Current Reviews in Clinical and Experimental Pharmacology - Volume 20, Issue 3, 2025
Volume 20, Issue 3, 2025
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The Antioxidant Properties and Cardiovascular, Antidiabetic, and Renal Effects of Trimetazidine Described in Research on Experimental Models
More LessExperimental studies have played an essential role in drug identification and development in biomedical research. These studies also have applications in conducting postmarketing evaluations to elucidate the mechanisms responsible for their actions. Preclinical studies on marketed drugs have led to the discovery of new mechanisms or biological effects, opening the possibility of expanding their therapeutic applications. Since its discovery, trimetazidine has been used as an antianginal drug. However, after its commercialization, the molecular actions and impact of this drug on ischemic and non-ischemic pathologies have become known. This article presents the mechanisms and antioxidant actions of trimetazidine associated with the effects observed in experimental models of heart disease, nephropathy, and diabetes mellitus. A non-systematic search of the PubMed database was performed using terms related to our objectives. We selected articles on studies focused on cardioprotection, nephroprotection, antioxidants, or diabetic heart disease, which were carried out in preclinical experimental models. The information compiled in this review shows that trimetazidine is effective in reducing damage associated with oxidative stress, as evaluated in different experimental models. The cardioprotective and nephroprotective effects of this drug have been demonstrated in ischemic and non-ischemic models.
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Acetylcholine and Depression: Scrutinizing Future Therapeutic Targets for Novel Drug Development
Authors: Arzoo Pannu and Ramesh K. GoyalDepression, a pervasive and disabling mental health disorder, presents a global healthcare challenge. Despite persistent research on its etiology and pathophysiology, many aspects remain unclear. Predominant neurobiological research and traditional pharmacotherapies have pointed out the monoamine hypothesis as a pivotal factor in the pathophysiology of depression. However, emerging perspectives on the monoamine hypothesis highlight the significance of the cholinergic system, a major regulator of diverse CNS functions encompassing attention, arousal, cognition, and memory. Cognitive impairments were frequently observed in depression along with other symptoms i.e. low mood and anhedonia. A comprehensive literature search was conducted across multiple databases (PubMed, Scopus, and Web of Science) from their inception until May 2023. We screened 1,200 articles, of which 400 full-text articles were assessed for eligibility, and 231 studies met the inclusion criteria. The review included both pre-clinical and clinical studies focusing on the role of acetylcholine (ACh) and its receptors in depression. Data extraction and quality assessment were performed independently by two reviewers. In literature, both pre-clinical and clinical studies suggest that elevated central ACh levels may contribute to depression, prompting investigations into intervention strategies targeting mAChRs/nAChRs and AChE. These receptors have become a critical target in drug-design strategies aimed at addressing depression-like symptoms. In addition, research has demonstrated a significant antidepressant-like effect of AChEIs in a dose-dependent manner in animal models. Hence, this evidence over the past decades underscores the pivotal role of the cholinergic system in mood regulation, offering promise for novel depression treatments. In this review, we tried to summarize the historical evolution of the cholinergic system from early discoveries to its role in the pathophysiology of depression. It presents evidence for the involvement of mAChRs and nAChRs, as well as AChE, in depression. By outlining the cholinergic theory of depression, this review suggests a novel therapeutic approach, emphasizing the role of ACh in the complex depression pathophysiology, and presenting avenues for further research and the development of targeted interventions.
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Understanding Diabetic Wounds: A Review of Mechanisms, Pathophysiology, and Multimodal Management Strategies
Authors: Manisha, Niharika, Praveen Gaur, Radha Goel, Kanak Lata and Rosaline MishraIntroductionDiabetic wounds are a prevalent and impairing consequence of diabetes mellitus that significantly impacts people's lives and global healthcare systems. Because of disturbances in the wound-healing cascade, these intricate, persistent wounds frequently refuse to heal. Focusing on diabetic wound formation, this study seeks to clarify the complex mechanisms and pathophysiology involved while offering a thorough overview of modern multimodal therapy techniques. The etiology of diabetic wounds entails a complex interplay between tissue destruction caused by hyperglycemia, neuropathy, ischemia, and compromised immune response. Extended inflammation, abnormal protease activity, and low oxygen levels in the tissue exacerbate the healing process. Comprehending these pathogenic mechanisms is essential for formulating efficacious therapeutic strategies.
MethodologyA thorough evaluation of the literature was done. Databases like SciFinder, ScienceDirect, PubMed, Google, Google Scholar, and the Egyptian Knowledge Bank were used to find pertinent publications. More than 200 articles and databases were studied to constitute this paper. The accuracy of the retrieved data was carefully reviewed and cross-checked. The current review aims to define wounds, various methods of classification, and various advancements for wound management. Several multidisciplinary strategies, including debridement, unloading, antimicrobial stewardship, and innovative therapeutics, are currently needed to manage diabetic wounds. Debridement—the excision of non-viable tissue—is necessary to create an environment that is conducive to recovery. Biomechanical interventions and offloading help to prevent additional tissue damage caused by repetitive stress. Antimicrobial treatments fight infections, which are a common diabetic wound consequence. Promising supplementary treatments are provided by developments in cellular and tissue-based products, ozone therapy growth factors, bioengineered skin substitutes, and hyperbaric oxygen therapy.
ResultsAfter applying article selection criteria and reviewing the quality of the methodology a total of 200 articles were selected to be included in the review. In this review, intricate interactions between peripheral neuropathy, vascular insufficiency, and hyperglycemia in the pathophysiology of diabetic wounds are explained. The efficacy of multimodal therapies is discussed in detail.
DiscussionA thorough comprehension of the complex mechanisms that underlie diabetic wounds is essential for efficient therapy. This review emphasizes how important multimodal approaches are to treating the complex pathophysiology of these wounds. Clinicians can greatly enhance the prognosis of patients with diabetic foot ulcers by addressing vascular insufficiency, neuropathy, infection, and poor healing.
ConclusionTimely wound resolution remains a key difficulty despite the implementation of multimodal methods. To customize therapies, personalized medicine strategies utilizing genetic and proteomic biomarkers must be the main focus of future research. Furthermore, cutting-edge biotechnologies with the potential to transform diabetic wound treatment include optogenetics and nanomedicine.
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Bigels as Novel Drug Delivery Systems: A Systematic Review on Efficiency and Influential Factors
BackgroundBigles are novel formulation merging two phase of hydrogel and organogel revealing dual properties to release active agents based on their lipophilic or hydrophilic nature.
MethodsA systematic search was conducted in PubMed, Scopus, and ISI Web of Science to find eligible studies evaluating the efficiency of bigels in drug release. 20 articles were included in the analysis based on the defined criteria.
ResultsThe results indicated that several different natural materials were used for bigel making. Span (52.38%) and Sunflower oil (23.80%) were the most solvents used for organogel formation. Also, gelatin, agar, gums, and other types of biopolymer were used as hydroglators. Most research (33.33%) focused on the release of metronidazole from bigel structure. Also, the range of drug release rates was 1.59 - 100% and in 42.85% of studies was >90%. The nature, content, and properties of both organogel and hydrogel and some process variables such as temperature, mixing speed and storage conditions were highlighted as the main influential factors on bigel formation and its bioactivity.
ConclusionBigels are an innovative structure that provides desired physicochemical and rheological properties for industrial applications. Excellent biocompatibility and in vitro / ex vivo results have been documented for developed bigels. In this regard, an optimal preparation method is very important to show superior therapeutic effects.
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Effectiveness and Tolerability of Various 5-Fluorouracil Formulations as Adjuvant Therapies for Vitiligo Management: A Systematic Review and Meta-Analysis
Authors: Neveen A. Kohaf, Sameh M. Sarsik, Samar Salman and Omnya M. AminBackgroundAll vitiligo treatments are restricted, and no known treatment reliably produces repigmentation. In this study, we investigated the efficacy and safety of 5-Fluorouracil (5FU) as adjuvant therapy in treating vitiligo.
MethodsUsing five significant databases, an electronic systematic search of the literature was conducted. Randomized Clinical Trials (RCTs) that investigated 5FU for treating vitiligo in humans were selected for a meta-analysis and systematic review. This study was conducted by following PROSPERO (CRD42022345736).
ResultsA total of 10 studies involving 302 patients were included in our systematic review. The meta-analysis of eight studies revealed that the combination of 5FU with microneedling showed a statistically significant superior effect in comparison with other treatment modalities in inducing >75% repigmentation (OR= 4.47; 95%CI= (2.39, 8.35), P < 0.00001). 5FU with microneedling versus microneedling alone showed higher efficacy of 5FU with statistically significant results (OR= 4.22; 95%CI= (1.55, 11.44), P= 0.005). Regarding the influence of different formulations of 5FU, the meta-regression revealed that the highest efficacy was achieved when microneedling was combined with liposomal formulations. There were not any reported severe side effects related to 5FU.
Conclusion5FU as an adjuvant treatment for vitiligo was found to be more effective in achieving ≥75% repigmentation rates.
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