant risk factor by promoting inflammation and cartilage degradation. Ulvan and Ulva oligosaccharides derived from Ulva sp. seaweed have shown anti-inflammatory properties that may be beneficial in this context. Therefore, the aim of this research was to determine the protective effect of ulvan and Ulva oligosaccharides from Ulva sp. on monosodium iodoacetate (MIA)-induced inflammation in SW1353 cells and in a high-fat-diet/ACL-meniscus-injury rat model of osteoarthritis. The Ulva extract (UE) was hydrolyzed with cellulase to obtain Ulva hydrolysate (UH). The rats were treated using UE (50 mg/kg) and three different doses of UH (UH1, 50 mg/kg; UH2, 100 mg/kg; UH5, 250 mg/kg). In addition, UH contains higher levels of total sugars (22.8 ± 1.3%) and sulfated groups (18.4 ± 0.2%) compared with UE (19.6% and 15.5%, respectively). Treatment with UE and UH significantly reduce matrix metalloproteinase-3 (MMP-3) and interleukin-6 levels and increase collagen type II alpha 1 level in MIA-induced SW1353 cells. The animal study revealed that UE and UH significantly decrease triglyceride (TG), total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) levels. These treatments also reduced nitric oxide levels in OA rats and inhibited pro-inflammatory cytokines and mediators, MMP-3, and C-terminal cross-linked telopeptides of type II collagen (CTX-II). Additionally, UE and UH treatment reduced proteoglycan loss in cartilage lesions in OA rats after six weeks of treatment. These findings suggest that Ulvan and Ulva oligosaccharides from Ulva sp. may have potential as treatments for osteoarthritis.

The online version contains supplementary material available at 10.1186/s40643-026-01012-9.

## Linked entities

- **Genes:** MMP3 (matrix metallopeptidase 3) [NCBI Gene 4314], IL6 (interleukin 6) [NCBI Gene 395337]
- **Chemicals:** nitric oxide (PubChem CID 145068)
- **Diseases:** osteoarthritis (MONDO:0005178)
- **Species:** Ulva sp. (taxon 2812607), Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, Col2a1 (collagen type II alpha 1 chain) [NCBI Gene 25412] {aka CG2A1A, COLLII}, MIA (MIA SH3 domain containing) [NCBI Gene 8190] {aka CD-RAP, MIA1}, Keap1 (Kelch-like ECH-associated protein 1) [NCBI Gene 117519] {aka Inrf2}, Cpox (coproporphyrinogen oxidase) [NCBI Gene 304024], Ptgs2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 29527] {aka COX-2, Cox2, PGHS-2, PHS II, Pghs2}, Nfe2l2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 83619], PTGS2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 5743] {aka COX-2, COX2, GRIPGHS, PGG/HS, PGHS-2, PHS-2}, Mia (MIA SH3 domain containing) [NCBI Gene 81510] {aka Cdrap, Mia1}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Il1b (interleukin 1 beta) [NCBI Gene 24494] {aka IL-1F2}, MMP3 (matrix metallopeptidase 3) [NCBI Gene 4314] {aka CHDS6, MMP-3, SL-1, STMY, STMY1, STR1}, COX2 (cytochrome c oxidase subunit II) [NCBI Gene 4513] {aka COII, MTCO2}, COL2A1 (collagen type II alpha 1 chain) [NCBI Gene 1280] {aka ACG2, ANFH, ANFH1, AOM, COL11A3, EDMMD}, Tumor necrosis factor [NCBI Gene 103694380], IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, Mmp3 (matrix metallopeptidase 3) [NCBI Gene 171045] {aka MMP-3, SL-1}, Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}
- **Diseases:** ligamentous meniscal injury (MESH:D010007), stiffness (MESH:C566112), gastrointestinal irritation (MESH:D005767), infection (MESH:D007239), joint disease (MESH:D007592), knee OA (MESH:D020370), OBOA (MESH:D009140), postoperative (MESH:D019106), medial meniscus (MESH:D000070600), medial (MESH:D020423), chondrosarcoma (MESH:D002813), Inflammatory (MESH:D007249), degenerative disease (MESH:D019636), pain (MESH:D010146), ACL (MESH:D000070598), Obesity (MESH:D009765), OA (MESH:D010003), cartilage breakdown (MESH:D002357)
- **Chemicals:** Safranin-O (MESH:C009195), MMx (-), glucuronic acid (MESH:D020723), n-butanol (MESH:D020001), penicillin (MESH:D010406), oligosaccharides (MESH:D009844), rhamnose (MESH:D012210), carbohydrate (MESH:D002241), 3,6-anhydrogalactose (MESH:C117625), CO2 (MESH:D002245), polyphenols (MESH:D059808), Zoletil (MESH:C006131), xylose (MESH:D014994), cefazolin (MESH:D002437), lipid (MESH:D008055), Ulvan (MESH:C571831), sulfuric acid (MESH:C033158), glucosamine sulfate (MESH:D005944), glucose (MESH:D005947), fucose (MESH:D005643), formaldehyde (MESH:D005557), mannose (MESH:D008358), methanol (MESH:D000432), silica gel (MESH:D058428), paraffin (MESH:D010232), Fat (MESH:D005223), sulfate (MESH:D013431), Carrageenan (MESH:D002351), sugar (MESH:D000073893), Polysaccharides (MESH:D011134), iduronic acid (MESH:D007067), Fucoidans (MESH:C007789), streptomycin (MESH:D013307), uronic acid (MESH:D014574), monosaccharide (MESH:D009005), TG (MESH:D014280), ester (MESH:D004952), water (MESH:D014867), phenol (MESH:D019800), PGE2 (MESH:D015232), disaccharide (MESH:D004187), Monosodium iodoacetate (MESH:D019807), acetic acid (MESH:D019342), galactose (MESH:D005690), NO (MESH:D009569), cholesterol (MESH:D002784), ethanol (MESH:D000431)
- **Species:** Ulva meridionalis (species) [taxon 434723], Phaeophyceae (brown algae, class) [taxon 2870], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Rhodophyta (red algae, phylum) [taxon 2763], Ulva ohnoi (species) [taxon 240864], Ulva arasakii (sea lettuce, species) [taxon 3119], Ulva (sea lettuces, genus) [taxon 3118], Ulva sp. (species) [taxon 2812607]
- **Cell lines:** SW1353 — Homo sapiens (Human), Primary central chondrosarcoma, Cancer cell line (CVCL_0543)

## Full text

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## Figures

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## References

28 references — full list in the complete paper: https://tomesphere.com/paper/PMC12950125/full.md

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Source: https://tomesphere.com/paper/PMC12950125