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Aim: Cyclophosphamide (CP) is a commonly used chemotherapeutic agent despite its toxic adverse effects, including hepatotoxicity. Ellagic acid (EA) is an antioxidant agent and exhibits free radical scavenging activities. In this experimental study, the effects of EA on CP-induced liver injury were investigated. Material and Methods: Twenty-four Sprague-Dawley rats (180-220 gr) were separated into four equal groups. A single dose of 150 mg/kg CP was given intraperitoneally to generate hepatotoxicity. Different doses (50 and 75 mg/kg) of EA were administered orally 20 minutes before, 4 and 8 hours after CP administration. The histopathological evaluation of kidney tissues and immunohistochemical evaluation for caspase-3 were conducted as well as the serum biochemical analyses. Results: CP treated group exhibited a significant increase in serum hepatic enzymes, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), compared to the control group. Similarly, the total triglycerides (TG) and very-low-density lipoprotein cholesterol (VLDL-C) levels increased significantly. Additionally, the high-density lipoprotein cholesterol (HDL-C) levels decreased, which was not significant, compared to the control group. At both EA doses, VLDL-C, AST, ALT levels decreased significantly while HDL-C level revealed a significant increase. 75 mg/kg EA treatment caused a non-significant elevation in total cholesterol (TC) concentration. Microscopic analysis showed a significant congestion, edema, degeneration and necrosis in the livers of CP administered group. However, edema, degeneration, and necrosis were significantly reduced in animals treated with EA-75. In addition, caspase-3 expression significantly decreased in EA-75 group. Conclusion: These results indicate the protective effects of EA in CP-induced hepatotoxicity in rats. [ABSTRACT FROM AUTHOR]

The aim of the present research is to evaluate the antiurolithiatic effect of the various extracts prepared fromthe fruits of Viburnum opulus L., in regard to its ethnobotanical record. To induce urolithiasis, 70mg/kg sodiumoxalate was injected to the rats which were housed individually in metabolic cages.The test materials were applied during 7 days. Biochemical (urine and serum parameters), histopathological and antioxidant (TBARs, TSH and GSH) assays were conducted. The urine samples were examined by light microscope for the determination of the calciumoxalate crystals. Lyophilized juice of V. opulus (LJVO) and lyophilized commercial juice of V. opulus (LCJVO) exerted potential antiurolithiatic activity which was attributed to its diuretic effect along with the inhibitory action on the oxalate levels and free radical production. We also determined the chlorogenic acid content of the LJVO by high-performance liquid chromatography (HPLC). Chlorogenic acid was determined by using Supelcosil LC-18 (250 × 4.6 mm, 5 μm) column and acetonitrile: water: 0.2% o-phosphoric acid as a mobile phase. The chlorogenic acid content of V. opulus was found to be 0.3227mg/mL in fruit juice. The results obtained in this study have provided a scientific evidence for the traditional usage of V. opulus on passing kidney stones in Turkish folk medicine. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Endometriosis is a gynecological disorder characterized by the presence of endometrial tissue outside the uterine cavity. The fruits of Viburnum opulus L. have been used to treat gynecological disorders including primary and secondary dysmenorrhea and ovarian cysts. Materials and methods Air-dried and powdered fruits of V. opulus were extracted sequentially with n -hexane, ethyl acetate (EtOAc), and methanol (MeOH), respectively for four days. Endometriosis was induced by suturing 15 mm piece of endometrium into abdominal wall of Sprague Dawley rats. In second laparotomy, the dimensions of endometrial implants were measured and intra-abdominal adhesions were scored. The abdomen was closed. Extracts were daily administered to the rats. At the end of the experiment, rats were sacrified and endometriotic foci areas and intra-abdominal adhesions were re-evaluated. The tissues were also histopathologically investigated. Furthermore, tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) levels of peritoneal fluid were measured. HPLC analyses were conducted on the most potent EtOAc and MeOH extracts to determine the amount of the major compound, chlorogenic acid. Results The endometriotic volumes were found to be reduced significantly in the EtOAc extract-administered group to 30.1 mm 3 and in the MeOH extract-administered group to 34.7 mm 3 as compared to the control group. No adhesion was observed in the reference and EtOAc groups. Histopathological data also supported the results. Both EtOAc and MeOH extract-administered groups displayed significant remission in the levels of TNF-α, VEGF and IL-6. When the active extracts were subjected to HPLC analysis, chlorogenic acid was found to be the major compound and the amount of this compound was calculated as 0.5112±0.0012 mg and 1.7072±0.0277 mg/100 mg extract, repectively. Conclusions The results of the present study indicate that the effectiveness of the fruit extract of V. opulus could be partially attributed chlorogenic acid. Other phenolic compounds could potentiate the activity due to their amount. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Alnus species have been used for the treatment of rheumatism, hemorrhoids and for wound healing in folk medicine. Materials and methods Aqueous and methanol extracts of A. glutinosa (L.) Gaertner subsp. glutinosa, A. orientalis Decne. var. orientalis and A. orientalis var. pubescens Dippel leaves were evaluated for their wound healing, anti-inflammatory and antioxidant activities. In vivo wound models of linear incision and circular excision were performed. “Inhibition of acetic acid-induced capillary permeability”, “carrageenan-induced hind paw edema” and T”PA-induced ear edema” assays were applied to determine the anti-inflammatory effects. For the antioxidant activity assessment, DPPH and ABTS radicals scavenging effect, reducing power and denaturation of nonspecific hydroxyl radical-targeted 2-deoxyribose were used. In vitro inhibitory effects on enzymes hyaluronidase, collagenase and elastase were evaluated. The methanol extract of the leaves of A. glutinosa subsp. glutinosa (MB), the most potent extract, was fractionated by bioassay-guided fractionation technique. The structure of the isolated compound was determined as shikimic acid by using NMR and IR analyses. Results MB increased the wound tension by 42.79% value and provided a contraction by 51.58%. Wound tension, contraction capacity and tissue hydroxyproline levels were increased with the application of the fraction EtOAc: MeOH (Fr. D), subfraction D 27–38 and shikimic acid. In the “inhibition of acetic acid-induced capillary permeability” assay, MB, Fr. D, subfraction D 27–38 and shikimic acid inhibited the permeability with significant inhibition values of 30.22%, 32.46%, 38.24% and 27.19%, respectively. In carrageenan-induced hind paw edema model, MB displayed 29.1% inhibition. Likewise, Fr. D, subfraction D 27–38 , and shikimic acid were found to exhibit remarkable anti-inflammatory and antioxidant effects. Shikimic acid exhibited significant inhibitory effect (38.24%) on the hyaluronidase enzyme. Conclusions This is the first and unique study that investigates wound healing, anti-inflammatory and antioxidant effects of some Alnus taxons growing in Turkey. According to the results, shikimic acid was found to be the major compound responsible from the activity. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Thuja occidentalis L. (Cupressaceae) has been used in folk medicine for the treatment of rheumatism, amenorrhea, cystitis, and uterine carcinomas, and as an abortifacient and contraceptive. Aim of the study The present study aimed to determine whether T. occidentalis oil and α-thujone could be beneficial in the treatment of polycystic ovary syndrome (PCOS). Materials and methods T. occidentalis oil and α-thujone were administered to rats with letrozole-induced PCOS for 21 days. At the end of 21 days, the rats were sacrificed and blood samples were taken by cardiac puncture. The levels of serum gonadotropins, steroids, blood lipid, leptin, and glucose and the values of antioxidant parameters were measured. Results The results demonstrated that estradiol and progesterone levels significantly increased, while luteinizing hormone (LH) and testosterone levels decreased in the T. occidentalis- and α-thujone-administered groups. The plasma low-density lipoprotein-cholesterol (LDL-C), leptin, and glucose concentrations were also significantly decreased in the T. occidentalis and α-thujone groups when compared to the control group. Histopathological findings demonstrated that the T. occidentalis and α-thujone groups displayed good healing. According to the phytochemical analyses, 25 compounds were identified in the T. occidentalis oil. The main constituents of the oil were the monoterpene ketones α- and β-thujone, fenchone, and sabinene, as well as the diterpenes beyerene and rimuene. Conclusion T. occidentalis essential oil and its active component, α -thujone, can be used for the treatment of PCOS without inducing osteoporosis. [ABSTRACT FROM AUTHOR]

Ethnobotanical surveys indicated that in the traditional medicines worldwide, several Juniperus species are utilized as antihelmintic, diuretic, stimulant, antiseptic, carminative, stomachic, antirheumatic, antifungal, and for wound healing. In the present study, essential oils obtained from heartwood samples of Juniperus virginiana L., Juniperus occidentalis Hook. and Juniperus ashei J. Buchholz were evaluated for wound healing and anti-inflammatory activities by using in vivo experimental methods. The essential oils were obtained by the supercritical carbon dioxide extraction method. Linear incision and circular excision wound models were performed for the wound-healing activity assessment. The tissues were also evaluated for the hydroxyproline content as well as histopathologically. To evaluate the anti-inflammatory activity of the essential oils, the test used was an acetic acid-induced increase in capillary permeability. The essential oil of J. occidentalis showed the highest activity on the in vivo biological activity models. Additionaly, the oil of J. virginiana was found highly effective in the anti-inflammatory activity method. The experimental data demonstrated that essential oil of J. occidentalis displayed significant wound-healing and anti-inflammatory activities. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Pseudevernia furfuracea (L.) Zopf (Parmeliaceae) is a common epiphytic lichen in the conifer-hardwood forest of Anatolia. This species is used in traditional medicine in Turkey as a treatment for wounds, eczema and hemorrhoids. Aim of the study: The present study was designed to investigate the active compounds from Pseudevernia. furfuracea, and the isolation studies yielded atraric acid (Aslan et al., 2006) as the major compound and a mixture of methyl hematommate (Baumann, 1960) and methyl chlorohematommate (Bayır et al., 2006). Furthermore, methanolic extract from thalli of Pseudevernia. furfuracea and its fractions and isolates (Aslan et al., 2006; Baumann, 1960; Bayır et al., 2006) were investigated for in vitro antimicrobial and antioxidant activities, and in vivo antinociceptive, anti-inflammatory and wound healing activities. Material and methods: Antimicrobial activities of the samples were determined by using the disc diffusion technique. 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay was used as a rapid TLC screening method to evaluate the antioxidant activity of Pseudevernia. furfuracea. The thiobarbituric acid (TBA) test was used to assess the efficacy of the extracts in protecting liposomes from lipid peroxidation. In vivo inhibitory effect of the extracts on the carrageenan-induced hind paw edema model in mice was studied for the assessment of anti-inflammatory activity. p-Benzoquinone-induced abdominal constriction test was used to explore the antinociceptive effects of the extracts. Moreover, the wound healing potential of the plant extracts that were evaluated by using in vivo incision and excision wound models on rats and mice, were comparatively assessed with a reference ointment Madecassol®. Results: Significant antimicrobial activities were observed against Gram (+) microorganisms and Candida krusei and Candida. dubliniensis in dichloromethane (DCM) and ethyl acetate (EtOAc) extracts and isolates. The methanol (MeOH), DCM and EtOAc extracts of the lichen were found to possess moderate inhibitory activity on lipid peroxidation. Methanolic extract of the lichen was found to possess significant inhibitory activity on the carrageenan-induced hind paw edema model in mice whereas the other fractions did not show any activity. While DCM and EtOAc extracts and fractions showed notable anti-inflammatory activity on carrageenan-induced hind paw edema model without inducing any apparent acute toxicity or gastric damage. Moreover, topical application of the ointment prepared with MeOH extract and EtOAc fraction onto the incised wounds exerted remarkable wound healing activity. Conclusion: The results of these experimental studies exhibited that nonpolar fractions of Pseudevernia. furfuracea have significant antimicrobial activity against especially Candida species and polar fractions (especially MeOH) display antioxidant, anti-inflammatory, antinociceptive and wound healing activities. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: According to ethnobotanical data, Pinus species have been used against rheumatic pain and for wound healing in Turkish folk medicine. Essential oils from the cones and needles of five different Pinus species (Pinus brutia Ten., Pinus halepensis Mill., Pinus nigra Arn., Pinus pinea L. and Pinus sylvestris L.) were evaluated for their in vivo wound healing and anti-inflammatory activities. Materials and methods: In vivo wound healing activity of the ointments prepared from essential oils was evaluated by linear incision and circular excision experimental wound models subsequently histopathological analysis and hydroxyproline content. Furthermore, the essential oils were screened for anti-hyaluronidase activity. Additionally anti-inflammatory activity was assessed by using the method of Whittle, which is based on the inhibition of acetic acid-induced increase in capillary permeability. Results: The essential oils obtained from the cones of Pinus pinea and Pinus halepensis demonstrated the highest effects on the wound healing activity models. On the other hand, the rest of the essential oils did not show any significant wound healing and anti-inflammatory activities. Conclusion: The experimental study revealed that essential oils obtained from the cones of Pinus pinea and Pinus halepensis display remarkable wound healing activity. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: In Turkish folk medicine Ranunculus species are used for wound healing and for the treatment of rheumatism. The present study was conducted to evaluate in vivo wound healing and anti-inflammatory properties of Ranunculus pedatus and Ranunculus constantinapolitanus. Material and methods: In vivo wound healing activity of the extracts prepared from Ranunculus pedatus and Ranunculus constantinapolitanus was evaluated by linear incision and circular excision wound models. Hydroxyproline content of the treated tissues was also assessed. We also studied the anti-inflammatory activity using Whittle method with some modifications. Results: Methanolic extract of Ranunculus pedatus showed significant wound healing effect both in incision (31.4%) and excision (55.74%) wound models. Methanolic extract of both Ranunculus pedatus and Ranunculus constantinapolitanus demonstrated anti-inflammatory activity with the inhibition value of 26.2% and 23.3% respectively, at the dose of 100mg/kg. Hydroxyproline content of the tissues treated with the methanolic and aqueous extracts of Ranunculus pedatus and methanolic extract of Ranunculus constantinapolitanus were found to be significantly higher than that of the other extracts. Conclusion: The experimental data revealed that Ranunculus pedatus showed significant wound healing and anti-inflammatory effect. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: The leaves of Michauxia species are used for the treatment of wounds in Turkish traditional medicine. In the present study, wound healing, anti-inflammatory and antioxidant activities of the extracts obtained from the root and herb of 5 species of Michauxia collected in different parts of Turkey were evaluated. Material and methods: In vivo incision and excision wound models were used in order to assess the wound healing effects of the methanolic extracts of the plants. Skin samples 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. TBA (thiobarbituric acid) test, qualitative and quantitative DPPH (2,2-diphenyl-1-picrylhydrazyl) tests were used to evaluate the antioxidant activity. Results: Noteworthy wound healing activity was observed for the ointment formulation prepared with 1% Michauxia nuda (root) and Michauxia tchihatchewii (herb) extracts. The results of histopathological evaluation supported the outcome of incision and excision wound models. Moreover, the Michauxia nuda (root) exerted remarkable anti-inflammatory effect. The highest antioxidant activity was observed with the ethyl acetate extract of Michauxia tchihatchewii herb. Conclusion: The experimental study revealed that Michauxia displays remarkable wound healing and anti-inflammatory and antioxidant activities. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Ethnobotanical surveys revealed that Abies bornmulleriana, Abies cilicica, Abies nordmanniana and Cedrus libani have been used to promote wound healing in Turkish folk medicine. Four different fir species (Abies cilicica subsp. cilicica, Abies nordmanniana subsp. bornmulleriana, Abies nordmanniana subsp. equi-trojani, and Abies nordmanniana subsp. nordmanniana), Cedrus libani and Picea orientalis were assessed for their in vivo wound healing and anti-inflammatory activities. Materials and methods: The essential oils from six different coniferous cones were used. In vivo wound healing activity of the plants was evaluated by linear incision and circular excision experimental wound models subsequently histopathological analysis. The healing potential was comparatively assessed with a reference ointment Madecassol®, which contains 1% extract of Centella asiatica. Additionally acetic acid-induced capillary permeability test was used for the oils’ anti-inflammatory activity. Results: The essential oils from Cedrus libani and Abies cilicica subsp. cilicica demonstrated the highest activities on the both wound models. Moreover, the oil from Abies nordmanniana subsp. bornmulleriana was found generally highly effective. On the other hand, the rest of the species did not show any remarkable wound healing effect. Results of the present study support the continued and expanded utilization of these plant species employed in Turkish folk medicine. Conclusion: The experimental study revealed that Cedrus libani and Abies cilicica subsp. cilicica display remarkable wound healing and anti-inflammatory activities. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance Scorzonera species are mainly used against arteriosclerosis, kidney diseases, hypertension, diabetes mellitus and rheumatism, as well as for pain relief and wound healing in Turkish folk medicine. In the current study, aerial parts and roots of Scorzonera cinerea, Scorzonera incisa, Scorzonera latifolia, Scorzonera mollis ssp. szowitsii, Scorzonera parviflora, and Scorzonera tomentosa collected from different regions of Anatolia and yakı sakızı which is prepared by drying the latex is obtained from the roots of Scorzonera latifolia were evaluated for their wound healing and anti-inflammatory effects. Materials and methods: In vivo wound healing activity of the plants was evaluated by linear incision and circular excision wound models. Hydroxyproline content of the treated tissues was also assessed. Acetic acid-induced capillary permeability test was used for anti-inflammatory activity. For the determination of the active constituents, a new high performance liquid chromatographic method was developed. Precision of the developed method was performed by the evaluation of intra-day and inter-day variations of the each standard at limits of quantification (LOQ) levels. Results: The aqueous methanolic extracts of Scorzonera latifolia, Scorzonera mollis ssp. szowitsii demonstrated the highest activities. The main compound was detected as chlorogenic acid both in roots and aerial parts of the most Scorzonera species and hyperoside or rutin was determined as one of the main component of the aerial parts. Conclusion: The experimental study revealed that methanol–water extracts from aerial parts of Scorzonera latifolia and Scorzonera mollis ssp. szowitsii were found to have better activity on the wound healing compared to the other extracts and control groups. This might be due to the combined effect of the constituents present in the extracts. [Copyright &y& Elsevier]

Abstract: Aim of the study: Ononis L. species have been used for healing of wounds, eczema and rheumatic complaints, against skin cancer and lesions and topically used as antiseptic and antimicrobial agent in folk medicine. In the present study, the aqueous and methanolic extracts of three endemic Ononis species growing in Turkey, including Ononis sessilifolia Bornm., Ononis basiadnata Hub.–Mor. and Ononis macrosperma Hub.–Mor. were assessed for their in vivo wound healing and anti-inflammatory activities. Materials and methods: In vivo wound healing activities of the plants were evaluated by using linear incision and circular excision experimental models subsequently histopathological analysis. The healing potential was comparatively assessed with a reference ointment Madecassol®, which contains 1% extract of Centella asiatica. 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 aqueous and ethanolic extracts of the aerial parts of O. macrosperma demonstrated the highest activity in both wound models and significant anti-inflammatory activity in acetic acid-induced increase in capillary permeability test. Furthermore, ethanolic extract of the aerial parts of O. sessilifolia showed anti-inflammatory effect but was devoid of wound healing activity. The rest of the species did not show remarkable wound healing effect. Ethyl acetate fraction of O. macrosperma ethanolic extract demonstrated significant but reduced wound healing activity, which revealed a possible combined effect. The results of histopathological examination supported the outcome of linear incision and circular excision wound models. Conclusion: The experimental study revealed that the aerial parts of O. macrosperma display remarkable wound healing and anti-inflammatory activities. [Copyright &y& Elsevier]

Aim of the study: The leaves, flowers, and whole aerial parts of Verbascum L. (Scrophulariaceae) species are used to treat eczema and other types of inflammatory skin conditions and as a desiccant for wounds in Turkish traditional medicine. In the present study, the methanolic extracts of 13 Verbascum species growing in Turkey, including Verbascum chionophyllum Hub.-Mor., Verbascum cilicicum Boiss., Verbascum dudleyanum (Hub.-Mor.) Hub.-Mor., Verbascum lasianthum Boiss., Verbascum latisepalum Hub.-Mor., Verbascum mucronatum Lam., Verbascum olympicum Boiss., Verbascum pterocalycinum var. mutense Hub.-Mor., Verbascum pycnostachyum Boiss. & Heldr., Verbascum salviifolium Boiss., Verbascum splendidum Boiss., Verbascum stachydifolium Boiss. & Heldr and Verbascum uschackense (Murb.) Hub.-Mor. were assessed for their in vivo wound healing activity. Material and methods: In vivo wound healing activity of the plants were evaluated by linear incision and circular excision experimental models subsequently histopathological analysis. The healing potential was comparatively assessed with a reference ointment Madecassol®, which contains 1% extract of Centella asiatica. Results: The methanolic extracts of Verbascum olympicum, Verbascum stachydifolium and Verbascum uschackense demonstrated the highest activities on the both wound models. Moreover, the methanolic extracts of Verbascum latisepalum, Verbascum mucronatum, and Verbascum pterocalycinum var. mutense were found generally highly effective. On the other hand, the rest of the species did not show any remarkable wound healing effect. Results of the present study support the continued and expanded utilization of these plant species employed in Turkish folk medicine. Conclusion: The experimental study revealed that Verbascum species display remarkable wound healing activity. [Copyright &y& Elsevier]