Chemotherapeutic potential of betanin/capecitabine combination targeting colon cancer: experimental and bioinformatic studies exploring NFκB and cyclin D1 interplay.

Introduction: Betanin (C24H26N2O13) is safe to use as food additives approved by the FDA with anti-inflammatory and anticancer effects in many types of cancer cell lines. The current experiment was designed to test the chemotherapeutic effect of the combination of betanin with the standard chemotherapeutic agent, capecitabine, against chemically induced colon cancer in mice. Methods: Bioinformatic approach was designed to get information about the possible mechanisms through which the drugs may control cancer development. Five groups of mice were assigned as, (i) saline, (ii) colon cancer, (iii) betanin, (iv) capecitabine and (v) betanin/capecitabine. Drugs were given orally for a period of six weeks. Colon tissues were separated and used for biological assays and histopathology. Results: In addition, the mRNA expression of TNF-α (4.58-fold), NFκB (5.33-fold), IL-1ß (4.99-fold), cyclin D1 (4.07-fold), and IL-6 (3.55-fold) and protein levels showed several folds increases versus the saline group. Tumor histopathology scores in the colon cancer group (including cryptic distortion and hyperplasia) and immunostaining for NFκB (2.94-fold) were high while periodic-acid Schiff staining demonstrated poor mucin content (33% of the saline group). These pathologic manifestations were reduced remarkably in betanin/capecitabine group. Conclusion: Collectively, our findings demonstrated the usefulness of betanin/capecitabine combination in targeting colon cancer and highlighted that betanin is a promising adjuvant therapy to capecitabine in treating colon cancer patients.

α-Hederin Saponin Augments the Chemopreventive Effect of Cisplatin against Ehrlich Tumors and Bioinformatic Approach Identifying the Role of SDF1/CXCR4/p-AKT-1/NFκB Signaling.

Stromal cell-derived factor-1 (SDF1) and its C-X-C chemokine receptor type 4 receptor (CXCR4) are significant mediators for cancer cells' proliferation, and we studied their expression in Ehrlich solid tumors (ESTs) grown in mice. α-Hederin is a pentacyclic triterpenoid saponin found in Hedera or Nigella species with biological activity that involves suppression of growth of breast cancer cell lines. The aim of this study was to explore the chemopreventive activity of α-hederin with/without cisplatin; this was achieved by measuring the reduction in tumor masses and the downregulation in SDF1/CXCR4/pAKT signaling proteins and nuclear factor kappa B (NFκB). Ehrlich carcinoma cells were injected in four groups of Swiss albino female mice (Group1: EST control group, Group2: EST + α-hederin group, Group3: EST + cisplatin group, and Group4: EST+α-hederin/cisplatin treated group). Tumors were dissected and weighed, one EST was processed for histopathological staining with hematoxylin and eosin (HE), and the second MC was frozen and processed for estimation of signaling proteins. Computational analysis for these target proteins interactions showed direct-ordered interactions. The dissected solid tumors revealed decreases in tumor masses (~21%) and diminished viable tumor regions with significant necrotic surrounds, particularly with the combination regimens. Immunohistochemistry showed reductions (~50%) in intratumoral NFκß in the mouse group that received the combination therapy. The combination treatment lowered the SDF1/CXCR4/p-AKT proteins in ESTs compared to the control. In conclusion, α-hederin augmented the chemotherapeutic potential of cisplatin against ESTs; this effect was at least partly mediated through suppressing the chemokine SDF1/CXCR4/p-AKT/NFκB signaling. Further studies are recommended to verify the chemotherapeutic potential of α-hederin in other breast cancer models.

Features, applications, and sustainability of lipid nanoparticles in cosmeceuticals.

Cosmeceuticals are a branch of cosmetic products that forms a bridge between cosmetic and drug products. It is a fast-growing branch of the cosmetic industry, especially after the introduction of novel formulation and manufacturing techniques such as lipid nanoparticles (LNPs). These LNPs-based cosmeceutical products offer several advantages such as enhanced bioavailability of cosmeceutical active ingredients (CAIs), improved aesthetic appeal, and stability of the final products. However, the use of these LNPs may raise some concerns about possible side effects of these LNPs and potential hazards to the customer's health. Accordingly, an update that focuses on the use of this important branch of nanoparticles is necessary since most review papers are dealing with all types of nanocarriers in the same review with little focus on LNPs. Therefore, in the current review, a detailed analysis of the advantages and disadvantages of LNPs in this field was highlighted, to emphasize the LNPs-based cosmeceuticals on the market, as well as the potential risk posed by LNPs on exposure and recently introduced regulatory guidelines to address them. In addition, if these products can be a candidate as products that meet the sustainable development goals raised by the UN are discussed.

Formulation, Physical Stability, and the Clinical Effectiveness of Extemporaneous Ivermectin Oral Solution.

Ivermectin is a gamma amino butyric acid (GABA)-gated-Cl-channels modulator, which has been used orally in the treatment of numerous parasitic infections. The study target was to set up a stable, efficient 0.2% w/v ivermectin solution, which would be achieved from pure ivermectin powder as a source of the active pharmaceutical ingredient. Several trial solutions were prepared. The most fitting solution, with respect to its organoleptic properties, was chosen for additional investigation, including the solution's physical stability. Two storage conditions, room temperature (25°C, 60% relative humidity) and accelerated stability chambers (40°C, 75% relative humidity) were subjected to guarantee the physical stability of the solution through the 3-month study period. Furthermore, other quality tests were assessed, (e.g., pH, assay, organoleptic properties, microbial contamination) for the same latter period. Quantification of ivermectin was validated utilizing a high-performance liquid chromatography analytical method. The adopted solution showed accepted organoleptic properties. The pH of the solutions was approximately 5 and remained unchanged during the stability study. The mean percent of remained ivermectin solution was close to 97% ± 0.2 at room temperature. Ivermectin solution was additionally tested for microbial contamination, and it was free from any microbial contamination (E. coli bacteria: Negative/mL, yeast and molds count: <10 cfu/mL and aerobic microbial count results in <10 cfu/mL). The adopted formula showed the best physical stability within at least the three months of storage at both room and accelerated conditions. Ivermectin solution was successfully prepared from its pure powder. This formula provides a stable, efficient oral solution for those who suffer from swallowing difficulties or patients in the intensive care unit who cannot receive the medication in a solid dosage form. Using the suggested formula, community and hospital pharmacists could prepare an effective, high quality ivermectin oral solution using pure ivermectin powder.

Montelukast, current indications and prospective future applications.

INTRODUCTION: Montelukast is recommended for the treatment of asthma, exercise -induced bronchospasm and allergic rhinitis. Several trials demonstrated potential therapeutic effects in other respiratory conditions, and different animal-model-based studies explored potential pharmacological actions in non-respiratory conditions. AREAS COVERED: Clinical investigations on the pharmacotherapeutic effects of montelukast, in addition to in-vivo studies on animal models of non-respiratory diseases. The data discussed in this review were mainly obtained from clinical randomized trials, real-life studies, and studies based on animal models as approve of concept. As a condition, all of the discussed articles were published in journals cited by Pubmed. Expert commentary: The current clinical data are in favor of montelukast use in the management of chronic asthma as an add-on or alternative therapy to the inhaled corticosteroids. Further clinical trials are required to confirm the effectiveness and feasibility of montelukast for the treatment of conditions other than the current clinical indications.