Håvard Hoel

• Hoel, Håvard; Petkowicz, Carmen; Eidsvåg, Victoria; Øynebråten, Inger; Corthay, Alexandre Benoit & Maurer, Juliana Bello Baron [Vis alle 7 forfattere av denne artikkelen] (2026). Comparative toll-like receptor and dectin-1a activation by structurally diverse plant polysaccharides. Carbohydrate Research. ISSN 0008-6215. 567. doi: 10.1016/j.carres.2026.110003. Fulltekst i vitenarkiv Vis sammendrag

  Naturally derived polysaccharides can activate pattern recognition receptors (PRRs) like Toll-like receptors (TLRs) and Dectin-1, but structure-activity relationships remain unclear. Here, we screened several plant-derived polysaccharides using HEK-Blue™ reporter cells expressing human Toll-like receptor (hTLR) 2, hTLR2/1, hTLR2/6, hTLR3, hTLR4, hTLR5 or hDectin-1a, THP1-Blue™ NF-κB cells and mouse bone marrow-derived macrophages to investigate the correlation between structural features and activity. The polysaccharides included pectins from Gentiana purpurea (GP-AP), Angelica archangelica subsp. archangelica (A-A2-I), Daphne mezereum (DMP-ED-I), Citrullus lanatus (FW), Coffea arabica (CAP) and Citrus sp. (CPA), an arabinogalactan protein (AGP) rich extract from Persea americana (FRAGP), and an arabinoxylan from Livistonia chinensis (LCP). Activation of THP1-Blue™ cells and BMDMs, and interaction with hTLR4 and hTLR2/6 correlated with rhamnogalacturonan-I (RG-I) backbones with galactan, including arabinogalactan-II (AG-II), side chains (GP-AP and DMP-ED-I), and by the presence of AGPs (FRAGP). The presence of 4-O-Me-GlcA in A-A2-I was seemingly negatively correlated with activation of hTLR2/6, despite presence of AG-II structures. The homogalacturonan-rich (HG) polysaccharides investigated in this study, FW, CAP and CPA, did not activate hTLR4 and hTLR2/6, suggesting that HG alone was insufficient for PRR engagement in these models. Several RG-I containing pectins activated hDectin-1a, and higher Mw generally enhanced activity. The AGP and xylose-rich polysaccharides tested in this study did not activate hDectin-1a, and the arabinoxylan LCP was inactive in all assays. None of the polysaccharides activated hTLR3 or hTLR5. In conclusion, several polysaccharides activated multiple PRRs, seemingly associated with presence of RG-I domains with neutral side chains.

• Hoel, Håvard; Carvalho, Mariana Mazetto de; Fu, Yu Ping; Chan, Emily; Hamre, Anne Grethe & Sørnes, Kristian [Vis alle 9 forfattere av denne artikkelen] (2026). Comprehensive structural characterization of pectin, arabinan and galactan from Gentiana purpurea L. roots and their immunostimulatory effects. Carbohydrate Polymer Technologies and Applications. 14. doi: 10.1016/j.carpta.2026.101117. Fulltekst i vitenarkiv Vis sammendrag

  The roots of Gentiana purpurea L. have historically been an important herbal drug in Norwegian folk medicine. Due to its content of bitter compounds, it was used to treat digestive ailments, but it was also boiled in water for use against infections. Previous work has shown promising immunostimulatory effects of a polysaccharide enriched fraction from G. purpurea, and therefore the aim of this present study was to further isolate and characterize these polysaccharides and investigate their immunogenic properties. One acidic polysaccharide fraction (Gentiana Purpurea Acidic Polysaccharides, GP-AP) and one neutral (Gentiana Purpurea Neutral Polysaccharides, GP-NP) were isolated by anion-exchange chromatography from the ethanol precipitate of G. purpurea root water extract, and their structures were characterized by SEC-MALS, GC, GC–MS and NMR. GP-AP was shown to contain pectin type structures such as homogalacturonan and rhamnogalacturonan type I backbones, as well as neutral structures such as arabinogalactan type I and highly branched arabinans. GP-NP had similar neutral polysaccharides as GP-AP, with high amounts of highly branched arabinans. GP-AP was able to cause an immunostimulatory response in J774.A1 macrophages, likely partly through interaction with TLR 4, whilst GP-NP was inactive.

• Hoel, Håvard; Boer, Hugo de; Kool, Anneleen & Wangensteen, Helle (2024). Analysis of bitter compounds in traditional preparations of Gentiana purpurea L. Fitoterapia. ISSN 0367-326X. 175. doi: 10.1016/j.fitote.2024.105932. Fulltekst i vitenarkiv Vis sammendrag

  Roots of Gentiana purpurea are known to have an intense bitter taste due to its high content of secoiridoids. In folk medicine roots have commonly been prepared as water decoctions, soaked in ethanol, or boiled with milk, wine, or beer. The aim of this study was to explore how various historical preparation methods influence yields of major bitter compounds in G. purpurea. HPLC-DAD analysis revealed that maceration with 40% and 70% ethanol, boiling with acetic acid (3% and 6%), vinegar and raw milk gave the highest extraction yields of gentiopicrin. Erythrocentaurin was detected when the roots were added to cold water before boiling, possibly because of enzymatic degradation. In contrast, erythrocentaurin was not detected in preparations where roots were added to boiling water, or when they were extracted with acetic acid or alcohol. The results stress the significance of traditional preparation methods to optimize yield of bioactive compounds.

• Zhang, Lin; Ulriksen, Emilie Steinbakk; Hoel, Håvard; Sandvik, Lene; Malterud, Karl Egil & Inngjerdingen, Kari Tvete [Vis alle 8 forfattere av denne artikkelen] (2023). Phytochemical characterization and anti-inflammatory activity of a water extract of Gentiana purpurea roots. Journal of Ethnopharmacology. ISSN 0378-8741. 301. doi: 10.1016/j.jep.2022.115818. Fulltekst i vitenarkiv Vis sammendrag

  Ethnopharmacological relevance Gentiana purpurea was one of the most important medicinal plants in Norway during the 18th and 19th centuries, and the roots were used against different types of gastrointestinal and airway diseases. Aim of the study To explore the content of bioactive compounds in a water extract from the roots, a preparation commonly used in traditional medicine in Norway, to assess the anti-inflammatory potential, and furthermore to quantify the major bitter compounds in both roots and leaves. Materials and methods G. purpurea roots were boiled in water, the water extract applied on a Diaion HP20 column and further fractionated with Sephadex LH20, reverse phase C18 and normal phase silica gel to obtain the low molecular compounds. 1D NMR, 2D NMR, and ESI-MS were used for structure elucidation. HPLC-DAD analysis was used for quantification. The inhibition of TNF-α secretion in ConA stimulated peripheral blood mononuclear cells (PBMCs) was investigated. Results Eleven compounds were isolated and identified from the hot water extract of G. purpurea roots. Gentiopicrin, amarogentin, erythrocentaurin and gentiogenal showed dose-dependent inhibition of TNF-α secretion. Gentiopicrin is the major secondary metabolite in the roots, while sweroside dominates in the leaves. Conclusions The present work gives a comprehensive overview of the major low-molecular weight compounds in the water extracts of G. purpurea, including metabolites produced during the decoction process, and show new anti-inflammatory activities for the native bitter compounds as well as the metabolites produced during preparation of the crude drug.

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• Hoel, Håvard & Wangensteen, Helle (2023). Quantification of bitter compounds in (un)traditional preparations of Gentiana purpurea roots. Fulltekst i vitenarkiv
• Helleve, Torstein; Hoel, Håvard & Wangensteen, Helle (2023). Oversett av vitskapen: Bitter plante frå folkemedisinen kan ha heilande effekt. [Internet]. https://forskning.no. Fulltekst i vitenarkiv
• Helleve, Torstein; Hoel, Håvard & Wangensteen, Helle (2023). Forsmådd og bitter folkemedisinplante under lupa. [Internet]. https://titan.uio.no. Fulltekst i vitenarkiv
• Hoel, Håvard & Inngjerdingen, Kari Tvete (2023). Naturmedisiner fra glemmeboken. Fulltekst i vitenarkiv
• Hoel, Håvard & Wangensteen, Helle (2022). Kvantifisering av bitterstoffer i (u)tradisjonelle tilberedninger av søterot (Gentiana purpurea). Fulltekst i vitenarkiv
• Zhang, Lin; Sandvik, Lene; Hoel, Håvard; Malterud, Karl Egil; Inngjerdingen, Kari Tvete & Wangensteen, Helle (2022). Phytochemical screening of Gentiana purpurea, an important Norwegian medicinal plant. Fulltekst i vitenarkiv
• Zhang, Lin; Sandvik, Lene; Ulriksen, Emilie Steinbakk; Hoel, Håvard; Malterud, Karl Egil & Inngjerdingen, Kari Tvete [Vis alle 8 forfattere av denne artikkelen] (2022). Søterot, en bitter og glemt norsk medisinplante. Fulltekst i vitenarkiv
• Hoel, Håvard; Inngjerdingen, Kari Tvete & Wangensteen, Helle (2026). Comparative structure–activity relationship of naturally derived polysaccharides targeting pattern recognition receptors. Universitetet i Oslo. Fulltekst i vitenarkiv Vis sammendrag

  Due to their low toxicity and ability to activate the immune system, the use of polysaccharides from plants and fungi have been proposed in cancer therapy and vaccine development. Despite these well-known abilities, the relationship between chemical structure and immunostimulatory activity remains unclear. In this thesis, polysaccharides from plants and one fungus were tested for the ability to activate immune cells through interaction with proteins which recognize infections, known as pattern recognition receptors (PRRs). The results show that some polysaccharide structures are more active towards certain PRRs than others, and that highly branched pectin type polysaccharides from the plant cell wall are amongst the most active. On the other hand, polysaccharides which were more linear were less active, or lacked immunostimulatory properties altogether. One pectin isolated from the Norwegian medicinal plant Gentiana purpurea L. showed activation of multiple PRRs, and its structure was therefore comprehensively characterized. This pectin was modified by removing specific parts of molecule, and its immunostimulatory effects were tested again. Depending on which part was removed, the activity either increased or decreased, indicating that specific structural properties of the polysaccharide are more associated with activation of specific PRRs than others. These results provide further insight into the correlation between polysaccharide structure and immunostimulatory activity.

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