Curr. Pharm. Des. [JOURNAL]
Sun
200 papers
Molecular Insights into the MdtABC Efflux Pump Genes in Clinical Salmonella typhi Isolates from Typhoid Patients.
Muhammad, Azam S, Rehman N … +5 more , Alhegaili AS, Khan I, Samad FU, Ahmad A, Ali S
Curr Pharm Des · 2026 Mar · PMID 41832696 · Publisher ↗
INTRODUCTION: Typhoid fever is a potentially fatal systemic infection caused by Salmonella typhi (S. typhi), a Gram-negative, rod-shaped, facultative anaerobe. This study aimed to characterize the efflux pump genes, mole...
INTRODUCTION: Typhoid fever is a potentially fatal systemic infection caused by Salmonella typhi (S. typhi), a Gram-negative, rod-shaped, facultative anaerobe. This study aimed to characterize the efflux pump genes, molecular mutations, and antibiotic susceptibility patterns in clinical isolates. METHODS: A total of 2950 blood samples were collected from suspected typhoid patients. Of these, 380 (12.88%) bacterial isolates were recovered, of which 236 (62.10%) were Gram-negative. S. typhi was detected in 95 isolates (25% of all bacterial isolates), corresponding to an overall prevalence of 3.22%. Identification was performed using API 20-E strips and partial 16S rRNA gene sequencing. RESULTS: Resistance profiling classified the isolates into multidrug-resistant (MDR, 13.68%) and extensively drug-resistant (XDR, 86.31%) categories. High resistance was observed to ampicillin (98.94%) and chloramphenicol (93.68%), whereas no resistance was detected to azithromycin or meropenem. Minimum inhibitory concentration (MIC) testing using E-Strips showed the highest MIC values for trimethoprimsulfamethoxazole (MIC50: 0.125 μg/ml, MIC90: 0.50 μg/ml) and the lowest for ciprofloxacin (MIC₅₀: 0.008 μg/ml, MIC₉₀: 0.023 μg/ml). Among the efflux pump genes, mdtB (32.63%) was the most prevalent, followed by mdtC (30.52%) and mdtA (29.47%). Multiple mutations were identified and evaluated using the I-Mutant 2.0 server. Protein structures were modeled using trRosetta and Discovery Studio. Phylogenetic analysis using MEGA-11 revealed evolutionary relationships with other Salmonella enterica serovars. DISCUSSION: A serious public health issue that increases mortality and morbidity rates worldwide is antibiotic resistance. Among the mechanisms underlying antibiotic resistance in bacteria are degradation of antibiotics and/or modification of enzymes, changing drug targets to alter the affinity of antibiotics, altering bacterial surfaces by changing the expression of external membrane proteins, and active bacterial efflux of drugs. The drug's binding affinity can be changed by mutations in efflux pump genes that change the shape of the substrate- binding pocket. These structural alterations may improve the pump's capacity to identify and eliminate antibiotics, reducing intracellular drug levels and increasing resistance to several drugs. CONCLUSION: This study highlights the alarming rise of multidrug resistance in S. typhi isolates and identifies key genetic mutations that may influence efflux pump function, potentially contributing to enhanced antibiotic resistance.
The JN.1 Variant: Emergence and Global Spread.
Rani P, Nandal R, Gupta V … +1 more , Kumar D
Curr Pharm Des · 2026 Mar · PMID 41832695 · Publisher ↗
The emergence of the COVID-19 JN.1 variant has garnered global attention due to its increasing prevalence across multiple regions. First identified in August 2023, JN.1 is a descendant of the Omicron subvariant BA.2.86....
The emergence of the COVID-19 JN.1 variant has garnered global attention due to its increasing prevalence across multiple regions. First identified in August 2023, JN.1 is a descendant of the Omicron subvariant BA.2.86. Common clinical symptoms associated with JN.1 infection include sore throat, fever, dry cough, nausea, and vomiting. Although the World Health Organization has classified JN.1 as a Variant of Interest, it currently poses a low global health risk. Nonetheless, its enhanced transmissibility, particularly in cold and dry climates, warrants close monitoring. This review provides an in-depth analysis of JN.1's biological profile, epidemiological trends, transmissibility, immune-evasion capabilities, and vaccine responsiveness. A detailed literature review was conducted between January 2023 and August 2024, focusing on recent research regarding the spread and clinical implications of JN.1. Current evidence indicates that the L4555 spike protein mutation is the primary factor contributing to JN.1's increased infectivity and stronger immune evasion compared to earlier variants. The variant demonstrated a steady rise in transmission rates from November 2023 to March 2024. Despite these challenges, existing vaccines continue to offer substantial protection against the severe illness associated with this variant. Antiviral medications such as Lagevrio, Veklury, and Paxlovid also remain effective against JN.1. Continuous surveillance approaches, including digital tracking systems, wastewater monitoring, and genomic sequencing, are essential for the early detection and control of JN.1.
Nanomicelles in Ocular Drug Delivery: Overcoming Barriers and Enhancing Therapeutic Efficacy.
Krishnaswami V, Janakiraman K, Sethuraman V … +1 more , Raja J
Curr Pharm Des · 2026 Mar · PMID 41832694 · Publisher ↗
This study provides a comprehensive overview of nanomicelle-based drug delivery methods used to treat ocular disorders. A review of current literature was conducted by scanning electronic databases up until December 2024...
This study provides a comprehensive overview of nanomicelle-based drug delivery methods used to treat ocular disorders. A review of current literature was conducted by scanning electronic databases up until December 2024, including PubMed, Scopus, Web of Science, and Google Scholar. Keywords such as "Nanomicelles" and specific ocular conditions including "Glaucoma," "Conjunctivitis," "Cataract," and "Retinopathy" were used to identify relevant material. Original research articles, reviews, and clinical trials were given special attention. Administering drugs to the eye remains one of the most challenging tasks among various drug delivery systems. Delivering drugs to the posterior pole or the delicate anatomical layers of the eye poses a substantial challenge for researchers and pharmacologists. Conventional formulations often exhibit inadequate corneal penetration, poor absorption, or noticeable adverse visual effects. Nanotechnology has greatly facilitated the development of novel therapeutic strategies for ocular disorders. Nanomicelle-based formulations benefit significantly from the nano-delivery platform. Nanomicelles can overcome anatomical barriers and clearance processes. Depending on the polymer used, nanomicelles can be engineered and released to meet specific requirements. They are notable for their small size, low toxicity, ability to improve drug penetration through ocular epithelia with minimal irritation, enhancement of hydrophobic drug solubility, achievement of therapeutic concentrations, and prevention or reduction of drug degradation. This study highlights the use of nanomicellar-based delivery systems in treating ocular diseases such as diabetic retinopathy, glaucoma, age-related macular degeneration, cataract, conjunctivitis, keratitis, and retinoblastoma.
Advancements in Mouth Dissolving Films: Emerging Technologies, Polymers, and Drug Delivery Strategies with an Overview of Anti-Hypertensive and Anti-Depressant Drugs.
Mohammed J, Nalluri BN
Curr Pharm Des · 2026 Mar · PMID 41832693 · Publisher ↗
Mouth-Dissolving Films (MDFs) have revolutionized drug delivery systems due to a non-invasive route of administration and improved patient adherence. This article reviews the integration of novel drug delivery technologi...
Mouth-Dissolving Films (MDFs) have revolutionized drug delivery systems due to a non-invasive route of administration and improved patient adherence. This article reviews the integration of novel drug delivery technologies, inventive polymers, and modern manufacturing processes into MDFs. Industrial revolution technologies such as 3D printing, electrospinning, and hot melt extrusion, enable precision, customization, and scalability for efficient production, overcoming the other conventional methods' precision limitations. Moreover, the incorporation of novel natural, synthetic, and biodegradable polymers increases the stability, mechanical properties, and environmental impact of MDFs. On the other hand, synthetic polymers, such as polyvinyl alcohol and polyethylene glycol, provide uniformity and control, while pullulan and xanthan gum are much more affordable natural polymers. Even though polylactic acid and polycaprolactone are more expensive biodegradable polymers, they are more environmentally beneficial. MDFs enable the integration of novel drug-delivery methods, such as hydrogels, liposomes, microspheres, and even nanoparticles, to enhance therapeutic effectiveness through improved bioavailability, enhanced absorption, and controlled release. Most importantly, the use of 3D printing technology improves all aspects of MDF production, providing us with the possibility of personalization for medicine with complicated shapes where disintegration and dose delivery are needed. This review presents an insightful perspective on the forthcoming advancements and initiatives to be upgraded in MDFs and how innovations can mitigate existing challenges in the manufacturing and delivery of MDFs. In this regard, the continuous improvement of these domains will contribute significantly towards the production of effective and convenient means of drug delivery.
Machine Learning Algorithm for Nanomedicine: AI Curated Nanocarriers for Cancer Treatment.
Kumar A, Qasim S, Sharma A … +2 more , Gugulothu D, Verma S
Curr Pharm Des · 2026 Mar · PMID 41832692 · Publisher ↗
Cancer remains a major global health challenge due to its genetic variability and intricate molecular mechanisms, which complicate the development of effective therapies. This review elucidates the integration of AI-driv...
Cancer remains a major global health challenge due to its genetic variability and intricate molecular mechanisms, which complicate the development of effective therapies. This review elucidates the integration of AI-driven methodologies in nanoparticle (NP) design, optimizing drug delivery systems (DDSs) for targeted cancer therapy. AI's predictive analytics facilitate the rational design of nanocarriers, enhancing drug bioavailability, optimizing pharmacokinetics, and improving tumor penetration. The incorporation of machine learning (ML) models accelerates NP fabrication, enabling real-time simulation of tumor dynamics and drug release kinetics. Furthermore, AI-powered platforms, such as EVOnano, simulate in silico tumor microenvironments to refine nanocarrier functionalities. This synergy fosters the development of next-generation smart therapeutics, wherein adaptive nanomedicines exhibit enhanced tumor specificity while mitigating systemic toxicity. Challenges, such as nanoparticle scalability, AI interpretability, and biological heterogeneity, persist, necessitating interdisciplinary advances. Nevertheless, AI-assisted nanomedicine signifies a paradigm shift towards highly efficacious, patient-tailored cancer interventions, revolutionizing treatment landscapes and propelling oncology into a new frontier of data-driven, precision-based therapeutics.
Advancing Global Drug Safety: Challenges and Future Perspectives in Pharmacovigilance.
Avadhani NS, Satya Sri NR, Rathee S … +2 more , Soni S, Patil UK
Curr Pharm Des · 2026 Mar · PMID 41832691 · Publisher ↗
Adverse Drug Reactions (ADRs) pose significant challenges to patient safety, healthcare systems, and public health worldwide. As the pharmaceutical landscape expands with complex therapies such as biologics and biosimila...
Adverse Drug Reactions (ADRs) pose significant challenges to patient safety, healthcare systems, and public health worldwide. As the pharmaceutical landscape expands with complex therapies such as biologics and biosimilars, the need for robust pharmacovigilance systems has become paramount. This review provides a comprehensive overview of ADRs, their classification, underlying mechanisms, and associated clinical and economic impacts. It explores global pharmacovigilance frameworks, including the WHO Programme for International Drug Monitoring, and examines the roles of major regulatory bodies such as the FDA, EMA, CDSCO, and MHRA in ensuring drug safety. Special emphasis is placed on the challenges faced by developing countries, including underreporting and inadequate infrastructure, alongside strategies to overcome these barriers through capacity building and technology integration. The review also highlights advancements in pharmacovigilance methodologies, including the application of artificial intelligence, big data analytics, blockchain, and IoT devices, to enhance ADR detection, reporting, and management. Case studies and regional pharmacovigilance systems are analyzed to illustrate best practices and areas for improvement. Additionally, the role of pharmacovigilance in the context of the COVID-19 pandemic underscores the necessity for adaptive frameworks during global health crises. By addressing current challenges and emerging trends, this review aims to provide actionable insights to improve drug safety monitoring and foster global cooperation in pharmacovigilance practices.
The Role of Phytosomes in Enhancing the Bioavailability and Efficacy of Herbal Phytoconstituents with Anxiolytic Potential - A Comprehensive Review.
Mahima, Mazumder A, Pentela B
Curr Pharm Des · 2026 Mar · PMID 41832690 · Publisher ↗
Anxiety disorders are among the most common mental health illnesses in the world, impacting millions of people from a wide range of backgrounds. Herbal anxiolytics have gained significant attention as natural therapeutic...
Anxiety disorders are among the most common mental health illnesses in the world, impacting millions of people from a wide range of backgrounds. Herbal anxiolytics have gained significant attention as natural therapeutic alternatives. However, many of these botanical extracts exhibit poor bioavailability, limiting their therapeutic efficacy. Phytosome technology has appeared as a cutting-edge method of drug delivery intended to improve the bioavailability and efficacy of herbal compounds. This review comprehensively explores the potential of phytosomes to improve the pharmacokinetics and bioavailability of anxiolytic herbs, focusing on their formulation strategies, delivery advantages, and the prospects for their application in anxiety management. While a substantial body of studies has examined the development and formulation of phytosomes for various therapeutic applications, few have specifically evaluated their anxiolytic properties. Additionally, this paper examines safety considerations, regulatory aspects, and future research directions essential for optimizing phytosome-based anxiolytic interventions. By bridging traditional herbal medicine with advanced drug delivery systems, phytosomes present a transformative strategy to enhance the therapeutic bioavailability and efficacy of herbal-based treatments for anxiety disorders.
Shengjiang Xiexin Decoction Mitigates Irinotecan-Triggered Delayed-Onset Diarrhea by Modulating Short-Chain Fatty Acids and the TLR4-MyD88-JNK/ NF-κB Pathway.
Deng C, Gao Y, Chen D … +3 more , Chen C, Wang Q, Jia L
Curr Pharm Des · 2026 Mar · PMID 41832689 · Publisher ↗
INTRODUCTION: Delayed-onset diarrhea, a common adverse reaction to irinotecan, affects both the effectiveness of chemotherapy and the quality of life of cancer patients. This type of diarrhea has been effectively treated...
INTRODUCTION: Delayed-onset diarrhea, a common adverse reaction to irinotecan, affects both the effectiveness of chemotherapy and the quality of life of cancer patients. This type of diarrhea has been effectively treated with Shengjiang Xiexin decoction (SXD), a staple in traditional Chinese medicine (TCM). This study sought to clarify the pharmacological mechanism by which SXD alleviates irinotecan-induced diarrhea. METHODS: Irinotecan-triggered delayed-onset diarrhea was modeled in rats, and effectiveness was investigated by evaluating body weight, diarrhea score, and intestinal mucosal pathology. The research investigated tight junction protein expressions in intestinal epithelial cells (IECs), especially Zonula occludens-1 (ZO-1) and occludin, by immunofluorescence (IF) labeling. Furthermore, intestinal permeability was evaluated utilizing the fluorescence-labeled isothiocyanate (FITC) glucan technique. Intestinal short-chain fatty acids (SCFAs) were quantified by use of ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), and colorimetric analysis was utilized to assess β-glucuronidase activity in the gut. Finally, the mRNA expressions of TLR4-Myd88-JNK/NF-κB and Muc2 in the gut were quantified by use of reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). RESULTS: SXD had considerable protective benefits in rats, alleviating body weight loss, decreasing diarrhea scores, and diminishing intestinal mucosal damage and permeability. The therapy increased the expression of ZO-1 and occludin proteins, therefore preserving the integrity of the intestinal mucosal barrier. Moreover, SXD significantly elevated SCFA levels in the gut while reducing β-glucuronidase activity. SXD reduced the mRNA levels of JNK, NF-κB, Myd88, and TLR4, while increasing those of Muc2 in rat jejunum tissues. DISCUSSION: SXD ameliorates irinotecan-induced diarrhea via a multi-mechanism approach, including inhibition of bacterial β-glucuronidase, restoration of beneficial short-chain fatty acids, enhancement of intestinal barrier integrity, and suppression of the TLR4/MyD88/NF-κB inflammatory pathway. CONCLUSION: This study provides a foundation for further investigation of SXD as a complementary strategy to improve the safety of irinotecan chemotherapy.
A Short Review and Update on Epidemiology, Treatment, and Management of Herpes Zoster (Shingles) Infection.
Behera D, Belemkar S
Curr Pharm Des · 2026 Mar · PMID 41832688 · Publisher ↗
Herpes zoster, also known as shingles, is caused by the reactivation of the Varicella-Zoster Virus (VZV), which remains dormant in the cranial sensory nerve ganglia and spinal dorsal root ganglia after the initial VZV in...
Herpes zoster, also known as shingles, is caused by the reactivation of the Varicella-Zoster Virus (VZV), which remains dormant in the cranial sensory nerve ganglia and spinal dorsal root ganglia after the initial VZV infection is cured in a patient. When it reactivates, it travels down the nerve to the skin, causing a painful rash and blisters. The pathophysiology involves viral replication in nerve cells, inflammation, and subsequent skin lesions. Herpes zoster can have a significant impact on an individual's physical, psychological, and social well-being. While the condition is usually not life-threatening, it can cause painful and debilitating complications. Herpes zoster can cause significant morbidity, primarily due to Postherpetic Neuralgia (PHN), a persistent neuropathic pain condition. While acute pain during the initial HZ rash can be intense, PHN can be debilitating and significantly impact a patient's quality of life. Other complications, though less common, can include vision loss, neurological problems, and secondary bacterial infections. Herpes zoster (HZ), which has a lifelong risk of 20 to 30% that rises with age, is a prevalent disease in the elderly and immunocompromised patients and leads to increased healthcare costs. The primary goals of HZ management are to minimize and prevent Postherpetic Neuralgia (PHN) and Zoster-Associated Pain (ZAP), as well as to promote a speedy recovery from the viral infection. The treatment of infection requires the use of antivirals that combat viral replication. However, only a few antivirals, such as acyclovir, famciclovir, valacyclovir, amenamevir, and brivudine, have clinical licenses for the treatment of HZ. Thankfully, several novel HZ medications have been proposed and studied, including new antivirals that target various Herpesviridae species. Regular immunization with available vaccines has demonstrated a significant impact on lowering the incidence of HZ and PHN in people over 60 years of age. This article reviews the etiology, epidemiology, pathophysiology, clinical features, evaluation, and available treatments and vaccines for the management of HZ infection, using articles and reviews available in public databases to date (PubMed, Scopus, Embase, and manual searches of Google Scholar). In addition, the differences in safety and effectiveness between the antivirals that are currently licensed for the treatment of HZ, the potential use of novel antivirals in the future for treating HZ, and the antivirals' therapeutic or preventive effects on ZAP or PHN are also discussed.
Association of Monocyte Chemoattractant Protein-1 and Endothelin-1 Genes with Cardiac Pro-Β-Type Natriuretic Peptide Levels in Obese Hypertensive Patients.
Hussein MA, Al-Qaim ZH, Ramadan Youssuf A … +3 more , Kenawy MA, Ali WA, Mohamed ZN
Curr Pharm Des · 2026 Mar · PMID 41832687 · Publisher ↗
INTRODUCTION: Obesity and hypertension synergistically increase cardiovascular risk, with Monocyte Chemoattractant Protein-1 (MCP-1), Endothelin-1 (ET-1), and Pro-B-Type Natriuretic Peptide (Pro- BNP) implicated in vascu...
INTRODUCTION: Obesity and hypertension synergistically increase cardiovascular risk, with Monocyte Chemoattractant Protein-1 (MCP-1), Endothelin-1 (ET-1), and Pro-B-Type Natriuretic Peptide (Pro- BNP) implicated in vascular dysfunction and cardiac stress. However, their combined role in obesity-driven hypertension remains poorly understood. This study aimed to investigate the associations between MCP-1, ET-1, and Pro-BNP levels in obese hypertensive patients and evaluate their collective contribution to disease pathogenesis. METHODS: This prospective, non-randomized clinical study enrolled 97 adult male participants, stratified into four groups: healthy controls (n = 22), overweight normotensive individuals (n = 25), class I obese hypertensive patients (n = 25), and class II obese hypertensive patients (n = 25). Blood samples were collected and analyzed for metabolic parameters (fasting glucose, insulin, lipid profile), oxidative stress markers (MDA, GSH, SOD), and inflammatory cytokines (VEGF, IL-1β, IL-9). Gene expression levels of MCP-1, ET-1, and Pro-BNP were quantified using real-time PCR, while protein expression was assessed via Western blotting. Statistical analyses included one-way ANOVA with Bonferroni correction, Pearson correlation coefficients, and multivariable linear regression models adjusted for age, BMI, metabolic, and oxidative stress parameters. RESULTS: Class II obese hypertensive patients exhibited the highest systolic and diastolic blood pressure, body mass index, and the most severe metabolic dysregulation, including elevated fasting glucose, insulin resistance, and dyslipidemia. Oxidative stress was significantly increased, as indicated by elevated MDA levels and reduced GSH and SOD activity. Inflammatory cytokines, including VEGF, IL-1β, and IL-9, were markedly elevated in this group. Gene and protein expression levels of Pro-BNP, ET-1, and MCP-1 were significantly upregulated in a stepwise manner across the groups, with class II patients showing the highest expression. Specifically, protein levels of Pro-BNP, ET-1, and MCP-1 were increased by 204.8%, 222.2%, and 180.6%, respectively, compared with healthy controls (all p < 0.05). Strong positive correlations were observed between Pro-BNP and both ET-1 and MCP-1 (r = 0.991, p < 0.001 for both). Receiver operating characteristic (ROC) analysis demonstrated high predictive accuracy for Pro-BNP (AUC = 0.94), ET-1 (AUC = 0.89), and MCP-1 (AUC = 0.92), with a combined biomarker panel achieving an AUC of 0.97. DISCUSSION: The robust interrelationships among MCP-1, ET-1, and Pro-BNP suggest their synergistic involvement in promoting vascular inflammation, endothelial dysfunction, and cardiac stress in obesity-related hypertension. These biomarkers may serve as diagnostic indicators and therapeutic targets. Limitations include the male-only cohort and cross-sectional design. CONCLUSION: The robust interrelationships among MCP-1, ET-1, and Pro-BNP suggest their synergistic involvement in promoting vascular inflammation, endothelial dysfunction, and cardiac stress in obesity-related hypertension. These biomarkers may serve as valuable diagnostic indicators and potential therapeutic targets. Further interventional studies are warranted to validate their clinical utility and explore targeted treatment strategies.
Breaking Barriers: Advancing Transdermal Drug Delivery for Bioactive Compounds.
Soni S, Rathee S, Patil UK
Curr Pharm Des · 2026 Mar · PMID 41832686 · Publisher ↗
Transdermal Drug Delivery (TDD) has emerged as a promising alternative to conventional routes of administration, offering controlled drug release, improved bioavailability, and patient compliance. Recent advancements in...
Transdermal Drug Delivery (TDD) has emerged as a promising alternative to conventional routes of administration, offering controlled drug release, improved bioavailability, and patient compliance. Recent advancements in formulation strategies, penetration enhancers, and novel carrier systems have significantly enhanced the efficacy of transdermal drug delivery. This review comprehensively discusses the fundamental principles, advantages, and limitations of TDD while exploring innovative approaches, including Microneedles (MN), nanoformulations, and iontophoresis, to overcome skin permeability barriers. Furthermore, we highlight recent advancements in polymeric systems and bioresponsive technologies that have revolutionized transdermal therapeutics. Despite notable progress, challenges such as drug stability, skin irritation, and limited drug permeability persist. Addressing these concerns through interdisciplinary research and technological innovations is crucial for further expanding the scope of TDD. This review provides an in-depth analysis of current trends, challenges, and future perspectives to advance transdermal therapeutic systems for enhanced clinical applications.
Jiawei Zaoqi Decoction Attenuates Polycystic Ovary Syndrome by Inhibiting AGE-RAGE-Mediated Cell Senescence of Granulosa Cells.
Tang H, Ouyang X, Chong XE … +4 more , Yang Y, Fu J, Zhou Q, Li L
Curr Pharm Des · 2026 Mar · PMID 41832685 · Publisher ↗
INTRODUCTION: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder characterized by hormonal imbalances, ovarian dysfunction, and metabolic irregularities. Jiawei Zaoqi Decoction (JWZQD), a Traditional Chin...
INTRODUCTION: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder characterized by hormonal imbalances, ovarian dysfunction, and metabolic irregularities. Jiawei Zaoqi Decoction (JWZQD), a Traditional Chinese Medicine (TCM) formulation, has shown potential as a multi-targeted therapeutic intervention for PCOS. However, its underlying mechanisms remain unclear. In this study, we explored the therapeutic effects and molecular mechanisms of JWZQD in managing PCOS. METHODS: We employed a multi-model approach integrating clinical data, animal models, and mechanistic assays. Clinical efficacy was evaluated in a cohort of PCOS patients, while a letrozole- induced rat model combined with a high-fat diet was used to assess reproductive and metabolic outcomes. Network pharmacology, Gene Ontology, KEGG enrichment, and protein-protein interaction analyses were applied to identify key targets and pathways. Granulosa-cell experiments under oxidative stress and insulin stimulation were performed for functional validation. RESULTS: JWZQD administration significantly decreased serum luteinizing hormone and testosterone levels, improved insulin, and restored estrous cyclicity in PCOS patients and rats. Histology and ultrasound revealed reduced cystic follicles and normalized ovarian stroma. Bioinformatic analyses identified cellular senescence and AGE-RAGE signaling as core pathways, with quercetin and fisetin emerging as critical bioactive compounds. In vitro, quercetin and fisetin suppressed senescence markers (p21, p53, γH2AX) and rescued granulosa-cell proliferative capacity, confirming the network predictions. DISCUSSION: These findings provide mechanistic insight into how JWZQD ameliorates PCOS, highlighting its multi-targeted regulation of endocrine, metabolic, and ovarian functions. Importantly, our results suggest that targeting granulosa-cell senescence may represent a novel therapeutic strategy. CONCLUSION: JWZQD mitigates PCOS by modulating AGE-RAGE-mediated granulosa-cell senescence through its active compounds quercetin and fisetin. This study supports the clinical potential of JWZQD as an alternative or complementary therapy for PCOS.
Next-Generation Wound Care: The Role of Nanocarriers in Accelerating Healing and Regeneration.
Shravya C, Rathee S, Soni S … +1 more , Jain SK
Curr Pharm Des · 2026 Mar · PMID 41832684 · Publisher ↗
Wound healing is a complex biological process consisting of four key phases: hemostasis, inflammation, proliferation, and remodeling. While acute wounds typically heal without complications, chronic wounds present a majo...
Wound healing is a complex biological process consisting of four key phases: hemostasis, inflammation, proliferation, and remodeling. While acute wounds typically heal without complications, chronic wounds present a major healthcare concern due to persistent infections, poor drug delivery, and delayed tissue regeneration. Nanotechnology has emerged as a promising tool for enhancing wound care by improving drug delivery, reducing microbial load, and supporting tissue repair. This review highlights the application of various nanocarriers, including liposomes, niosomes, hydrogels, and solid lipid nanoparticles, for wound management. These systems enhance drug retention at the wound site, control release profiles, and promote cell proliferation and angiogenesis. Many also exhibit antimicrobial and anti-inflammatory properties, making them suitable for chronic wound treatment. The integration of phytochemical-based compounds into nanosystems is discussed, offering sustainable, biocompatible, and cost-effective approaches. Hybrid platforms, such as nanocomposite hydrogels and bioactive nanoparticles, are presented for their improved healing outcomes and multifunctional performance. Furthermore, the review includes recent patents to reflect technological advancements and innovation in this field. Despite promising developments, challenges such as scalability, cost, and regulatory considerations remain. Future research should focus on improving the design, safety, and accessibility of nanotechnology-based wound therapies.
Anti-Melanogenic Potential of Emulsions Containing Jaboticaba Peel Extract (Plynia peruviana (Poir.) Govaerts).
Goelzer Neto CF, da Silveira VC, Bernardi LS … +5 more , Matte BF, Tramontina D, Rodrigues NS, Alba GL, Bertol CD
Curr Pharm Des · 2026 Mar · PMID 41832683 · Publisher ↗
INTRODUCTION: Skin hyperpigmentation is a common concern that can significantly impact aesthetic perception and self-esteem. Consequently, there is growing interest in identifying natural inhibitors of melanin synthesis...
INTRODUCTION: Skin hyperpigmentation is a common concern that can significantly impact aesthetic perception and self-esteem. Consequently, there is growing interest in identifying natural inhibitors of melanin synthesis to develop cosmetic formulations that are effective, safe, and sustainable. This study aimed to develop, characterize, and evaluate the in vitro anti-melanogenic potential of emulsions containing jaboticaba (Plynia peruviana (Poir.) Govaerts) peel extract in combination with azelaic acid (AA). METHODS: Four distinct formulations were prepared: TAAJ (AA + jaboticaba extract, with turbo-shear mixing), AAJ (AA + jaboticaba extract, without high-shear mixing), TAAAE (AA + ellagic acid (EA), with turbo- shear mixing), and TAA (AA, with turbo-shear mixing). All formulations underwent physicochemical characterization and statistical analysis. RESULTS: Particle sizes ranged from 295.20 to 630.50 nm, with polydispersity index (PDI) values between 0.1 and 1.0, and zeta potential from -6.82 to +2.02 mV. Jaboticaba peel extract demonstrated excellent performance in both antioxidant assays and mushroom tyrosinase inhibition, surpassing conventional agents. TAAJ exhibited the highest anti-melanogenic activity, achieving the greatest tyrosinase inhibition and the lowest IC50. TAAJ and AAJ showed the strongest copper-ion chelating activity, while jaboticaba peel extract and TAAAE also displayed chelating capacity; TAA showed none. TAA induced the most significant reduction in melanin synthesis in B16F10 melanoma cells. DISCUSSION: Among the tested formulations, the most promising was selected based on macroscopic characteristics, presenting a homogeneous, milky appearance without phase separation. This suggests that all tested formulations exhibited some degree of anti-melanogenic activity, likely through distinct mechanisms influenced by the complex interactions among their active components. CONCLUSION: To the best of our knowledge, no previous studies have investigated jaboticaba peel extract for skin hyperpigmentation. These findings highlight jaboticaba peel extract-an agro-industrial byproduct-as a promising and eco-friendly ingredient for hyperpigmentation treatment, supporting the development of innovative cosmetic formulations leveraging sustainable, plant-based resources.
Molecular Landscape of Natural Compounds and Tailored Signaling Pathways in the Battle Against Breast Cancer.
Jain M, Goel A
Curr Pharm Des · 2026 Mar · PMID 41832682 · Publisher ↗
Breast cancer remains the most frequently occurring disease among women, making its global mitigation a daunting task. Current treatment modalities face numerous challenges, including multidrug resistance and distinct ad...
Breast cancer remains the most frequently occurring disease among women, making its global mitigation a daunting task. Current treatment modalities face numerous challenges, including multidrug resistance and distinct adverse side effects. This situation necessitates the development of novel therapeutics. Breast cancer is a complex disease with diverse architecture, involving numerous signaling pathways and mechanisms that interact with each other. About 70% of anticancer drugs are plant-derived. These phytochemicals target the signaling pathways involved in cell proliferation, apoptosis, autophagy, metastasis, and breast cancer stem cell development (PI3K/Akt/mTOR pathway, Wnt/β-catenin signaling, Hedgehog (Hh), JAK-STAT pathway, NF-κB) by modulating them. These bioactive compounds and their structural derivatives have contributed to drug discovery and pharmacotherapy for breast cancer. Natural compounds, through synergistic effects, suppress breast cancer progression. Studies, in vitro and in vivo, have described the effectiveness of these isolated compounds against breast cancer. These extensive studies reveal the latent potential of these phytochemicals as a new strategy against breast carcinogenesis. To increase bioavailability and absorption, novel approaches have also been developed, such as the encapsulation of phytocompounds in lipid carriers, micelles, liposomes, and nanoparticles. Nevertheless, further comprehensive investigations are still required to determine the efficacy of these compounds. This review focuses on the important signaling cascades involved in breast cancer, which are potential targets of phytochemicals that ultimately impede cancer cell progression.
The Effects and Mechanisms of Traditional Chinese Medicine and Extracts on Stem Cells and the Application of Stem Cells to Treat Disease: A Review.
Fang Y, Yu X, Feng Z … +4 more , Qin F, Zheng Z, Zhu Y, Jiang B
Curr Pharm Des · 2026 Mar · PMID 41832681 · Publisher ↗
This review examines the synergistic effects and mechanisms of Traditional Chinese Medicine (TCM) and its extracts on mesenchymal stem cells (MSCs), with a focus on enhancing MSC proliferation, differentiation, and immun...
This review examines the synergistic effects and mechanisms of Traditional Chinese Medicine (TCM) and its extracts on mesenchymal stem cells (MSCs), with a focus on enhancing MSC proliferation, differentiation, and immunomodulation for therapeutic applications. A comprehensive analysis of studies from the past five years was conducted, evaluating interactions between TCM/extracts and MSC types (bone marrow-, adipose-, and umbilical cord-derived MSCs) through molecular pathways (e.g., PI3K/Akt, Wnt/β- catenin, TGF-β/Smad) and microRNA regulation. In vitro, in vivo, and clinical trial data were synthesized. TCM and extracts significantly upregulated osteogenic/adipogenic differentiation in bone marrow mesenchymal stem cells via miR-335-5p/PTEN and Runx2 pathways, enhanced the viability of adipose-derived mesenchymal stem cells under oxidative stress via Sirt1/Akt activation, and improved the immunomodulation of umbilical cord mesenchymal stem cells by increasing anti-inflammatory factors (HGF, PGE2). Combined MSC-TCM therapies accelerated diabetic ulcer healing (via the miR-146A-NF-κB axis), reduced liver fibrosis (via miR-19b-3p), and mitigated stroke/arthritis symptoms. TCM synergizes with MSCs through multipathway crosstalk and miRNA regulation, amplifying therapeutic efficacy in degenerative, inflammatory, and ischemic diseases. Clinical translation requires standardized TCM dosing and large-scale trials to validate safety and the durability of mechanistic effects. Specifically, the combination of Icariin and BMSCs for bone disorders, and resveratrol combined with ADSCs for diabetic complications, has demonstrated remarkable synergistic effects, thus highlighting their potential as priorities for future clinical translation.
Breast Cancer: A Comprehensive Review of Current Knowledge and Emerging Trends.
Bansal S, Verma S
Curr Pharm Des · 2026 Mar · PMID 41832680 · Publisher ↗
Breast cancer has a wide range of causes, symptoms, and predicting factors, which is the most common type of cancer in women. Risk factors associated with genes, lifestyle, hormones and the environment all have an impact...
Breast cancer has a wide range of causes, symptoms, and predicting factors, which is the most common type of cancer in women. Risk factors associated with genes, lifestyle, hormones and the environment all have an impact on its growth. Although women are the disease's primary sufferers, episodes of male breast cancer make up a small percentage. Diagnostic techniques differ, ranging from imaging and biomarker studies to novel approaches like AI-based detection, all of which improve early detection and ultimately outcome. Despite a delayed decline in mortality rates, issues such as prolonged toxicities, drug resistance and discrepancies in care remain. Latest advancements in nanotechnology, precision pharmaceuticals, and fusion medicines raise the feasibility of safer, more efficient treatment. The continued importance of metastatic disease as a leading cause of death reinforces the need for innovative approaches to organizing long-term care. Emerging scholarship is beginning to clarify the issue of health inequities, including inequities with respect to socioeconomic class, race, geography, and breast cancer outcomes. As we broaden opportunities to identify pathways for earlier detection and personalize treatment pathways through advances in blood-based liquid biopsies and non-invasive monitoring approaches, and more acceptable ways of including patients in clinical trials, patients are also recognizing the growing importance of patient-centred approaches to organizing survivorship care and a socio-psychological framework for care in comprehensive treatment. Future studies on therapeutic combinations of drugs and biomarker-directed therapy will require future advances in health inequities, prevention, diagnosis, and individualization of care in diverse populations.
Impact of Volatile Organic Compounds on Liver Function in Adolescents: Mediation and Preventive Insights from NHANES.
Yao X, You C, Zhou M … +6 more , Zhou H, Tang C, Zhang H, Wang X, Jin W, Zhang L
Curr Pharm Des · 2026 Mar · PMID 41832679 · Publisher ↗
BACKGROUND: Environmental exposure to volatile organic compounds (VOCs) may adversely affect liver function, particularly in adolescents; however, the evidence remains scarce. OBJECTIVE: This study aimed to evaluate the...
BACKGROUND: Environmental exposure to volatile organic compounds (VOCs) may adversely affect liver function, particularly in adolescents; however, the evidence remains scarce. OBJECTIVE: This study aimed to evaluate the individual and combined effects of VOCs exposure on liver function in adolescents, as well as the potential mediating role of lactate dehydrogenase (LDH) and possible intervention strategies. METHODS: In total, 1,280 adolescents aged 12-19 years from the National Health and Nutrition Examination Survey were studied to examine the associations between 15 VOC metabolites and 4 liver function indicators. Four statistical models were employed to assess the associations, including weighted linear regression, restricted cubic splines, weighted quantile sum (WQS), and Bayesian kernel machine regression (BKMR). Mediation analysis was performed to evaluate whether LDH mediated or partially explained these associations. RESULTS: Among the 15 individual VOC metabolites, 8 were observed to have a significant association with specific liver function indicators. The WQS and BKMR models consistently identified significant associations between VOC mixtures and elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). Additionally, AMCC [parent VOC (pVOC): N, N-dimethylformamide] and HMPMA (pVOC: crotonaldehyde) were identified as major contributors to the combined effect. Mediation analysis showed the potential mediation effect of serum LDH on these associations. Moreover, the adverse effect of VOC exposure on adolescent liver function was significantly mitigated with adequate vitamin D intake. DISCUSSION: The results indicate that VOC exposure is positively associated with elevated liver function indicators in adolescents, with AMCC and HMPMA as main contributors. The mediating role of LDH suggests that oxidative stress may serve as a key mechanistic pathway underlying VOC-induced liver injury. Additionally, adequate vitamin D intake appears to mitigate these adverse effects. CONCLUSION: Our findings revealed a positive association between exposure to VOC and liver function in adolescents, and suggest that LDH may be a potential mechanism for VOC-induced liver injury. Supplementing with vitamin D may help protect adolescent liver function from the effects of VOC exposure.
Tacrolimus for Dry Eye Disease: Translational Insights from Animal Models and Clinical Studies into Molecular Pathways and Anti-Inflammatory Mechanisms.
Ivraghi MS, Golmohammadi M, Abbood RS … +6 more , Baldaniya L, Sharma R, Abohassan M, Zwamel AH, Devi S, Zamanian MY
Curr Pharm Des · 2026 Mar · PMID 41832678 · Publisher ↗
Tacrolimus (TAC) is recognized as a promising therapy for Dry Eye Disease (DED). Recent experimental studies indicate that TAC formulations, such as nanoemulsions and liposomes, notably improve tear production, stabilize...
Tacrolimus (TAC) is recognized as a promising therapy for Dry Eye Disease (DED). Recent experimental studies indicate that TAC formulations, such as nanoemulsions and liposomes, notably improve tear production, stabilize the tear film, and reduce corneal damage in animal models. TAC achieves these effects by inhibiting T-cell activation and suppressing the production of inflammatory cytokines, primarily through the NF-κB signaling pathway. Clinical trials report that topical TAC, especially at 0.03% concentration, significantly alleviates both symptoms and signs in patients with Sjögren's syndrome and ocular graft-versushost disease. Critical clinical improvements include higher Schirmer test values, prolonged tear film break-up time, and decreased ocular surface staining. Comparative analyses suggest that TAC is at least as effective as cyclosporine and offers a favorable safety profile. Combining TAC with agents such as sodium hyaluronate may further enhance therapeutic outcomes. Despite the need for further studies to optimize dose and longterm safety, current evidence supports the use of TAC as an effective solution for individuals with refractory or severe DED, providing a vital option where conventional treatments may fail.
Prediction and Classification of Liposomal Release and Stability Using Machine Learning Based on Ethanol and Tergitol 15-S Surfactants.
Hwang JS, Pomseethong P, Kim JC
Curr Pharm Des · 2026 Mar · PMID 41832677 · Publisher ↗
INTRODUCTION: Liposomes are bilayered vesicles capable of encapsulating both hydrophilic and hydrophobic compounds, making them widely used in pharmaceuticals and cosmetics due to their excellent biocompatibility and ver...
INTRODUCTION: Liposomes are bilayered vesicles capable of encapsulating both hydrophilic and hydrophobic compounds, making them widely used in pharmaceuticals and cosmetics due to their excellent biocompatibility and versatility. However, they are structurally vulnerable to additives, such as ethanol and surfactants, which are often unavoidable during formulation. Therefore, it is essential to evaluate the effects of these components on liposomal stability and release behavior. METHOD: Second-order multiple linear regression models were developed to predict liposomal release based on ethanol and five Tergitol™ 15-S surfactant concentrations. Nonlinear interactions were visualized using 3D regression surfaces. Liposomal stability was classified into four categories using K-nearest neighbors, logistic regression, and stochastic gradient descent algorithms. All models were implemented in Python using Scikit-Learn and Matplotlib. RESULT: All regression models demonstrated high predictive accuracy, with R² values of 0.9611-0.9899 and mean absolute errors (MAE) of 2.19%-5.44%. No overfitting was observed. Among the classification models, logistic regression achieved the highest test accuracy (87.98%), followed by SGD (80.12%) and KNN (80.88%). DISCUSSION: Tergitol concentration had a greater impact on liposomal release than ethanol. Surfactants with higher HLB values showed weaker interactions with the lipid bilayer, resulting in reduced release. This aligns with previous findings that highly hydrophilic surfactants have limited bilayer penetration. The models effectively captured nonlinear interactions and offer practical utility for formulation prediction. CONCLUSION: This study evaluated the stability of liposomes under various concentrations of ethanol and Tergitol surfactants and classified them using machine learning algorithms. The developed models can be effectively applied to formulation design in liposome-based systems, including pharmaceutical and cosmetic applications.
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