Current Drug Research Reviews - Online First

Alzheimer's Disease (AD) progresses pathophysiologically several years before noticeable symptoms emerge, indicating a pre-symptomatic or pre-clinical phase. Early identification of pre-clinical AD requires sensitive, specific, and reliable biomarkers. This review aimed to explore and evaluate radiological biomarkers and neurochemical biomarkers for pre-clinical AD and to emphasize advancements needed for diagnostic tools that allow early detection, comprehensive assessment, and continuous tracking of AD progression.

A comprehensive review of radiological and neurochemical markers in medical research. The analysis focused on their sensitivity, specificity, and reliability for detecting pre-clinical AD stages.

Identified radiological biomarkers include advanced imaging techniques (e.g., PET scans and MRI) that detect structural and functional changes in the brain. Neurochemical biomarkers, such as amyloid-beta and tau proteins, are promising indicators detectable in Cerebrospinal Fluid (CSF) and blood. Emerging technologies are improving biomarker detection accuracy, enabling the identification of AD even in asymptomatic individuals.

Radiological biomarkers, including PET and MRI, offer insights into Alzheimer's-related brain changes, while neurochemical markers like amyloid-beta and tau proteins aid early detection through CSF and blood analysis. Advances in technology enhance diagnostic precision, enabling the identification of asymptomatic cases, crucial for early intervention and improved patient outcomes.

Biomarker discovery for pre-clinical AD is essential for early intervention and improved patient outcomes. Continued research is crucial to enhance diagnostic tools for early detection and to track disease progression comprehensively. Future investigations must prioritize the refinement and validation of these biomarkers for clinical application.

Diabetes and its associated complications encompass a range of comorbidities, including issues like impaired wound healing and chronic ulceration. It is very important to find an effective and economical way to manage diabetes and its complications. This review seeks to outline the mechanisms of action and potential drug targets of specific medicinal plants and derived compounds in healing diabetic wounds. Additionally, it aims to offer scientific evidence and research insights for their clinical application.

A literature search was conducted using Google Scholar, PubMed, and Scopus for articles on diabetic wound healing published between 2001 and December 2024. Using relevant keywords, 3122 articles were identified. After screening and applying exclusion criteria, 63 studies were selected and categorized into medicinal plants, plant-derived molecules, and clinical studies to explore potential therapeutic targets.

Chronic diabetic wounds (DW) exhibit impaired healing across all wound repair phases, i.e., hemostasis, inflammation, proliferation, and remodelling. During hemostasis, defective coagulation and impaired platelet aggregation delay initial wound closure. The inflammatory phase is characterized by persistent inflammation, driven by elevated pro-inflammatory cytokines (e.g., TNF-α, IL-6), reduced anti-inflammatory mediators, and dysregulated NF-κB, MAPK, and PI3K/Akt signalling pathways, which exacerbate tissue damage. In the proliferative phase, diminished levels of growth factors (e.g., VEGF, PDGF) and disrupted signalling cascades impair angiogenesis, fibroblast proliferation, and extracellular matrix (ECM) synthesis, hindering tissue regeneration. The remodelling phase is compromised by chronic inflammation and an imbalance in matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) activity, resulting in defective collagen reorganization, reduced tensile strength, and poor wound maturation. Herbal medicines demonstrate potential in ameliorating these impairments by modulating dysregulated pathways, exerting anti-inflammatory, antioxidant, and pro-angiogenic effects, and promoting balanced wound repair across all phases. Nevertheless, rigorous scientific validation and standardized documentation of traditional medicinal practices are essential to confirm their therapeutic efficacy and safety in DW management.

Diabetic wound management remains a major clinical challenge due to the limited efficacy and side effects of standard therapies. Medicinal plants and their bioactive compounds show promising healing potential through multi-targeted mechanisms. This review highlights a key research gap in the mechanistic understanding and clinical validation of traditional remedies, offering novel insights into targeting pathways like NF-κB, MAPK, and PI3K/Akt for improved diabetic wound care.

Preservatives are widely used chemical agents that inhibit microbial growth and extend the shelf life of food and pharmaceutical products. However, growing concerns over the potential adverse effects of synthetic preservatives, such as parabens and benzoates, have emphasized the need for precise and reliable analytical methods for their detection and quantification.

This review evaluates and compares various analytical techniques employed for preservative analysis in pharmaceutical formulations, including chromatographic (HPLC, GC-MS), spectroscopic (UV-Vis), electrophoretic (CE), and electrochemical methods. Parameters such as sensitivity, accuracy, separation efficiency, and applicability in complex matrices were assessed across different techniques.

High-performance liquid chromatography (HPLC) demonstrated superior sensitivity with detection limits as low as 0.01 µg/mL and excellent linearity (R² > 0.999), making it the most widely adopted method. Capillary electrophoresis (CE) provided rapid analysis within 10 minutes and high recovery rates (>98%). UV-Vis spectroscopy, although economical, faced challenges in analyzing complex samples due to spectral overlapping. Gas chromatography–mass spectrometry (GC-MS) excelled in identifying volatile preservatives through enhanced structural elucidation.

HPLC emerged as the gold standard for routine preservative analysis due to its high precision (RSD < 2%), versatility, and ability to quantify multiple preservatives concurrently. While GC-MS offers detailed structural insight, it is more suited for specific applications. Emerging methods like UPLC and CE are gaining attention for their speed and reduced solvent usage, aligning with green analytical chemistry principles.

Robust and sensitive analytical techniques are essential for the accurate determination of preservatives to ensure pharmaceutical safety and regulatory compliance. Continued innovation and optimization in analytical methodologies enhances the reliability of preservative monitoring and contributes significantly to public health risk assessment.

The oral route is a preferred method for drug administration; however, lipophilic drugs often suffer from poor water solubility, significantly limiting their therapeutic effectiveness. Traditional approaches like complexation, micronization, and solid dispersion have been explored, but each comes with inherent limitations.

Self-Emulsifying Drug Delivery Systems (SEDDS) have emerged as a promising strategy to address solubility challenges. These systems incorporate drug molecules into a mixture of oils, surfactants, and cosolvents to enhance solubility. Ternary phase diagrams are frequently utilized to determine optimal component ratios for effective formulation.

SEDDS maintain drugs in a solubilized form within gastrointestinal fluids and protect peptide drugs from enzymatic degradation-a common issue in conventional formulations. They also facilitate the formation of stable emulsions at the target site, enhancing drug absorption. Additionally, the ability of SEDDS to traverse the blood-brain barrier (BBB) increases their applicability in treating neurological disorders.

The findings emphasize the utility of SEDDS in overcoming the solubility and stability challenges faced by poorly water-soluble drugs. Their capacity to enhance drug absorption and protect bioactive molecules from degradation aligns with current efforts to improve oral drug delivery systems. However, formulation complexities and variability in in vivo performance remain areas requiring further investigation.

This review outlines the formulation strategies, characterization methods, and evaluation techniques for SEDDS, emphasizing their potential in enhancing the bioavailability of poorly soluble drugs, particularly those aimed at the central nervous system. SEDDS offer a promising platform for improving therapeutic outcomes across diverse clinical settings.

K⁺ channels play a key role in the development of the vasodilation response, which is compromised in diabetes.

In this study, the effects of the potassium channel activator cromakalim on aortic function were investigated in streptozotocin (STZ)-diabetic rats at short (1 week), medium (8 weeks), and long-term (14 weeks) durations, including a group treated with insulin for 14 weeks.

Compared with the control group, cromakalim-induced concentration-dependent vasodilation was reduced in the aortas of 8 and 14-week streptozotocin-diabetic rats (p < 0.05). Daily insulin treatment during the long-term (14 weeks) durations normalized the vasodilation response to cromakalim in the aortas of 14-week streptozotocin-diabetic rats.

Studies with cromakalim on diabetic rat aortic K⁺ channels are limited. Dose-dependent cromakalim-induced vasodilation was investigated in 8- and 12-week STZ-diabetic rat aortas and was found to be reduced. The impaired vasodilation responses were improved in the STZ-diabetic group with chronic insulin treatment. The results of these studies were similar to those of our study.

These findings indicate that potassium channel activity and vascular vasodilation ability decrease in the aortas of streptozotocin-diabetic rats depending on the duration of diabetes. In contrast, potassium channel activity and vascular vasodilation ability return to normal with insulin treatment in 14-week streptozotocin-diabetic aortas.

This review focuses on the various natural and synthetic antioxidants which affect cellular signalling and mitochondrial dynamics for managing diabetes and its complications including other variety of diseases or traumas.

Information in the current review was gathered from electronic scientific resources like google scholar, science direct, springer link and via the PubMed website using the Boolean Method and a variety of keywords.

The results of the present study revealed that a number of 110 antioxidants have been identified to improve mitochondrial health, offering potential treatments for diabetes and a spectrum of other diseases. Naturally occurring antioxidants such as polyphenols and flavonoids present in fruits and plants, have demonstrated the ability to attenuate oxidative stress and enhance mitochondrial performance thereby helps in the management of diabetes and various other health complications. From among the polyphenol’s resveratrol, mitoQ, quercetin and curcumin has been discussed in the review.

The analysis indicates a strong correlation between antioxidant activity and mitochondrial function, underscoring their role in disease prevention and therapy. These antioxidants not only reduce oxidative damage but also regulate signalling pathways involved in inflammation and energy metabolism. Their dual action makes them promising agents in managing diabetes and potentially other chronic diseases.

The conclusion offers a concise yet comprehensive overview for researchers and industries in highlighting the therapeutic promise of antioxidant interventions in addressing diverse health conditions through enhanced mitochondrial function.