Bioengineering / Biyomühendislik
Permanent URI for this collectionhttps://hdl.handle.net/11147/4529
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Article Citation - WoS: 8Citation - Scopus: 12Adjuvant Potency of Astragaloside Vii Embedded Cholesterol Nanoparticles for H3n2 Influenza Vaccine(TÜBİTAK, 2020) Genç, Rukan; Yakuboğulları, Nilgün; Nalbantsoy, Ayşe; Coven, Fethiye; Bedir, ErdalAdjuvants are substances that increase the immune response to a given antigen. In the development of novel vaccine adjuvants/systems, saponins are one of the most attractive molecules due to their altered immunomodulatory activities. In this study, we tried to develop PEG (polyethylene glycol)/cholesterol-based lipid nanoparticles (LNPs) to deliver the Astragaloside VII (AST-VII) and potentiate adjuvant properties of AST-VII for the influenza vaccine. In the formation of PEG/cholesterol/AST-VII-based LNPs (PEG300: Chol-AST-VII LNPs), 3 different primary solvents (acetone, ethanol, and chloroform) were evaluated, employing their effects on hydrodynamic particle size, distribution, surface chemistry, and colloidal stability. Prepared nanoparticles were simply admixtured with inactivated influenza antigen (H3N2) and applied to PMA (phorbol 12-myristate 13-acetate)-ionomycin treated human whole blood to evaluate their cytokine release profile. PEG300: Chol-AST-VII LNPs (80.2 +/- 7.7 nm) were obtained using chloroform as a desolvation agent. Co-treatment of PMA-ionomycin with AST-VII and PEG300: Chol-AST-VII LNPs significantly increased the levels of IL-2 and IFN-gamma, compared to PMA-ionomycin alone. In the presence of H3N2, AST-VII was able to augment IL-17A, while PEG300: Chol-AST-VII LNPs stimulated the production of IFN-gamma. Hemolysis was only observed in PEG300: Chol-AST-VII LNPs (250 mu g/mL) treatment. AST-VII and AST-VII-integrated LNPs could be used as efficacious adjuvants for an inactivated H3N2 vaccine in vitro, and cytokine response through Th1/Th17 route was reported.Article 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: 11Citation - Scopus: 11Secondary Metabolites From Astragalus Karjaginii Boriss and the Evaluation of Their Effects on Cytokine Release and Hemolysis(Elsevier Ltd., 2017) Aslanipour, Behnaz; Gülcemal, Derya; Nalbantsoy, Ayşe; Yusufoğlu, Hasan; Bedir, ErdalA new cycloartane sapogenol and a new cycloartane xyloside were isolated from Astragalus karjaginii BORISS along with thirteen known compounds. The structures of the new compounds were established as 3-oxo-6α,16β,24(S),25-tetrahydroxycycloartane (1) and 6-O-β-D-xylopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane (2) by 1D- and 2D-NMR experiments as well as ESIMS and HRMS analyses. The presence of the keto function at position 3 was reported for the first time for cyclocanthogenol sapogenin of Astragalus genus. In vitro immunomodulatory effects of the new compounds (1 and 2) along with the n-BuOH and MeOH extracts of A. karjaginii at two different doses (3 and 6 μg) were tested on human whole blood for in vitro cytokine release (IL-2, IL-17A and IFN-γ) and hemolytic activities. The results confirmed that compound 2, a monodesmosidic saponin, had the strongest effect on the induction of both IL-2 (6 μg, 6345.41 ± 0.12 pg/mL (× 5), P < 0.001) and a slight effect upon IL-17A (3 μg, 5217.85 ± 0.72 pg/mL, P < 0.05) cytokines compared to the other test compounds and positive controls (AST VII: Astragaloside VII; and QS-21: Quillaja saponin 21). All tested extracts and molecules also induced release of IFN-γ remarkably ranging between 5031.95 ± 0.05 pg/mL, P < 0.001 for MeOH extract (6 μg) and 5877.08 ± 0.06 pg/mL, P < 0.001 for compound 1 (6 μg) compared to QS-21 (6 μg, 5924.87 ± 0.1 pg/mL, P < 0.001). Administration of AST VII and other test compounds did not cause any hemolytic activity, whereas QS-21 resulted a noteworthy hemolysis.Article Citation - WoS: 17Citation - Scopus: 19Cycloartane-Type Glycosides From Astragalus Brachycalyx Fischer and Their Effects on Cytokine Release and Hemolysis(Elsevier Ltd., 2017) Aslanipour, Behnaz; Gülcemal, Derya; Nalbantsoy, Ayşe; Yusufoğlu, Hasan; Bedir, ErdalTwo new tridesmosidic cycloartane-type triterpene glycosides (1 and 2) were isolated from the methanolic extract of the roots of Astragalus brachycalyx FISCHER (A. brachycalyx) along with ten (3–12) known cycloartane-type triterpene glycosides. Structures of the new compounds were established as 3-O-β-D-xylopyranosyl-6-O-β-D-glucopyranosyl-16-O-β-D-glucopyranosyl-3β,6α,16β,24(S)-25-pentahydroxycycloartane (1), 3-O-[α-L-arabinopyranosyl-(1→2)-β-D-xylopyranosyl]-6-O-β-D-glucopyranosyl-16-O-β-D-glucopyranosyl-3β,6α,16β,24(S)-25-pentahydroxycycloartane (2), by using 1D and 2D-NMR techniques and mass spectrometry. In vitro immunomodulatory effects and hemolytic activities of the new saponins (1 and 2) and acetylated form of 1 (1a) were studied together with the BuOH and MeOH extracts of Astragalus brachycalyx. The results have proven that tridesmosidic Astragalus cycloartanes are noteworthy immunomodulatory compounds via induction of cytokine production, namely IL-2 and IFN-γ. The test compounds also resulted slight hemolysis at very high doses substantiating a safer profile compared to the positive control QS-21.