24(R, S)-Saringosterol – From artefact to a biological medical agent

Kenneth Vanbrabanta,b, David Van Meelb,c, Anja Kerksiekb, Silvia Friedrichb, Marco Dubbeldamd, Melissa Schepersa,e, Katharina Gutbrodf, Peter Dörmannf, Hong-Bing Liug, Monique T. Mulderh, Tim Vanmierloa,e, Dieter Lütjohannb

a Neuro-immune connect & repair lab, Biomedical research institute, Hasselt University, Martelarenlaan 42, 3500 Hasselt, Belgium, bInstitute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Venusberg-Campus 1, D-53127 Bonn, Germany, cChemie and biobased technologie, Avans Hogeschool, Onderwijsboulevard 5223, ‘s-Hertogenbosch, The Netherlands, dStichting Zeeschelp, Oosthavendijk 7, 4493BK Kamperland, The Netherlands, eSchool for mental health and neuroscience, Maastricht University, Universiteitssingel 50, 6229ER Maastricht, The Netherlands, fInstitute of Molecular Physiology and Biotechnology of Plants (IMBIO), University of Bonn, Karlrobert-Kreiten-Str. 13, 53115 Bonn, Germany, gKey Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Yushan Road 5, 266003, Qingdao, China, hDepartment of Internal Medicine, Laboratory of Vascular Medicine, Erasmus MC University Medical Center, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands

Enhancing the cholesterol turnover in the brain via activation of liver x receptors (LXR) can restore memory in a mouse model for Alzheimer’s disease (AD). The edible Asian brown alga Sargassum fusiforme (Hijiki) contains high amounts of oxysterols such as 24(S)-saringosterol that are a potent liver x receptor (LXR) agonists. We aimed to find native European seaweed species with contents of 24(S)-saringosterol that are comparable to those found in Sargassum fusiforme. Additionally, we hypothesize that seasonal variations modify the amount of 24(S)-saringosterol in seaweeds. Sterols and oxysterols were extracted with chloroform/methanol from various seaweed species harvested in the Eastern Scheldt in different seasons between October 2016 and September 2017. Identification and quantification of the lipids was performed by gas chromatography (GC)- mass spectrometry and GC- flame ionization detection. We confirmed that brown algae Undaria pinnatifida harvested in February and Sargassum muticum harvested in October contained the highest amounts of 24(R,S)-Saringosterol (32.4 ± 15.25 µg/g and 32.95 ± 2.91 µg/g, mean ±S.D., respectively) and its precursor fucosterol (1.48 ± 0.11 mg/g), higher than Sargassum fusiforme (20.94 ± 3.00, mean ±S.D.), while Ascophyllum nodosum and Fucus vesiculosus and Fucus serratus contained amounts of 24(R,S)-Saringosterol (22.09 ± 3.45 µg/g, 18.04 ± 0.52 µg/g and 19.47 ± 9.01 µg/g, mean ±S.D., respectively) comparable to Sargassum fusiforme. In other algae only minor amounts of these sterols were observed. The green algae Ulva lactuca (0.29 mg/g fucosterols and 10.3 µg/g saringosterol) and Codium species (not detectable), and all investigated red algae did not contain any 24(R,S)-saringosterol or fucosterol. In the Eastern Scheldt algae harvested in September/October delivered the highest yield for 24(R,S)-saringosterol, with the exception of Undaria pinnatifida that showed the highest levels in February. We showed that exposure of lipid extracts of Ulva lactuca to sunlight at room temperature or in the presence of oxygen to UV-C light lead to the quantitative conversion of fucosterol into 24(R,S)-saringosterol. Exposing pure fucosterol to UV-light did not convert any fucosterol into 24(R,S)-saringosterol underscoring the requirement of seaweed constituents in the conversion of fucosterol into 24(R,S)-saringosterol. In conclusion, we showed that brown seaweeds harvested from the Eastern Scheldt contain amounts of 24(S)-saringosterol comparable to Sargassum fusiforme, varying per season and showing the highest amounts in spring. In accordance with these observations the amount of 24(S)-saringosterol in the brown seaweeds can be modulated by light.