Journal of Pharmacology, Genetics and Molecular Biology
The Journal of Pharmacology, Genetics and Molecular Biology (JPGMB)is an international, peer-reviewed, multidisciplinary journal devoted to pharmacology and medical Sciences. JPGMB aims to increase the impact of pharmaceutical research in academia and industry, with a strong emphasis on quality and originality. JPGMB publishes Original Research Articles, Short Communications, and Review Articles in all pharmaceutical, medical, Dental, and integrated medical sciences.
Pathophysiological Insights into Parkinson’s Disease Progression
Parkinson disease (PD) is a progressive and multifactorial neurodegenerative disease, which is mainly caused by the selective destruction of dopaminergic neurons in the substantia nigra pars compacta, and causes the typical motor symptom of bradykinesia, resting tremor, rigidity, and postural instability. In addition to these motor defects, PD has a wide range of non-motor symptoms, such as cognitive, mood, sleep, and autonomic deficiency, all of which decrease the quality of life of patients considerably. PD has a complicated pathophysiology comprising genetic predisposition (e.g., SNCA, LRRK2, PARK gene mutations), environmentally triggered, mitochondrial dysfunction, oxidative stress, chronic neuroinflammation, and aggregation and prion-like propagation of α-synuclein. Neurotoxin-induced, genetic, and α-synuclein pre-formed fibril (PFF) systems have proven essential in the understanding of these mechanisms and as a result of the knowledge led to an understanding of the loss of dopaminergic neurons, misfolding of α-synuclein, glial-mediated neuroinflammation, and both motor and non-motor symptoms. Moreover, the models provide critical platforms on preclinical analysis of therapeutic interventions, such as antioxidant therapies, anti-aggregates, immunomodulatory therapies, and those that promote non-motor symptoms and thus improved clinical outcomes and development of holistic disease-modifying interventions.
Parkinson’s Disease, Dopaminergic Degeneration, Α-Synuclein Aggregation, Neuroinflammation, Neurotoxin Models, Genetic Models, Pre-Formed Fibril Models, Non-Motor Symptoms.
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Novel Biomarkers for Early Diagnosis of Alzheimer’s Disease
Alzheimer's disease (AD) is a progressive neurodegenerative disease for which early detection is essential but frequently difficult because of intrusive and expensive diagnostic techniques. The purpose of this study was to assess new biomarkers for AD early detection in blood and cerebrospinal fluid (CSF). 120 participants, ages 55 to 80, participated in a cross-sectional observational study that included patients with mild cognitive impairment (MCI), early-stage AD, and cognitively normal controls. Biomarker analyses, such as amyloid-beta (Aβ42), total tau, phosphorylated tau, neurofilament light chain (NfL), and miRNA panels, were conducted in addition to cognitive tests (MMSE and MoCA). The findings revealed a progressive decline in cognitive function and notable changes in biomarker levels among groups, with tau, phosphorylated tau, NfL, and miRNA levels rising with the severity of the disease and Aβ42 falling. Strong correlations between biomarkers and cognitive scores as well as statistically significant group differences were validated by one-way ANOVA and Pearson correlation analyses. These results support the use of blood and CSF biomarkers in clinical screening and intervention strategies by highlighting their potential as sensitive, minimally invasive tools for early AD diagnosis.
Alzheimer’s disease, early diagnosis, biomarkers, cerebrospinal fluid, blood-based biomarkers, mild cognitive impairment, amyloid-beta, tau, miRNA.
Targeting Inflammatory Pathways in Rheumatoid Arthritis Therapy
Rheumatoid arthritis (RA), is a chronic autoimmune disease characterized by chronic inflammation of the synovium, cartilage and bone erosion and is mediated in large part by maladaptive inflammatory mechanisms. The preclinical analyses on animal models such as collagen induced arthritis (CIA), adjuvant induced arthritis (AIA) and transgenic mice on TNF have given necessary knowledge on the molecular basis of RA pathogenesis and treatment protocols. This review is a synthesis of the existing evidence on the use of these models in order to target key pro-inflammatory cytokines (TNF- α, IL- 6, IL- 1) and intracellular signaling cascades (JAK -STAT, NF- - 00, MAPK, PI3K/Akt) to reduce joint inflammation, osteoclast activity, and tissue damage. Also, the use of emerging strategies like nanoparticle-based drug delivery delivers a tissue specific target, drug stability and less systemic toxicity. These preclinical studies are critically examined in terms of strengths, limitations and translational potential, combination and multi-target studies are proposed to counter-act redundancy in pathways, and gaps in future studies are highlighted. At last, these results indicate the critical role of animal models in informing the design of new therapeutic interventions that are more effective and safer to use in the treatment of RA.
Rheumatoid Arthritis, Inflammatory Pathways, Cytokine Inhibition, TNF-α, IL-6, IL-1, JAK-STAT Signaling, NF-Κb, MAPK, PI3K/Akt, Animal Models.
Advances in Nanomedicine for Treatment of Neurological Disorders
Nanomedicine has become a revolutionary approach to the management of neurological conditions, providing the innovative means of addressing the flaws of the traditional treatment methods. The review concentrates on preclinical animal research, emphasizing on the progress of nanoparticles-based delivery systems, liposomes, micelles, dendrimers and nanogels, which have the potential to increase the drug transport across the blood-brain barrier, specific brain targeting, and controlled, sustained delivery of therapeutic agents. The main results indicate that functionalized nanoparticles are able to suppress neuroinflammatory signals, eliminate reactive oxygen species, and prevent neuroprotection and neuroregeneration, and thus enhance the cognitive and motor outcomes in models of Alzheimer disease, Parkinson disease, stroke, and traumatic brain injury. Although these are encouraging findings, there are still issues to deal with, including long-term safety, biocompatibility, scalability of synthesis, and translational feasibility, which means that further studies must be performed to maximize the effectiveness and enable a clinical implementation. Although, comprehensive, preclinical data highlights the potential of nanomedicine as a means of transforming treatment approaches to central nervous system disease so that more specific, effective, and safer treatment approaches can be provided in the future.
Nanomedicine, Neurological Disorders, Blood-Brain Barrier, Nanoparticles, Liposomes, Micelles, Dendrimers, Nanogels
Role of Nanoparticles in Targeted Drug Delivery Systems
Nanoparticles have become a game changer and the multifunctional system in delivery of drugs to be used in addressing the shortfalls of traditional therapeutic i.e. low solubility, systemic clearance and lack of targeting that tends to diminish effect and increase side effects. To date, preclinical animal models have shown that varying platforms of nanoparticles, including polymeric nanoparticles, liposomes, solid lipid nanoparticles, metallic nanoparticles, dendrimers, and quantum dots, have the potential to improve therapeutic outcome by determining the accumulation of drugs within the body, by controlling and prolonging their release, and by improving bioavailability as well as selective deposition in target tissues. These systems have demonstrated to have potential in a vast field of applications including oncology, neurodegenerative disorders, antimicrobial therapy and anti-inflammatory treatment. The safety and biocompatibility of polymeric and lipid-based nanoparticles are typically favorable, and with metallic nanoparticles, although these types of nanoparticles are multifunctional and have theranostic potential, there is a risk of accumulation or toxicity over time. The animal research has also emphasized the key role of particle size, surface functionalization and composition in determining pharmacokinetics, biodistribution and therapeutic efficacy. However, interspecies variability, large-scale synthesis that can be reproduced and reproducible, standard toxicity tests and optimization of targeting strategies are still critical barriers to clinical translation. Further research on biodegradable nanoparticle substitutes, long-term safety analysis, and comparative studies done systematically are necessary to ensure full utilization of the potential of nanoparticle-based drug delivery system and develop it to a safe, effective, and clinically viable drug delivery system.
Nanoparticles, Targeted Drug Delivery, Polymeric Nanoparticles, Liposomes, Metallic Nanoparticles, Dendrimers, Quantum Dots, Preclinical Studies
Role of Artificial Intelligence in Predicting and Managing Infectious Diseases
Infectious diseases in animals present considerable threats to livestock productivity, wildlife health, and global ecological equilibrium, with outbreaks of diseases such as avian influenza, foot-and-mouth disease, African swine fever, and bovine tuberculosis resulting in significant economic losses and potential zoonotic hazards. Conventional surveillance and management techniques often encounter constraints in velocity, scalability, and precision, underscoring the need for creative alternatives. Artificial Intelligence (AI) has become a pivotal instrument for forecasting, observing, and controlling animal infectious illnesses via the analysis of intricate datasets, including animal movement patterns, environmental factors, pathogen genetics, and agricultural management records. Machine learning, deep learning, and data-driven simulations enable the early detection of outbreaks, risk assessment, hotspot identification, optimization of vaccination regimens, biosecurity monitoring, and the modeling of containment tactics. The integration of IoT devices, drones, and remote sensing allows continuous real-time monitoring of extensive livestock and animal populations. AI-driven methodologies exhibit superior prediction accuracy, swift responsiveness, and optimized resource allocation relative to conventional techniques, despite ongoing hurdles like data quality, processing requirements, and practical application. The use of AI in veterinary epidemiology signifies a transition from reactive to proactive disease management, enhancing worldwide readiness, diminishing economic losses, alleviating zoonotic hazards, and fostering sustainable animal health and ecological preservation.
Artificial Intelligence, Infectious Diseases, Livestock, Wildlife, Disease Prediction, Disease Management, Veterinary Epidemiology, Machine Learning, Deep Learning, Biosecurity, IoT
Role of Antioxidants in The Management of Chronic Kidney Disease
Chronic kidney disease (CKD) is a chronic disease that is characterized by the gradual impairment of renal activity, which is mostly caused by oxidative stress, inflammation, and fibrosis. The accumulation of reactive oxygen species (ROS) adds to the endothelial dysfunction, tubular damage, and extracellular deposition, and enhances the development of the disease. Nrf2 activators, natural (curcumin and resveratrol) and synthetic (bardoxol methyl) are all antioxidant therapies that have demonstrated the potential to reduce oxidative damage, regulate inflammatory and fibrotic responses, and conserve renal function in preclinical models. The natural antioxidants have anti-inflammatory and antifibrotic effects, whereas synthetic antioxidants have multidirector effects of high activity. Although mechanistic understanding is being encouraged, bioavailability, variation in dosing, and species-specific differences are some of the challenges, which limit clinical translation. To prove the effectiveness of antioxidant-based interventions, future studies need to concentrate on rigorous clinical studies, optimal delivery methods, and patient stratification. Altogether, antioxidants are an attractive adjunctive management option to enhance the traditional CKD treatment and reduce the rate of the disease.
Chronic Kidney Disease, Oxidative Stress, Antioxidants, Nrf2 Activators, Curcumin, Resveratrol, Renal Fibrosis, Bardoxolone Methyl
New Horizons in The Treatment of Ovarian Cancer
Ovarian cancer is one of the most fatal gynecological cancers because of its asymptomatic development, delayed detection, elevated recurrence rates, and resistance to chemotherapy, highlighting the critical need for novel treatment approaches. Pre-clinical research using various animal models—such as syngeneic, xenograft, and genetically altered mice—have been crucial in clarifying tumor biology, immunological interactions, metastatic behavior, and treatment responses. These models enable systematic assessment of traditional chemotherapies, targeted treatments, immunotherapies, and nanotechnology-based drug delivery systems, offering insights into effectiveness, pharmacokinetics, toxicity, and resistance mechanisms in an in vivo setting. Syngeneic models facilitate the exploration of immune-mediated therapy, xenografts provide the evaluation of human tumor-targeted interventions, and genetically altered mice mimic critical genetic alterations and tumorigenic pathways, hence augmenting translational value. Pre-clinical data indicate that novel therapies—such as PARP inhibitors, VEGF antagonists, immune checkpoint inhibitors, and nanoparticle-based therapeutic formulations—can enhance tumor shrinkage, extend life, and diminish systemic toxicity. Notwithstanding their limitations, such as the poor reproduction of human tumor heterogeneity and disparities in immune systems, animal models are essential for connecting laboratory research with therapeutic application. This review consolidates advancements in animal-based ovarian cancer research, assesses model-specific advantages and disadvantages, and underscores the incorporation of traditional and novel medicines to formulate safer, more effective, and individualized treatment approaches.
Ovarian Cancer, Animal Models, Syngeneic Mice, Xenograft, Genetically Engineered Mice, Pre-Clinical Studies
Nanotechnology in the Treatment of Skin Disorders Such as Psoriasis
Psoriasis is a chronic, immune-mediated inflammatory skin condition that markedly impacts patients' quality of life and presents difficulties for efficient therapy because to inadequate medication penetration, systemic adverse effects, and restricted therapeutic retention. Traditional treatments, such as topical corticosteroids, systemic medications, and phototherapy, often demonstrate inadequate effectiveness and side effects, prompting the investigation of innovative drug delivery methods. Nanotechnology has emerged as a viable methodology in dermatology, providing nanoscale drug delivery systems including liposomes, niosomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), polymeric nanoparticles, nanoemulsions, dendrimers, and metallic nanoparticles. Pre-clinical studies utilizing murine and rodent models of psoriasis have shown that these nanocarrier systems improve skin penetration, facilitate controlled and sustained drug release, enhance the stability of therapeutic agents, and modulate inflammatory and oxidative pathways, leading to superior lesion healing, diminished epidermal hyperplasia, and reduced cytokine expression relative to conventional treatments. Notwithstanding their potential effectiveness, issues such as intricate synthesis, possible immunogenicity, unpredictability in drug loading, and insufficient long-term safety evidence must be resolved to guarantee their use in clinical practice. Nanotechnology-based formulations provide a revolutionary and precise approach to pre-clinical psoriasis care, offering insights into the creation of safer, more effective, and patient-centric medications.
Psoriasis, Nanotechnology, Nanocarriers, Liposomes, Solid Lipid Nanoparticles, Nanostructured Lipid Carriers
Current Challenges in The Treatment of Autoimmune Disorders
The broad and diverse category of chronic diseases known as autoimmune disorders is caused by the body's immune system mistakenly attacking its own cells and tissues, which leads to tissue damage, organ failure, and persistent inflammation. Because of their complex etiology, which includes genetic, environmental, and immunological variables, these disorders—which include multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes—present serious therapeutic issues. There has been little progress in creating long-lasting and efficient medicines, even with significant advances in immunology and therapeutic approaches. Understanding the pathophysiology of diseases, assessing immunomodulatory tactics, and forecasting the possible effectiveness of new treatments have all benefited greatly from the use of animal models. This review focuses on the current difficulties in treating autoimmune disorders as they have been identified by animal-based research. These difficulties include species-specific immune responses, translational gaps between preclinical and clinical outcomes, variability in disease manifestation, and limitations of current preclinical models. Additionally, it talks about methodological strategies, the advantages and disadvantages of various animal models, and new discoveries in treatments meant to alter immune responses.
Autoimmune Disorders, Animal Models, Immunotherapy, Disease Pathophysiology, Systemic Lupus Erythematosus, Type 1 Diabetes, Therapeutic Challenges, Immunomodulation.
Comparative Study of Beta-Blockers On Cardiac Function
The use of beta-blockers in the management of cardiovascular diseases is widespread; however, the effects of these drugs on individual cardiac functions differ with regard to their pharmacological characteristics. The present study sought to comparatively determine the effects of three of the frequently used beta-blockers, Atenol, Metoprolol, and Propranol on cardiac functionality in adult Wistar rats. A total of forty male rats were assigned randomly in four groups with a control group and were fed with the corresponding beta-blocker as an oral dose over a period of four weeks. They measured cardiac parameters such as heart rate, the left ventricular ejection fraction (LVEF), fractional shortening and systolic blood pressure at the baseline and the end of treatment. Findings indicated that beta-blockers all had significant effects on the heart rate with Propranol having the most effect. Metoprolol was the most significant in terms of increasing left ventricular performance and cardiac contractility and Atenolol was moderate and Propranolol was not significant in terms of LVEF and fractional shortening. Every drug had a significant effect in reducing systolic blood pressure with Propranol recording the greatest decrease. These results indicate the differences on the effects of beta-blockers on cardiac performance which support the personalized application of Metoprolol to improve myocardial contractility and Propranol to regulate the heart rate and blood pressure.
Beta-blockers, Atenolol, Metoprolol, Propranolol, Cardiac function, Heart rate, Systolic blood pressure, Wistar rats, Cardiovascular pharmacology
Comparative Pharmacological Study of Statins in Hyperlipidemia
Hyperlipidemia is regarded as one of the leading risk factors of cardiovascular diseases and statins are trendy to regulate the elevated levels of lipids by inhibiting the action of HMG-Coa reductase. Lipid-lowering agents include atorvastatin, simvastatin and rosuvastatin and have already been established to play a relatively similar role with reference to hyperlipidemic Wistar rats as has been established in this study. The high-fat ration has been exposed to 50 male rats which are randomly divided into four slices and hyperlipidemia is developed. The value of the statins has been determined after 28 days and at initiation and end of treatment of the lipid parameters which include the total cholesterol(TC), triglycerides(TG), total low density lipoprotein cholesterol (LDL-C) and total high density lipoprotein cholesterol (HDL-C). The findings showed that the statins and TC TG LDL- C and HDL- C rise were gigantic in all statin treated groups except hyperlipidemic controls in the topmost level with the most effective statin being rosuvastatin. Post hoc and one-way ANOVA confirmed significantly different statins when rejecting the null hypothesis and confirmed further difference between the statins. The results add preclinical supporting information to the higher lipid-lowering capacity of rosuvastatin and could offer comparative information on future pharmacological studies and the improvement of the catheterization approaches in fighting lipid hypercarbohydrates in animals.
Hyperlipidemia, Statins, Atorvastatin, Simvastatin, Rosuvastatin, Lipid Profile, Wistar Rats, HMG-CoA Reductase Inhibitors, Preclinical Study, Cardiovascular Risk.
Advances In Stem Cell Therapy for Cardiovascular Diseases
Cardiovascular diseases (CVDs) are a major global health concern, but current treatment methods mostly aim at alleviating symptoms rather than repairing damaged heart tissue. It has been suggested that stem cell therapy might be a viable regenerative option for restoring cardiac function by direct differentiation, paracrine signaling, immunomodulation, and angiogenesis. Mesenchymal stem cells (MSCs), cardiac stem cells (CSCs), and induced pluripotent stem cells (iPSCs) have therapeutic potential, according to preclinical study. Biomaterial scaffolding and improved delivery methods also lead to improved cell survival, retention, and integration. Although the outcomes are encouraging, shortcomings associated with this approach include low long-term engraftment, immune rejection, tumorigenicity, and inconsistency in outcomes, which discourage clinical translation. Current studies that have aimed to address these limitations through improved cell selection, combination therapy, biomaterials engineering, and personalized therapies, promise to overcome these obstacles and provide the community with the possibility to transform cardiovascular care beyond palliative care to actual myocardial regeneration.
Cardiovascular Diseases, Stem Cell Therapy, Mesenchymal Stem Cells, Cardiac Stem Cells, Induced Pluripotent Stem Cells, Cardiac Regeneration, Paracrine Signaling, Biomaterial Scaffolds
Antioxidants' Function in The Treatment of Chronic Kidney Disease
Chronic kidney disease (CKD) is a progressive disorder, which is associated with progressive loss of renal functionality, having oxidative stress as one of the key mechanisms that contribute to inflammation, fibrosis, and tissue damage. Studies on animals have been becoming increasingly interested in the therapeutic value of antioxidants in alleviating these pathogenic events. This review summarizes the evidence available on natural antioxidants, such as vitamins, polyphenols and flavonoids, and synthetic antioxidants, such as N-acetylcysteine and enzymatic mimetics, such as Tempol, in preclinical models of CKD. The evidence suggests that these agents are useful in reducing reactive oxygen species, increasing endogenous antioxidant defenses, preserving mitochondrial functions, and regulating pro-inflammatory, pro-fibrotic signaling pathways, which reduce renal injury and improve its functions. Comparative analysis has revealed that natural antioxidants present multi-targeted protection with limitations on bioavailability, synthetic antioxidants give strong intracellular protection mainly in renal tissues and enzyme mimetics have both renal and systemic cardiovascular effects. Even with these positive results, animal models, dosages, and long-term research are variable, thus making translation a problem. This review highlights the possibility of antioxidant therapy as an adjunctive intervention in the management of CKD and the need to have standard preclinical studies to maximize its efficacy and ease its future use in the clinical scene.
Chronic Kidney Disease, CKD, Oxidative Stress, Antioxidants, N-Acetylcysteine, Tempol, Polyphenols, Flavonoids, Renal Protection
Genetic and Epigenetic Factors in Breast Cancer Progression
Genetic and epigenetic processes are intertwined in a complex manner in order to enhance the development of breast cancer by regulating the fundamental cellular processes including DNA repair, proliferation, differentiation and metastasis. This review provides an overview of the findings of animal model experiments to explain the causes of the significant changes in genetic aspect including RAD51C mutations and dys-regulation of the BAF chromatin remodeling complex and epigenetic alterations, such as DNA methylation, histone modification, and microRNA dys-regulation. The animal models are where the researcher can study the mechanism by which these changes of the molecules cause tumorigenesis, stimulate tumor growth and metastatic potential. The data received in the course of such studies denotes the dynamism and reversibility of the epigenetic processes which may be utilized in treating diseases by selectively regulating the expression of the said molecules with an aim of modifying DNA methylation, histone-modifying enzymes, and miRNAs. Integration of genetic and epigenetic understanding will not only enhance our understanding of breast cancer biology, but also design the precision therapies, and also expose potential biomarkers that can be utilized to identify and diagnose the disease at the earliest phase. In total, the significance of the animal-based research in the context of finding mechanistic information and design interventions to limit the occurrence of breast cancer is highlighted in this review as a foundation of the subsequent use of the translation research and clinical interventions.
Breast Cancer, Genetic Mutations, Epigenetic Modifications, RAD51C, BAF Complex, DNA Methylation, Histone Modifications, Micrornas, Tumor Progression, Animal Models.
Emerging Therapeutic Approaches in Prostate Cancer Management
Prostate cancer is also a major contributor of cancer morbidity and mortality in men all over the world, and this issue has necessitated the innovation of effective and novel treatment modalities. The review is based on recently developed methods that were tested in preclinical animal models, such as nanomedicine-based targeted delivery systems, immunotherapies, gene-editing interventions, and natural phytochemicals. The rodent and murine studies have provided evidence that these strategies have the potential to improve tumor specificity, increase the bioavailability of drugs, overcome the problem of multidrug resistance, and minimize systemic toxicity in comparison to other conventional treatment methods. The combination and multi-targeted interventions especially the ones based on the incorporation of nanocarriers into chemotherapeutics or natural compounds exhibit a synergistic effect on anti-tumor activities and enhanced safety profiles. Although with good preclinical results, translational problems such as optimization of animal models, long-term safety and mechanistic knowledge have to be resolved before being used in clinical practice. Altogether, these new treatment methods provide a strong basis of safe, more effective, and personalized treatment of prostate cancer.
Prostate Cancer, Emerging Therapies, Nanomedicine, Immunotherapy, Gene Therapy, Phytochemicals, Animal Models, Targeted Drug Delivery.
Protective Effects of Neeli Bhringraj Oil Against Hair Breakage and Strengthening Damaged Hair Fibers: Scientific Evidence from an In-Vitro Fatigue Test Model
Objective Hair fall due to breakage is a widespread concern influenced by multiple intrinsic and extrinsic factors such as heat styling, chemical treatments, pollution, and UV exposure. Herbal oils, particularly those used in Ayurvedic practice, have long been valued for their ability to protect and nourish hair. This study aimed to evaluate the efficacy of Neeli Bhringraj oil, a traditional Ayurvedic formulation, in reducing hair breakage and improving tensile strength using in-vitro fatigue test model. Methods Standardized human hair swatches were deliberately damaged through surfactant washes, heat, UV, and pollution exposure. Damaged swatches were randomized and treated for 12 cycles with either Neeli Bhringraj oil (test group) and another with control. After treatment, swatches underwent wet fatigue testing using the TESTRONIX Tensile Strength Tester, where broken fibers were collected and analyzed. Statistical significance was assessed using paired two-tailed t-tests (p <0.05). Results The Neeli Bhringraj oil group showed significantly fewer broken fibers (11.67 ± 4.46) compared to the control group (21.67 ± 9.69, p <0.01). This corresponded to a 4.19-fold improvement or 76.11% reduction in breakage. Fragment analysis further revealed fewer short-length fibers (<6.25 cm) in the test group, indicating stronger tensile resilience. Conclusion This study confirms that Neeli Bhringraj oil (Neela Bhringadi) provides substantial protection against hair breakage and effectively strengthens damaged hair fibers. By forming a protective layer and nourishing the hair shaft, the oil minimizes damage from environmental and mechanical stressors. These findings validate the traditional use of Neeli Bhringraj oil and support its potential as an evidence-based intervention for reducing hair fall and improving overall hair health.
Role of Cannabinoids in Chronic Pain Management: A Pharmacodynamic Perspective
Chronic pain has been shown to be a huge health burden worldwide with just about 20-30 per cent of the adult population being affected, greatly affecting their quality of life, day to day functioning and their mental health. The standard pain relievers involving opioids and non-steroidal anti-inflammatory drugs have their drawbacks to safety, tolerance and effectiveness over vast periods, hence requiring alternative agents. Cannabinoids, especially tetrahydrocannabinol (THC) and cannabidiol (CBD) have been found to offer great potential as therapeutic agents in their multimodal mode of pharmacodynamic action. This review summarises existing results regarding the pharmacodynamics of cannabinoids in pain management, noting that they exert central CB1 receptor-mediated nociceptive transmission blockade as well as peripheral CB2 receptor-mediated anti-inflammatory effects and influence of neurotransmitter systems such as the GABAergic, glutamatergic and opioid systems. There is evidence to show consistent efficacies in neuropathic pain and promising adjunctive effects on cancer pain, and occasional, but emerging areas of usage taking place in nociceptive pain. Nevertheless, obstacles exist with regards to the methodological heterogeneity, the dosage variability, the safety oriented cognitive and cardiovascular adverse effects and the pharmacodynamic variability caused by genetic polymorphism and drug interactions. Future directions in research need to be centred on further mechanistic research, large clinical trials of standardised dosing in larger populations and subtype specific delivery of medicine with pharmacogenetic profiling to study optimisation of medicine delivery to patients. Recognizing the pharmacodynamics of cannabinoids has key implications in the process of evidence-based incorporation of cannabinoids into clinical practice, in the enhancement of chronic pain control methods, and the creation of safe and effective cannabinoid-based pain relievers.
Tetrahydrocannabinol, Cannabidiol, Chronic Pain, Methodological Heterogeneity, Pharmacodynamic
The Pharmacogenetics of Opioid Metabolism: A Clinical Perspective
The given review provides an extensive overview of the pharmacogenetics of opioid metabolism as viewed through the prism of animal-based clinical studies, focusing on genetic variability as the fundamental aspect of drug response modulation. By taking an approach of synthesizing findings of rodent and canine, the paper aims at focusing on crucial metabolic enzymes of CYP2D, CYP3A, and UGT1A/2B, and membrane transporter ABCB1 (P-glycoprotein) in order to understand how naturally existing or induced experimentally genetic polymorphisms interact with opioid biotransformation, analgesic efficacy, and adverse effect profile. As an example, the variations in CYP2D isoforms across rat strains have strong implications on codeine-to-morphine conversion, and MDR1-deficient canines exhibit an enhanced sensitivity of the central nervous system towards opioids because of poor efflux capability. Such learnings are incredibly significant, not only to veterinary medicine itself, as a way to dose opioids by breed, but also to human drug development, which relies heavily upon animal models in preclinical screening and risk measures. The review also singles out research gaps that are critical such the lack of Genomic databases to animals and limited genetic diversity within experimental populations. It recommends that more cross-species studies need to be done, and multi-omics methods should be integrated and that more humanized animal models need to be generated to increase translation correctness. Finally, the knowledge of pharmacogenetic processes in animals improves different safety, efficacy and species-specific therapeutic approaches to opioid therapy
Pharmacogenetics, Opioid Metabolism, CYP450 Enzymes, ABCB1 Transporter, Animal Models, Veterinary Pharmacology
Pharmacological Modulation of Gut Microbiota in Metabolic Syndrome
Gut microbiota has been identified as a regulator of metabolic health, especially the metabolism syndrome (MetS), which is a multifactorial disease, including obesity, insulin resistance, dyslipidemia, and hypertension. Recent preclinical models involving rodents exposed to high-fat diets have demonstrated therapeutic benefits of pharmacological agents (e.g. metformin, berberine, and probiotics, prebiotics, and bile acid modulators, to mention a few) not only on direct molecular targets but also on the gut microbiome. These agents Walter U. [2016] Enhance the abundance of probiotic microbial taxa such as Akkermansia muciniphila and Bifidobacterium, Short chain fatty acid (SCFA) production, and improve gut barrier integrity as well as attenuate systemic inflammation and metabolic endotoxemia. The review is critical in assessing the methods, results, and actions taken by these interventions to improve host-microbiota interactions in the alleviation of MetS characteristics, such as raised insulin sensitivity, glucose, and lipid metabolism. It is also discussing some critical drawbacks of existing preclinical models, including species-level disparities in microbiota and the brevity of observation, which could be problematic to translate to clinical settings. It gives prominence on the implications on microbiota-modulating treatments, integrations of microbiome-modulating adjuncts, and how this can be studied further, such as long-term studies and individual approaches to treatment. On balance, it is possible to talk about pharmacological modulation of the microbiome of the gut as the new promising way of improving treatment outcomes of MetS and its sustainability.
Gut Microbiota, Metabolic Syndrome, Metformin, Berberine, SCFAS, Dysbiosis, Bile Acid Modulators, Preclinical Studies
Pharmacological Evaluation of Novel Antidiabetic Agents Targeting GLP-1 Receptors
Diabetes mellitus is a long-term metabolic illness that makes it hard for the body to make and use insulin, which causes high blood sugar levels and other problems. Because they have glucose-dependent insulinotropic actions and the potential to protect β-cells, glucagon-like peptide-1 (GLP-1) receptor agonists have become intriguing drugs for treating diabetes. Using an alloxan-induced diabetic rat model, this study attempted to pharmacologically test two new antidiabetic drugs that target GLP-1 receptors. Thirty Wistar rats were split into five groups and given treatment for 21 days. There was a normal control group, a diabetic control group, a conventional drug group (Exenatide), and two test drug groups. We looked at fasting blood glucose levels, body weight, serum insulin, lipid profiles, and pancreatic histology. The results showed that both test pharmaceuticals lowered blood glucose levels and improved metabolic parameters more than the diabetic control group. Test Drug A worked as well as Exenatide. Histological investigation showed that β-cells were able to grow again in the groups that were treated. Using one-way ANOVA to look at the data statistically showed that these results were important (p < 0.05). The study finds that the new drugs, especially Test Drug A, have strong antidiabetic potential through processes that include the GLP-1 receptor. More research is needed in long-term and clinical settings.
GLP-1 receptor agonists, Antidiabetic agents, Diabetes mellitus, Insulin secretion, Blood glucose control
Pharmacogenomic Profiling for Personalized Treatment of Major Depressive Disorder
Depression is the leading mental health issue, major depressive disorder (MDD) is diagnosed in more than 264 million people worlds over and there is a significant heterogeneity in the response of individuals to antidepressant treatment. The use of traditional approaches tends to be based on a trial-and-error approach, resulting in a long-term suffering process, high costs of healthcare avenues, and the risk of suicide. The study examines how a pharmacogenomic profile could be used in individualizing antidepressants among patients with MDD. Based on a cohort sample of 150 patients with MDD, genotypic differences in CYP2D6, CYP2C19, SLC6A4 and HTR2A were measured in order to establish a relationship between their drug metabolism and treatment reaction. The result of our analysis shows a considerable statistically significant association between genotype pattern and clinical outcomes, especially the SSRIs and tricyclic antidepressants. The paper has come to the conclusion that pharmacogenomic-guided therapy offers massive improvements in the effectiveness of treatment, the reduction of bad effects, and can transform the psychiatric treatment approach. These findings justify the introduction of pharmacogenomic screening practice into routine psychiatric care to maximize antidepressant treatment and enhance the quality of life of MDD patients.
Major Depressive Disorder (MDD), Pharmacogenomics, Antidepressant Therapy, Personalized Medicine, CYP2D6, CYP2C19
Investigating The Neuroprotective Role of Curcumin in Alzheimer's Disease Models
Alzheimer disease (AD) is a pathological worsening process of neurodegenerative disease characterised by impaired thinking, memory and behavioural problems, which have a considerable health impact worldwide. There is no disease-altering treatment at the present day that can help limit the progression of the disease, which is why there is the strong necessity to develop a disease-modifying medication. Natural therapeutic explores in curcumin A polyphenolic compound, curcumin found in Curcuma longa (turmeric) has gained a lot of interests to potential natural therapeutic agent because of its powerful antioxidant, anti-inflammatory, anti-amyloid and chelation towards metals. This review provides a comprehensive study on the neuroprotective effects of curcumin in the case of Alzheimer disease, its biochemical and pharmacological profile in its application regarding unique chemical content, bioactive compounds of curcumin, and pharmacokinetic constraints, like poor bioavailability. In vitro studies at the preclinical level show that curcumin can limit neurotoxicity caused by amyloid beta, prevent the formation of aggregates, and limit oxidative and inflammatory injuries and in vivo-based rodent trials report both cognitive and behavioural enhancements as well as the decrease of amyloid plaque and hyperphosphorylation of tau proteins. However, several limitations like low bioavailability, absence of large-scale, clinical trials, and insufficiency of long range safety make clinical implementation poor. The future study is needed to create a nano formulation, which will improve its bioavailability and combination therapies, which will produce a synergistic neuroprotective effect. In general, curcumin has a large potential as effective safe multi-targeted therapy against Alzheimer disease and its relevance should be further investigated due to conducting well-conducted human trials that may determine its effectiveness.
Alzheimer’s disease, Neurodegenerative disease, Curcumin, Polyphenols, Neuroprotection
Integration of Pharmacogenomics into Clinical Practice: Opportunities and Challenges
This potential of precision veterinary medicine to be implemented through the use of pharmacogenomics (PGx) by animal-based clinical practice is immense. This review brings out the species and breed specific genomic differences which affect drug clearance, and effectiveness and toxicity in animals. It also looks into the importance of principal active enzymes, including cytochrome P450s, UGTs and ABC transporters and the employment of genetically altered animal models, including CYP knockout mice and Beagles, in comprehending gene drug relationship. Methodologies used in veterinary PGx research, regulatory and ethical considerations and the utility of animal pharmacogenomics in drug discovery in animal preclinical studies are also discussed in the review. In spite of substantial advantages of the field, which are associated with better therapeutic results, fewer side effects, and a higher level of ethical animal tests, it has specific restrictions connected with unfinished genomic databases and the absence of guidelines on clinical implementation. In the current paper, the authors point at the necessity of joint efforts to develop genomic data, standardize veterinary testing procedures, and develop a framework that will promote incorporating PGx into standard veterinary practice and support the One Health approach
Pharmacogenomics, Veterinary Medicine, Drug Metabolism, Animal Models, Precision Therapy
Influence of HLA Alleles in Adverse Drug Reactions: A Pharmacogenetic Study
Adverse drug reactions (ADRs) especially immune mediated ADRs are a major challenge to clinical pharmacology and drug development. There is a mounting evidence that certain alleles of the Human Leukocyte Antigen (HLA) such as HLA-B15:02, HLA-B57:01 and HLA-A*31:01 predispose individuals to severe hypersensitivity reactions when exposed to carbamazepine, abacavir, and allopurinol, respectively. The use of transgenic mouse models that express these HLA alleles in this pharmacogenetic study was utilized to understand their contribution in the pathogenesis of immune-based ADRs. In transgenic mice, the rate of hypersensitivity symptoms was significantly higher after drug administration, and the concentration of cytokines (especially TNF-alpha and IFN-gamma) in the serum was higher, as well as T-cell activation (CD69+, CD25+) compared to the control mice. Immune-mediated tissue inflammation in HLA-expressing groups was further confirmed using histopathological evaluations. The results they report are highly representative of known clinical trends in humans and give direct in vivo support to the relationship between HLA polymorphisms and drug-induced immunotoxicity. The analysis shows the usefulness of HLA-transgenic mouse as predictive model of preclinical immunogenicity profiling that can be incorporated into the early stage drug safety testing and development of personalized medicine.
Adverse Drug Reactions (Adrs), Hla Alleles, Hypersensitivity, Transgenic Mouse Model, Carbamazepine, Abacavir, Allopurinol
Impact Of CYP450 Gene Variants On Warfarin Dosing In the Indian Population
Warfarin is a common oral anticoagulant that has narrow therapeutic index and high inter-individual variability in dose response and is primarily determined by the genetic polymorphisms of drug-metabolizing enzymes. This paper explores the effects of gene variants CYP2C9 and CYP4F2, typical of Indian population, on the pharmacokinetics and pharmacodynamics of warfarin in genetically simulated Wistar rat models. The forty-eight rats were divided into six groups according to their genotypes and received warfarin at 0.2 mg/kg/day during five days. Metabolic clearance and anticoagulant response were measured by the determination of the plasma warfarin levels and prothrombin time (PT). The findings indicated that rats with CYP2C9 *1/*2 and *3/*3 genotype had a significantly greater concentration of warfarin in the plasma and PT that was extended compared to the wild-type, which are indications of reduced clearance and sensitivity to anticoagulants. In the same way, CYP4F2 *1/*3 and *3/*3 genotypes had significant but moderate alterations in both parameters. The results are reflective of clinical data in human beings and the usefulness of preclinical genetic models in the study of pharmacogenetic variation. The research supports the possibility of genotype-specific personalized dosing of warfarin with an emphasis on a genetically diverse population like India.
Warfarin, CYP2C9 Polymorphism, CYP4F2 Polymorphism, Pharmacogenetics, Prothrombin Time, Rat Model
Genome-Wide Association Study of Statin-Induced Myopathy
Statins are very common lipid-lowering drugs that have been proven to be effective in preventing cardiovascular risk. Nevertheless, the development of statin-induced myopathy, which is manifested as muscle pain, weakness, and in severe cases, rhabdomyolysis, tends to undermine their clinical utility. In human studies, genetic predisposition has been postulated; however, the confounding variables make it hard to define the mechanistic knowledge. In this research, a genome-wide association study (GWAS) framework is applied in secondary data of animal models to determine genetic determinants that are related to statin-induced muscle toxicity. The meta-analysis of several rodent studies and combination of biochemical biomarkers allowed the identification of five important genes (Slco1b2, Cyp3a1, Ugt1a1, Abcc2, and Coq2) that were significantly correlated to greater susceptibility to statin-induced myopathy. The significant association between Slco1b2 and Coq2 with an increased creatine kinase and lactate dehydrogenase and marked histopathological muscle destruction demonstrates that they are the most important factors in the myotoxic reaction. Mechanisms in which impaired drug transport, altered metabolism, and mitochondrial dysfunction were recognized were marked using functional pathway mapping. These results endorse the translational potential of genetic screening in the prediction of statin intolerance and form a solid basis to establish personalized treatment and less harmful lipid-lowering drugs.
Statin, Induced, Myopathy, Genome, Wide, Association, Study (GWAS), Pharmacogenomics, Animal Models, Genetic Biomarkers
Genetic Markers for Predicting Cancer Immunotherapy Response
Immune checkpoint blockade and cancer immunotherapy have revised the cancer treatment therapeutic environment, but patient reactions are excessively difference. The targeted population in this systematic review is animal trials in order to understand any genetic markers effecting the efficacy of the immunotherapy. The research tries using murine models like syngeneic, genetic engineered mice and humanized mice to define key genes that are determinants of therapeutic response (PD-L1, IFN-gamma, JAK1/2, CTNNB1 and EZH2). High expression of PD-L1 and IFN-γ reported positive correlation with response and survival whereas mutation in JAK1/2 and CTNNB1 activation reported resistance because of ineffective immune infiltration and stimulation events. Inhibition of EZH2 increased immune activity partly which indicates the role of epigenetic control. The predictive value of these markers was confirmed by the analysis of data via ANOVA, Kaplan-Meier survival curves, correlation, and bioinformatics tools. Animal models will continue to be essential to mechanisms, despite species-related and methodological limitation. These results confirm the use of genetic profiling in personalized immunotherapy strategies and point to the importance of additional translational data in models more humanized as well as multi-omics.
Cancer immunotherapy, Genetic markers, Animal models, Immune, checkpoint inhibitors, Preclinical, trials, Personalised, medicine, Tumour, microenvironment, Biomarker prediction; CRISPR; T-cell infiltration
Exploring The Cardioprotective Potential of Natural Flavonoids in Ischemia Models
Flavonoids are classes of polyphenolics compounds in many fruits and medicinal plants that have been found to possess substantial cardioprotective capabilities in pre-clinical models of myocardi AL-SAWFY (2017). This is a review of their role in the inhibition of myocardial damage by exhibiting multimodal actions such as antioxidant protection, anti-inflammatory, anti-apoptotic, and autophagic processes. Most flavonoids like quercetin, kaempferol, apigenin ligature, luteolin, naringenin, and hesperidin have a consistent effect on rodent models, where they reduce infarct size, increase cardiac performance and protect the integrity of the mitochondrion. Mechanically, their activity mimics the Nrf2/ARE and PI3K/Akt signaling, inhibition of NF-kB and MAPK signaling as well as AMPK/mTOR controlled autophagic flow to improve the survival of cardiomyocytes and tissue recovery. Clinical translation of these encouraging findings is hampered by shortcomings in bioavailability, a lack of pharmacokinetic data and inability to demonstrate or elicit a response in comorbid or large animal models. To make full use of the therapeutic effect of flavonoids in ischemic heart disease, future studies should fill these gaps by applying standardized protocols, long-term studies, as well as human trials. Their versatile nature and multi-targeted activity, along with non-toxicity in animal investigations lead to the possibility of using flavonoids as effective supplementary methods or supplements to traditional approaches of cardioprotection.
Flavonoids, Ischemia-Reperfusion Injury, Cardioprotection, Oxidative Stress, Inflammation, Apoptosis, Autophagy, Myocardial Infarction
Evaluation of Drug–Drug Interactions in Polypharmacy Among Elderly Patients
With the growing prevalence of comorbidities among the elderly population, polypharmacy has become a common practice, raising significant concerns about drug–drug interactions (DDIs). This retrospective observational study aimed to evaluate the prevalence, severity, and clinical implications of DDIs in elderly patients aged 65 years and above who were prescribed five or more medications during hospitalization at a tertiary care hospital. Data from 150 patient records were analyzed using Lexicomp® and Micromedex® drug interaction checkers. The findings revealed that 78.7% of patients experienced at least one potential DDI, with a total of 439 interactions identified—of which 55.4% were of moderate severity and 22.3% were major. A statistically significant association (p < 0.001) was observed between the number of medications and the occurrence of DDIs. The most frequent interacting drug classes included antihypertensives with NSAIDs, anticoagulants with antibiotics, and oral hypoglycemics with corticosteroids. The study highlights the need for routine DDI screening, rational prescribing, and interdisciplinary collaboration to enhance medication safety in geriatric care.
Polypharmacy, Drug–Drug Interactions, Elderly Patients, Geriatric Pharmacotherapy, Retrospective Study, Lexicomp, SPSS, Medication Safety.