Current pharmaceutical design最新文献

{"title":"A Review on Mechanisms of Action and Signaling Pathways of Natural Anti-hyperpigmentation Agents.","authors":"Jaanvi Khanna, Anshula Mehra, Manikay Mahajan, Vridhi Sachdeva, Jyoti Bhardwaj, Maninderdeep Kaur, Prabha Kumari, Arprita Malhan, Neena Bedi","doi":"10.2174/0113816128483347260927073907","DOIUrl":"https://doi.org/10.2174/0113816128483347260927073907","url":null,"abstract":"<p><p>Hyperpigmentation is a dermatological condition characterized by excessive melanin production, resulting in skin darkening. Intrinsic and extrinsic mediators, including ultraviolet (UV) radiation, hormonal changes, inflammation, and genetic predisposition, contribute to hyperpigmentation pathogenesis. The current review thoroughly examines the biological processes involved in hyperpigmentation, with particular emphasis on its signaling pathways, particularly the cyclic adenosine monophosphate (cAMP), wingless-related integration site (Wnt)/β-catenin, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and mitogen-activated protein kinase (MAPK), thereby providing mechanistic insights that may facilitate the development of effective treatments. The review also evaluates the safety, toxicity, and therapeutic efficacy of TYR inhibitors, arbutin, azelaic acid, ellagic acid, kojic acid, resveratrol, and the melanosome inhibitor niacinamide, for managing hyperpigmentation. Additionally, the review summarizes the in vitro and in vivo studies of these agents and other emerging plant extracts. Recent advances in the use of plant extracts for hyperpigmentation have shown promising efficacy; nevertheless, their translation into clinical and commercial applications remains limited. This limited translation might be attributed to the challenges related to standardization and the paucity of clinical evidence regarding long-term safety. Moreover, ongoing studies on natural anti-hyperpigmentation agents have highlighted the critical role of patent analyses in the advancement of biomedical research. This review provides a strategic direction for researchers to assess the safety, efficacy, and toxicity profiles of natural anti-hyperpigmentation agents.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166000","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":"Cannabinoids for Acute Pain Management: A Contemporary Scoping Review of Evidence, Mechanisms, and Clinical Implications.","authors":"Canan Akman, Asli Bahar Ucar, Ozlem Inci, Mehmet Unaldi, Busra Erdem, Bilgen Ozkaya, Gokhan Yilmaz, Ozgur Karcioglu","doi":"10.2174/0113816128510427260927100857","DOIUrl":"https://doi.org/10.2174/0113816128510427260927100857","url":null,"abstract":"<p><strong>Background: </strong>The global opioid crisis has intensified interest in non-opioid and opioid-sparing analgesic strategies, including cannabinoids. Despite the expanding legal landscape for cannabis and a rapidly growing cannabinoid market, the clinical evidence for cannabinoid use in acute pain management remains inconsistent and largely of low quality.</p><p><strong>Methods: </strong>This contemporary scoping review was conducted and reported in accordance with the PRISMA extension for Scoping Reviews (PRISMA-ScR). A systematic search of six electronic databases (Cochrane Central Register of Controlled Trials (CENTRAL), PubMed/MEDLINE, ClinicalKey, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and BIOSIS) was performed for literature published between 1 January 2016 and 5 April 2026, with the final database search executed on 5 April 2026, addressing the pharmacology, mechanisms of action, clinical efficacy, safety, and perioperative implications of cannabinoids in acute and postoperative pain. Two blinded reviewers independently screened records and charted data against predefined eligibility criteria; discrepancies were resolved by a third author. Findings are summarized narratively and in tabular format, and the study selection process is depicted in a PRISMA flow diagram.</p><p><strong>Results: </strong>Preclinical evidence supports robust antinociceptive effects of cannabinoids through multiple receptor pathways; however, these findings have not translated reliably into human acute pain models. Metaanalytic data demonstrate either no significant reduction in acute pain scores with cannabinoids versus placebo, or only small, clinically uncertain improvements. The opioid-sparing effect, while promising in preclinical and some chronic pain studies, has not been demonstrated for acute postoperative pain. A notable exception is a 2024 randomized trial showing a 40% reduction in opioid requirements with perioperative dronabinol after cardiac surgery. Safety data indicate that non-serious adverse events (dizziness, nausea, sedation) are consistently more frequent with cannabinoids than placebo. The 2023 American Society of Regional Anesthesia and Pain Medicine (ASRA) consensus guidelines now formalize 21 recommendations for perioperative cannabinoid management.</p><p><strong>Conclusion: </strong>While the biological rationale for cannabinoid analgesia is compelling, the clinical evidence base for acute pain remains insufficient to support routine use. Cannabinoids may serve as adjuncts in specific populations, but require careful patient selection, dose titration, and safety monitoring. Well-designed, large randomized controlled trials targeting defined acute pain populations are urgently needed.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166110","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":"Approaches to Enhance the Regenerative Potential of MSC-derived Extracellular Vesicles (MSCEV): A Promising Cell-free Therapy for Osteoarthritis.","authors":"Timea Spakova, Zuzana Váczy, Denisa Harvanová","doi":"10.2174/0113816128533677260928172026","DOIUrl":"https://doi.org/10.2174/0113816128533677260928172026","url":null,"abstract":"<p><p>Osteoarthritis therapy remains a big challenge since no causative treatment options are available so far. Current preclinical studies report that extracellular vesicles derived from mesenchymal stem cells have high potential to change disease evolution and protect the cartilage matrix. Extracellular vesicles are diverse nanoscale, membrane-bound particles that mediate and regulate intercellular communication. Their therapeutic efficacy in terms of clinical translation is highly dependent on the status of mesenchymal stem cells. Mesenchymal stem cells have been shown to respond to different aspects of the injury microenvironment. Recent research has explored the use of diverse stimuli to enhance stem cell secretion and improve the biological activity of released extracellular vesicles. The most common approach to influence the profile and biological activities of mesenchymal stem cell-derived factors is to recreate a pro-inflammatory environment mimicking an in vivo pathological setting, but other promising methods also deserve to be investigated. This narrative review summarizes and discusses recent strategies aimed at enhancing the regenerative and supportive effect of mesenchymal stem cell-derived extracellular vesicles by improving the secretion capacity of cells via different stimulation, with a focus on the development and clinical translation of engineered vesicles for joint disorders. Relevant literature was identified through searches of PubMed and Web of Science for peer-reviewed articles published between 2018 and 2026, with priority given to experimental, translational, and clinical studies investigating MSCEVs in OA and approaches for modifying their production, cargo, targeting, or delivery.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165321","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":"Identification of the Proapoptotic Mechanism of Astragalosides in Rheumatoid Arthritis Therapy Based on HPLC, Bioinformatics and Network Pharmacology.","authors":"Tingting Li, Yihang Zhu, Mengru Li, Xiaoya Cui, Hui Jiang","doi":"10.2174/0113816128510958260922075558","DOIUrl":"https://doi.org/10.2174/0113816128510958260922075558","url":null,"abstract":"<p><strong>Introduction: </strong>Astragalosides (ASTs), principal active saponins derived from Astragalus, exert prominent therapeutic efficacy against Rheumatoid Arthritis (RA). However, few studies have investigated the molecular mechanism of ASTs in RA therapy.</p><p><strong>Methods: </strong>AST components were qualitatively and quantitatively analyzed by HPLC. RA-related Differentially Expressed Genes (DEGs) were acquired from the GSE77298 dataset, and AST target genes were predicted via multiple databases. Core hub genes and signaling pathways were screened through bioinformatics analyses, including GO/KEGG enrichment, PPI network and MCODE modularity analysis. Molecular docking was performed to evaluate the binding affinity between ASTs and core apoptotic genes. Cell phenotypic assays, qRT-PCR, Western blot and CASP8 siRNA interference experiments were conducted to validate the regulatory effect of ASTs on the CASP8-ATM-XIAP-CASP3 axis in MH7A cells.</p><p><strong>Results: </strong>In total, 5781 DEGs were obtained from the GSE77298 dataset, 496 ASTs-related genes were predicted, among which 156 intersected. They were enriched in 3345 significant GO terms and 121 significant KEGG pathways. Bioinformatic and experimental analyses validated that ATM, CASP8, and XIAP mediate AST-induced MH7A cell apoptosis via the CASP8-ATM-XIAP-CASP3 axis.</p><p><strong>Discussion: </strong>ASTs decrease cellular proliferation and induce apoptosis in MH7A cells. Moreover, ASTs reduced the expression of XIAP and increased the expression of ATM and CASP8 at both the mRNA and protein levels. In addition, ASTs reversed the effects of siRNA-mediated CASP8 silencing on the mRNA expression of CASP3, ATM, and XIAP.</p><p><strong>Conclusion: </strong>ASTs can promote apoptosis in MH7A cells, and the underlying mechanism may involve regulation of the CASP8-ATM-XIAP-CASP3 signaling axis.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164508","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":"Identification of Lead Compounds for Pesticides using Computer Aided Drug Discovery.","authors":"Fatima Aslam, Abdul Razzaq, Hussain Dawood, Salman Qadri, Zulqurnain Khan, Muhammad Aziz-Ur-Rehman","doi":"10.2174/0113816128399605251012122039","DOIUrl":"https://doi.org/10.2174/0113816128399605251012122039","url":null,"abstract":"<p><strong>Introduction: </strong>The agricultural sector heavily relies on pesticides to mitigate the impact of pest infestations. In recent years, Computer-Aided Drug Discovery (CADD) has become popular in the pharmaceutical industry for its cost and time efficiency. The proposed research uses CADD methodologies to identify lead compounds for pesticide development.</p><p><strong>Methods: </strong>This study focuses on pharmacophore properties and Chemically Advanced Template Search (CATS) descriptors to assess the similarity score against known pesticides. Similarity metrics, including the Tanimoto coefficient and Cosine similarity, were used to ensure precise molecular similarity. The Analysis of Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADME-T) properties, along with physicochemical characteristics, enhances the understanding of newly identified lead compounds. Furthermore, the Hao filter was applied to physicochemical properties to screen pesticide-like compounds. The Hao filter criteria included molecular weight (≤ 435), number of rotatable bonds (≤9), number of hydrogen bond donors (≤2), number of hydrogen bond acceptors (≤ 6), and logP (≤ 6).</p><p><strong>Results: </strong>Subsequently, from the initial pool of 120 lead compounds, 75 compounds were identified as meeting the criteria of the Hao filter, demonstrating their potential as promising pesticide candidates.</p><p><strong>Discussion: </strong>This study underscores the utility of CADD in facilitating the identification and prioritization of potential pesticide candidates.</p><p><strong>Conclusion: </strong>The findings provide insights into the integration of computational approaches in agrochemical discovery.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164855","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":"Phytochemical Composition, Pharmacological Activities, and Clinical Evidence of <i>Bacopa monnieri</i> in Cognitive and Memory Enhancement.","authors":"Bhagavathi Sundaram Sivamaruthi, Periyanaina Kesika, Karthikeyan Alagarsamy, Natarajan Sisubalan, Durairaj Ragu Varman, Natarajan Vijay, Chaiyavat Chaiyasut","doi":"10.2174/0113816128496771260919124515","DOIUrl":"https://doi.org/10.2174/0113816128496771260919124515","url":null,"abstract":"<p><p>Bacopa monnieri (B. monnieri), a traditional Ayurvedic nootropic herb, has garnered growing scientific attention for its diverse pharmacological activities and potential therapeutic relevance across neurological, metabolic, inflammatory, and oncological disorders. This review consolidates current evidence on the phytochemical composition, bioactivity, molecular mechanisms, and clinical efficacy of B. monnieri and its major bioactive constituents, particularly bacosides, bacopasides, and bacopasaponins. Preclinical investigations have demonstrated that B. monnieri exhibits antioxidant, anti-inflammatory, anti-amyloidogenic, and neuroprotective properties, mediated by modulation of cholinergic, serotonergic, glutamatergic, and GABAergic systems and by enhancement of long-term potentiation, synaptic plasticity, and dendritic arborization. Emerging in silico and systems pharmacology approaches identify multi-target interactions and modulate pathways linked to neurodegeneration, glucose metabolism, and cancer progression. Clinical trials across healthy populations, mild cognitive impairment, Alzheimer's disease, and Parkinson's disease indicate that chronic supplementation improves memory consolidation, cognitive processing, emotional well-being, and sleep architecture. Additionally, accumulating evidence supports its role in metabolic regulation, including enhanced insulin sensitivity, β-cell protection, and attenuation of diabetes-associated neurodegeneration, supported by multi-omics and network pharmacology analyses. Anticancer studies reveal synergistic effects of bacopaside derivatives in reducing tumour cell proliferation, migration, and aquaporin-mediated invasion. Collectively, the evidence positions B. monnieri as a multi-target botanical with translational promise in cognitive enhancement and as a complementary therapeutic candidate across metabolic, neurodegenerative, inflammatory, and cancer models. Future research should prioritize the development of standardized extracts, long-term safety evaluation, mechanistic validation in humans, and precision medicine stratification to optimize clinical applications.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134639","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":"Development of Selenized Phytosomes for Sustained Release of Berberine and Synergistic Hypoglycemic Effect.","authors":"Hao Kang, JInhua Wu, Duanduan Sun, Xingwang Zhang","doi":"10.2174/0113816128512130260922075457","DOIUrl":"https://doi.org/10.2174/0113816128512130260922075457","url":null,"abstract":"<p><strong>Introduction: </strong>The phytomedicine Berberine (Ber) exhibits hypoglycemic activity but suffers from poor oral efficacy. Selenium offers synergistic antidiabetic potential yet has a narrow therapeutic window. This study aimed to develop selenium‑decorated berberine phytosomes (Se@Ber‑PTs, i.e., phytosomes coated with a functional selenium layer) to enhance the combined hypoglycemic effects.</p><p><strong>Methods: </strong>Se@Ber‑PTs were prepared by covalent coupling under a heated, nitrogen‑purged atmosphere, followed by thin‑film hydration, and then in situ reduction of sodium selenite with glutathione. The engineered nano-systems were thoroughly characterized for particle size, ζ‑potential, morphology, FTIR, and in vitro release. Subsequently, hypoglycemic effects were evaluated in alloxan‑induced diabetic rats after oral administration.</p><p><strong>Results: </strong>Se@Ber-PTs exhibited uniform core-shell nanovesicles with an average size of 109 nm, a PDI of 0.07, a ζ-potential of -21.42 mV, a drug loading of 5.27 ± 0.44%, and an encapsulation efficiency of 85.36 ± 3.75%, confirming successful selenium layering. The formulation showed the most sustained drug release, achieving a 24-hour cumulative release of 26% in pH 6.8 PBS. In diabetic rats, it produced a more pronounced and prolonged reduction in blood glucose compared with raw berberine and non-selenized phytosomes.</p><p><strong>Discussion: </strong>The selenium layer acts as a physical barrier for sustained release and provides intrinsic hypoglycemic activity, synergizing with berberine. This dual mechanism addresses the short duration of action and enhances the oral hypoglycemic efficacy while harnessing the safety of nano‑selenium, supporting selenized phytosomes as a versatile oral platform for poorly absorbed phytomedicines.</p><p><strong>Conclusion: </strong>Selenization of berberine phytosomes provides a physical barrier for sustained release and introduces intrinsic hypoglycemic activity, yielding a synergistic enhancement of oral antidiabetic efficacy. These findings suggest that Se@Ber‑PTs hold promise as an effective oral formulation for diabetes management.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135413","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":"Natural Products as Anti-Angiogenic Agents: Molecular Targets, Signaling Pathways, and Mechanistic Insights.","authors":"Gajendra Singh Thakur, Sunny Rathee, Sakshi Soni, Vijay Pratap Ahirwar, Umesh K Patil","doi":"10.2174/0113816128487214260915180414","DOIUrl":"https://doi.org/10.2174/0113816128487214260915180414","url":null,"abstract":"<p><p>Angiogenesis, the process of forming new blood vessels from pre-existing vasculature, is a tightly regulated physiological process that is essential for embryonic development, wound healing, tissue regeneration, and the maintenance of normal tissue homeostasis. However, its pathological activation plays a pivotal role in tumor progression, chronic inflammation, and other angiogenesis-dependent diseases. Current antiangiogenic therapies, though clinically effective, are often limited by toxicity, resistance, and high costs. In this context, natural products have emerged as promising sources of bioactive molecules with potent antiangiogenic activity and minimal adverse effects. This review comprehensively discusses the molecular pathways underlying angiogenesis, including the regulatory roles of VEGF, FGF, HIF-1α, COX-2, NF-κB, and PI3K/Akt/mTOR cascades, and their modulation by natural compounds. Various phytoconstituents, including curcumin, resveratrol, quercetin, kaempferol, epigallocatechin gallate, withaferin A, betulinic acid, and marine- derived metabolites, exhibit anti-angiogenic activity by inhibiting endothelial cell proliferation, migration, and extracellular matrix degradation, while simultaneously downregulating key angiogenic signalling pathways. Structure-activity relationship (SAR) insights reveal that polyphenolic and terpenoid scaffolds play crucial roles in these mechanisms. The review also highlights experimental models used for anti-angiogenic evaluation and discusses clinical translation challenges related to bioavailability and formulation optimization. Overall, natural products represent a diverse and sustainable reservoir for developing next-generation antiangiogenic therapeutics, offering multi-targeted mechanisms and improved safety profiles suitable for cancer prevention and treatment.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134564","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":"ZhiXiaoSanZheng Decoction Ameliorates HGPA-induced HK-2 Cell Injury and Mitochondrial Metabolic Imbalance by Regulating the AMPK/PPARα/CPT1A Pathway.","authors":"Huixi Chen, Chenhui Xia, Yaotan Li, Weiwei Sun, Yaoxian Wang","doi":"10.2174/0113816128525206260914061658","DOIUrl":"https://doi.org/10.2174/0113816128525206260914061658","url":null,"abstract":"<p><strong>Introduction: </strong>ZhiXiaoSanZheng Decoction (ZXSZD) is a modern clinical Traditional Chinese Medicine (TCM) formula that exerts favorable clinical efficacy in the treatment of Diabetic Kidney Disease (DKD). However, its potential renal tubular protective mechanism remains unclear.</p><p><strong>Methods: </strong>Ultra-high-performance liquid chromatography-tandem mass spectrometry was employed to analyze and characterize the chemical ingredients of ZXSZD. An in vitro cell model was established by stimulating HK-2 cells with High Glucose-Palmitic Acid (HGPA) to mimic the metabolic microenvironment of DKD. Oil Red O staining was performed to assess intracellular lipid accumulation. Western blot and immunofluorescence assays were used to determine the protein expression levels of key molecules in the AMPK/ PPARα/CPT1A signaling pathway. Additionally, mitochondrial membrane potential, intracellular ATP content, activities of mitochondrial respiratory chain complexes (I and IV), oxidative stress levels, and concentrations of inflammatory cytokines were quantified.</p><p><strong>Results: </strong>A total of 141 chemical ingredients were preliminarily identified in ZXSZD. In HGPA-induced HK- 2 cells, ZXSZD significantly attenuated intracellular lipid accumulation, upregulated the protein expression of p-AMPK, PPARα, and CPT1A, ameliorated energy metabolism impairment and mitochondrial dysfunction, and suppressed oxidative stress as well as inflammatory responses.</p><p><strong>Discussion: </strong>The results indicate that ginkgolide effectively binds and stabilizes the ApoE4 N-terminal domain, supporting its potential role in modulating a key pathological factor in Alzheimer's disease. Its superior pharmacokinetic profile and interaction dynamics compared with those of curcumin and resveratrol suggest broader therapeutic relevance. These in silico insights provide a mechanistic basis for further investigation into ginkgolide's neuroprotective effects.</p><p><strong>Conclusion: </strong>ZXSZD ameliorates energy metabolism impairment and mitochondrial dysfunction in HGPAinduced HK-2 cells by activating the AMPK/PPARα/CPT1A signaling pathway, while also inhibiting oxidative stress and inflammation.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105024","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":"FZD10 and Diseases: From Molecular Mechanisms to the Potential of Targeted Therapy.","authors":"Qi Liu, Yulu Zheng, Chengfu Yuan","doi":"10.2174/0113816128505369260922104215","DOIUrl":"https://doi.org/10.2174/0113816128505369260922104215","url":null,"abstract":"<p><p>Frizzled class receptor 10 (FZD10) is a member of the Frizzled family of seven-transmembrane receptors. It mediates Wnt signaling through both canonical (β-catenin) and non-canonical (planar cell polarity and Ca²⁺) pathways, thereby regulating cell proliferation, differentiation, migration, apoptosis, and stem cell self-renewal. Dysregulation of FZD10-resulting from altered expression, aberrant promoter methylation, or functional impairment-has been linked to multiple human diseases, including cancers, metabolic and inflammatory disorders, and neurodegenerative conditions. In malignant tumors, FZD10 shows tissue-specific oncogenic activity. It is overexpressed in synovial sarcoma, colorectal cancer, gastric cancer, hepatocellular carcinoma, cervical cancer, ovarian cancer, nasopharyngeal carcinoma, non-small cell lung cancer, and renal cell carcinoma, but downregulated in esophageal squamous cell carcinoma. This restricted expression pattern makes FZD10 a potential biomarker for diagnosis and prognosis, as well as a candidate for targeted therapy. This review summarizes current knowledge on FZD10, covering its gene and protein structure, signaling mechanisms, and roles in various diseases. We also discuss its diagnostic and prognostic value in different cancers, and review recent progress in FZD10-targeted strategies, including antibodies, radioimmunotherapy, small-molecule inhibitors, drug repurposing, exosome-based delivery, and gene editing. Current limitations, such as the context-dependent functions of FZD10 and the safety issues associated with targeted agents, are also discussed. Future studies are needed to clarify the mechanistic basis of FZD10 action and to develop biomarkers for patient stratification.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134454","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}