(923.3) Fucoidan as an inhibitor of pro-inflammatory cytokines: Potential candidate for treating inflammatory-related conditions

Poster Board Number: B201

Tauseef Ahmad (University of Tasmania), Muhammad Ishaq (University of Tasmania), Mathew Eapen (University of Tasmania), Neeraj Singh (University of Tasmania), Ahyoung Park (Marinova Pty Ltd.,), Sam Karpiniec (Marinova Pty Ltd.,), Damien Stringer (Marinova Pty Ltd.,), Helen Fitton (RD Advisor), Vanni Caruso (University of Tasmania), Rajaraman Eri (University of Tasmania)

Fucoidans are bio-functional sulfated, complex, fucose-rich polymers found in brown seaweeds. Fucoidans are favourable worldwide, particularly amongst the nutraceutical and pharmaceutical industry due to their promising therapeutic effects. Their applaudable biological functions are attributed to their unique biological structure. Fucoidans have been shown to have multiple biological activities, including anti-inflammatory effects, and are recognised to inhibit inflammatory processes via several pathways such as enzyme inhibition and selectin blockade, and have demonstrated inhibition of inflammatory pathologies in-vivo. Inflammation is a part of the complex biological response of living systems against harmful stimuli and is involved in the pathogenesis of diverse diseases, including arthritis, Inflammatory Bowel diseases, cancer, and allergies.In this current research, several fucoidan extracts from Undaria pinnatifida, Fucus vesiculosus, Macrocystis pyrifera, Ascophyllum nodosum, and Laminaria japonica were assessed for inhibition of pro-inflammatory cytokine production (TNF-α, IL-1β, and IL-6) in LPS induced human macrophage cell line (THP-1) and human peripheral blood mononuclear cells (PBMCs). Furthermore, we also sought to catalogue these extracts based on their anti-inflammatory effects in the current in-vitro cell model.

Material and methods

MTT cell viability assay was performed to assess the cytotoxicity of fucoidan extracts. Furthermore, a dose-response for fucoidan extracts was performed in LPS induced THP-1 cells and PBMCs after pre-treatment for 24 hours and levels of TNF-α, IL-1β, and IL-6 cytokines were measured using Enzyme-Linked Immunosorbent Assay (ELISA).

 Results

MTT cell viability assay revealed that fucoidan extracts displayed no signs of cytotoxicity in THP-1 cells and PBMCs after incubation of 48 hours. Sandwich ELISA results exhibited that all fucoidan extracts reduced cytokine production in LPS stimulated PBMCs and human THP-1 cells in a dose-dependent fashion. Notably, the lower molecular fucoidan (5-30 kDa) extract from Macrocystis pyrifera was a highly effective inhibitor of pro-inflammatory cytokine at lower concentrations. Fucoidan extracts from all species demonstrated significant anti-inflammatory effects; however, the lower molecular weight extracts showed maximal effects at low concentrations. These observations on various fucoidan extracts offer insight into strategies that improve their efficacy against inflammation-related pathology.

ConclusionWe have successfully catalogued many fucoidan extracts based on their efficacy in LPS induced macrophages and PBMCs in down-regulating major pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), potential targets in human inflammatory conditions. Further investigation would provide additional insights about the mechanism of action to test for therapeutic applications as an anti-inflammatory medication.

This research was funded by Marinova Pty Ltd., Cambridge, TAS 7170, Australia





Effects of multiple fucoidan extracts on LPS induced pro-inflammatory cytokine TNF-α in human THP-1. Cells were pre-treated with several fucoidan extracts. UPF and its derived extracts (A–C), FVF and its derived extracts (D–F), MPF and derived extracts (G–I), FVC (J), ANF (K) and LJF (L) with indicated doses (10, 50, 100, and 200 µg/mL) for 24 h before LPS treatment (0.5 µg/mL), supernatants were isolated, and the amounts of TNF-α was measured.; Effects of multiple fucoidan extracts on LPS induced pro-inflammatory cytokine, IL-1β in human THP-1 monocyte cells. Cells were pre-treated with several fucoidan extracts. UPF and its derived extracts (A–C), FVF and its derived extracts (D–F), MPF and derived extracts (G–I), FVC (J), ANF (K) and LJF (L) with indicated doses (10, 50, 100, and 200 µg/mL) for 24 h before LPS treatment for 24 h (0.5 µg/mL), supernatants were isolated, and the amounts of TNF-α were subsequently measured.