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Current Pharmaceutical Design - Volume 31, Issue 25, 2025

Volume 31, Issue 25

Volume 31, Issue 25, 2025

    • Therapeutic Effects and Mechanisms of Icaritin in Parkinson's Disease

      https://doi.org/10.2174/0113816128344629250115074105

      Parkinson's Disease (PD) is a neurodegenerative disorder of the central nervous system (CNS). Given the increasing age of the general population, PD has emerged as a significant public health and societal concern, impacting both individual well-being and socioeconomic progress. The present interventions have proven insufficient in impeding the progressive nature of PD. Consequently, it is imperative to promptly identify efficacious strategies for the prevention and treatment of PD. Icaritin (ICT) is a flavonoid extracted from Epimedium Brevicornu Maxim that is a phytoestrogen with antitumour, anti-inflammatory, antioxidant, antiaging, and neuroprotective properties. This paper reviews the protective effect of ICT on dopaminergic neurons through anti-oxidative stress, improving mitochondrial function, inhibiting neuroinflammatory responses, reducing Lewy body formation, and decreasing apoptosis. The primary objective of this article is to provide valuable insights and serve as a reference for the potential use of ICT in the prevention and treatment of PD.

    • Potential New Treatments for Chronic Kidney Diseases: A Concise Review

      https://doi.org/10.2174/0113816128360091250117040009

      Chronic Kidney Disease (CKD) affects about 37 million Americans. Approximately 20% of patients with high blood pressure and 33% of patients with diabetes have kidney disease. CKD is most common among people aged 65 or older and is slightly more common in women. It substantially impacts certain ethnic groups more than others and is associated with a huge financial burden. End-Stage Kidney Disease (ESKD) is treated with dialysis or a kidney transplantation. CKD and ESKD are very detrimental and expensive illnesses, demanding creative therapeutic interventions to enable better management and enhanced clinical outcomes. Toward this goal, agents from various novel drug classes showed promising safety and efficacy in patients with varying severity of CKD in several phase 2 studies. This concise review will shed light on the clinical trials of runcaciguat, cotadutide, osocimab, and Endothelin Receptor Antagonists (ERAs) in patients with CKD and/or ESKD. These drugs were retrieved following surveying the Clinical Trial database as well as the Pubmed database, both maintained by the US National Library of Medicine.

    • Inorganic Nanoparticles-based Drug Delivery Systems for Neurodegenerative Diseases Therapy

      https://doi.org/10.2174/0113816128352935250116064725

      Neurodegenerative disorders (NDs) are highly prevalent among the aging population. It primarily affects the central nervous system (CNS), but the effects are also observed in the peripheral nervous system. Neural degeneration is a progressive loss of structure and function of neurons, which may ultimately involve cell death. The blood-brain barrier (BBB), which separates peripheral blood circulation from the central nervous system, is essential for maintaining intracerebral homeostasis. Drug delivery systems based on nanomaterials (NDDSs) employ nanoparticles (NPs) as their drug transport vehicles. Moreover, nanotechnology-based methods usually involve numerous nanosized carrier platforms, which potentiate the effect of the therapeutic agents in the therapy of NDs, especially in diagnosis and drug delivery, with negligible side effects. In addition, nanotechnology-based techniques have offered several strategies to cross BBB to intensify the bioavailability of drug moieties in the brain. In the last few years, diverse kinds of nanoparticles (NPs) have been developed by incorporating various biocompatible components (., polysaccharide-based NPs, polymeric NPs, selenium NPs, AuNPs, protein-based NPs, gadolinium NPs, .), that showed great therapeutic benefits against NDs. The discussion concluded with a look at the opportunities and problems that come with NDDSs in modern basic and clinical research.

    • Naringenin Attenuates Ox-LDL-induced Injury in HUVECs by Regulating Lipophagy Partly through the SOCE Pathway

      https://doi.org/10.2174/0113816128335261241216110529
      Objective

      Naringenin (NAR) is a naturally occurring tiny molecule that has a significant role in lipid metabolism. However, the molecular mechanism by which NAR is involved in lipid metabolism to protect ECs is not clear. This study aims to investigate the effect of NAR on autophagy in oxidized low-density lipoprotein (ox-LDL)-treated human umbilical vein endothelial cells (HUVECs) and its potential molecular mechanisms.

      Methods

      Oxidized LDL-induced HUVECs injury was treated with NAR. Chloroquine was used as an autophagy inhibitor. Ionomycin (Iono) and 2-aminoethoxydiphenylborate (2-APB) were used as an SOCE pathway agonist and an inhibitor, respectively. The autophagy levels in HUVECs were determined by quantitative real-time PCR, Western blot, and immunofluorescence methods. The concentration of calcium ions in HUVECs was measured by flow cytometry.

      Results

      The findings revealed that NAR increased the viability of ox-LDL-impaired HUVECs. NAR increased the level of autophagy and decreased lipid accumulation in ox-LDL-treated HUVECs, which could interfere with chloroquine. Moreover, NAR significantly downregulated the expression of STIM1 and ORAI1 proteins and Ca2+ levels in the SOCE, which could be interfered with Iono or 2-APB, respectively.

      Conclusion

      In summary, NAR can increase autophagy levels and decrease lipid accumulation in HUVECs, eventually protecting against ox-LDL-induced injury in HUVECs, which is associated with inhibition of the SOCE pathway.

    • Unraveling the Therapeutic Potential of Scutellarin for Clear Cell Renal Cell Carcinoma: A Comprehensive Molecular Analysis

      https://doi.org/10.2174/0113816128340451241224055536
      Background

      Clear cell renal cell carcinoma (ccRCC), the most common subtype of renal cell carcinoma, is a significant global health issue. Despite advancements in surgery and systemic therapies, drug resistance remains a challenge, and more effective treatments are needed. Scutellarin, a natural flavonoid with anticancer properties, is a promising therapeutic option for ccRCC.

      Methods

      This present study identified the potential target genes of scutellarin by searching four databases and utilized the TCGA-KIRC and GSE53757 datasets to identify ccRCC features genes. Protein-protein interaction networks and molecular complex detection analyses determined the hub genes through which scutellarin acts on ccRCC. Differential expression, receiver operating characteristic analysis, survival, and immune cell infiltration analyses were conducted successively on these hub genes in tumor and normal tissues to verify their clinical significance. The intracellular mechanism of the hub genes was explored using a single-cell dataset (GSE222703) to elucidate the intracellular pathway through which scutellarin exerts its anti-ccRCC effects. At last, molecular docking and molecular dynamics simulations were performed to confirm the stability of the receptor protein of the hub gene binding to scutellarin.

      Results

      158 scutellarin targets were collected and identified through database searches. Analyzing the TCGA-KIRC and GSE53757 datasets separately identified finally 132 ccRCC feature genes through differential expression analysis and WGCNA. Protein-protein interaction network and molecular complex detection analyses revealed 26 hub genes potentially involved in key pathways of scutellarin in ccRCC. Differential expression analysis revealed significant differences in the expression of these hub genes between tumor and normal tissues. Receiver operating characteristic analysis demonstrated the fine diagnostic efficacy of these hub genes. Survival analysis indicated that the hub genes TYMS and CDCA2 were associated with a better prognosis, whereas the remaining hub genes had a poorer prognosis. Enrichment analysis revealed that hub genes mainly involved oxidative stress and cell cycle regulation. Single-cell RNA sequencing analysis suggested that most hub genes exert their effects on T helper cells. Molecular docking results showed stable docking of hub genes with scutellarin, except for SPAG5 and ASPM. Molecular dynamics simulations of the most stable docking sites, KIF20A, TYMS, and KIF18B, indicated stable complex formation compared with that of the internal reference protein GAPDH.

      Conclusion

      This integrated study provides a comprehensive analysis of the molecular targets and pathways affected by scutellarin in ccRCC. The identified hub genes and their related pathways present exciting prospects for therapeutic intervention and highlight the potential of scutellarin as a novel treatment for ccRCC. Additional research is necessary to investigate the precise molecular mechanisms and therapeutic advantages of scutellarin in preclinical and clinical contexts.

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