Browsing by Author "Akkol, Esra Kupeli"
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Article Anti-Inflammatory and Antinociceptive Features of Bryonia Alba L.: as a Possible Alternative in Treating Rheumatism(de Gruyter Poland Sp Zoo, 2019) Ilhan, Mert; Dereli, Fatma Tugce Airagac; Tulmen, Ibrahim; Akkol, Esra KupeliBryonia species have traditionally been used as a diuretic and laxative, to reduce edema and relieve joint pain. B. alba roots are used especially to treat rheumatic pain and applied to painful joints in Turkish folk medicine. B. alba roots were extracted with n-hexane, ethyl acetate (EtOAc), and methanol, successively. The carrageenan-induced hind paw edema model and the Whittle method were used to evaluate the anti-inflammatory activity of the extracts in mice. The p-benzoquinone-induced abdominal constriction test and tail flick test were used to evaluate the antinociceptive activity of the extracts in mice. DPPH-radical-scavenging activity, ABTS radical-scavenging activity, total antioxidant activity, and hydroxyl radical-scavenging activity were assessed. Furthermore, the total phenolic and total flavonoid contents were calculated for all the extracts. The EtOAc extract prepared from B. alba roots had the most promising anti-inflammatory, antinociceptive, and antioxidant activities. Moreover, it had high phenolic and flavonoid contents. Therefore, B. alba roots could be alternative treatment method for rheumatic disorders.Article Appraisal of the Antimicrobial and Cytotoxic Potentials of Nanoparticles Biosynthesized From the Extracts of Pelargonium Quercetorum Agnew(Imr Press, 2021) Dumlupinar, Berrak; Karatoprak, Gokce Seker; Firat, Mehmet; Akkol, Esra KupeliAim: The aim of this study is the synthesis of nanosilver particles (AgNPs) from Pelargonium quercetorum Agnew. (Geraniaceae) and evaluation of the antimicrobial and the cytotoxic potential of AgNPs. Methods: The synthesized AgNPs were evaluated for antimicrobial and anticancer efficacy using the minimum inhibition concentration method and MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium bromide) assay. Results: The AgNPs inhibited approximately 90% the growth of gram-positive Staphylococcus aureus and gram-negative Esh-erichia coli and yeast Candida albicans pathogens at a concentration of 500 mu g/mL. The synthesized AgNPs showed excellent toxicity in MCF-7 cells, and specifically, pq70 AgNP inhibited the growth of MCF-7 cells by 52% at a concentration of 3.125 mu g/mL. Conclusion: It was determined that the AgNPs, which had been synthesized from extracts that contained a high phenolic composition, were smaller in size, and showed high anticancer and antimicrobial properties.Article Assessment of Antidepressant Effect of the Aerial Parts of Micromeria Myrtifolia Boiss. & Hohen on Mice(Mdpi, 2019) Akkol, Esra Kupeli; Dereli, Fatma Tugce Guragac; Ilhan, MertThe currently available antidepressant agents necessitate the development of newer alternatives because of their serious adverse effects and costs. Traditional medicinal knowledge is likely the key that opens the door to discover new medicines. In Turkish folk medicine, the infusion prepared from aerial parts of Micromeria myrtifolia Boiss. & Hohen is used as pleasure and medicinal tea for its relaxing action. The present research was conceived to confirm the antidepressant's potential of this traditional medicinal plant. In this process, first of all, the collected and shade-dried aerial parts of M. myrtifolia were powdered and then, extracted using solvents with different polarity as follows; n-hexane, ethyl acetate (EtOAc), and methanol (MeOH). The antidepressant activity of the extracts was evaluated by using several in vivo and in vitro experimental models of depression. When the data obtained from the control and experimental groups were compared, it was determined that the MeOH extract was the most active. The active components of this extract were isolated and identified utilizing various chromatographic separation techniques. The MeOH extract was applied to reversed phase (RP-18) column chromatography to obtain five main fractions and they were tested on antidepressant activity models. The isolated compounds from the obtained fractions were elucidated as rosmarinic acid (1), myricetin (2), apigenin (3), and naringenin (4) which were assumed to be responsible for the antidepressant activity of the aerial parts. According to the results, rosmarinic acid, myricetin, apigenin, and naringenin showed statistically significant activity on forced swimming test and tetrabenazine-induced ptosis models, whereas only rosmarinic acid showed statistically significant activity on the tail suspension test. Apigenin displayed the highest inhibitory activity on MAO A and B enzymes. Studies in the future should be performed to investigate the antidepressant activity mechanism of these natural compounds. The current research could be an important step in the development of the new agents that can be used in the treatment of depression.Article Beneficial Effects of Ajuga Chamaepitys (L.) Schreber Subsp. Chia (Schreber) and Its Iridoids on the Colitis Model: Histopathological and Biochemical Evidence(Pergamon-elsevier Science Ltd, 2020) Akkol, Esra Kupeli; Ilhan, Mert; Karpuz, Busra; Tastan, Hakki; Sobarzo-Sanchez, Eduardo; Khan, HaroonIn Turkish folk medicine, aerial parts of Ajuga chamaepitys (L.) Schreber subsp. chia (Schreber) are used for the treatment of diarrhea. The crude methanolic extract of aerial parts of A. chamaepitys subsp. chia was sequentially fractionated into five subextracts; n-hexane, dichloromethane, ethyl acetate, n-butanol and aqueous extracts. Effects of the methanol extract, subextracts and fractions were investigated in acetic acid-induced rat colitis model. The MeOH extract and n-BuOH subextract have regulated the caspase-3, myelopemxidase, TNF-alpha, IL-6 levels and antioxidant parameters. After confirmation of the activity against ulcerative colitis, n-BuOH subextract was subjected to more chromatographic separation for the isolation of compounds ajugoside (1), asperulosidic acid (2) and deacetyl-asperulosidic acid (3). As a conclusion, A. chamaepitys subsp. chia can be used in cell, tissue, or individual-specific treatments that will be developed in the future treatment of IBD, or as a complementary therapeutic agent that contributes to these treatments.Article Bioactivity-Guided Isolation of Flavonoids From Urtica Dioica L. and Their Effect on Endometriosis Rat Model(Elsevier Ireland Ltd, 2019) Ilhan, Mert; Ali, Zulfiqar; Khan, Ikhlas A.; Tastan, Hakki; Akkol, Esra KupeliEthnopharmacological relevance: Urtica dioica L. has been used traditionally for centuries. U. dioica leaves and roots are used as a blood purifier, emmenagogue, and diuretic, as well as to treat menstrual hemorrhage, rheumatism, and eczema. The present study aimed to evaluate the activity of U. dioica L. aerial parts in endometriosis rat model. Materials and methods: To evaluate the effects of the plant in endometriosis, n-hexane, ethyl acetate (EtOAc), and methanol (MeOH) extracts were prepared from the aerial parts of the plant and utilized in a rat surgical endometriosis model. In this model, adhesion scores of endometriotic implants and the spherical volumes of ectopic uterine tissues were evaluated. In addition to these parameters, tumor necrosis factor alpha (TNF-alpha), vascular endothelial growth factor (VEGF), and interleukin-6 (IL-6) levels of the peritoneal fluids were evaluated. Furthermore, histopathological studies were conducted on the endometriotic tissues. Results: Post-treatment implant volumes and adhesion scores were significantly reduced in the reference and the MeOH extract treated groups. Significant differences were found between the peritoneal TNF-a, VEGF, and IL-6 levels of MeOH extract treated group and those of control group. Moreover, histopathological findings supported the biological activity results. Furthermore, isolation studies were conducted on the MeOH extract, which showed prominent activity in the rat endometriosis model. Rutin (1), isoquercetin (2), the mixture of kaempferol-3-O-rutinoside (nicotiflorin) (3a) and isorhamnetin-3-O-rutinoside (narcissin) (3b) (3), the mixture of kaempferol-3-O-glucoside (astragalin) (4a) and isorhamnetin-3-O-glucoside (4b) (4) were isolated from the active fraction. Conclusions: The present study demonstrated that aerial parts of U. dioica exhibited promising activity in the endometriosis rat model due to its flavonoids.Article Discovery of New Antidepressant Agents: in Vivo Study on Anthemis Wiedemanniana Fisch & Mey(Elsevier Ireland Ltd, 2018) Derelia, Fatma Tugce Guragac; Ilhan, Mert; Akkol, Esra KupeliEthnopharmacological relevance: Many of the currently available antidepressants have serious adverse effects and are also expensive. Traditional medicines are major sources of original drugs, and their role in effective treatment is remarkable. In Turkish folk medicine, decoctions and infusions are prepared from the flowers of Anthemis wiedemanniana Fisch. & Mey. They exert antispasmodic and sedative effects and are also used for treating urinary inflammations. The present study was designed to evaluate the antidepressant activity of A. wiedemanniana, which is used against central nervous system disorders in Turkish folk medicine. Materials and methods: n-Hexane, ethyl acetate, and methanol (MeOH) extracts were prepared from the flowers of the plant. The antidepressant potentials of these extracts were evaluated in mouse models using the forced swimming test, tail suspension test, and antagonism of tetrabenazine-induced ptosis, hypothermia, and suppression of locomotor activity. The results were compared with those in control and reference groups, and active constituents of the plant were determined. The MeOH extract of A. wiedemanniana was subjected to various chromatographic separation techniques, leading to the isolation and identification of the active component(s). Results: After confirmation of the antidepressant activity, the MeOH extract was subjected to successive solvent partitioning using solvents of increasing polarity, yielding four subextracts. Each subextract was tested on the same biological activity models. Fraction B was found to have the highest activity and subjected to further chromatographic separation. Isolated germacronolide-type sesquiterpene lactones were elucidated as tatridin A (1) and tanachin (1-epi-tatridin B) (2), which were responsible for the antidepressant activity of the flowers. Conclusions: This study explored the antidepressant potential of A. wiedemanniana. Using bioassay-guided fractionation and isolation techniques, tatridin A and tanachin (1-epi-tatridin B) were determined as the main active components of the flowers. Further antidepressant mechanistic studies should be conducted for exploring the activity of these compounds against depression. This study can be an important step in the discovery of newer antidepressants.Article Effective Eradication of Pinworms (Syphacia Obvelata and Aspiculuris Tetraptera) With Polygonum Cognatum Meissn(Academic Press inc Elsevier Science, 2019) Dereli, Fatma Tugce Guragac; Ilhan, Mert; Kozan, Esma; Akkol, Esra KupeliPolygonum cognatum Meissn. (Polygonaceae) is a wild edible plant known locally as "solucanotu, madimak" in Turkey and it has been used for various purposes, such as diuretic and antidiabetic, as well to treat oxyuris and worms internally in humans. The present study was carried out to investigate the anthelmintic activity of various extracts were obtained from the aerial parts of P. cognatum in order to justify its traditional usage in Turkish folk medicine. n-Hexane, ethyl acetate and methanol extracts were prepared from the aerial parts of the plant, successively. The anthelmintic potentials of these extracts were evaluated on mice naturally infected with Syphacia obvelata and Aspiculuris tetraptera. Cellophane perianal tape test and fecal flotation test were used for the activity screening. The results were compared with control and reference groups. In addition to all these experiments, the total amount of phenolic compounds and tannin contents thought to be responsible for the activity were evaluated for all extracts. According to the results, it has been found that the methanolic extract reduced the number of S. obvelata (66.8%) and A. tetraptera (73.4%) eggs. Moreover, the methanolic extract include higher amount of total phenolic compound (48.75 +/- 0.82 mg of GA/g of extract) and tannin (30.04 +/- 0.22 mg TA/g of extract) than n-Hexane (17.21 +/- 0.75 mg of GA/g of extract; 6.82 +/- 0.41 mg TA/g of extract) and ethyl acetate (25.06 +/- 0.94 mg of GA/g of extract; 10.29 +/- 0.34 mg TA/g of extract); therefore the anthelmintic activity could be related to these constituents. The present study explored the anthelmintic potential of P. cognatum. Further studies should be conducted into the mechanism of these compounds' against helminths. This study can be an important step in the discovery of new anthelmintic agents.Article An Effective Phytoconstituent Aconitine: a Realistic Approach for the Treatment of Trigeminal Neuralgia(Wiley, 2021) Cankal, Dilek; Akkol, Esra Kupeli; Kilinc, Yeliz; Ilhan, Mert; Capasso, RaffaeleTrigeminal neuralgia pain remains a challenge to treat. Natural compounds may be promising options for relieving pain. This study was aimed at investigating the effects of aconitine in a rat model of trigeminal neuralgia pain. Infraorbital nerve chronic constriction injury was performed in adult Wistar Albino rats. After the neuropathic pain developed, the rats were assigned to one of the treatment groups: carbamazepine 40 or 80mg/kg; aconitine 0.25, 0.50, or 0.75mg/kg; or saline injection (control group). Behavioral testing with von Frey filaments and the rotarod test were carried out before the surgical procedure and on the 24th to 29th postoperative days. Following the completion of tests, ipsilateral and contralateral spinal cords were harvested for Western blot analyses to assess NR-1 protein expression. ANOVA followed by Mann-Whitney U test was performed for the statistical analyses. P values of <0.05 were considered significant. Aconitine significantly reduced mechanical sensitivity in a dose-dependent manner. A significant reduction in motor coordination was noted for the higher doses of aconitine which was similar with the 40 and 80mg/kg doses of carbamazepine. NR-1 expression was reduced in the ipsilateral spinal cord, whereas no significant difference was noted between the groups in the expression of NR-1 in the contralateral spinal cord. Aconitine had a significant pain relieving effect, which was similar to carbamazepine, in a dose-dependent manner. Aconitine may be an alternative pharmacological agent for the control of trigeminal neuralgia pain.Article Efficacy of Pyrus Elaeagnifolia Subsp. Elaeagnifolia in Acetic Acid-Induced Colitis Model(de Gruyter Poland Sp Z O O, 2019) Ilhan, Mert; Akkol, Esra Kupeli; Tastan, Hakki; Dereli, Fatma Tugce Guragac; Tumen, IbrahimIn Turkish folk medicine, the fruits of Pyrus elaeagnifolia subsp. elaeagnifolia have been used to treat diarrhea and detoxify poisonous snake bites by enlarging the wound. The aim of the study was to confirm the ethnopharmacological usage of the plant using in vivo and in vitro models. Experimental colitis was performed under anesthesia by intrarectal administration of acetic acid in rats, and the extracts were administered orally. The colonic malondialdehyde (MDA), tumor necrosis factor (TNF-alpha), interleukin-6 (IL-6), and nitrite levels, in addition to the myeloperoxidase (MPO) and caspase-3 activities, were measured to determine the effects of the plant extracts. The methanol (MeOH) extract revealed a significant decrease in MPO and caspase-3 levels. The MeOH extract was found to have the highest total tannin content. It was also found to have significant antioxidant (p < 0.01) and anti-inflammatory activities (p < 0.05) in acetic acid induced colitis rat model . According to our results, the present study exhibited a decrease in MDA, nitrite, IL-6, and TNF-alpha levels in the colon tissue and blood in the MeOH extract treated group. The findings of this study can help in treating various disorders, such as Clostridium difficile infection, irritable bowel syndrome, and inflammatory bowel diseases.Article Evaluation of the Chemopreventive Effects of Ankaferd Bloodstopper in 7,12-Dimethylbenz[a]anthracene Oral Epithelial Dysplasia(Springer Heidelberg, 2018) Ozle, Murat; Cankal, Dilek A. Ugar; Ilhan, Mert; Keles, Hikmet; Akkol, Esra KupeliObjectivesAnkaferd BloodStopper (R) (ABS) is an herbal extract which has been used historically as a hemostatic agent in traditional Turkish medicine. ABS comprises of standardized mixture of herbs Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum, and Urtica dioica. In addition to its hemostatic effects, the herb ABS contains some other biological effects including antioxidant and antitumoral properties. The aim of this study is to investigate the chemopreventive effects of ABS in 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral epithelial dysplasia.Materials and methodsA total of 40 Sprague Dawley rats were randomly divided into four groups. Group 1 animals received DMBA alone, and group 2 animals received both DMBA and Ankaferd. Group 3 animals received ABS alone while group 4 animals served as control group and received only liquid paraffine. All animals were sacrificed, and tissue samples were analyzed histologically at the end of the experimental period (14weeks).ResultsHistological studies have shown that the buccal pouches of animals treated with DMBA alone revealed severe dysplasia while only mild or no dysplasia were noticed in DMBA + ABS group. Ankaferd were administered to animals and control group showed no dysplasia or other oral lesions.ConclusionThe results suggest that Ankaferd Bloodstopper (R) has chemopreventive effect against DMBA-induced oral epithelial dysplasia.Clinical relevanceAnkaferd Bloodstopper (R) could be used as a supportive treatment option of cancer in oral and maxillofacial surgery since it possesses chemopreventive effect.Article Identification of the Main Active Antidepressant Constituents in a Traditional Turkish Medicinal Plant, Centaurea Kurdica Reichardt(Elsevier Ireland Ltd, 2020) Dereli, Fatma Tugce Guragac; Ilhan, Mert; Akkol, Esra KupeliEthnopharmacological relevance: In Turkish folk medicine, infusions and decoctions prepared from the flowers, fruits and aerial parts of Centaurea kurdica Reichardt (Asteraceae) are used as sedative and antidepressant-like effects of various sedative plants have been identified in many studies. The present study was designed to evaluate the antidepressant activity of this plant. Materials and methods: n-Hexane, ethyl acetate (EtOAc), and methanol (MeOH) extracts were prepared from the branches with leaves and also flowers of the plant. Antidepressant potentials of these extracts were researched by using the forced swimming test, tail suspension test, and antagonism of tetrabenazine-induced ptosis, hypothermia, and suppression of locomotor activity. Results: After determination of high antidepressant potentials of MeOH extract prepared from flowers and nhexane extract prepared from branches with leaves, isolation studies were carried out on these two extracts and the main active components were determined as beta-amyrin, mixture of beta-sitosterol and stigmasterol and costunolide for the branches with leaves and quercitrin, isoquercetin and naringenin-7-O-glucopyranoside for the flowers. Conclusions: As a result of the mechanistic and toxicity studies planned on this plant, it is thought that C. kurdica may be a glimmer of hope for depressed patients.Article In Vitro Enzyme Inhibitory Activity of Ten Ferulago W. Koch Species Growing in Turkey(inst Tecnologia Parana, 2022) Akkol, Esra Kupeli; Gunbatan, Tugba; Gurbuz, Ilhan; Duman, Hayri; Kilic, Ceyda Sibel; Ilhan, MertFerulago species are traditionally used for the treatment of skin diseases, bronchitis, and depression, to increase body strength, as an immunostimulant, aphrodisiac and sedative in Anatolia. In this study, hyaluronidase, collagenase and elastase inhibitory potential relevant to wound healing activities of ethanol extracts from the roots of ten Ferulago species [F. cassia Boiss., F. humilis Boiss., F. isaurica Pesmen, F. longistylis Boiss., F. mascrosciadia Boiss. & Balansa, F. sandrasica Pesmen & Quezel, F. setifolia K. Koch., F. silaifolia (Boiss.) Boiss., F. trojana Akalin & Pimenov formerly known as F. sylvatica (Besser) Rchb. and F. syriaca Boiss.] were investigated. Ethanol extracts of F. mascrosciadia and F. syriaca were the most active ones against collagenase and elastase, respectively. In vitro wound healing activity of ten Ferulago species is reported for the first time in the current study.Article Inhibitory Activity of Podospermum Canum and Its Active Components on Collagenase, Elastase and Hyaluronidase Enzymes(Academic Press inc Elsevier Science, 2019) Acikara, Ozlem Bahadir; Ilhan, Mert; Kurtul, Ekin; Smejkal, Karel; Akkol, Esra KupeliPresent study is aimed to investigate in vitro inhibitory effects of the extract prepared from the aerial parts of Podospermum canum (syn: Scorzonera cana var. jacquiniana) (Asteraceae) on hyaluronidase, collagenase, and elastase enzymes using a bioassay-guided fractionation. Inhibitory effects of the extract, sub-extracts, fractions obtained by column chromatography, and isolated compounds on collagenase, elastase, and hyaluronidase were performed by using in vitro enzyme inhibitory assays based on spectrophotometric evaluation. The methanolic extract obtained from P. canum exhibited strong inhibitory activities on elastase and collagenase while the insignificant activity was observed on hyaluronidase. Through bioactivity-guided fractionation, the ethyl acetate and remaining water sub-extracts obtained from the methanolic extract displayed significant inhibitory activities on collagenase and elastase, while petroleum ether and chloroform extracts did not show any inhibitory activity. Eleven known compounds: arbutin, 6'-O-caffeoylarbutin, cichoriin, 3,5-dicaffeoylquinic acid methyl ester, apigenin 7-O-beta-glucoside, luteolin 7-O-beta-glucoside, apigenin 7-O-beta-rutinoside, isoorientin, orientin, vitexin, procatechuic acid, and new compound 4-hydroxy-benzoic acid 4-(6-O-alpha-rhamnopyranosyl-beta-glucopyranosyl) benzyl ester have been obtained from ethyl acetate sub-extract. Results of the present study have revealed that apigenin 7-O-beta-glucoside, luteolin 7-O-beta-glucoside, apigenin 7-O-beta-rutinoside, and isoorientin showed potent enzyme inhibitory activities. However, methanolic extract of P. canum displayed a greater inhibitory activity than fractions and isolated compounds both on collagenase and elastase.Article Inhibitory Activity of Scorzonera Latifolia and Its Components on Enzymes Connected With Healing Process(Elsevier Ireland Ltd, 2019) Akkol, Esra Kupeli; Smejkal, Karel; Kurtul, Ekin; Ilhan, Mert; Guragac, Fatma Tugce; Iscan, Gulcin Saltan; Budesinsky, MilosEthnopharmacological relevance: Scorzonera latifolia (Fisch. & Mey.) DC. (Asteraceae) grows naturally in Eastern Anatolia, northeastern Iran, and Caucasus. Latex of S. latifolia roots is used in Turkish folk medicine for its analgesic effects, externally to cure infertility in women, and internally as an antihelmintic. The milk obtained from the stem of the Scorzonera species is used for wound healing activity. Antinociceptive, anti-inflammatory, wound-healing, antioxidant, and antimicrobial activities have previously been reported for S. latifolia. Aim of the study: A methanol extract of the aerial parts of Scorzonera latifolia that had been shown to possess wound-healing activity, was used to elucidate the possible mechanism of the wound-healing activity and to identify the compound(s) responsible for the effect by means of bioassay-guided fractionation. Materials and methods: The wound-healing activity potential of methanol extract of S. latifolia was detected by evaluating the inhibitory activity on the collagenase, hyaluronidase and elastase, which play important roles in the wound-healing process. Succesive fractionation of the methanol extract using petroleum ether, chloroform, ethyl acetate, respectively, and the residual wateryielded four respective fractions. The ethyl acetate part, which was determined as the most active fraction, was selected for further separation using chromatographic techniques. Results: Ethylacetate fraction exhibited significant inhibitory activities on collagenase and elastase. Chromatographic separation of the ethylacetate extract yielded an active subfraction, from which was used to isolate quercetin-3-O-beta-apiofuranosyl-(1"'-> 2 '')-beta-D-glucopyranoside (1), quercetin-3-O-alpha-rhamnopyranosyl(1 -> 6)-beta-D-galactopyranoside (2), isoorientin (3), and 7-methylisoorientin (4). Of the compounds tested, 7-methylisoorientin (4) exerted inhibitory activity on collagenase and elastase, while quercetin-3-O-beta-apiofuranosyl-(1"' -> 2 '')-beta-glucopyranoside (1) inhibited collagenase only. None of the fractions, or isolated compounds showed any inhibitory effect on hyaluronidase. It must be mentioned, that in vitro tests showed that compounds 1-4 inhibit the collagenase and elastase and could help wound-healing process. However, the inhibititory effect of the methanol extract appears to be greater than that of both of the ethylacetate fraction, subfraction G and the isolated compounds, which suggest that a synergistic interaction of several compounds could be responsible for the wound-healing activity of the aerial parts of S. latifolia.Article The Investigation of the Potential Antidepressant-Like Activity of Xanthium Orientale Subsp. Italicum (Moretti) Greuter in Rodents(Elsevier Ireland Ltd, 2020) Dereli, Fatma Tugce Guragac; Ilhan, Mert; Sobarzo-Sanchez, Eduardo; Akkol, Esra KupeliEthnopharmacological relevance: Ethnobotanical surveys revealed that Xanthium orientale subsp. italicum (Moretti) Greuter has been used against central nervous system disorders in Turkish folk medicine. The aim of the present study is to verify the folkloric assertion on this plant. The compounds responsible for the activity were investigated using bioassay-guided fractionation procedures. Materials and methods: The antidepressant activity of the aqueous, n-hexane, ethyl acetate (EtOAc), methanol (MeOH) extracts; fractions and isolated compounds from active MeOH extract were evaluated by using the in vitro MAO inhibition assay and three different in vivo models namely forced swimming test, tail suspension test, and antagonism of tetrabenazine-induced ptosis, hypothermia, and suppression of locomotor activity. The results were compared with control and reference groups, and active compounds of the plant have been determined. Through the bioassay-guided fractionation procedures, two compounds were isolated from the active fraction and their structures were elucidated by spectroscopic methods. Results: The MeOH extract of the plant was found to possess antidepressant-like activity. This extract was then subjected to chromatographic techniques. Isolated sesquiterpene lactones were elucidated as xanthatin (1) and xanthinosin (2), which were responsible for the antidepressant-like activity. Conclusions: This study discovered the antidepressant potential of X. orientale subsp. italicum. Using bioassay-guided fractionation and isolation techniques, xanthatin (1) and xanthinosin (2) were determined as the main active components of the leaves.Article Isolation and Identification of Triterpenes From Anthemis Austriaca Jacq. Through Bioactivity-Guided Fractionation on Polycystic Ovary Syndrome Rat Model(Springer Heidelberg, 2020) Ilhan, Mert; Ali, Zulfiqar; Khan, Ikhlas A.; Tastan, Hakki; Akkol, Esra KupeliPurpose This study aimed to assess the activity of A. austriaca flowers in treating polycystic ovary syndrome (PCOS) in rats. Methods A letrozole-induced PCOS rat model was used to evaluate the activity potential of A. austriaca flowers. For this purpose, extracts of different polarity were prepared from A. austriaca flowers using n-hexane, ethyl acetate, and methanol. Serum luteinizing hormone, follicle-stimulating hormone, progesterone, testosterone, estradiol, serum leptin, lipid, and glucose levels were tested. Moreover, the antioxidant activity was evaluated by calculating superoxide dismutase, malondialdehyde, catalase, and glutathione peroxidase levels. Following the biological activity studies, phytochemical studies were conducted on the active extract to detect the compound(s) responsible for the activity. Results The treatment with n-hexane extract contributed to regulating serum gonadotropin and steroid hormone levels. The plasma level of high-density lipoprotein cholesterol was significantly higher than that of the control group, while the levels of low-density lipoprotein cholesterol, leptin, and glucose were significantly lower than those of the control group. Also, the n-hexane extract showed significant antioxidant activity in the PCOS rat model. Since the n-hexane extract was found to be active, isolation studies were performed on this extract and three main fractions were obtained from the n-hexane extract. Those fractions also were tested on letrozole-induced PCOS rat model. As a result, three triterpenoids, beta-amyrin palmitate, taraxasterol acetate, and taraxasterol were isolated and identified from Fr. B which is the most active fraction. Conclusion n-Hexane extract and Fr. B obtained from this extract showed statistically significant activity in the letrozole-induced PCOS rat model and three triterpene-type compounds were isolated from Fr. B.Article New Drug Discovery From Medicinal Plants and Phytoconstituents for Depressive Disorders(Bentham Science Publ, 2019) Dereli, Fatma Tugce Guragac; Ilhan, Mert; Akkol, Esra KupeliBackground & Objective: Depression, a risk factor for several serious diseases, is a highly prevalent and life-threatening psychiatric disorder. It can affect the individual's position in life and reduce the living standards. The research on the use of medicinal plants in treating this disease has increased enormously because of the possible low rehabilitation rate and side effects of available synthetic drugs, such as sexual dysfunction, nausea, fatigue, insomnia, hypersomnia, and weight gain. Conclusion: Therefore, this review aimed to draw attention to the antidepressant effects of culinary herbs and traditional medicinal plants and their active components, thereby promoting their use in the development of more potent antidepressants with improved side effect profile.Article A New Isoflavane-4 Derivative From Melilotus Officinalis (L.) Pall(Taylor & Francis Ltd, 2019) Ilhan, Mert; Ali, Zulfiqar; Khan, Ikhlas A.; Akkol, Esra KupeliA new isoflavane derivative, melilofficinaside together with seven other metabolites including coumarin, uridine, methyl-alpha-d-fructofuranoside, and flavonoid glucosides were isolated from the aerial parts of Melilotus officinalis (L.) Pall. [GRAPHICS] .Article Novel Drug Targets With Traditional Herbal Medicines for Overcoming Endometriosis(Bentham Science Publ Ltd, 2019) Ilhan, Mert; Dereli, Fatma Tugce Guragac; Akkol, Esra KupeliEndometriosis is a disease in which the lining of the endometrium is found outside of the uterus. Recent medical treatments for endometriosis have adverse effects, limiting their long-term use. Furthermore, the recurrence of the disease after the cessation of therapy is quite common, and most patients need to continue treatment to maintain a hypoestrogenic environment till conception. Notwithstanding recent advances in computational and chemical practices, traditional medicines are considered the most consistent sources for the discovery of new drugs. Numerous medicinal plants and plant-derived compounds have been tested against gynecological disorders, mainly endometriosis. This review aimed to describe the pharmacological activity profile of the medicinal plants and their active ingredients and draw attention to the discovery of multitargeted drug molecules for rational therapy.Article Phytochemical Composition and Biological Activities of Arctium Minus (Hill) Bernh.: a Potential Candidate as Antioxidant, Enzyme Inhibitor, and Cytotoxic Agent(Mdpi, 2022) Ilgun, Selen; Karatoprak, Gokce Seker; Polat, Derya Cicek; Safak, Esra Kongul; Yildiz, Gulsum; Akkol, Esra Kupeli; Sobarzo-Sanchez, EduardoArctium minus (Hill) Bernh. (Asteraceae), which has a wide distribution area in Turkey, is a medicinally important plant. Eighty percent methanol extracts of the leaf, flower head, and root parts of A. minus were prepared and their sub-fractions were obtained. Spectrophotometric and chromatographic (high-performance liquid chromatography) techniques were used to assess the phytochemical composition. The extracts were evaluated for antioxidant activity by diphenyl-2-picrylhydrazil radical (DPPH?), 2,2 '-Azino-bis 3-ethylbenzothiazoline-6-sulfonic acid (ABTS(?+)) radical scavenging, and beta-carotene linoleic acid bleaching assays. Furthermore, the extracts were subjected to alpha-amylase, alpha-glucosidase, lipoxygenase, and tyrosinase enzyme inhibition tests. The cytotoxic effects of extracts were investigated on MCF-7 and MDA-MB-231 breast cancer cell lines. The richest extract in terms of phenolic compounds was identified as the ethyl acetate sub-fraction of the root extract (364.37 +/- 7.18 mg(GAE)/g(extact)). Furthermore, chlorogenic acid (8.855 +/- 0.175%) and rutin (8.359 +/- 0.125%) were identified as the primary components in the leaves' ethyl acetate sub-fraction. According to all methods, it was observed that the extracts with the highest antioxidant activity were the flower and leaf ethyl acetate fractions. Additionally, ABTS radical scavenging activity of roots' ethyl acetate sub-fraction (2.51 +/- 0.09 mmol/L Trolox) was observed to be as effective as that of flower and leaf ethyl acetate fractions at 0.5 mg/mL. In the beta-carotene linoleic acid bleaching assay, leaves' methanol extract showed the highest antioxidant capacity (1422.47 +/- 76.85) at 30 min. The enzyme activity data showed that alpha-glucosidase enzyme inhibition of leaf dichloromethane extract was moderately high, with an 87.12 +/- 8.06% inhibition value. Lipoxygenase enzyme inhibition was weakly detected in all sub-fractions. Leaf methanol extract, leaf butanol, and root ethyl acetate sub-fractions showed 99% tyrosinase enzyme inhibition. Finally, it was discovered that dichloromethane extracts of leaves, roots, and flowers had high cytotoxic effects on the MDA-MB-231 cell line, with IC50 values of 21.39 +/- 2.43, 13.41 +/- 2.37, and 10.80 +/- 1.26 mu g/mL, respectively. The evaluation of the plant extracts in terms of several bioactivity tests revealed extremely positive outcomes. The data of this study, in which all parts of the plant were investigated in detail for the first time, offer promising results for future research.