€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****FASEB JOURNAL***** Bomser JA Madhavi DL Singletary K Smith MA Induction of NAD(P)H:(quinone-acceptor) Oxido-reductase in murine hepatoma cells (Hepa 1c1c7) by fruit (Vaccinium) extracts (Meeting abstract). In: FASEB J (1995) 9(4):A993 ISSN: 0892-6638 The liver detoxification enzyme NAD(P)H:(quinone-acceptor) oxidoreductase (QR) functions to inactivate electrophilic forms of carcinogens, providing a mechanism for the inhibition of carcinogenesis. Extracts of four Vaccinium species (blueberry, cranberry, lingonberry and bilberry) were screened for anticarcinogenic substances by testing their ability to induce QR in Hepa 1c1c7 cells. The concentration of vaccinium extract, expressed as tannic acid equivalents (TAE), required to double QR specific activity (designated CDqr) was used as an indicator of induction potency. Anthocyanin and crude extracts of the four vaccinium species were inactive in QR induction. Ethyl acetate extracts were potent QR inducers. Cdqr values for ethyl acetate extracts of blueberry, cranberry, lingonberry and bilberry were 4.0, 4.0, 2.0 and 1.0 ng TAE, respectively. Thus, these extracts contain potential anticarcinogens. Further fractionation of the bilberry ethyl acetate extract revealed that the majority of inducer potency was contained in a hexane/chloroform sub-fraction (Cdqr= 0.3 ng TAE). Analysis of this sub-fraction of the bilberry ethyl acetate extract is necessary to identify the compounds responsible for the induction of QR. Registry Numbers: EC 1.6.99.2 (NAD(P)H Dehydrogenase (Quinone)) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ANNALES PHARMACEUTIQUES FRANCAISES***** Fraisse D Carnat A Lamaison JL [Polyphenolic composition of the leaf of bilberry] Composition polyphenolique de la feuille de myrtille. In: Ann Pharm Fr (1996) 54(6):280-3 ISSN: 0003-4509 (Published in French) Dried leaves of 14 harvested batches and one batch from commercial origine of Vaccinium myrtillus L present a similar polyphenolic pattern. The mean levels of the harvested batches and the levels of the commercial batch were respectively: total polyphenol compounds 12.98 and 10.62%, tannins 7.84 and 7.43%, total flavonoid compounds 2.98 and 2.20% (spectrophotometry), 1.41 and 1.16% (HPLC), quercetin 3-glucuronide 1.02 and 0.83%, hyperoside 0.22 and 0.16%, chlorogenic acid 3.66 and 1.58%. The levels were higher in young leaves and lower in old leaves. A specific chromatographic profile of the flavonoid compounds and a determination method of the tannin or the total polyphenol content were proposed in a standardization purpose. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY***** Setti L Fevereiro P Melo EP Pifferi PG Cabral JM Aires-Barros MR Superactivity of peroxidase solubilized in reversed micellar systems. In: Appl Biochem Biotechnol (1995 Dec) 55(3):207-18 ISSN: 0273-2289 Vaccinium mirtyllus peroxidase solubilized in reversed micelles was used for the oxidation of guaiacol. Some relevant parameters for the enzymatic activity, such as pH, w(o) (molar ratio water/surfactant), surfactant type and concentration, and cosurfactant concentration, were investigated. The peroxidase showed higher activities in reversed micelles than in aqueous solution. The stability of the peroxidase in reversed micelles was also studied, namely, the effect of w(o) and temperature on enzyme deactivation. The peroxidase displayed higher stabilities in CTAB/hexanol in isooctane reversed micelles, with half-life times higher than 500 h. Registry Numbers: EC 1.11.1. (Peroxidases) 111-27-3 (1-hexanol) 540-84-1 (2,2,4-trimethylpentane) 6899-10-1 (cetrimonium) 90-05-1 (Guaiacol) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ARZNEIMITTEL-FORSCHUNG***** Colantuoni A Bertuglia S Magistretti MJ Donato L Effects of Vaccinium Myrtillus anthocyanosides on arterial vasomotion. In: Arzneimittelforschung (1991 Sep) 41(9):905-9 ISSN: 0004-4172 The effects of Vaccinium Myrtillus anthocyanosides (Myrtocyan, VMA; CAS 84082-34-8) on arteriolar vasomotion were assessed in cheek pouch microcirculation of anesthetized hamsters and in skeletal muscle microvasculature of unanesthetized hamster skin fold window preparation. Intravenously injected VMA induced vasomotion in cheek pouch arterioles and terminal arterioles with higher frequency in smaller vessels. In the skeletal muscle arteriolar networks VMA increased vasomotion frequency and amplitude in all vessel orders. The results indicate that VMA are effective in promoting and enhancing arteriolar rhythmic diameter changes, that play a role in the redistribution of microvascular blood flow and interstitial fluid formation. Registry Numbers: 84082-34-8 (Myrtocyan) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Morazzoni P Livio S Scilingo A Malandrino S Vaccinium myrtillus anthocyanosides pharmacokinetics in rats. In: Arzneimittelforschung (1991 Feb) 41(2):128-31 ISSN: 0004-4172 The pharmacokinetics of Vaccinium myrtillus anthocyanosides (VMA) have been investigated in male rats. After intravenous administration anthocyanosides undergo a rapid body distribution and their disappearance from the blood is suitably fitted by a three- compartment pharmacokinetic model. The elimination occurs mostly through urine and bile. After a single oral administration the plasma concentrations of anthocyanosides reach peak level after 15 min and then rapidly decline within 2 h. The extent of cumulative urinary and biliary elimination together with the gastrointestinal recovery demonstrates an absorption of about 5%. No hepatic first-pass effect has been observed. Despite of the modest gastrointestinal absorption and the low absolute bioavailability (1.2% of the administered dose), the plasmatic peak levels (2-3 micrograms/ml) measured after the oral treatment are in the range of biological activity reported for these substances. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Lietti A Forni G Studies on Vaccinium myrtillus anthocyanosides. II. Aspects of anthocyanins pharmacokinetics in the rat. In: Arzneimittelforschung (1976) 26(5):832-5 ISSN: 0004-4172 Vaccinium myrtillus anthocyanins adminstered by i.v. or i.p. route to the rat undergo a rapid body distribution and in part also are easily eliminated such as to fit a three-compartments pharmacokinetic model. The anthocyanins elimination occurs mostly through urine and bile. The slight difference between the amount of anthocyanins eliminated after i.v. and after i.p. application shows a modest liver extracion of these substances. Vaccinium myrtillus anthocyanins possess a greater affinity for some tissues, namely kidneys and skin rather than for plasma. This fact could explain the long-lasting activity of anthocyanins on capillary resistance which is still elevated when plasma levels of these substances are no more detectable. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Lietti A Cristoni A Picci M Studies on Vaccinium myrtillus anthocyanosides. I. Vasoprotective and antiinflammatory activity. In: Arzneimittelforschung (1976) 26(5):829-32 ISSN: 0004-4172 A Vaccinium myrtillus anthocyanosides preparation (equivalent to 25% of anthocyanidins) demonstrated significant vasoprotective and antioedema properties in exerimental animals. In rabbits, the skin capillary permeability increase, due to chloroform, was reduced both after i.p. (25--100 mg/kg) and oral administration (200--400 mg/kg) of anthocyanosides. Their activity was more lasting in comparison to rutin or mepyramine and this did not seem to be due to a specific antagonism towards inflammatory process mediators such as histamine or bradykinin. Experiments carried out in rats demonstrated that Vacinium myrtillus anthocyanosides were effective both in skin capillary permeability test as well as on vascular resistance of rats fed a P factor deficient diet. In the former test effective doses were in the range of 25--100 mg/kg (by oral route). In both the animal species investigated, anthocyanosides were two-fold more active when compared to the flavonoid rutin. Vaccinium myrtillus anthocyanosides by oral route inhibited carrageein paw oedema in rats showing a dose-response relationship. An antioedema activity was detected also after i.v. or topical application. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Magistretti MJ Conti M Cristoni A Antiulcer activity of an anthocyanidin from Vaccinium myrtillus. In: Arzneimittelforschung (1988 May) 38(5):686-90 ISSN: 0004-4172 The antiulcer effects of 3,5,7-trihydroxy-2-(3,4-dihydroxyphenyl)-1- benzopyrylium chloride (IdB 1027) were assessed in various experimental models. Given orally, IdB 1027 antagonized gastric ulcerations induced by pylorus ligation, stress, nonsteroidal antiinflammatory drugs, ethanol, reserpine, histamine and duodenal ulceration induced by mercaptamine (cysteamine). Moreover it antagonized chronic gastric ulcers induced by acetic acid. Given intraperitoneally, it was more potent than after oral administration. IdB 1027 did not affect gastric secretion in pylorus-ligated rats and increased gastric mucus in normal animals both in the absence and in the presence of indometacin treatment. Tolerability was very good. These results indicate that IdB 1027 possesses a promising antiulcer activity, probably by potentiating the defensive barriers of the gastrointestinal mucosa. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ **CHUNG-KUO CHUNG YAO TSA CHIH CHINA JOURNAL OF CHINESE MATERIA MEDICA* Shang S Chen Y [Chemical constituents of Vaccinium scopulorum W.W. Smith] In: Chung Kuo Chung Yao Tsa Chih (1992 Apr) 17(4):230-2, 256 ISSN: 1001-5302 (Published in Chinese) Seven compounds were isolated from the radix of Vaccinium scopulorum. On the basis of spectral analysis, physico-chemical constants and derivative preparations, they were identified as beta-amyrin, 3-epi- ursolic acid, methyl maslinate, 3 beta-acetoxy-delta 7-cholest-7-ene, protocatechuic acid, ethyl n-hexacosanoate and ethyl n-tetracosanoate respectively. Registry Numbers: 22425-82-7 (methyl maslinate) 508-02-1 (Oleanolic Acid) 559-70-6 (amyrin) 77-52-1 (ursolic acid) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****FARMACO. EDIZIONE PRATICA***** Cristoni A Magistretti MJ Antiulcer and healing activity of Vaccinium myrtillus anthocyanosides. In: Farmaco [Prat] (1987 Feb) 42(2):29-43 ISSN: 0014-827X [No Abstract Available] €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF ETHNOPHARMACOLOGY***** Tunon H Olavsdotter C Bohlin L Evaluation of anti-inflammatory activity of some Swedish medicinal plants. Inhibition of prostaglandin biosynthesis and PAF-induced exocytosis. In: J Ethnopharmacol (1995 Oct) 48(2):61-76 ISSN: 0378-8741 Plants used in Swedish traditional medicine to treat inflammatory diseases and/or wounds were selected, based on literature data, for evaluation of inhibitory activity on prostaglandin biosynthesis and platelet activating factor (PAF)-induced exocytosis in vitro. Fifty- nine water extracts from 52 different plants in 28 families were tested. A number of plants, e.g. Calluna vulgaris, Corylus avellana, Geum urbanum, Juniperus communis, Polygonum aviculare, Potentilla erecta and Salix caprea were found to be active in both assays. The most potent cyclooxygenase inhibitors were extracts of Calluna vulgaris, Potentilla erecta and Salix caprea. None of the extracts inhibited just the prostaglandin biosynthesis. In the PAF-test, high inhibition was obtained by 19 extracts, the most potent of which were from Geum rivale, G. urbanum, Solanum dulcamara, Symphytum x uplandicum and Vaccinium vitis-idaea. The in vitro effects in relation to the traditional use, chemical contents and botanical classification, as well as the possibilities and the limitations of the methods are discussed. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF MEDICINE***** Robert AM Godeau G Moati F Miskulin M Action of anthocyanosides of Vaccinium myrtillis on the permeability of the blood brain barrier. In: J Med (1977) 8(5):321-32 ISSN: 0025-7850 Proteases and especially collagenase injected into the lateral brain ventricles of rats are able to increase the permeability of the blood- brain barrier to trypan blue. Treatment of the rats with anthocyanosides of Vaccinium myrtillis diminishes the permeability increasing effect of collagenase and accelerate the recovery of normal permeability. This effect seems to be related to a less effective enzymatic attack on collagen, as hydroxyproline content in the CSF is increased less after collagenase injection in treated animals than in untreated controls. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PHARMACOLOGICAL RESEARCH***** Saija A Princi P D'Amico N De Pasquale R Costa G Effect of Vaccinium myrtillus anthocyanins on triiodothyronine transport into brain in the rat. In: Pharmacol Res (1990 Sep-Oct) 22 Suppl 3:59-60 ISSN: 1043-6618 [No Abstract Available] Registry Numbers: 6893-02-3 (Triiodothyronine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Bertuglia S Malandrino S Colantuoni A Effect of Vaccinium myrtillus anthocyanosides on ischaemia reperfusion injury in hamster cheek pouch microcirculation. In: Pharmacol Res (1995 Mar-Apr) 31(3-4):183-7 ISSN: 1043-6618 The effects of Vaccinium myrtillus anthocyanosides (VMA) on ischaemia reperfusion injury were investigated in the hamster cheek pouch microcirculation. Ischaemia was induced by clamping the cheek pouch for 30 min followed by 30 min of reperfusion. The microvasculature was visualized by a fluorescence technique. VMA [10 mg (100 g body weight)-1] were orally administered for 2 and 4 weeks. The number of adhering leukocytes to venular vessel walls, the perfused capillary length, the increase in permeability, the arteriolar diameter changes were determined. Ischaemia and reperfusion were associated with increased number of leukocytes sticking to venules, decreased number of perfused capillaries, and increased permeability. VMA decreased the number of leukocytes sticking to the venular wall and preserved the capillary perfusion; the increase in permeability was significantly reduced after reperfusion. VMA saved the arteriolar tone and induced the appearance of rhythmic diameter changes of arterioles. These results demonstrate the ability of Vaccinium myrtillus anthocyanosides to reduce microvascular impairments due to ischaemia reperfusion injury, with preservation of endothelium, attenuation of leukocyte adhesion and improvement of capillary perfusion. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PLANTA MEDICA***** Bomser J Madhavi DL Singletary K Smith MA In vitro anticancer activity of fruit extracts from Vaccinium species. In: Planta Med (1996 Jun) 62(3):212-6 ISSN: 0032-0943 Fruit extracts of four Vaccinium species (lowbush blueberry, bilberry, cranberry, and lingonberry) were screened for anticarcinogenic compounds by a combination of fractionation and in vitro testing of their ability to induce the Phase II xenobiotic detoxification enzyme quinone reductase (QR) and to inhibit the induction of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine synthesis, by the tumor promoter phorbol 12-myristate 13- acetate (TPA). The crude extracts, anthocyanin and proanthocyanidin fractions were not highly active in QR induction whereas the ethyl acetate extracts were active QR inducers. The concentrations required to double QR activity (designated CDqr) for the ethyl acetate extracts of lowbush blueberry, cranberry, lingonberry, and bilberry were 4.2, 3.7, 1.3, and 1.0 microgram tannic acid equivalents (TAE), respectively, Further fractionation of the bilberry ethyl acetate extract revealed that the majority of inducer potency was contained in a hexane/chloroform subfraction (CDqr = 0.07 microgram TAE). In contrast to their effects on QR, crude extracts of lowbush blueberry, cranberry, and lingonberry were active inhibitors of ODC activity. The concentrations of these crude extracts needed to inhibit ODC activity by 50% (designated IC50) were 8.0, 7.0, and 9.0 micrograms TAE, respectively. The greatest activity in these extracts appeared to be contained in the polymeric proanthocyanidin fractions of the lowbush blueberry, cranberry, and lingonberry fruits (IC50 = 3.0, 6.0, and 5.0 micrograms TAE, respectively). The anthocyanidin and ethyl acetate extracts of the four Vaccinium species were either inactive or relatively weak inhibitors of ODC activity. Thus, components of the hexane/chloroform fraction of bilberry and of the proanthocyanidin fraction of lowbush blueberry, cranberry, and lingonberry exhibit potential anticarcinogenic activity as evaluated by in vitro screening tests. Registry Numbers: EC 1.6.99.2 (NAD(P)H Dehydrogenase (Quinone)) EC 4.1.1.17 (Ornithine Decarboxylase) 16561-29-8 (Tetradecanoylphorbol Acetate) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Costantino L Albasini A Rastelli G Benvenuti S Activity of polyphenolic crude extracts as scavengers of superoxide radicals and inhibitors of xanthine oxidase. In: Planta Med (1992 Aug) 58(4):342-4 ISSN: 0032-0943 In view of the pharmacological interest in phenolic substances, we have determined the total amount of anthocyanins and polyphenols present in the berries of several cultivars of Ribes, Rubus, and Vaccinium genera. The in vitro antiradical activity of the crude extracts on chemically-generated superoxide radicals as well as the inhibitory activity towards the enzyme xanthine oxidase were studied. All the crude extracts examined showed a remarkably high activity towards chemically-generated superoxide radicals. The activities were greater than those expected on the basis of the quantities of anthocyanins and polyphenols present in the samples. Furthermore, the extracts showed a certain inhibitory activity towards xanthine oxidase. Ribes nigrum extracts exhibit the highest activity, being the richest in both anthocyanins and polyphenols. On the other hand, Ribes rubrum extracts seem to contain more active substances than the other crude extracts. Registry Numbers: EC 1.1.3.22 (Xanthine Oxidase) 11062-77-4 (Superoxides) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****THROMBOSIS RESEARCH***** Cignarella A Nastasi M Cavalli E Puglisi L Novel lipid-lowering properties of Vaccinium myrtillus L. leaves, a traditional antidiabetic treatment, in several models of rat dyslipidaemia: a comparison with ciprofibrate. In: Thromb Res (1996 Dec 1) 84(5):311-22 ISSN: 0049-3848 Vaccinium myrtillus L. (blueberry) leaf infusions are traditionally used as a folk medicine treatment of diabetes. To further define this therapeutical action, a dried hydroalcoholic extract of the leaf was administered orally to streptozotocin-diabetic rats for 4 days. Plasma glucose levels were consistently found to drop by about 26% at two different stages of diabetes. Unexpectedly, plasma triglyceride (TG) were also decreased by 39% following treatment. Subsequent to the latter observation, possible lipid-lowering properties of the extract were investigated on other models of hyperlipidaemia and ciprofibrate, a well-established hypolipidaemic drug, was used as a reference compound. Both drug reduced TG levels of rats on hyperlipidaemic diet in a dose-dependent fashion. When administered at single doses over the same experimental period, blueberry and ciprofibrate were effective in lowering TG concentrations in ethanol- treated normolipidaemic animals and in genetically hyperlipidaemic Yoshida rats. Unlike ciprofibrate, however, blueberry failed to prevent the rise in plasma TG elicited by fructose and did not affect free fatty acid levels in any of the above experimental conditions. In rats treated with Triton WR-1339, blueberry feeding induced an hypolipidaemic activity one hour after injection but proved to be ineffective at later time points, thus suggesting that its hypolipidaemic action may reflect improved TG-rich lipoprotein catabolism. In addition, ciprofibrate and the extract were tested for antithrombotic activity using a collagen-triggered model of venous thrombosis in diabetic and Yoshida rats. Only ciprofibrate, however, significantly reduced thrombus formation in diabetics, possibly because of its effects on free fatty acid metabolism, whereas no effect was observed in Yoshida rats. In conclusion, the present findings indicate that active consituent(s) of Vaccinium myrtillus L. leaves may prove potentially useful for treatment of dyslipidaemiae associated with impaired TG-rich lipoprotein clearance. Registry Numbers: 52214-84-3 (ciprofibrate) 84082-34-8 (Myrtocyan) 882-09-7 (Clofibric Acid) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****VOPROSY VIRUSOLOGII***** Fokina GI Roikhel' VM Frolova MP Frolova TV Pogodina VV [The antiviral action of medicinal plant extracts in experimental tick-borne encephalitis] Protivovirusnoe deistvie ekstraktov lekarstvennykh rastenii pri eksperimental'nom kleshchevom entsefalite. In: Vopr Virusol (1993 Jul-Aug) 38(4):170-3 ISSN: 0507-4088 (Published in Russian) Some mechanisms of inducing resistance to experimental infection with tick-borne encephalitis virus were studied in experimental mice treated with aqueous extracts of berries of Vaccinium vitis-idaea, black currant, Vaccinium myrtillus, and of greater celandine grass. The condition of the immune system organs (spleen and thymus) after treatment with the extracts under study was analysed. A correlation was found between the degree of developing resistance to infection, virus accumulation in the brain, blood, spleen and thymus and changes in some parameters (spleen and thymus indices) of these immunocompetent organs. Possible mechanisms of induction of resistance to virus by herb extracts are discussed. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€