Abstract: Background: Esculetin, scientifically referred to as 6,7-dihydroxycoumarin, functions as the primary bioactive constituent found in Cortex Fraxini (commonly known as ash bark), an ancient Asian medicinal substance. Herbal practitioners utilize the outer layer of the branch or stem bark of Cortex Fraxini for its gentle and safe medicinal properties and its potential as a nutritional component. In contemporary times, the landscape has undergone a notable transformation due to the emergence of a wide range of innovative 6,7-dihydroxycoumarin derivatives. The recent surge of innovation has sparked a heightened interest in understanding the molecular mechanisms that underlie the effects of Cortex Fraxini and 6,7-dihydroxycoumarin in clinical applications. Aim: This succinct review seeks to build up the extensive knowledge accumulated in the past decade concerning the synthesis, pharmacological profiles and principles linked to 6,7-dihydroxycoumarin and its chemical analogues. Furthermore, we aim to provide a concise yet inclusive overview of the unique characteristics of 6,7-dihydroxycoumarin. Conclusion: Satisfying these aims can enhance the comprehension of the diverse possibilities presented by this chemical and its related compounds across different research and application domains.

Abstract: Background: Statins have demonstrated various beneficial clinical outcomes, not only in patients with elevated cholesterol levels but also in those with normal levels, a collective phenomenon known as pleiotropic effects. In the cardiovascular system, statins exhibit numerous pleiotropic effects, including the improvement of endothelial function by enhancing nitric oxide synthesis, anti-inflammatory actions, and antioxidant properties. Similarly, within the gastrointestinal tract, statins confer advantageous pleiotropic effects. Aim: This review delves into the potential mechanisms underpinning the gastroprotective impact of statins against indomethacin-induced gastric ulcers. In particular, the administration of statins resulted in a notable elevation in the levels of NO and PGE2 in the mucosa of the stomach. These results substantiate the gastroprotective role of statin is attributed to scavenging of free radicals, elevation of nitric oxide levels, and enhancement of prostaglandin E2 levels. Conclusion: To sum up, the results indicate that statins could be a preferable therapeutic choice for individuals who are susceptible to developing gastric ulcers as a result of NSAIDs usage.

Abstract: Background: Mirabegron operates through a distinct mechanism compared to antimuscarinic agents. Its activation of β3-adrenoceptors results in the relaxation of the bladder during the filling phase of micturition. The activation of β3-adrenoceptors, which are connected to Gs-proteins, is hypothesized to be the mechanism of mirabegron-induced smooth muscle relaxation. This coupling stimulates adenylyl cyclase, leading to an elevation of intracellular levels of cyclic adenosine monophosphate (cAMP). However, in rat and human corpus cavernosum, mirabegron induces relaxation through distinct mechanisms independently through the nitric oxide/cyclic guanosine monophosphate (NO-cGMP) pathway. Consequently, the precise mechanism by which mirabegron enhances relaxation is still not fully known. Aim: The main goal is to delve deeper into the complex mechanisms by which mirabegron causes smooth muscle relaxation in many tissues. Conclusion: Mirabegron and similar β3-adrenoceptor agonists hold promise for treating not only overactive bladder but also a range of other conditions including heart failure and metabolic disorders.

Abstract: Background: Topical corticosteroids (TCs) are widely used for dermatologic diseases. Unfortunately, there exists many adverse effects (local and systemic). These adverse effects are comparable to those observed when glucocorticoids are administered systemically, but they are typically less severe. Aim: To assess the systemic adverse effects of topical clobetasol (TCL) and counterfeit cosmetic products (CCP) on Iraqi women. Methods and patients: This was a cross-sectional observational study; carried out from October 2022 to March 2023. Patients visited the outpatient clinic of the Department Dermatology and Venereology in Abu-al Khasib Hospital in Basra City, Iraq. Patients may be categorized into two distinct groups: the first group of subjects utilized TCL (n=31), while the second group consisted of patients with CCP (n=32), and the remaining participants were designated as the control group (n=35). A specialized dermatologist conducted a clinical examination to make a diagnosis. A questionnaire was collected, and blood samples were obtained for laboratory investigations. Results: TCs suppressed vitamin D (Vit-D), interlukin-6 (IL-6), testosterone, and estrogen and reduced cortisol concentrations significantly. TCs elevated red blood cells (RBC), neutrophils percent (NEU%), and hemoglobin (HB) levels significantly and prolong bleeding time. While not affecting WBCs, PLT, MPV, MCH, MCV, ACTH, or insulin levels, with decreased in HCT, MCHC, Eos%, and Lym% for all groups in comparison to control group. Conclusion: Topical corticosteroids are extensively used, mostly for the treatment of dermatological conditions. However, they can be misused for their cosmetic effects as fairness creams. TCs misuse is a big problem in Iraq, resulting in massive skin effects and systemic deterioration, such as hematological and hormonal effects. Nevertheless, the general population remains ignorant of the systemic adverse effects. Educational activities targeting the public are suggested to address the systemic deterioration.

Abstract: Background: Cilnidipine, a common hypertension medication, is now being studied for its potential to improve insulin sensitivity, which plays a key role in regulating blood sugar levels. Recent research suggests that cilnidipine may benefit individuals with both hypertension and insulin resistance, offering a promising avenue for further investigation and potential therapeutic applications. Objective: The present study aimed to investigate the influence of cilnidipine on insulin sensitivity, seeking to comprehend how this medication affects the body's capacity to utilize insulin efficiently. Methods: The current literature search was conducted using diverse databases, primarily including PubMed, Elsevier, Google Scholar, and the Iraqi Virtual Science Library. The search was limited to publications up to [2009-2023], and the keywords "Cilnidipine" and "Insulin Sensitivity" were used to identify relevant articles. Inclusion and exclusion criteria were applied to filter the search results, and the number of papers retrieved meeting these criteria was recorded for further analysis. Results: indicate that cilnidipine may have a positive impact on insulin sensitivity in individuals with hypertension and type 2 diabetes. This suggests that cilnidipine could potentially be a beneficial therapeutic option for addressing insulin resistance in these patients. However, it is crucial to note that further research is necessary to confirm these findings and evaluate the long-term effects of cilnidipine on insulin sensitivity. Conclusion: The results of this study indicate a potential positive impact of cilnidipine on insulin sensitivity in individuals with both hypertension and type 2 diabetes. This suggests that cilnidipine could serve as a promising therapeutic option for addressing insulin resistance in these patients.

Abstract: Background: for a long time, natural bio-actives have been used to treat, cure, and prevent illnesses. Fruit seed crude extracts have been found to have various beneficial biological activities, such as anti-inflammatory, antioxidant, and antitumoral potential. Methods: this study investigated quince seed extract made using absolute ethanol as a solvent regarding flavonoid and phenolic content, as well as antioxidant, anti-inflammatory, and anticancer properties. The extract was obtained using two methods, microwave-facilitated extraction and sequential microwave-ultrasound-assisted extraction. Results: the extract from the microwave-facilitated method had higher flavonoid and phenolic content with superior antioxidant activity. Hydroxyl free radical and DPPH assays' IC50 were 121.04±1.10 and 112.98±1.02, respectively, compared to the sequential method, which had IC50 values of 193.19±0.86 and 187.23±0.95. The microwave method also displayed significantly higher inhibitory activity against inflammatory enzymes and selectivity against COX2 compared to the sequential one. However, the extracts did not exhibit any antiproliferative effect on malignant or healthy cellular lines at the applied concentrations, and they did not enhance the effectiveness of 5-FU (5-Fluorouracil) in preventing the growth of cancerous cells. However, the mutual application in general results in increasing the IC50 value of 5-FU toward the healthy cellular line (MCF-A10). Therefore, the mutual application of these extracts with 5-FU can be seen as a protective measure. Conclusion: the crude extract obtained through the microwave-facilitated method had better TPC, TFC, antioxidant, anti-inflammatory activity, and protective potential than the sequential method.

Abstract: Background: The rise of resistance to numerous effective antimicrobic drugs and the necessity to investigate alternative agents to address this emerge are conspicuously underscored. Aim: The aim is to evaluate the TPC (total phenolic contents), TFC (total flavonoidal contents), and the antimicrobial activity of two quince seeds extracts and their combination with commercial antimicrobial drugs. Methods: In this work two ethanolic extracts (Qu-1 and Qu-2) were prepared from quince seeds using two methods, microwave (M.wv) and sequential microwave-sonication assisted extraction (MSAE). The quantification of total phenolic content TFC and total flavonoid content TFC in these extracts were conducted using Folin-Ciocalteu and AlCl3 method respectively. The extracts, along with its combination with conventional antibiotics were tested for antimicrobial activity against a variety of aerobic and anaerobic bacteria using ciprofloxacin and metronidazole as references, respectively. The extracts were also tested against fungi (C. albicans and A. niger) using the standard, nystatin. Results: TPC and TFC for Qu-1 were 2.2578±1.82 μg GAE/g crude solid, 1.4901±1.76 μg RU/g crude solid respectively, while these values for Qu-2 were 1.0341±2.05 μg GAE/g and 0.7342±1.53 μg RU/g. Both extracts showed antimicrobial effectiveness against all examined pathogens with Qu-1 showing superior effectiveness. So, there is a positive association between TPC, TFC and antimicrobial activity. The combination of Qu-1 can enhances both the antifungal and anti-aerobic effects of NYS and CIP by reducing MFC and MBC and their corresponding potency factor. On the contrary, the Qu-2-antibiotic combination does not show any modification. Both extracts have microbicidal activity based on MBC/MIC ratio which is lower than 4. Conclusion: Quince seed extracts, especially Qu-1, show promise in fighting microbial infections. They could be used alone or in combination with antibiotics. Further research and development may lead to the development of new antimicrobials to address the growing issue of resistance.

Abstract: Background: Coumarin chemical moiety and its-based molecules attracted a lot of research attention by chemists of natural products and organic synthesis. This attention works in two directions: synthetic approaches and biological activities. Methods: In this work, salicylaldehyde was condensed via a thermosonication-catalyzed Knoevenagel reaction with malonic acid, giving coumarin-3-carboxylic acid. The latter was esterified through its carboxylic acid with various 2-functionalized phenols under a thermosonication-promoted SOCl2-catalized esterification reaction. The four 3-esterified coumarins (SY1–SY4) were characterized by different spectrophotometer analyzers, including FTIR, 1H-NMR, and 13C-NMR. Four cell lines of malignant type and one of normal class were used to specify the antitumor activity and biocompatibility of the synthetic SY1-SY4, respectively, by employing the MTT-probing methodology. Results: The outcomes indicated the accuracy of the proposed molecular structures, and the synthetic compounds have poor, with the exception of SY1, antitumor activity. Also, the antiproliferative effect of the three compounds (SY2-SY4) is roughly similar against malignant and normal cells. On the other hand, the compound SY1 demonstrated good antitumor activity against the malignant cells used but a poor inhibitory effect toward normal cells. Conclusion: The author concluded from these findings that the molecular structure of SY1 can offer a promising template to synthesize more potent and biocompatible antitumor agents with a coumarin chemical nucleus.   

Abstract: Background and objectives: Amiodarone is an antiarrhythmic medication used to treat abnormal heart rhythms. This study aimed to analyse the histological variations in ovarian follicles of rats after treatment with different doses of amiodarone and evaluate its effects on follicular growth parameters. Methods: Thirty female albino rats were divided into control, therapeutic dose (20 mg/kg), and toxic dose (200 mg/kg) groups. Hormonal analysis showed insignificant changes in the therapeutic group but significant declines in follicle-stimulating hormone, estrogen, and increases in luteinizing hormone and prolactin in the toxic group. Results: Morphometric analysis revealed non-significant changes in primordial and primary follicles across groups but significant declines in secondary and mature follicles in the toxic group compared to the control. Histological examination showed mild variations in the therapeutic group but serious disturbances in ovarian follicular architecture, increased collagen fibres, congestion, inflammation, and corpora lutea hypertrophy in the toxic group. The degenerative effects were dose-related, confirming the safety of a low therapeutic dose. Conclusion: Amiodarone inflicts dose-dependent damage to the ovaries. Doctors can safely prescribe therapeutic doses tailored to patients' medical status.

Abstract: Background: Angiotensin-converting enzyme (ACE) Inhibitors are medications pivotal in cardiovascular disease management, impacting the renin-angiotensin system which plays a critical role in cardiovascular health. These inhibitors not only modulate blood pressure and fluid balance but also influence adipose-derived hormones like visfatin and apelin. These adipokines are intricately linked with cardiovascular function and interact with the renin-angiotensin system, thereby affecting cardiovascular disease outcomes. Understanding the interplay between ACE inhibitors, visfatin, and apelin is crucial for optimizing therapeutic strategies in cardiovascular disease management. Visfatin is primarily expressed in visceral adipose tissue and is associated with hypertension, vascular inflammation, and insulin resistance. Elevated serum levels of visfatin correlate with increased systolic and diastolic blood pressure. Apelin, acting through the G protein-coupled receptor APJ, is implicated in cardiac system diseases and can lower arterial blood pressure, improving cardiac output. Different apelin isoforms have varying efficacies in arterial pressure regulation. ACE inhibitors, widely prescribed for hypertension and heart failure, are found to modulate serum levels of apelin and visfatin, potentially augmenting their cardioprotective effects. Aim: This review article aims to elucidate the effects of angiotensin-converting enzyme (ACE) inhibitors on the serum levels of visfatin and apelin and their implications for cardiovascular disease management. Conclusion: The interactions between ACE inhibitors, visfatin, and apelin present promising avenues for targeted therapies in hypertension and cardiovascular diseases. Despite some inconsistencies in the research, understanding these interactions could lead to novel therapeutic approaches and enhanced cardiovascular care.