The present study aimed to investigate the potential of nanospanlastics for boosting the bioavailability of epigallocatechin gallate (EGCG). EGCG has valuable effects like anti-inflammation, anti-oxidation, and anti-tumorigenesis. Unfortunately, it has a low oral bioavailability due to its limited permeation and poor stability. To overcome these pitfalls, EGCG was fabricated as a nanospanlastic. Nanospanlastics are flexible nanovesicles that are composed of surfactants and edge activators (EAs). EAs improve the deformability of spanlastics by acting as a destabilizing factor of their vesicular membranes. EGCG-loaded spanlastics were prepared by an ethanol injection method, according to 2³ factorial design, to explore the impact of different independent variables on entrapment efficiency (EE%), % drug released after 12 h (Q_12h), and particle size (PS). In vitro characterization, ex vivo intestinal permeation test, and pharmacokinetic study of the optimized formula were performed. A newly developed RP-HPLC technique was adopted for the estimation of EGCG. The optimized formula (F4) demonstrated more prolonged drug release and a significant improvement in the EE%, permeability, deformability and stability than the corresponding niosomes. The pharmacokinetic study investigated that F4 had a more sustained drug release and a higher bioavailability than the conventional niosomes and free drugs. Nanospanlastics could be a promising approach for improving the bioavailability of EGCG.

Probiotics and antioxidants have a definite improving effect in cardiovascular diseases. This study aims at mitigating doxorubicin toxicity on cardiac function through consuming a functional food. Five groups of adult male Sprague-Dawley rats were used along 22 weeks. Group I received 30 g/kg/day food enriched with yogurt, green tea extract, and carrots (80, 0.84, and 100 g/kg diet, respectively) from the first week, group II received carvedilol 30 mg/kg/day orally from week 17, group III received both carvedilol and tested food, and groups IV and V were +ve and –ve control groups, respectively. In week 17, cardiomyopathy was induced by i.p. injection of 2.5 mg/kg doxorubicin every 48 h for 2 weeks. Histopathological and electrophysiological examinations and biochemical analysis were done. Lipid peroxidation, antioxidant effect, heart failure compensatory mediators, and proinflammatory cytokines were assessed. Tested food normalized time between the start of Q wave and the end of T wave on electrocardiogram (QT interval) and heart rate compared to the doxorubicin group ( P <.05). It also improved hypertrophy indicated by a significant ( P <.05) decrease in heart/body weight ratio, angiotensin-II (Ang-II), and atrial natriuretic peptide (ANP) serum levels. Histopathological examination of cardiac sections from the tested food group revealed less marked vacuolization and low perivascular fibrosis percentage (0.7803±0.04). A significant ( P <.001) decrease in serum creatine kinase-membrane bound, lactate dehydrogenase, triglycerides, cholesterol, low-density lipoprotein cholesterol, and tissue malondialdehyde (MDA) levels was observed in addition to an increase in serum Na ⁺ /K ⁺ ATP1A1 and cardiac reduced glutathione (GSH) levels. Tested food also lowered the inflammatory cytokines tumor necrosis factor- α (TNF- α ) and interleukin-6 (IL-6) serum levels significantly ( P <.01). Probiotic food containing Lactobacillus acidophilus , green tea, and carrots can improve membrane integrity and cardiac contractility in doxorubicin-induced cardiomyopathy by decreasing TNF- α , IL-6, MDA, increasing GSH, and modulating compensatory mediators such as Ang-II and ANP.

Introduction: Azithromycin, a widely used antibacterial agent, is also considered the cornerstone of the management protocols for COVID-19 infection, particularly in Egypt, due to its antiviral impact and preventive effects against secondary bacterial infections. However, even at pharmacological doses, azithromycin develops rapid cardiac toxicity. Objectives: Our study here aims at investigating the cardioprotective potentials of lactoferrin, a natural compound used primarily for boosting intestinal iron absorption, to counteract azithromycin-induced cardiac toxicity in experimental rats when administered concurrently. Methods: Male Sprague Dawley rats received either lactoferrin (200 mg/kg/day, orally) or saline for 10 days. Induction of cardiac toxicity was initiated on the 6th day via oral administration of azithromycin (20mg/kg/day, orally) for 5 successive days, concurrently with either lactoferrin or vehicle. Cardiac injuries were confirmed via Electrocardiogram (ECG) recording, assessment of cardiac function biomarkers, assessment of cardiac expression of nuclear factor erythroid 2–related factor 2 (Nrf2), interleukin-1β (IL-1β) and IL-10, measurement of cardiac oxidant/antioxidant balance, immunohistochemical staining against toll-like receptor-4 (TLR4), and nuclear factor-κB (NF-κB), and histopathological examination of HE-stained cardiac specimens. Results: Administration of azithromycin denoted a significant cardiac tissue injury as demonstrated by upregulated serum levels of cardiac biomarkers, namely total creatine Kinase (CK), Creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and Alkaline phosphatase (ALP). Furthermore, it upregulated cardiac content of malondialdehyde (MDA) and nitric oxide (NO) and cardiac inflammatory markers, such as TLR4, NF-κB, and IL-1β. Similarly, azithromycin-downregulated reduced glutathione (GSH) cardiac content and the anti-inflammatory protective indicators, IL-10 and Nrf2. Additionally, azithromycin-induced cardiotoxicity was evinced by ECG pattern and histopathologic deterioration. Oral Lactoferrin showed cardioprotective potentials and counteracted the azithromycin-induced cardiac toxicity, downregulating cardiac biomarkers. Moreover, it restored cardiac oxidant/antioxidant balance, decreased cardiac TLR4, NF-κB, and IL-1β expression, and increased IL-10 and Nrf2 expression. Lactoferrin Cardioprotective potentials were also evinced by enhanced ECG pattern and histopathological examination. Conclusion: Finally, we support the use of lactoferrin with azithromycin intake that induced cardiac toxicity.

Objective: The current study aimed to investigate and compare the efficiency of the total extract and ethyl acetate (EtOAc) extract of Mangifera indica leaves to attenuate iron overload-induced hepatic and splenic dysfunctions, using an in-vivo iron-overload rat model. Methods: Rats received water supplemented with iron for 2 months, followed by treatment with either total extract or EtOAc extract of M. indica leaves for an extra 2 months. Results: Rats treated with EtOAc fraction of M. indica leaves, and the total extract, had significantly diminished iron accumulation within hepatic and splenic tissues. Both extracts normalized the hepatic enzymatic and non-enzymatic biomarkers like alkaline phosphatase (ALP), alanine aminotransferase (AST), and total bilirubin. Moreover, they restored the oxidants/antioxidants balance within the liver and spleen tissues. Additionally, they suppressed HO-1 levels, increased Nrf2 expression, and downregulated MMP-9 expression. Conclusion: Briefly, M. indica extracts showed iron-chelation, antioxidant, and antifibrotic potentials. These findings pointed out the usefulness of the mango leaves as a natural, affordable by-product in managing iron overload complications. However, the results also demonstrated that EtOAc extract is more accountable for such activities.