Sulfated galactan from Kappaphycus alvarezii as a UV-protective agent: A modulator of matrix metalloproteinase and genotoxic stress in human dermal fibroblast cells

Thankachan, Theresa and Chakraborty, Kajal and Mereeta, T J and Pai, Ashwin A and Vijay, Anoop P and Bose, Chaithanya (2026) Sulfated galactan from Kappaphycus alvarezii as a UV-protective agent: A modulator of matrix metalloproteinase and genotoxic stress in human dermal fibroblast cells. Food Bioscience, 83. pp. 1-15. ISSN 2212-4306

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Abstract

Chronic ultraviolet (UV) exposure increases the incidence of skin cancers and related effects, such as sunburn, photoaging, and precancerous lesions. Photoprotective agents, particularly sulfated galactans derived from Rhodophyceae, are emerging as promising natural resources. This study investigates a sulfated galactan (KAP-3) isolated from Kappaphycus alvarezii, composed of (1 → 3)/(1 → 4) linked β-Galp4S and α-3,6-AnGalp units, as a potential cytoprotective agent for human dermal fibroblast (HDF) cells. Preliminary assessment revealed that KAP-3 possesses an ultra-protective sun protection factor (SPF) above the benchmark value of 20, with a concentration-dependent increase up to 800 ppm, where a maximal SPF of 33.45 was achieved. Within the concentration range of 15.62-62.5 μg/mL, KAP-3 preserved 70.80-93.21% of HDF cells from UV-A induced apoptosis by protecting membrane integrity and preventing DNA damage. Administration of KAP-3 (62.5 μg/mL) markedly reduced mitochondrial superoxide levels (∼73%) relative to UV-A irradiated HDF cells. Similarly, KAP-3 significantly restored UV-A induced oxidative imbalance in HDF cells by reducing nitric oxide production by 49% and DNA damage by 80%, comparable to epigallocatechin gallate (EGCG; 22 μM). Finally, KAP-3 reduced the UV-A induced matrix metalloproteinase (MMP)-1 and 9 expressions by 2.64- and 2.40-fold, respectively, showing efficacy comparable to EGCG. The distinctive structure, sulfate groups and 1 → 3/1 → 4 glycosidic linkages in KAP-3 enable the suppression of radical generation, leading to reduced mitochondrial damage, DNA damage, and MMP activation in HDF cells through modulation of enzyme inhibition. Collectively, these multifunctional activities of KAP-3 position it as a strong candidate for pharmaceutical applications aimed at mitigating UV-induced oxidative damage.

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