Aim: Cinchonine (CN) and its isomer cinchonidine (CD), two of the common cinchona alkaloids, are wildly used as antimalarial drugs. However, the effects of CN and CD on the auditory system are unknown.
Methods: Molecular docking and molecular dynamics (MD) simulation were used for predicting effective drugs. The CCK-8 assay was conducted for assessing cell viability in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells. MitoSox Red staining revealed reactive oxygen species (ROS) amounts. TMRM staining was used to assess the mitochondrial membrane potential (ΔΨm). Immunofluorescence staining of myosin 7a was used to examine hair cells (HCs) in cisplatin-treated neonatal mouse cochlear explants, while TUJ-1 immunostaining was used for the detection of spiral ganglion neurons (SGNs). Cleaved caspase-3 and TUNEL immunostaining were utilized for apoptosis assessment. Immunoblot was carried out to detect PI3K-AKT signaling effectors.
Results: Pretreatment with CN or CD significantly increased cell viability and reduced mitochondrial dysfunction and ROS accumulation in cisplatin-treated HEI-OC1 cells. Immunofluorescent staining of cochlear explants showed that CN and CD attenuated cisplatin-induced damage to SGNs and HCs. Immunoblot revealed that CN and CD downregulated the expression of cleaved caspase-3 and activated PI3K-AKT signaling in cisplatin-injured HEI-OC1 cells.
Conclusion: CD and CN can reduce ototoxicity caused by cisplatin and might help treat cisplatin-associated hearing loss.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10848099 | PMC |
| http://dx.doi.org/10.1111/cns.14403 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Network Toxicology and Molecular Docking Analysis of Tetracycline-Induced Acute Pancreatitis: Unveiling Core Mechanisms and Targets.
Toxics
December 2024
West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
Acute pancreatitis (AP), induced by tetracycline, a widely used antibiotic, poses significant clinical and toxicological challenges, yet its molecular mechanisms remain unclear. This study aims to promote drug toxicology strategies for the effective investigation of the putative toxicity and potential molecular mechanisms of antibiotic drugs through the study of tetracycline in AP. Using the SwissTargetPrediction, SEA Search, Super-PRED, GeneCards, Drugbank, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Database (TTD), we identified 259 potential targets associated with tetracycline exposure and AP.
View Article and Find Full Text PDFRevealing the Mechanism of Baroni in Depression Treatment Through Integrated Network Pharmacology and Transcriptomic Analysis.
Pharmaceuticals (Basel)
December 2024
School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China.
: Baroni (HCB) is a traditional herb for the treatment of depression in China. However, the active constituents and the underlying mechanisms of its antidepressant effects remain unclear. The aim of this study was to identify the bioactive constituents of HCB and elucidate its underlying mechanism for the treatment of depression.
View Article and Find Full Text PDFSparstolonin B Reduces Estrogen-Dependent Proliferation in Cancer Cells: Possible Role of Ceramide and PI3K/AKT/mTOR Inhibition.
Pharmaceuticals (Basel)
November 2024
Department of Medical Biochemistry, Faculty of Medicine, Akdeniz University, Antalya 07070, Turkey.
The aim of this study was to determine the effect of Sparstolonin B (SsnB) on cell proliferation and apoptosis in human breast cancer (MCF-7) and human ovarian epithelial cancer (OVCAR-3) cell lines in the presence and absence of estradiol hemihydrate (ES). Phosphoinositol-3 kinase (PI3K), phosphorylated protein kinase B alpha (p-AKT), phosphorylated mTOR (mechanistic target of rapamycin) signaling proteins, and sphingomyelin/ceramide metabolites were also measured within the scope of the study. The anti-proliferative effects of SsnB therapy were evaluated over a range of times and concentrations.
View Article and Find Full Text PDFPhytosome-Encapsulated 6-Gingerol- and 6-Shogaol-Enriched Extracts from Roscoe Protect Against Oxidative Stress-Induced Neurotoxicity.
Molecules
December 2024
Biomedical Research Unit, Faculty of Medicine, Mahasarakham University, Mahasarakham 44000, Thailand.
The rising prevalence of neurodegenerative disorders underscores the urgent need for effective interventions to prevent neuronal cell death. This study evaluates the neuroprotective potential of phytosome-encapsulated 6-gingerol- and 6-shogaol-enriched extracts from Roscoe (6GS), bioactive compounds renowned for their antioxidant and anti-inflammatory properties. The novel phytosome encapsulation technology employed enhances the bioavailability and stability of these compounds, offering superior therapeutic potential compared to conventional formulations.
View Article and Find Full Text PDFThe Activity of 1,8-Dihydroanthraquinone Derivatives in Nervous System Cancers.
Molecules
December 2024
Department of Biochemistry and Molecular Biology, Medical University of Lublin, 1 Chodzki Str., 20-093 Lublin, Poland.
Primary and metastatic tumors of the nervous system represent a diverse group of neoplasms, each characterized by distinct biological features, prognostic outcomes, and therapeutic approaches. Due to their molecular complexity and heterogeneity, nervous system cancers (NSCs) pose significant clinical challenges. For decades, plants and their natural products with established anticancer properties have played a pivotal role in the treatment of various medical conditions, including cancers.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!