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.

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-((3-D-glucopyranosyloxy)-4-[(7-hydroxy-6-methoxy-2oxo-2H-chromen-3-yl)oxy]phenyl)propanoic acid (9), and 7-hydroxycoumarin-5,8-di-(3-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 NOinhibitory activity of compounds 9 and 11.

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-beta-D-glucopyranoside, and daphnogitin-7-O-beta-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-alpha secretion in Con A stimulated peripheral blood mononuclear cells (PBMCs) with 71.3 +/- 3.4 and 83.5 +/- 11.5% inhibition, respectively, at 50 mu M.

Plants used in traditional medicine in the management of epilepsy could potentially yield novel drug compounds with antiepileptic properties. The medicinal plant Securidaca longepedunculata is widely used in traditional medicine in the African continent, and epilepsy is among several indications. Limited knowledge is available on its toxicity and medicinal effects, such as anticonvulsant activities. This study explores the potential in vivo inhibition of seizure-like paroxysms and toxicity effects of dichloromethane (DCM) and ethanol (EtOH) extracts, as well as isolated xanthones and benzoates of S. longepedunculata. Ten phenolic compounds were isolated from the DCM extract. All of the substances were identified by nuclear magnetic resonance spectroscopy. Assays for toxicity and inhibition of pentylenetetrazole (PTZ)-induced seizure-like paroxysms were performed in zebrafish larvae. Among the compounds assessed in the assay for maximum tolerated concentration (MTC), benzyl-2-hydroxy-6-methoxy-benzoate (MTC 12.5 μM), 4,8-dihydroxy-1,2,3,5,6-pentamethoxyxanthone (MTC 25 μM), and 1,7-dihydroxy-4-methoxyxanthone (MTC 6.25 μM) were the most toxic. The DCM extract, 1,7-dihydroxy-4-methoxyxanthone and 2-hydroxy-1,7-dimethoxyxanthone displayed the most significant inhibition of paroxysms by altering the locomotor behavior in GABAA receptor antagonist, PTZ, which induced seizures in larval zebrafish. The EtOH extract, benzyl benzoate, and benzyl-2-hydroxy-6-methoxy-benzoate unexpectedly increased locomotor activity in treated larval zebrafish and decreased locomotor activity in nontreated larval zebrafish, seemingly due to paradoxical excitation. The results reveal promising medicinal activities of this plant, contributing to our understanding of its use as an antiepileptic drug. It also shows us the presence of potentially new lead compounds for future drug development.

Natural products obtained from marine organisms continue to be a rich source of novel structural architecture and of importance in drug discovery, medicine, and health. However, the success of such endeavors depends on the exact structural elucidation and access to sufficient material, often by stereoselective total synthesis, of the isolated natural product of interest. (−)-Mucosin (1), a fatty acid derivative, previously presumed to contain a rare cis-bicyclo[4.3.0]non-3-ene moiety, has since been shown to be the trans-congener. Analytically, the fused bicyclic ring system in (−)-1 constitutes a particular challenge in order to establish its relative and absolute stereochemistry. Herein, data from biological evaluations, NMR and molecular modeling studies of (−)-1 are presented. An overview of the synthetic strategies enabling the exact structural elucidation of (−)-mucosin (1) is also presented.

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.

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-alpha 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. Gen-tiopicrin, amarogentin, erythrocentaurin and gentiogenal showed dose-dependent inhibition of TNF-alpha 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 prep-aration of the crude drug.

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.

Aconitum septentrionale Koelle (Ranunculaceae family) is a medicinal plant widely distributed in Norway, Sweden and Russia, and well known for its toxicity. Alkaloids, such as lappaconitine, lappaconine and septontrionin [1], [2], [3], as well as lipids and organic acids [4], [5] have previously been identified in the plant. The high content of alkaloids is responsible for the poisonous effects of the plant, which also limits its utilization. However, other types of bioactive natural products like phenolics and polysaccharides that are present in most Aconitum plants, have not been studied in A. septentrionale yet. The aim of this study was to explore the content of phenolics and polysaccharides in a water extract of this plant, and to study their immunomodulating effects.

Gentiana purpurea L. (Gentianaceae family) was one of the most important medicinal plants in Norway in the 19th and 20th centuries, both for veterinary and human use. Indications were all kind of stomach diseases, especially diarrhea, but also chest diseases such as bronchitis, and to treat coughing and the cold. The roots are known for the intense bitterness, which can be explained by the high content of secoirioids. Secoiridoids, such as gentiopicroside and amarogentin have previously been identified in the plant [1], however a detailed overview of the metabolites in the traditional preparations that were commonly used has not previously been described. The aim of the presented study was to perform a phytochemical screening of water and ethanol extracts of G. purpurea.

Background Few clinical studies evaluate interventions to reduce oral discomfort among patients in palliative care. Aim This study examines the efficacy of a Salvia officinalis (SO) based herbal mouth rinse compared to conventional normal saline (NS) in order to improve oral health. Design A block-randomized controlled trial. Data were collected before and after a 4-day intervention with either SO ( n =44) or NS ( n =44). Numerical rating scales (NRS, 0–10) and 12 items from the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Oral Health 17 (EORTC QLQ-OH17) measured patient-reported oral symptoms. An oral examination was performed before and after the intervention. Setting/participants This study included adult patients with late-stage cancer in an inpatient hospice unit. Results Of the 88 patients included (mean age=63.9 years, SD=10.6), 73 (83%) completed the study. At baseline, 78% reported dry mouth on the EORTC QLQ-OH17, and 80% rated dry mouth ≥4 on the NRS. Total oral health scores based on the 12 EORTC QLQ-OH17 items improved similarly in both groups ( p <0.001). However, dry mouth ratings on both the EORTC QLQ-OH17 ( p =0.036) and NRS ( p =0.045) improved more in the SO group than in the NS group. Plaque on the teeth improved in both the SO ( p =0.008) and NS ( p =0.018) groups, but plaque on the tongue and erythema only improved with NS. Conclusions This study did not detect an overall significant difference between SO and NS. Both mouth rinses improved oral health parameters, indicating that systematic assessment and oral care may reduce oral discomfort. Trial registration NCT02067572

Abstract Zanthoxylum zanthoxyloides, syn. Fagara zanthoxyloides, is a tree growing in West Africa and is used in traditional medicine against a variety of diseases, including malaria. In the work reported here, root bark and stem bark extracts of this tree, as well as compounds isolated from the extracts, have been investigated for activity in vitro against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. In addition, toxicity against nauplii of the brine shrimp Artemia salina has been studied. Dichloromethane extracts of the root bark and stem bark, and a methanol extract of the stem bark, showed anti-parasitic activity towards chloroquine-sensitive as well as chloroquine-resistant P. falciparum, with IC50 values between 1 and 10 µg/mL. Among the isolated compounds, bis-dihydrochelerythrinyl ether, buesgenine, chelerythrine, γ-fagarine, skimmianine, and pellitorine were the most active, with IC50 values of less than 5 µg/mL. The dichloromethane extracts were toxic to brine shrimp nauplii, with LC50 values of less than 1 µg/mL. Methanol extracts were much less toxic (LC50 between 50 and 100 µg/mL). Among the isolated substances, bis-dihydrochelethrinyl ether was the most toxic (LC50 ca. 2 µg/mL).

Inflammation associated with sexually transmitted infection (STIs) often results from delayed diagnosis or treatment, and may result in life-threatening complications. The root or stem bark of plants selected in this study are used by traditional healers in the management of STIs and to treat the associated inflammation. This study evaluated the anti-inflammatory activities of 12 South African medicinal plants used traditionally in the treatment of STIs and the associated inflammation. Acetone extracts were tested for anti-inflammatory activity against 15-lipoxygenase (15-LOX), xanthine oxidase (XO) and inducible nitric oxide production in lipopolysaccharide (LPS) stimulated RAW 264.7 macrophage cells. The free radical and nitric oxide scavenging capacity was determined using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and nitric oxide inhibition assays. The MTT assay was used to determine the cytotoxic effect of the extracts on RAW 264.7 macrophages and Vero cells. Preliminary phytochemical analysis was carried out using NMR spectroscopy, Gas Chromatography Mass Spectroscopy (GC-MS) analysis and the determination of total phenolic and flavonoid contents. The root bark extract of Lannea schweinfurthii had the highest inhibitory activity against 15-LOX (IC50 = 40 +/- 3 mu g/mL) while C. abbreviata best inhibited XO (IC50 = 46.8 +/- 1.5 mu g/mL). Extracts of Ficus abutilifolia, Faurea saligna and Zanthoxylum capense showed significant suppression of inducible nitric oxide production with IC50 values comparable to quercetin (IC50 < 30.0 mu g/mL). The extracts of C. abbreviata and F. abutilifolia had significantly higher radical scavenging activities compared to ascorbic acid. Most of the extracts showed little or no cytotoxicity against the tested cell lines. Phytochemical analysis pointed to the presence of diverse classes of secondary metabolites as well as the presence of proanthocyanidins as the major constituents of the most active extracts in the anti-inflammatory assays. For most of the plants, this study provides the first report of 15-LOX inhibition and xanthine oxidase inhibition. The activity of most of the tested extracts supports the administration of these plants by traditional healers in the treatment of STIs and their associated inflammation. (C) 2019 SAAB. Published by Elsevier B.V. All rights reserved.

Greek mountain tea, Sideritis scardica, has a long history in traditional medicine. Currently, S. scardica is investigated for its pharmacological activity in the central nervous system in which cognition-enhancing and neuroprotective properties have been described [1]-[2]. Dried leaves of S. scardica were extracted with 80 % ethanol, and the extract was suspended in distilled water and successively extracted with solvents of increasing polarity. Selected extracts were fractionated by different chromatographic techniques and isolated compounds identified by NMR spectroscopy. Isolated compounds and extracts were tested in antioxidant and anti-inflammatory in vitro systems, as well as in cholinesterase inhibition assays. The 80% ethanol extract was found to contain flavones (glycosides of isoscutellarein and hypolaetin), phenylethanoids (mainly verbascoside) and chlorogenic acid as the main constituents. Antioxidant and anti-inflammatory effects were ascribed to the high content of polyphenols in the 80% ethanol extract. No inhibition of acetylcholine- or butyrylcholinesterases was observed. Antioxidant and anti-inflammatory effects are suggested to play a protective role in the pathogenesis of neurodegenerative diseases. Our findings may seem to be in compliance with previous in vivo findings and should be followed up in future studies.

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.

Malaria is a serious tropical disease and an important cause of death among African children. Zanthoxylum zanthoxyloides is a West African tree that is used against malaria and other diseases by traditional healers. Usually, the bark is used, but it is not well known which constituents are responsible for the anti-malaria effect. The anti-malaria effects of substances isolated from the root bark and stem bark extracts of this tree were tested. Twenty substances were isolated and identified from the extracts. Seven of these have not been reported previously from this plant: The alkaloids buesgenine, 6-hydroxydihydrochelerythrine, bis-dihydrochelerythrinyl ether, dictamnine and (-)-p-synephrine, the coumarin 6,7,8-trimethoxycoumarin, and neochlorogenic acid. The dichloromethane extracts of the root bark and stem bark and the methanol extract of the stem bark killed the protozoa Plasmodium falciparum, the organism that gives malaria, with IC50 values between 1 and 10 µg/ml. This effect was observed both towards chloroquine sensitive and chloroquine resistant protozoa. Among the isolated substances, the alkaloids skimmianine, γ-fagarine and bis-dihydrochelerythrinyl ether showed good antiplasmodial effect.

The ethnopharmacology, chemistry and pharmacology of four Malian medicinal plants, Biophytum umbraculum, Burkea africana, Lannea velutina and Terminalia macroptera are reviewed. These plants are used by traditional healers against numerous ailments: malaria, gastrointestinal diseases, wounds, sexually transmitted diseases, insect bites and snake bites, etc. The scientific evidence for these uses is, however, limited. From the chemical and pharmacological evidence presented here, it seems possible that the use in traditional medicine of these plants may have a rational basis, although more clinical studies are needed.

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.

Ethnopharmacological relevance: Biophytum umbraculum Welw. (Oxalidaceae) is a highly valued African medicinal plant used for treatment of cerebral malaria, a critical complication of falciparum malaria. Aim of the study: To provide additional information about traditional use of B. umbraculum and to test plant extracts and isolated compounds for in vitro activities related to cerebral malaria.Materials and methods: The traditional practitioners were questioned about indication, mode of processing/application, dosage and local name of B. umbraculum. Organic extracts and some main constituents of the plant were investigated for anti-malaria, anti-complement activity and inhibition of NO secretion in a RAW 264.7 cell line.Results: Treatment of cerebral malaria was the main use of B. umbraculum (fidelity level 56%). The ethyl acetate extract showed anti-complement activity (ICH50 5.7 +/- 1.6 mu g/ml), inhibition of macrophage activation (IC50 16.4 +/- 1.3 mu g/ml) and in vitro antiplasmodial activity (IC50 K1 5.6 +/- 0.13 mu g/ml, IC50 NF54 6.7 +/- 0.03 mu g/ml). The main constituents (flavone C-glycosides) did not contribute to the activity of the extract.Conclusion: Inhibition of complement activation and anti-inflammatory activity of B. umbraculum observed in this study might be possible targets for adjunctive therapy in cerebral malaria together with its antiplasmodial activity. However, clinical trials are necessary to evaluate the activity due to the complex pathogenesis of cerebral malaria. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Ethnopharmacological relevance: Syzygium guineense has been traditionally used in Mali in West Africa for the treatment of different diseases such as stomach problems, wounds, inflammations and various female disorders.Aims of the study: (1) To perform an ethnopharmacological survey on the traditional use of S. guineense among Malian healers. (2) To isolate and identify chemical constituents from S. guineense leaves and to study their radical scavenging and enzyme inhibitory effects.Materials and methods: In four different districts in Mali, 44 healers were interviewed about their medicinal use of S. guineense. A methanol extract of the leaves of this tree was prepared and further fractionated using different chromatographic methods. Isolated compounds were identified by 1D and 2D NMR spectroscopy. Extracts and isolated compounds were investigated as DPPH radical scavengers and as inhibitors of xanthine oxidase and 15-lipoxygenase, and the methanol extract was tested for toxicity towards Artemia salina nauplii.Results: Major uses by Malian healers were against dermatosis, pain, malaria/fever and for wound healing. There was little consensus about the use in the different districts. Leaves were most commonly used. From the methanol leaf extract, the flavonoids gallocatechin (1), myricetin (2), myricetin-3-O-glucoside (3), myricetin-3-O-rhamnoside (4), myricetin-3-O-glucuronide (5) and myricetin-3-O-beta-D-(6 ''-galloyOgalactoside (6), the gallotannins 1,2,3,6-tetra-O-galloyl-beta-D-glucose (7) and 1,2,3,4,6-penta-O-galloyl-P-D-glucose (8), and the ellagitannins casuarictin (9) and casuarinin (10) were isolated. These ten polyphenols are all new for the species. The crude methanol extract was active as a radical scavenger and as an inhibitor of xanthine oxidase and 15-lipoxygenase. Among the isolated compounds, pentagalloylglucose was the best enzyme inhibitor (IC50 25 +/- 4 mu M for 15-lipoxygenase, 8 +/- 1 mu M for xanthine oxidase), while casuarictin (IC50 3.9 +/- 0.1 mu M), casuarinin (IC50 4.5 +/- 0.3 mu M) and pentagalloylglucose (IC50 5 +/- 1 mu M) showed the highest radical scavenging activity. The methanol extract was non-toxic to Artemia salina nauplii.Conclusion: S. guineense leaves are commonly used among Malian healers, however the traditional practice varies a lot between different regions. The leaves of S. guineense are rich in polyphenols; several are galloylated, either as galloylated flavonoids, gallotannins or ellagitannins. The high content of biologically active polyphenols might be important for medicinal effects of this plant and might give a rationale for the widespread usage of S. guineense in Mali. (C) 2016 Elsevier Ireland Ltd. All rights reserved.