WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7150
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Article Citation - WoS: 7Citation - Scopus: 7Neo-Clerodanes From Teucrium Divaricatum Subsp. Divaricatum and Their Biological Activity Assessment(Elsevier, 2023) Aydoğan, Fadime; Ali, Zülfiqar; Zülfiqar, Fazila; Karaalp, Canan; Khan, Ikhlas A.; Bedir, ErdalFifteen neo-clerodane diterpenoids (1–15), including two undescribed glycosides, teudivaricosides A (1) and B (2), together with a known iridoid glycoside (16) and a phenylpropanoid glycoside (17) from the whole plant of Teucrium divaricatum subsp. divaricatum were isolated. Their structures were determined by spectral data analysis including 1D and 2D NMR and HRESIMS. Neo-clerodane diterpenoids were evaluated for their anti-inflammatory, and antimicrobial activities. None of them showed significant antimicrobial activity against various bacterial and fungal strains (up to 20 µg/mL). All tested compounds were inactive up to the highest tested concentration of 50 µM on iNOS inhibitory activity.Article Citation - WoS: 13Citation - Scopus: 15The Role of Cycloastragenol at the Intersection of Nrf2/Are, Telomerase, and Proteasome Activity(Elsevier, 2022) Yılmaz, Sinem; Bedir, Erdal; Ballar Kırmızıbayrak, PetekAging is well-characterized by the gradual decline of cellular functionality. As redox balance, proteostasis, and telomerase systems have been found to be associated with aging and age-related diseases, targeting these systems with small compounds has been considered a promising therapeutic approach. Cycloastragenol (CA), a small molecule telomerase activator obtained from Astragalus species, has been reported to positively affect several age-related pathophysiologies, but the mechanisms underlying CA activity have yet to be reported. Here, we presented that CA increased NRF2 nuclear localization and activity leading to upregulation of cytoprotective enzymes and attenuation of oxidative stress-induced ROS levels. Furthermore, CA-mediated induction of telomerase activity was found to be regulated by NRF2. CA not only increased the expression of hTERT but also its nuclear localization via upregulating the Hsp90-chaperon complex. In addition to modulating nuclear hTERT levels at unstressed conditions, CA alleviated oxidative stress-induced mitochondrial hTERT levels while increasing nuclear hTERT levels. Concomitantly, H2O2-induced mitochondrial ROS level was found to be significantly decreased by CA administration. Our data also revealed that CA strongly enhanced proteasome activity and assembly. More importantly, the proteasome activator effect of CA is dependent on the induction of telomerase activity, which is mediated by NRF2 system. In conclusion, our results not only revealed the cross-talk among NRF2, telomerase, and proteasome systems but also that CA functions at the intersection of these three major aging-related cellular pathways.Article Citation - WoS: 5Citation - Scopus: 6Undescribed Polyether Ionophores From Streptomyces Cacaoi and Their Antibacterial and Antiproliferative Activities(Elsevier, 2022) Gezer, Emre; Üner, Göklem; Küçüksolak, Melis; Kurt, Mustafa Ünver; Doğan, Gamze; Ballar Kırmızıbayrak, Petek; Bedir, ErdalPolyether ionophores represent a large group of naturally occurring compounds mainly produced by Streptomyces species. With previously proven varieties of bioactivity including antibacterial, antifungal, antiparasitic, antiviral and anti-tumor effects, the discovery of undescribed polyethers leading to development of efficient therapeutics has become important. As part of our research on polyether-rich Streptomyces cacaoi, we previously performed modification studies on fermentation conditions to induce synthesis of specialized metabolites. Here, we report four undescribed and nine known polyether compounds from S. cacaoi grown in optimized conditions. Antimicrobial activity assays revealed that four compounds, including the undescribed (6), showed strong inhibitory effects over both Bacillus subtilis and methicillin-resistant Staphylococcus aureus (MRSA) growth. Additionally, K41-A and its C15-demethoxy derivative exhibited significant cytotoxicity. These results signified that selectivity of C15-demethoxy K41-A towards cancer cells was higher than K41-A, which prompted us to conduct mechanistic experiments. These studies showed that this uninvestigated compound acts as a multitarget compound by inhibiting autophagic flux, inducing reactive oxygen species formation, abolishing proteasome activity, and stimulating ER stress. Consequently, the optimized fermentation conditions of S. cacaoi led to the isolation of undescribed and known polyethers displaying promising activities.Article Citation - WoS: 12Citation - Scopus: 12Isolation of Rosmarinic Acid and Methyl Rosmarinate as Lipoxygenase Inhibitors From Salvia Palaestina Benth. by Activity-Guided Fractionation(Elsevier, 2021) İçen, Mehmet Sina; Gürbüz, İlhan; Bedir, Erdal; Günbatan, Tuğba; Demirci, FatihSalvia palaestina aqueous and methanol extracts were prepared from the aerial parts, which were evaluated for the in vitro anti-inflammatory properties using the lipoxygenase (LO) enzyme inhibition assay. While the aqueous extract showed no activity at test concentrations, a significant (p < 0.001) lipoxygenase inhibition was detected for the methanol extract with 29% inhibition. Activity guided fractionation was carried out on the methanol extract via liquid-liquid partitioning using n-hexane, dichloromethane, ethyl acetate, and n-butanol. The ethyl acetate fraction showed statistically the best inhibition among the sub-fractions with 70% inhibition (p < 0.0001). The compounds responsible for the activity were purified, and their structures were established as rosmarinic acid, and methyl rosmarinate by spectroscopic methods. IC50 values of rosmarinic acid, and methyl rosmarinate were calculated as 0.21 and 0.02 ?M, respectively. In conclusion, the in vitro anti-inflammatory potential of S. palaestina was associated to rosmarinic acid, and methyl rosmarinate, for the first time to the best of our knowledge. © 2021 SAABArticle Citation - WoS: 21Citation - Scopus: 21Development of Adjuvant Nanocarrier Systems for Seasonal Influenza a (h3n2) Vaccine Based on Astragaloside Vii and Gum Tragacanth (aps)(Elsevier, 2019) Yakuboğulları, Nilgün; Genç, Rukan; Coven, Fethiye; Nalbantsoy, Ayşe; Bedir, ErdalAdjuvants are chemical/biological substances that are used in vaccines to increase the immunogenicity of antigens. A few adjuvants have been developed for use in human vaccines because of their limitations including lack of efficacy, unacceptable local or systemic toxicity, the difficulty of manufacturing, poor stability, and high cost. For that reasons, novel adjuvants/adjuvant systems are under search. Astragaloside VII (AST-VII), isolated from Astragalus trojanus, exhibited significant cellular and humoral immune responses. The polysaccharides (APS) obtained from the roots of Astragalus species have been used in traditional Chinese medicine and possess strong immunomodulatory properties. In the present study, the immunomodulatory effects of a newly developed nanocarrier system (APNS: APS containing carrier) and its AST-VII containing formulation (ANS: AST-VII + APNS), on seasonal influenza A (H3N2) vaccine were investigated. Inactivated H3N2 alone or its combinations with test compounds/formulations were intramuscularly injected into Swiss albino mice. Four weeks after immunization, the immune responses were evaluated in terms of antibody and cytokine responses as well as splenocyte proliferation. APNS demonstrated Th2 mediated response by increasing IgG1 antibody titers, whereas ANS showed response towards Th1/Th2 balance and Th17 by producing of IFN-gamma, IL-17A and IgG2a. Based on these results, we propose that APNS and ANS are good candidates to be utilized in seasonal influenza A vaccines as adjuvants/carrier systems. (C) 2019 Elsevier Ltd. All rights reserved.Article Citation - WoS: 24Citation - Scopus: 23Polyethers Isolated From the Marine Actinobacterium Streptomyces Cacaoi Inhibit Autophagy and Induce Apoptosis in Cancer Cells(Elsevier, 2019) Khan, Nasar; Yılmaz, Sinem; Aksoy, Semiha; Uzel, Ataç; Tosun, Çiğdem; Ballar Kırmızıbayrak, Petek; Bedir, ErdalPolyether compounds, a large group of biologically active metabolites produced by Streptomyces species have been reported to show a variety of bioactivity such as antibacterial, antifungal, antiparasitic, antiviral, and tumour cell cytotoxicity. Since some of these compounds target cancer stem cells and multi-drug resistant cancer cells, this family of compounds have become of high interest. In this study, three polyether-type metabolites (1-3), one of which was a new natural product (3), were isolated from the marine derived Streptomyces cacaoi via antimicrobial activity-guided fractionation studies. As several polyether compounds with structural similarity such as monensin have been linked with autophagy and cell death, we first assessed the cytotoxicity of these three compounds. Compounds 2 and 3, but not 1, were found to be cytotoxic in several cell lines with a higher potency towards cancer cells. Furthermore, 2 and 3 caused accumulation of both autophagy flux markers LC3-II and p62 along with cleavage of caspase-3, caspase-9 and poly (ADP-ribose) polymerase 1 (PARP-1). Interestingly, prolonged treatment of the compounds caused a dramatic downregulation of the proteins related to autophagasome formation in a dose dependent manner. Our findings provide insights on the molecular mechanisms of the polyether-type polyketides, and signify their potency as chemotherapeutic agents through inhibiting autophagy and inducing apoptosis.Article Citation - WoS: 7Citation - Scopus: 8Investigations on the Anti-Ulcerogenic Activity of Sideritis Caesarea H. Duman, Aytaç & Başer(Elsevier, 2020) Günbatan, Tuğba; Gürbüz, İlhan; Bedir, Erdal; Gençler Özkan, Ayşe Mine; Özçınar, ÖzgeEthnopharmacological relevance: Aerial parts of Sideritis caesarea H. Duman, Aytac & Baser are used for complaints such as stomach-aches, and intestinal spasms as traditional medicine in Kayseri, Turkey. Aim of study: To investigate the anti-ulcerogenic activity by using bioassay guided fractionation technique (BAGF) and to identify the compound(s) that are responsible for anti-ulcerogenic activity through ethanol-induced anti-ulcerogenic activity model in vivo. Materials and methods: Liquid-liquid partition and then different chromatographic techniques were utilized for the BAGF of the ethanol (80%) extract of the aerial parts of Sideritis caesarea. Ethanol-induced gastric ulcer method on rats was employed for the determination of the anti-ulcerogenic activity, and the ulcer index was also calculated for anti-ulcerogenic activity detection. Results: The ethanol (80%) extract of S. caesarea showed statistically potent anti-ulcerogenic activity (95.9% ulcer inhibition, p < 0.001). Among the liquid-liquid fractions, strongest anti-ulcerogenic activity was observed with the ethyl acetate fraction (91.4% inhibition, p< 0.001) and therefore BAGF studies were proceeded with the ethyl acetate fraction. Two anti-ulcerogenic flavonoids {4'-O-methylhypolaetin-7-O-[6'''-O-acetyl-beta-D-allopyranosyl-(1 -> 2)]- 6 ''-O-acetyl-beta-D-glucopyranoside and isoscutellarein-7-O-[6'''-O-acetyl-beta-D-allopyranosyl-(1 -> 2)]-6 ''-O-acetyl-beta-D-glucopyranoside} were isolated from this fraction together with a sesquiterpene glycoside [(2E,6E)-2,6,10-trimethyl-2,6,11-dodecatriene-1,10-diol-1-O-beta-D-glucopyranoside] and two additional flavonoids {4'-O-methylhypolaetin-7-O-[6'''-O-acetyl-beta-D-allopyranosyl-(1 -> 2)]-beta-D-glucopyranoside and isoscutellarein- 7-O-[6'''-O-acetyl-beta-D-allopyranosyl-(1 -> 2)]-beta-D-glucopyranoside}. Conclusions: Traditional use of S. caesarea in the treatment of stomach-aches was supported by this study and four flavonoids were isolated by using BAGF method and two of them were determined to have significant antiulcerogenic activity. Additionally, (2E,6E)-2,6,10-trimethyl-2,6,11-dodecatriene-1,10-diol-1-O-beta-D-glucopyranoside was obtained from a Sideritis genus for the first time.Article Citation - WoS: 13Citation - Scopus: 14Evaluation of the Potential Aphrodisiac Activity of Sesquiterpenoids From Roots of Ferula Huber-Morathii Pesmen in Male Rats(Elsevier, 2020) Aydoğan, Fadime; Baykan, Sura; Soliman, Gamal A.; Yusufoğlu, Hasan; Bedir, ErdalEthnopharmacological relevance: Several species of Ferula L. genus have been used in traditional Turkish medicine as aphrodisiac to treat male sexual dysfunction. Especially, roots and oleo gum resin of F. elaeochytris Korovin, F. communis L., F. assa-foetida L. and F. gummosa Boiss. were claimed to be used for aphrodisiac activity, menstrual regulation and treatment of gastric pain in Anatolia. Ferula L. is represented by 23 taxa in Turkey, 13 of which are endemic species. F. huber-morathii Pesmen (FHM), an endemic plant, is popularly known as "helizan, cagsir". Aim of the study: This study aimed to isolate sesquiterpenoids from the roots of Ferula huber-morathii (FHM) and to confirm their aphrodisiac potential in male rats. Material and methods: In a preliminary experiment, the effects of aqueous (H2O) and chloroform (CHCl3) extracts of FHM were tested for their potential aphrodisiac activities in male rats. Then, sesquiterpene derivatives were isolated from the active chloroform extract of FHM roots (FHM-R) and characterized (TLC, 1D, 2D NMR, HR-MS and CD). Moreover, some of the isolates with adequate quantities were evaluated for their possible aphrodisiac effects on male rats. Single doses (10 mg/kg BW) of sildenafil citrate (SC, positive control), gummosin, mogoltavidin, deacetylkellerin, ferukrin acetate with kellerin, elaeochytrin-A and ferutinin were administered or-ally by gavages to male Wistar albino rats. Mount latency (ML), mount frequency (MF), intromission latency (IL), intromission frequency (IF), ejaculation latency (EL) and postejaculatory interval (PEI) were studied. In addition, copulatory efficiency (CE) and intercopulatory efficiency (ICE) were calculated. Results: The preliminary experiment revealed that the chloroform extract was the main source of the active compounds as it showed the higher aphrodisiac activity while the aqueous extract was found to be inactive. Eleven sesquiterpene derivatives, viz. gummosin, mogoltavidin, farnesiferol A, deacetylkellerin, ferukrin acetate, kellerin, teuclatriol, feruhermonin C, ferutinin, elaeochytrin A and teferidin, were isolated from the FHM-CHCl3 extract. Oral administration of deacetylkellerin, elaeochytrin-A and ferutinin significantly increased MF and IF. The ML and IL were significantly reduced, and ejaculation latencies were prolonged. Administration of these sesquiterpenoids also reduced the PEI. The present results revealed that ferutinin was the most effective aph-rodisiac compound compared to other sesquiterpenoids. The results of 10 mg/kg of ferutinin are comparable to SC, the positive control. The results revealed that gummosin, mogoltavidin and ferukrin acetate with kellerin did not significantly alter the aphrodisiac parameters. Conclusions: This study has established that the CHCl3 extract of FHM root contains sesquiterpene derivatives, especially coumarin ethers and benzoic esters. Findings of the present study demonstrate that the chloroform extract and some of the sesquiterpene derivatives significantly stimulates sexual behavior in male rats, thus suggesting that F. huber-morathii possesses an aphrodisiac activity.