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001-es BibID:	BIBFORM124993
035-os BibID:	(Scopus)85200812472 (WOS)001294526600001
Első szerző:	Balta, Cornel
Cím:	Chrysin-loaded calixarene-cyclodextrin ternary drug delivery system inhibits TGF-β and galectin-1 mediated pathways in diabetic liver fibrosis / Cornel Balta, Hildegard Herman, Alina Ciceu, Caterina Claudia Lepre, Bianca Mladin, Marcel Rosu, Daniela Oatis, Marina Russo, Victor Eduard Peteu, Mihaela Gherghiceanu, Ferenc Fenyvesi, Coralia Cotoraci, Maria Consiglia Trotta, Michele D'Amico, Anca Hermenean
Dátum:	2024
ISSN:	0006-2952
Megjegyzések:	This study investigated the efficacy of a new chrysin-loaded calixarene-cyclodextrin ternary drug delivery system (DDS) in reversing liver fibrosis in a mouse model of chronic diabetes. The system was designed to enhance the solubility and bioavailability of chrysin (CHR) and calixarene 0118 (OTX008). Adult male CD1 mice received streptozotocin (STZ) injections to induce diabetes. After 20 weeks, they underwent intraperitoneal treatments twice weekly for a two-week period. Histological analyses revealed that long-term hyperglycaemia increased liver fibrosis and altered hepatic ultrastructure, characterized by lipid accumulation, hepatic stellate cell activation, and collagen deposition. The treatment with the chrysin-loaded DDS restored liver structure closely to normal levels, as opposed to the minimal impact observed with sulfobutylated ?-cyclodextrin (SBECD) alone. The treatment significantly decreased serum activities of alanine /aspartate transaminases and reduced the gene expression of collagen type I (Col-I). It also modulated the transforming growth factor beta 1 (TGF-?1)/Smad signalling pathway, inhibiting the activation and proliferation of hepatic stellate cells. The treatment led to a downregulation of the TGF-?1 gene and its receptors TGF?R1 and TGF?R2, together with a decrease in Smad 2 and 3 mRNA levels. Conversely, Smad 7 mRNA expression was increased by the DDS. Furthermore, it downregulated galectin-1 (Gal-1) gene and protein levels, which correlated with fibrotic markers. In conclusion, the chrysin-loaded calixarene-cyclodextrin ternary DDS presents a promising therapeutic approach for diabetic liver fibrosis, effectively targeting fibrotic pathways and restoring hepatic function and structure. ? 2024
Tárgyszavak:	Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk Calixarene Chronic diabetes Chrysin Cyclodextrin Drug delivery system Liver fibrosis
Megjelenés:	Biochemical Pharmacology. - 229 (2024), p. 116474, p. 1-10. -
További szerzők:	Herman, Hildegard Ciceu, Alina Lepre, Caterina Claudia Mladin, Bianca Rosu, Marcel Oatis, Daniela Russo, Marina Peteu, Victor Eduard Gherghiceanu, Mihaela Fenyvesi Ferenc (1977-) (gyógyszerész, gyógyszertechnológus) Cotoraci, Coralia Trotta, Maria Consiglia D'Amico, Michele Hermenean, Anca
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001-es BibID:	BIBFORM075559
035-os BibID:	(scopus)85051666187 (wos)000441409800001
Első szerző:	Gharbia, Sami
Cím:	Enhancement of Silymarin Anti-fibrotic Effects by Complexation With Hydroxypropyl (HPBCD) and Randomly Methylated (RAMEB) β-Cyclodextrins in a Mouse Model of Liver Fibrosis / Sami Gharbia, Cornel Balta, Hildegard Herman, Marcel Rosu, Judit Váradi, Ildikó Bácskay, Miklós Vecsernyés, Szilvia Gyöngyösi, Ferenc Fenyvesi, Sorina N. Voicu, Miruna S. Stan, Roxana E. Cristian, Anca Dinischiotu, Anca Hermenean
Dátum:	2018
ISSN:	1663-9812
Tárgyszavak:	Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Frontiers in Pharmacology. - 9 (2018), p. 1-18. -
További szerzők:	Balta, Cornel Herman, Hildegard Rosu, Marcel Váradi Judit (1973-) (gyógyszerész, gyógyszertechnológus) Bácskay Ildikó (1969-) (gyógyszerész, gyógyszertechnológus) Vecsernyés Miklós (1959-) (gyógyszertechnológus, endokrinológus) Gyöngyösi Szilvia (1983-) (anyagmérnök, gépészmérnök) Fenyvesi Ferenc (1977-) (gyógyszerész, gyógyszertechnológus) Voicu, Sorina N. Stan, Miruna Cristian, Roxana E. Dinischiotu, Anca Hermenean, Anca
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001-es BibID:	BIBFORM117746
035-os BibID:	(Scopus)85181199885 (WoS)001133248900001
Első szerző:	Trotta, Maria Consiglia
Cím:	Chrysin-based supramolecular cyclodextrin-calixarene drug delivery system : a novel approach for attenuating cardiac fibrosis in chronic diabetes / Maria Consiglia Trotta, Hildegard Herman, Alina Ciceu, Bianca Mladin, Marcel Rosu, Caterina Claudia Lepre, Marina Russo, Ildikó Bácskay, Ferenc Fenyvesi, Raffaele Marfella, Anca Hermenean, Cornel Balta, Michele D'Amico
Dátum:	2023
ISSN:	1663-9812
Megjegyzések:	Introduction: Cardiac fibrosis is strongly induced by diabetic conditions. Both chrysin (CHR) and calixarene OTX008, a specific inhibitor of galectin 1 (Gal-1), seem able to reduce transforming growth factor beta (TGF-?)/SMAD pro-fibrotic pathways, but their use is limited to their low solubility. Therefore, we formulated a dual-action supramolecular system, combining CHR with sulfobutylated ?-cyclodextrin (SBECD) and OTX008 (SBECD + OTX + CHR). Here we aimed to test the anti-fibrotic effects of SBECD + OTX + CHR in hyperglycemic H9c2 cardiomyocytes and in a mouse model of chronic diabetes. Methods: H9c2 cardiomyocytes were exposed to normal (NG, 5.5 mM) or high glucose (HG, 33 mM) for 48 h, then treated with SBECD + OTX + CHR (containing OTX008 0.75?1.25?2.5 ?M) or the single compounds for 6 days. TGF-?/SMAD pathways, Mitogen-Activated Protein Kinases (MAPKs) and Gal-1 levels were assayed by Enzyme-Linked Immunosorbent Assays (ELISAs) or Real-Time Quantitative Reverse Transcription Polymerase chain reaction (qRT-PCR). Adult CD1 male mice received a single intraperitoneal (i.p.) administration of streptozotocin (STZ) at a dosage of 102 mg/kg body weight. From the second week of diabetes, mice received 2 times/week the following i.p. treatments: OTX (5 mg/kg)-SBECD; OTX (5 mg/kg)-SBECD-CHR, SBECD-CHR, SBECD. After a 22-week period of diabetes, mice were euthanized and cardiac tissue used for tissue staining, ELISA, qRT-PCR aimed to analyse TGF-?/SMAD, extracellular matrix (ECM) components and Gal-1. Results: In H9c2 cells exposed to HG, SBECD + OTX + CHR significantly ameliorated the damaged morphology and reduced TGF-?1, its receptors (TGF?R1 and TGF?R2), SMAD2/4, MAPKs and Gal-1. Accordingly, these markers were reduced also in cardiac tissue from chronic diabetes, in which an amelioration of cardiac remodeling and ECM was evident. In both settings, SBECD + OTX + CHR was the most effective treatment compared to the other ones. Conclusion: The CHR-based supramolecular SBECD-calixarene drug delivery system, by enhancing the solubility and the bioavailability of both CHR and calixarene OTX008, and by combining their effects, showed a strong anti-fibrotic activity in rat cardiomyocytes and in cardiac tissue from mice with chronic diabetes. Also an improved cardiac tissue remodeling was evident. Therefore, new drug delivery system, which could be considered as a novel putative therapeutic strategy for the treatment of diabetes-induced cardiac fibrosis.
Tárgyszavak:	Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk chrysin cyclodextrin calixarene drug delivery system cardiac fibrosis chronic diabetes
Megjelenés:	Frontiers in Pharmacology. - 14 (2023), p. 1-17. -
További szerzők:	Herman, Hildegard Ciceu, Alina Mladin, Bianca Rosu, Marcel Lepre, Caterina Claudia Russo, Marina Bácskay Ildikó (1969-) (gyógyszerész, gyógyszertechnológus) Fenyvesi Ferenc (1977-) (gyógyszerész, gyógyszertechnológus) Marfella, Raffaele Hermenean, Anca Balta, Cornel D'Amico, Michele
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