Investigation of Enzyme Inhibitory Activities, Antioxidant Activities, and Chemical Properties of Pistacia vera Leaves Using LC-QTOF-MS and RP-HPLC.

Since the leaves of some Pistacia species are used in traditional folk medicine for diabetes, this study investigated the in vitro antidiabetic effect (α-glucosidase and α-amylase) of Pistacia vera leaves. Additionally, the current study investigated the antihypercholesterolemic (cholesterol esterase), antiobesity (pancreatic lipase), and antioxidant activities (i.e., total antioxidant capacity, DPPH (2,2-Diphenyl-1-picrylhydrazyl) radical scavenging activity, metal chelating activity, and ferric-reducing antioxidant power) of P. vera leaves. The aqueous-alcoholic leaf extract inhibited α-amylase, α-glucosidase, and pancreatic lipase with the half-maximal inhibitory concentration values of 7.74 ± 0.72, 11.08 ± 3.96, and 168.43 ± 26.10 µg/mL, respectively. It was determined that the crude extract had high DPPH radical scavenging activity, ferric-reducing power, and moderate metal chelating activity. The ethyl acetate (EtOAc) subextract obtained by the liquid-liquid fractionation of the crude extract showed potent α-amylase and α-glucosidase inhibitory activities. The EtOAc subextract (5.794 ± 0.027 g/100 g subextract) was standardized by reversed-phase high-performance liquid chromatography based on ß-pentagalloyl glucose, which showed inhibitory effects on both amylase and glucosidase enzymes. Fifteen compounds, seven of which are organic acid derivatives and eight of which are flavonoids, were identified by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) analysis in the crude extract of P. vera leaves. Seven of the fifteen phenolic compounds detected in the crude extract by LC-QTOF-MS have both glucosidase and amylase inhibitory effects. As a result, P. vera leaves can be a potential source for compounds with high antioxidant effects that show inhibitory effects on enzymes involved in carbohydrate digestion in the prevention and treatment of diabetes or can be evaluated as a standardized extract.

Activity-guided isolation of α-amylase, α-glucosidase, and pancreatic lipase inhibitory compounds from Rhus coriaria L.

The leaves and fruits of Rhus coriaria are traditionally used in Turkey for the treatment of diabetes. The aim of the present study is to determine α-amylase, α-glucosidase, and pancreatic lipase inhibitory activities of R. coriaria leaf and fruit ethanol extracts (80%), and to isolate active compounds against these enzymes. As a result of the activity-guided isolation, the active compounds were determined as the amentoflavone, agathisflavone, and 1,2,3,4,6-penta-O-galloyl-ß-glucopyranose. Agathisflavone, amentoflavone, and penta-O-galloyl-ß-glucopyranose inhibited α-glucosidase with 11.4 ± 0.9, 11.3 ± 0.7, and 4.1 ± 0.1 µM IC50 values, respectively. Furthermore, penta-O-galloyl-ß-glucopyranose inhibited α-amylase with 6.32 ± 0.18 µM IC50 . These three compounds also significantly inhibited (P < 0.05) pancreatic lipase. The results of high-performance liquid chromatography analysis showed that penta-O-galloyl-ß-D-glycopyranose was one of the main compounds in both fruit and leaf extracts. Therefore, it may be considered that R. coriaria fruit and leaf extracts can be standardized on this substance and used in the development of both medicinal products and functional food for diabetes. PRACTICAL APPLICATION: Rhus coriaria (Sumac) is one of the plants that is well known and used around the world as a spice. It is also used against diabetes traditionally. The determination of effective compounds can lead to the standardization and development of both medicinal products and functional foods for diabetes. While the fruits of the plant are used as a spice all around the world, the leaves are generally throw away; therefore, the usage of the leaves to the food and medical industry can lead to beneficial effects on the economy.

Nephroprotective effect of Ferulago angulata flowers on N-nitrosodimethylamine-induced nephrotoxicity in rats and its phytochemical profile.

The present study was designed to assess the phytochemical content of Ferulago angulata (FA) and possible in vivo nephroprotective effect of FA administration on trace elements, minerals, MDA and GSH in kidney and liver tissue samples, serum vitamin (α-tocopherol, retinol, cholecalciferol, phylloquinone), TSA, and LSA in a rat model of DMN-induced nephrotoxicity. In the study, Wistar albino rats were assigned to six groups: Control (0.9% NaCl), (DMN 10 mg/kg), (FA 150 mg/kg), (DMN + FA 150 mg/kg), (FA 300 mg/kg), and (DMN + FA 300 mg/kg). Rats were intraperitoneally given DMN for the first 7 days. Renal injury caused by DMN was proved by the histopathological alterations. The FA (300 mg/kg) treatment significantly normalized Se, Cr, Ca levels in liver and Co level in kidney tissue samples. These observed positive effects are due to the phytochemical content of the plant. The flower extract of FA (300 mg/kg) can be used for the prevention of kidney damage. PRACTICAL APPLICATIONS: Ferulago angulata flowers are used in traditional medicine for treat kidney and liver digestive system diseases. This species is endemic taxa of the family Apiaceae, which has been used both as food and therapeutics because of their phytochemical composition. In this study, the phenolic characterization of FA flower was used to a new RP-HPLC method, as well as the biological activity of FA flower and possible in vivo nephroprotective effect of FA flowers on trace elements, minerals, MDA and GSH in kidney and liver tissue samples and vitamins, TSA, and LSA in serum samples a rat model of DMN-induced nephrotoxicity. It was found that high level of phenolic compounds (chlorogenic acid, vanillic acid, 2-hydroxycinnamic acid) present in the flower extract of F. angulata has positive effects and antioxidant properties. Due to its phenolic content, FA flower extract could protect for kidney damage and can be used as antioxidants in the food additive and pharmaceutical industry.

Evaluation of the lifespan extension effects of several Turkish medicinal plants in Caenorhabditis elegans.

Research on longevity is important to both prolong lifespan and support healthy aging. Natural products are widely being utilized and used as new resources for drug molecules. Caenorhabditis elegans is an advantageous organism for longevity research and age-related diseases. In this study, we tested a number of plant extracts for their effects on C. elegans longevity. In lifespan assays, agesynchronized wild-type C. elegans specimens were treated with different concentrations of plant extracts. Plant extracts were prepared as either infusions or decoctions, similar to their traditional utilization. Hedera helix L. (Araliaceae) extended lifespan in worms in a concentration-dependent manner. The mean survival rates in the H. helix-treated groups were significantly higher, by 23.7% when applied at 1000 µg/mL, 16% when applied at 500 µg/mL, and 16% when applied at 250 µg/mL, compared to the control group. HPLC analysis identified chlorogenic acid as the major component of H. helix. Salvia verticillata L. (Lamiaceae) and Myrtus communis L. (Myrtaceae) treatments resulted in median lifespan extension. Maximum lifespan was extended in worms by Rubus sanctus Schreb. (Rosaceae) treatment. This study provided the first evidence demonstrating the possible lifespan-extending effects of a group of Turkish medicinal plants in an in vivo model, C. elegans.

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.

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 plant's aerial parts and may suggest a realistic explanation for its traditonal usage in epilepsy.

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.

In vivo anti-inflammatory and antinociceptive activity of the crude extract and fractions from Rosa canina L. fruits.

The aqueous and ethanol extracts of Rosa canina L. (Rosaceae) fruits and the fractions prepared from the latter were investigated for their anti-inflammatory and antinociceptive activities in several in vivo experimental models. The ethanolic extract was shown to possess significant inhibitory activity against inflammatory models (i.e., carrageenan-induced and PGE(1)-induced hind paw edema models, as well as on acetic acid-induced increase in a capillary permeability model) and on a pain model based on the inhibition of p-benzoquinone-induced writhing in mice. Hexane, chloroform, ethylacetate, n-butanol and the remaining water fractions were obtained through bioassay-guided fractionation. Ethylacetate and n-butanol fractions displayed potent anti-inflammatory and antinociceptive activities at a dose of 919 mg/kg without inducing acute toxicity. Further attempts to isolate and define the active constituent(s) were inconclusive, possibly due to the synergistic interaction of components in the extract.

In vivo antidiabetic and antioxidant potential of Helichrysum plicatum ssp. plicatum capitulums in streptozotocin-induced-diabetic rats.

Helichrysum species (Asteraceae) are widely found in Anatolia. Decoction prepared from the capitulums of Helichrysum plicatum ssp. plicatum is used to alleviate the symptoms of diabetes mellitus in folk medicine. In the present study, the hypoglycaemic and antioxidant potential of Helichrysum plicatum ssp. plicatum was evaluated by using in vivo methods in normal and streptozotocin-induced-diabetic rats. After the oral administration of water and ethanolic extracts at doses of 500mg/kg body weight prepared from the capitulums of plant, blood glucose levels were monitored at specific intervals. Tolbutamide was used as a reference drug at a dose of 100mg/kg. The experimental data indicated that water and ethanol extracts of capitulums demonstrate significant antihyperglycaemic and antioxidant activity in streptozotocin-induced rats which confirmed the folkloric utilization. In order to assess the role of polyphenolic components in the relevant activity, phenolic and flavonoid contents of each extract were also determined in terms of total phenols: 113.5+/-8.6mg (gallic acid equivalent/1g extract) and total flavanoids 50.5+/-1.9mg (quercetin equivalent/1g extract) for ethanol extract, total phenols: 75.9+/-3.7, flavonoids: 31.5+/-2.3 for water extract using Folin-Ciocalteu reagent.