Didem Deliorman 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.

Evaluation of hepatoprotective effect of Gentiana olivieri herbs on subacute administration and isolation of active principle

Hepatoprotective effect of Gentiana olivieri Griseb. (Gentianaceae) flowering herbs on subacute administration were studied using in vivo models in rats. For the activity assessment on carbon tetrachloride-induced hepatic damage following biochemical parameters were evaluated; plasma and hepatic tissue malondialdehyde formation, and liver tissue glutathione level, as well as plasma transaminase enzyme levels (aspartate transferase and alanine transferase). Results of biochemical tests were also confirmed by histopathological examination. Through bioassay-guided fractionation procedures isoorientin, a known C-glycosylflavone, was isolated from the ethyl acetate fraction as the active antihepatotoxic constituent by silica gel column chromatography. Isoorientin exhibited significant hepatoprotective effect at 15 mg/kg b.w. dose.

Anti-inflammatory and antinociceptive activity of flavonoids isolated from Viscum album ssp. album.

Abstract Viscum album L. has been used in the indigenous systems of medicine for treatment of headache and some inflammatory diseases. In order to evaluate this information, antinociceptive and anti-inflammatory activities of the five flavonoids (5,7-dimethoxy naringenin or 4′,6′- dimethoxy chalcononaringenin) derivatives, isolated from the ethyl acetate fraction of the extract from V. album ssp. album, were investigated, namely 5,7-dimethoxy-flavanone-4′-O- β-ᴅ-glucopyranoside (1), 2′-hydroxy-4′,6′-dimethoxy-chalcone-4-O-β-ᴅ-glucopyranoside (2), 5,7-dimethoxy-flavanone-4′-O-[2″-O-(5‴-O-trans-cinnamoyl)-β-ᴅ-apiofuranosyl]-β-ᴅ-glucopyranoside (3), 2′-hydroxy-4′,6′-dimethoxy-chalcone-4-O-[2″-O-(5‴-O-trans-cinnamoyl)-β-ᴅ-apiofuranosyl]- β-ᴅ-glucopyranoside (4), 5,7-dimethoxy-flavanone-4′-O-[β-d-apiofuranosyl- (152)]-β-ᴅ-glucopyranoside (5). For the antinociceptive activity assessment the p-benzoquinone- induced writhing test and for the anti-inflammatory activity the carrageenan-induced hind paw edema model in mice were used. The ethyl acetate fraction in a dose of 250 mg/kg as well as compounds 2 and 5 in a 30 mg/kg dose were shown to possess remarkable antinociceptive and anti-inflammatory activities per os without inducing any apparent acute toxicity as well as gastric damage

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.

In vivo activity assessment of a “honey-bee pollen mix” formulation

Honey-bee pollen mix (HBM) formulation is claimed to be effective for the treatment of asthma, bronchitis, cancers, peptic ulcers, colitis, various types of infections including hepatitis B, and rheumatism by the herb dealers in northeast Turkey. In the present study, in vivo antinociceptive, anti-inflammatory, gastroprotective and antioxidant effects of pure honey and HBM formulation were evaluated comparatively. HBM did not show any significant gastroprotective activity in a single administration at 250 mg/kg dose, whereas a weak activity was observed after three days of successive administration at 500 mg/kg dose. On the other hand, HBM displayed significant antinociceptive (p <0.01) and anti-inflammatory (p <0.01) activities at 500 mg/kg dose orally without inducing any apparent acute toxicity or gastric damage. HBM was also shown to possess potent antilipidperoxidant activity (p <0.01) at 500 mg/kg dose against acetaminophen-induced liver necrosis model in mice. On the other hand, pure honey did not exert any remarkable antinociceptive, anti-inflammatory and gastroprotective activity, but a potent antilipidperoxidant activity (p <0.01) was determined. Results have clearly proved that mixing pure honey with bee pollen significantly increased the healing potential of honey and provided additional support for its traditional use. Total phenolic and flavonoid contents of HBM were found to be 145 and 59.3 mg/100 g of honey, which were estimated as gallic acid and quercetin equivalents, respectively.

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.

Fatty acid composition of Viscum album subspecies from Turkey

The lipophylic extracts of three Viscum album subspecies growing on different host plants in Turkey were comparatively analyzed for derived methyl esters of their fatty acids by capillary gas chromatography-mass spectrometry (GC-MS). The sample of V. album ssp. album growing on apricot trees was remarkably rich in palmitic acid (11.47%). Arachidic acid was found in only ssp. austriacum and ssp. abietis samples. The unsaturated fatty acids, mainly oleic and linoleic acids, were identified in nine lipophylic extracts obtained from V. album samples belonging to ssp. album. The amounts of linoleic and oleic acid were the highest in the sample of ssp. album growing on apricot trees (12.18 and 9.19%, respectively).

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.