Helle Wangensteen

• Hoel, Håvard; Carvalho, Mariana Mazetto de; Fu, Yu Ping; Chan, Emily; Hamre, Anne Grethe & Sørnes, Kristian [Show all 9 contributors for this article] (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. Full text in Research Archive Show summary

  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.

• Bada, Lucía; Butt, Hussain Shakeel; Quezada, Elías; Picos, Aitor; Wangensteen, Helle & Inngjerdingen, Kari Tvete [Show all 8 contributors for this article] (2025). Antitumor Activity, Mechanisms of Action and Phytochemical Profiling of Sub-Fractions Obtained from Ulex gallii Planch. (Fabaceae): A Medicinal Plant from Galicia (Spain). Molecules. ISSN 1431-5157. 30(4). doi: 10.3390/molecules30040972. Full text in Research Archive
• Mohamed, Warsan Nora; Butt, Hussain Shakeel; Schmidt, Thomas J.; Eltvik, Andrea Angelov; Wu, Desheng & Malterud, Karl Egil [Show all 9 contributors for this article] (2025). Biflavonoids and bi- and tricoumarins from Daphne mezereum and inhibition of TNF-α secretion. Phytochemistry. ISSN 0031-9422. 229. doi: 10.1016/j.phytochem.2024.114308. Full text in Research Archive Show summary

  Daphne mezereum L. (Thymelaeaceae) was an important medicinal plant in Norway during the 18th and 19th centuries and used against diseases such as diarrhea, swelling, stomach pain, and tuberculosis. Five previously undescribed phenolic compounds, including two biflavonoids with a catechin core structure, two tricoumarins, and one bicoumarin, together with ten known compounds were isolated from a 50% EtOH extract of the bark of D. mezereum. Using NMR, HRESIMS, acid hydrolysis, and circular dichroism spectra, the biflavonoids were identified as 3′-hydroxygenkwanol A and 3′-hydroxydihydrodaphnodorin B, and the coumarins were identified as 3‴-O-acetyltriumbellin, triumbellin 4‴-O-β-d-glucopyranoside, and daphnogitin-7-O-β-d-glucopyranoside. The absolute configuration of dihydrodaphnodorin B was for the first time established as 2R, 3S, 2″S, 3″S. Daphnin, syringin, 3′-hydroxydihydrodaphnodorin B, dihydrodaphnodorin B, and neochamaejasmin A and B were identified as the major secondary metabolites in the extract. Neochamaejasmin A and B showed the most potent inhibition of TNF-α secretion in Con A stimulated peripheral blood mononuclear cells (PBMCs) with 71.3 ± 3.4 and 83.5 ± 11.5% inhibition, respectively, at 50 μM.

• Sandvik, Lene; Goodman, Christopher Dean; Malterud, Karl Egil & Wangensteen, Helle (2025). Novel compounds from Gentiana purpurea L. and their anti-plasmodial evaluation. Fitoterapia. ISSN 0367-326X. 185, p. 106713–106713. doi: 10.1016/j.fitote.2025.106713. Full text in Research Archive Show summary

  Gentiana pupurea L. (Gentianaceae) is an important medicinal plant in Norway and the bitter roots were used against a number of diseases, often related to gastrointestinal ailments and respiratory diseases. Gentian species are reported to be used against malaria in several geographic regions, and in vitro and computational experiments indicate that secoiridoids have an anti-plasmodial effect. Three previously undescribed compounds; the biphenyl secoiridoid glycoside 5′′-deoxyamaroswerin, the benzophenone 6′′-O-sinapoyl-2,4,3′-trihydroxy-benzophenone-6-O-β-glucopyranoside, and the benzyl benzoate (3-hydroxy-2-methoxybenzyl)-2,3-dihydroxybenzoate, together with eleven other low-molecular compounds were isolated from the 70 % ethanol extract of G. purpurea roots. The structures were elucidated by 1D and 2D NMR methods and high-resolution mass spectrometry. No in vitro anti-plasmodial activity was observed for the 70 % ethanol extract, swertiamarin, sweroside, gentiopicrin, amaroswerin, amarogentin, 5′′-deoxyamaroswerin, and amaropanin obtained from G. purpurea.

• Eltvik, Andrea Angelov; Inngjerdingen, Marit & Wangensteen, Helle (2025). In vitro anti-inflammatory properties of twelve Norwegian medicinal plants. Journal of Ethnopharmacology. ISSN 0378-8741. 352. doi: 10.1016/j.jep.2025.120159. Full text in Research Archive Show summary

  Ethnopharmacological relevance Today, inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease represent a major health burden in Western societies. Such diseases are treated with drugs aiming at suppressing inflammatory symptoms. In Norway, several medicinal plants share a history of ethnomedical use towards the treatment of various inflammatory conditions which could represent sources of new anti-inflammatory drugs. Aim of the study This study focused on exploring the potential of understudied traditional medicinal plants used in Norway to treat inflammation of different origin. Through phytochemical and biological screening methods, we aimed to identify plants with anti-inflammatory properties that also showed a high proportion of phenolic compounds. Based on these results, such plants would be of interest and relevance for further work including isolation and characterization of phytochemicals that could serve as novel anti-inflammatory drugs. Materials and methods A systematic literature survey of historical records from the 1800s and onwards was performed searching for plants used to treat various inflammatory diseases. Twelve plants were selected and subjected to accelerated solvent extraction to obtain extracts rich in phenolic compounds, namely dichloromethane and 80 % ethanol extracts. These were studied in bioassays assessing their in vitro anti-inflammatory effects. Their ability to inhibit nitric oxide (NO) and TNF-α cytokine production was measured, and their protection against indomethacin induced damage of the intestinal epithelial barrier was evaluated using differentiated Caco-2 cells. The total phenolic content of the extracts was determined, and 1H NMR spectroscopy and HPLC-DAD was performed for phytochemical profiling. Results Several of the plants presented moderate to high bioactivity, namely Matricaria discoidea, Alnus incana, Geranium sylvaticum, Antennaria dioica, Tanacetum vulgare and Malva moschata. A stronger effect was observed among the dichloromethane extracts in NO and TNF-α inhibition, while the 80 % ethanol extracts showed greater protection of the barrier integrity. M. discoidea, A. incana and G. sylvaticum are of particular interest, presenting consistently high bioactivity. Their 1H NMR spectra also showed a high proportion of phenolic compounds. Conclusion Both A. incana and M. discoidea are scarcely studied regarding their bioactivity and chemical composition, being potential candidates for the discovery of novel anti-inflammatory drugs. Based on the results obtained from this study, further work will focus on these two plants, including isolation of phenolic compounds and assessing their biological activities.

• Butt, Hussain Shakeel; Bada, Lucía; Malterud, Karl Egil; Inngjerdingen, Kari Tvete & Wangensteen, Helle (2025). New coumarins from a hot water extract of Daphne mezereum bark. Phytochemistry Letters. ISSN 1874-3900. 67. doi: 10.1016/j.phytol.2025.102954. Full text in Research Archive Show summary

  This study aimed to investigate the low-molecular weight compounds in a hot water extract of the bark of Daphne mezereum L. (Thymelaceae), a medicinal plant with a longstanding medicinal use in Scandinavia. Among the fourteen isolated compounds, two coumarin glycosides are reported for the first time, and four known compounds were reported in D. mezereum for the first time. Their structures were elucidated by NMR, HRESIMS and methanolysis. The new compounds were identified as 3-(2-(β-d-glucopyranosyloxy)-4-[(7-hydroxy-6-methoxy-2-oxo-2H-chromen-3-yl)oxy]phenyl)propanoic acid (9), and 7-hydroxycoumarin-5,8-di-β-d-glucopyranoside (11). Cytotoxic effects were assessed by the MTT assay, while the anti-inflammatory effects were assessed by measuring the inhibition of NO-release by dendritic cells. The results revealed negligible cytotoxic effect and NO-inhibitory activity of compounds 9 and 11.

• Butt, Hussain Shakeel; Ulriksen, Emilie Steinbakk; Rise, Frode; Wangensteen, Helle; Duus, Jens Øllgaard & Inngjerdingen, Marit [Show all 7 contributors for this article] (2024). Structural elucidation of novel pro-inflammatory polysaccharides from Daphne mezereum L. Carbohydrate Polymers. ISSN 0144-8617. 324:121554, p. 1–15. doi: 10.1016/j.carbpol.2023.121554. Full text in Research Archive Show summary

  Daphne mezereum L., an important medicinal plant in Scandinavian folk medicine, was used to treat ailments such as diarrhea, swelling and stomach pain. A range of natural compounds have been isolated, but little attention has been given to the polysaccharides in this plant. Previous work in our group have shown that a polysaccharide enriched fraction from the bark of D. mezereum exhibited pro-inflammatory effects. To pursue this further, the aim of the present work was to isolate and characterize these polysaccharides. From the ethanol-precipitate of a water extract, one neutral (DMP-NF) and one acidic (DMP-AF) fraction was isolated by anion-exchange chromatography. GC, GC–MS and 1D- and 2D-NMR were used to characterize the polysaccharide structures. DMP-NF appeared to be a mixture of arabinan, arabinogalactan and hemicelluloses such as xyloglucan, mannan and xylan. DMP-AF contained a pectic polysaccharide mainly consisting of an unusually long homogalacturonan backbone. Enzymatic treatment by pectinase of DMP-AF yielded DMP-ED, which contained a rhamnogalacturonan-I backbone with arabinan, galactan and arabinogalactan side chains. Both DMP-NF and DMP-ED induced IFN-γ and TNF-α secretion in peripheral blood mononuclear cells (PBMCs), DMP-ED being the most potent fraction. DMP-AF was less active, which might be due to a less sterically available rhamnogalacturonan-I domain.

• Menuawy, Ahmed El; Brüning, Thomas; Eiriz, Iván; Hähnel, Urs; Marthe, Frank & Möhle, Luisa [Show all 11 contributors for this article] (2024). Apolar Extracts of St. John’s Wort Alleviate the Effects of β-Amyloid Toxicity in Early Alzheimer’s Disease. International Journal of Molecular Sciences. ISSN 1661-6596. 25:1301(2), p. 1–16. doi: 10.3390/ijms25021301. Full text in Research Archive Show summary

  Hypericum perforatum (St. John’s wort) has been described to be beneficial for the treatment of Alzheimer’s disease (AD). Different extractions have demonstrated efficiency in mice and humans, esp. extracts with a low hypericin and hyperforin content to reduce side effects such as phototoxicity. In order to systematically elucidate the therapeutic effects of H. perforatum extracts with different polarities, APP-transgenic mice were treated with a total ethanol extract (TE), a polar extract obtained from TE, and an apolar supercritical CO2 (scCO2) extract. The scCO2 extract was formulated with silicon dioxide (SiO2) for better oral application. APP-transgenic mice were treated with several extracts (total, polar, apolar) at different concentrations. We established an early treatment paradigm from the age of 40 days until the age of 80 days, starting before the onset of cerebral β-amyloid (Aβ) deposition at 45 days of age. Their effects on intracerebral soluble and insoluble Aβ were analyzed using biochemical analyses. Our study confirms that the scCO2 H. perforatum formulation shows better biological activity against Aβ-related pathological effects than the TE or polar extracts. Clinically, the treatment resulted in a dose-dependent improvement in food intake with augmentation of the body weight, and, biochemically, it resulted in a significant reduction in both soluble and insoluble Aβ (−27% and −25%, respectively). We therefore recommend apolar H. perforatum extracts for the early oral treatment of patients with mild cognitive impairment or early AD.

• Moussavi, Nastaran; Ent, Wietske van der; Diallo, Drissa; Sanogo, Rokia; Malterud, Karl Egil & Esguerra, Camila V. [Show all 7 contributors for this article] (2024). Inhibition of Seizure-Like Paroxysms and Toxicity Effects of Securidaca longepedunculata Extracts and Constituents in Zebrafish Danio rerio. ACS Chemical Neuroscience. 15(3), p. 617–628. doi: 10.1021/acschemneuro.3c00642. Full text in Research Archive
• Bjune, Katrine; halvorsen, pia skovholt; Wangensteen, Helle; Leren, Trond Paul; Bogsrud, Martin Prøven & Strøm, Thea Bismo (2024). Flavonoids regulate LDLR through different mechanisms tied to their specific structures. Journal of Lipid Research. ISSN 0022-2275. 65(5). doi: 10.1016/j.jlr.2024.100539. Full text in Research Archive Show summary

  Flavonoids, polyphenolic compounds found in plant-based diets, are associated with reduced risk of cardiovascular disease and longevity. These components are reported to reduce plasma levels of low-density lipoprotein (LDL) through an upregulation of the LDL receptor (LDLR), but the mechanism is still largely unknown. In this study, we have systematically screened the effect of 12 flavonoids from six different flavonoid subclasses on the effect on LDLR. This paper provides an in-depth analysis on how these flavonoids affect LDLR regulation and functionality. We found that most but not all of the tested flavonoids increased LDLR mRNA levels. Surprisingly, this increase was attributed to different regulatory mechanisms, such as enhanced LDLR promoter activity, LDLR mRNA stabilization, or LDLR protein stabilization, of which specific effectual parts of the flavonoid molecular structure could be assigned. These types of comparative analysis of various flavonoids enhance clarity and deepen the understanding of how the different structures of flavonoids affect LDLR regulation. Our data offer useful insights that may guide future research in developing therapeutic approaches for cardiovascular health.

• 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. Full text in Research Archive Show summary

  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.

• Moussavi, Nastaran; Mounkoro, Pakuy Pierre; Dembele, Seydou; Ballo, Ngolo; Togola, Adiaratou & Diallo, Drissa [Show all 9 contributors for this article] (2024). Polyherbal combinations used by traditional health practitioners against mental illnesses in Bamako, Mali, West Africa. Plants. 13(3). doi: 10.3390/plants13030454. Full text in Research Archive Show summary

  This study explores the traditional knowledge of plants used by traditional health practitioners (THPs) in the treatment of symptoms or syndromes related to mental illnesses in the district of Bamako in Mali, along with the identification of affiliated traditional treating methods. An exploratory and cross-sectional ethnopharmacological survey was conducted in the district of Bamako. The Malian Federation of Associations of Therapists and Herbalists (FEMATH) assisted in the identification and inclusion of the THPs. Data sampling included semi-structured interviews, questionnaires, and in-depth interviews. Quantitative data were evaluated by analysing reports of the use of different medicinal plants and the number of participants. Fifteen THPs belonging to the district of Bamako participated. In total, 43 medicinal plants belonging to 22 plant families were used by the THPs. The most cited plant species was Securidaca longepedunculata (violet tree), followed by Khaya senegalensis (African mahogany) and Boscia integrifolia (rough-leaved shepherds tree). A great number of herbal combinations, preparation methods, and administration routes were used, often with honey as an adjuvant. To our knowledge, this is the first ethnobotanical survey on the use of medicinal plants in the treatment of all types of mental disorders in Bamako.

• Mueck, Felicitas; Scotti, Francesca; Mauvisseau, Quentin; Thorbek, Birgitte Lisbeth Graae; Wangensteen, Helle & Boer, Hugo de (2024). Three-tiered authentication of herbal traditional Chinese medicine ingredients used in women’s health provides progressive qualitative and quantitative insight. Frontiers in Pharmacology. 15. doi: 10.3389/fphar.2024.1353434. Full text in Research Archive Show summary

  Traditional Chinese Medicine (TCM) herbal products are increasingly used in Europe, but prevalent authentication methods have significant gaps in detection. In this study, three authentication methods were tested in a tiered approach to improve accuracy on a collection of 51 TCM plant ingredients obtained on the European market. We show the relative performance of conventional barcoding, metabarcoding and standardized chromatographic profiling for TCM ingredients used in one of the most diagnosed disease patterns in women, endometriosis. DNA barcoding using marker ITS2 and chromatographic profiling are methods of choice reported by regulatory authorities and relevant national pharmacopeias. HPTLC was shown to be a valuable authentication tool, combined with metabarcoding, which gives an increased resolution on species diversity, despite dealing with highly processed herbal ingredients. Conventional DNA barcoding as a recommended method was shown to be an insufficient tool for authentication of these samples, while DNA metabarcoding yields an insight into biological contaminants. We conclude that a tiered identification strategy can provide progressive qualitative and quantitative insight in an integrative approach for quality control of processed herbal ingredients.

• Zhang, Lin; Ulriksen, Emilie Steinbakk; Hoel, Håvard; Sandvik, Lene; Malterud, Karl Egil & Inngjerdingen, Kari Tvete [Show all 8 contributors for this article] (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. Full text in Research Archive Show summary

  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.

• Fu, Yu-ping; Li, Cen-Yu; Zou, Yuanfeng; Peng, Xi; Paulsen, Berit Smestad & Wangensteen, Helle [Show all 7 contributors for this article] (2023). Bioactive polysaccharides in different plant parts of Aconitum carmichaelii. Journal of the Science of Food and Agriculture. ISSN 0022-5142. 104(2). doi: 10.1002/jsfa.12967. Full text in Research Archive Show summary

  Abstract BACKGROUND Aconitum carmichaelii is an industrially cultivated medicinal plant in China and its lateral and mother roots are used in traditional Chinese medicine due to the presence of alkaloids. However, the rootlets and aerial parts are discarded after collection of the roots, and the non‐toxic polysaccharides in this plant have attracted less attention than the alkaloids and poisonous features. In this study, five neutral and 14 acidic polysaccharide fractions were isolated systematically from different plant parts of A. carmichaelii , and their structural features and bioactivity were studied and compared. RESULTS The neutral fraction isolated from the rootlets differed from those isolated from the lateral and mother roots. It consisted of less starch and more possible mannans, galactans, and/or xyloglucans, being similar to those of the aerial parts. Pectic polysaccharides containing homogalacturonan and branched type‐I rhamnogalacturonan (RG‐I) were present in all plant parts of A. carmichaelii . However, more arabinogalactan (AG)‐II side chains in the RG‐I backbone were present in the aerial parts of the plants, while more amounts of arabinans were found in the roots. Various immunomodulatory effects were observed, determined by complement fixation activity and anti‐inflammatory effects on the intestinal epithelial cells of all polysaccharide fractions. CONCLUSION This study highlighted the diversity of polysaccharides present in A. carmichaelii , especially in the unutilized plant parts, and showed their potential medicinal value. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

• Fu, Yu-ping; Malterud, Karl Egil; Hamre, Anne Grethe; Inngjerdingen, Kari Tvete & Wangensteen, Helle (2023). Polysaccharides and Bioactive Phenolics from Aconitum septentrionale Roots. Chemistry and Biodiversity. ISSN 1612-1872. 20(8). doi: 10.1002/cbdv.202300161. Full text in Research Archive Show summary

  Abstract Aconitum septentrionale is known to contain toxic diterpene alkaloids, while other bioactive compounds in the plant remain unclear. The aim of this study was to explore the phenolic compounds and polysaccharides from the water extract of A. septentrionale roots. Fifteen phenolic compounds were isolated and identified by NMR and MS, including fourteen known and one new dianthramide glucoside (2‐[[2‐(β‐D‐glucopyranosyloxy)‐5‐hydroxybenzoyl]amino]‐4,5‐dihydroxybenzoic acid methyl ester, 14 ). One neutral (complex of glucans with minor amounts of mannans) and two acidic polysaccharide fractions (complexes of pectic polysaccharides and glucans) were also obtained. Hydroxytyrosol ( 1 ), hydroxytyrosol‐1‐ O ‐β‐glucoside ( 2 ) and bracteanolide A ( 7 ) inhibited the release of nitric oxide by dendritic cells. Magnoflorine ( 8 ) and 2‐[[2‐(β‐D‐glucopyranosyloxy)‐5‐hydroxybenzoyl]amino]‐5‐hydroxybenzoic acid methyl ester ( 12 ) inhibited 15‐lipoxygenase, and bracteanolide A ( 7 ) was a moderate inhibitor of xanthine oxidase. This study is the first to describe the diversity of phenolics and polysaccharides from A. septentrionale and their anti‐inflammatory and anti‐oxidant activities.

• Mueck, Felicitas; Scotti, Francesca; Mauvisseau, Quentin; Raclariu, Ancuta Cristina; Schrøder-Nielsen, Audun & Wangensteen, Helle [Show all 7 contributors for this article] (2023). Complementary authentication of Chinese herbal products to treat endometriosis using DNA metabarcoding and HPTLC shows a high level of variability. Frontiers in Pharmacology. 14. doi: 10.3389/fphar.2023.1305410. Full text in Research Archive
• Moussavi, Nastaran; Azizullah, Hasina; Malterud, Karl Egil; Inngjerdingen, Kari Tvete & Wangensteen, Helle (2022). Immunomodulating polyphenols from Sideritis scardica. Journal of Functional Foods. ISSN 1756-4646. 96. doi: 10.1016/j.jff.2022.105197. Full text in Research Archive Show summary

  The herb Sideritis scardica is used in traditional medicine in the Balkan Peninsula. Limited information exists on its health effects, such as improvement of cognitive functions. This study explores the in vitro anti-inflammatory effects of extracts and polyphenols of S. scardica with focus on neurodegenerative disease. BuOH, DCM and EtOAc fractions were isolated from the crude EtOH extract of aerial parts of S. scardica and further purified by chromatographic methods. Eleven phenolic compounds were isolated. The extracts and compounds were assessed for immunomodulatory, enzyme-interacting and cytotoxic properties. The crude extract, EtOAc fraction and precipitate, BuOH fraction, verbascoside and acetylallosylglucosyl-isoscutellarein 4′-methylether displayed DPPH scavenging activity. The EtOAc fraction and echinaticin displayed XO inhibiting activity. The DCM fraction reduced nitric oxide production in D2SC/1 dendritic cells and demonstrated potent activity in a human complement assay. Verbascoside and chlorogenic acid lowered NO levels without affecting cell viability in D2SC/1 dendritic cells. The results reveal a broad-spectrum activity of this herb, which might potentially serve as a multi-target system in Alzheimer’s disease.

• Fu, Yuping; Zou, Yuan-Feng; Lei, Fei-Yi; Wangensteen, Helle & Inngjerdingen, Kari Tvete (2022). Aconitum carmichaelii Debeaux: A systematic review on traditional use, and the chemical structures and pharmacological properties of polysaccharides and phenolic compounds in the roots. Journal of Ethnopharmacology. ISSN 0378-8741. 291. doi: 10.1016/j.jep.2022.115148. Full text in Research Archive
• Puventhiran, Nithuja; Malterud, Karl Egil; Wangensteen, Helle & Gjelstad, Astrid (2022). Plantebaserte legemidler – er de forbudt i idrett? Norsk Farmaceutisk Tidsskrift (NFT). ISSN 0029-1935. 7, p. 48–50. Full text in Research Archive
• Fu, Yu-ping; Li, Cen-Yu; Peng, Xi; Wangensteen, Helle; Inngjerdingen, Kari Tvete & Zou, Yuan-Feng (2022). Pectic polysaccharides from Aconitum carmichaelii leaves protects against DSS-induced ulcerative colitis in mice through modulations of metabolism and microbiota composition. Biomedicine & Pharmacotherapy. ISSN 0753-3322. 155. doi: 10.1016/j.biopha.2022.113767. Full text in Research Archive Show summary

  The industrial processing of Aconitum carmichaelii roots for use in Traditional Chinese Medicine generates a high amount of waste material, especially leaves. An acidic polysaccharide fraction isolated from these unutilized leaves, AL-I, was in our previous work shown to contain pectic polysaccharides. This study aimed to investigate the protective effect of AL-I on ulcerative colitis for the possible application of A. carmichaelii leaves in the treatment of intestinal inflammatory diseases. AL-I was found to alleviate symptoms and colonic pathological injury in colitis mice, and ameliorate the levels of inflammatory indices in serum and colon. The production of short- and branched-chain fatty acids was also restored by AL-I. The observed protective effect could be due to the inhibition of NOD1 and TLR4 activation, the promotion of gene transcription of tight-junction proteins, and the modulation of gut microbiota composition like Bacteroides, Dubosiella, Alistipes and Prevotella,. A regulation of serum metabolomic profiles being relevant to the bacterial change, such as D-mannose 6-phosphate, D-erythrose 4-phosphate and uric acid, was also observed.

• Fu, Yu-ping; Li, Cen-Yu; Peng, Xi; Zou, Yuan-Feng; Rise, Frode & Paulsen, Berit Smestad [Show all 8 contributors for this article] (2022). Polysaccharides from Aconitum carmichaelii leaves: Structure, immunomodulatory and anti-inflammatory activities. Carbohydrate Polymers. ISSN 0144-8617. 291, p. 119655–119655. doi: 10.1016/j.carbpol.2022.119655. Full text in Research Archive Show summary

  Roots of Aconitum carmichaelii are used in Asian countries due to its content of bioactive alkaloids. In the production of root preparations, tons of leaves are usually discarded, leading to a huge waste of herbal material. The aim of this study is to investigate the polysaccharides in these unutilized leaves. A neutral polysaccharide (AL-N) appeared to be a mixture of heteromannans, and two purified acidic polysaccharides (AL-I-I and AL-I-II) were shown to be pectins containing a homogalacturonan backbone substituted with terminal β-Xylp-units. AL-I-I consisted of a type-I rhamnogalacturonan core, with arabinan and type-II arabinogalactan domains while AL-I-II was less branched. AL-N and AL-I-I were able to modulate the complement system, while AL-I-II was inactive. Interestingly, AL-N, AL-I-I and AL-I-II were shown to exert anti-inflammatory effects on porcine enterocyte IPEC-J2 cells. AL-I-I and AL-I-II were able to down-regulate the expression of toll-like receptor 4 (TLR4) and nucleotide-binding oligomerization domain 1 (NOD1).

• Ulriksen, Emilie Steinbakk; Butt, Hussain Shakeel; Ohrvik, Ane; Blakeney, Rebecca Angelica; Kool, Anneleen & Wangensteen, Helle [Show all 8 contributors for this article] (2022). The discovery of novel immunomodulatory medicinal plants by combination of historical text reviews and immunological screening assays. Journal of Ethnopharmacology. ISSN 0378-8741. 296. doi: 10.1016/j.jep.2022.115402. Full text in Research Archive Show summary

  This study investigates the utilization of medicinal plants in Scandinavian folk medicine for treating diseases believed to involve the immune system. The methodology involves screening water extracts from medicinal plants that have been previously overlooked, aiming to identify potential new reservoirs of immunomodulatory compounds.

• Saroja, Seethapathy Gopalakrishnan; Wold, Christian Winther; Ravikumar, Kaliamoorthy; Boer, Hugo de & Wangensteen, Helle (2021). Ethnopharmacology, biological activities and chemical compounds of Canarium strictum: An important resin-yielding medicinal tree in India. Fitoterapia. ISSN 0367-326X. 152, p. 104920–104920. doi: 10.1016/j.fitote.2021.104920. Full text in Research Archive Show summary

  The resin of Canarium strictum Roxb. is used for rheumatism and asthma; the bark is used as a mosquito repellent. The major compounds in the resin are triterpenoids, but as no studies have been performed on the bark, this study investigated this economically important resource. Ten folk healers were interviewed about their medicinal uses of C. strictum. Resin and bark were extracted with dichloromethane followed by methanol using accelerated solvent extraction. The extracts were fractionated using different chromatographic methods, and isolated compounds were identified by NMR spectroscopy and GC–MS. Resin and bark extracts were investigated for DPPH radical scavenging, 15-lipoxygenase inhibition, effects on nitric oxide (NO) production in LPS-activated dendritic D2SC/I cells and toxicity against Artemia salina nauplii. Traditional healers used resin to treat colds, airway afflictions and rheumatoid arthritis. α-Amyrin and β-amyrin were identified as the major constituents in the dichloromethane resin extract. From the stem bark, procyanidins, gallic acid, methyl gallate, scopoletin, 3,3′-di-O-methylellagic acid 4-O-α-arabinofuranoside and elephantorrhizol (3,3′,4′,5,6,7,8-heptahydroxyflavan) were isolated and identified. By GC–MS, α-amyrin and β-amyrin and their acetates, lupeol, and taraxasterol were identified. Radical scavenging, 15-lipoxygenase inhibitory activity and inhibition of NO production was observed from resin and bark extracts, and no toxicity towards Artemia salina nauplii was found. Triterpenoids and procyanidins are the major compounds in C. strictum resin and stem bark, respectively. The high content of triterpenoids might contribute to anti-inflammatory effects and give a rationale for the widespread usage of the resin in India.

• Wold, Christian Winther; Gerwick, William H.; Wangensteen, Helle & Inngjerdingen, Kari Tvete (2020). Bioactive triterpenoids and water-soluble melanin from Inonotus obliquus (Chaga) with immunomodulatory activity. Journal of Functional Foods. ISSN 1756-4646. 71. doi: 10.1016/j.jff.2020.104025. Full text in Research Archive
• Saroja, Seethapathy Gopalakrishnan; Raclariu, Ancuta Cristina; Anmarkrud, Jarl Andreas; Wangensteen, Helle & Boer, Hugo de (2019). DNA Metabarcoding Authentication of Ayurvedic Herbal Products on the European Market Raises Concerns of Quality and Fidelity. Frontiers in Plant Science. 10, p. 1–11. doi: 10.3389/fpls.2019.00068. Full text in Research Archive
• Goodman, Christopher Dean; Hoang, An Thuy; Diallo, Drissa; Malterud, Karl Egil; McFadden, Geoffrey & Wangensteen, Helle (2019). Anti-plasmodial effects of Zanthoxylum zanthoxyloides. Planta Medica. ISSN 0032-0943. 85(13), p. 1073–1079. doi: 10.1055/a-0973-0067. Full text in Research Archive
• Shulha, Oleksandr; Çiçek, Serhat Sezai; Wangensteen, Helle; Kroes, Janina; Mäder, Malte & Girreser, Ulrich [Show all 14 contributors for this article] (2019). Lignans and sesquiterpene lactones from Hypochaeris radicata subsp. neapolitana (Asteraceae, Cichorieae). Phytochemistry. ISSN 0031-9422. 165, p. 112047–-. doi: 10.1016/j.phytochem.2019.05.020. Full text in Research Archive Show summary

  Four undescribed lignans and two undescribed sesquiterpenic acids, together with three known compounds (hypochoeroside C, hypochoeroside D, and 5-O-caffeoylshikimic acid) were isolated from the roots of Hypochaeris radicata subsp. neapolitana (Asteraceae, Cichorieae). The lignans were identified as 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-β-D-glucopyranoside, 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-β-D-glucopyranosyl-2′-O-methacrylate, (7S,8R,8′R)-7-(3,4-dihydroxyphenyl)-3′,4′-dihydroxy-7,8,7′,8′-tetrahydronaphtho [8,8′-c]furan-1(3H)-one, and (7S,8R,8′R)-7-(3,4-dihydroxyphenyl)-3′,4′-dihydroxy-8'-(hydroxymethyl)-7,8,7′,8′-tetrahydronaphthalen-8-carboxylic acid. The two sesquiterpenic acids were identified as the ring open precursors of hypochoerosides C and D. Structures were elucidated using NMR and HRMS. Absolute configurations of (7S,8R,8′R)-7-(3,4-dihydroxyphenyl)-3′,4′-dihydroxy-7,8,7′,8′-tetrahydronaphtho [8,8′-c]furan-1(3H)-one and (7S,8R,8′R)-7-(3,4-dihydroxyphenyl)-3′,4′-dihydroxy-8'-(hydroxymethyl)-7,8,7′,8′-tetrahydronaphthalen-8-carboxylic acid were determined using electronic circular dichroism (ECD) spectroscopy. 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-β-D-glucopyranoside was evaluated for its anti-proliferative activity against myeloma cell lines MM1S, U266, and NCI-H929 and showed cytotoxicity at 100 mM against MM1S strain. No neurotoxicity was observed for major compounds 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-β-D-glucopyranoside, hypochoeroside C, and hypochoeroside D in a fluorescence assay measuring neurite outgrowth in dorsal root ganglion (DRG) neurons. Additionally, compounds 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-β-D-glucopyranoside, hypochoeroside C, hypochoeroside D, and hypochoerosidic acid D were quantified in unstressed and drought-stressed plants using HPLC-DAD. Drought-stressed plants were found to contain lower concentrations of the lignan 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-β-D-glucopyranoside and sesquiterpene lactone hypochoeroside C.

• Saroja, Seethapathy Gopalakrishnan; Tadesse, Margey; Urumarudappa, Santhosh Kumar J.; Gunaga, Srikanth V.; Vasudeva, Ramesh & Malterud, Karl Egil [Show all 10 contributors for this article] (2018). Authentication of Garcinia fruits and food supplements using DNA barcoding and NMR spectroscopy. Scientific Reports. 8:10561, p. 1–12. doi: 10.1038/s41598-018-28635-z. Full text in Research Archive Show summary

  Garcinia L. (Clusiaceae) fruits are a rich source of (−)-hydroxycitric acid, and this has gained considerable attention as an anti-obesity agent and a popular weight loss food supplement. In this study, we assessed adulteration of morphologically similar samples of Garcinia using DNA barcoding, and used NMR to quantify the content of (−)-hydroxycitric acid and (−)-hydroxycitric acid lactone in raw herbal drugs and Garcinia food supplements. DNA barcoding revealed that mostly G. gummi-gutta (previously known as G. cambogia) and G. indica were traded in Indian herbal markets, and there was no adulteration. The content of (−)-hydroxycitric acid and (−)-hydroxycitric acid lactone in the two species varied from 1.7% to 16.3%, and 3.5% to 20.7% respectively. Analysis of ten Garcinia food supplements revealed a large variation in the content of (−)-hydroxycitric acid, from 29 mg (4.6%) to 289 mg (50.6%) content per capsule or tablet. Only one product contained quantifiable amounts of (−)-hydroxycitric acid lactone. Furthermore the study demonstrates that DNA barcoding and NMR could be effectively used as a regulatory tool to authenticate Garcinia fruit rinds and food supplements.

• Saroja, Seethapathy Gopalakrishnan; Kaliamoorthy, Ravikumar; Paulsen, Berit Smestad; Boer, Hugo de & Wangensteen, Helle (2018). Ethnobotany of dioecious species: Traditional knowledge on dioecious plants in India. Journal of Ethnopharmacology. ISSN 0378-8741. 221, p. 56–64. doi: 10.1016/j.jep.2018.04.011. Full text in Research Archive Show summary

  Ethnopharmacological relevance More than 15,000 angiosperm species are dioecious, i.e., having distinct male and female individual plants. The allocation of resources between male and female plants is different, and also variation in secondary metabolites and sex-biased herbivory is reported among dioecious plants. However, little is known about the ethnobotany of dioecious species and whether preferences exist for a specific gender, e.g., in food, medicine or timber. Aim of the study The aim of this study was: 1) to study whether Indian folk healers have preference for plant genders, and to document their knowledge and use of dioecious species; 2) to understand the concept of plant gender in Indian systems of medicine and folk medicine, and whether Ayurvedic literature includes any references to gender preference. Materials and methods Lists of dioecious plants used in Indian systems of medicine and folk medicine were compiled. Ethnobotanical data was collected on perceptions and awareness of dioecious plants, and preferences of use of specific genders of dioecious species using semi-structured interviews with folk healers in Tamil Nadu, India. In addition, twenty Ayurvedic doctors were interviewed to gain insight into the concept of plant gender in Ayurveda. Results Indian systems of medicine contain 5–7% dioecious species, and this estimate is congruent the number of dioecious species in flowering plants in general. Informants recognized the phenomenon of dioecy in 31 out of 40 species, and reported gender preferences for 13 species with respect to uses as timber, food and medicine. Among informants different plant traits such as plant size, fruit size, and visibility of fruits determines the perception of a plant being a male or female. Ayurvedic classical literature provides no straightforward evidence on gender preferences in preparation of medicines or treatment illness, however it contains details about reproductive morphology and sexual differentiation of plants. Conclusions A knowledge gap exists in ethnobotanical and ethnopharmacological literature on traditional knowledge of dioecious plants. From this explorative study it is evident that people have traditional knowledge on plant gender and preferential usages towards one gender. Based on this, we propose that researchers conducting ethnobotanical and ethnopharmacological studies should consider documenting traditional knowledge on sexual systems of plants, and test the existence of gender specific usages in their conceptual framework and hypothesis testing. Incorporating such concepts could provide new dimensions of scientific knowledge with potential implications to conservation biology, chemical ecology, ethnoecology and drug discovery.

• Areta, José; Austarheim, Ingvild; Wangensteen, Helle & Capelli, Carlo (2017). Metabolic and performance effects of Yerba Mate on well-trained cyclists. Medicine & Science in Sports & Exercise. ISSN 0195-9131. 50(4), p. 817–826. doi: 10.1249/MSS.0000000000001482. Full text in Research Archive Show summary

  Introduction: Yerba Mate (YM) is a South-American plant, rich in polyphenols, saponins and xanthines, of growing scientific interest due to its metabolic effects. YM has been shown to increase fat utilization during exercise in untrained humans, but its effects on well-trained individuals during exercise are unknown. Methods: We characterized metabolic and physical performance effects of YM in eleven well-trained male cyclists. In a double-blind crossover design, participants ingested 5 g of YM or placebo (PL; maltodextrin) daily for 5 days, and 1 h prior to experimental trials. Results: Ergometer-based tests included a submaximal step-test (SST) at 30-80% of O2max (6 x 5 min stages), followed by a cycloergometer-based time-trial test to complete mechanical work (~30min, TT; n=9). Before and during tests, blood and respiratory gas samples were collected. YM increased resting plasma adrenaline concentration (P=0.002), and fat utilization by 23% at 30-50% O2max vs PL (Effect sizes Glass’ ∆ [ES]±95%CI, 0.8±0.55) correlating strongly with post-SST plasma [glycerol] (r=0.758). Treatment effects on rates of perceived exertion, heart rate and gross efficiency were unclear during SST. Respiratory exchange ratio during TT indicated carbohydrate-dependence and did not differ between treatments (PL, 0.95±0.03[SD]; YM, 0.95±0.02). TT performance showed a small (ES, 0.38±0.33) but significant (P=0.0278) improvement with YM (PL, 30.1±1.8[SD]; YM, 29.4±1.4 min; 2.2%±2[95%CI]) with average increase of 7W power-output (ES=0.2±0.19; P=0.0418; 2.3%±2[95%CI]) and 2.8% O2 (P=0.019). Pacing displayed lower power-output after 30% of total TT workload in PL vs YM. Conclusion: YM increased fat utilization during submaximal exercise and improved TT performance, but performance-enhancement effect was unrelated to measures of substrate metabolism during maximal exercise.

• Ho, Giang Thanh Thi; Nguyen, Thi Kim Yen; Kase, Eili Tranheim; Tadesse, Margey; Barsett, Hilde & Wangensteen, Helle (2017). Enhanced glucose uptake in human liver cells and inhibition of carbohydrate hydrolyzing enzymes by nordic berry extracts. Molecules. ISSN 1431-5157. 22(10). doi: 10.3390/molecules22101806. Full text in Research Archive Show summary

  A Western lifestyle with low physical activity and a diet rich in sugar, fat and processed food contribute to higher incidences of diabetes and obesity. Enhanced glucose uptake in human liver cells was observed after treatment with phenolic extracts from different Nordic berries. All berry extracts showed higher inhibition against α-amylase and α-glucosidase than the anti-diabetic agent acarbose. Total phenolic content and phenolic profiles in addition to antioxidant activities, were also investigated. The berries were extracted with 80% methanol on an accelerated solvent extraction system (ASE) and then purified by C-18 solid phase extraction (SPE). Among the ASE methanol extracts, black chokeberry, crowberry and elderberry extracts showed high stimulation of glucose uptake in HepG2 cells and also considerable inhibitory effect towards carbohydrate hydrolyzing enzymes. SPE extracts with higher concentrations of phenolics, resulted in increased glucose uptake and enhanced inhibition of α-amylase and α-glucosidase compared to the ASE extracts. Crowberry and cloudberry were the most potent 15-lipoxygenase inhibitors, while bog whortleberry and lingonberry were the most active xanthine oxidase inhibitors. These results increase the value of these berries as a component of a healthy Nordic diet and have a potential benefit against diabetes.

• Ho, Giang Thanh Thi; Wangensteen, Helle & Barsett, Hilde (2017). Elderberry and elderflower extracts, phenolic compounds, and metabolites and their effect on complement, RAW 264.7 macrophages and dendritic cells. International Journal of Molecular Sciences. ISSN 1661-6596. 18(3). doi: 10.3390/ijms18030584. Full text in Research Archive Show summary

  Modulation of complement activity and inhibition of nitric oxide (NO) production by macrophages and dendritic cells may have therapeutic value in inflammatory diseases. Elderberry and elderflower extracts, constituents, and metabolites were investigated for their effects on the complement system, and on NO production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages and murine dendritic D2SC/I cells. The EtOH crude extracts from elderberry and elderflower and the isolated anthocyanins and procyanidins possessed strong complement fixating activity and strong inhibitory activity on NO production in RAW cells and dendritic cells. Phenolic compounds in the range of 0.1–100 µM showed a dose-dependent inhibition of NO production, with quercetin, rutin, and kaempferol as the most potent ones. Among the metabolites, caffeic acid and 3,4-dihydroxyphenylacetic acid showed the strongest inhibitory effects on NO production in both cell lines, without having cytotoxic effect. Only 4-methylcatechol was cytotoxic at the highest tested concentration (100 µM). Elderberry and elderflower constituents may possess inflammatory modulating activity, which increases their nutritional value.

• Ho, Giang Thanh Thi; Kase, Eili Tranheim; Wangensteen, Helle & Barsett, Hilde (2017). Effect of phenolic compounds from elderflowers on glucose- and fatty acid uptake in human myotubes and HepG2-Cells. Molecules. ISSN 1431-5157. 22(90), p. 1–15. doi: 10.3390/molecules22010090. Full text in Research Archive Show summary

  Type 2 diabetes (T2D) is manifested by progressive metabolic impairments in tissues such as skeletal muscle and liver, and these tissues become less responsive to insulin, leading to hyperglycemia. In the present study, stimulation of glucose and oleic acid uptake by elderflower extracts, constituents and metabolites were tested in vitro using the HepG2 hepatocellular liver carcinoma cell line and human skeletal muscle cells. Among the crude extracts, the 96% EtOH extract showed the highest increase in glucose and oleic acid uptake in human skeletal muscle cells and HepG2-cells. The flavonoids and phenolic acids contained therein were potent stimulators of glucose and fatty acid uptake in a dose-dependent manner. Most of the phenolic constituents and several of the metabolites showed high antioxidant activity and showed considerably higher α-amylase and α-glucosidase inhibition than acarbose. Elderflower might therefore be valuable as a functional food against diabetes.

• Ho, Giang Thanh Thi; Kase, Eili Tranheim; Wangensteen, Helle & Barsett, Hilde (2017). Phenolic Elderberry Extracts, Anthocyanins, Procyanidins, and Metabolites Influence Glucose and Fatty Acid Uptake in Human Skeletal Muscle Cells. Journal of Agricultural and Food Chemistry. ISSN 0021-8561. 65(13), p. 2677–2685. doi: 10.1021/acs.jafc.6b05582. Full text in Research Archive
• Saroja, Seethapathy Gopalakrishnan & Wangensteen, Helle (2017). Skyggesidene ved åpen publisering: indiske forskere utnyttes av røvertidsskrifter. Nytt Norsk Tidsskrift (NNT). ISSN 0800-336X. 33, p. 165–173. doi: 10.18261/issn.1891-1781-2017-02-05. Full text in Research Archive
• Ho, Giang Thanh Thi; Zou, Yuan-Feng; Wangensteen, Helle & Barsett, Hilde (2016). RG-I regions from elderflower pectins substituted on GalA are strong immunomodulators. International Journal of Biological Macromolecules. ISSN 0141-8130. 92, p. 731–738. doi: 10.1016/j.ijbiomac.2016.07.090. Full text in Research Archive
• Nguyen, Thuy Lan; Rusten, Anders; Skogsrud, Mona; Malterud, Karl Egil; Diallo, Drissa & Paulsen, Berit Smestad [Show all 7 contributors for this article] (2016). Flavonoids, gallotannins and ellagitannins in Syzygium guineense and the traditional use among Malian healers. Journal of Ethnopharmacology. ISSN 0378-8741. 192, p. 450–458. doi: 10.1016/j.jep.2016.09.035. Full text in Research Archive
• Austarheim, Ingvild; Pham, Anh Thu; Nguyen, Celine; Zou, Yuanfeng; Diallo, Drissa & Malterud, Karl Egil [Show all 7 contributors for this article] (2016). Antiplasmodial, anti-complement and anti-inflammatory in vitro effects of Biophytum umbraculum Welw. traditionally used against cerebral malaria in Mali. Journal of Ethnopharmacology. ISSN 0378-8741. 190, p. 159–164. doi: 10.1016/j.jep.2016.05.058. Full text in Research Archive
• Wangensteen, Helle; Ho, Giang Thanh Thi; Tadesse, Margey; Miles, Christopher Owen; Moussaavi, Nastaran & Mikolo, Bertin [Show all 7 contributors for this article] (2016). A new benzophenanthridine alkaloid and other bioactive constituents from the stem bark of Zanthoxylum heitzii. Fitoterapia. ISSN 0367-326X. 109, p. 196–200. doi: 10.1016/j.fitote.2016.01.012. Full text in Research Archive
• Ho, Giang Thanh Thi; Zou, Yuan-Feng; Aslaksen, Torun Helene; Wangensteen, Helle & Barsett, Hilde (2016). Structural characterization of bioactive pectic polysaccharides from elderflowers (Sambuci flos). Carbohydrate Polymers. ISSN 0144-8617. 135, p. 128–137. doi: 10.1016/j.carbpol.2015.08.056. Full text in Research Archive
• Goodman, Christopher Dean; Austarheim, Ingvild; Mollard, Vanessa; Mikolo, Bertin; Malterud, Karl Egil & McFadden, Geoffrey [Show all 7 contributors for this article] (2016). Natural products from Zanthoxylum heitzii with potent activity against the malaria parasite. Malaria Journal. 15(481). doi: 10.1186/s12936-016-1533-x. Full text in Research Archive Show summary

  Background Zanthoxylum heitzii (Rutaceae) (olon) is used in traditional medicine in Central and West Africa to treat malaria. To identify novel compounds with anti-parasitic activity and validate medicinal usage, extracts and compounds isolated from this tree were tested against the erythrocytic stages of the human malaria parasite Plasmodium falciparum and for inhibition of transmission in rodent malaria parasite Plasmodium berghei. Results Hexane bark extract showed activity against P. falciparum (IC50 0.050 μg/ml), while leaf and seed extracts were inactive. Fractionation of the hexane bark extract led to the identification of three active constituents; dihydronitidine, pellitories and heitziquinone. Dihydronitidine was the most active compound with an IC50 value of 0.0089 µg/ml (25 nM). This compound was slow acting, requiring 50 % longer exposure time than standard anti-malarials to reach full efficacy. Heitziquinone and pellitorine were less potent, with IC50 values of 3.55 μg/ml and 1.96 µg/ml, but were fast-acting. Plasmodium berghei ookinete conversion was also inhibited by the hexane extract (IC50 1.75 µg/ml), dihydronitidine (0.59 µg/ml) and heitziquinone (6.2 µg/ml). Water extracts of Z. heitzii bark contain only low levels of dihydronitidine and show modest anti-parasitic activity. Conclusions Three compounds with anti-parasitic activity were identified in Z. heitzii bark extract. The alkaloid dihydronitidine is the most effective of these, accounting for the bulk of activity in both erythrocytic and transmission-blocking assays. These compounds may present good leads for development of novel anti-malarials and add to the understanding of the chemical basis of the anti-parasitic activity in these classes of natural product.

• Wangensteen, Helle; Diallo, Drissa & Paulsen, Berit Smestad (2015). Medicinal plants from Mali: Chemistry and biology. Journal of Ethnopharmacology. ISSN 0378-8741. 176, p. 429–437. doi: 10.1016/j.jep.2015.11.030. Full text in Research Archive
• Moussaavi, Nastaran; Malterud, Karl Egil; Mikolo, Bertin; Dawes, Dag; Chandre, Fabrice & Corbel, Vincent [Show all 9 contributors for this article] (2015). Identification of chemical constituents of Zanthoxylum heitzii stem bark and their insecticidal activity against the malaria mosquito Anopheles gambiae. Parasites & Vectors. 8:503. doi: 10.1186/s13071-015-1113-x. Full text in Research Archive Show summary

  Background Zanthoxylum heitzii bark extracts have insecticidal properties and have been reported to be used against malaria in Western Africa. Previously, it has been shown that a hexane extract of the bark is toxic to adult females of the mosquito Anopheles gambiae, a malaria vector. As part of our project on the control of malaria vectors using plant extracts, the phytochemistry of Z. heitzii bark hexane extract has been investigated with the aim to identify the major components with adulticidal and larvicidal effects on An. gambiae. Methods Z. heitzii stem bark was extracted with hexane, and the extract was fractionated to isolate major components from the bark, identified by NMR spectroscopy. Isolated compounds were tested for toxicity towards adult female An. gambiae mosquitoes and for larvicidal effects towards An. gambiae. Results The alkaloid dihydronitidine, the sesquiterpenoid caryophyllene oxide, the amide pellitorine and the lignan sesamin were identified as the major constituents in Z. heitzii bark. Pellitorine was toxic to both adult insects (LD50 50 ng/mg insect) and larvae (LD50 13 μg/ml). None of the other compounds were toxic to adults, but caryophyllene oxide and sesamin exhibited moderate larvicidal effects (LD50 > 150 μg/ml). A mixture of the four compounds in the same ratio as in the hexane extract showed higher toxicity (LD50 34 ng/mg insect) towards adult insects than the pure compounds. Conclusion The toxicity of Z. heitzii bark hexane extract to An. gambiae is mostly due to pellitorine, although interactions between pellitorine and other, inactive constituents may enhance the activity of the extract.

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• Wangensteen, Helle (2024). Aloe vera. Store Norske Leksikon (Nettutgaven). Full text in Research Archive
• Wangensteen, Helle (2024). Akonitin. Store Norske Leksikon (Nettutgaven). Full text in Research Archive
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• Inngjerdingen, Kari Tvete; Wangensteen, Helle & Eide, Thea (2024). Melk og antibiotika blir krøll? Dette bør du vite om uheldige kombinasjoner av matvarer, kosttilskudd og medisiner. [Internet]. Sykepleien. Full text in Research Archive
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• Helleve, Torstein; Hoel, Håvard & Wangensteen, Helle (2023). Oversett av vitskapen: Bitter plante frå folkemedisinen kan ha heilande effekt. [Internet]. https://forskning.no. Full text in Research Archive
• Helleve, Torstein; Hoel, Håvard & Wangensteen, Helle (2023). Forsmådd og bitter folkemedisinplante under lupa. [Internet]. https://titan.uio.no. Full text in Research Archive
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• 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. Full text in Research Archive
• Fu, Yu-Ping; Zou, Yuan-Feng; Malterud, Karl Egil; Inngjerdingen, Kari Tvete & Wangensteen, Helle (2022). Phenolics and polysaccharides isolated from the roots of Aconitum septentrionale, a Norwegian medicinal plant. Full text in Research Archive
• Zhang, Lin; Sandvik, Lene; Ulriksen, Emilie Steinbakk; Hoel, Håvard; Malterud, Karl Egil & Inngjerdingen, Kari Tvete [Show all 8 contributors for this article] (2022). Søterot, en bitter og glemt norsk medisinplante. Full text in Research Archive
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• Butt, Hussain Shakeel; Ulriksen, Emilie Steinbakk; Wangensteen, Helle; Ohrvik, Ane; Inngjerdingen, Marit & Inngjerdingen, Kari Tvete (2022). Bioactive polysaccharides from Daphne mezereum and Angelica archangelica subsp archangelica. Full text in Research Archive
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• Wangensteen, Helle (2022). Sagradabark. Store Norske Leksikon (Nettutgaven). Full text in Research Archive
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• Moussavi, Nastaran; Azizullah, Hasina; Malterud, Karl Egil; Inngjerdingen, Kari Tvete & Wangensteen, Helle (2021). Greek mountain tea, Sideritis scardica, a medicinal plant from the Mediterranean and Balkans with antioxidant and anti-inflammatory activities. Full text in Research Archive
• Wangensteen, Helle (2021). Flavonoider. Store medisinske leksikon (Nettutgaven). Full text in Research Archive
• Wold, Christian Winther; Corthay, Alexandre; Wangensteen, Helle & Inngjerdingen, Kari Tvete (2020). Myteomspunnen kjuke frå folkemedisin til mogleg kreftbehandling. www.forskning.no. Full text in Research Archive
• Inngjerdingen, Kari Tvete; Inngjerdingen, Marit; Wangensteen, Helle; Butt, Hussain Shakeel; Ulriksen, Emilie & Steien, Tore Rasmussen (2020). Graver i skogen og arkiver på leting etter nygamle legemidler. [Journal]. Norsk Farmaceutisk Tidsskrift (NFT). Full text in Research Archive
• Inngjerdingen, Marit & Wangensteen, Helle (2020). På jakt etter medisinplanter. [Journal]. Avisa Valdres. Full text in Research Archive
• Wangensteen, Helle (2019). pasjonsblomst - medisinplante. Store medisinske leksikon (Nettutgaven). Full text in Research Archive
• Wangensteen, Helle (2019). kjerringrokk. Store medisinske leksikon (Nettutgaven). Full text in Research Archive
• Wangensteen, Helle & Baker, Dilan (2019). prikkperikum - medisinplante. Store medisinske leksikon (Nettutgaven). Full text in Research Archive
• Moussavi, Nastaran; Azizullah, Hasina; Pahnke, Jens; Malterud, Karl Egil; Inngjerdingen, Kari Tvete & Wangensteen, Helle (2019). Greek mountain tea, a medicinal plant from the Mediterranean countries and Balkan. Full text in Research Archive
• Stevanovic, Stanislava; Malterud, Karl Egil; Sanogo, Rokia & Wangensteen, Helle (2019). Bioaktive stoffer i Ficus platyphylla, en afrikansk medisinplante. Full text in Research Archive
• Moussavi, Nastaran; Azizullah, Hasina; Pahnke, Jens; Malterud, Karl Egil; Inngjerdingen, Kari Tvete & Wangensteen, Helle (2019). Greek mountain tea, a medicinal plant from Mediterranean countries and Balkan. Full text in Research Archive
• Saroja, Seethapathy Gopalakrishnan; Tadesse, Margey; Malterud, Karl Egil; Shaanker, R.U.; Boer, Hugo de & Ravikanth, G. [Show all 7 contributors for this article] (2018). DNA strekkodeanalyser og kvantitativ NMR spektroskopi av garciniafrukter og ekstrakter. Full text in Research Archive
• Moussavi, Nastaran; Malterud, Karl Egil; Mikolo, Bertin; Chandre, Fabrice; Corbel, Vincent & Wangensteen, Helle (2018). Natural products of Zanthoxylum heitzii stem bark and their insecticidal activity aginst the malaria mosquito Anopheles gambiae. Full text in Research Archive
• Areta, José; Austarheim, Ingvild; Wangensteen, Helle & Capelli, Carlo (2018). Response. Medicine & Science in Sports & Exercise. ISSN 0195-9131. 50(7), p. 1526–1526. doi: 10.1249/MSS.0000000000001584. Full text in Research Archive
• Wangensteen, Helle; Moussavi, Nastaran; Malterud, Karl Egil & Røsjø, Bjarne (2018). UiO-forskning om malaria gikk verden rundt. [Internet]. titan.uio.no/node/3058. Full text in Research Archive
• Azizullah, Hasina; Pahnke, Jens; Moussavi, Nastaran; Malterud, Karl Egil & Wangensteen, Helle (2018). Gresk fjellte, en medisinplante fra middelhavslandene og Balkan. Full text in Research Archive
• Wangensteen, Helle (2017). Farmakognosi. Store medisinske leksikon (Nettutgaven). Full text in Research Archive
• Wangensteen, Helle (2017). Naturlegemidler. Store medisinske leksikon (Nettutgaven). Full text in Research Archive
• Wangensteen, Helle (2017). Plantebasert legemiddel. Store medisinske leksikon (Nettutgaven). Full text in Research Archive
• Wangensteen, Helle & Barsett, Hilde (2017). Urinveisinfeksjon: - Tranebær gir lite eller ingen bivirkninger og er trygt å bruke for de aller fleste. [Internet]. kk.no. Full text in Research Archive
• Ho, Giang Thanh Thi; Wangensteen, Helle & Barsett, Hilde (2017). Svarthyll kan motvirke diabetes. Titan.uio.no. Full text in Research Archive
• Røsjø, Bjarne; Wangensteen, Helle & Malterud, Karl Egil (2017). African trees kill both malaria mosquitos and the parasite. [Internet]. http://www.alphagalileo.org/ViewItem.aspx?ItemId=171936&Cult. Full text in Research Archive Show summary

  English version of "Naturstoffer fra samme tre dreper både malariamyggen og -parasitten" (titan.uio.no). See also: https://www.sciencedaily.com/releases/2017/01/170125093825.htm http://beforeitsnews.com/science-and-technology/2017/01/african-trees-kill-both-malaria-mosquitos-and-the-parasite-2872054.html http://www.ineffableisland.com/2017/01/african-trees-kill-both-malaria.html

• Hoang, An Thuy; Goodman, Christopher Dean; Diallo, Drissa; Malterud, Karl Egil & Wangensteen, Helle (2017). Antimalarial activities of Zanthoxylum zanthoxyloides. Full text in Research Archive
• Wangensteen, Helle; Malterud, Karl Egil & Røsjø, Bjarne (2017). Naturstoffer fra samme tre dreper både malariamyggen og parasitten. [Internet]. titan.uio.no/node/2075. Full text in Research Archive
• Wangensteen, Helle; Hoang, An Thuy; Goodman, Christopher Dean; Diallo, Drissa & Malterud, Karl Egil (2017). Zanthoxylum zanthoxyloides - an African medicinal tree with antimalarial effects. Full text in Research Archive
• Hoang, An Thuy; Goodman, Christopher Dean; Diallo, Drissa; Malterud, Karl Egil & Wangensteen, Helle (2016). En afrikansk medisinplante mot malaria. Full text in Research Archive
• Malterud, Karl Egil; Wangensteen, Helle & Hanger, Mari Rian (2016). Afrikansk medisinplante virksom mot malaria. [Internet]. http://www.dagensmedisin.no/pharma/. Full text in Research Archive
• Wangensteen, Helle (2016). Ethnopharmacology and traditional medicine - tools to find new medicinal agents. Full text in Research Archive
• Ho, Giang Thanh Thi; Wangensteen, Helle & Barsett, Hilde (2016). RG-I regions from elderflower pectins substituted on GalA are strong immunomodulators. Full text in Research Archive
• Ho, Giang Thanh Thi; Wangensteen, Helle & Barsett, Hilde (2016). Bioactive compounds in flowers and fruits of Sambucus nigra L. Full text in Research Archive
• Moussavi, Nastaran; Austarheim, Ingvild; Goodman, Dean; Malterud, Karl Egil & Wangensteen, Helle (2015). Zanthoxylum heitzii, a possible anti-malaria medicine. Full text in Research Archive
• Hoel, Håvard; Inngjerdingen, Kari Tvete & Wangensteen, Helle (2026). Comparative structure–activity relationship of naturally derived polysaccharides targeting pattern recognition receptors. Universitetet i Oslo. Full text in Research Archive Show summary

  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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