Pentacyclic triterpenes have attracted significant scientific interest due to their notable biological activities against inflammation, cancer, liver diseases, oxidative stress, and bacterial infections. They are commonly found in fruits and vegetables and are marketed globally as nutritional supplements. Examples of pentacyclic triterpenoids include ursolic acid, oleanolic acid, boswellic acid, lupeol, betulinic acid, maslinic acid, and asiatic acid. The low water solubility, poor permeability, and limited bioavailability of pentacyclic triterpenoids hinder their therapeutic potential. The development of nanoformulations has the potential to address these limitations by facilitating effective distribution and improving therapeutic efficacy. This review provides a thorough discussion of the sources, biological activities, and mechanisms of action of pentacyclic triterpenoids. It also offers a comprehensive analysis of their integration with nanotechnological systems, including solid lipid nanoparticles, liposomes, dendrimers, polymeric micelles, silver nanoparticles, gold nanoparticles, chitosan nanoparticles, and nanostructured lipid carriers. The databases PubMed, Google Scholar, and ScienceDirect were carefully examined for relevant information. A comprehensive literature search was conducted using peer-reviewed articles published between 2000 and 2025. Review and research articles containing adequate scientific detail were included, while documents written in languages other than English were excluded. Published patents related to nanoformulations of pentacyclic triterpenoids are also briefly summarized. The clinical applications of pentacyclic triterpenoids currently in various clinical phases are outlined as well.
Introduction: Cardiovascular Diseases (CVDs) and Gastrointestinal Disorders (GIDs) show significant comorbidity. We established a rat model of chronic atrophic gastritis (CAG) complicated by acute myocardial ischemia (AMI) to investigate the protective effects and mechanisms of Wei Nai An Capsule (WNAC) on CAG and AMI.
Methods: Potential mechanisms were predicted by using network pharmacology and GEO database analysis. To model CAG, we combined intragastric administration of alcohol, sodium deoxycholate, and ammonia. Injections of β-adrenergic agonist isoproterenol modeled the AMI. Histopathological observations were performed, and gastric pH, cardiac marker enzyme levels, cardiac electrical activity, and mRNA expression in the animals were monitored.
Results: Network pharmacology and GEO database analyses suggested that WNAC's positive effect on acute myocardial ischemia complicated by chronic atrophic gastritis is associated with the PI3K-AKT signaling pathway. In the model of acute myocardial ischemia complicated by chronic atrophic gastritis, WNAC significantly decreased the elevated ST-segment on the electrocardiogram, reduced gastric pH, reduced levels of markers of cardiac injury, and reduced the mRNA expression of IκBα, PI3K, NF-κB-p65, and COX2 in cardiac and gastric tissues.
Discussion: This study demonstrated the crucial need to suppress pro-inflammatory pathways in the treatment of the comorbidity between CVDs and GIDs. However, additional experiments could further strengthen the causal inference.
Conclusion: This research indicated that WNAC can be successfully implemented to treat the comorbidity of CVDs and GIDs and provides strong evidence for the discovery of new indications of WNAC in clinical practice.
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.
Introduction: In-Stent Restenosis (ISR) remains a challenging complication following vascular interventions. Colchicine, a well-known anti-inflammatory agent, has shown potential in reducing ISR, but its multi-target mechanisms remain unclear. This study aims to elucidate the pharmacological mechanisms of colchicine against ISR using an integrated approach.
Methods: Colchicine- and ISR-related targets were identified from multiple public databases. Overlapping targets were analyzed using Gene Ontology (GO), KEGG pathways, and Protein-Protein Interaction (PPI) networks. Hub genes were identified using the MCODE and CytoHubba algorithms and subjected to Reactome enrichment analysis. Molecular docking assessed colchicine's binding affinity to hub proteins. A rat carotid artery balloon injury model was used to evaluate colchicine's therapeutic effect, focusing on histological and molecular changes.
Results: A total of 30 overlapping targets were identified, primarily enriched in atherosclerosis-related and inflammatory signaling pathways. Three key targets, including TGF-β1, ICAM1, and VCAM1, were identified as central to extracellular matrix organization and inflammatory pathways. Molecular docking revealed strong binding affinity between colchicine and these targets (binding energy < -5 kcal/mol). In vivo, colchicine significantly attenuated neointimal hyperplasia, reduced collagen deposition, and downregulated the expression of TGF-β1, ICAM1, and VCAM1 at both mRNA and protein levels.
Discussion: Our findings suggest that colchicine suppresses ISR by simultaneously modulating inflammatory and fibrotic processes. The identification of TGF-β1, ICAM1, and VCAM1 as hub targets underscores their roles in neointimal development and highlights colchicine's potential to regulate multiple pathological pathways. Compared with conventional drug-eluting stent agents that primarily inhibit smooth muscle cell proliferation, colchicine offers complementary advantages through dual anti-inflammatory and anti-fibrotic mechanisms. Nonetheless, further studies are warranted to optimize drug delivery strategies, explore dose-response relationships, and compare colchicine with standard stent-based therapies.
Conclusion: Colchicine may exert anti-restenotic effects by suppressing inflammatory and fibrotic mediators such as TGF-β1, ICAM1, and VCAM1. These findings suggest a possible multi-target mechanism and support further investigation into its therapeutic potential in ISR.
The pharmaceutical sector requires strong and flexible quality systems to achieve operational excellence and regulatory compliance. Integrating Quality Risk Management (QRM) frameworks with Electronic Quality Management Systems (EQMS) provides a transformative approach to quality management across the pharmaceutical value chain. This paper investigates how EQMS and QRM can work together to promote proactive compliance, reduce process variability, and foster a culture of continuous improvement. While QRM offers a systematic process for identifying, evaluating, and managing quality risks throughout the product lifecycle, EQMS technologies provide real-time data collection, optimized documentation, automated workflows, and streamlined regulatory reporting. The integration of these systems enhances risk-based decision- making by addressing deviations, non-conformances, and change controls through analytics, trend analysis, and predictive modeling. Current industry practices, regulatory requirements from organizations such as the FDA and EMA, and technological developments that facilitate this integration, such as cloud-based EQMS systems and AI-enabled risk assessment tools, are critically assessed in this article. To demonstrate how integrated systems have facilitated faster time-to-market, reduced compliance gaps, and improved audit readiness, case studies and implementation models are examined. Additional considerations include system validation, user acceptance, and data integrity. Ultimately, EQMS and QRM integration represents a shift from reactive to proactive quality management, in line with ICH Q9 and ICH Q10 principles, positioning pharmaceutical firms to succeed in an increasingly complex and competitive regulatory environment. For stakeholders aiming to enhance quality outcomes through risk-based governance and digital transformation, this evaluation provides a strategic framework.
Calcium channel blockers (CCBs) regulate calcium ion transport across cell membranes and are central to the management of hypertension, angina, arrhythmias, and cerebrovascular disorders, with emerging roles in neurological and oncological diseases. Most CCBs undergo significant first-pass metabolism mediated by cytochrome P450, which affects their interindividual variability, dosage, and bioavailability. Recent research highlights the potential of T-type CCBs in cancer treatment and the use of nanocarriers to overcome their low bioavailability and rapid metabolism. Since the introduction of verapamil in the 1960s, newer drugs with improved selectivity and safety, such as cilnidipine and azelnidipine, have been developed. Despite their widespread use, challenges remain in maximizing long-term efficacy, minimizing side effects, and individualizing treatment. This review provides an updated overview of the pharmacokinetics, pharmacodynamics, and therapeutic applications of dihydropyridine and non-dihydropyridine CCBs, while identifying research gaps and future directions to enhance their clinical utility. By integrating established pharmacological knowledge with recent advances, this study underscores the continued relevance of CCBs in modern medicine.
Probiotics, traditionally recognized for their role in gastrointestinal health, have recently been investigated for their potential influence on cognitive function through modulation of the gut-brain axis (GBA). This review summarizes the current clinical evidence and mechanistic insights on the role of probiotic interventions in mitigating cognitive decline and enhancing brain function, particularly in older adults and individuals with neuropsychiatric conditions. Cognitive impairments in the elderly, driven by neurodegeneration, vascular compromise, inflammation, and lifestyle factors, present significant challenges to public health systems. Several randomized controlled trials have demonstrated the beneficial effects of specific probiotic strains, such as Bifidobacterium breve A1, Lactiplantibacillus plantarum P8, and multispecies formulations, in improving memory, attention, and emotional regulation in populations with mild cognitive impairment, Alzheimer's disease, major depressive disorder, and schizophrenia. The cognitive improvements are linked to various mechanisms, including anti-inflammatory and antioxidant activities, modulation of neurotransmitter levels, maintenance of gut barrier integrity, and shifts in gut microbiota composition favoring beneficial taxa. However, not all interventions have yielded significant effects, suggesting strain-specific efficacy and interindividual variability in response. The present study discusses the limitations of existing studies and emphasizes the need for personalized approaches and rigorous, long-term clinical trials. Overall, probiotics show promise as adjunctive agents for preserving cognitive health and managing neurodegenerative and psychiatric disorders via modulation of the microbiota-GBA.
Wound healing is a highly intricate biological process that progresses through sequential phases: haemostasis, inflammation, proliferation, and remodelling, each regulated by a series of cellular and molecular mechanisms. The healing process is often impaired by chronic inflammation, oxidative stress, infections, and other pathological conditions, resulting in delayed tissue regeneration. Natural flavonoids, with their antioxidant, anti-inflammatory, antimicrobial, and pro-angiogenic properties, have gained significant attention as potential therapeutic agents for enhancing wound repair. However, their clinical application remains constrained by challenges such as poor water solubility, low bioavailability, rapid metabolism, and instability under physiological conditions. To address these limitations, polymer-based delivery systems-including hydrogels, nanofibers, nanoparticles, and hybrid formulations-have been developed using natural, synthetic, and semi-synthetic polymers. These systems offer improved drug encapsulation, sustained release, targeted delivery, and enhanced stability, thereby optimizing the therapeutic potential of flavonoids in wound management. This review comprehensively discusses the characteristics, selection criteria, and mechanisms of polymer and hybrid systems employed for flavonoid delivery, along with their synergistic effects on tissue regeneration. Furthermore, it provides a translational framework for designing multifunctional wound healing platforms, highlighting the promise of polymeric carriers in overcoming pharmacokinetic barriers and achieving improved clinical outcomes.
Introduction: Ping An Fang Yu Yin (PAFYY) is a traditional Chinese herbal tea formula commonly used to treat respiratory infections, including COVID-19. Previous research indicates potential antiinflammatory activities; however, the underlying mechanisms remain unclear. This study aimed to investigate the mechanisms underlying the therapeutic effects of PAFYY, specifically its electron-transport and bioenergetic properties, through network pharmacology, electrochemical analysis, and Microbial Fuel Cell (MFC) assessments.
Methods: Active compounds and their respective targets were identified via database searches. Proteinprotein interaction networks were constructed using the STRING database and further analyzed using Cytoscape and MCODE software. Molecular docking was employed to assess the binding affinity between identified key compounds and their targets. Cyclic voltammetry (CV) and MFC assays evaluated the electrontransport characteristics of PAFYY water and ethanol extracts.
Results: The analysis identified 298 active compounds associated with 1,940 biological targets, highlighting key targets including EP300, CREBBP, ESR1, AKT1, MAPK3, MAPK1, and STAT3. GO and KEGG pathway enrichment analyses revealed that PAFYY significantly influences immune system processes and neuronal signaling pathways. Molecular docking confirmed the anti-inflammatory and antiviral potential of the identified active compounds. Additionally, electrochemical studies demonstrated that PAFYY contains electroactive substances mediating electron-driven redox reactions.
Discussion: Recent studies have demonstrated that traditional Chinese herbal teas contain electron shuttles capable of mediating electron transfer in electrogenic bacteria. Emerging evidence further indicates that electroactive plant polyphenols can modulate microbial ecology through redox-mediated mechanisms. Our findings suggest that PAFYY may act on the microbiota-immune axis, with its electron-shuttling constituents contributing not only to direct cellular effects and antioxidant activity but also to modulation of the gut microbiome in ways that support antiviral immunity and attenuate inflammation. These results may inform future research into the mechanistic basis of medicinal herbs, while highlighting the potential of MFCs as a functional screening platform for identifying bioactive redox compounds.
Conclusion: The anti-COVID-19 properties of PAFYY may be largely attributed to its electron-transport capabilities, mediated through electroactive compounds. These findings provide novel insights into the mechanistic basis of traditional Chinese medicine prescriptions, potentially enhancing their therapeutic application.
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