Afaf F. Almuqati

Background/Objectives: Breast cancer remains one of the most prevalent malignancies worldwide, highlighting the need for safer and more effective therapeutic strategies. Curcumin has shown considerable anticancer potential; however, its clinical application is limited by poor aqueous solubility and low skin permeability. Methods: Therefore, a curcumin-loaded microemulsion (CUR-ME) was developed and optimized using a Box–Behnken design, followed by incorporation into a Carbopol 934 gel for topical breast cancer therapy. Results: The optimized formulation exhibited a particle size of 177.4 nm, a polydispersity index of 0.1309, and a zeta potential of −4.45 mV, indicating favorable physicochemical characteristics. CUR-ME demonstrated superior dose-dependent cytotoxicity against MCF-7 breast cancer cells, with a lower IC₅₀ 8.89 µg/mL than free curcumin IC₅₀ 9.83 µg/mL. Furthermore, Hoechst 33342 staining and the DCFDA assay confirmed enhanced apoptosis and intracellular reactive oxygen species generation in CUR-ME-treated cells, indicating improved cellular uptake and anticancer activity. Rheological and texture profile analyses demonstrated suitable viscosity, firmness, and spreadability for topical application. In vitro drug release revealed sustained release from the CUR-ME gel, achieved through the polymeric gel matrix, which increased viscosity, entrapped microemulsion droplets, and acted as a diffusion barrier to prolong drug retention and release. Confocal laser scanning microscopy further confirmed enhanced skin penetration of CUR-ME. Conclusions: Collectively, these findings demonstrate that the developed CUR-ME gel is a promising topical drug delivery system with sustained release, improved skin retention, and enhanced therapeutic potential for breast cancer management.

Background/Objectives: Artemisia annua essential oil (EO) possesses diverse biological activities; however, its practical application is limited by volatility, instability, and poor bioavailability. This study aimed to develop chitosan-coated nanostructured lipid carriers (CH-NLCs) for efficient encapsulation and delivery of A. annua EO and to evaluate their physicochemical characteristics and biological performance. Methods: The nanoformulation exhibited favorable physicochemical properties, including a high encapsulation efficiency (85.97 ± 1.30%) and a strongly positive surface charge (approximately +45 mV), indicating good colloidal stability. Structural analyses by SEM, FTIR, and XRD confirmed successful encapsulation of the EO within the nanocarrier matrix. Results: The CH-NLC formulation significantly enhanced larvicidal activity against Aedes aegypti larvae, reducing the LC₅₀ value from 213 ppm for the free EO to 142 ppm. Enhanced antifungal activity was also observed, with 47–56% greater inhibition against Malassezia furfur, Trichophyton mentagrophytes, and Candida albicans compared with the free EO. Furthermore, CH-NLC demonstrated improved cytotoxic activity against skin cancer cell lines, achieving IC₅₀ values of 21.4 ± 1.7 µg/mL and 30.1 ± 1.6 µg/mL against A431 and A375 cells, respectively, while maintaining lower toxicity toward normal HaCaT keratinocytes. Mechanistic investigations revealed enhanced apoptosis and an approximately 3-fold increase in intracellular reactive oxygen species (ROS) levels in treated cancer cells. Conclusions: Collectively, these findings indicate that chitosan-coated nanostructured lipid carriers effectively improve the stability and biological efficacy of A. annua essential oil and represent a promising platform for future biomedical and biocidal applications.

Plant phytochemicals are bioactive substances that offer various biological and health benefits. The cardiotoxicity of 5-fluorouracil (5-FU) restricts its applicability in cancer treatment. The bioactive rosmarinic acid (RA) is an antioxidant and anti-inflammatory polyphenol. This study elucidated the protective efficacy of RA against 5-FU-associated cardiac injury in mice. Mice received RA (25 or 50 mg/kg, orally) for 10 days and then were treated with 5-FU (150 mg/kg) on the 8th day. 5-FU-intoxicated mice demonstrated higher lactate dehydrogenase, creatine kinase-MB, and troponin I levels with various cardiac histopathological alterations. 5-FU-injected mice showed a significant rise in cardiac protein carbonyl and malondialdehyde, associated with reduced myocardial glutathione content and catalase and superoxide dismutase activities. RA pretreatment of 5-FU-treated mice attenuated cardiac injury, decreased protein carbonyl and MDA levels, and promoted antioxidant defense mechanisms in the myocardium. Furthermore, RA significantly reduced cardiac inflammatory response by decreasing the expression of cardiac NF-κB p65 and proinflammatory cytokines in the heart. RA also mitigated 5-FU-induced cardiac apoptosis by attenuation of cardiac levels of Bcl-2, Bax, and caspase-3. It also restored the cardiac Nrf2/HO-1 signaling pathway. Collectively, RA exerts significant cardioprotective effects on 5-FU-induced cardiac injury, and therefore RA could be used as a potential effective adjuvant in alleviating myocardial injury associated with increased oxidative stress and inflammation. Please see Corrigendum

The objective of this research was to develop a mucoadhesive delivery system that improves permeation for the administration of poorly absorbed oral medications. Thiolation of xanthan gum (XGM) was carried out by esterification with mercaptobutyric acid. Fourier-transformed infrared spectroscopy was used to confirm thiol-derivatization. Using Ellman’s technique, it was revealed that the xanthan-mercaptobutyric acid conjugate had 4.7 mM of thiol groups in 2 mg/mL of polymeric solution. Using mucosa of sheep intestine, the mucoadhesive properties of XGM and thiolated xanthan gum (TXGM) nanoparticles were investigated and we found that TXGM had a longer bioadhesion time than XGM. The disulfide link that forms between mucus and thiolated XGM explains why it has better mucoadhesive properties than XGM. A study on in vitro miconazole (MCZ) release using phosphate buffer (pH 6.8) found that TXGM nanoparticles released MCZ more steadily than MCZ dispersion did. A 1-fold increase in the permeation of MCZ was observed from nanoparticles using albino rat intestine compared to MCZ. Albino rats were used to test the pharmacokinetics of MCZ, and the results showed a 4.5-fold increase in bioavailability. In conclusion, the thiolation of XGM enhances its bioavailability, controlled release of MCZ for a long period of time, and mucoadhesive activity.

Background: The research is aimed at exploring the potential of marigold petal tea (MPT), rich in polyphenol contents, against oxidative stress and obesity in a rat model following a high‐fat‐sugar diet (HFSD).Methods: The MPT was prepared through the customary method of decoction and was subjected to analysis for its polyphenol composition using reversed‐phase high‐performance liquid chromatography (RP‐HPLC). Two specific doses of MPT, namely, 250 and 500 mg/kg body weight (BW), were chosen for the study—referred to as MPT‐250 and MPT‐500, respectively.Result: The main phenolic acids and flavonoids identified in MPT, with concentrations exceeding 10 mg/100 mL of tea, included catechin, rutin, salicylic acid, gallic acid, sinapic acid, chlorogenic acid, cinnamic acid, and ellagic acid. The total phenolic (TP) and total flavonoid (TF) contents in MPT were measured to be 5.53 and 7.73 mg/g, respectively. Additionally, MPT demonstrated a 57.2% scavenging capacity with 2,2‐diphenyl‐1‐picrylhydrazyl radical. Notably, the administration of a higher dose (MPT‐500) showed a significant reduction in body mass index (BMI) and a 51.24% reduction in the rate of increase in BW compared to the HFSD group. The findings indicated that all the treatment groups, that is, orlistat treatment (OT), MPT‐250, and MPT‐500 groups, experienced reduced levels of serum total cholesterol (TC), triglyceride (TG), and markers of lipoproteins in contrast to the HFSD group. Moreover, MPT helped restore the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH), thereby demonstrating its potential in combating oxidative stress. The MPT‐500 group also displayed decreased liver and kidney weights and an improved atherogenic index when compared to the HFSD group.Conclusion: The results clearly indicate that a high dosage of MPT showed antiobesity activity which was comparable to the same effects produced by the conventional drug orlistat.

Taxifolin (TA) is a natural flavonoid found in many foods and medicinal plants with well-documented antioxidant and anti-inflammatory properties. Cyclophosphamide (CP) is an effective antineoplastic and immunosuppressive agent; however, it is associated with numerous adverse events, including hepatotoxicity. Herein, we aimed to investigate the potential protective effects of TA using a mouse model of CP-induced hepatotoxicity. Mice were co-treated with TA (25 and 50 mg/kg, orally) and CP (30 mg/kg, i.p.) for 10 consecutive days and sacrificed 24 hours later. CP induced increased transaminases (ALT and AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) paralleled with pronounced histopathological alterations in the liver. Moreover, hepatic tissues of CP-injected mice showed increased malondialdehyde (MDA), protein carbonyl, and nitric oxide (NO) levels, accompanied by decreased antioxidant defenses (glutathione [GSH], superoxide dismutase [SOD], and catalase [CAT]). Livers of CP-injected mice also showed increased inflammatory response (nuclear transcription factor kappa-B [NF-κB] p65 activation, increased levels of proinflammatory cytokines tumor necrosis factor alpha [TNF-α], interleukin 1 beta [IL-1β], and IL-6) and apoptosis (decreased Bcl-2 and increased Bax and caspase-3 expression levels). Remarkably, TA ameliorated markers of liver injury and histological damage in CP-injected mice. TA treatment also attenuated numerous markers of oxidative stress, inflammation, and apoptosis in the liver of CP-injected mice. This was accompanied by increased nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) expression in the liver tissues of CP-injected mice. Taken together, this study indicates that TA may represent a promising new avenue to prevent/treat CP-induced hepatotoxicity and perhaps other liver diseases associated with oxidative stress and inflammation.

Cancer continues to be leading cause of death globally, with nearly 7 million deaths per year. Despite significant progress in cancer research and treatment, there remain several challenges to overcome, including drug resistance, the presence of cancer stem cells, and high interstitial fluid pressure in tumors. To tackle these challenges, targeted therapy, specifically targeting HER2 (Human Epidermal Growth Factor Receptor 2) as well as EGFR (Epidermal Growth Factor Receptor), is considered a promising approach in cancer treatment. In recent years, phytocompounds have gained recognition as a potential source of chemopreventive and chemotherapeutic agents in tumor cancer treatment. Phytocompounds are compounds derived from medicinal plants that have the potential to treat and prevent cancer. This study aimed to investigate phytocompounds from Prunus amygdalus var amara seeds as inhibitors against EGFR and HER2 enzymes using in silico methods. In this study, fourteen phytocompounds were isolated from Prunus amygdalus var amara seeds and subjected to molecular docking studies to determine their ability to bind to EGFR and HER2 enzymes. The results showed that diosgenin and monohydroxy spirostanol exhibited binding energies comparable to those of the reference drugs, tak-285, and lapatinib. Furthermore, the drug-likeness and ADMET predictions, performed using the admetSAR 2.0 web-server tool, suggested that diosgenin and monohydroxy spirostanol have similar safety and ADMET properties as the reference drugs. To get deeper insight into the structural steadiness and flexibility of the complexes formed between these compounds and theEGFR and HER2 proteins, molecular dynamics simulations were performed for 100 ns. The results showed that the hit phytocompounds did not significantly affect the stability of the EGFR and HER2 proteins and were able to form stable interactions with the catalytic binding sites of the proteins. Additionally, the MM-PBSA analysis revealed that the binding free energy estimates for diosgenin and monohydroxy spirostanol is comparable to the reference drug, lapatinib. This study provides evidence that diosgenin and monohydroxy spirostanol may have the potential to act as dual suppressors of EGFR and HER2. Additional in vivo and in vitro research are needed to certify these results and assess their efficacy and safety as cancer therapy agents. The experimental data reported and these results are in agreement.

The extract of P. amygdalus var. amara is known for its health benefits, which include lowering diabetes and heart disease risks. In eight human tumor cell lines, P. amygdalus var. amara demonstrated potent anti-cancer activity, including NB4, Huh-7, A-549, SKOV-3, PC-3, T-24, U937, and Hep-2. There was a notable change in the morphology of nearly all cancer cell lines, and cancer cells continued to exist. Incubation for 12 h, 24 h, 48 h, or 72 h resulted in the lowest viable cell concentration at 48 h, which was 34.65% lower than that of the non-treated cells. During exposure to the extract, the majority of cells lost their typical morphology and shrank in size. According to the cell viability data, the P. amygdalus var. amara treatment significantly decreased the cancer cells’ growth in most cancer cell lines when doses and time were taken into consideration.

Cisplatin (CIS) is an effective chemotherapeutic agent used in the treatment of several malignancies. The clinical use of CIS is associated with adverse effects, including acute kidney injury (AKI). Oxidative stress and inflammation are key events in the development of CIS-induced AKI. This study investigated the protective effect of taxifolin (TAX), a bioactive flavonoid with promising health-promoting properties, on CIS-induced nephrotoxicity in mice. TAX was orally given to mice for 10 days and a single dose of CIS was injected at day 7. Serum blood urea nitrogen (BUN) and creatinine were elevated, and multiple histopathological alterations were observed in the kidney of CIS-administered mice. CIS increased renal malondialdehyde (MDA), nitric oxide (NO), nuclear factor-kappaB (NF-κB) p65, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β, and decreased cellular antioxidants in mice. TAX remarkably prevented kidney injury, ameliorated serum BUN and creatinine, and renal MDA, NO, NF-κB p65, and pro-inflammatory cytokines, and boosted antioxidant defenses in CIS-administered mice. TAX downregulated Bax and caspase-3, and upregulated Bcl-2. These effects were associated with upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) expression and heme oxygenase (HO)-1 activity in CIS-administered mice. In conclusion, TAX prevented CIS-induced AKI by mitigating tissue injury, oxidative stress, inflammation, and cell death. The protective efficacy of TAX was associated with the upregulation of Nrf2/HO-1 signaling.