Behavioral effects of Chaenomeles maulei fruit juice in rats with impaired circadian rhythm.

INTRODUCTION: Impaired circadian rhythm (ICR) is a commonly used model of mild stress. The fruit juice of Chaenomeles japonica var. maulei (Mast.) Lavall'e (CMFJ) is rich in polyphenols known for their anti-inflammatory, antioxidant, and neuroprotective properties. AIM: The aim of this study was to investigate the effects of CMFJ on the behavior of rats subjected to ICR. MATERIALS AND METHODS: Male Wistar rats were divided into five groups of 10 animals each: control group (without ICR), the ICR, ICR+CMFJ2.5, ICR+CMFJ5, and ICR+CMFJ10 groups. ICR was induced by exposing rats to 14 days of constant light. Over these days, oral treatment was administered with distilled water (the control and ICR groups) and CMFJ at doses 2.5, 5, and 10 ml/kg for the respective groups. Then we performed the open field test, the social interaction test (SIT), and the forced swim test (FST) to assess rats' locomotion, anxiety, and the depressive-like behavior, respectively. RESULTS: The ICR animals increased their horizontal and vertical locomotion when compared to the controls. The ICR rats did not change significantly the social interaction time in the SIT test and immobility time in the FST. The horizontal and vertical activity of the ICR+CMFJ10 rats was reduced in comparison with ICR animals. Compared to ICR rats, the animals treated with CMFJ at doses of 2.5 and 10 ml/kg demonstrated an improved social interaction and decreased immobility time in the FST. CONCLUSIONS: ]CMFJ prevented the development of ICR-induced hyperactivity and showed an anxiolytic-like and antidepressant-like effect, probably due to its high polyphenol content.

Behavioral effects of Aronia melanocarpa fruit juice in a rat model of ovariectomy-induced estrogen deficit.

INTRODUCTION: The ovariectomized rat is a model used to mimic the changes in female organism during menopause. Aroniamelanocarpa fruit juice (AMFJ) is extremely rich in phenolic substances (procyanidins, flavonoids and phenolic acids).

Effects of ovariectomy-induced estrogen deficit on rat behaviour, lipid metabolism, inflammation, bone mineral density, and turnover.

AIM: The objective of the present study was to make a complex evaluation of behaviour, lipid metabolism, inflammation, and bone turnover in an ovariectomized rat model used to simulate postmenopausal clinical findings. MATERIALS AND METHODS: Female Wistar rats were divided into 2 groups of 16 animals each: sham operated (SO) animals and ovariectomized (OVX) animals. Three months after the operation, a battery of behavioural tests was performed including an open field test (OFT), elevated pus-maze test (EPM), the social interaction test (SIT), the forced swim test (FST), and a hot plate test (HPT). At termination of experiment, weight gain and fat deposits (total and retroperitoneal) were measured. Serum concentrations of blood lipids were determined. Tumor necrosis factor alpha (TNF-alpha) and alkaline phosphatase (ALP) serum concentrations were used for evaluation of the inflammation and bone turnover, respectively. Femur bone mineral density (BMD) was evaluated using dual energy X-ray absorptiometry. RESULTS: OVX rats did not demonstrate any significant behavioural changes in OFT and EPM tests but showed a decreased interaction time in SIT and an increased immobility time in FST test which indicated anxiety and depression. The OVX rats had a significantly lower pain sensitivity threshold. They had greater weight gain, increased total and retroperitoneal fat deposits, as well as elevated total fat/body weight and retroperitoneal fat/body weight ratios. Blood cholesterol, ALP and TNF-alpha of the OVX group were also significantly higher. Femur BMD of OVX rats was slightly but not significantly reduced. CONCLUSIONS: Estrogen deficiency in OVX rats caused depression, anxiety, hyperalgesia, obesity, dyslipidemia, and inflammation before the reduction in bone mineral density was prominent.

Protective effects of Aronia melanocarpa juices either alone or combined with extracts from Rosa canina or Alchemilla vulgaris in a rat model of indomethacin-induced gastric ulcers.

The aim of the study was to investigate the effects of four Aronia melanocarpa-based juices in a rat model of indomethacin-induced gastric ulceration. THE JUICES WERE: AM1 and AM2 (produced from aronia fruits at 20 °C and 60 °C, respectively), AMRC (a mixture of AM2 with Rosa canina extract) and AMAV (aronia juice with Alchemilla vulgaris). Male Wistar rats were used. Each of the juices (10 ml/kg) was administered for 10 days. Indomethacin (30 mg/kg) was injected subcutaneously and after 4 h, the effects were estimated. Indomethacin caused heavy destructions of the gastric mucosa, increased the expression of Bax and decreased the expression of Bcl-2, induced a certain increase in lipid peroxidation and a slight decrease in gastric PGE2 content. The pretreatment with the juices reduced the severity of indomethacin-induced gastric lesions and antagonized the effects of indomethacin on apoptosis and lipid peroxidation. The highest was the protective effect of AMAV, the juice with the highest polyphenolic content. The protective effect of Aronia melanocarpa-based juices against indomethacin-induced gastric lesions could be attributed to their polyphenolic contents. The mechanism involved to the highest extent in the protective effect of the juices was the inhibition of apoptosis.

Aronia melanocarpa (Michx.) Elliot fruit juice reveals neuroprotective effect and improves cognitive and locomotor functions of aged rats.

The aim of the study was to investigate the effect of polyphenol-rich Aronia melanocarpa (Michx.) Elliot juice (AMJ) on learning ability and memory, and brain morphology of aged rats. A model of healthy male Wistar rats (24 months of age) divided in 2 groups was used: AMJ group supplemented orally with AMJ (10 mL/kg for 105 days) and old control (CO) group without supplementation. Activity cage test showed that AMJ supplemented rats increased the number of vertical movements compared with old controls (p < 0.05). In active avoidance test, supplemented rats increased the number of avoidances on 3rd, 4th and 5th days of learning session, compared with the respective day of old controls (p < 0.05). AMJ supplementation did not affect the mean neuronal number in the dentate gyrus but significantly increased the density of nerve fibers in the perforant path of the hippocampus (p < 0.05). AMJ supplementation increased acetylcholinesterase activity in hippocampus, which is a marker of improved functional activity of the cholinergic neurons. These results indicate that AMJ induced ameliorating changes in the ability of old rats to learn tasks and improved their locomotor functions. AMJ showed a neuroprotective effect by increasing the density of nerve fibers in the hippocampal perforant pathway.

Effects of Chaenomeles maulei Fruit Juice on Reserpine-induced Behavioral Changes in Rats.

BACKGROUND: The fruit juice from. AIM: The aim of the current study was to investigate the effects of. MATERIALS AND METHODS: The experimental design included a total of 50 animals, divided in the following groups: control, R, R+CMFJ2.5, R+CMFJ5, and R+CMFJ10. All groups except the control received a single intraperitoneal injection of reserpine while the Control group was injected with the vehicle. CMFJ was applied through an orogastric cannula at 0, 19, and 23 hours after reserpine injection at doses of 2.5 ml/kg, 5 ml/kg, and 10 ml/kg to groups R+CMFJ2.5, R+CMFJ5, and R+CMFJ10, respectively. The groups control and R received distilled water (10 ml/kg) at the same time points. The open field test (OFT) and the forced swim test (FST) were carried out. In the OFT, crossings and rearings were recorded as a measure of locomotor activity. In the FST, the immobility time served as a measure of depressive-like behavior. RESULTS: In the OFT, the number of crossings of rats were significantly reduced (p<0.05) by reserpine. CMFJ antagonized the effects of reserpine on rat locomotor activity. In the FST, reserpine caused an insignificant reduction of the immobility time while CMFJ reversed this effect probably by increasing the locomotor activity. CONCLUSION: CMFJ reversed reserpine-induced hypokinesia in rats. This effect of CMFJ might be attributed to the polyphenols found in very high concentrations in the juice.

Aronia melanocarpa fruit juice ameliorates the symptoms of inflammatory bowel disease in TNBS-induced colitis in rats.

Trinitrobenzensulfonic acid (TNBS) is commonly used to induce an experimental inflammatory bowel disease (IBD) model. Oxidative stress and inflammation have been proposed as mechanisms underlying the pathophysiology of IBD. Aronia melanocarpa fruit juice (AMFJ) is extremely rich in polyphenolic substances, mainly proanthocyanidins, flavonoids and phenolic acids. The aim of this study was to evaluate the effect of AMFJ in a rat TNBSinduced colitis model and to compare the effect of the juice with that of sulfasalazine. Colitis was induced by TNBS in male Wistar rats. After the induction of colitis, AMFJ at three doses (2.5, 5 and 10 mL/kg) and sulfasalazine (400 mg/kg) were administered orally till the 14th experimental day. Severity of colitis was assessed by macroscopic and histopathological criteria. Oxidative stress was evaluated by the concentration of thiobarbituric acid reactive substances (TBARS). TNBS caused severe colonic damage. AMFJ dose-dependently ameliorated TNBS-induced colitis. It improved the macroscopic and microscopic signs of colitis, and prevented the increase of colonic TBARS concentrations. Regarding different indices, the effect of AMFJ was comparable or even higher than that of sulfasalazine. In conclusion, the ameliorative effects of AMFJ in the experimental TNBSinduced colitis might be the result of its potent antioxidant and antiinflammatory properties.

Effects of Aronia melanocarpa Fruit Juice on Isolated Rat Hepatocytes.

BACKGROUND: Aronia melanocarpa (Michx.) Elliot fruits are very rich in polyphenols - procyanidins, flavonoids, and phenolic acids. OBJECTIVE: On rat hepatocytes, isolated by two-stepped collagenase perfusion, we investigated the effect of A. melanocarpa fruit juice (AMFJ) in two models of liver toxicity caused by (i) metabolic bioactivation of carbon tetrachloride (CCl4), and (ii) tert-butyl hydroperoxide (t-BuOOH)-induced oxidative stress. MATERIALS AND METHODS: Isolated rat hepatocytes are a suitable model for hepatotoxicity studies. We determined the main parameters of the functional and metabolic status of rat hepatocytes: Cell viability (measured by trypan blue exclusion) and the levels of lactate dehydrogenase (LDH), reduced glutathione (GSH), and malondialdehyde (MDA). These parameters were used to investigate the protective effects of AMFJ in the two toxicity models. The effects of AMFJ were compared with those of silymarin. The cells were treated either with AMFJ or silymarin at increasing concentrations of 5 µg/ml, 10 µg/ml, 30 µg/ml, 50 µg/ml, and 100 µg/ml which were used for measuring of IC50. RESULTS: In both toxicity models - CCl4 and t-BuOOH, AMFJ showed statistically significant cytoprotective and antioxidant activities. AMFJ prevented the loss of cell viability and GSH depletion, decreased LDH leakage and MDA production. The effects of AMFJ at the concentrations of 5, 10, 30, and 50 µg/ml were similar to those of the same concentrations of silymarin, while the effect of the highest AMFJ concentration of 100 µg/ml was higher than that of the same silymarin concentration. The effects were concentration-dependent and more prominent in the t-BuOOH model, compared to those in the CCl4 model. CONCLUSION: The cytoprotective and antioxidant effects of AMFJ established in this study might be due to its polyphenolic ingredients, which could influence the cytochrome P450-mediated metabolism of the experimental hepatotoxic substances (CCl4 and t-BuOOH) and could act as free radical scavengers. The stronger effects of the highest AMFJ concentration in comparison with that of silymarin were possibly due to the combined presence of different polyphenols in the juice. SUMMARY: On rat hepatocytes, isolated by two-stepped collagenase perfusion, we investigated the effect of Aronia melanocarpa fruit juice (AMFJ) in two models of liver toxicity caused by i) metabolic bioactivation of carbon tetrachloride (CCl4), and ii) tert-butyl hydroperoxide (t-BuOOH)-induced oxidative stress. In both toxicity models - CCl4 and t-BuOOH, AMFJ showed statistically significant cytoprotective and antioxidant activities. AMFJ prevented the loss of cell viability and GSH depletion, decreased LDH leakage and MDA production. The effects of AMFJ at the concentrations of 5, 10, 30, and 50 µg/ml were similar to those of the same concentrations of silymarin, while the effect of the highest AMFJ concentration of 100 µg/ml was higher than that of the same silymarin concentration. The effects were concentration-dependent and were more prominent in the t-BuOOH model, compared to those in the CCl4 model.

Memory effects of Aronia melanocarpa fruit juice in a passive avoidance test in rats.

AIM: To study the effect of Aronia melanocarpa fruit juice on memory in male Wistar rats. MATERIALS AND METHODS: The juice was administered orally for 7, 14, 21 and 30 days at doses of 2.5 ml/kg, 5 ml/kg and 10 ml/kg. Memory was assessed in the one-way passive avoidance task (step through) which consisted of one training session and two retention tests (3 hours and 24 hours after training). The variables measured were the latency time to step into the dark compartment of the apparatus and the learning criterion (remaining in the illuminated compartment for at least 180 sec). RESULTS: Oral administration of Aronia melanocarpa fruit juice for 7 and 14 days resulted in a dose-dependent tendency to increase the latency time and the learning criterion compared to saline-treated controls but the effect failed to reach statistical significance. After 21 days of treatment, the juice dose-dependently prolonged the latency time at the retention tests, the effect being significant at doses of 5 ml/kg and 10 ml/kg. Applied for 30 days, the juice in all the tested doses increased significantly the latency time at the retention tests and the dose of 10 ml/kg significantly increased the percentage of rats reaching the learning criterion. CONCLUSION: These findings suggest that Aronia melanocarpa fruit juice could improve memory in rats. The effect is probably due to the polyphenolic ingredients of the juice which have been shown to be involved in learning and memory processes.

Effect of Aronia melanocarpa fruit juice on amiodarone-induced pneumotoxicity in rats.

BACKGROUND: The fruits of Aronia melanocarpa (Michx.) Elliot is extremely rich in biologically active polyphenols. OBJECTIVE: We studied the protective effect of A. melanocarpa fruit juice (AMFJ) in a model of amiodarone (AD)-induced pneumotoxicity in rats. MATERIALS AND METHODS: AD was instilled intratracheally on days 0 and 2 (6.25 mg/kg). AMFJ (5 mL/kg and 10 mL/kg) was given orally from day 1 to days 2, 4, 9, and 10 to rats, which were sacrificed respectively on days 3, 5, 10, and 28 when biochemical, cytological, and immunological assays were performed. RESULTS: AMFJ antagonized AD-induced increase of the lung weight coefficient. In bronchoalveolar lavage fluid, AD increased significantly the protein content, total cell count, polymorphonuclear cells, lymphocytes and the activity of lactate dehydrogenase, acid phosphatase and alkaline phosphatase on days 3 and 5. In AMFJ-treated rats these indices of direct toxic damage did not differ significantly from the control values. In lung tissue, AD induced oxidative stress measured by malondialdehyde content and fibrosis assessed by the hydroxyproline level. AMFJ prevented these effects of AD. In rat serum, AD caused a significant elevation of interleukin IL-6 on days 3 and 5, and a decrease of IL-10 on day 3. In AMFJ-treated rats, these indices of inflammation had values that did not differ significantly from the control ones. CONCLUSION: AMFJ could have a protective effect against AD-induced pulmonary toxicity as evidenced by the reduced signs of AD-induced direct toxic damage, oxidative stress, inflammation, and fibrosis.

Protective effect of Aronia melanocarpa fruit juice in a model of cisplatin-induced cytotoxicity in vitro.

AIM: The aim of the present study was to investigate the protective potential of Aronia melanocarpa fruit juice in a model of cisplatin-induced cytotoxicity in the human embryonal kidney cell line HEK293T. MATERIALS AND METHODS: The cellular viability was assessed using the MTT-dye reduction assay based on the reduction of the yellow tetrazolium dye MTT to a violet formazan product via the mitochondrial succinate dehydrogenase in viable cells. Cisplatin was applied in various concentrations either alone or after a 24-hour pretreatment of the cells with Aronia melanocarpa fruit juice at 0.1 and 0.05 mg/ml. The half maximal inhibitory concentrations (IC50 values) were derived from the concentration-response curves to cisplatin. RESULTS: Applied alone, the anticancer drug caused a prominent decrease of cellular viability with IC50 8.3 +/- 1.1 microM. The juice proved to significantly ameliorate the in vitro cytotoxicity of the platinum drug, in a concentration-dependent manner. The pretreatment of the cells with Aronia melanocarpa fruit juice resulted in a significant increase (p < 0.001) of IC50 for cisplatin to 25.1 +/- 2.7 microM (at 0.05 mg/ml) and 34.4 +/- 3.4 microM (at 0.1 mg/ml), respectively. CONCLUSION: The protective effect of Aronia melanocarpa fruit juice observed in this study is most probably due to its well appreciated antioxidant activity as oxidative stress plays a central role in the toxic effects of cisplatin.

Electron spin resonance measurement of radical scavenging activity of Aronia melanocarpa fruit juice.

BACKGROUND: The fruits of Aronia melanocarpa (Michx.) Elliot contain large amounts of phenolic substances, mainly procyanidins, anthocyanins and other flavonoids, and phenolic acids. The ability of phenolic substances to act as antioxidants has been well established. OBJECTIVE: In this study, we investigated the radical scavenging activity of A. melanocarpa fruit juice (AMFJ). MATERIALS AND METHODS: The method used was electron spin resonance (ESR) spectroscopy. The galvinoxyl free radical was used as a scavenging object. AMFJ was added to the galvinoxyl free radical solution. The measure of the radical scavenging activity was the decrease of signal intensity. RESULTS: AMFJ showed a potent antiradical activity causing a strong and rapid decrease of signal intensity as a function of time and juice concentration. This effect of AMFJ was probably due to the activity of its phenolic constituents. CONCLUSION: The ESR measurements in this study showed a pronounced radical scavenging effect of AMFJ, an important mechanism of its antioxidant activity.

A model of experimental acute hematogenous pyelonephritis in the rat.

The OBJECTIVE of the study was to create a model of acute hematogenous pyelonephritis in the rat without causing urinary retention by ligation of the ureter. Mixed bacterial suspension containing 1.5 x 10(6) colony-forming units (CFU) of S. aureus and 3.0 x 10(6) CFU of E. coli was inoculated in the caudal vein at a dose of 0.5 ml/kg. Control animals received the same amount of saline solution. Pyelonephritis was confirmed by lab urine tests and histopathological study of the kidneys. Infected animals initially developed sepsis with a significant increase of leukocytes and C-reactive protein in the blood. Originally only bacteriuria was found in the urine of experimental animals, but later, in the course of the development of pyelonephritis (12-18 days), leucocyturia and active leukocytes (glitter cells) were also available in urine. The levels of beta-2 microglobulin in the urine of infected animals (4.02 +/- 0.04 mmol/l on day 16 and 4.18 + 0.07 mmol/l on day 18) were significantly highly increased (p <0.0001) in comparison with the value of the control group (0.088 +/- 0.005 mmol/l). In the early days the histopathological examination of the kidneys established erythrocyte stasis. Later leukocyte infiltrates were observed in the interstitial tissue around the kidney tubules, glomeruli and vascular walls, and inflammatory cell infiltration and degenerative changes were present in the epithelium of the canaliculi. Combined hematogenous infection with S. aureus and E. coli led to the development of pyelonephritis in rats. The pathology in the kidney tubules was confirmed by histopathological study and by the elevated levels of beta-2 microglobulin and the presence of active leukocytes in urine.

Current knowledge of Aronia melanocarpa as a medicinal plant.

Aronia melanocarpa, native to eastern North America, has become popular in Eastern Europe and Russia. Aronia melanocarpa fruits are one of the richest plant sources of phenolic substances, mainly anthocyanins--glycosides of cyanidin. Anthocyanins are water soluble pigments accounting for the dark blue and even black color of the fruits. Administered orally they can be absorbed as intact glycosides. Aronia melanocarpa fruit juice and anthocyanins derived from the fruits have been studied intensively for the last 15 years. Most of the effects of Aronia melanocarpa anthocyanins are due to their high antioxidative activity. Our investigations have demonstrated a remarkable hepatoprotective, a very good gastroprotective and a pronounced anti-inflammatory effect of Aronia melanocarpa fruit juice in rats as well as a bacteriostatic activity in vitro against Staphylococcus aureus and Escherichia coli and an antiviral activity against type A influenza virus. Research of other authors has demonstrated that Aronia melanocarpa anthocyanins can normalize the carbohydrate metabolism in diabetic patients and in streptozotocin-diabetic rats, have an in vitro antimutagenic activity and exhibit a distinct immunomodulatory activity in human lymphocyte cultures and in patients with breast cancer, suppress the growth of human HT-29 colon cancer cells, inhibit the N-nitrosamine formation in rats and decrease the toxicity and cumulation of cadmium in liver and kidneys. Currently, there are no data in literature about any unwanted and toxic effects of Aronia melanocarpa fruits, juice and extracts.

Protective effect of Aronia melanocarpa fruit juice pretreatment in a model of carbon tetrachloride-induced hepatotoxicity in rats.

UNLABELLED: The main active ingredients of Aronia melanocarpa fruit juice (AMFJ) are phenolic substances, mainly flavonoids from the anthocyanin subclass. AIM: The aim of the present study was to investigate the effect of AMFJ applied as pretreatment in a model of carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. MATERIAL AND METHODS: AMFJ was given orally to rats for 2 days at doses of 5, 10 and 20 ml/kg either alone or as pretreatment before the oral application of CCl4 (0.2 ml/kg, 2 days). The plasma activities of aspartate transaminase (AST) and alanine transaminase (ALT) were measured as markers of the liver cell damage. The levels of malondialdehyde (MDA), a lipid peroxidation marker, were determined in rat liver and plasma. RESULTS: Administration of CCl4 caused an elevation of plasma AST and ALT activities. It also induced an elevation of MDA levels in rat liver and plasma. AMFJ applied alone in the tested doses did not cause any significant changes in the measured enzyme activities and in MDA levels. AMFJ applied as pretreatment prevented the CCl4-induced increase of AST and ALT activities, and also prevented the elevation of plasma and liver MDA levels. CONCLUSIONS: AMFJ showed a protective effect in a model of CCl4-induced hepatotoxicity in rats. This effect might be due to the antioxidant activity of its active ingredients.

Protective effect of BP 2-94, a histamine H3-receptor agonist prodrug, in a model of carbon tetrachloride-induced hepatotoxicity in rats.

UNLABELLED: BP 2-94 is a prodrug of the H3-receptor agonist (R)-alpha-methylhistamine [(R)-alpha-MeHA]. BP 2-94 displayed anti-inflammatory, antinociceptive and ulcero-protective properties in experimental animals. AIM: The aim of the present study was to investigate the effect of BP 2-94 in a model of carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. MATERIALS AND METHODS: In order to investigate the effect of BP 2-94 it was applied to rats either alone (20, 40 and 60 micromol kg(-1), 4 days) or as a pretreatment (20, 40 and 60 micromol kg(-1), 4 days) before the application of CCl4 (0,2 ml kg(-1), 2 days). RESULTS: BP 2-94 in the tested doses did not cause significant changes in the plasma aspartate transaminase (AST) and alanine transaminase (ALT) activities and the liver microscopic appearance was normal. Hepatocyte damage, as evident by local areas of liver necrosis and elevated levels of plasma AST and ALT, occurred in rats following acute exposure to CCl4 (0,2 ml kg(-1), 2 days). BP 2-94 applied as a pretreatment dose-dependently reduced the necrotic changes in rat liver and inhibited the increase of plasma AST and ALT activities in response to CCl4. CONCLUSIONS: BP 2-94 had a hepatoprotective effect in a model of CCl4-induced toxicity in rats. This effect might be due the H3-agonistic activity of its active metabolite (R)-alpha-MeHA.