Nilüfer Orhan

Hypoglycemic activity and antioxidant potential of some medicinal plants traditionally used in Turkey for diabetes.

Cydonia oblonga Mill. (Rosaceae) leaves, Helianthus tuberosus L. (Asteraceae) tubers, and Allium porrum L. (Liliaceae) bulbs are used as a folk remedy for the treatment of diabetes and they are also consumed as food in Turkey. In the present study, the antidiabetic and antioxidant activities of the ethanol extracts of these plants were studied in normal and streptozotocin-induced diabetic rats for 5 days. All extracts were administrated orally to rats at the doses of 250 and 500 mg/kg. Blood glucose level was measured according to glucose oxidase method. In order to determine antioxidant activity, thiobarbituric acid reactive substance (TBARS) and reduced glutathione (GSH) levels in liver, kidney, and heart tissues were measured by using spectrophotometric methods. Oral administration of Cydonia oblonga (500 mg/kg) and Allium porrum (500 mg/kg) extracts for 5 days in diabetic rats caused a decrease in blood glucose levels by 33.8% and 18.0%, respectively. Moreover, Allium porrum and Cydonia oblonga extracts induced significant alleviation on only heart tissue TBARS levels (44.6 and 45.7%), Helianthus tuberosus and Allium porrum extracts showed an inhibitory effect on kidney tissue TBARS levels (24.5 and 14.8%). None of the extracts restored GSH levels in kidney, liver, and heart tissues of diabetic rats.

Antidiabetic Effect and Antioxidant Potential of Rosa canina Fruits

Rosa canina L. fruits (Rosaceae) are used to treat diabetes in Anatolia traditionally. In this study, the ethanol extract of R. canina fruits and its fractions were screened for their antioxidant, hypoglycaemic and antidiabetic activities. The ethanol extract that was administered for 7 days possessed a remarkable hypoglycemic effect at 250 mg/kg dose in streptozotocin (STZ) induced diabetic rats. Then it was fractionated through successive solvent extractions to yield CHCl 3 Fr., EtOAc Fr., n -BuOH Fr. and R-H 2 O Fr. respectively. These fractions were administrated to normal plus glucose hyperglycemic rats. Additionally the subacute antidiabetic activities of the fractions were studied in diabetic rats for 7 days. The experimental data indicated that R-H 2 O Fr. Possessed significant antidiabetic activity (50-62%) in diabetic rats. Also, a minor hypoglycemic effect was observed in normoglycemic plus glucose-hyperglycemic animals treated with R-H 2 O Fr. (15%). In vitro antioxidant experiments revealed that EtOAc Fr. Showed the highest radical scavenging activity on DPPH (79.5±0.4%), whereas CHCl 3 Fr. exhibited the maximum reducing power. The highest total phenolic content was observed in CHCl 3 Fr. (18.5±0.6% gallic acid equivalent g/g fraction) but no correlation was observed between the antidiabetic activity of fractions and their phenolic contents. Our findings support the traditional usage of R. canina fruits as a folk remedy in the treatment of diabetes in Turkey.

Insights into cholinesterase inhibitory and antioxidant activities of five Juniperus species.

In vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory and antioxidant activities of the aqueous and ethanol extracts of the leaves, ripe fruits, and unripe fruits of Juniperus communis ssp. nana, Juniperus oxycedrus ssp. oxycedrus, Juniperus sabina, Juniperus foetidissima, and Juniperus excelsa were investigated in the present study. Cholinesterase inhibition of the extracts was screened using ELISA microplate reader. Antioxidant activity of the extracts was tested by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide radical scavenging, ferrous ion-chelating, and ferric-reducing antioxidant power (FRAP) assays. Total phenol and flavonoid contents of the extracts were determined spectrophotometrically. The extracts had low or no inhibition towards AChE, whereas the leaf aqueous extract of J. foetidissima showed the highest BChE inhibition (93.94 ± 0.01%). The leaf extracts usually exerted higher antioxidant activity. We herein describe the first study on anticholinesterase and antioxidant activity by the methods of ferrous ion-chelating, superoxide radical scavenging, and ferric-reducing antioxidant power (FRAP) assays of the mentioned Juniperus species.

In vivo and in vitro antidiabetic effect of Cistus laurifolius L. and detection of major phenolic compounds by UPLC-TOF-MS analysis.

ETHNOPHARMACOLOGICAL RELEVANCE In Turkish folk medicine, various parts of Cistus laurifolius L. are used to treat gastric ulcer and various types of pains. Additionally the tea prepared from the leaves is used to decrease symptoms of diabetes. MATERIALS AND METHODS In the present study, the hypoglycemic effects of aqueous and ethanol extracts of Cistus laurifolius were investigated in normal, glucose loaded hyperglycemic and streptozocin (STZ)-induced diabetic rats. α-Glucosidase and α-amylase enzyme inhibitory effects were determined to evaluate the mechanism of action. Total phenolic content of the extracts were determined by using Folin-Ciocalteu reagent and Ultra Performance Liquid Chromatography-Time of Flight Mass Spectrometer (UPLC-TOF-MS) was used to detect the major phenolic compounds in the extract. RESULTS Results indicated that blood glucose levels of the STZ-induced diabetic rats were decreased by ethanol extract at of 250 and 500mg/kg doses as compared to control group (16%-34%). In glucose loaded animals, extracts have shown a weak hypoglycemic effect (11%-20%). Additionally, the ethanol extract of Cistus laurifolius is found to be a potent inhibitor of α-glucosidase and α-amylase, possibly due to several polyphenolic compounds present within the extract. Twelve major flavonoids (apigenin, quercetin, kaempferol, naringenin, quercitrin and their derivatives), gallic, ellagic and chlorogenic acid in chromatographic fingerprint were analyzed by the on-line UPLC-TOF-MS system. CONCLUSIONS Due to having inhibitory effect on blood glucose level and carbohydrate digesting enzymes (α-glucosidase and α-amylase), Cistus laurifolius leaves might be beneficial for diabetic patients.

A bioactivity guided study on the antidiabetic activity of Juniperus oxycedrus subsp. oxycedrus L. leaves.

ETHNOPHARMACOLOGICAL RELEVANCE Juniperus (Cupressaceae) species are widely used as folk medicine in spreading countries. Decoction of Juniperus oxycedrus subsp. oxycedrus L. leaves is used internally to lower blood glucose levels in Turkey. AIM OF THE STUDY To determine hypoglycaemic and antidiabetic activities of Juniperus oxycedrus subsp. oxycedrus leaves and to identify active compounds through bioactivity guided isolation technique. MATERIALS AND METHODS Ethanol and water extracts of Juniperus oxycedrus subsp. oxycedrus (Joso), leaves on oral administration were studied using in vivo models in normal, glucose-hyperglycemic and streptozotocin-induced diabetic rats. Through in vivo bioactivity-guided fractionation processes, a nonpolar fraction was separated from the n-hexane subextract by silica gel column chromatography as the main active fraction. Subfractions of this fraction was found to possess antidiabetic activity and their chemical composition was investigated by GC-FID and GC-MS, simultaneously. RESULTS This is the first report on the antidiabetic constituents of Joso leaves. Fatty acids, such as palmitic, linoleic and linolenic acid were found as the major compounds in subfractions. CONCLUSION Results indicated that Joso leaf extract and its active constituents might be beneficial for diabetes mellitus.

Effects of Juniperus oxycedrus ssp. oxycedrus on tissue lipid peroxidation, trace elements (Cu, Zn, Fe) and blood glucose levels in experimental diabetes.

ETHNOPHARMACOLOGICAL RELEVANCE Juniperus oxycedrus L. (Cupressaceae) fruits and leaves are used internally and pounded fruits are eaten for diabetes in Turkey. AIM OF THE STUDY To evaluate the interrelationships between the levels of chosen trace elements (copper, iron, and zinc) and hepatic, renal lipid peroxidation (TBARS) in streptozotocin-induced diabetic rats treated with Juniperus oxycedrus ssp. oxycedrus (J.o.s.o.) leaf and fruit extracts for 10 days. MATERIALS AND METHODS J.o.s.o. fruit and leaf extracts were administered in STZ-induced diabetic rats, at doses of 500 and 1000 mg/kg. The blood glucose levels were measured in the 1st, 4th, 7th and 10th day of experiment. Fe, Cu, and Zn contents and lipid peroxidation levels of liver and kidney tissues were determined by atomic absorption spectrophotometry and ultraviolet spectrophotometry, respectively. RESULTS Treatment of diabetic rats with the J.o.s.o. fruit and leaf extracts decreased the blood glucose levels and both the levels of lipid peroxidation in liver and kidney tissues. J.o.s.o. extracts have augmented Zn concentrations in liver of STZ-induced diabetic rats. CONCLUSIONS Results indicated that J.o.s.o. fruit and leaf extracts might be beneficial for diabetes and its complications.

UPLC-TOF-MS analysis of Galium spurium towards its neuroprotective and anticonvulsant activities

ETHNOPHARMACOLOGICAL RELEVANCE Galium species have been reported to be used against epilepsy in traditional Turkish folk medicine. AIM OF STUDY The present work was undertaken to evaluate the in vivo anticonvulsant and in vitro neuroprotective effects of Galium spurium L. and to determine the major constituents by UPLC-TOF-MS. MATERIALS AND METHODS Anticonvulsant activity of the aerial parts of Galium spurium was investigated using pentylenetetrazole, picrotoxin, and maximal electroshock-induced seizure animal models. In order to evaluate the safety, neurotoxicity (Rota rod test) of the ethanol extract was also determined. In vitro neuroprotective effect of the ethanol extract of Galium spurium was assessed by acetylcholinesterase and butrylcholinesterase inhibitions. Ultra Performance Liquid Chromatography-Time of Flight Mass Spectrometer (UPLC-TOF-MS) was used to identify the major compounds in the extract. RESULTS In pentylenetetrazole-induced seizure, the ethanol extract at doses of 250 and 1000mg/kg prolonged the onset of seizures. Similarly, Galium spurium (250 and 500mg/kg) significantly delayed the onset of picrotoxin-induced seizures in mice and these doses also exhibited 12.5% and 17% protection, respectively, against picrotoxin-induced seizures. Furthermore, Galium spurium extract showed a significant protective effect against maximal electroshock-induced seizures at doses of 250 and 1000mg/kg (50% and 37.5%, respectively) and also all tested doses prolonged the onset of seizures. No motor co-ordination was observed with intraperitoneal injection of Galium spurium extract at doses of 500 and 1000mg/kg. The extract exhibited 16.2% inhibition against butrylcholinesterase at 200μg/mL concentration, whereas it did not inhibit acetylcholinesterase. Phytochemical analysis of the extract based on the MS data by UPLC-TOF-MS, ten major compounds (phenolic and triterpenic acids, flavonoids and iridoids) were determined. CONCLUSIONS The results indicate that Galium spurium may have anticonvulsant activity against picrotoxin and maximal electroshock-induced seizures in mice. Phenolic acids, flavonoids and iridoids might be responsible for anticonvulsant activity. The results offer possible beneficial effects by the plants aerial parts and may suggest a realistic explanation for its traditonal usage in epilepsy.

Identification of hypoglycaemic compounds from berries of Juniperus oxycedrus subsp. oxycedrus through bioactivity guided isolation technique

ETHNOPHARMACOLOGICAL RELEVANCE Decoction of Juniperus oxycedrus subsp. oxycedrus L. (Cupressaceae) berries is used internally as tea and pounded fruits are consumed to lower blood glucose levels in Turkey. AIM OF THE STUDY To evaluate hypoglycaemic and antidiabetic activity of J. oxycedrus subsp. oxycedrus berries and to identify active compounds through bioactivity guided isolation technique. MATERIAL AND METHODS Hypoglycaemic effect of J. oxycedrus subsp. oxycedrus (Joso) berry extracts on oral administration was studied using in vivo models in normal, glucose-hyperglycaemic rats. Streptozotocin induced diabetic rats were used to examine antidiabetic activity of Joso extracts, subextracts, fractions, subfractions and shikimic acid (SA). RESULTS Through in vivo bioactivity-guided fractionation processes, shikimic acid, 4-O-β-d-glucopyranosyl ferulic acid and oleuropeic acid-8-O-β-d-glucopyranoside were isolated from the n-butanol subextract by silica gel and reverse phase column chromatography as the main active ingredient of the active subfraction. After 8 days administration of the major compound shikimic acid, blood glucose levels (24%), malondialdehyde levels in kidney tissues (63-64%) and liver enzymes (AST, ALT, ALP) of diabetic rats were decreased. CONCLUSION Results indicated that Joso berry extract and its active constituents might be beneficial for diabetes and its complications.

Preventive treatment of calcium oxalate crystal deposition with immortal flowers

ETHNOPHARMACOLOGICAL RELEVANCE A number of medicinal plants are used for their diuretic, urolithiatic and anti-inflammatory effects on urinary system problems in Turkey and the most common traditional remedy for kidney stones is the tea of immortal flowers. The aim of this study is to evaluate the preventive effect of infusions prepared from capitulums of Helichrysum graveolens (M.Bieb.) Sweet (HG) and Helichrysum stoechas ssp. barellieri (Ten.) Nyman (HS) on formation of kidney stones. MATERIALS AND METHOD Sodium oxalate (Ox-70mg/kg intraperitoneally) was used to induce kidney stones on Wistar albino rats. At the same time, two different doses of the plant extracts (HG: 62.5 and 125mg/kg; HS: 78 and 156mg/kg) were dissolved in the drinking water and administered to animals for 5 days. Potassium citrate was used as positive control in the experiments. During the experiment, water intake, urine volume and body weights of the animals were recorded. At the end of the experiments, liver, kidney and body weights of the animals were determined; biochemical analysis were conducted on urine, blood and plasma samples. Histopathological changes in kidney tissues were examined and statistical analysis were evaluated. RESULTS HS extract showed the highest preventive effect at 156mg/kg dose (stone formation score: 1.16), whereas a number of kidney stones were maximum in sodium oxalate group (stone formation score: 2.66). Helichrysum extracts decreased urine oxalate and uric acid levels and increased citrate levels significantly. In addition, Helichrysum extracts regulated the negative changes in biochemical and hematological parameters occurred after Ox injection. CONCLUSIONS We conclude that Helichrysum extracts could reduce the formation and growth of kidney stones in Ox-induced urolithiasis and can be beneficial for patients with recurrent stones. In addition, this is the first study on the preventive effect of immortal flowers.

Effect of Gentiana olivieri on experimental epilepsy models

Background: Flowering herbs of Gentiana olivieri Griseb. (Gentianaceae) are widely used as bitter tonic, stomachic, stimulant of appetite, antipyretic, anticonvulsant, antidiabetic and for mental problems in the different regions of Turkey. Objective: To establish the anticonvulsant activity potential of G. olivieri. Materials and Methods: In this work, the ethanol extract of G. olivieri was tested in three doses (200, 750 and 1000 mg/kg) for anticonvulsant activity against seizures produced in mice by pentylenetetrazole (PTZ), picrotoxin (PIC) and maximal electroshock (MES). Neurotoxicity of the ethanol extract was also determined by the Rota rod test to evaluate the safety. Ethosuximide (150 mg/kg), diazepam (0.5 mg/kg) and carbamazepine (30 mg/kg) were used as reference drugs. Results: Intraperitonally, injection of the extract significantly prolonged the onset of seizures at doses of 200 and 750 mg/kg, but did not alter the incidence of PTZ-induced seizures. Onset of PIC-induced seizures was delayed by the injection of the extract (1000 mg/kg). Moreover, only 750 mg/kg of the extract protected 25% of the mice against PIC-induced seizures. On the other hand, G. olivieri extract (200, 750 and 1000 mg/kg) showed a significant protective effect against MES-induced seizures. In the Rota rod test, the ethanol extract (200 mg/kg, ip) induced disturbance in motor coordination. Conclusion: The results indicate that G. olivieri has possessed anticonvulsant activity against MES-induced seizures in mice.