Curr. Pharm. Des. [JOURNAL]
Sun
200 papers
Leveraging Untargeted Metabolomics and Molecular Dynamics Simulation Unraveling the Multi-Target Mechanism of Taohong Siwu Decoction against Pulmonary Hypertension.
Wang X, Wang Y, Wang H … +5 more , Zeng Z, Huo Y, Tian L, Guo J, Chen Y
Curr Pharm Des · 2026 May · PMID 42220130 · Publisher ↗
INTRODUCTION: Pulmonary hypertension (PH) is a complex disease with diverse etiologies and limited treatment options. Taohong Siwu Decoction (THSWD), a traditional Chinese medicine formula, has shown potential therapeuti...
INTRODUCTION: Pulmonary hypertension (PH) is a complex disease with diverse etiologies and limited treatment options. Taohong Siwu Decoction (THSWD), a traditional Chinese medicine formula, has shown potential therapeutic benefits for PH, yet its underlying pharmacological mechanisms remain poorly defined. This study aimed to systematically investigate the specific mechanisms through which THSWD exerts its anti-PH effects using an integrated pharmacological strategy. METHODS: We employed a comprehensive approach combining in vivo experimentation and multi-omics analysis. A rat model of PH was established to evaluate the therapeutic effects of THSWD. Hemodynamic parameters, pulmonary vascular remodeling, and right ventricular hypertrophy were assessed. Key markers of proliferation (PCNA) and inflammation (NF-κB, CD68) were analyzed. Furthermore, network pharmacology was utilized to identify potential active ingredients and core targets, which were validated through molecular docking and molecular dynamics simulations. Untargeted metabolomics was conducted to identify associated metabolic biomarkers and pathways. RESULTS: Treatment with THSWD significantly ameliorated PH progression, as evidenced by reduced right ventricular systolic pressure, attenuated pulmonary vascular remodeling, and decreased right ventricular hypertrophy in rat models. THSWD downregulated the expression of PCNA and suppressed inflammatory responses, indicated by reduced NF-κB activation and CD68 levels. Network pharmacology identified luteolin, quercetin, kaempferol, and β-sitosterol as key active components and highlighted the HIF-1α/VEGF signaling pathway as a central target. Molecular simulations confirmed stable binding between these components and HIF-1α/VEGFA, with particularly strong interactions observed for β-sitosterol-HIF-1α, quercetin-HIF-1α, and luteolin-VEGFA. Metabolomic analysis revealed that THSWD modulated metabolites, including 12-hydroxyicosanoic acid, 7-methylguanine, and lapachenole, suggesting involvement of the arachidonic acid metabolic pathway. DISCUSSION: The findings indicate that THSWD mitigates PH through multi-target mechanisms, primarily by inhibiting HIF-1α/VEGF-mediated pulmonary vascular remodeling and right ventricular hypertrophy, and by modulating arachidonic acid metabolism to restore metabolic homeostasis. The study provides a mechanistic link between the formula's traditional use and modern pharmacological actions, highlighting its potential as a multi-component therapy for PH. CONCLUSION: THSWD effectively attenuates experimental PH by delaying pulmonary vascular remodeling and right ventricular hypertrophy. Its therapeutic effects are mediated through regulation of the HIF-1α/VEGFA signaling pathway and correction of metabolic imbalances in the arachidonic acid pathway. This integrated evidence supports the further development of THSWD as a promising therapeutic strategy for PH.
Exploring the Potential of Dendrimers in Skin Drug Delivery: Applications and Advances.
Saldanha MC, Dubey A, Pierre MBR
Curr Pharm Des · 2026 May · PMID 42220129 · Publisher ↗
Dendrimers (DDs) have become a pioneering tool in dermatological nanomedicine thanks to their branched nanostructure, high precision, and multifunctional nature. The purpose of this review is to highlight the revolutiona...
Dendrimers (DDs) have become a pioneering tool in dermatological nanomedicine thanks to their branched nanostructure, high precision, and multifunctional nature. The purpose of this review is to highlight the revolutionary potential of DDs regarding the primary barrier for skin drug delivery - the stratum corneum. The enhanced solubility, controlled drug release, and facilitated drug penetration achieved by the customized dendrimer architecture are described in terms of diffusion, degradation, and stimuli-responsive mechanisms. The latest achievements are critically assessed through the topical approaches for psoriasis, wound healing, and skin cancer treatment, as well as transdermal delivery for systemic vaccines and gene therapy. The essential aspect of surface engineering is also analyzed in terms of its dual-edged features-chemical functionalization optimizes skin affinity and therapeutic specificity while addressing toxicological issues. Quantitative data from the literature have been provided to support the benefits, such as a 4.5-fold increase in the transdermal flux of indomethacin using PAMAM G4 and 2.7-fold and 2.5-fold increases in the bioavailability of ketoprofen and diflunisal, respectively. Moreover, in the studies applying dendrimers combined with sonophoresis, the permeability results demonstrated a noticeable trend - e.g., 935.21 μg/cm2 versus 56.69 μg/cm2 permeation, which indicates the possibility of synergism with physical enhancement methods Moreover, in the studies applying dendrimers combined with sonophoresis, the permeability results demonstrated a noticeable trend - e.g., 935.21 μg/cm2 versus 56.69 μg/cm2 permeation, which indicates the possibility of synergism with physical enhancement methods. To ensure successful transfer to clinics, an increased focus on long-term safety, synthesis scalability, and reproducibility is needed. This article provides an in-depth, objective, and holistic assessment of dendrimers as a versatile, continually expanding and improving toolkit for targeted skin therapies.
In Silico Evaluation of Bioactive Compounds Isolated from Scleroderma citrinum Against H1N1 and Acetylcholinesterase: A Post-COVID Perspective.
Bolinget E, Hsieh CY, Sevilla UT … +1 more , Tsai PW
Curr Pharm Des · 2026 May · PMID 42220128 · Publisher ↗
INTRODUCTION: Scleroderma citrinum (syn. Scleroderma aurantium and Scleroderma vulgare) is a mycorrhizal mushroom with known toxic effects but also holds potential for bioactive compound discovery. This study aimed to is...
INTRODUCTION: Scleroderma citrinum (syn. Scleroderma aurantium and Scleroderma vulgare) is a mycorrhizal mushroom with known toxic effects but also holds potential for bioactive compound discovery. This study aimed to isolate and identify secondary metabolites from the fruiting bodies of S. citrinum and evaluate their potential antiviral and neuroprotective properties. MATERIALS AND METHODS: The fruiting bodies of S. citrinum were freeze-dried, ground and extracted in CH2Cl2 for 3 days. The extract was filtered, evaporated under vacuum and subjected to successive washing with petroleum ether and Et2O. Chromatographic separation was performed using gradient elution with increasing proportions of ethyl acetate in petroleum ether. Structural elucidation of isolated compounds was achieved via 1D and 2D NMR spectroscopy. Molecular docking analyses assessed the binding affinities of compounds to target enzymes relevant to antiviral and neuroprotective pathways. Selected docked complexes were further evaluated by molecular dynamics simulations (RMSD analysis) and MMGBSA/MMPBSA binding free-energy calculations. RESULTS: The chemical investigation resulted in the isolation of the following three compounds: 3,25-dihydroxy-22-acetoxylanosta-8,23-diene, ergosterol, and triacylglycerols. The molecular docking study revealed that 3,25-dihydroxy-22-acetoxylanosta-8, 23-diene exhibited high binding affinities to PARP1 and CDC25B, exceeding that of Tamiflu, suggesting potent antiviral activity. Ergosterol showed superior affinity for PTGS2 indicating potential anti-inflammatory effects. Both have inhibitory potential against Acetylcholinesterase (AChE), surpassing galantamine, thus suggesting neuroprotective effects. Molecular dynamics simulations showed stable protein backbones and ligand behaviors consistent with sustained binding, and MMGBSA/MMPBSA analyses provided complementary energetic support beyond docking scores. DISCUSSION: This study isolated and identified 3,25-dihydroxy-22-acetoxylanosta-8,23-diene and ergosterol from Scleroderma citrinum, confirming their structures via comprehensive NMR analyses. Molecular docking revealed strong multi-target binding potential for both compounds, with affinities toward influenza-related proteins (PARP1, CDC25B, PTGS2) and acetylcholinesterase exceeding those of standard drugs such as Tamiflu and galantamine. These results align with previous reports of lanostane triterpenes and ergosterol exhibiting antiviral, anti-inflammatory, and neuroprotective properties. These docking results were further supported by MD stability metrics and MMGBSA/MMPBSA endpoint free-energy analyses. The dual-action profile suggests their promise as lead compounds for therapies addressing both H1N1 influenza and neurodegenerative conditions, warranting further in vitro and in vivo validation. CONCLUSION: Three compounds were successfully isolated from S. citrinum, with molecular docking analyses indicating significant potential as antiviral and neuroprotective agents. The lanostane derivative and ergosterol warrant further biological validation, including in vitro and in vivo studies, to explore their therapeutic applications. Orthogonal MD and MMGBSA/MMPBSA analyses provided additional support for the stability and energetic favorability of the predicted binding modes.
Potential Protective Effect of All-trans Retinoic Acid Against Hypoxia Induced Injury in Renal Tubular Epithelial Cells.
Lin W, Chen W, Lin S … +3 more , Liao C, Lin Y, Zhou T
Curr Pharm Des · 2026 May · PMID 42163746 · Publisher ↗
BACKGROUND: Acute kidney injury (AKI) involves inflammatory infiltration and renal tubular epithelial cells (RTECs) damage. Maladaptive repair post-AKI may lead to chronic kidney disease. All-trans retinoic acid (ATRA) s...
BACKGROUND: Acute kidney injury (AKI) involves inflammatory infiltration and renal tubular epithelial cells (RTECs) damage. Maladaptive repair post-AKI may lead to chronic kidney disease. All-trans retinoic acid (ATRA) shows protective effects against renal fibrosis, but its mechanism remains unclear. This study investigated whether ATRA alleviates RTECs injury induced by oxygen and glucose deprivation/ reperfusion (OGD/R) and whether it was associated with the RARα/RXRα-LMX1B pathway. METHODS: An OGD/R model was established using NRK-52E cells, divided into four groups: normal control (NC), OGD/R, Dimethyl sulfoxide (DMSO)+OGD/R, and ATRA+OGD/R. Cell morphology, viability (Cell Counting Kit-8 assay), apoptosis (flow cytometry), and protein levels (Western blot) of transforming growth factor-beta 1 (TGF-β1), α-smooth muscle actin (α-SMA)， retinoic acid receptor alpha (RARα), retinoid X receptor alpha (RXRα), and LIM homeobox transcription factor 1-beta (LMX1B) were assessed. All experiments were independently repeated three times. RESULTS AND DISCUSSION: OGD/R treatment caused significant cell damage, reduced cell viability, and increased cell apoptosis rate compared to the NC group. The protein expressions of TGF-β1 and α-SMA in the OGD/R group were significantly higher than those in the NC group (p<0.05), but decreased after being pretreated with ATRA (p<0.05). The protein expressions of RARα, RXRα, and LMX1B were downregulated after being treated with OGD/R (p<0.05). In the ATRA+OGD/R group, the expressions of RARα and LMX1B increased (p<0.05), while the expression of RXRα was further reduced (p<0.05) when compared to the DMSO+OGD/R group. Correlation analysis showed that the protein expressions of RARα, RXRα, and LMX1B were not only negatively correlated with TGF-β1 (r=-0.643, -0.879, -0.839, p<0.05), but also with α- SMA (r=-0.755, -0.894, -0.816, p<0.05). LMX1B was positively correlated with RARα and RXRα (r=0.766, 0.776, p<0.05), while RARα was also positively correlated with RXRα (r=0.755, p<0.05). CONCLUSION: ATRA mitigates hypoxia-induced RTECs injury and was associated with the expressions of RARα, RXRα, and LMX1B.
Multi-Target Neuroprotection of Salvia officinalis Aqueous Extract in a Scopolamine-Induced Model of Alzheimer's Disease: Comparative Efficacy Versus Donepezil.
Abdalla EA, Fayed AM, Hussein MA … +2 more , Abdel-Aziz A, Mohamed ZN
Curr Pharm Des · 2026 May · PMID 42163745 · Publisher ↗
INTRODUCTION: Alzheimer's disease (AD) is a complex, age-related, neurodegenerative disorder that involves cognitive deterioration, oxidative stress, and neuroinflammation. Symptomatic relief is limited with conventional...
INTRODUCTION: Alzheimer's disease (AD) is a complex, age-related, neurodegenerative disorder that involves cognitive deterioration, oxidative stress, and neuroinflammation. Symptomatic relief is limited with conventional treatments such as donepezil, sparking a significant interest in multi-target botanicals. We examined the neuroprotective effects of Salvia officinalis aqueous extract (SAGE) on a scopolamine-induced animal model of AD and the related molecular mechanisms regarding GABRA5α, GSK-3β, and pERK pathways. METHODS: SAGE was characterized using phytochemical profiling and antioxidant assays. IC50 values were determined in vitro for inhibitor activity against GABRA5α and GSK-3β. In vivo experiments included assessment of behavior (Morris water maze), assays for oxidative stress and inflammation, gene expression studies by qPCR, and histopathology of hippocampal tissue. Efficacy versus donepezil was compared. Statistical significance was based on one-way ANOVA followed by Tukey's post-hoc test (p < 0.05) for robust comparisons between all treatment groups. RESULTS: The SAGE had strong antioxidant abilities and was able to inhibit GABRA5α and GSK-3β in a target-specific way. SAGE treatment greatly enhanced spatial learning and memory, retained the redox equilibrium, decreased neuroinflammatory markers, and normalized AChE activity. Gene expression was found to modulate favourably for GABRA5α, GSK-3β and pERK. Histological findings confirmed neuronal preservation. In all parameters, SAGE was more effective than donepezil. The present findings demonstrated the therapeutic potential of SAGE's phenolics to mitigate oxidative cascades, including those suggested as contributing factors to AD pathology. DISCUSSION: The superior multi-modal efficacy of SAGE over donepezil due to its phenolic-rich phytochemical profile and capacity to modulate oxidative, inflammatory, and neuronal pathways is demonstrated. This is encouraging, and additional studies should be conducted to investigate pharmacokinetics, mechanistic and clinical significance. CONCLUSION: S. officinalis AE strongly protects the brain against scopolamine-induced AD-like neuropathology in a superior way over standard treatment via altered multi-targets. Its characteristics promote its further development as a natural therapeutic candidate for AD treatment. There are however constraints, such as nodescription of the pharmacokinetic profiling and no tau/Aβ quantification. Prospective studies with these endpoints and chronic dosing schedules should now address the issue of long-term effectiveness and safety.
Drug-Drug Interaction and Initial Dosage Optimization of Tacrolimus in Pediatric Nephrotic Syndrome Patients Based on Real-World Data and Model-Informed Precision Dosing.
Zheng ZQ, Zhang Y, Shi QY … +7 more , Yang Y, Wang ZM, Wang Q, He SM, Chen X, Miao L, Wang DD
Curr Pharm Des · 2026 May · PMID 42163744 · Publisher ↗
OBJECTIVE: Tacrolimus is a calcineurin inhibitor and holds an important position in the treatment of Pediatric Nephrotic Syndrome (PNS). However, the pharmacokinetics of tacrolimus are influenced by multiple factors, esp...
OBJECTIVE: Tacrolimus is a calcineurin inhibitor and holds an important position in the treatment of Pediatric Nephrotic Syndrome (PNS). However, the pharmacokinetics of tacrolimus are influenced by multiple factors, especially when combined with other medications. This study aims to explore Drug-Drug Interaction (DDI) and initial dosage optimization of tacrolimus in PNS based on real-world data and Model-Informed Precision Dosing (MIPD). METHODS: The PNS patient data included demographic, clinical laboratory, and combined drug data. Population Pharmacokinetics (PPK) to study DDI and to optimize the initial dosage of tacrolimus in PNS patients was used. RESULTS: In the final tacrolimus PPK model of PNS patients, wuzhi capsule affected tacrolimus, and when PNS patients took wuzhi capsule at the same time, the clearance rate of tacrolimus decreased by 43%. Furthermore, the initial dosage regimen of tacrolimus for PNS was recommended. When PNS patients were not taking wuzhi capsules, the recommended tacrolimus dosages for 10 kg-23 kg and 23 kg-60 kg pediatric patients were 0.12 mg/kg and 0.10 mg/kg, respectively. When PNS patients were taking wuzhi capsules, the recommended dosage of tacrolimus for 10 kg-60 kg pediatric patients was 0.08 mg/kg. DISCUSSION: This study explored DDI and initial dosage optimization of tacrolimus in PNS patients based on real-world data and MIPD, and wuzhi capsule with tacrolimus had DDI. CONCLUSION: The present study recommended an initial tacrolimus dosage regimen for PNS based on the wuzhi capsule.
Feiyanning Suppresses Lung Cancer by Targeting Cancer Stem Cell Stemness and NLRP3 Inflammasome.
Wang S, Wang L, Su W … +2 more , Lu Y, Xu Z
Curr Pharm Des · 2026 May · PMID 42163743 · Publisher ↗
INTRODUCTION: Lung cancer stem cells (LCSCs) are closely linked to lung cancer progression and drug resistance, and are regulated by the inflammatory microenvironment, such as NLR family pyrin domain containing 3 (NLRP3)...
INTRODUCTION: Lung cancer stem cells (LCSCs) are closely linked to lung cancer progression and drug resistance, and are regulated by the inflammatory microenvironment, such as NLR family pyrin domain containing 3 (NLRP3) inflammasome. Feiyanning (FYN) is a Traditional Chinese Medicine with therapeutic potential for lung cancer. However, its mechanism remains elusive. This study aimed to investigate whether FYN suppresses lung cancer progression by modulating LCSCs and the NLRP3 inflammasome. METHODS: A A549 tumor-bearing mouse model was established, and FYN and an NLRP3 inhibitor were administered to evaluate their anti-lung cancer efficacy. A549 side population (SP) stem cells as LCSCs were sorted by flow cytometry and cultured. The effects of FYN on the proliferation and metastasis of A549 cells and LCSCs were evaluated by CCK-8 and Transwell assays. The effects of FYN on the stemness of LCSCs and inflammasome NLRP3 in A549 cells and tumor tissues were verified by RT-PCR, Western blot, flow cytometry, and immunohistochemistry. RESULTS: In vitro and in vivo experiments demonstrated that FYN suppressed lung cancer cell proliferation and metastasis while downregulating key NLRP3 inflammasome components (NLRP3, ASC, caspase-1). FYN inhibited the proliferation and metastasis of LCSCs sorted by flow cytometry. Western Blot analysis revealed consistent downregulation of stem cell markers (CD44 and CD133) and stem cell stemness markers (Nanog, OCT4, and Notch1) in FYN-treated LCSCs. Notably, NLRP3 knockdown further enhanced the inhibitory effects of FYN on the metastasis and self-renewal ability of LCSCs, thereby further suppressing the progression of lung cancer. DISCUSSION: FYN exerted anti-lung cancer effects by suppressing the proliferation and metastasis of lung cancer cells and LCSCs both in vitro and in vivo by inhibiting NLRP3 activation. CONCLUSION: Our findings demonstrated that FYN exerts its anti-tumor effects by targeting NLRP3 inflammasome- mediated LCSC activation and identified a novel link between the NLRP3 inflammasome and LCSCs. The results also provided novel mechanistic insights and a potential TCM-based therapeutic strategy for lung cancer intervention.
Electrochemical Analysis and in silico Evaluation of Tamarindus indica Linn Fruit Pulp Extract for Potential Antidepressant Effects.
Matel AJC, Chen BY, Hsieh CY … +2 more , De Castro-Cruz KA, Tsai PW
Curr Pharm Des · 2026 May · PMID 42163742 · Publisher ↗
INTRODUCTION: Depression involves neurotransmitter imbalance, HPA axis dysfunction, neuroinflammation, and impaired neuroplasticity. The limitations of SSRIs and SNRIs have prompted interest in plant- derived alternative...
INTRODUCTION: Depression involves neurotransmitter imbalance, HPA axis dysfunction, neuroinflammation, and impaired neuroplasticity. The limitations of SSRIs and SNRIs have prompted interest in plant- derived alternatives. Tamarindus indica Linn. fruit pulp (TIL-P) contains bioactive compounds with antioxidant, anti-inflammatory, and neuroprotective properties, yet its antidepressant potential is underexplored. MATERIALS AND METHODS: Water and ethanol extracts were analyzed for phenolic, flavonoid, and tannin content. Electrochemical activity was assessed via Microbial Fuel Cells (MFCs). Network pharmacology identified depression- related targets, and molecular docking evaluated interactions with key proteins, using fluoxetine as a control. RESULTS: Water extract yielded a higher extraction efficiency (28.48%) than ethanol extract (17.34%). Ethanol extract had significantly higher flavonoid content, whereas water extract was richer in condensed tannins. MFC analysis showed the water extract at 2000 ppm had the highest amplification factor (1.51), while ethanol extract activity plateaued beyond 1000 ppm, likely due to organic acid-related bacterial growth inhibition. Network pharmacology identified nine hub genes (GAPDH, EGFR, CTNNB1, IL1B, ALB, SRC, TP53, TNF, AKT1) linked to depressive disorder pathways. Molecular docking revealed that catechin, cyanidin, and Pyran-4- one,2,3-dihydro-3,5-dihydroxy-6-methyl displayed strong binding affinities with ALB and EGFR, in some cases exceeding fluoxetine, indicating potential multi-target antidepressant effects. DISCUSSION: The combined electrochemical, phytochemical, and in silico results suggest that TIL-P contains polyphenolic compounds capable of modulating neuroinflammation, oxidative stress, and neurotransmitter-related signaling mechanistic pathways central to depression pathophysiology. Water extracts appeared more favorable for maximizing electrochemical activity, while ethanol extracts enriched flavonoids with strong docking affinities. These complementary solvent profiles highlight the potential of dual-extraction approaches to harness both tannin- and flavonoid-rich fractions for synergistic antidepressant effects. CONCLUSION: TIL-P, particularly its water-extracted polyphenolic constituents catechin, cyanidin, and Pyran-4- one,2,3-dihydro-3,5-dihydroxy-6-methyl, shows promise as a natural antidepressant candidate through neuroprotective, antioxidant, and anti-inflammatory mechanisms. These findings support further in vitro and in vivo studies to validate efficacy, safety, and mechanism of action.
Protective Mechanism of Licorice against Liver Injury Induced by Psoraleae Fructus and Epimedii Folium in Rats Based on Network Pharmacology and Metabolomics.
Ma T, Liu H, Hu M … +6 more , Lu D, Li R, Zheng L, Li Y, Chen S, Liu T
Curr Pharm Des · 2026 May · PMID 42163741 · Publisher ↗
BACKGROUND: The combination of Psoraleae Fructus (PF) with Epimedii Folium (EF) can cause drug-induced liver injury (DILI), which is a common type of hepatitis. Licorice (Lic) has been reported to mitigate the effects of...
BACKGROUND: The combination of Psoraleae Fructus (PF) with Epimedii Folium (EF) can cause drug-induced liver injury (DILI), which is a common type of hepatitis. Licorice (Lic) has been reported to mitigate the effects of hepatitis. However, the extent of Lic's protective effect against PF combined with EF -induced DILI and the underlying mechanisms remain unclear. METHODS: A rat model of PF+EF-induced liver injury was established under lipopolysaccharide stimulation, and the levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β)) were determined by using a kit to evaluate the hepatoprotective effect of Lic. In addition, the potential mechanisms of Lic's hepatoprotective effects were systematically studied using a combined approach of network pharmacology and metabolomics analysis, and ERK, p-ERK, p38, and p-p38 proteins were detected by Western blotting. RESULTS: Lic treatment significantly reduced serum levels of ALT, AST, TNF-α, IL-6, and IL-1β by approximately 46%, 40%, 22%, 11%, and 27%, respectively, and improved liver histopathology. Network pharmacology analysis identified 459 common targets shared between Lic and PF+EF-induced liver injury. Metabolomics revealed 12 differential metabolites, implicating pyrimidine and purine metabolism as the primary affected pathways. An integrated analysis of these metabolites and the 459 targets highlighted the mitogen- activated protein kinase (MAPK) pathway as the potential key mechanism through which Lic alleviates PF+EF-induced liver injury. DISCUSSION: Our results indicate that Lic alleviates PF+EF-induced liver injury by suppressing inflammatory responses and correcting metabolic perturbations. The combined network pharmacology, metabolomics, and protein expression analyses consistently point to the MAPK pathway as a pivotal mechanism mediating these hepatoprotective effects. These findings provide mechanistic support for the potential use of Lic in the prevention and treatment of DILI. CONCLUSION: Lic improves tissue injury and liver inflammation induced by PF+EF via regulating the MAPK pathway. This study provides a theoretical foundation for the therapeutic use of Lic in the treatment of hepatitis.
Investigating the Therapeutic Effect and Mechanism of Astragalus Mongholicus on Graves' Disease through Network Pharmacology.
Chen H, Yu Y, Xin J … +3 more , Chen J, Gu P, Shao S
Curr Pharm Des · 2026 May · PMID 42163740 · Publisher ↗
INTRODUCTION: Current treatments for Graves' disease have limitations, while emerging evidence suggests astragalus may modify disease progression. However, its precise mechanisms remain unclear. This study aims to system...
INTRODUCTION: Current treatments for Graves' disease have limitations, while emerging evidence suggests astragalus may modify disease progression. However, its precise mechanisms remain unclear. This study aims to systematically investigate the pharmacological basis of astragalus against Graves' disease, providing a theoretical foundation for novel therapeutic strategies. METHODS: Potential targets of astragalus and Graves' disease were collected from databases to construct a protein- protein interaction network. Gene Ontology and KEGG enrichment analyses were performed to identify key targets and pathways. Molecular docking was used to validate network pharmacology predictions. RESULTS: This study, utilizing network pharmacology, for the first time revealed that the principal bioactive constituents of Astragalus mongholicus in treating Graves' disease are quercetin, kaempferol, and 7-O-methylisomucronulatol. The mechanism of action is potentially mediated through the regulation of inflammatory factors such as the tumor necrosis factor-α pathway, interleukin-1β, and interleukin-6, thereby exerting multi-target anti-inflammatory effects and alleviating disease progression. Molecular docking results demonstrated that quercetin exhibits significant binding affinity with the key target TNF. DISCUSSION: Employing network pharmacology and molecular docking, this study reveals that Astragalus mongholicus, particularly through its active component quercetin, may treat Graves' disease by targeting the TNF-α signaling pathway and modulating key inflammatory cytokines such as IL-1β and IL-6. CONCLUSION: Our findings suggest that Astragalus mongholicus may exert therapeutic effects on Graves' disease via modulation of the TNF signaling pathway, providing novel insights into its mechanism of action.
Investigation of the Multi-target Regulation of Neurotransmitter Dysfunction By Xiaoer Huanglong Granule in Attention Deficit Hyperactivity Disorder: Network Pharmacology Combined with Experimental Validation.
Liu J, You L, Peng H … +6 more , Chang A, Qu C, Yin X, Guo P, Dong X, Ni J
Curr Pharm Des · 2026 May · PMID 42163739 · Publisher ↗
INTRODUCTION: The increasing global prevalence of attention deficit hyperactivity disorder (ADHD) and its substantial societal burden have intensified research efforts to elucidate its pathophysiology and therapeutic int...
INTRODUCTION: The increasing global prevalence of attention deficit hyperactivity disorder (ADHD) and its substantial societal burden have intensified research efforts to elucidate its pathophysiology and therapeutic interventions. Xiaoer Huanglong Granule (XHG), a well-established traditional Chinese herbal formulation, has demonstrated clinical efficacy in ADHD management and has been approved by the China National Medical Products Administration and successfully launched on the market. However, its pharmacological mechanisms remain incompletely understood. This study aims to systematically evaluate the therapeutic potential of the herbal formulation XHG in ADHD using an integrated approach that combines network pharmacology, behavioral assays, and molecular analyses. METHODS: We employed network pharmacology-based screening to identify bioactive compounds and target proteins associated with ADHD. Molecular docking simulations were conducted to assess binding affinities. Behavioral effects were evaluated using open-field and elevated plus maze tests, and protein expression levels were analyzed via Western blot. RESULTS: Network analysis identified six key bioactive compounds (methyl-L-phenylalanine, 1,4-β-Dmannotriose, aurantiamide acetate, N-cis-feruloyltyramine, timosaponin A-III, and apigenin) and five critical targets (TH, ADORA2A, SLC6A3, SLC6A4, COMT). Molecular docking confirmed strong binding interactions. Behavioral tests showed that XHG significantly reduced hyperlocomotion and impulsivity-like behaviors. Western blot analyses further revealed regulatory effects on key neurotransmitter-related proteins. DISCUSSION: This integrated study elucidates the multi-target neuroprotective mechanisms of XHG in ADHD and provides a modern scientific foundation for the application of traditional herbal medicine in treating neuropsychiatric disorders. CONCLUSION: This study provides the first comprehensive evidence supporting the neuroprotective properties of XHG in ADHD through multi-target mechanisms, offering a scientific basis for its clinical application as a potential therapeutic agent.
AI/ML Modelling and Standardization of Stability Assessment for Silver Nanoparticle Wound Dressings Aligned with Pharmaceutical Guidelines.
Agarwal A, Mazumder A, Salahuddin
Curr Pharm Des · 2026 May · PMID 42163738 · Publisher ↗
BACKGROUND: Antimicrobial wound dressings are widely used for infection control in acute and chronic wounds; however, unlike pharmaceuticals, there is no harmonized framework defining stability testing requirements (e.g....
BACKGROUND: Antimicrobial wound dressings are widely used for infection control in acute and chronic wounds; however, unlike pharmaceuticals, there is no harmonized framework defining stability testing requirements (e.g., real-time and accelerated aging conditions or performance parameters). This gap weakens quality assurance amid increasing antimicrobial resistance (AMR). OBJECTIVE: To develop a standardized framework for evaluating the physicochemical stability and sustained antimicrobial performance of antimicrobial wound dressings over their labelled shelf life. This was derived from established pharmaceutical principles. Long-term and accelerated stability studies, functional testing such as absorbency, WVTR, OTR, sterility, and biofilm inhibition, silver release, and antimicrobial activity via MIC and MBC were evaluated. An AI/ML model was used as a tool for trend analysis. METHOD: NSD01, NSD02, and NSD03 were three batches that were tested for long-term [at 25°C (±2°C) and 60% (±5%) RH] for two years and accelerated [40°C (±2°C) and 75% (±5%) RH] for six months. The parameters that were assessed included color, size, GSM, absorbency, sterility, WVTR, OTR, UV Visible spectroscopy, silver release (Franz diffusion, ICP MS), MIC/MBC assays (CLSI M07, A11), and Random Forest AI/ML modelling. RESULTS: Physical, chemical, and microbiological integrity was found as per specifications in both studies. Sustained antimicrobial activity was observed via MIC/MBC assays. Biofilm inhibition was found to be significant and long-term. AI/ML models provided insights about performance characteristics and trends. DISCUSSION: The findings suggest that a device-specific framework incorporating parameters of pharmaceutical stability testing and additional tests, such as sustained antimicrobial activity, can be used to assess commercially available dressings. The suggested AI/ML Model was used for explorative trend analysis. CONCLUSION: The standardized framework suggested here can be used as a tool for quality assurance. It can be used for data-based antimicrobial dressing assessment after the product has been marketed.
Network Pharmacology and Bioinformatics Analysis of the Mechanisms Underlying Nao Xue Ping in Intracerebral Hemorrhage Treatment.
He L, Wang X, Liu P … +2 more , Cui Q, Song J
Curr Pharm Des · 2026 May · PMID 42163737 · Publisher ↗
INTRODUCTION: Intracerebral hemorrhage (ICH) is a devastating subtype of stroke with high mortality and limited therapeutic options. Traditional Chinese medicine (TCM), such as Nao Xue Ping (NXP), has shown clinical effi...
INTRODUCTION: Intracerebral hemorrhage (ICH) is a devastating subtype of stroke with high mortality and limited therapeutic options. Traditional Chinese medicine (TCM), such as Nao Xue Ping (NXP), has shown clinical efficacy in ICH management, but its mechanisms remain unclear. METHODS: We employed network pharmacology and molecular docking to investigate the mechanisms of NXP. Active compounds were identified using TCMSP and ETCM databases, while GeneCards and OMIM databases provided ICH-related targets. Protein-protein interaction (PPI) networks, functional enrichment analysis, and molecular docking were performed to uncover key pathways and targets. To validate docking results, 100ns MD simulations and MM/GBSA calculations were performed to evaluate dynamic stability and binding free energies, while key targets were further validated using the GEO database. RESULTS: We identified 11 active compounds and 145 overlapping targets of Nao Xue Ping (NXP) in intracerebral hemorrhage (ICH). Twelve core targets were highlighted through PPI network analysis. Enrichment analyses revealed involvement in inflammation, angiogenesis, and oxidative stress pathways, including PI3KAkt, MAPK, and TNF signaling. Molecular docking confirmed strong binding between key compounds (e.g., rhein, kaempferol) and core targets. Subsequent MD simulations and MM/GBSA calculations verified the dynamic stability of high-affinity complexes, identifying van der Waals interactions as the primary binding driver. GEO validation identified 14 shared genes, with PTGS2 and HSP90AB1 as key therapeutic targets. DISCUSSION: This study systematically explored the mechanisms of Nao Xue Ping (NXP) in treating intracerebral hemorrhage (ICH) using network pharmacology, enrichment analysis, molecular docking, molecular dynamics (MD) simulations, MM/GBSA calculations, and transcriptomic validation. The results indicate that NXP exerts its therapeutic effects through multiple pathways involved in inflammation, oxidative stress, apoptosis, and angiogenesis. Core targets such as PTGS2 and HSP90AB1 were identified and validated using GEO datasets, highlighting their roles in mediating neuroinflammation, blood-brain barrier disruption, and ferroptosis. Molecular docking revealed strong binding affinities between active compounds (e.g., rhein, kaempferol) and these core targets. These findings provide a mechanistic rationale for the clinical efficacy of NXP and suggest that modulation of PTGS2 and HSP90AB1 pathways may offer promising therapeutic strategies for hemorrhagic stroke. CONCLUSION: NXP shows significant potential in treating ICH by targeting key pathways and molecules involved in neuroinflammation, oxidative stress, and tissue repair. Future studies should focus on experimental validation and clinical translation to fully elucidate its therapeutic efficacy and mechanisms in ICH management.
Extracellular Vesicles in Alzheimer's Disease: Mechanisms, Immunotherapy Links, and Clinical Translation.
Kishor K, Arora A, Yashika … +2 more , Yadav S, Singh A
Curr Pharm Des · 2026 May · PMID 42152645 · Publisher ↗
Alzheimer disease (AD) is a progressive neurodegenerative disorder characterized by synaptic dysfunction, neuroinflammation, and cognitive impairment. Although amyloid-β and tau continue to serve as core biomarkers and t...
Alzheimer disease (AD) is a progressive neurodegenerative disorder characterized by synaptic dysfunction, neuroinflammation, and cognitive impairment. Although amyloid-β and tau continue to serve as core biomarkers and therapeutic targets, the clinical efficacy of recent biologic agents targeting amyloid has led to a new paradigm in AD treatment. Nevertheless, emerging data show that lipid metabolism is an important and well-established aspect of AD pathophysiology rather than a new theory. Lipid processing in microglia, astrocytes, and neurons is disrupted, leading to chronic inflammation, impaired amyloid clearance, mitochondrial dysfunction, and synaptic dysfunction. This review critically analyzes how lipid accumulation and lipid droplet biology contribute to Alzheimer's disease using cellular, animal, and human studies. Special focus is placed on enzymatic regulators such as DGAT2, cholesterol transport, and neuron-glia metabolic linkages. This review synthesizes existing mechanistic and translational data to emphasize lipid dysregulation as a complementary therapeutic target and potential biomarker axis that may improve current amyloid- and taudirected therapeutic strategies.
Gabapentin and Pregabalin Overdoses and Their Management: An Update.
Akman C, Ucar AB, Erdem AB … +4 more , Ozkaya B, Ersan E, Erdem B, Karcioglu O
Curr Pharm Des · 2026 May · PMID 42152644 · Publisher ↗
INTRODUCTION/OBJECTIVE: Gabapentinoids are increasingly prescribed and utilized to treat various disorders, including neuropathic pain, post-herpetic neuralgia, and fibromyalgia. This article aims to highlight the advant...
INTRODUCTION/OBJECTIVE: Gabapentinoids are increasingly prescribed and utilized to treat various disorders, including neuropathic pain, post-herpetic neuralgia, and fibromyalgia. This article aims to highlight the advantages and disadvantages of gabapentinoids, specifically gabapentin and pregabalin, and address advancements and areas for improvement in the topic. METHODS: A systematic search was conducted to identify studies related to the issue in the literature. All English- language studies from 2005 to 2025 focusing on the effectiveness and safety profiles of the compounds were abstracted following searches in Google Scholar, PubMed, Scopus, Web of Science, and MEDLINE. Editorials, expert opinions, and retrospective studies were excluded from the analysis. RESULTS: These agents have been beneficial in cutting down the rates of opioid prescriptions. Many research studies showed that pregabalin prescription increased linearly over time, together with co-prescription with opioids in a substantial portion (more than one-fourth) of the total numbers. Lethal intoxications are mostly those with concurrent intake of other substances, especially opioids. DISCUSSION: Although gabapentinoids are getting wider recognition and are used more commonly worldwide in recent decades, clinicians should be aware of the inherent hazards of the agents. Decision-making algorithms and guidelines should address the pros and cons of this group in comparison to opioids and other alternatives in pain management in special groups, such as those with organ failures and important comorbidities. CONCLUSION: Prescribers of gabapentinoids need to pay attention to the use of these agents in special groups at high risk, and findings indicative of misuse and/or abuse have to be monitored properly.
Exploring the Inhibitory Effects of Compounds for the Treatment of Liver Fibrosis: A Computational and Microscopic Approach.
Mehtab A, Ali H, Ali I … +5 more , Abass KS, Alzahrani KJ, Shafique M, Jamil J, Almutairy B
Curr Pharm Des · 2026 May · PMID 42152643 · Publisher ↗
INTRODUCTION: Hepatic fibrosis, a chronic liver injury caused by autoimmune, alcoholic, viral, and non-alcoholic fatty liver disorders, leads to cirrhosis. Proteins that stimulate HSCs to initiate wound healing are suppr...
INTRODUCTION: Hepatic fibrosis, a chronic liver injury caused by autoimmune, alcoholic, viral, and non-alcoholic fatty liver disorders, leads to cirrhosis. Proteins that stimulate HSCs to initiate wound healing are suppressed as part of the treatment. This study aims to identify potential inhibitors of COX2, integrin, PDGF, TGF-β, and protein kinase C, validate in silico results, and compare inhibitory effects using scanning electron microscopy. METHODS: A database was used to identify proteins of interest, and inhibitors against specific proteins previously reported were selected. Ligand-protein interactions were evaluated through docking simulations using MOE, and the resulting complexes were analyzed using SwissADME. The study involved five groups of male rats, each weighing 200-240 g. The first group was a control without treatment or fibrosis induction, the second group was a negative control with CCl4 injection, and groups 3, 4, and 5 received silymarin, rutin, and sorafenib treatments, respectively, in addition to CCl4. RESULTS: The study demonstrated that three compounds-silymarin, rutin, and sorafenib-can inhibit six different proteins. Rutin interacts with multiple proteins and has a docking score of -7.5220. It acts as a P-gp substrate, crosses the blood-brain barrier persistently, and shows high gastrointestinal absorption. DISCUSSION: This work demonstrates how computer-aided drug design can be used to identify potent molecules targeting COX2, PKC, integrin, Claudin 2, TGF-β, and PDGF, advancing drug management and therapy of liver fibrosis. In vivo studies indicate that silymarin is the most effective compound for reducing enzyme levels. CONCLUSION: Microscopic examination of the CCl4 group indicated hepatocellular necrosis, inflammation, fibrosis, and bile duct proliferation, characterized by enlarged ductal cells, bile ductules, and extensive hepatocyte necrosis. Treatment with rutin, silymarin, and sorafenib improved CCl4-induced liver damage. Among these, rutin treatment restored liver architecture, reduced inflammation, lessened fibrosis, and caused minimal hepatocellular damage. Silymarin treatment reduced fibrosis, tissue damage, and inflammatory cell infiltration. Sorafenib treatment caused minimal to moderate hepatocyte damage while improving liver function by decreasing inflammation and fibrosis.
Efficacy of Pimpinella anisum L. in Menopausal Women with Psychological Symptoms: A Randomized Controlled Study Integrated with Machine Learning Analysis.
Begum A, Sultana A, Bin Heyat MB … +7 more , Rahman K, Akhtar F, Al-Huda Z, Banu T, Khaleeq K, Bian S, Sawan M
Curr Pharm Des · 2026 May · PMID 42152642 · Publisher ↗
INTRODUCTION: Menopausal women commonly experience psychological symptoms. These symptoms reduce their quality of life. Pimpinella anisum (anise) is an Unani remedy traditionally used for such problems. This study aimed...
INTRODUCTION: Menopausal women commonly experience psychological symptoms. These symptoms reduce their quality of life. Pimpinella anisum (anise) is an Unani remedy traditionally used for such problems. This study aimed to test the effects of anise on psychological and menopausal symptoms, along with appraising machine learning models in classifying treatment response between the anise and control groups. METHODS: A total of 60 menopausal women received either 4 g of anise per day or a matched placebo, administered in two divided doses over an eight-week period. Primary outcomes included the Depression, Anxiety, and Stress Scale 21 (DASS-21) in menopausal women. Secondary outcomes included overall Modified Kuppermen Index (MKI), Vaginal Health Index (VHI), and treatment satisfaction (MS-TSQ). Machine learning classifiers, including Gradient Boosting (GB), AdaBoost (AB), K-Nearest Neighbours (KNN), Naive Bayes (NB), and Random Forest (RF), were utilised. Safety was monitored weekly through interviews. Hepatic and renal function were evaluated at baseline and after 12 weeks. RESULTS: Baseline variables were similar between the two groups. Anise significantly reduced the DASS-21 scores compared to placebo at 8 weeks (p < 0.0001). At 8 weeks, participants receiving anise demonstrated significant improvements across multiple measures. DASS‑21 scores declined markedly compared with placebo (p < 0.0001), with more than 80% reporting no symptoms of depression, anxiety, or stress. MKI and VHI scores also improved significantly in the anise group (p < 0.0001), while the control group showed no notable change. Satisfaction ratings on the MS‑TSQ were high among anise recipients but low in the placebo arm. No adverse effects were observed. In addition, the KNN model achieved outstanding performance, correctly classifying group membership with 99.20% accuracy. DISCUSSION: Anise demonstrated significant benefits in reducing psychological and menopausal symptoms, with no adverse effects reported, supporting its potential as a safe non‑hormonal therapy. The strong performance of the KNN model additionally exemplifies how machine learning can improve menopausal research by precisely distinguishing treatment responses. Upcoming studies with larger and more varied populations will be important to endorse these findings and to discover long‑term outcomes. CONCLUSION: This research indicates that anise is a safe and effective alternative for relieving psychological symptoms in menopausal women. The KNN model reliably classified treatment outcomes, signifying that the integration of anise treatment with AI‑based assessment methods could enrich research on menopause care.
Structure-Based Design and Machine Learning-Driven Prioritization of EGFR Inhibitors.
Karlapudi AP, HimaBindu VK, Kumar D
Curr Pharm Des · 2026 May · PMID 42152641 · Publisher ↗
INTRODUCTION: The Epidermal Growth Factor Receptor (EGFR) is a significant target in cancer therapy as it facilitates tumor proliferation and persistence. EGFR Tyrosine Kinase Inhibitors (TKIs) have been shown to be effe...
INTRODUCTION: The Epidermal Growth Factor Receptor (EGFR) is a significant target in cancer therapy as it facilitates tumor proliferation and persistence. EGFR Tyrosine Kinase Inhibitors (TKIs) have been shown to be effective in clinical settings, but resistance mutations limit their long-term effectiveness. As a result, there remains a need for new and more effective EGFR inhibitors. METHODS: We synthesized a chemical library by adding 15 different R groups to a urea-aryl hydrazone core at the two para positions. This gave us 81 different structures. To determine pIC₅₀ values, molecular fingerprints were generated using PaDEL-Descriptor and subsequently used as input features for a pre-trained Random Forest regression model. Afterward, molecular docking and 100-nanosecond molecular dynamics simulations were used to assess the best candidates' ability to bind to the EGFR kinase structure and their stability. RESULTS: The scaffold-based enumeration yielded 81 compounds with distinct structures. A machine learning approach with a random forest model identified potential candidates with pIC₅₀ values greater than 6, indicating active status. Docking studies have demonstrated the stability of compounds that form hydrogen-bond interactions and hydrophobic contacts, comparable to those of Erlotinib. Molecular dynamics simulations have been employed to validate that these candidate complexes maintain stable interactions during the simulation time. DISCUSSION: The computational approach has identified potential lead molecules with stable binding poses and predicted their activity from inhibitory concentrations, yielding results comparable to those of approved drugs. The analysis based on selective halogenation substitution enhanced the stability of interactions, preserving the major hinge-region interaction as a hydrogen bond. The technique would offer a more comprehensive approach for prioritizing lead molecules and for refining new EGFR inhibitors. CONCLUSION: This research demonstrates the integration of scaffold-based chemical design and machine learning. Atomistic simulations speed up the search for EGFR inhibitors. This process produces drug-like candidates that are expected to perform effectively and remain stable, facilitating additional testing and improving cancer research.
Next-Generation Implant Technologies: Breakthroughs, Barriers, and the Road Ahead.
Shetty D, Rathee S, Jain SK
Curr Pharm Des · 2026 May · PMID 42152640 · Publisher ↗
Rapid advancements in medical devices and implant technologies have transformed healthcare, providing innovative solutions across orthopedics, cardiovascular, dentistry, neurology, and cosmetic applications. These implan...
Rapid advancements in medical devices and implant technologies have transformed healthcare, providing innovative solutions across orthopedics, cardiovascular, dentistry, neurology, and cosmetic applications. These implants enhance patient outcomes by restoring function and improving quality of life. This review highlights progress in materials, design strategies, manufacturing methods, and regulatory frameworks. The use of biocompatible metals, ceramics, polymers, and emerging biomaterials has improved implant durability, mechanical integrity, and compatibility. Fabrication techniques such as 3D printing and additive manufacturing now enable highly customized, patient-specific implants. Surface modifications, nanotechnology, and bioactive coatings further enhance osseointegration and reduce infection risks. Regulatory standards remain central to ensuring safety and efficacy, yet challenges persist, including long-term biocompatibility, immune responses, and high costs. Addressing these issues while harnessing technological innovations will be key to advancing the field. This article provides a comprehensive overview of current trends, challenges, and future directions to guide researchers, clinicians, and industry stakeholders in driving continued innovation.
Mechanistic Insights into Xihuang Wan against Bladder Cancer via PI3K/ AKT/BCL2-Mediated Apoptosis Inhibition: Integrated Network Pharmacology, Molecular Docking, Molecular Dynamics Simulations and Experimental Validation.
Li J, Zhang S, Yu S … +6 more , Shen Y, Chen K, Chen Z, Xu D, Liu H, Shen H
Curr Pharm Des · 2026 May · PMID 42152639 · Publisher ↗
INTRODUCTION: Bladder cancer (Blca) is highly recurrent with limited options for advanced disease, and the pharmacological basis of traditional Chinese medicine formulas such as Xihuang Wan (XHW) in Blca is poorly define...
INTRODUCTION: Bladder cancer (Blca) is highly recurrent with limited options for advanced disease, and the pharmacological basis of traditional Chinese medicine formulas such as Xihuang Wan (XHW) in Blca is poorly defined. This study investigated the anti-bladder cancer mechanism of XHW by identifying its core bioactive component and its modulation of PI3K/AKT/BCL2-mediated apoptosis. METHODS: Network pharmacology integrated TCMSP/SymMap and GeneCards/OMIM to identify active ingredients, Blca targets, and enriched pathways. Molecular docking and 100-ns molecular dynamics simulations evaluated the binding of the core component quercetin to key targets. CCK-8 and Western blot assays assessed XHW cytotoxicity, PI3K-AKT signaling, and apoptosis-related proteins in MB49 cells. Antitumor efficacy was confirmed in a C57BL/6 mouse MB49 subcutaneous xenograft model. RESULTS: We identified 110 common targets and highlighted quercetin as a central ingredient acting on AKT1 and BCL2. KEGG analysis implicated the PI3K-AKT pathway, and docking/simulations supported stable quercetin binding. XHW inhibited MB49 proliferation and suppressed tumor growth in vivo. XHW, similar to Wortmannin, reduced phosphorylated AKT, increased the Bax/Bcl-2 ratio, and elevated cleaved caspase-3, indicating mitochondrial apoptosis via PI3K-AKT inhibition. DISCUSSION: These findings indicate that XHW acts partly through functional inhibition of the PI3K/ AKT/BCL2 axis rather than nonspecific cytotoxicity. CONCLUSION: Xihuang Wan exerts anti-bladder cancer activity mainly through quercetin targeting the PI3K/AKT/BCL2 axis to inhibit tumor cell survival and trigger mitochondrial apoptosis, supporting further development of XHW and quercetin as adjunctive strategies for bladder cancer.
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