Naunyn-Schmiedeberg's archives of pharmacology最新文献

{"title":"Diacerein and myo-inositol alleviate letrozole-induced PCOS via modulation of HMGB1, SIRT1, and NF-kB: A comparative study.","authors":"Suzan A Khodir, Eman Sweed, Shaimaa Mohamed Motawea, Marwa A Al-Gholam, Sherin Sobhy Elnaidany, Mohamed Zakaria Sayer Dayer, Omnia Ameen","doi":"10.1007/s00210-024-03497-7","DOIUrl":"10.1007/s00210-024-03497-7","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is the most prevalent cause of anovulatory infertility in women. Myo-inositol supplementation has displayed effectiveness in curing PCOS patients. Diacerein, an anti-inflammatory medication, has not been extensively studied in the context of reproductive disorders. This study aimed to compare the role of myo-inositol and diacerein in PCOS and the probable mechanisms mediating their actions. Forty adult female rats were divided equally into the following: control, PCOS, PCOS+Myo-inositol, and PCOS+Diacerein groups. Rats were subjected to arterial blood pressure (ABP), electromyography (EMG), and uterine reactivity measurements. Blood samples were collected for measuring hormonal assays, glycemic state, lipid profile, oxidative stress, and inflammatory markers. Ovaries and uteri were extracted for histological examination, including hematoxylin and eosin staining, Masson's trichrome staining, immunohistochemistry, and rt-PCR analysis of ovarian tissues. PCOS was associated with significant increases in ABP, uterine frequency and amplitude of contraction, luteinizing hormone, testosterone, lipid, glycemic and inflammatory markers, malondialdehyde, high-mobility group box 1 (HMGB1), nuclear factor kappa (NF-kB), ovarian fibrosis, and endometrial thickening. In contrast, there was a significant reduction in follicular stimulating hormone, reduced glutathione, and Sirtuin 1 (SIRT1) when compared with control group. Both myo-inositol and diacerein counteract PCOS changes; but diacerein's effects were superior to myo-inositol's for all parameters, except for lipid and glycemic markers. Diacerein possessed anti-inflammatory properties and showed significant efficacy in mitigating the endocrinal, metabolic, and ovarian structural alterations linked to PCOS. Its beneficial actions likely stem from reducing oxidative stress, dyslipidemia, and hyperglycemia, potentially through the modulation of HMGB1, SIRT1, and NF-kB pathways.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"4179-4197"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hesperidin as a bioactive compound in citrus fruits reduces N-ethyl-N-nitrosourea-induced mortality and toxicity in mice: as a model for chronic lymphocytic leukemia.","authors":"Ahmad Salimi, Bahare Asgari, Saleh Khezri, Mahshad Pourgholi, Shadi Haddadi","doi":"10.1007/s00210-024-03531-8","DOIUrl":"10.1007/s00210-024-03531-8","url":null,"abstract":"<p><p>The current study is aimed at determining the preventive effects of hesperidin against death, weight changes, cellular damage, and oxidative stress in mice induced by n-ethyl-n-nitrosourea as a chronic lymphocytic leukemia (CLL) model. Female mice were pretreated with hesperidin (20 mg/kg, intraperitoneally, daily for 30 days). Next, the animals received a single intraperitoneal injection of 80 mg/kg ENU on the 30th. Changes in weight and mortality were monitored for 120 days, and then the animals were sacrificed and parameters such as reactive oxygen species (ROS), mitochondrial dysfunction, lysosomal membrane integrity, oxidized/reduced glutathione (GSH/GSSG), and malondialdehyde (MDA) were analyzed in isolated lymphocytes. Hesperidin significantly increases the survival of mice up to 86% and delay in death time and prevents weight changes after exposure to ENU. Also, hesperidin improved cellular toxicity parameters such as ROS formation, MMP collapse, lysosomal membrane destabilization, and lipid peroxidation in isolated lymphocytes. These results promisingly showed that pretreatment with hesperidin increases delay in death time and reduces mortality cellular toxicities consistent with the carcinogenicity of alkylating compounds. This study confirms that the consumption of hesperidin and citrus most likely inhibits alkylating agents-induced carcinogenicity and toxicity.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"4009-4018"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effects of astaxanthin solid lipid nanoparticle as a promising candidate against acute kidney injury in rats.","authors":"Akram Yarmohammadi, Elham Arkan, Houshang Najafi, Fatemeh Abbaszadeh, Khodabakhsh Rashidi, Sana Piri, Sajad Fakhri","doi":"10.1007/s00210-024-03543-4","DOIUrl":"10.1007/s00210-024-03543-4","url":null,"abstract":"<p><p>Acute kidney injury (AKI) is a sudden onset of renal injury that occurs within a few hours or days. Ischemia-reperfusion (IR) is a major cause of AKI. There are multiple dysregulated mechanisms behind the pathogenesis of AKI and IR which urges the need for finding multi-targeting therapies. Natural products are multi-targeting agents with promising sources of anti-inflammation, antioxidant, and antiapoptosis. Among them, astaxanthin (AST) is a keto-carotenoid with a high antioxidant potential. Using solid lipid nanoparticles (SLNs) as a novel formulation of AST helps to increase its efficacy and reduce side effects against AKI. After SLN preparation and loading of AST, the physicochemical properties were evaluated, using scanning electron microscopy (SEM) and dynamic light scattering (DLS) tests. For the in vivo study, 28 rats were divided into four groups, including sham, ischemia/reperfusion (I/R), and groups receiving protective and daily doses of AST-SLN (5 and 10 mg/kg, i.p.) during all 5 days before ischemia. Exactly 24 h after ischemia, kidneys were isolated for histological studies, and also, serum levels of catalase (CAT), glutathione (GSH), nitrite, blood urea, and creatinine were measured. The results indicated that intraperitoneal administration of SLN-AST reduced oxidative stress by decreasing serum nitrite levels, while increasing CAT and GSH. SLN-AST also improved renal function by decreasing serum urea and creatinine and preventing tissue damage. Therefore, SLN-AST could be a hopeful adjuvant candidate to prevent AKI by modulating renal function, preventing tissue damage, and through antioxidant mechanisms.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"4491-4502"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the effects of intravenous magnesium sulfate for prevention of colistin induced acute kidney injury: an open-label, placebo-controlled, block randomized clinical trial.","authors":"Sareh Hosseini, Ilad Alavi Darzam, Mahdi Amirdosara, Masoud Zangi, Zahra Sahraei","doi":"10.1007/s00210-024-03583-w","DOIUrl":"10.1007/s00210-024-03583-w","url":null,"abstract":"<p><p>Colistin, has reinstated as a last-resort antibiotic despite its known nephrotoxicity. The aim of this study was to determine the potential nephroprotective effects of Magnesium (Mg) Sulfate during colistin therapy. This study was an open-label, placebo-controlled, block-randomized clinical trial conducted from January 2023 to February 2024 involving 87 patients eligible for colistin therapy. Patients were randomly assigned to receive either Mg sulfate (16 mEq in 100 mL of normal saline) or 100 mL of normal saline as placebo before each dose of colistin. The primary outcome of the study was the incidence of Acute Kidney Injury (AKI) during the first week of colistin therapy, while the secondary outcomes included colistin dose adjustments, length of stay in the ICU and hospital, and overall mortality. This study was registered in The Iranian Registry of Clinical Trials (IRCT20130917014693N15; 2023-01-12). A total of 87 patients (46 in Mg and 41 in control group) completed the study. Fourteen patients (30.43%) in the Mg group and twenty-one patients (51.21%) in the control group developed AKI during the first week of colistin therapy (p = 0.048). Although AKI incidence was not statistically different between the groups in unadjusted Cox regression model (HR =0.51, 95% CI =0.26-1.01, P =0.057), it became significant after adjusting for confounding factors (HR =0.40,95% CI =0.18-0.86, P =0.021). The length of hospital stay was 48.62 ± 18.82 and 44.82 ± 20.23 days for Mg and control groups respectively (p=0.373). In the Mg group, 25 out of 46 patients (54.34 %) and in the control group, 24 out of 41 patients (58.53%) eventually expired (p=0.694). This study indicates that Mg sulfate significantly reduces AKI rates and prevents hypomagnesemia, optimizing dosing and enhancing patient safety during colistin therapy.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"4559-4570"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of carvacrol on hormonal, inflammatory, antioxidant changes, and ovarian reserve in polycystic ovary syndrome in Wistar rats.","authors":"İshak Gökçek, Gökhan Uyanık, Tolga Tutar, Ahmet Gözer","doi":"10.1007/s00210-024-03588-5","DOIUrl":"10.1007/s00210-024-03588-5","url":null,"abstract":"<p><p>The study, which explored the effects of carvacrol on female reproductive health, particularly in terms of hormonal, inflammatory, antioxidant, and ovarian reserves in polycystic ovary syndrome, could significantly influence future treatments and clinical practice. The study, conducted on thirty-five female Wistar albino rats, was designed to mimic the conditions of polycystic ovary syndrome in humans. The rats were randomly assigned into five groups: control (C), vehicle (V), polycystic ovary syndrome (PCOS), carvacrol (CAR), and polycystic ovary syndrome + carvacrol (PCOS + CAR). The following practices were applied to the groups during the study. Normal saline was administered to the C group, DMSO to the V group, letrozole (1 mg/kg/day) to the PCOS group, carvacrol (20 mg/kg) to the CAR group, and letrozole and carvacrol together to the PCOS + CAR group for twenty-one days. At the end of the administration, blood, and ovarian samples were taken for hormone analysis (E₂, and AMH), inflammatory (TNF-α, IL-6), oxidant-antioxidant analysis (malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GSH-Px), and catalase), and histopathological examinations. Ovary, and body weights were measured, and the ovary index was calculated. As a result, it was observed that carvacrol caused beneficial effects through inflammatory, and antioxidant mechanisms in PCOS.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"4607-4616"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fucoidan improves intestinal peristaltic function in rats with postoperative ileus.","authors":"Baoguo He, Zhenming Zhu, Zibin Tian, Dandan Wang, Yijing Li, Xiao Luan, Li Ma","doi":"10.1007/s00210-024-03587-6","DOIUrl":"10.1007/s00210-024-03587-6","url":null,"abstract":"<p><p>The effect of fucoidan on postoperative ileus (POI) has not been studied. In this study, how fucoidan ameliorates POI in a rat POI model was investigated. The results showed that in the model animals, when the first defecation time was prolonged, the amount of food consumed decreased, the small intestinal propulsion rate dramatically slowed, and the motility index (MI%) of the small intestine decreased. In vitro experiments revealed that the contractile response of small intestinal smooth muscle strips to carbachol (CCh) was reduced. Immunohistochemistry revealed evident macrophage infiltration in the intestinal muscularis. However, after oral pretreatment with fucoidan, the time to first defecation decreased, and food intake, the small intestinal propulsion rate, and MI% of the small intestine increased. Additionally, the contractile response of the intestinal strips to CCh became stronger, and macrophage infiltration decreased. Mechanistically, fucoidan alleviated POI by exerting anti-inflammatory and antioxidant effects as well as likely through the TrkB/ERK1/2/Akt signalling pathways. When POI occurred, the expression levels of inflammatory factors in the intestines significantly increased while the phosphorylation of TrkB, ERK1/2, and Akt significantly decreased; malondialdehyde (MDA) levels in the intestines increased but the levels of superoxide dismutase (SOD) and glutathione (GSH) decreased. In contrast, after pretreatment with fucoidan, the expression levels of inflammatory factors decreased; the phosphorylation levels of TrkB, ERK1/2, and Akt increased; the MDA level decreased; and SOD and GSH levels increased. Thus, fucoidan alleviated POI-induced impairment of rat intestinal motility through anti-inflammatory and antioxidant effects possibly associated with the TrkB/ERK1/2 and Akt signalling pathways.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"4593-4605"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curcumin ameliorates heatstroke-induced lung injury by activating the PI3K/AKT pathway.","authors":"Yizhan Wu, Fei Guo, Jiajia Li, Wenhui Shi, Laiyang Song, Jiangwei Liu","doi":"10.1007/s00210-024-03572-z","DOIUrl":"10.1007/s00210-024-03572-z","url":null,"abstract":"<p><p>Heatstroke (HS) poses a significant threat to public health. Curcumin, a polyphenolic compound, has been reported to possess anti-inflammatory and antioxidant properties. This study aimed to investigate the potential therapeutic effects of curcumin on HS-induced lung injury and to elucidate its underlying molecular mechanisms. We utilized network pharmacology to predict the potential targets of curcumin and determine its possible protective effects against HS. Molecular docking was performed to assess the affinity of curcumin to proteins. Forty mice were used for in vivo experiments to evaluate the therapeutic effects of curcumin, divided into four groups (n = 10 per group): normal control (NC), high-temperature control (HTC), low-dose curcumin heatstroke (H100c, 100 mg/kg/day), and high-dose curcumin heatstroke (H200c, 200 mg/kg/day). Furthermore, we evaluated lung pathology, ultrastructural alterations, and protein expression levels of key molecules. Molecular docking indicated a high binding affinity between curcumin and PIK3R1, AKT, and CASP3. In vivo experiments confirm that curcumin pretreatment significantly mitigates HS-induced lung tissue pathology and ultrastructural damage, with the H200c group showing notably greater improvement. Furthermore, curcumin pretreatment markedly enhances the activation of the PI3K/AKT pathway and suppresses the expression of cleaved caspase3, particularly in the H200c group. Our study suggests curcumin may alleviate HS-induced lung injury via the PI3K/AKT pathway, but limitations exist. We did not test key protein knockdown/overexpression, and PI3K/AKT may not be the only pathway. Human and mouse pharmacokinetic differences could affect clinical translation.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"4617-4632"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPR/Cas9 system: a novel approach to overcome chemotherapy and radiotherapy resistance in cancer.","authors":"Somaye Noruzi, Rezvan Mohammadi, Khadijeh Jamialahmadi","doi":"10.1007/s00210-024-03480-2","DOIUrl":"10.1007/s00210-024-03480-2","url":null,"abstract":"<p><p>Cancer presents a global health challenge with rising incidence and mortality. Despite treatment advances in cancer therapy, radiotherapy and chemotherapy remained the most common treatments for all types of cancers. However, resistance phenotype in cancer cells leads to unsatisfactory results in the efficiency of therapeutic strategies. Therefore, researchers strive to propose effective solutions to overcome treatment failure, which requires a deep knowledge of treatment-resistant mechanisms. The progression and occurrence of tumors can be attributed to gene mutation. Over the past decade, the emergence of clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR/Cas9) genome editing has revolutionized cancer research. This versatile technology enables cancer modeling, manipulation of specific DNA sequences, and genome-wide screening. CRISPR/Cas9 is an effective tool for identifying radio- and chemoresistance genes and offering potential adjunctive treatments to overcome tumor recurrence after chemo- and radiotherapy. This article aims to explain the potential of the CRISPR/Cas9 system in improving the effectiveness of chemo- and radiotherapy and ultimately overcoming treatment failure.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"3373-3408"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The negative chronotropic effects of (±)-propranolol and (±)-4-NO₂-propranolol in the rat isolated right atrium are due to blockade of the 6-nitrodopamine receptor.","authors":"Denis Lima Oliveira, Vinicius Francisco Cardoso, Jose Britto-Júnior, Vivian Fuguhara, Francesco Frecentese, Rosa Sparaco, Vincenzo Santagada, Giuseppe Caliendo, André Sampaio Pupo, Edson Antunes, Gilberto De Nucci","doi":"10.1007/s00210-024-03463-3","DOIUrl":"10.1007/s00210-024-03463-3","url":null,"abstract":"<p><p>The positive chronotropic action induced by 6-nitrodopamine (6-ND) is selectively blocked by β₁-adrenoceptor antagonists at concentrations that do not affect the positive chronotropic effect induced by dopamine, noradrenaline, and adrenaline. Here, the effects of ( ±)-propranolol, ( ±)-4-NO₂-propranolol, and ( ±)-7-NO₂-propranolol were investigated in the rat isolated right atrium. The atrium was mounted in glass chambers containing gassed (95%O₂:5%CO₂) and warmed (37 °C) Krebs-Henseleit's solution, and the isometric tension registered (PowerLab system). ( ±)-Propranolol, ( ±)-4-NO₂-propranolol, and ( ±)-7-NO₂-propranolol caused concentration-dependent falls in the spontaneous atrial frequency (pIC₅₀: 4.80 ± 0.10, 4.64 ± 0.10, and 4.95 ± 0.10, respectively). The calculated pA₂ values for ( ±)-propranolol, ( ±)-4-NO₂-propranolol, and ( ±)-7-NO₂-propranol on noradrenaline-induced positive chronotropism were 8.44 ± 0.08, 6.41 ± 0.07, and 9.21 ± 0.29, respectively. The positive chronotropism induced by 6-ND (10 pM) was blocked by ( ±)-propranolol (1 µM) and ( ±)-4-NO₂-propranolol (30 nM), whereas ( ±)-7-NO₂-propranolol (1 µM) had no effect on 6-ND-induced responses. The pIC₅₀ of ( ±)-propranolol, ( ±)-4-NO₂-propranolol, and ( ±)-7-NO₂-propranolol were significantly shifted to the right in L-NAME-treated atria. The discrepancy between pA₂ values of ( ±)-propranolol and its respective pIC₅₀ indicates that the falls in atrial rate induced by ( ±)-propranolol should not be attributed to b-adrenergic antagonism. The reduced chronotropism by ( ±)-propranolol was unaffected by the sodium channel inhibitors tetrodotoxin and lidocaine but that was abolished in atria pre-treated with ( ±)-4-NO₂-propranolol. The finding that ( ±)-propranolol reduces spontaneous atrial rate only in concentrations that affect 6-ND-induced positive chronotropism confirms the role of this catecholamine as an endogenous modulator of heart chronotropism. ( ±)-4-NO₂-Propranolol behaves as a selective antagonist of 6-ND in the rat isolated atrium.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"3965-3976"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glycosylation of chrysin with β-d-glucose tetraacetate (LQFM280) enhances its in vitro and in vivo neuroprotective effects against the toxicity induced by 3-nitropropionic acid.","authors":"Robbert Mota Pereira, Hericles Mesquita Campos, Pâmela Yasmin de Oliveira Ferreira, Nkaa Uchenna, Yohanny Souza Silva, Victor Ifeanyi Okoh, Letizia Pruccoli, Evilanna Lima Arruda, Luciano Morais Lião, Pedro Augusto Alves Mota, Jacqueline Alves Leite, Raphaela de Castro Georg, David Henriques da Matta, Fernanda Cristina Alcantara Dos Santos, Elson Alves Costa, Andrea Tarozzi, Ricardo Menegatti, Paulo César Ghedini","doi":"10.1007/s00210-024-03526-5","DOIUrl":"10.1007/s00210-024-03526-5","url":null,"abstract":"<p><p>Chrysin (CHR) is a naturally occurring flavonoid found in the human diet, recognized for its potential in preventing neurodegenerative diseases. However, its limited water solubility restricts its bioavailability and therapeutic applications. To address this issue and bolster the neuroprotective properties of CHR for potential nutraceutical or medicinal use, we investigated a novel compound, LQFM280, formed by conjugating CHR with β-d-glucose tetraacetate. We conducted both in vitro (using SH-SY5Y cells, mutant STHdhQ111/Q111 cells, and wild-type STHdhQ7/Q7 cells), and in vivo (mice) neurotoxicity experimental model induced by 3-nitropropionic acid, which mimic biological changes akin to Huntington's disease in humans. Compared to non-glycosylated CHR, LQFM280 showed superior in vitro effects in preventing neurotoxicity caused by increased mitochondrial vulnerability due to mutant huntingtin. In vivo findings demonstrated that LQFM280 has heightened efficacy in mitigating weight loss, memory and locomotor impairment, oxidative stress, and disruptions in the antioxidant defense system, as well as succinate dehydrogenase, and cholinesterase activities induced by 3-nitropropionic acid. These findings underscore the significant enhancement of chrysin's neuroprotective effects through glycosylation with β-d-glucose tetraacetate, positioning it as a promising candidate for use as a nutraceutical or food supplement to promote health benefits.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"4095-4109"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}