Antioxidant action of Vaccinium myrtillus extract on human low density lipoproteins in vitro: initial observations.

Fundam Clin Pharmacol, 11(1):35-40 1997

Oxidative modifications of low density lipoproteins (LDL) are now recognised as one of the major processes in atherogenesis. Various drugs, as well as a number of natural products, have been proposed to inhibit such processes. Among the naturally-occurring constituents of plants which appear to possess antioxidant activity are polyphenolic compounds such as flavonoids. The aqueous extract of Vaccinium myrtillus is rich in such molecules. In this report, we describe the in vitro antioxidative potential of this extract on human LDL. The copper-induced oxidative modification of these lipoproteins was assessed using 1) measurement of oxidative resistance as determined by the lag-phase preceding conjugated diene formation; 2) quantification of the amount of lipoperoxides and thiobarbituric acid-reactive substances generated, and measurement of the modification in the net negative electrical charge of the lipoproteins, over a 7-hour time course experiment. Trace amounts of V myrtillus extract (15 to 20 micrograms/mL) induce statistically significant changes in the oxidation behaviour of LDL, which include 1) prolongation of the lag-phase of conjugated diene production (P < 0.01); 2) reduction in the formation of lipoperoxides and of thiobarbituric acid-reactive substances up to 7 hours and especially between 1 and 5 hours (P < 0.01); and 3) inhibition of modification in the net negative charge of LDL. These results demonstrate that V myrtillus extract exerts potent protective action on LDL particles during in vitro copper-mediated oxidation. Calculation of IC50 values indicates that, on a molar basis, this extract may indeed be more potent than either ascorbic acid or butylated hydroxytoluene in the protection of LDL particles from oxidative stress.




Antiulcer activity of an anthocyanidin from Vaccinium myrtillus.

Arzneimittelforschung, 38(5):686-90 1988 May

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.




Studies on vascular permeability in hypertension: action of anthocyanosides.

Clin Physiol Biochem, 4(2):143-9 1986

The initial phase of renal hypertension induced by ligature of the abdominal aorta was accompanied by a transient increase in vascular permeability. This permeability increase has not the same intensity in all parts of the organism: it is greater in the skin and in the aorta wall than in the brain vessels. Treatment of rats with a flavonoid-type drug (anthocyanosides of Vaccinium myrtillus) for 12 days before the induction of hypertension kept the blood-brain barrier permeability normal and limited the increase in vascular permeability in the skin and the aorta wall. As previously demonstrated, the collagens of the blood vessel walls play an important role in the control of vascular permeability. Interaction of these collagens with the drug may be partly responsible for the protection against the permeability-increasing action of hypertension observed in the treated animals.




A natural flavonoid, IdB 1027, increases gastric luminal release of prostaglandin 2 in healthy subjects.

Ital J Gastroenterol, 22(5):288-90 1990 Oct

IdB 1027 is an anthocyanidin pigment occurring in bilberries. In laboratory animals this compound shows gastric protective effects without influencing acid secretion. To study how IdB 1027 would affect gastric luminal release of prostaglandin (PG) E2 and basal fluid and acid secretion, we have carried out 'steady state' perfusions of the stomach in 10 healthy males before and after oral administration of IdB 1027 (600 mg b.i.d.) for 10 days. Two subjects were excluded from the study due to a low recovery of perfusates. Gastric fluid secretion, acidity, and acid output were unaffected during IdB 1027 administration, while a significant rise in luminal concentration (403 (124-910) vs 216 (49-506) pg/ml: median and range; p less than 0.05; n = 8 and luminal release 6.5 (2.2-14.6) vs 1.9 (1.0-8.1) ng/15 min; p less than 0.02; n = 8) of PGE2 occurred. The marked increase in gastric mucosal release of PGE2 may explain the antiulcer and gastroprotective effects of IdB 1027 observed in animal experiments.




Studies on Vaccinium myrtillus anthocyanosides. I. Vasoprotective and antiinflammatory activity.

Arzneimittelforschung, 26(5):829-32 1976

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.




Effect of Vaccinium myrtillus anthocyanosides on ischaemia reperfusion injury in hamster cheek pouch microcirculation.

Pharmacol Res, 31(3-4):183-7 1995 Mar-Apr

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.




Effect of anthocyanins on human connective tissue metabolism in the human

Klin Monatsbl Augenheilkd, 1996 Dec, 209:6, 368-72

BACKGROUND: Diabetic retinopathy can lead to blindness. This is due to an abnormally increased synthesis of connective tissue in order to a) repair leaking capillaries and b) formation of new capillaries. METHOD: Twelve adult diabetics were treated with 600 mg anthocyanosides per day for two months. Samples of gingiva tissue were taken before and after treatment. Incubated with radio-active labeled amino acids, the measure of radioactivity from different connective tissue extracts can show a changed protein biosynthesis activity. RESULTS: The use of radio-active labeled amino acids show significant decrease of biosynthesis-activity of connective tissue especially polymeric collagen and structure-glycoproteins by anthocyanoside medication. CONCLUSIONS: Anthocyanosides help to prevent diabetics from injuries caused by malfunction of synthesis-activities throughout normal diabetic medical treatment.




Anthocyanosides in the treatment of retinopathies (author's transl)

Klin Monatsbl Augenheilkd, 1981 May, 178:5, 386-9

Thirty-one patients with various types of retinopathy were investigated with regard to the effect of anthocyanosides on the retinal vessels. Especially in patients with diabetic retinopathy, a positive influence on the permeability and tendency to hemorrhage was observed. The importance of internal treatment of the primary disease is pointed out.




In vitro anticancer activity of fruit extracts from Vaccinium species.

Planta Med, 1996 Jun, 62:3, 212-6

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.




Action of anthocyanosides of Vaccinium myrtillis on the permeability of the blood drain barrier.

J Med, 4(2):321-32 1977

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.




Influence of anthocyanoside treatment on the cholesterol-induced atherosclerosis in the rabbit.

Paroi Arterielle, 5(4):187-205 1979 Dec

We have studied the effect of treatment with anthocyanosides from Vaccinium myrtillis on cholesterol-induced atheroma of rabbits. We have found that the drug did not modify the serum cholesterol levels, but decreased the proliferation of the intima the extracellular matrix production the calcium and lipid deposition in the aorta, and the DNA and lipid contents. The alterations in the biochemical composition of the isolated brain microvessels were also diminished. The following mechanism may explain the protective action of the treatment: the collagen of the vessel walls participates in the control of vascular permeability. This permeability is increased by a cholesterol-rich diet. The protective drug interacts with collagen, increasing its cross-links, thus diminishing the permeability in small, as well as in large blood vessels.




Experiences in the medical treatment of progressive myopia (author's transl)

Klin Monatsbl Augenheilkd, 1977 Oct, 171:4, 616-9

In order to judge the effect of anthocyanosides and vitamine E (Difrarel E) on refraction, visual acuity and eye-fundus, we treated 36 patients with this speciality in progressive myopia. After an observation period of 14.5 months an average increase of myopia by 0.53 dpt per eye was demonstrated. The final examination of 29 patients showed a stabilization of the fundus-alterations, as well as a stable, or an improved visual acuity respectively. In 7 patients a moderate deterioration of the partial or overall medical findings occured. Our observations allow the conclusion that Difrarel E achieves therapeutically valuable results in the treatment of progressive myopia.




Antioxidant action of Vaccinium myrtillus extract on human low density lipoproteins in vitro: initial observations.

Fundam Clin Pharmacol, 11(1):35-40 1997

Oxidative modifications of low density lipoproteins (LDL) are now recognised as one of the major processes in atherogenesis. Various drugs, as well as a number of natural products, have been proposed to inhibit such processes. Among the naturally-occurring constituents of plants which appear to possess antioxidant activity are polyphenolic compounds such as flavonoids. The aqueous extract of Vaccinium myrtillus is rich in such molecules. In this report, we describe the in vitro antioxidative potential of this extract on human LDL. The copper-induced oxidative modification of these lipoproteins was assessed using 1) measurement of oxidative resistance as determined by the lag-phase preceding conjugated diene formation; 2) quantification of the amount of lipoperoxides and thiobarbituric acid-reactive substances generated, and measurement of the modification in the net negative electrical charge of the lipoproteins, over a 7-hour time course experiment. Trace amounts of V myrtillus extract (15 to 20 micrograms/mL) induce statistically significant changes in the oxidation behaviour of LDL, which include 1) prolongation of the lag-phase of conjugated diene production (P < 0.01); 2) reduction in the formation of lipoperoxides and of thiobarbituric acid-reactive substances up to 7 hours and especially between 1 and 5 hours (P < 0.01); and 3) inhibition of modification in the net negative charge of LDL. These results demonstrate that V myrtillus extract exerts potent protective action on LDL particles during in vitro copper-mediated oxidation. Calculation of IC50 values indicates that, on a molar basis, this extract may indeed be more potent than either ascorbic acid or butylated hydroxytoluene in the protection of LDL particles from oxidative stress.




Antiulcer activity of an anthocyanidin from Vaccinium myrtillus.

Arzneimittelforschung, 38(5):686-90 1988 May

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.




Studies on vascular permeability in hypertension: action of anthocyanosides.

Clin Physiol Biochem, 4(2):143-9 1986

The initial phase of renal hypertension induced by ligature of the abdominal aorta was accompanied by a transient increase in vascular permeability. This permeability increase has not the same intensity in all parts of the organism: it is greater in the skin and in the aorta wall than in the brain vessels. Treatment of rats with a flavonoid-type drug (anthocyanosides of Vaccinium myrtillus) for 12 days before the induction of hypertension kept the blood-brain barrier permeability normal and limited the increase in vascular permeability in the skin and the aorta wall. As previously demonstrated, the collagens of the blood vessel walls play an important role in the control of vascular permeability. Interaction of these collagens with the drug may be partly responsible for the protection against the permeability-increasing action of hypertension observed in the treated animals.




A natural flavonoid, IdB 1027, increases gastric luminal release of prostaglandin 2 in healthy subjects.

Ital J Gastroenterol, 22(5):288-90 1990 Oct

IdB 1027 is an anthocyanidin pigment occurring in bilberries. In laboratory animals this compound shows gastric protective effects without influencing acid secretion. To study how IdB 1027 would affect gastric luminal release of prostaglandin (PG) E2 and basal fluid and acid secretion, we have carried out 'steady state' perfusions of the stomach in 10 healthy males before and after oral administration of IdB 1027 (600 mg b.i.d.) for 10 days. Two subjects were excluded from the study due to a low recovery of perfusates. Gastric fluid secretion, acidity, and acid output were unaffected during IdB 1027 administration, while a significant rise in luminal concentration (403 (124-910) vs 216 (49-506) pg/ml: median and range; p less than 0.05; n = 8 and luminal release 6.5 (2.2-14.6) vs 1.9 (1.0-8.1) ng/15 min; p less than 0.02; n = 8) of PGE2 occurred. The marked increase in gastric mucosal release of PGE2 may explain the antiulcer and gastroprotective effects of IdB 1027 observed in animal experiments.




Studies on Vaccinium myrtillus anthocyanosides. I. Vasoprotective and antiinflammatory activity.

Arzneimittelforschung, 26(5):829-32 1976

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.




Effect of Vaccinium myrtillus anthocyanosides on ischaemia reperfusion injury in hamster cheek pouch microcirculation.

Pharmacol Res, 31(3-4):183-7 1995 Mar-Apr

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.




Effect of anthocyanins on human connective tissue metabolism in the human

Klin Monatsbl Augenheilkd, 1996 Dec, 209:6, 368-72

BACKGROUND: Diabetic retinopathy can lead to blindness. This is due to an abnormally increased synthesis of connective tissue in order to a) repair leaking capillaries and b) formation of new capillaries. METHOD: Twelve adult diabetics were treated with 600 mg anthocyanosides per day for two months. Samples of gingiva tissue were taken before and after treatment. Incubated with radio-active labeled amino acids, the measure of radioactivity from different connective tissue extracts can show a changed protein biosynthesis activity. RESULTS: The use of radio-active labeled amino acids show significant decrease of biosynthesis-activity of connective tissue especially polymeric collagen and structure-glycoproteins by anthocyanoside medication. CONCLUSIONS: Anthocyanosides help to prevent diabetics from injuries caused by malfunction of synthesis-activities throughout normal diabetic medical treatment.




Anthocyanosides in the treatment of retinopathies (author's transl)

Klin Monatsbl Augenheilkd, 1981 May, 178:5, 386-9

Thirty-one patients with various types of retinopathy were investigated with regard to the effect of anthocyanosides on the retinal vessels. Especially in patients with diabetic retinopathy, a positive influence on the permeability and tendency to hemorrhage was observed. The importance of internal treatment of the primary disease is pointed out.




In vitro anticancer activity of fruit extracts from Vaccinium species.

Planta Med, 1996 Jun, 62:3, 212-6

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.




Action of anthocyanosides of Vaccinium myrtillis on the permeability of the blood drain barrier.

J Med, 4(2):321-32 1977

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.




Influence of anthocyanoside treatment on the cholesterol-induced atherosclerosis in the rabbit.

Paroi Arterielle, 5(4):187-205 1979 Dec

We have studied the effect of treatment with anthocyanosides from Vaccinium myrtillis on cholesterol-induced atheroma of rabbits. We have found that the drug did not modify the serum cholesterol levels, but decreased the proliferation of the intima the extracellular matrix production the calcium and lipid deposition in the aorta, and the DNA and lipid contents. The alterations in the biochemical composition of the isolated brain microvessels were also diminished. The following mechanism may explain the protective action of the treatment: the collagen of the vessel walls participates in the control of vascular permeability. This permeability is increased by a cholesterol-rich diet. The protective drug interacts with collagen, increasing its cross-links, thus diminishing the permeability in small, as well as in large blood vessels.




Experiences in the medical treatment of progressive myopia (author's transl)

Klin Monatsbl Augenheilkd, 1977 Oct, 171:4, 616-9

In order to judge the effect of anthocyanosides and vitamine E (Difrarel E) on refraction, visual acuity and eye-fundus, we treated 36 patients with this speciality in progressive myopia. After an observation period of 14.5 months an average increase of myopia by 0.53 dpt per eye was demonstrated. The final examination of 29 patients showed a stabilization of the fundus-alterations, as well as a stable, or an improved visual acuity respectively. In 7 patients a moderate deterioration of the partial or overall medical findings occured. Our observations allow the conclusion that Difrarel E achieves therapeutically valuable results in the treatment of progressive myopia.