Curr. Pharm. Des. [JOURNAL]
Sun
200 papers
Emerging Trends in Targeted Molecular Therapies for Inflammatory Bowel Disease: Biologics and Small Molecules.
Borra PK, Chandra P, Raghav A … +3 more , Koneru A, Sachan N, Gautam MK
Curr Pharm Des · 2026 Jun · PMID 42283169 · Publisher ↗
INTRODUCTION: Crohn's Disease (CD) and Ulcerative Colitis (UC) are chronic Inflammatory Bowel Diseases (IBD) characterized by complex immune dysregulation and multifactorial pathogenesis. Conventional therapies often sho...
INTRODUCTION: Crohn's Disease (CD) and Ulcerative Colitis (UC) are chronic Inflammatory Bowel Diseases (IBD) characterized by complex immune dysregulation and multifactorial pathogenesis. Conventional therapies often show limited efficacy and are associated with substantial adverse effects. This review highlights recent advancements in targeted molecular therapies for IBD, emphasizing biologics, small molecules, and emerging delivery technologies. METHODS: A comprehensive literature search was conducted across the PubMed, Scopus, and Web of Science databases, focusing on studies published within the last 7 years. Relevant data on therapeutic mechanisms, clinical efficacy, safety, and cost-effectiveness were systematically extracted and critically analyzed. RESULTS: Biologic therapies, including anti-TNF agents (infliximab, adalimumab), integrin inhibitors (vedolizumab), and interleukin inhibitors (ustekinumab, risankizumab), have demonstrated significant improvements in remission and mucosal healing. However, challenges such as immunogenicity, loss of response, and high treatment costs persist. Small-molecule drugs, such as JAK inhibitors (tofacitinib, upadacitinib) and S1P receptor modulators (ozanimod), provide oral alternatives with rapid onset but entail systemic safety concerns. DISCUSSION: Novel therapeutic avenues, including TYK2 and HDAC inhibitors, as well as nanotechnology-based delivery systems, show encouraging potential in early trials. Accessibility and affordability remain major obstacles, particularly in low- and middle-income regions, highlighting the need for biosimilars and international policy support. CONCLUSION: Targeted molecular therapies have revolutionized IBD management by enabling precision treatment with enhanced efficacy and tolerability. Future efforts should focus on mitigating drug resistance, reducing costs, and integrating personalized medicine approaches to ensure global accessibility and sustainable disease control.
Integrating Network Pharmacology and Molecular Docking to Investigate the Action Mechanism of Poria Almond and Liquorice Decoction in Chronic Heart Failure: A Computational Prediction Study.
Chen Z, Xiao X, Zhao Y … +8 more , Li Y, Wang C, Zhao H, He B, Bai H, Zhao R, Zhang G, Feng J
Curr Pharm Des · 2026 Jun · PMID 42261165 · Publisher ↗
INTRODUCTION: Chronic heart failure (CHF) represents the end-stage progression of cardiac diseases, and its prognosis remains suboptimal. Poria Almond and Liquorice decoction(PALD), a traditional Chinese herbal formula,...
INTRODUCTION: Chronic heart failure (CHF) represents the end-stage progression of cardiac diseases, and its prognosis remains suboptimal. Poria Almond and Liquorice decoction(PALD), a traditional Chinese herbal formula, has demonstrated therapeutic efficacy in cardiovascular diseases, underscoring its promising potential for CHF management. Nevertheless, the underlying mechanisms of its action in CHF remain elusive. METHODS: First, a herb-component-target network was constructed to systematically identify the bioactive components of PALD and their potential protein targets. Concurrently, a protein-protein interaction (PPI) network was established to pinpoint key protein targets and core active ingredients in the CHF. Molecular docking was employed to validate the interactions between the primary active components of PALD and the predicted candidate targets. To further corroborate these findings, molecular docking was conducted. Furthermore, the R language was utilized for KEGG, GO, and DO enrichment analyses. RESULTS: Integrated bioinformatics and network pharmacology approaches predicted cerevisterol, licochalcone B, and hederagenin as core therapeutic candidates interacting with key signaling regulators such as SRC, PIK3CD, and PIK3CA. Molecular docking further validated potential binding of these compounds to inflammatory targets IL-6 and IL-1B, with cerevisterol showing binding energies of -6.227 kcal/mol (IL-6) and -6.607 kcal/mol (IL-1B), and hederagenin exhibiting -6.139 kcal/mol (IL-6) and -7.500 kcal/mol (IL-1B)-all values below the -6 kcal/mol threshold indicative of stable binding. These computational results suggest that PALD may exert multi-target effects against CHF-associated pathways, potentially through modulation of IL6/IL-1B-mediated inflammatory responses. DISCUSSION: By integrating network pharmacology, bioinformatics, and molecular docking, this study proposes a novel predictive framework suggesting that PALD may alleviate CHF by modulating the PI3K-AKT pathway and IL-6/IL-1B signaling to improve coronary artery function. While these findings are derived from computational models and require experimental confirmation, they provide a focused mechanistic hypothesis and a valuable roadmap for future in vitro and in vivo research into this traditional formula. CONCLUSION: PALD-derived bioactive constituents-cerevisterol, licochalcone B, and hederagenin- ameliorate coronary hemodynamics in chronic heart failure through coordinated inhibition of IL-6/IL-1Bmediated inflammatory responses and activation of PI3K/AKT signaling pathway. All proposed mechanisms are predictive and must be interpreted a.
Association Between Electron-Shuttling Capacity and Neuroprotective Potential of Huang-Lian-Jie-Du-Tang: A Bioelectrochemical, Biochemical and Computational Study.
Aspuria AJI, Chen BY, Tiongson SCM … +6 more , Aguila ANA, Zamora MMG, Hsieh CY, Hsueh CC, De Castro-Cruz KA, Tsai PW
Curr Pharm Des · 2026 Jun · PMID 42261164 · Publisher ↗
INTRODUCTION: Although the neuroprotective properties of Huang-Lian-Jie-Du-Tang (HLJDT) are well-documented, its specific redox mechanisms and capacity for mediating electron transfer remain poorly characterized. In this...
INTRODUCTION: Although the neuroprotective properties of Huang-Lian-Jie-Du-Tang (HLJDT) are well-documented, its specific redox mechanisms and capacity for mediating electron transfer remain poorly characterized. In this study, a combination of bioelectrochemical analysis using Microbial Fuel Cells (MFCs), biochemical assays, and computational docking data was used to analyze the correlation between the electronshuttling capability of HLJDT and its in vitro neuroprotective effects. METHODS: FRAP and DPPH activities were also determined to complement the quantification of the antioxidant potential and phytochemical content of HLJDT by total polyphenol, flavonoid, and condensed tannin assays. Electron-shuttling capacity and power density were measured using bioelectrochemical profiling with MFCs. The assessed neuroprotective potential was done through an in vitro acetylcholinesterase (AChE) inhibitory assay. Molecular docking of HLJDT compounds and in silico network pharmacology were performed to determine their interactions with neuroprotective targets. RESULTS: Phytochemical analysis indicated that ethanolic extracts, especially the traditional 3:2:2:3 formulation (HLJDT-B-E), were richest in flavonoids and condensed tannins, which were associated with high antioxidant activity (DPPH IC50 = 0.635 ± 0.008 mg/mL; FRAP = 127.237 ± 0.762 mg Trolox equivalent/g crude extract). The electron-shuttling capacity in MFCs was also highest in HLJDT-B-E, which produced the highest power density of 18.0662 ± 2.1622 mW/m2. The extract showed potent in vitro AChE inhibition (IC50 = 0.014 ± 0.0003 mg/mL), which was lower than that of the reference drug galantamine, in this set-up. Multitarget agent baicalin was discovered in molecular docking with high binding affinity towards the proteins associated with Parkinson's disease, such as MAO-B, which indicates a possible polypharmacological explanation for its actions. DISCUSSION: The results indicate a potential association between HLJDT's neuroprotective capacity and a synergistic effect of its antioxidant, electron-shuttling, and enzyme-inhibitory properties. The correlation between power density, antioxidant potency, and AChE inhibition suggests that electron-shuttling could be a redoxbased process that alleviates oxidative stress via alternative pathways beyond direct radical scavenging. CONCLUSION: The data reveal a correlative relationship between the electron-shuttling property of HLJDT and its neuroprotective effects in vitro. This bioelectrochemical and pharmacological compound model positions HLJDT as a highly promising multitarget therapeutic candidate and suggests electron-transfer capacity as a useful, novel index for characterizing neuroprotective natural products. Although the results offer a combined redox-based framework, neuroprotective effects were concluded based on in vitro and in silico models; direct validation in cellular or neuronal systems is required before any neuroprotective claims can be substantiated.
Genistein Mitigates High Glucose-induced Podocyte Injury by Modulating Autophagy via the mTOR Signal.
Shan Y, Cai Y, Lian Y … +6 more , Chen H, Huang H, Xu Z, Yan T, Jia J, Li D
Curr Pharm Des · 2026 Jun · PMID 42261163 · Publisher ↗
INTRODUCTION: High glucose (HG)-induced podocyte injury is closely associated with the dysregulation of autophagy processes. This study aimed to characterize autophagy-associated alterations in podocytes under HG conditi...
INTRODUCTION: High glucose (HG)-induced podocyte injury is closely associated with the dysregulation of autophagy processes. This study aimed to characterize autophagy-associated alterations in podocytes under HG conditions and to evaluate the effects of genistein treatment and changes on podocyte injury. METHODS: Podocytes were cultured under normal glucose (NG) or HG conditions and treated with genistein or rapamycin. Proteomic analyses, immunoblotting, immunofluorescence, and ultrastructural examinations were performed to assess autophagy- and mTOR-related features. In parallel, functional assays were conducted to evaluate podocyte adhesion, migration, cytoskeletal organization, and integrin β1 distribution. RESULTS: Exposure to HG reduced podocyte viability and was associated with increased mTOR phosphorylation, altered expression of autophagy-related markers, and impaired autophagic-lysosomal function. Proteomic analyses revealed the enrichment of DEPs in lysosome-, autophagy-, and mTOR-related pathways. These changes were accompanied by abnormal integrin β1 distribution, impaired cellular adhesion and migration, and cytoskeletal reorganization. Genistein treatment effectively attenuated these HG-induced changes, as evidenced by reduced mTOR phosphorylation and the restoration of autophagic-lysosomal function. DISCUSSION: These findings indicate that HG-induced podocyte injury is accompanied by coordinated perturbations in mTOR signaling, autophagic marker expression, and integrin β1-mediated cellular functions. The observed protective effects of genistein suggest its potential regulatory role in modulating these interconnected pathways. CONCLUSION: Genistein was associated with the alleviation of HG-induced podocyte injury, as well as changes in autophagy-lysosome-related markers and ultrastructural features suggestive of a partial restoration of autophagy- associated processes, potentially involving reduced mTOR phosphorylation.
Use of Antiemetic Agents and Other Symptomatic Treatment of Abdominal Conditions: Which are the best?
Akman C, Ozkaya B, Dehmen S … +1 more , Karcioglu O
Curr Pharm Des · 2026 Jun · PMID 42260775 · Publisher ↗
INTRODUCTION: The urgent management of the patient with acute abdominal pain and other conditions comprises a rapid cardiorespiratory evaluation and resuscitation to maintain hemodynamic stability and obtain an elaborate...
INTRODUCTION: The urgent management of the patient with acute abdominal pain and other conditions comprises a rapid cardiorespiratory evaluation and resuscitation to maintain hemodynamic stability and obtain an elaborate and focused history and examination. Following the exclusion of life-threatening diagnoses, symptomatic improvement in patients with gastrointestinal conditions is vital. Vomiting causes mild to severe dehydration, leading to hypovolemia, electrolyte imbalances, and other consequences. This narrative review provides an overview of symptomatic care and antiemetic management in the acute setting. METHODS: A systematic literature search was used to identify relevant articles. Consecutive trials in English published between 2005 and 2025 investigating the indications and use of antiemetic agents were abstracted from Google Scholar, PubMed, Scopus, and Web of Science. Case reports, editorials, and expert opinions were excluded from the analysis. RESULTS: Replacement of IV fluids combined with antiemetic agents is administered to patients with conditions causing intractable vomiting, such as pancreatitis, renal colic, hollow viscus obstruction, and appendicitis, based on the patient's clinical course. Emptying and decompression of the stomach contents with the nasogastric catheters may be necessary, as aspiration can often be encountered in patients with repeated vomiting. 5-Hydroxytryptamine 3 receptor antagonists are preferred as they act on central and peripheral receptors to prevent and treat vomiting. CONCLUSION: Patients with chief complaints of nausea and vomiting should prompt scrutiny for lifethreatening diagnoses initially, and then ruling out the other differential diagnoses, which need emergent interventions to prevent further deterioration. A `symptomatic` treatment not only ensures optimal cooperation and communication with the patient but also achieves physiological homeostasis. Measures to treat dehydration, pain, nausea, and vomiting should be individualized and implemented promptly with a multidisciplinary approach. Appropriate antiemetic agents should be selected to treat nausea and vomiting per evidence-based guidelines.
Transcript-Level Modulation of Drug-Metabolizing Enzymes by Echinacea, Salvia, and Thymus in Adult Male Rats: Implications for Herb-Drug Interactions.
Ahmed SH, Naguib MM, Seoudi DM … +1 more , El-Sayed WM
Curr Pharm Des · 2026 May · PMID 42227392 · Publisher ↗
BACKGROUND: Herb-Drug Interactions (HDIs) are a major clinical concern, as they may alter drug efficacy or cause toxicity. This study evaluated the potential HDIs of Echinacea purpurea, Thymus vulgaris, and Salvia offici...
BACKGROUND: Herb-Drug Interactions (HDIs) are a major clinical concern, as they may alter drug efficacy or cause toxicity. This study evaluated the potential HDIs of Echinacea purpurea, Thymus vulgaris, and Salvia officinalis by assessing their effects on Drug-Metabolizing Enzyme (DME) gene expression in rats. METHODS: Rats (n = 10/group) received Echinacea purpurea (50 mg/kg), Salvia officinalis (400 mg/kg), Thymus vulgaris (500 mg/kg), or vehicle for 15 days. Hepatic transcripts of Cyp3a1, Cyp2d1, Ephx1, Ugt1a1, Ces1, and Nqo1 were quantified by qPCR. Serum and hepatic biomarkers, oxidative stress indices, and histology of liver and kidney were also assessed. RESULTS: All extracts increased the mRNA levels of drug-metabolizing enzymes (2-8-fold) as measured by qPCR; protein expression and enzymatic activities were not assessed. Thymus vulgaris increased serum proteins and hepatic NO and GSH, while ALT rose in the Salvia officinalis and Thymus vulgaris groups. MDA was elevated in all groups. Histology showed mild hepatocellular vacuolation with Echinacea purpurea and minor hemorrhage with Thymus vulgaris. All extracts slightly increased serum creatinine with minimal renal lesions. DISCUSSION: These findings suggest that the three herbs may modulate DME expression at the transcript level and promote mild oxidative histopathological changes after subchronic exposure. Since only mRNA was measured, functional consequences for protein abundance and enzyme activity remain to be confirmed. CONCLUSION: Echinacea, Salvia, and Thymus may contribute to HDIs by altering DME gene expression and inducing early hepatic and renal stress in rats. Further studies at the protein, enzymatic, and pharmacokinetic levels are required to determine whether these findings have clinical relevance.
Protopanaxadiol as a Dual-Action Therapeutic Agent: Enhancing Radiotherapy Efficacy and Mitigating DMBA-Induced Breast Cancer through Multi-Target Mechanisms.
Mahmoud AA, Abdelrhman IG, Hussein MA … +7 more , Auf MA, Hamdy AM, Emara AA, Elsayed HA, Abuelkasem SS, El-Adl NI, Mosaad YO
Curr Pharm Des · 2026 May · PMID 42227391 · Publisher ↗
INTRODUCTION: Breast cancer remains a leading cause of cancer-related mortality, with radiotherapy often limited by tumor resistance and systemic toxicity. Protopanaxadiol (PPD), a bioactive ginsenoside metabolite, has e...
INTRODUCTION: Breast cancer remains a leading cause of cancer-related mortality, with radiotherapy often limited by tumor resistance and systemic toxicity. Protopanaxadiol (PPD), a bioactive ginsenoside metabolite, has emerged as a promising adjunct due to its multifaceted pharmacological properties. This study aimed to evaluate PPD's dual role as a radiosensitizer and cytoprotective agent in breast cancer, integrating in vitro, in vivo, and in silico approaches to elucidate its mechanisms. METHODS: In vitro cytotoxicity and cell cycle effects were assessed in MCF-7 cells treated with PPD alone or combined with γ-irradiation (6 Gy) using MTT assay and flow cytometry. A total of 96 female mice were used, including 60 for LD50 determination and 36 for efficacy evaluation. For in vivo studies, female albino mice (n=36) were divided into six groups: (1) normal control, (2) PPD alone (90 mg/kg orally for 8 weeks), (3) DMBA-induced breast cancer (7.5 mg/kg subcutaneously twice weekly for 4 weeks), (4) DMBA+PPD, (5) DMBA+ γ-irradiation (6 Gy/week for 3 weeks), and (6) DMBA+ γ-irradiation+ PPD. Haematological parameters (Hb%, RBCs, WBCs, serum iron), lipid profiles (TC, TG, HDL-C), oxidative stress markers (GSH, SOD, CAT, MDA), and apoptotic proteins (Bax, Bcl-2, caspase-3/9, p53) were analyzed in blood and tissue samples. Gene expression of HIF-1α, PHD2, and NF-κB was evaluated by qRT-PCR. Histopathological examination of breast tissue assessed morphological changes. Molecular docking predicted PPD's binding affinity to target proteins (HIF-1α, NF-κB, PHD2), and ADMET analysis evaluated pharmacokinetic properties. RESULTS: PPD significantly enhanced the cytotoxic effects of γ-irradiation, reducing the IC50 by 41%, and induced cell cycle arrest at both G0/G1 and G2/M phases. In vivo, PPD restored haematological parameters (increased Hb%, RBCs, and iron; decreased WBCs), improved lipid profiles (reduced total cholesterol and triglycerides; increased HDL-C), and mitigated oxidative stress (elevated GSH, SOD, and CAT; decreased MDA). It rebalanced apoptotic markers (downregulated Bax, caspase-3, caspase-9, and p53; upregulated Bcl- 2) and modulated gene expression (suppressed HIF-1α and NF-κB; enhanced PHD2). Histopathology confirmed reduced malignancy and fibrosis. Molecular docking revealed strong binding to HIF-1α (-9.16 kcal/mol), NF-κB (-8.88 kcal/mol), and PHD2 (-8.23 kcal/mol). ADMET profiling indicated favourable drug-likeness and safety. DISCUSSION: These findings demonstrate that PPD exerts multimodal anti-cancer effects by enhancing radiosensitivity, rebalancing oxidative status, and modulating hypoxia and inflammation pathways. Its high docking affinities and pharmacokinetic traits suggest clinical potential. Limitations include the absence of metastatic or long-term survival models. CONCLUSION: PPD demonstrates a unique dual capacity to enhance radiotherapy efficacy while protecting against treatment-induced toxicity, mediated through multi-target regulation of hypoxia, inflammation, and apoptosis pathways. These findings position PPD as a promising candidate for adjunctive breast cancer therapy, warranting further clinical exploration.
Network-Based Identification of Ginkgo biloba Targets for Sudden Sensorineural Hearing Loss Intervention.
Huang Q, Ren Y, Zhu Z … +3 more , Chen L, Liao X, Yin S
Curr Pharm Des · 2026 May · PMID 42227390 · Publisher ↗
INTRODUCTION: Ginkgo biloba extract (GBE) is commonly used to treat sudden sensorineural hearing loss (SSNHL), but its mechanisms are not fully understood. This study aimed to identify the bioactive components and therap...
INTRODUCTION: Ginkgo biloba extract (GBE) is commonly used to treat sudden sensorineural hearing loss (SSNHL), but its mechanisms are not fully understood. This study aimed to identify the bioactive components and therapeutic targets of GBE in SSNHL using network pharmacology and molecular docking. METHODS: Bioactive compounds of GBE were sourced from the TCMSP database, and their potential targets, along with SSNHL-related genes, were obtained from the GeneCards database. PPI networks were created using STRING and visualized with Cytoscape. Functional enrichment analyses, including GO and KEGG, were performed using the "clusterProfiler" package in R. CB-Dock molecular docking was used to confirm the binding affinities between key GBE components and main protein targets. RESULTS: Twenty-seven bioactive GBE components and 223 potential targets were identified, overlapping with 744 SSNHL-related targets to determine 24 key therapeutic targets. Enriched GO terms included organic/ carboxylic/fatty acid catabolic process, neuron apoptotic process, lipid modification, membrane raft, membrane microdomain, mitochondrial inner membrane, kinase regulator activity, kinase activator activity, and organic acid binding. KEGG pathways implicated allograft rejection, adipocytokine signaling, and biosynthesis of unsaturated fatty acids. Molecular docking confirmed favorable binding affinities between GBE constituents and core targets, suggesting biologically plausible interactions. DISCUSSION: Potential targets for screening encompassed genes, such as KCNH2, BDNF, NOS3, ADIPOQ, and CASP3, among others. CONCLUSION: This study elucidated the potential molecular mechanism through which GBE exerts its therapeutic effects in SSNHL, thereby establishing a rationale for subsequent experimental and clinical investigations.
Unveiling the Mechanisms of Liujunzi Decoction in COVID-19/Lung Cancer Comorbidity: A Network Pharmacology and Molecular Docking Study.
Yang P, Li Q, Zuo J … +3 more , Chu T, Shu X, Shu P
Curr Pharm Des · 2026 May · PMID 42227389 · Publisher ↗
OBJECTIVE: This study aimed to investigate the mechanism of action of Liujunzi decoction (LJZD) in the treatment of coronavirus disease 2019 (COVID-19) combined with lung cancer based on network pharmacology and molecula...
OBJECTIVE: This study aimed to investigate the mechanism of action of Liujunzi decoction (LJZD) in the treatment of coronavirus disease 2019 (COVID-19) combined with lung cancer based on network pharmacology and molecular docking. METHODS: First, we screened target information related to LJZD, COVID-19, and lung cancer from public databases, such as TCMSP, GeneCards, Drugbank, OMIM, and TTD. Then, we used the Evenn platform, String online database, and Cytoscape 3.7.1 software to obtain the common drug-disease targets and construct a PPI network and a "herb-ingredient-target" network. Next, we selected core targets based on their degree values and performed GO and KEGG enrichment analysis using the Metascape database and bioinformatics platforms. We then conducted molecular docking analysis using software, like AutoDockTools and Vina, to compare the binding affinity between core targets and key ingredients of Liujunzi decoction and core targets with Nutlin-3a. Finally, we performed molecular dynamics simulations on AKT1 and quercetin using the GROMACS software. RESULTS: A total of 125 active ingredients of LJZD were screened, of which 107 could bind to 94 common targets and exert therapeutic effects. The common targets were mainly enriched in 1807 GO-enriched entries and 191 KEGG signaling pathways. Molecular docking confirmed a strong affinity between the core target and key components, as well as a binding mode of the key components of Liujunzi decoction similar to TP53 activator Nutlin-3a. The molecular dynamics simulation results indicated AKT1 to bind to quercetin in a stable and tight manner. DISCUSSION: This first systematic network pharmacology study of LJZD in COVID-19/lung cancer comorbidity reveals that its therapeutic potential likely arises from synergistic interactions among multiple active compounds (notably quercetin and β-sitosterol) and core targets (TP53, AKT1, VEGFA). This multi-target profile aligns with the TCM principle of "treating different diseases with the same treatment. The comparable binding affinity of LJZD components to the TP53 activator Nutlin-3a suggests a shared mechanistic basis. Enrichment of pathways central to both diseases-including HIF-1 (hypoxia/angiogenesis) and AGE-RAGE (inflammation/ fibrosis)-indicates that LJZD may simultaneously modulate shared pathological processes. These computational findings provide a pharmacological rationale for LJZD's clinical application and establish a foundation for future experimental validation. CONCLUSION: LJZD may achieve the goal of treating COVID-19/lung cancer patients by potentially acting on genes, such as TP53, AKT1, VEGFA, and regulating signaling pathways and biological cellular processes, including pathways of cancer, lipid and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, cell senescence, chemical cancer-reactive oxygen species, and HIF-1 signaling pathway, through active ingredients, such as quercetin, β-sitosterol, and others.
Tanshinone IIA Inhibits Epithelial-Mesenchymal Transition in Colitis-Associated Cancer in Mice by Regulating PTEN and ATPase Inhibitory Factor 1.
Zhang K, Jiang C, Liu Y … +6 more , Liu W, Wang Q, Chen Z, Gong X, Zhao J, Yan T
Curr Pharm Des · 2026 May · PMID 42227388 · Publisher ↗
INTRODUCTION: Chronic inflammation in patients with inflammatory bowel disease (IBD) significantly increases the risk of developing gastrointestinal malignancies. Although Tanshinone IIA (TanIIA) has demonstrated biologi...
INTRODUCTION: Chronic inflammation in patients with inflammatory bowel disease (IBD) significantly increases the risk of developing gastrointestinal malignancies. Although Tanshinone IIA (TanIIA) has demonstrated biological activity against IBD, its specific effects on colitis-associated cancer (CAC) remain poorly understood. This study aimed to elucidate the therapeutic impact of TanIIA in CAC and to investigate its underlying molecular mechanisms. METHODS: A murine model of CAC was established using azoxymethane (AOM) and dextran sulfate sodium (DSS). Phenotypic measurements were recorded, and colon pathology was assessed using hematoxylin and eosin (H&E) staining. Quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry (IHC) were performed to examine the expression of colonic phosphatase and tensin homolog (PTEN), interleukin-17 (IL-17), NAD(P)H quinone oxidoreductase 1 (NQO1), E-cadherin, and N-cadherin. RESULTS: TanIIA modulated the PTEN/IL-17 axis to reduce tumor burden at week 10. By week 13, however, TanIIA did not reduce tumor size due to NQO1-mediated reactive oxygen species (ROS) generation, which influenced ATPase inhibitory factor 1 (IF1) expression in colon tissues and subsequently reversed epithelial-mesenchymal transition (EMT). DISCUSSION: While TanIIA failed to decrease late-stage tumor size, it effectively inhibited tumor initiation via the PTEN/IL-17 axis and suppressed metastatic potential through ROS-triggered IF1 upregulation. The absence of in vitro and clinical validation, however, necessitates further studies before clinical application. CONCLUSION: TanIIA limits CAC progression in vivo by modulating early-stage tumor initiation through the PTEN/IL-17 axis and late-stage EMT via ROS-mediated IF1 regulation, highlighting its potential as a therapeutic candidate for CAC and anti-metastatic treatment.
Integrated Network Pharmacology, Transcriptomics, and Experimental Validation Identify PI3K-AKT and STAT3 as Key Pathways for Pien Tze Huang Against Liver and Colorectal Cancers.
Hong Y, Xi W, Liu X … +7 more , Guo H, Zhang J, Yuan J, Chen S, Wang S, Chi G, Yu C
Curr Pharm Des · 2026 May · PMID 42227387 · Publisher ↗
INTRODUCTION: Pien Tze Huang (PZH), a classic Traditional Chinese Medicine (TCM), has long been used for treating inflammation and cancer, yet its pharmacological mechanisms against liver cancer and Colorectal Cancer (CR...
INTRODUCTION: Pien Tze Huang (PZH), a classic Traditional Chinese Medicine (TCM), has long been used for treating inflammation and cancer, yet its pharmacological mechanisms against liver cancer and Colorectal Cancer (CRC) remain incompletely understood. This study aims to elucidate the potential antitumor targets, signaling pathways, and functional effects of PZH against liver cancer and CRC. METHODS: Network pharmacology was applied to identify the active components of PZH from the TCMSP database and predict their potential targets, while disease-associated targets were retrieved from GeneCards. Core targets and pathways were screened via Protein-Protein Interaction (PPI) network analysis and functional enrichment (GO/KEGG) using Metascape. Molecular simulation was performed to assess the binding of key components to core targets. Experimental validation in Huh7, HCT116, and RKO cells included assessments of cell viability, cell cycle, protein expression, and transcriptomic profiling using CCK-8, flow cytometry, Western blot, and RNA sequencing, respectively. RESULTS: A total of 15 active components of PZH were identified, corresponding to 353 potential targets, among which 138 and 102 overlap with liver cancer and CRC, respectively. Network analysis identified AKT1, STAT3, EGFR, and ESR1 as core targets, which were enriched in PI3K-AKT, STAT3, ErbB, and PD-L1/PD-1 checkpoint pathways. Molecular simulation suggested favorable binding affinities of muscone and quercetin with AKT1, and of ginsenoside F2 and ginsenoside Rh2 with STAT3. In vitro, PZH inhibited cell proliferation, induced G1/S phase arrest, and downregulated Cyclin D1, PCNA, c-Myc, and PD-L1. Mechanistically, PZH selectively suppressed PI3K-AKT and STAT3 signaling, and combined treatment with four active components produced consistent inhibition of these pathways and downstream targets. DISCUSSION: These findings suggest that PZH may exert anti-tumor effects through coordinated modulation of PI3K-AKT and STAT3 signaling pathways, which are key regulators of tumor cell proliferation and immune evasion. The suppression of PD-L1 expression further implies a potential role of PZH in modulating tumor immune escape in addition to inhibiting tumor growth. Moreover, the integration of network pharmacology, molecular simulation, and experimental validation provides a framework for understanding the multi-target nature of traditional Chinese medicine and may facilitate the discovery of synergistic therapeutic mechanisms in complex diseases such as cancer. CONCLUSION: PZH exerts multi-component and multi-target anti-tumor effects against liver cancer and CRC, primarily by inhibiting PI3K-AKT and STAT3 signaling, thereby suppressing tumor cell proliferation and PD-L1 expression. These findings provide a mechanistic rationale for the traditional use of PZH and suggest its potential as a candidate for further preclinical investigation in liver cancer and CRC.
Emerging Utility of Artificial Intelligence Driven Medical Robots in Health Care: A Review.
Nagime PV, Kamble A, Kumar A … +1 more , Singh S
Curr Pharm Des · 2026 May · PMID 42227386 · Publisher ↗
The incorporation of Artificial Intelligence (AI) into medical robotics has transformed contemporary healthcare by improving precision, efficiency, and personalization in clinical treatments. This paper offers a thorough...
The incorporation of Artificial Intelligence (AI) into medical robotics has transformed contemporary healthcare by improving precision, efficiency, and personalization in clinical treatments. This paper offers a thorough examination of AI-driven medical robots, emphasizing their transformative capabilities in diagnosis, surgery, rehabilitation, and patient care. Artificial intelligence algorithms, especially those utilizing machine learning and deep learning frameworks, empower medical robots to execute intricate tasks, including image-guided surgery, self-navigating, making decisions in real time, and adaptive learning. Surgical robots integrated with AI enhance minimally invasive treatments by providing exceptional precision and minimizing patient trauma, whereas diagnostic robots facilitate early illness identification through pattern recognition in imaging and genetic data. Rehabilitation robots, equipped with AI, provide personalized therapy by continuously assessing and adjusting to the patient's advancement. Moreover, socially helpful robots employ natural language processing (NLP) and affective computing to aid elderly and disabled patients via interactive care. Notwithstanding these gains, problems endure, encompassing ethical dilemmas, data privacy issues, regulatory adherence, and the necessity for rigorous validation in clinical environments. The paper examines the present state of AI-driven medical robotic systems, assesses ongoing clinical trials, and considers future trajectories, highlighting the imperative for cross-disciplinary cooperation among engineers, data scientists, physicians, and legislators. This study objectively evaluates the features and limitations of AI-driven medical robots, highlighting their significance as essential instruments in advancing precision medicine and transforming the global healthcare landscape through intelligent automation and improved patient-centred solutions.
Exploring Combination Therapy for the Management of Psychotic Disorders: A Comprehensive Review.
Sharma S, Behl DS, Suri P … +4 more , Sharma T, Rai G, Gauba P, Dang S
Curr Pharm Des · 2026 May · PMID 42227385 · Publisher ↗
Schizophrenia is a severe brain disorder impacting approximately 1% of the overall world population. A large number of FDA-approved antipsychotics are available in the market for the management of schizophrenia and other...
Schizophrenia is a severe brain disorder impacting approximately 1% of the overall world population. A large number of FDA-approved antipsychotics are available in the market for the management of schizophrenia and other related disorders. However, 20-30% of patients exhibit treatment resistance, known as pharmacoresistant or refractory schizophrenia, where monotherapy proves to be ineffective. This review describes the various prevalent psychotic disorders, the antipsychotic mechanism of action, and drug resistance in monotherapy. The review highlights the significance of combination drug therapy in addressing treatmentresistant disorders, and various pre-clinical and clinical studies reported for combination therapy, along with modified delivery methods of antipsychotics and their combinations. For this purpose, we obtained evidence from preclinical and clinical studies investigating combinations, including other antipsychotics, mood stabilizers, NMDA receptor modulators, and anti-inflammatory agents. Combination therapy illustrates synergistic effects, enhanced symptom control, and reduced toxicity compared to monotherapy. Adjunctive use of natural compounds may alleviate oxidative stress, neuroinflammation, and neural toxicity. Modified drug-delivery systems further improve therapeutic efficacy. Overall, combination drug therapy represents a potential strategy for treatment-resistant schizophrenia by targeting multiple neurotransmitter pathways and associated pathophysiological mechanisms. Continued clinical validation and optimization of delivery methods are essential to establish their role in complete disease control.
Real-World Study on the Efficacy and Safety of Incadronate Disodium in Treating Bone Metastases of Advanced Breast Cancer.
Zhu A, Gui X, Zhang R … +4 more , Liang X, Shao B, Di L, Song G
Curr Pharm Des · 2026 May · PMID 42227384 · Publisher ↗
BACKGROUND: Bone is one of the most common sites of metastasis in advanced breast cancer. Incadronate disodium, a third-generation bisphosphonate, has demonstrated efficacy in relieving bone-related symptoms. However, th...
BACKGROUND: Bone is one of the most common sites of metastasis in advanced breast cancer. Incadronate disodium, a third-generation bisphosphonate, has demonstrated efficacy in relieving bone-related symptoms. However, there are few studies on the efficacy and safety specifically for bone metastases in advanced breast cancer. The study aims to evaluate the efficacy and safety of incadronate disodium in the treatment of bone metastases in patients with advanced breast cancer. METHODS: A retrospective real-world analysis was conducted on patients with advanced breast cancer and bone metastases who received incadronate disodium at our department from August 2021 to March 2024. Patients were assessed for bone pain relief, mobility improvement, and related adverse effects. RESULTS: A total of 181 patients were included. For all patients whose effects could be evaluated (n = 160), the overall pain relief rate was 81.6%, and the overall mobility improvement rate was 88.9%. Patients with more severe baseline pain experienced greater pain relief, while those with less severe pain had fewer mobility limitations and better improvements after treatment. The main adverse effects were fever, fatigue, elevated transaminases, myalgia, and anorexia. No cases of jaw osteonecrosis occurred. DISCUSSION: In this study, incadronate disodium showed high rates of pain relief and improved mobility, with greater benefits observed in patients with more severe baseline pain and with a favorable safety profile. Longterm safety monitoring indicated minimal impact on renal function and electrolytes, though attention is needed for potential risks like Medication-Related Osteonecrosis of the Jaw (MRONJ) and hypocalcemia. Pre-treatment dental evaluation and daily calcium/vitamin D supplementation are recommended to mitigate these risks. The study also notes that switching to incadronate after disease progression can be beneficial. However, as a single-center retrospective study without a control group, these findings require further validation through prospective randomized controlled trials. CONCLUSION: Incadronate disodium is effective and safe in relieving bone pain and improving mobility in advanced breast cancer patients with bone metastases. It represents a promising treatment option for this patient population.
Unveiling the Theranostic Potential of Aptamer Functionalized Materials for Viral Infections.
Taj T, Madan A, Siddiqui MA … +6 more , Islam A, Pal T, Sen A, Pal R, Ghosh S, Dey S
Curr Pharm Des · 2026 May · PMID 42227383 · Publisher ↗
INTRODUCTION: Aptamers are short single-stranded nucleic acids or peptides that can bind to specific targets with high affinity and specificity, making them promising tools for diagnostic and therapeutic applications. Th...
INTRODUCTION: Aptamers are short single-stranded nucleic acids or peptides that can bind to specific targets with high affinity and specificity, making them promising tools for diagnostic and therapeutic applications. Their ability to detect and neutralize viral pathogens with precision has garnered significant attention, particularly in the development of innovative theranostic strategies. METHODS: This review provides a comprehensive overview of aptamers, detailing their unique features and various types. It explores the theranostic potential of aptamers and functionalized aptamers in the diagnosis and treatment of viral pathogens. Additionally, a comparative analysis is presented, highlighting the advantages and limitations of aptamer-based detection methods in contrast to other conventional techniques for the identification of viral pathogens. RESULTS: The results of this review highlight the significant potential of aptamers in the detection and therapy. Aptamers show high specificity, sensitivity, and versatility compared to conventional diagnostic methods. Functionalized aptamers further enhance their applicability by improving target recognition and therapeutic efficiency. DISCUSSION: The comparative analysis indicates that aptamer-based approaches offer advantages such as rapid detection, cost-effectiveness, and adaptability for various viral targets. CONCLUSION: Overall, the findings support the growing interest in aptamers as promising tools for theranostic applications in virology. However, further research is needed on in vivo applications and clinical translation to establish their efficacy in real-world settings.
Efficacy and Safety of Telitacicept in Systemic Lupus Erythematosus.
Ma X, Wang Y, Liang Y … +4 more , Chen W, Zheng L, Zhou Y, Zhou T
Curr Pharm Des · 2026 May · PMID 42227382 · Publisher ↗
INTRODUCTION: Telitacicept, a biological agent, was approved by the National Medical Products Administration (NMPA) for the treatment of systemic lupus erythematosus (SLE). This meta-analysis aims to evaluate the efficac...
INTRODUCTION: Telitacicept, a biological agent, was approved by the National Medical Products Administration (NMPA) for the treatment of systemic lupus erythematosus (SLE). This meta-analysis aims to evaluate the efficacy and safety of telitacicept in SLE. METHOD: A systematic search was conducted for relevant studies from Web of Science, PubMed, the Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang, covering the period up to January 7, 2025. Randomized controlled trials (RCTs) and observational studies (OSs) were included. RESULT: Ninety studies were included in this study, including three RCTs and 16 OSs. The result from RCTs showed that telitacicept significantly improved the Systemic Lupus Erythematosus Respondent Index-4 (SRI4) response (RR = 2.23, 95% CI: 1.92~2.59, p<0.00001) and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score (RR = 1.95, 95% CI: 1.69~2.24, p<0.00001). The pooled results of OSs showed that the SRI-4 response rate increased to 75% (95% CI: 70%~80%), and the SLEDAI score decreased by 7.00 (95% CI: -7.36~-6.64) compared to baseline. Compared with belimumab, telitacicept significantly improved the SRI-4 response rate and SLEDAI score and facilitated early attainment of Lupus Low Disease Activity State (LLDAS) (RR = 1.20, 95% CI: 1.00~1.43, p=0.048; WMD = -1.38, 95% CI: -2.75~-0.01, p=0.048; RR = 1.47, 95% CI: 1.07~2.01, p=0.017). Compared with the control group, the telitacicept group significantly improved the total renal response rates (RR=1.23, 95% CI: 1.11~1.37, p<0.001) and complete renal response rates (RR=2.04, 95% CI: 1.55~2.69, p < 0.001). Regarding safety, the most common adverse events (AEs) reported were infections, such as respiratory infections, urinary tract infections, and herpes. The overall incidence of AEs with telitacicept was 41% (95% CI: 25%~58%), and the incidence of serious AEs was 10% (95% CI: 7%~13%). There was no significant difference in AE incidence compared with belimumab (RR = 0.99, 95% CI: 0.70 ~ 1.40, p=0.949). DISCUSSION: Telitacicept significantly improves SRI-4 response and reduces SLEDAI scores in SLE/LN patients, with 160 mg showing optimal efficacy. Telitacicept outperformed belimumab, likely due to dual BAFF/APRIL inhibition. Safety profiles were acceptable with mostly mild-to-moderate adverse events. However, limited RCTs and geographic restrictions to Chinese populations necessitate further multicenter trials for broader validation. CONCLUSION: Telitacicept is an effective and safe treatment for SLE. However, more clinical studies should be conducted to confirm it.
Exploring the Mechanisms Underlying the Effects of Cortex Moutan and Its Active Ingredients on Kidney Injury Through Network Pharmacology and Experimental Validation.
Yu J, Wang C, Wei W
Curr Pharm Des · 2026 May · PMID 42227381 · Publisher ↗
INTRODUCTION: Cortex Moutan (CM), the root bark of Paeonia suffruticosa, is a valuable herb. This study systematically explored the mechanisms of CM, providing an experimental basis for the use of its active ingredient q...
INTRODUCTION: Cortex Moutan (CM), the root bark of Paeonia suffruticosa, is a valuable herb. This study systematically explored the mechanisms of CM, providing an experimental basis for the use of its active ingredient quercetin as an important compound to treat kidney injury (KI). METHODS: Network pharmacology and molecular docking were employed to identify the active ingredients, key molecules, and signaling pathways of CM in the treatment of KI. Cellular and molecular biology assays validated its anti-KI effects and underlying mechanisms. Additionally, reports of cisplatin-related AE were analyzed via the FDA AE reporting system. RESULTS: Quercetin, (+)-catechin, and kaempferol were identified as major active ingredients of CM, with AKT1, TNF-α, IL-1β, and BCL-2 as key molecules. GO analysis revealed the involvement of cytokine activity and receptor ligand activation, whereas KEGG analysis revealed the involvement of the TNF signaling pathway. Molecular docking confirmed the stable binding between quercetin and AKT1. In cisplatin-induced mouse and NRK-52E cell-KI models, quercetin reversed cisplatin cytotoxicity by reducing ROS levels, downregulating Tnf-α and Bax/Bcl-2 expressions, and inhibiting AKT1, p-p65, p-IκB, and BAX/BCL-2. DISCUSSION: Previous studies have shown that CM exerts kidney-protective effects by regulating NO/cytokine levels, inhibiting NF-κB activation, and reducing ROS levels. As a vital component of CM, quercetin mediates multitarget renoprotection, as validated in animal KI models, but its development is limited by insufficient clinical data and low bioavailability. CONCLUSION: This study revealed the critical role of quercetin in the effects of CM against KI, with its relevant signaling pathway potentially correlated with TNF-α/AKT1/NF-κB.
Microbiota-Sensitive Nanocarriers for the Targeted Delivery of Therapeutic Agents into the Gut: Advanced Treatment Strategy for Inflammatory Bowel Disease.
Kumar D, Malviya R, Sridhar SB … +2 more , Wadhwa T, Shareef J
Curr Pharm Des · 2026 May · PMID 42227380 · Publisher ↗
Inflammatory bowel disease (IBD) is a gastrointestinal condition that impacts millions of individuals across the globe, causing recurring inflammation and serious consequences. Traditional treatments, like corticosteroid...
Inflammatory bowel disease (IBD) is a gastrointestinal condition that impacts millions of individuals across the globe, causing recurring inflammation and serious consequences. Traditional treatments, like corticosteroids and immunosuppressants, can cause systemic adverse effects owing to their lack of targeted delivery. Nanotechnology-based techniques, especially microbiota-sensitive nanocarriers, provide a potential route to more effective and targeted treatment. This study aims to explore the potential of microbiota-sensitive nanocarriers to enhance targeted drug delivery for inflammation associated with IBD. Microbiota-sensitive nanocarriers have been established to specifically deliver therapeutic agents in response to changes in pH, redox status, and enzyme activity that occur in the gut. The regulated release of drugs at the target location is ensured by these nanocarriers, as their size and surface features enable them to penetrate the mucus barrier and remain in the inflammatory areas. These minimise negative effects by reducing systemic drug absorption and increasing therapeutic effectiveness via interactions with the gut bacteria. Moreover, such nanocarriers enhance the total bioavailability of the drug and protect it against degradation in the gastrointestinal tract. In conclusion, microbiota-sensitive nanocarriers have tremendous potential for improving IBD treatment outcomes by delivering targeted, localized drug delivery and minimizing adverse effects associated with traditional therapies.
Mechanism Analysis of Fuzheng Xiaokui Formula in Treating Recurrent Aphthous Ulcers Based on Network Pharmacology.
Wang Y, Pan D, Shao T … +4 more , Huang X, Liang Y, Xu M, Jiang X
Curr Pharm Des · 2026 May · PMID 42220132 · Publisher ↗
INTRODUCTION: Recurrent Aphthous Ulcers (RAU), the most common oral mucosal disorder, represent a chronic inflammatory condition that significantly impacts patients' quality of life. Fuzheng Xiaokui Formula (FZXKF), an e...
INTRODUCTION: Recurrent Aphthous Ulcers (RAU), the most common oral mucosal disorder, represent a chronic inflammatory condition that significantly impacts patients' quality of life. Fuzheng Xiaokui Formula (FZXKF), an empirical prescription derived from veteran traditional Chinese medicine practitioners, has demonstrated remarkable clinical efficacy in preliminary applications. This study aimed to systematically identify the potential anti-RAU active components of FZXKF and elucidate their underlying mechanisms. METHODS: Public databases were utilized to identify the primary functional ingredients and targets of FZXKF and RAU-related genes. The herb-ingredient-target and protein-protein interaction (PPI) networks were constructed and analyzed using Cytoscape 3.10.3 to identify active ingredients and core targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to identify relevant biological mechanisms and signaling pathways. Molecular docking was performed to validate interactions between key components and targets. RESULTS: A total of 105 active components and 829 potential targets were preliminarily screened from FZXKF. Cross-referencing these with 2,903 RAU-related targets yielded 397 common targets. The 20 main active ingredients identified included glaucoside,c_qt, baicalein, isoflavanone, isorhamnetin, peonidin, etc. PPI network analysis identified 10 core targets (e.g., SRC, PIK3R1, PIK3CA, STAT3). Enrichment analysis revealed that the biological processes primarily involved responses to xenobiotic stimulus, protein phosphorylation, and oxidative stress, with significant enrichment in the PI3K-Akt, MAPK, Ras, and Rap1 signaling pathways. Molecular docking results showed strong binding affinity of primary bioactive ingredients toward core targets. DISCUSSION: These findings provided a theoretical foundation for the clinical potential of FZXKF in RAU management. Further research is needed to clarify the mechanisms of its specific active components and targets on ulcer healing. CONCLUSION: This study successfully predicted the multi-component, multi-target, and multi-pathway mechanisms of FZXKF in treating RAU and provided a basis for further investigation into its molecular mechanisms.
From History to Innovation: Pathophysiology and the Evolving Landscape of Urolithiasis Diagnosis and Treatment.
Rastogi A, Mazumder A, Pentela B
Curr Pharm Des · 2026 May · PMID 42220131 · Publisher ↗
Urolithiasis is a multicomponent illness described by the production of calcified stones within the urinary tract. It remains an important global health issue due to its frequency, recurrence, and cost. Urine supersatura...
Urolithiasis is a multicomponent illness described by the production of calcified stones within the urinary tract. It remains an important global health issue due to its frequency, recurrence, and cost. Urine supersaturation, crystal nucleation, development, aggregation, and retention are all steps in the stone formation process that are influenced by environmental, genetic, and metabolic factors. Calcium oxalate and calcium phosphate account for the majority of cases, whereas uric acid or infection stones develop in the context of particular metabolic or infectious conditions. Breakthroughs in molecular science have uncovered mechanisms such as crystal adhesion, oxidative stress, inflammation, and tubular injury, advancing understanding of disease development. The identification of genetic variants in transporters and metabolic enzymes by genetic studies shows hereditary susceptibility. Innovative diagnostics such as Dual-Energy Computed Tomography (DECT), ultra-low-dose imaging, and machine learning now enable accurate non-invasive characterisation of stones. Technologies like Fourier-Transform Infrared (FTIR), Raman, and micro-spectroscopy, complemented by intraoperative sampling, also facilitate enhanced stone composition analysis. Treatment modalities have evolved from traditional pharmacologic agents like citrate, thiazides, and allopurinol to emerging drugs that target molecular pathways of nucleation and aggregation. New precision-based therapies and innovative formulations are designed to reduce recurrence and enhance outcomes. The future direction focuses on incorporating molecular diagnostics, genomics, and artificial intelligence into practice for individualised management. This review discusses the mechanisms, classification, molecular and genetic determinants, and therapeutic breakthroughs in urolithiasis, emphasising the transition from conventional to emerging approaches and indicating future directions for better patient care.
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