Current pharmaceutical design最新文献

Introduction: Hypertension is a major global health concern, and the exploration of natural compounds as potential antihypertensive agents has been a recent area of study.. The ancient medicinal tree Terminalia arjuna is very potent for treating cardiovascular conditions. Its bark is rich in bioactive compounds, such as flavonoids, tannins, and triterpenoids, which exhibit cardioprotective properties.

Methods: This research focused on identifying and characterizing antihypertensive phytoconstituents of Terminalia arjuna through molecular docking, dynamic simulations, and DFT studies. We systematically screened bioactive compounds from the plant for their ability to interact with key targets (PDB:2X96), which are involved in the regulation of blood pressure using AutoDock Tools 1.5.7. The dynamic behavior of the complexes was evaluated using molecular dynamics (MD) simulation in the GROMACS package program (version 2022.2). DFT calculations were performed using DMol3 (Discovery Studio Client) to determine molecular electronic properties.

Results: We identified Quercetin and Ellagic acid as promising ligands with strong binding affinities and significant pre-ADMET analysis database. Further, molecular dynamics simulations (500 ns) provided insights into the stability and binding modes of these selected compounds, highlighting their potential for long-term efficacy. DFT calculations were employed to evaluate the electronic properties, such as frontier molecular orbital analysis and electrostatic potential mapping, revealing the reactivity and interaction profiles of the compounds. The docking scores and MMGBSA binding free energy value of Ellagic acid with AnCE-RXPA380 complex target protein were found to be -9.5 and -17.94 kcal/mol, respectively, which is higher as compared to Captopril (--5.7 and --4.36 kcal/mol kJ/mol).

Discussion: Ellagic acid exhibits more conventional hydrogen binding efficiency at 2X96 receptor with GLN A:361, THR A:364, ASP A:360, LYS A:495, and GLN A:265, respectively, providing a scientific basis for its use in hypertension management Furthermore.

Conclusion: Our results suggest that Ellagic acid from Terminalia arjuna possesses significant antihypertensive potential due to the highest binding efficiency with 2X96 receptor. However, in vitro, and in vivo experimentation are needed to validate the antihypertensive potential of Ellagic acid in the future.

As an advancement of 3D printing, 4D printing introduces a time dimension, enabling the fabrication of dynamic, adaptable biological devices. In contrast to stable 3D-printed systems, 4D-printed systems employ intelligent materials, such as shape-memory polymers and hydrogels, that respond to environmental stimuli, such as pH, temperature, and light. Major developments include adaptable implants for applications like tracheal support and cancer therapy, as well as customized, stimuli-responsive hydrogel capsules that enable controlled drug release, thereby enhancing the patient's health, decreasing adverse effects, and increasing accuracy. Nevertheless, several challenges remain, specifically in managing degradation rates, ensuring biocompatibility, and optimizing material selection for clinical studies. As research continues, 4D bioprinting is anticipated to become the main tool for creating personalized, efficient, and adaptive biomedical systems, thereby changing the face of future healthcare and treatment methods. This editorial provides an overview of innovative approaches and demonstrates the importance of 4D printing in the medical field. It highlights the crucial role of 4D printing over 3D printing by incorporating the time dimension, making the resulting devices dynamic and adaptive rather than static. These smart features of the innovative 4D-printed tool have led to significant advancements in medical applications, including customized tracheal support implants and personalized drug-delivery capsules.

Introduction: Cardiac hypertrophy, often a maladaptive response to sustained cardiac workload, can lead to heart failure and increased mortality. Traditional Unani formulation Khamira Gaozaban Sada (KGS) is evaluated for its cardioprotective effects in preclinical models. The objectives are to assess the efficacy of KGS in reducing cardiac workload and preventing pathological remodeling in L-NAME-induced hypertension and isoproterenol (ISO)-induced cardiac hypertrophy models, and to identify its underlying mechanisms and safety profile.

Methods: Two doses of KGS (1000 and 2000 mg/kg b.w.) were administered in L-NAME and ISO-induced rat models. Hemodynamic parameters, biochemical markers, histopathological, and echocardiographic assessments were evaluated. Immunohistochemistry for eNOS expression was performed. In vitro, ISO-induced cytotoxicity and calcium overload were assessed in H9C2 cells. CYP inhibition and metabolite docking studies were also conducted.

Results: In the L-NAME model, high-dose KGS reduced SBP and RR intervals and enhanced cardiac eNOS expression, indicating reduced cardiac workload. In the ISO model, high-dose KGS significantly attenuated QTc prolongation, SBP elevation, and biomarker levels and ameliorated myocardial histopathological damage. Echocardiography showed decreased LV mass and wall thickness, confirming reduced cardiac remodeling. In vitro, KGS showed protective effects on H9C2 cells at 200 μg/mL by reducing ISO-induced cytotoxicity and calcium overload. CYP inhibition was minimal. Metabolite profiling identified 19 tentative metabolites; tiliroside and trehalose showed strong docking affinity toward eNOS and β1-adrenergic receptors, respectively.

Discussion: This study demonstrated that high-dose KGS offers significant cardioprotection by attenuating LNAME- induced hypertension and ISO-induced cardiac hypertrophy through improved eNOS expression, reduced fibrosis, oxidative stress, and intracellular calcium overload. It restored cardiac structure and function, normalized key biochemical markers (Ang-II, NA, Aldosterone, ANP), and enhanced electrical conductance without notable cytotoxicity or CYP enzyme inhibition. LC -MS and docking studies identified bioactive metabolites targeting eNOS and β1 receptors, supporting a multi-target mechanism.

Conclusion: KGS exhibits significant cardioprotective effects by reducing cardiac workload, improving myocardial structure, and attenuating hypertrophic responses. Its low CYP inhibition potential supports its use as an adjuvant therapy for hypertensive and hypertrophic cardiac conditions.

Objectives: Type 2 diabetes mellitus (T2DM) is a major global public health challenge, currently affecting over 537 million adults, with projections reaching 783 million by 2045. India contributes over 17% of global T2DM cases, significantly adding to the disease burden. Hyperglycemia-induced oxidative stress plays a crucial role in T2DM pathogenesis by disrupting the balance between reactive oxygen species (ROS) production and antioxidant defence mechanisms. This imbalance activates pathological pathways, including polyol and hexosamine biosynthesis, promotes advanced glycation end-products (AGEs) formation, increases protein kinase C (PKC) activity, and triggers inflammation, leading to vascular complications.

Methods: This study systematically examines literature reviews published between 2010 and 2024 in peerreviewed journals indexed in databases such as PubMed, Web of Science, Scopus, ScienceDirect, and Google Scholar. The research utilizes search terms about diabetic microvascular and macrovascular complications, their pathogenesis, and therapeutic management.

Results: Microvascular complications, arising from damage to small blood vessels, encompass diabetic nephropathy, retinopathy, neuropathy, and sexual dysfunction. Macrovascular complications, resulting from large blood vessel impairment, increase the risk of cardiovascular diseases, including coronary artery disease, peripheral arterial disease, stroke, and heart failure.

Conclusion: The effective management of vascular complications necessitates a comprehensive approach, incorporating strict glycaemic control, lifestyle modifications, and pharmacological interventions such as Renin- Angiotensin-Aldosterone System (RAAS) blockers, Sodium-Glucose Cotransporter-2 (SGLT2) inhibitors (e.g., dapagliflozin), phosphodiesterase-5 inhibitors (PDE5i) (e.g., sildenafil citrate), glucagon-like peptide-1 receptor agonists, and anti- vascular endothelial growth factor (VEGF) therapies (e.g., aflibercept). Early diagnosis, risk factor management, and targeted treatment strategies are crucial for improving patient outcomes and mitigating disease progression.

Introduction: Immunomodulatory disorders, such as autoimmune diseases, inflammatory conditions, and viral infections, stem from immune system dysregulation and often resist conventional therapies. Stem cells, particularly mesenchymal (MSCs) and hematopoietic stem cells (HSCs), possess immunomodulatory and regenerative properties, offering a promising therapeutic alternative.

Methodology: A systematic literature review was conducted using databases, including PubMed, Scopus, Web of Science, and Google Scholar, for studies published between 1996 and 2025. A total of 287 articles were screened, and 132 were selected based on relevance, quality, and focus on stem cell biology, immunoregulatory mechanisms, and therapeutic applications.

Results: Stem cells demonstrated significant capacity to regulate immune responses, suppress the production of inflammatory cytokines, enhance regulatory T-cell populations, and promote tissue regeneration. HSCs are effectively used in hematologic malignancies and immune reconstitution, while MSCs show promise in treating conditions, such as rheumatoid arthritis, diabetes mellitus, and influenza-induced lung injury. Emerging evidence also supports the role of cancer stem cells (CSCs) in targeted cancer therapies.

Discussion: Stem cells offer a mechanism-driven approach to restoring immune balance and repairing tissue damage. However, variability in clinical outcomes, ethical concerns, and safety risks, such as tumorigenesis, limit their translation into clinical practice. Advances in cell derivation, immunomodulatory profiling, and delivery systems are critical to optimizing outcomes.

Conclusion: Stem cell-based therapies represent a paradigm shift in the treatment of immunomodulatory disorders by addressing the root cause of immune dysfunction. Continued research, ethical oversight, and clinical validation are crucial for transitioning stem cell therapy into routine medical practice.

Osteoarthritis (OA) is a leading cause of chronic pain and disability, particularly among the elderly. Despite its high global prevalence, the underlying mechanisms of OA are still not fully understood, and current treatments are largely limited to symptomatic relief. Exosomes, small extracellular vesicles involved in cell-to-cell communication, have recently gained attention for their diagnostic and therapeutic potential in OA. In particular, exosomes derived from Mesenchymal Stem Cells (MSCs) can modulate chondrocyte proliferation, apoptosis, autophagy, and inflammation. Emerging evidence also highlights the role of exosomal non-coding RNAs (ncRNAs), including miRNAs, lncRNAs, and circRNAs, in regulating cartilage degradation and subchondral bone remodeling. This review offers a comprehensive synthesis of current knowledge on the role of exosomes in OA, with a unique focus on their dual function as biomarkers and therapeutic tools. We further highlight the promise of exosome-based Drug Delivery Systems (DDSs) and propose future directions for integrating exosome technologies into OA treatment strategies. This work emphasizes the translational potential of exosomes as disease-modifying agents and regenerative tools in osteoarthritis.

Vagina is one of the crucial parts of the female reproductive system and is often afflicted by various diseases. Vulvovaginal candidiasis (VVC) is the most common disease caused by Candida species. VVC affects nearly 75% of women at least once in their lifetime and exhibits a high recurrence rate. Current firstline treatments for VVC include antifungal agents such as azoles, polyenes and echinocandins. Emerging therapies like herbal remedies, probiotics and immunotherapeutic vaccines are also available, with azoles being the most commonly used. While effective, these therapies are often limited by drawbacks, including resistance development, adverse effects and suboptimal therapeutic outcomes. Conventional forms of dosage, such as creams, tablets and intravenous infusions, have shown limited success in addressing the complexity of VVC, particularly biofilm formation, which impedes therapeutic efficacy. To overcome these challenges, novel drug delivery systems (NDDS) are being explored, including lipid-based carriers, inorganic nanocarriers, microneedles, nanofibers and in situ gels, which offer enhanced drug delivery and improved bioavailability. Additionally, polymers used in vaginal drug delivery have shown potential in improving the stability and release profiles of formulations. In this review, a comprehensive overview of the pathophysiology and therapeutic strategies has been provided, along with recent advancements in novel drug delivery systems. It highlights their potential and ability to overcome current therapeutic challenges and pave the way for more effective and patient-friendly management of the condition.

Heart failure (HF) is a critical global health concern, affecting women due to unique biological, epidemiological, and sociocultural factors. Despite accounting for a significant percentage of cardiovascular disease (CVD) mortality among women, HF remains unexplored, particularly in areas such as gender-specific diagnostic challenges and therapeutic strategies. This review explores the intricate pathophysiology of HF, focusing on inflammation, oxidative stress, endothelial dysfunction, and fibrosis as pivotal contributors to disease progression. Moreover, it highlights advancements in pharmacological treatments, including ARNI, SGLT2 inhibitors, and novel therapeutic agents like vericiguat (for selective patients) and omecamtiv mecarbil (modest benefits), while addressing the potential of lifestyle interventions, such as diet, exercise, in mitigating HF risk. Artificial intelligence emerges as a promising potential for enhancing diagnostic precision, patient management, and outcome prediction, heralding a new era in HF care. By integrating gender-specific research and innovations, this study aims to refine strategies for improving women's cardiac health, ultimately reducing the global burden of HF.

Pulmonary drug delivery systems have emerged as non-invasive and effective platforms for treating intrapulmonary and extrapulmonary conditions, allowing for direct drug administration to the lungs or systemic delivery via pulmonary absorption. The lungs' large surface area and extensive alveolar network facilitate rapid absorption of drugs at high concentrations, allowing for lower dosing, reduced systemic side effects, and improved therapeutic outcomes through targeted delivery. Nanotechnology further enhances pulmonary drug delivery systems by encapsulating drugs in nanoparticles, which can improve drug stability, promote cellular uptake, enable passive targeting, and offer controlled release profiles. With the increasing incidence of respiratory diseases and growing interest in pulmonary delivery for both local and systemic therapy, a deeper understanding of respiratory drug delivery mechanisms is critical. This review provides a comprehensive overview of pulmonary drug delivery systems, beginning with conventional delivery systems and their clinical applications. It then examines the challenges affecting the efficacy of inhaled therapies and explores recent advancements, particularly nanoparticle formulations, that aim to improve drug targeting, bioavailability, and patient adherence. The review concludes by highlighting ongoing challenges and outlining future perspectives for the development of more efficient and patient-centric pulmonary drug delivery strategies. Ultimately, nanoparticle-based systems offer a promising alternative for improving the treatment of pulmonary and systemic infections, supporting better patient outcomes and advancing precision respiratory medicine.