Karl Egil Malterud

Saponins from the roots of Panax notoginseng

Abstract The glycosidic fraction from the dried roots of Panax notoginseng (Burk.) F.H.Chen exhibited an inhibitory effect on zoospore motility of Aphanomyces cochlioides . Further study on this fraction afforded fourteen dammarane-type saponins. Their structures were determined on the basis of spectroscopic and chemical methods. Eleven were known compounds, and the three new ones were 3- O -[β- d -glucopyranosyl (1→6)-β- d -glucopyranosyl]-20- O -β- d -glucopyranosyl 3β, 12β, 20 ( S )-trihydroxydammar-24-ene, 3- O -β- d -glucopyranosyl 20- O -[α- l -arabinopyranosyl (1→2)-β- d -glucopyranosyl] 3β, 12β, 20 ( S )-trihydroxydammar-24-ene and 6- O -β- d -glucopyranosyl 20- O -β- d -glucopyranosyl 3β, 6α, 12β, 20 ( S ), 25-pentahydroxydammar-23-ene, respectively. Each saponin displayed good inhibitory effects on zoospore motility.

Extracts, anthocyanins and procyanidins from Aronia melanocarpa as radical scavengers and enzyme inhibitors.

Extracts, subfractions, isolated anthocyanins and isolated procyanidins B2, B5 and C1 from the berries and bark of Aronia melanocarpa were investigated for their antioxidant and enzyme inhibitory activities. Four different bioassays were used, namely scavenging of the diphenylpicrylhydrazyl (DPPH) radical, inhibition of 15-lipoxygenase (15-LO), inhibition of xanthine oxidase (XO) and inhibition of α-glucosidase. Among the anthocyanins, cyanidin 3-arabinoside possessed the strongest and cyanidin 3-xyloside the weakest radical scavenging and enzyme inhibitory activity. These effects seem to be influenced by the sugar units linked to the anthocyanidin. Subfractions enriched in procyanidins were found to be potent α-glucosidase inhibitors; they possessed high radical scavenging properties, strong inhibitory activity towards 15-LO and moderate inhibitory activity towards XO. Trimeric procyanidin C1 showed higher activity in the biological assays compared to the dimeric procyanidins B2 and B5. This study suggests that different polyphenolic compounds of A. melanocarpa can have beneficial effects in reducing blood glucose levels due to inhibition of α-glucosidase and may have a potential to alleviate oxidative stress.

Bioactive polyphenols in Ximenia americana and the traditional use among Malian healers.

ETHNOPHARMACOLOGICAL RELEVANCE Ximenia americana is a medicinal bushy, spiny shrub or small tree used in Mali in West Africa for treatment of various diseases, most common are infectious and inflammatory ailments. AIMS OF THE STUDY (1) To perform an ethnopharmacological survey on the traditional use of Ximenia americana among healers in Mali. (2) To isolate and identify chemical constituents from the ethanol extract of Ximenia americana leaves and to study their radical scavenging and enzyme inhibitory effects. MATERIALS AND METHODS In five different districts in Mali, 38 healers were interviewed about their medicinal use of Ximenia americana. An aqueous ethanol extract of the leaves of this tree was prepared and further fractionated with liquid-liquid extraction, VersaFlash and Sephadex LH-20 column chromatography, and preparative HPLC. Isolated compounds were identified by 1D and 2D NMR spectroscopy. Extracts, subfractions and isolated compounds were investigated as DPPH radical scavengers and as inhibitors of xanthine oxidase and 15-lipoxygenase. RESULTS Major areas of use by Malian healers were against throat infection, amenorrhea and as tonic. Fractionation of the ethanol extract led to the isolation and identification of the cyanogenic glycoside sambunigrin (1), which is previously known from the plant. Additionally, gallic acid (2) and the gallotannins β-glucogalline (3) and 1,6-digalloyl-β-glucopyranose (4) were found. The following flavonoids were isolated: quercetin (5), quercitrin (quercetin-3-O-α-rhamnopyranoside) (6), avicularin (quercetin-3-O-α-arabinofuranoside) (7), quercetin-3-O-β-xylopyranoside (8), quercetin-3-O-(6″-galloyl)-β-glucopyranoside (9) and kaempferol-3-O-(6″-galloyl)-β-glucopyranoside (10). The flavonoids were active both as enzyme inhibitors and DPPH radical scavengers. CONCLUSION Sambunigrin (1) was the main compound in the EtOAc soluble fraction of the alcoholic extract of Ximenia americana leaves. Gallic acid (2), gallotannins (3-4) and flavonoids (5-10) were identified for the first time in the genus Ximenia. The identified compounds may give a rationale for the traditional use of Ximenia americana in Mali. Healers interviewed reported the use against throat infections, amenorrhea, as tonic, for wound healing and against pain.

Two new C-methylated flavonoids from Myrica gale

Abstract From the leaves of Myrica gale 2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone has been isolated. The fruits yielded 2′-hydroxy-4′,6′-dimethoxy-3′-methyldihydrochalcone. The constitutions were deduced from spectroscopic data and confirmed by synthesis.

Effect of cholesterol feeding on the susceptibility of lipoproteins to oxidative modification

In previous studies we have shown that the liver endothelial and Kupffer cells in hypercholesterolemic rabbits are very active in endocytosis of low-density lipoprotein (LDL) and beta-very-low-density lipoprotein (beta-VLDL) (Nenseter et al. (1992) J. Lipid Res. 33, 867-877; Gudmundsen et al. (1993) J. Lipid Res. 34, 589-600). These data raised the question whether subfractions of LDL and beta-VLDL were modified in vivo to forms recognized by the scavenger/oxidized LDL receptors of the non-parenchymal liver cells. The purpose of the present study was to address this question by assessing the effect of cholesterol feeding on the susceptibility of the lipoproteins to oxidative modification in vitro. In addition, the effect of HDL on the lipid peroxidation of LDL was evaluated. LDL and beta-VLDL were isolated from rabbits given a diet supplemented with cholesterol (2% w/w) for 3 weeks. The extent of Cu(2+)-catalyzed oxidation of the lipoproteins was compared with that of LDL from control-fed rabbits. Extent of oxidation assessed by formation of conjugated dienes, lipid peroxides, thiobarbituric acid-reactive substances, relative electrophoretic mobility and uptake of lipoproteins by J774 macrophages suggested that LDL and beta-VLDL from the hypercholesterolemic rabbits were more susceptible to oxidation than LDL from normolipidemic rabbits. HDL protected LDL and beta-VLDL from lipid peroxidation in vitro. Taken together, the increased susceptibility of LDL and beta-VLDL to oxidative modification in vitro, combined with the low levels of alpha-tocopherol, and the reduced ratio of HDL to LDL cholesterol observed in the hypercholesterolemic rabbits, and the protective effect of HDL on the lipid peroxidation of LDL, support the probability that oxidative modification of LDL and beta-VLDL occur in vivo in the hypercholesterolemic rabbits.

Structural features and complement fixing activity of polysaccharides from Codonopsis pilosula Nannf. var. modesta L.T.Shen roots

Two pectic polysaccharides, 50 WCP-II-I and 100 WCP-II-I, were obtained from 50 and 100 °C water extracts of Codonopsis pilosula roots by ion exchange chromatography and gel filtration. The study of the sub-fractions obtained after pectinase degradation showed that the complement fixation activities of these pectins are expressed mainly by their ramified regions. The structure studies of native and sub-fractions showed the 50 WCP-II-I is a pectic polysaccharide, with long homogalacturonan regions (some of the galacturonic acid units were methyl esterified), interrupted by one short rhamnogalacturonan I (RG-I) region. The side chains of the RG-I region are arabinogalactan type I (AG-I) and type II (AG-II) attached on position 4 of rhamnose. The 100 WCP-II-I has two main ramified regions, one is galacturonan region with AG-I side chain on position 2 of GalA, and the other one is RG-I region with AG-II side chain on position 4 of Rha.

Inhibition of lipid peroxidation in low-density lipoprotein by the flavonoid myrigalone B and ascorbic acid☆

Lipid peroxidation in human LDL (0.05 mg protein/mL) incubated with Cu(2+)-ions (5 microM) in vitro was dose-dependently inhibited by the flavonoid myrigalone B (MyB) and by ascorbic acid. MyB at 6 microM increased the oxidation lag time by 135 +/- 24 min (approximately 5-fold compared to controls) and reduced the maximum oxidation rate by 46 +/- 5%. Ascorbic acid, at 9 microM, increased the lag time by 179 +/- 29 min (6-fold compared to controls) but did not affect the maximum oxidation rate. The increase in lag time induced by MyB was enhanced in the presence of ascorbic acid. Their effects were additive, except when both were present at the highest concentration tested, when a significant potentiation, giving an increase in lag time of approximately 2 hr more than the sum of separate effects, occurred. Concentration-time curves for MyB in the absence and presence of ascorbic acid showed that the vitamin protected MyB against deterioration during incubation, and indicated that the net consumption of MyB in the oxidation process was reduced. No differences were observed when ordinary ascorbic acid and Ester-C, a commercial vitamin C product, were compared. In conclusion, MyB and ascorbic acid seem to interact in a way that further improves the antioxidant status of the LDL particle relative to each substance separately.

A comparison of bioactive aqueous extracts and polysaccharide fractions from roots of wild and cultivated Cochlospermum tinctorium A. Rich

In Malian traditional medicine the roots of Cochlospermum tinctorium are used in the treatment of gastric ulcer, but extending harvesting is causing a growing concern of a dramatic reduction in the wild plant population. In the present study cultivation of C. tinctorium is evaluated, and structural components and bioactive properties of crude water extracts and isolated polysaccharide fractions from roots of wild and cultivated C. tinctorium are compared. The crude water extracts were shown to contain starch, pectin- and inulin-type polysaccharides, in addition to phenolic substances and protein, while the isolated acidic polysaccharide fractions contained mainly monosaccharides typical for pectins. The monosaccharide compositions of the polysaccharide fractions from roots of wild versus cultivated plants were comparable, albeit the yields in the cultivated roots were lower. Furthermore, the crude extracts and isolated polysaccharide fractions from wild and cultivated roots exhibited similar complement fixating activities, but were not able to activate macrophages. The crude extracts from cultivated roots were also shown to be moderate radical scavengers. The present study has shown that roots of cultivated C. tinctorium contain the same types of bioactive polysaccharides as the wild roots. However, in order to utilize roots of cultivated C. tinctorium in traditional medicine the cultivation method should be improved.

Terminalia macroptera, its current medicinal use and future perspectives.

The tree Terminalia macroptera (Combretaceae) is widespread in Western Africa, and in this area, different parts have been utilized in the treatment of various diseases. In this article, we report on the medicinal use of T. macroptera in three different districts in Mali (Siby, Dioïla and Dogonland), based on interviews with 78 healers in these districts. Roots, root bark, stem bark, leaves and fruits have all been employed by healers, as has parasitic Loranthus species growing on the tree. Major areas of use comprise treatment of wounds and sores, infections, pain, cough, tuberculosis and hepatitis. Some of the medicinal uses of T. macroptera appear to be rationally explained by its chemical constituents.

Immunomodulating Activity of Aronia melanocarpa Polyphenols

The immunomodulating effects of isolated proanthocyanidin-rich fractions, procyanidins C1, B5 and B2 and anthocyanins of Aronia melanocarpa were investigated. In this work, the complement-modulating activities, the inhibitory activities on nitric oxide (NO) production in LPS-induced RAW 264.7 macrophages and effects on cell viability of these polyphenols were studied. Several of the proanthocyanidin-rich fractions, the procyanidins C1, B5 and B2 and the cyanidin aglycone possessed strong complement-fixing activities. Cyanidin 3-glucoside possessed stronger activity than the other anthocyanins. Procyanidins C1, B5 and B2 and proanthocyanidin-rich fractions having an average degree of polymerization (PD) of 7 and 34 showed inhibitory activities on NO production in LPS-stimulated RAW 264.7 mouse macrophages. All, except for the fraction containing proanthocyanidins with PD 34, showed inhibitory effects without affecting cell viability. This study suggests that polyphenolic compounds of A. melanocarpa may have beneficial effects as immunomodulators and anti-inflammatory agents.