Current Pharmaceutical Design[JOURNAL]
Sun
200 papers
Role of Phenolic Nanocompounds in Inflammatory Disorders: Current View and Future Aspects.
Gautam RK, Shen B, Kamal MA
Curr Pharm Des · 2026 Jul · PMID 42393876 · Publisher ↗
Abstract loading — click title to view on PubMed.
Overcoming Physiological Barriers in Brain Tumor Therapy: Advances in Nanomedicine, Ultramolecular Pharmaceuticals, and Targeted Drug Delivery.
Sharma S, Sharma R
Curr Pharm Des · 2026 Jun · PMID 42381326 · Publisher ↗
Targeting brain tumors remains a formidable challenge due to the presence of complex physiological barriers, notably the blood-brain barrier (BBB), the blood-brain tumor barrier (BBTB), and the nose- tobrain barrier. The...
Targeting brain tumors remains a formidable challenge due to the presence of complex physiological barriers, notably the blood-brain barrier (BBB), the blood-brain tumor barrier (BBTB), and the nose- tobrain barrier. These barriers hinder effective drug delivery, limiting therapeutic efficacy. This review provides a comprehensive analysis of the anatomical and molecular characteristics of these barriers, with particular emphasis on the heterogeneity of the BBTB and its implications for targeted drug transport. A detailed overview of various brain tumor types-including glioblastoma, pediatric brain tumors, and brain metastases-is presented alongside a critical evaluation of existing therapeutic modalities. The review highlights the advancement of ultramolecular pharmaceuticals specifically engineered to circumvent the BBTB, focusing on both transvascular and cell-mediated delivery mechanisms. The role of nanomedicine in modulating the immune response and altering the tumor microenvironment is explored as a promising avenue for enhancing therapeutic outcomes. Particular emphasis is placed on nanogels as a versatile and efficient drug delivery platform. Key fabrication techniques such as precipitation polymerization, emulsion polymerization, self-assembly, and micro-templating methods are thoroughly discussed, alongside strategies for polymer crosslinking to enhance stability and functionality. In addition, the review addresses preclinical evaluation strategies, including in vitro models (e.g., BBB-mimicking systems, tumor spheroids) and in vivo studies in animal models, to assess the safety, biodistribution, and therapeutic efficacy of nanogel-based systems. Finally, current clinical progress, challenges, and future perspectives are presented, underscoring the urgent need for innovative, targeted, and personalized drug delivery approaches. This review aims to guide future research in overcoming delivery obstacles and improving outcomes for patients with brain tumors through the strategic integration of advanced nanotechnology and molecular targeting.
Breathing Life into Research: The Transformative Potential of Lung-on-a-Chip Technology.
Shenoy J, Greeny A, Seenivasan R … +4 more , Halagali P, Rathnanand M, Manikkath J, Tippavajhala VK
Curr Pharm Des · 2026 Jun · PMID 42381325 · Publisher ↗
Lung-on-a-chip devices are an advanced microengineering tool for simulating human lung physiology in vitro. This device is designed to precisely replicate the in-vivo conditions of the lung parenchyma while ensuring dura...
Lung-on-a-chip devices are an advanced microengineering tool for simulating human lung physiology in vitro. This device is designed to precisely replicate the in-vivo conditions of the lung parenchyma while ensuring durability and ease of use. It features an innovative reversible bonding mechanism that allows precise regulation of cell concentrations on the membrane by providing convenient access to both sides of the membrane. Currently, preclinical drug development research relies on expensive, time-consuming murine testing because cell culture models cannot replicate the intricate, organ-level disease progression observed in humans. Some of the shortcomings of these two-dimensional in vitro and animal models have been addressed by the development of Lung-on-a-Chip models. It offers significant advantages over conventional approaches and has demonstrated great promise for cytotoxicity testing, disease modelling, and drug discovery. However, there are several unique, inherent, and translational challenges to rephrasing these devices from the lab to mainstream operations. This review explores the characteristics and innovative features of the Lung-on-a-chip paradigm for biomedicine, its current and future applications, and key challenges, including concerns about nonsupervisory pathways, device design, material selection, scalability, and natural realism. It also highlights other translational features of the Lung-on-a-chip to illustrate the significance of this state-of-the-art for medical research.
Cross-Tissue Transcriptome-Wide Association Study Prioritizes Candidate Genes and Compound-Associated Signatures for Osteoarthritis.
Zhang N, Hu X, Chen G … +4 more , Liu Y, Ni P, Wang Y, Zheng S
Curr Pharm Des · 2026 Jun · PMID 42381324 · Publisher ↗
INTRODUCTION: Osteoarthritis (OA) is a chronic degenerative joint disease with a high global prevalence. It is characterized by cartilage degradation, synovial inflammation, and persistent joint pain, which substantially...
INTRODUCTION: Osteoarthritis (OA) is a chronic degenerative joint disease with a high global prevalence. It is characterized by cartilage degradation, synovial inflammation, and persistent joint pain, which substantially impair quality of life. Current therapies mainly alleviate symptoms rather than prevent or reverse structural joint damage. Although numerous OA-associated loci have been identified, most reside in noncoding regions, and their downstream effector genes and regulatory mechanisms remain incompletely understood. Therefore, clarifying how these variants influence gene expression is essential for prioritizing candidate genes and improving the molecular interpretation of OA susceptibility loci. METHODS: Publicly available OA Genome-Wide Association Study (GWAS) summary statistics were integrated with Expression Quantitative Trait Locus (eQTL) data from the Genotype-Tissue Expression (GTEx) project. Cross-tissue and single-tissue transcriptome-wide association analyses were performed using UTMOST and FUSION, respectively. Candidate genes were then evaluated using COJO, MAGMA, Summary-databased Mendelian Randomization (SMR), Bayesian colocalization, and Mendelian Randomization (MR) analyses. GeneMANIA was used for network-based functional annotation, and Enrichr with the DSigDB library was used for compound-signature enrichment analysis. RESULTS: Cross-tissue TWAS identified 20 significant genes for knee OA and 12 for hip OA after FDR correction. Integration of UTMOST, FUSION, COJO, and MAGMA prioritized TACC3 and LTBP1 for knee OA and TMEM129 for hip OA. SMR, colocalization, and MR analyses provided additional but variable levels of statistical support across tissues. GeneMANIA indicated biologically relevant functional networks for LTBP1 and TACC3, whereas TMEM129 showed limited network enrichment. Enrichr/DSigDB analysis identified significant compound-signature enrichment terms overlapping the prioritized genes. DISCUSSION: These findings provide integrative statistical evidence linking OA-associated loci to gene regulation and prioritize TACC3, LTBP1, and TMEM129 as candidate genes associated with OA susceptibility. However, the strength of evidence differed across analytical frameworks, and the biological interpretation of tissue-specific signals remains to be validated in joint-relevant tissues and functional models. CONCLUSION: This study prioritized TACC3, LTBP1, and TMEM129 as candidate genes associated with OA susceptibility through integrated cross-tissue and single-tissue transcriptomic analyses. These findings improve the functional interpretation of OA GWAS loci and provide testable hypotheses for future validation in joint-relevant QTL datasets and experimental models.
Emerging Role of AI in Gastroenterology and Hepatology: Revolutionizing Medical Device-Assisted Diagnosis.
Pal R, Bhowmick M, Bhowmick P … +4 more , Bhui U, Das J, Bishayee R, Kumar B
Curr Pharm Des · 2026 Jun · PMID 42381323 · Publisher ↗
Recent advancements in AI have emerged in the diagnosis of different diseases by enhancing the analysis of various medical imaging. Similarly, the engagement of AI in gastroenterology and hepatology is changing the metho...
Recent advancements in AI have emerged in the diagnosis of different diseases by enhancing the analysis of various medical imaging. Similarly, the engagement of AI in gastroenterology and hepatology is changing the methods of diagnosis and developing new computational methodology for more specific and targeted analysis of different medical devices. AI applies new algorithm-based approaches such as machine learning, deep learning, and language processing for the histopathological assessment, endoscopic imaging, and radiological assessment. New endoscopic imaging techniques are more specific for the detection of polyp rates, thus increasing targeted screening of colorectal cancer. Another approach, like AI-enabled imaging techniques, makes it possible for the early detection and targeted staging of hepatic disorders such as nonalcoholic fatty liver disease (NAFLD), cirrhosis, and hepatocellular carcinoma (HCC). In histopathological assessment, AI automated the high-throughput detection of malignancies in cells. The review paper enlightened on the application of AI in characterization, prognostication, and detection of GI and Hepatobiliary disorders. The engagement of AI enhances the diagnostic efficacy, reduces the chances of human error, and enlightens the therapeutic intervention. However, the AI-based techniques are limited in performance and have not reached the mark in regulatory constraints. Future developments should emphasize cross-platform interoperability, algorithmic improvement, and clinician education to optimize AI's therapeutic use in hepatology and gastroenterology.
Nanostructured Lipid Carriers in Drug Targeting: Characterization, Patents, and Recent Innovations.
Alam R, Nehal N, Unnithan D … +7 more , Chauhan APS, Singh H, Pushadapu VVSK, Parveen R, Vohora D, Khan S, Ali J
Curr Pharm Des · 2026 Jun · PMID 42381322 · Publisher ↗
The second-generation lipid-based nanocarrier system, nanostructured lipid carriers (NLCs), has received much attention due to their distinct properties that enable them to address the various limitations that afflict bo...
The second-generation lipid-based nanocarrier system, nanostructured lipid carriers (NLCs), has received much attention due to their distinct properties that enable them to address the various limitations that afflict both solid lipid nanoparticles and the conventional delivery system. The special structure (solid lipids/liquid lipids blend) of NLCs provides a better encapsulation, stability, controlled release, and biocompatibility of drugs, therefore, leading to the effective transportation of hydrophilic and lipophilic drugs. This review briefly examines the design methods, formulation strategies, and other more sophisticated characterization methods, such as traditional characterization (e.g., dynamic light scattering (DLS) and X-ray diffraction) and new methods (e.g., cryo-EM and small-angle X-ray scattering (SAXS) that provide an effect on particle size, lipid crystallinity, and release kinetics. The review notes Process Analytical Technology (PAT) and its ability to aid the real-time monitoring and scale-up production of NLC products. Recent dosage forms that have been used as therapeutic agents that involve the use of NLCs are critically discussed, such as the following routes of administration: oral, transdermal, nasal, ocular, pulmonary, and targeted delivery. Moreover, we will review how NLCs can serve to improve bioavailability, enhance patient compliance, and provide sitespecific action of drug delivery. A recent analysis of patents is reviewed to identify where innovative space is being created regarding surface functionalization, hybrid systems, and combinatorial therapies, as well as the challenges faced, such as regulatory implications and translational opportunities. This work provides a summary of the formulation science, characterization methods, and patent data to offer an overview of the current state and prospective future work of NLCs with respect to drug targeting, delivery, and the nanomedicine field.
Corrigendum to: miRNA in Diagnosis and Therapeutics of Tuberculosis: Importance in Latent and Brain Associated Pathologies.
Gupta P, Kumar R, Niranjan R
Curr Pharm Des · 2026 · PMID 42338153 · Publisher ↗
The publisher identified, after publication of this article [1], that the publication year was incorrectly printed as 2024 instead of 2025. This error has now been corrected. The original article can be found online at:...
The publisher identified, after publication of this article [1], that the publication year was incorrectly printed as 2024 instead of 2025. This error has now been corrected. The original article can be found online at: https://www.eurekaselect.com/article/149361 We regret the error and apologize to readers. Details of the correction: Original Received Dates: October 24, 2024 Accepted: March 21, 2024 Corrected ; Received Dates: October 24, 2025 Accepted: March 21, 2025.
Combining Network Pharmacology, Machine Learning, Molecular Docking, and Experimental Validation to Explore the Mechanism of Danggui-Shaoyao-San in treating Rheumatoid arthritis.
Xu R, Liu Y, Guo Y … +4 more , Xu Q, Liu D, Li X, Li N
Curr Pharm Des · 2026 Jun · PMID 42337901 · Publisher ↗
BACKGROUND: Danggui-Shaoyao-San (DSS) demonstrates clinical efficacy in rheumatoid arthritis (RA), but its bioactive constituents and molecular mechanisms remain insufficiently characterized. PURPOSE: To elucidate the sy...
BACKGROUND: Danggui-Shaoyao-San (DSS) demonstrates clinical efficacy in rheumatoid arthritis (RA), but its bioactive constituents and molecular mechanisms remain insufficiently characterized. PURPOSE: To elucidate the synergistic mechanisms of DSS in treating RA by integrating network pharmacology, machine learning, molecular docking, and dynamics simulations to identify core bioactive compounds and targets, followed by experimental validation of therapeutic efficacy. METHODS: Active compounds and targets of DSS were retrieved from TCMSP and UniProt databases, supplemented by SwissTargetPrediction and TCMIP. In GeneCards, DrugBank, and OMIM, RA-related genes were curated. Cytoscape 3.10. 3 and STRING were used to create compound-target and protein-protein interaction (PPI) networks. The prioritization of core targets was done using topological analysis and tested by molecular docking and molecular dynamics simulations. The in vivo impact of DSS was tested on the CIA model. HE staining measured synovitis, cartilage erosion, and bone erosion. ELISA was used to measure serum levels of TNF-α, IL-1β, IL-6, IL-8, MMP-1, and MMP-3. RESULTS: We identified 45 bioactive compounds in DSS at work with 913 possible targets. Bioinformatics analysis showed that there were 2,484 targets that are RA-integrated, with 410 overlapping targets. TP53 and SRC came up as regulatory nodes. The results of molecular docking showed high affinity of binding between TP53/SRC and four major DSS compounds: alisol C, myricanone, mandenol, and kaempferol. Complex stability was confirmed by molecular dynamics simulations. DSS in the animal category made a significant reduction in the severity scores of arthritis, as well as reducing the paw swelling, as opposed to their counterparts in the model group. The histopathology proved that there was attenuated inflammation in the synovium and cartilage matrix conservation. The activity of pro-inflammatory mediators in serum was suppressed greatly. DISCUSSION: The research has shown that a combination of computational-experimental approach can help to unravel the polypharmacology of a complicated traditional formula. The extension of our discoveries on the synergies of DSS core compounds selects active targets and states that the compounds have roles in common pathways of oncogenesis and metabolism. The paper offers a strong mechanistic background of clinical application of DSS and sets a template to modernize the old medicines. CONCLUSION: DSS exerts anti-RA effects through synergistic interactions of alisol C, myricanone, kaempferol, and mandenol with core targets, modulating oncogenic, metabolic, and inflammatory pathways. This integrative strategy deciphers DSS's polypharmacology and provides a mechanistic foundation for clinical application.
Clinical Utilization of Beers Criteria and STOPP-START Algorithm in Elderly Patients: Emphasis on Neuropsychiatric Medications.
Akman C, Erdem AB, Ersan E … +5 more , Erdem B, Ünaldi M, Ucar AB, Han Bozatli SB, Karcıoglu O
Curr Pharm Des · 2026 Jun · PMID 42333555 · Publisher ↗
Polypharmacy (the chronic concurrent use of five or more pharmaceutical agents) is independently associated with Adverse Drug Events (ADEs), functional decline, and mortality in older adults. Age-related physiological ch...
Polypharmacy (the chronic concurrent use of five or more pharmaceutical agents) is independently associated with Adverse Drug Events (ADEs), functional decline, and mortality in older adults. Age-related physiological changes - including impaired renal and hepatic clearance, increased volume of drug distribution, and heightened pharmacodynamic sensitivity - substantially amplify the risk of medication-related harm in geriatric populations. The likelihood of developing an ADE increases proportionally with the number of drugs prescribed, irrespective of patient age or comorbidity burden, and parallels rates of hospitalization and functional deterioration. Neuropsychiatric medications-including benzodiazepines, antipsychotics, antidepressants, and mood stabilizers-are disproportionately implicated in falls, delirium, cognitive impairment, cerebrovascular events, and excess mortality. Measures to improve clinician awareness of rational neuropsychiatric prescribing across primary, specialist, and acute care settings are therefore a priority in geriatric medicine. Various explicit prescribing tools have been developed to identify Potentially Inappropriate Prescribing (PIP). Among these, the American Geriatrics Society Beers Criteria and the European STOPP-START algorithm are the most widely validated and adopted. This review provides a structured, evidence-based analysis of these tools, with emphasis on polypharmacy burden, PIP epidemiology, deprescribing frameworks, multidisciplinary decision-making, and the specific mechanistic and clinical risks associated with geriatric neuropsychiatric medications.
Halofantrine Upregulates ATP6V0D2 and Induces Cytotoxic Autophagy in GBM Models.
Huang N, Tang K, Liu GQ … +3 more , Zhong ML, Deng JG, Chen W
Curr Pharm Des · 2026 Jun · PMID 42333554 · Publisher ↗
BACKGROUND: Halofantrine (halo) is an antimalarial drug that has recently been proven to have the potential to treat Glioblastoma (GBM). OBJECTIVE: The aim of the study is to explore the inhibitory effect of halos on GBM...
BACKGROUND: Halofantrine (halo) is an antimalarial drug that has recently been proven to have the potential to treat Glioblastoma (GBM). OBJECTIVE: The aim of the study is to explore the inhibitory effect of halos on GBM and its mechanism. METHODS: The expression of ATP6V0D2 in GBM was analyzed using the Cancer Genome Atlas (TCGA), the comprehensive database of gene expression, and clinical patient samples. In vitro, we evaluated the inhibitory effect of halo on U251 cells; qPCR, Western blot, and immunofluorescence were used to detect the changes in ATP6V0D2 and autophagy-related genes and proteins. Transmission electron microscopy was used to detect the formation of autophagosomes. A stable ATP6V0D2 knockdown and overexpression model was constructed in U251 cells to verify the criticality of ATP6V0D2. The in vivo anti-tumor effect and mechanism of halo were evaluated using a U251 cell axillary tumor-bearing mouse model (independent experiment repeat number (n = 5) and tail vein administration injection. RESULTS: The expression level of ATP6V0D2 is relatively low in GBM patients. Halo upregulates ATP6V0D2 and induces cytotoxic autophagy (TA) in U251. Knockdown of ATP6V0D2 can inhibit halo-mediated TA and cytotoxicity, while overexpression can enhance these effects. Halo also demonstrated significant anti-GBM activity in vivo, and its mechanism was consistent with the results of in vitro studies. DISCUSSION: This study has preliminarily demonstrated that the anti-malarial drug halo can promote autophagy in GBM cells by upregulating the ATP6V0D2 gene, thereby exerting an anti-GBM effect. So far, no experimental studies have been conducted on the permeability of the blood-brain barrier within the halo body. Furthermore, the potential cardiac toxicity of halo is a point that deserves particular attention. CONCLUSION: Halo triggers cytotoxic autophagy in U251 cells by upregulating ATP6V0D2, establishing the key tumor suppressor factor status of ATP6V0D2 in GBM.
Multi-Component Synergy in Hepatic Trauma Repair: Network Pharmacology and Molecular Docking Decipher Panax Notoginseng's PI3K-Akt Pathway Activation.
Zhao Y, Liu B, Zhang C … +7 more , Ren K, Wang H, Li Y, Chen Z, Feng J, Zhang G, Gao R
Curr Pharm Des · 2026 Jun · PMID 42333553 · Publisher ↗
BACKGROUND: A rising trend in the incidence of hepatic trauma has been noted annually over recent years. Panax Notoginseng (PN) is renowned for its hemostatic and wound-healing properties, but its multicomponent mechanis...
BACKGROUND: A rising trend in the incidence of hepatic trauma has been noted annually over recent years. Panax Notoginseng (PN) is renowned for its hemostatic and wound-healing properties, but its multicomponent mechanism against hepatic trauma remains unclear. OBJECTIVE: This study aimed to decipher the multi-component, multi-target mechanisms of PN in treating hepatic trauma by integrating network pharmacology, molecular docking, and in vivo experimental validation. METHODS: The bioactive constituents of PN and their corresponding protein targets were acquired from the TCMSP database. Hepatic trauma-associated genes were sourced from the GeneCards and OMIM databases. A comprehensive drug-component-target network and a protein-protein interaction (PPI) network were constructed to identify core compounds and hub targets. Functional enrichment analyses (GO and KEGG) were performed to delineate involved biological processes and signaling pathways. Molecular docking and Molecular Dynamics Simulations assessed the binding affinities between pivotal components and targets. Finally, the anti-inflammatory effect of PN was experimentally verified in a rat model of mechanical hepatic trauma. RESULTS: Our analysis identified seven primary bioactive compounds in PN. Among these, quercetin, β-sitosterol, and stigmasterol were discerned as the most influential based on network topology. PPI network analysis revealed AKT1, IL-6, and TNF as central hub targets. Enrichment analysis implicated several key pathways, most notably the PI3K-Akt, TNF, and IL-17 signaling pathways. Molecular docking and Molecular Dynamics Simulations confirmed stable binding conformations between the top compounds and the core targets, with favorable binding energies. Crucially, in vivo experimentation on mechanical hepatic trauma demonstrated that PN administration significantly suppressed the mRNA expression levels of pivotal proinflammatory cytokines (TNF-α, IL-6, and IL-1β) in injured liver tissue, thereby providing direct experimental corroboration for our computational predictions. DISCUSSION: This study fills the critical gap in understanding the multi-component mechanism of PN against hepatic trauma, which remains unclear despite its long-standing clinical use for hemostasis and wound healing. Unlike previous research focusing on single saponin components, our work reveals the synergistic hepato- protective effects of PN's core bioactive compounds via coordinated modulation of inflammatory cascades and pro-survival signaling pathways. Our integrated in silico and in vivo validation provides robust mechanistic support for PN's clinical repurposing and offers promising leads for developing novel adjuvant therapies for hepatic trauma. CONCLUSION: This study reveals that PN alleviates hepatic trauma through a multi-component synergy mechanism, primarily by targeting the PI3K-Akt pathway and inhibiting inflammation. Our findings provide a solid foundation for its future experimental confirmation and clinical application.
Network Pharmacology Analysis and Animal Experiment Validation of Penthorum chinense Pursh in Treating Cholestatic Liver Disease.
Li X, Feng Y, Wu C … +4 more , Ouyang M, Hu X, Zhang Z, Dong X
Curr Pharm Des · 2026 Jun · PMID 42312511 · Publisher ↗
INTRODUCTION: Cholestatic Liver Disease (CLD) remains a major clinical challenge because currently available therapies show limited efficacy in current therapies in a subset of patients. Penthorum chinense Pursh. (PCP),...
INTRODUCTION: Cholestatic Liver Disease (CLD) remains a major clinical challenge because currently available therapies show limited efficacy in current therapies in a subset of patients. Penthorum chinense Pursh. (PCP), A traditional Miao ethnomedicine has reported hepatoprotective activity; however, its bioactive constituents and mechanisms in CLD remain unexplored. METHODS: An integrated strategy combining network pharmacology, molecular docking, 100 ns Molecular Dynamics (MD) simulations, and in vivo validation was applied. Active compounds and targets of PCP were identified through literature mining and database screening. Binding propensities between selected compounds and core targets were evaluated by molecular docking and MD. A mouse model of CLD induced by 0.1% 3,5-Diethoxycarbonyl-1,4-dihydrocollidine (DDC) was used for multi-dimensional validation through serum biochemistry, histopathology, proteomics, and protein expression analyses. RESULTS: A total of 32 bioactive compounds of PCP and 74 overlapping CLD-associated targets were identified. On the basis of the results of the protein-protein interaction and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, five potential active flavonoid components (kaempferol, luteolin, pinocembrin-7-O- β-D-glucoside (PCBG), pinocembrin chalcone, and quercetin) and core targets were selected to explore the mechanism of PCP in CLD. The molecular docking results indicated that there were good interactions between serine/threonine kinase proteins (AKT) and all five flavonoids, and PCBG showed potent or strong binding activity with Peroxisome Proliferator-Activated Receptor Gamma (PPARG), matrix metalloproteinase 9 (MMP9), interleukin-6 (IL6), Hypoxia-Inducible Factor 1 alpha (HIF), apoptosis regulator Bcl-2 (BCL2), and AKT1. In DDC-fed mice, PCP significantly improved biochemical and histopathological indices of cholestatic injury, altered proteomic signatures related to cellular processes/signaling and metabolism, and significantly decreased the phosphorylation levels of phosphatidylinositol 3-kinase (PI3K), AKT, and mammalian Target Of Rapamycin (mTOR). DISCUSSION: Integrating computational analyses with experimental validation suggests that PCP may exert anti-cholestatic effects primarily via flavonoid constituents (notably PCBG) through suppression of the PI3K/ AKT pathway. These findings suggest that PCP represents a promising novel treatment strategy for CLD. Further clinical studies are warranted to evaluate the efficacy of PCP-derived compounds, especially PCBG, in patients with this disease. CONCLUSION: This study integrates network pharmacology with experimental validation to implicate the PI3K/ AKT signaling as a key pathway targeted by PCP in CLD, providing a scientific basis for the clinical application of Gansukeli in CLD.
Polyphenols in Cancer Therapy: Recent Advances, Mechanistic Pathways, and Therapeutic Insights.
Mehra A, Mittal A
Curr Pharm Des · 2026 Jun · PMID 42312510 · Publisher ↗
Polyphenols are naturally occurring compounds characterized by multiple hydroxyl groups attached to aromatic rings. They are broadly classified into four major groups: flavonoids, phenolic acids, lignans, and stilbenes....
Polyphenols are naturally occurring compounds characterized by multiple hydroxyl groups attached to aromatic rings. They are broadly classified into four major groups: flavonoids, phenolic acids, lignans, and stilbenes. They act through a number of multiple signalling pathways, including MAPK, PI3K/ Akt, NF-κB, and STAT3 pathways, which induce apoptosis and programmed cancer cell death, which is frequently linked to the development of cancer. Additionally, polyphenols have synergistic effects with chemotherapeutic medications, which makes them attractive options for individual and combination therapy. This review includes studies published between 2019 and 2025 on polyphenols with anti-cancer potential in both in vitro and in vivo analysis. This review integrates recent evidence with a mechanism-based mapping of polyphenol classes to specific anticancer signaling pathways, offering an updated and clinically relevant perspective rarely captured in earlier reviews.
Glycycoumarin Induces G2/M Cell Cycle Arrest and Apoptosis in Non-Small-Cell Lung Cancer Cells via Suppressing the PI3K/AKT/mTOR/HIF-1α Pathway.
Guo Y, Wu X, Liang P … +4 more , Li X, Zhou W, Wu Z, Ye L
Curr Pharm Des · 2026 Jun · PMID 42312509 · Publisher ↗
INTRODUCTION: Current therapies for Non-Small Cell Lung Cancer (NSCLC) are frequently compromised by drug resistance and adverse effects. Glycycoumarin (GCM), a natural coumarin derived from licorice, has been shown to e...
INTRODUCTION: Current therapies for Non-Small Cell Lung Cancer (NSCLC) are frequently compromised by drug resistance and adverse effects. Glycycoumarin (GCM), a natural coumarin derived from licorice, has been shown to exhibit anticancer properties. Nevertheless, its mechanisms of action against NSCLC remain ambiguous. This study aimed to investigate the antitumor effects of GCM on NSCLC and clarify the underlying molecular mechanism through an integrative approach. METHODS: The bioactivity of GCM on NSCLC cells was assessed using crystal violet staining, colony formation, migration, and invasion assays, as well as flow cytometry. In vivo efficacy was evaluated utilizing xenograft tumor models. Network pharmacology, molecular docking, and dynamic simulation were employed for mechanistic prediction, followed by experimental validation through Western blot and RT-qPCR. RESULTS: GCM induced G2/M phase arrest, apoptosis, and a significant inhibition of A549 cell proliferation. Subsequent in vivo investigations demonstrated that GCM administration suppressed the growth of transplanted tumors in the A549 xenograft model. Network pharmacology analysis revealed that PI3K/AKT and HIF-1 signaling were important mediators, with AKT1, mTOR, PIK3CA, Bcl2, and HIF-1α among the core targets. The stable binding of GCM to these targets was predicted using molecular docking and dynamics. Experimental validation showed that GCM inhibited the progression of NSCLC by controlling the expression of the PI3K/AKT/mTOR/HIF-1α pathway. DISCUSSION: This is the first study to demonstrate the anticancer efficacy of GCM in NSCLC. GCM appears to act on multiple targets within the PI3K/AKT/mTOR/HIF-1α axis, which may offer advantages in overcoming therapeutic resistance. The multi-target mechanism of action, combined with its safety profile, supports GCM as a potential agent for further preclinical evaluation in NSCLC. CONCLUSION: GCM impedes NSCLC progression by inducing cell cycle arrest and apoptosis, potentially via the suppression of the PI3K/AKT/mTOR/HIF-1α signaling axis.
Atorvastatin Enhances Doxorubicin Efficacy in Breast Cancer Through Convergent Disruption of Drug Efflux, Heat-Shock Response, and DNA Hypermethylation.
Khafagy SZ, El-Baz HA, Elshal MF
Curr Pharm Des · 2026 Jun · PMID 42312508 · Publisher ↗
INTRODUCTION: Drug resistance limits the efficacy of anthracycline-based chemotherapy in breast cancer. This study investigated whether atorvastatin (ATR) enhances doxorubicin (DOX) activity by coordinating the disruptio...
INTRODUCTION: Drug resistance limits the efficacy of anthracycline-based chemotherapy in breast cancer. This study investigated whether atorvastatin (ATR) enhances doxorubicin (DOX) activity by coordinating the disruption of multiple resistance pathways in MCF-7 cells. METHODS: Cytotoxicity and drug interaction were quantified by MTT assay and Chou-Talalay analysis, respectively. Modulation of the cell death processes was assessed at the molecular level by evaluating Bcl-2 and Bax expression with qRT-PCR, while at the protein level, apoptosis was analyzed by Annexin V assay using flow cytometry. Global DNA methylation patterns were determined using 5-methylcytosine (5-mC)-targeted ELISA. Molecular docking simulations characterized ATR's binding interactions with P-glycoprotein (P-gp) and Heat Shock Factor-1 (HSF-1). RESULTS: ATR and DOX produced consistent synergism (CI < 1) with a favorable dose-reduction index (DRI > 1) for DOX. The ATR-DOX combination also markedly shifted the Bcl-2/Bax balance toward apoptosis and increased apoptotic cells from 13.5% to 62% (~4.6-fold). The combination suppressed DOX-induced upregulation of HSP90 and HSP60 and significantly mitigated global DNA hypermethylation. In silico docking predicted favorable binding of ATR to P-glycoprotein (-10.24 kcal/mol) and Heat Shock Factor-1 DNA-binding domain (-6.69 kcal/mol), supporting potential modulation of drug efflux and stress-response pathways. DISCUSSION: Collectively, atorvastatin enhances DOX cytotoxicity through integrated effects on efflux regulation, proteostasis, epigenetic regulation, and apoptotic priming. CONCLUSION: Given its established clinical safety, atorvastatin represents a practical candidate for repurposing to improve anthracycline-based breast cancer therapy.
Curcumin in Acne Management: A Narrative Review of Mechanisms and Efficacy.
Chen Y, Zhang X, Zeng R
Curr Pharm Des · 2026 Jun · PMID 42304909 · Publisher ↗
INTRODUCTION: Acne vulgaris is a prevalent dermatological condition characterized by the involvement of Cutibacterium acnes, inflammation, and follicular hyperkeratinization, among other factors. Curcumin, a polyphenolic...
INTRODUCTION: Acne vulgaris is a prevalent dermatological condition characterized by the involvement of Cutibacterium acnes, inflammation, and follicular hyperkeratinization, among other factors. Curcumin, a polyphenolic compound derived from turmeric, exhibits multifaceted anti-inflammatory and antibacterial properties. This review aims to elucidate its mechanisms of action, evaluate preclinical and clinical evidence, explore formulation strategies, and identify research gaps. METHODS: A comprehensive literature search was performed in the PubMed database, covering the period from its inception to March 2026. The search strategy incorporated a combination of keywords and Medical Subject Headings (MeSH) terms pertinent to curcumin (e.g., "curcumin," "turmeric"), acne (e.g., "acne vulgaris," "Cutibacterium acnes"), and related mechanisms and applications (e.g., "anti-inflammatory," "drug delivery systems"). The inclusion criteria encompassed original research articles, clinical trials, and systematic reviews published in peer-reviewed journals with full-text availability in English. RESULTS: Curcumin demonstrates multi-target anti-inflammatory properties by inhibiting critical pathways involved in the pathogenesis of acne and exhibits significant antibacterial activity against Cutibacterium acnes. Its efficacy is notably enhanced when utilized in conjunction with innovative delivery systems. Preclinical studies have validated its favorable safety profile, while clinical trials have indicated preliminary efficacy. CONCLUSION: Curcumin demonstrates the ability to concurrently target multiple pathogenic pathways in acne. Emerging delivery systems appear promising for addressing bioavailability challenges, and their favorable safety profile positions curcumin as a promising adjunctive treatment for acne vulgaris. Future research should prioritize conducting large-scale, randomized controlled trials with extended follow-up durations, standardized formulations, and comprehensive pharmacokinetic evaluations to establish dose-response relationships, thereby facilitating clinical translation.
Wound Healing with Nature: A Systematic Review on Recent Advances and Smart Integration in Herbal-Based Polymeric Films for Wound Healing.
Omsatyam, Singh SR, Singh LP … +1 more , Kumar D
Curr Pharm Des · 2026 Apr · PMID 42299005 · Publisher ↗
INTRODUCTION: Chronic and acute wounds remain a significant burden in clinical settings, frequently complicated by infection, delayed healing, and poor patient adherence. Traditional dressings primarily act as protective...
INTRODUCTION: Chronic and acute wounds remain a significant burden in clinical settings, frequently complicated by infection, delayed healing, and poor patient adherence. Traditional dressings primarily act as protective barriers and provide minimal active support to the wound environment. In recent years, herbal- based polymeric films have gained attention as innovative dressings that combine the therapeutic benefits of plant-derived compounds with advances in biomaterial design. METHODS: A systematic review was carried out in accordance with PRISMA 2020 guidelines using PubMed, Scopus, Web of Science, and Science Direct. Relevant studies on herbal-loaded polymeric films for wound healing were selected based on predefined criteria, and findings were qualitatively analyzed due to variations in study design and materials. RESULTS: A total of 101 studies met the inclusion criteria. Overall, herbal-based polymeric films showed encouraging outcomes, with reported wound closure rates of 75-95% within 14 days. Improvements included better collagen formation, faster epithelialization, and antimicrobial activity with inhibition zones ranging from 15-25 mm against common pathogens. Advanced platforms such as electrospun nanofibers, 3D-printed scaffolds, and stimuli-responsive systems demonstrated controlled drug release and enhanced tissue repair. DISCUSSION: The combined effect of polymers and herbal bioactives appears to strengthen antimicrobial action, regulate inflammation, and promote tissue regeneration. However, concerns regarding standardization, formulation stability, regulatory pathways, and limited clinical trials remain important challenges. CONCLUSION: Herbal-based polymeric films offer a promising and sustainable approach to modern wound management, though further refinement and clinical validation are necessary for routine clinical adoption.
Cholangiocarcinoma in the Era of Precision Medicine: Emerging Insights and Therapeutic Strategies.
Agarwal A, Rashid S, James L … +1 more , Mattei J
Curr Pharm Des · 2026 Apr · PMID 42299004 · Publisher ↗
INTRODUCTION/OBJECTIVE: Cholangiocarcinoma is an aggressive malignancy of the biliary tract, with increasing global incidence and poor prognosis due to frequent late-stage diagnosis and nonspecific symptoms. It encompass...
INTRODUCTION/OBJECTIVE: Cholangiocarcinoma is an aggressive malignancy of the biliary tract, with increasing global incidence and poor prognosis due to frequent late-stage diagnosis and nonspecific symptoms. It encompasses intrahepatic, perihilar, and distal subtypes, each with distinct clinical characteristics. This review outlines current and emerging therapeutic strategies for the treatment of resectable and advanced cholangiocarcinoma, with a focus on adjuvant therapies, systemic chemotherapy, immunotherapy, and targeted molecular approaches. METHODS: A comprehensive literature search was conducted across major medical databases. Relevant randomized controlled trials, meta-analyses, clinical guidelines, and high-quality observational studies were reviewed. Emphasis was placed on recent evidence and emerging treatment modalities with clinical significance. RESULTS: Capecitabine remains the standard adjuvant chemotherapy regimen following resection, although optimal regimens are currently under investigation. Gemcitabine-cisplatin is the first-line chemotherapy regimen for advanced disease. Immunotherapy has shown benefit, especially in patients with microsatellite instability. Promising advances lie in targeted therapies, including fibroblast growth factor receptor inhibitors and isocitrate dehydrogenase 1 inhibitors, which have demonstrated improved outcomes in molecularly selected patients. DISCUSSION: The treatment landscape of cholangiocarcinoma continues to evolve. While chemotherapy remains foundational, increasing molecular characterization may offer improved disease control in selected subgroups. CONCLUSION: Advances in molecular profiling and immunotherapy are reshaping the management of cholangiocarcinoma, enabling more personalized treatment strategies. Continued integration of precision oncology into clinical practice and prospective trials will be critical to improving outcomes for cholangiocarcinoma moving forward.
Receptor for Advanced Glycation End Products (RAGE) Ligand Axis as a Mediator of Inflammation and Oxidative Stress in Cancer: Implications for Cancer Progression and Therapeutic Targeting.
Mondal S, Chakraborty P, Ghatak S … +2 more , Gautam MK, Mukherjee TK
Curr Pharm Des · 2026 Jun · PMID 42283171 · Publisher ↗
The Receptor for Advanced Glycation End Products (RAGEs) is a cell surface immunoglobulin class of molecules. RAGE is also recognized as a Pattern Recognition Receptor (PRR), which influences innate immune responses. RAG...
The Receptor for Advanced Glycation End Products (RAGEs) is a cell surface immunoglobulin class of molecules. RAGE is also recognized as a Pattern Recognition Receptor (PRR), which influences innate immune responses. RAGE also influences adaptive immune responses. The promoter of the RAGE gene can bind to proinflammatory transcription factors such as NF-κB, which activate RAGE transcription and subsequent expression. Once expressed, RAGE interacts with seemingly unrelated ligands, such as AGE, HMGB1, S100, and others, and the RAGE-ligand(s) axis triggers inflammation and oxidative stress and sustains a vicious cycle of self-propagation. Exposure to inflammatory and oxidative stress responses is a hallmark of complications in different cancers, including their proliferation, survival, angiogenesis, invasion, metastasis, and apoptosis. In the tumor immune microenvironment, the RAGE-ligand(s) axis inhibits antitumor immunity by activating Myeloid-Derived Suppressor Cells (MDSCs) and Tumor-Associated Macrophages (TAMs/M2 macrophages) and by suppressing tumor suppressor proteins such as p53 and PTEN. Paradoxically, under normal physiological conditions, high RAGE expression in lung tissues protects this organ from cancer initiation. Multiple factors, including the diverse functions of RAGE splice variants, may influence lung-specific RAGE expression and activity. This comprehensive review illustrates the various mechanisms through which the RAGE-ligand(s) axis promotes the development of multiple cancers, including lung cancer, highlighting the role of inflammation generated by RAGE-ligand(s) interactions in the progression of different cancers. In addition, the therapeutic relevance of targeting the RAGE-ligand axis and highlights emerging strategies to modulate pathological RAGE signaling in cancer is discussed.
Kunxian Capsule Exerts Antitumor Effects by Activating the IL-17 Signaling Pathway to Inhibit the Proliferation, Apoptosis, Cell Cycle, and Induce Reactive Oxygen Species Production in C8166 Tumor Cells.
Wang XD, Ma XN, Fang CS … +5 more , Qin RA, He FL, Lin YB, Xu Q, Li N
Curr Pharm Des · 2026 Jun · PMID 42283170 · Publisher ↗
INTRODUCTION: Kunxian capsule (KXJN), a patented traditional Chinese medicine used for autoimmune diseases, remains unexplored in oncology. This study investigated its potential antitumor effects against adult T-cell leu...
INTRODUCTION: Kunxian capsule (KXJN), a patented traditional Chinese medicine used for autoimmune diseases, remains unexplored in oncology. This study investigated its potential antitumor effects against adult T-cell leukemia/lymphoma (A-ATL). METHODS: Network pharmacology identified KXJN-related targets from TCMSP and UniProt, and A-ATLassociated DEGs from GEO. Candidate targets and pathways were analyzed via Microbiotics and String. In vitro validation used C8166 cells, assessing proliferation (MTT assay), apoptosis, cell cycle, ROS production (flow cytometry), and protein/mRNA expression (Western blot, RT-qPCR). RESULTS: A total of 106 potential targets of KXJN were identified against A-ATL, with core nodes (JUN, IL-6, TNF) linked to the IL-17 pathway and other pathways. KXJN dose- and time-dependently inhibited C8166 proliferation, promoted apoptosis, and increased ROS. It activated the IL-17 pathway, upregulating associated proteins (ACT1, IL-17RA, TRAF6), core targets (JUN, IL-6, TNF), and cytokines (CXCL1, CXCL2, CCL20). DISCUSSION: KXJN exerts antitumor effects on C8166 cells by suppressing proliferation, inducing apoptosis and ROS, activating IL-17 signaling, and modulating cell cycle progression. CONCLUSION: These findings highlight KXJN's potential in tumor therapy, though further in vitro and in vivo studies are required to elucidate its precise mechanisms.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe