Gürbüz, I. | Yeşilada, Erdem

Article | 2007 | Journal of Ethnopharmacology112 ( 2 ) , pp.284 - 291

The guaianolide type sesquiterpene lactones chlorojanerin, 13-acetyl solstitialin A and solstitialin A were identified as the anti-ulcerogenic components of the chloroform extract of the aerial parts of Centaurea solstitialis ssp. solstitialis (Asteraceae). In this study, these compounds were investigated by using various in vivo ulcer models in rats and mice. Chlorojanerin was shown to be significantly effective in preventing the induction of lesions by ethanol- (EtOH-) (both oral and subcutaneous administration), indomethacin-, indomethacin plus HCl/EtOH-, NG-nitro-l-arginine methyl ester plus EtOH-, N-ethylmaleimide plus EtOH-, w . . .ater immersion and restraint stress, and serotonin, as well as inhibiting titratable gastric acidity and acid output, and increasing gastric pH, but was ineffective in the prevention of ulcers induced by pyloric ligation, diethyldithiocarbamate, and cysteamine, and had no effect on gastric secretion volume or peptic activity. A mixture of 13-acetyl solstitialin A (95%) and solstitialin A (5%) was found to be significantly effective against EtOH-induced lesions on oral administration but was ineffective when administered subcutaneously. This mixture was also found to be effective in preventing lesions induced by EtOH, indomethacin, indomethacin plus HCl/EtOH, NG-nitro-l-arginine methyl ester plus EtOH, N-ethylmaleimide plus EtOH, water immersion and restraint stress, serotonin and cysteamine, as well as inhibiting titratable gastric acidity and titratable acid output, and gastric pH, but was found ineffective against the pyloric ligation-induced and diethyldithiocarbamate-induced ulcerogenesis models, as well as gastric secretion volume and peptic activity. On the other hand, active compounds did not show any toxic effect on acute toxicity (3 days administration) evaluation tests in mice. © 2007 Elsevier Ireland Ltd. All rights reserved Daha fazlası Daha az

Süntar, I. | Küpeli Akkol, E. | Keles, H. | Yeşilada, Erdem | Sarker, S.D. | Arroo, R. | Baykal, T.

Article | 2012 | Journal of Ethnopharmacology141 ( 3 ) , pp.1058 - 1070

Ethnopharmacological relevance: In Turkish traditional medicine, the aerial parts of Daphne oleoides Schreber subsp. kurdica (DOK) have been used to treat malaria, rheumatism and for wound healing. The aim was to evaluate the ethnopharmacological usage of the plant using in vivo and in vitro pharmacological experimental models, and to perform bioassay-guided fractionation of the 85% methanolic extract of DOK for the isolation and identification of active wound-healing component(s) and to elucidate possible mechanism of the wound-healing activity. Materials and methods: In vivo wound-healing activity was evaluated by the linear incis . . .ion and the circular excision wound models. Anti-inflammatory and antioxidant activities, which are known to support the wound healing process, were also assessed by the Whittle method and the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical-scavenging assays, respectively. The total phenolic content of the extract and subextracts was estimated to establish any correlation between the phenolic content and the antioxidant activity. The methanolic extract of DOK was subjected to various chromatographic separation techniques leading to the isolation and identification of the active component(s). Furthermore, in vitro hyaluronidase, collagenase and elastase enzymes inhibitory activity assays were conducted on the active components to explore the activity pathways of the remedy. Results: After confirmation of the wound-healing activity, the methanolic extract was subjected to successive solvent partitioning using solvents of increasing polarity creating five subextracts. Each subextract was tested on the same biological activity model and the ethyl acetate (EtOAc) subextract had the highest activity. The EtOAc subextract was subjected to further chromatographic separation for the isolation of components 1, 2 and 3. The structures of these compounds were elucidated as daphnetin (1), demethyldaphnoretin 7-O-glucoside (2) and luteolin-7-O-glucoside (3). Further in vivo testing revealed that luteolin-7-O-glucoside was responsible for the wound-healing activity of the aerial parts. It was also found to exert significant anti-inflammatory, antioxidant, anti-hyaluronidase and anti-collagenase activities. Conclusion: The present study explored the wound-healing potential of Daphne oleoides subsp. kurdica. Through bioassay-guided fractionation and isolation techniques, luteolin-7-O-glucoside was determined as the main active component of the aerial parts. This compound exerts its activity through inhibition of hyaluronidase and collagenase enzymes activity as well as interfering with the inflammatory stage. © 2012 Elsevier Ireland Ltd. All rights reserved Daha fazlası Daha az

Gurbuz, I. | Yeşilada, Erdem | Ito, S.

Article | 2009 | Journal of Ethnopharmacology121 ( 3 ) , pp.360 - 365

Ethnopharmacological relevance: The aerial parts of Eqiusetum palustre L. is used to treat peptic ulcer in Karaman, Turkey. Aim of the study: The present study was undertaken to evaluate the in vivo gastroprotective potential and structure elucidation of the active constituent(s) through bioassay-guided fractionation procedures by using ethanol (EtOH)-induced ulcerogenesis model in rats. Material and methods: The 80% ethanol extract of the aerial parts was subjected to subsequent separation procedures such as solvent-solvent partition and column chromatography through bioassay-guided fractionation techniques to isolate the active an . . .ti-ulcer component(s) by using the EtOH-induced ulcer model in rats. The ulcer index was used to evaluate and to calculate the gastroprotection percentage. Results: The subextracts, n-butanol and remaining H2O, of Equisetum palustre showed potent in vivo gastroprotective activity. Bioassay-guided fractionation has revealed that a flavonol diglucoside, was isolated as an active constituent from the n-BuOH subextract of Equisetum palustre. Structure elucidation by standard spectroscopic techniques (1H NMR, 13C NMR and DEPT, etc.) revealed that this compound as kaempferol-3-O-1¨-ß-d-glucopyranosyl-3-O-1¨'-ß-d-glucopyranoside, which provided remarkable protection at 250 and 500 mg/kg doses (69.5 and 98.5% ulcer inhibition, respectively) against ethanol-induced gastric lesions. Conclusion: Experimental data confirmed the ethnobotanical usage of Equisetum palustre, with scientific evidence, in Turkey. Additionally, kaempferol-3-O-1¨-ß-d-glucopyranosyl-3-O-1¨'-ß-d-glucopyranoside, a known compound, was defined as an anti-ulcerogenic compound in the present work for the first time. © 2008 Elsevier Ireland Ltd. All rights reserved Daha fazlası Daha az

Süntar, I.P. | Akkol, E.K. | Yalçin, F.N. | Koca, U. | Keleş, H. | Yeşilada, Erdem

Article | 2010 | Journal of Ethnopharmacology129 ( 1 ) , pp.106 - 114

Yeşilada, Erdem | Gurbuz, I.

Article | 2010 | Journal of Ethnopharmacology131 ( 1 ) , pp.17 - 21

Ethnopharmacological relevance: The aerial parts of Equisetum palustre L. are used to treat peptic ulcer disease in Turkey. In a previous study, a flavonol diglucoside i.e., kaempferol 3-O-1¨-ß-d-glucopyranosyl-3-O-1¨'-ß-d-glucopyranoside (KGG) was isolated as the major antiulcerogenic constituent from the plant. Aim of the study: The present study was undertaken to evaluate the antiulcer activity profile of KGG using various in vivo experimental ulcer models as well as by assessing gastric biochemical parameters. Material and methods: KGG was obtained from the ethanol extract of the aerial parts of the plant by successive chromatog . . .raphical methods. The activity profile of the compound was investigated using several ulcerogenesis models such as indomethacin-, indomethacin plus HCl/EtOH-, cysteamine-, serotonin-, NG-nitro-l-arginine methyl ester plus EtOH-, diethyldithiocarbamate-, N-ethylmaleimide plus EtOH-, water immersion and restraint stress-, pyloric ligation-induced ulcers. In addition, effects of KGG on the biochemical parameters of gastric juice; i.e., inhibition of titratable gastric acidity, acid output, gastric pH, gastric secretion volume and peptic activity were studied. Results: KGG exerted statistically significant gastroprotective activity against indomethacin-, indomethacin plus HCl/EtOH- and N-ethylmaleimide plus EtOH-induced ulcerogenesis. Moreover, KGG demonstrated weak activity against NG-nitro-l-arginine methyl ester plus EtOH, water immersion and immobilization-induced stress, pyloric ligation-induced and diethyldithiocarbamate-induced gastric ulcer models, and also it was ineffective in the prevention of ulcers induced by serotonin and cysteamine. On the other hand, among the gastric biochemical parameters studied, KGG was only found to increase the gastric acid pH from 2.03 to 3.35. Conclusion: Results of this investigation have clearly demonstrated that KGG was found to improve the cytoprotective mechanisms of the gastric mucosa. On the other hand, a weak activity profile was observed on the parameters affecting the gastric acidity (water immersion and restraint-induced-, pyloric ligation-induced-ulcerogenesis and titratable acidity). © 2010 Elsevier Ireland Ltd Daha fazlası Daha az

Akkol, E.K. | Arif, R. | Ergun, F. | Yeşilada, Erdem

Article | 2009 | Journal of Ethnopharmacology122 ( 2 ) , pp.210 - 215

Ethnopharmacological relevance: Several Centaurea species are used to alleviate pain and inflammatory symptoms in rheumatoid arthritis, high fever, and head ache in Turkish folk medicine. Aim of the study: The effectiveness of extracts, fractions and subfractions from dried Centaurea solstitialis L. subsp. solstitialis (CSS) (Asteraceae) roots and aerial parts were studied on mice. Materials and methods: The antinociceptive and antipyretic effects of Centaurea solstitialis L. subsp. solstitialis have been investigated by using p-benzoquinone-induced writhing reflex for antinociceptive activity and Freund's Complete Adjuvant-induced . . .pyrexia model for antipyretic activity assessment in mice. Results: The ethanolic extract from the aerial parts of the plant was shown to possess significant antinociceptive (p < 0.01) and antipyretic activities (p < 0.01). The extract was then submitted to subsequent solvent extractions and chromatographic processes. Through bioassay-guided fractionation and isolation procedures two sesquiterpene lactones, solstitialin A and acetyl solstitialin, were isolated and defined as the active components of CSS. On the other hand, a comparative study was conducted on another species, Centaurea depressa Bieb., which has no similar folkloric utilization. Following the same fractionation chart same compounds were defined as the active ingredients. Conclusion: Results of the present study proved that aerial part of CSS possesses antinociceptive and antipyretic activities supporting the folkloric assertion in Turkish folk medicine. However, these effects seem not limited to CSS, some other Centaurea species, in fact, having no folkloric use might be equally active. © 2009 Elsevier Ireland Ltd. All rights reserved Daha fazlası Daha az

Süntar, I. | Akkol, E.K. | Keleş, H. | Oktem, A. | Başer, K.H.C. | Yeşilada, E.

Article | 2011 | Journal of Ethnopharmacology134 ( 1 ) , pp.89 - 96

Aim of the study: Hypericum perforatum L. (Hypericaceae), olive oil (Oleaceae), Origanum Tourn ex L. and Salvia L. species (Lamiaceae) are used against inflammatory disorders and for healing of skin wounds in traditional Turkish medicine. A new ointment formulation was developed to provide more efficient wound healing activity. The content of the formulation was as follows; olive oil extract of flowering aerial parts of Hypericum perforatum L., olive oil, an equivalent mixture of Origanum majorana L. and Origanum minutiflorum Schwrd. et Davis essential oils (Origani aetheroleum), Salvia triloba L. essential oil. The aim of the prese . . .nt study is to assess the wound healing potential of this new formulation by using in vivo and in vitro models as well as histopathological methods. Materials and methods: For the evaluation of wound healing potential of this formulation (HPP crème mit Rotöl ointment) in vivo wound healing experimental models were employed on rats and mice and the efficiency was comparatively assessed against a reference ointment Madecassol®. Tissue sections were also evaluated histopathologically. Furthermore, the wound healing activity of each component was also investigated individually to determine the improvement in the healing capacity of the formulation. Results: The ointments of HPP crème mit Rotöl and Hypericum perforatum L. demonstrated the highest activities on both wound models when compared to reference ointment Madecassol®, while the other ingredients did not show any remarkable wound healing effect. However, the efficacy of the formulation was remarkably higher than the Hypericum L. ointment alone which was also confirmed by histopathological evaluation. On the other hand, the formulation did not reduce elastase activity in vitro, but inhibited the collagenase activity. HPP crème mit Rotöl also exerted bactericidal and candicidal activities. Conclusions: The experimental studies revealed that HPP crème mit Rotöl formulation displays remarkable wound healing activity. To be acting on the different stages of wound healing process could be considered as a beneficial effect of the formulation for the treatment of wounds. © 2010 Elsevier Ireland Ltd Daha fazlası Daha az

Akkol, E.K. | Koca, U. | Peşin, I. | Yilmazer, D. | Toker, G. | Yeşilada, E.

Article | 2009 | Journal of Ethnopharmacology124 ( 1 ) , pp.137 - 141

Ethnopharmacological relevance: The roots of Arnebia densiflora (Nordm.) Ledeb. (Boraginaceae), which is an endemic plant for Turkey, have been used for healing of wounds in folk medicine. The extract of the roots in olive oil and mostly the root barks was applied onto open wounds for rapid healing. Aim of the study: To evaluate the wound healing activity of the roots, extracts were prepared with different solvents; hexane, chloroform, ethyl acetate and methanol, respectively from the roots of Arnebia densiflora. Materials and methods: Incision by using tensiometer and excision models were employed on mice and rats. Results: Signifi . . .cant wound healing activity was observed with the ointment formulation prepared by using hexane extract at 1% concentration on the mentioned models. The results of histopathological examination supported the outcome of both incision and excision wound models. The wound healing effect was comparatively evaluated with a reference ointment Madecassol®. Conclusion: The experimental data demonstrated that Arnebia densiflora displayed remarkable wound healing activity. © 2009 Daha fazlası Daha az

Tosun, A. | Akkol, E.K. | Bahadir, O. | Yeşilada, E.

Article | 2008 | Journal of Ethnopharmacology120 ( 3 ) , pp.378 - 381

Ethnopharmacological relevance: Roots of Onosma species are used for the treatment of various disorders such as bronchitis, tonsillitis, hemorrhoids as well as alleviating pains in folk medicine in Turkey. Aim of the study: The chloroform and ethanol (70%) extracts obtained from the roots of Onosma species (Boraginaceae) growing in Turkey, Onosma aucheranum DC., Onosma isauricum Boiss. and Heldr. (endemic), Onosma sericeum Willd., Onosma tauricum Pallas ex Willd. var. brevifolium DC. (endemic) and Onosma tauricum Pallas ex Willd. var. tauricum (Syn: Onosma velenovskyi Davidov) were evaluated for in vivo anti-inflammatory and antinoc . . .iceptive activities. Materials and methods: For the preliminary screening, carrageenan-induced hind paw edema for the anti-inflammatory activity and, p-benzoquinone-induced abdominal constriction test for the antinociceptive activity were used in mice. Results: The chloroform extracts from Onosma aucheranum and Onosma isauricum and ethanolic extracts from Onosma isauricum and Onosma sericeum demonstrated 28.0%, 34.3%, 24.6% and, 27.5% inhibition in p-benzoquinone-induced abdominal constriction test. The chloroform and ethanol (70%) extracts of Onosma isauricum and ethanol (70%) extract of Onosma sericeum also exhibited marked inhibition, ranging between 12.3-27.3%, 10.5-25.3%, 8.2-22.6%, respectively, in carrageenan-induced hind paw edema model at 100 mg/kg dose without gastric damage and the activity was quite comparable to indomethacin (32.0-38.4% inhibition) as a reference sample. Neither death nor gastric bleeding was observed for any of the plant extracts during the acute toxicity evaluation. Conclusion: The experimental data demonstrated that Onosma aucheranum, Onosma isauricum and Onosma sericeum displayed remarkable anti-inflammatory and antinociceptive activities. © 2008 Daha fazlası Daha az

Koca, U. | Süntar, I.P. | Keles, H. | Yeşilada, Erdem | Akkol, E.K.

Article | 2009 | Journal of Ethnopharmacology126 ( 3 ) , pp.551 - 556

Aim of the study: Several Centaurea species (Asteraceae) are used in Turkish folk medicine to alleviate pain and inflammatory symptoms in rheumatoid arthritis, high fever, head ache and for wound healing. Particularly, the aerial part of Centaurea iberica Trev. ex Spreng. has been practiced on wounds for healing. In order to evaluate the anti-inflammatory and wound healing activities of the plant, extracts were prepared with variety of solvents: hexane, chloroform, ethyl acetate and aqueous methanol (85%) from the aerial parts of Centaurea iberica. Materials and methods: The incision by using tensiometer and excision models were use . . .d in order to assess the effect of the plant extracts on wound healing in mice and rats. Results were also evaluated histopathologically. In vivo inhibitory effect of the extracts on acetic acid-induced increase in capillary permeability was studied for the assessment of anti-inflammatory activity. Results: The wound healing effect was comparatively evaluated with a reference ointment Madecassol®. Noteworthy wound healing activity was observed for the ointment formulation prepared with 1% methanol extract. The results of histopathological evaluation supported the outcome of both incision and excision wound models. Moreover, the methanol extract exerted remarkable wound healing activity and also demonstrated a significant and dose-dependent anti-inflammatory activity. Conclusion: The experimental study revealed that Centaurea iberica displays remarkable wound healing and anti-inflammatory activity. © 2009 Elsevier Ireland Ltd. All rights reserved Daha fazlası Daha az

Charehsaz, M. | Reis, R. | Helvacioglu, S. | Sipahi, H. | Guzelmeric, E. | Acar, E.T. | Aydin, A.

Article | 2016 | Journal of Ethnopharmacology194 , pp.506 - 512

Ethnopharmacological relevance Styrax liquidus is a resinous exudate (balsam) obtained from the wounded trunk of the Liquidambar orientalis Mill. (Hamamelidaceae). Styrax has been used for treatment of various ailments in Turkish folk medicine such as skin problems, peptic ulcers, nocturnal enuresis, parasitic infections, antiseptic or as expectorant. Aim of study In spite of frequent use of styrax in Turkish folk medicine as well as once as a stabilizer in perfumery industry, negative reports have been noticed by the international authority for restriction its use based on some limited evidences from an in vitro study. The aim of t . . .he present study was to evaluate the genotoxic and cytotoxic potential of styrax and its ethanolic extract using in vivo and in vitro assays, as well as an antimutagenic assay and also to determine its phenolic constituents with chromatographic analysis. Materials and methods In vitro mutagenicity and antimutagenicity of styrax and its ethanolic extract were evaluated by Ames test performed on Salmonella TA98 and TA100 strains with and without metabolic activation (10– 30,000 µg/plate). The genotoxicity was also studied in vivo by chromosomal aberrations assay on bone marrow of Balb C mice with different its concentrations (500–2000 mg/kg body weight). Cytotoxicity has been evaluated by the MTT assay using L929 cell line. Its phenolic constituents were determined by HPLC analysis. Results Genotoxicological investigations of styrax or its ethanolic extract showed that none of the tested concentrations induced a significant increase in the revertant number of TA98 and TA100 strains with or without metabolic activation, indicating no mutagenicity to the tested strains. Also results indicated that up to 2000 mg/kg body weight, styrax is not genotoxic in mammalian bone marrow chromosome aberration test in vivo. In cytotoxicity study, the IC50 values of styrax and its ethanolic extract were found to be 50.22±1.80 and 59.69±11.77 µg/mL, respectively. Among the studied reference standards the major phenolic acids in styrax balsam was found to be p-coumaric acid (2.95 mg/g), while in its ethanolic extract not only p-coumaric acid (11.46 mg/g), but also gallic acid (1.60 mg/g) were found to the main components. Conclusion The findings of the present study provide scientific basis to the safety of styrax from the viewpoint of genotoxicity risk, and in fact, it was found to be beneficial against genotoxicity. © 2016 Elsevier Ireland Lt Daha fazlası Daha az

Küçükkurt, I. | Ince, S. | Keleş, H. | Küpeli Akkol, E. | Avci, G. | Yeşilada, E. | Bacak, E.

Article | 2010 | Journal of Ethnopharmacology129 ( 1 ) , pp.18 - 22

Aim of the study: Seeds of Aesculus hippocastanum L. have long been used in European phytotherapy to treat inflammatory and vascular problems. In Turkish folk medicine, tea prepared from the crushed seeds was used to pass kidney stone and against stomach ache, while a fraction of seed was swallowed to alleviate hemorroids symptoms.In order to evaluate the in vivo effects of escin mixture from Aesculus hippocastanum seed on the blood and tissue antioxidant defense systems in standard pellet diet (SPD) and in high-fat diet (HFD) consumed male mice. Materials and methods: Escin mixture was obtained from the ethanol extract of seeds. Es . . .cin mixture was administered orally to male mice fed either standard pellet diet (SPD) or high-fat diet (HFD) at 100. mg/kg doses daily for 5 weeks and the tissue (liver, kidney and heart) and blood samples were collected at the end of experimental period. The effect of escin mixture on the plasma antioxidant activity; blood and tissue malondialdehyde (MDA) and reduced glutathione (GSH) levels; erythrocyte and tissue superoxide dismutase (SOD) and catalase activity (CAT) in SPD and HFD consumed animals were experimentally studied. Results: Escin mixture prohibited the adverse effects of oxidative stress and showed a protective effect on the liver architecture both in SPD and HFD consumed male mice. Escin mixture prohibited the adverse effects of oxidative stress and showed a protective effect on the liver architecture both in SPD and HFD consumed male mice. Combined administration of high-fat diet with escin mixture decreased blood ( Daha fazlası Daha az