Baicalein prevents capecitabine-induced heart damage in female Wistar rats and enhances its anticancer potential in MCF-7 breast cancer cells.

AIM: We investigated the ability of baicalein (BAI) to enhance the anticancer potential of capecitabine (CAP) in the MCF-7 cell line and its protective effect on CAP-induced cardiotoxicity in female Wistar rats. METHODS AND KEY FINDINGS: In vitro study involved evaluating the effect of BAI and/or CAP on cell viability, cell cycle progression, and BAX and Bcl2 gene expression in MCF-7 cells. Co-treatment of BAI with CAP significantly reduced the viability of MCF-7 cells, improved their cytotoxic effect, markedly elevated the percentage of the sub-G1 population, drastically reduced the G2/M population, and significantly altered the mRNA expression of BAX and Bcl2 genes compared with each treatment alone. In vivo study revealed that the oral administration of CAP (140 mg/kg BW) to adult female rats significantly elevated the levels of serum creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), tumor necrosis factor (TNF)-α, and interleukin (IL)-1ß and cardiac TNF-α, IL-1ß malondialdehyde (MDA) concentration, whereas it reduced the serum and cardiac total antioxidant capacity (TAC), level of cardiac glutathione (GSH) and activity of glutathione peroxidase (GPx) with a vast array of circulatory, inflammatory, degenerative, and necrotic alterations in the cardiac tissue. Furthermore, CAP administration significantly upregulated the mRNA expression of NF-κB, TLR4, MyD88, ATF6, CHOP, and JNK genes. Concurrent administration of BAI (200 mg/kg BW) and CAP significantly improved the biochemical alterations and cardiac oxidant/antioxidant status and architecture. In addition, it modulated the TLR4/MyD88/NF-κB pathway and endoplasmic reticulum stress. SIGNIFICANCE: Altogether, BAI can augment the anticancer potential of CAP and alleviate its cardiotoxic effects during cancer treatment.

Chitosan propolis nanocomposite alone or in combination with apramycin: an alternative therapy for multidrug-resistant Salmonella Typhimurium in rabbits: in vitro and in vivo study.

Introduction. The emergence of multidrug-resistant Salmonella Typhimurium strains has increased the need for safe, alternative therapies from natural sources with antibacterial properties.Hypothesis/Gap Statement. There are no published data regarding the use of chitosan propolis nanocomposite (CPNP) either alone or in combination with antibiotics as antimicrobials against S. Typhimurium, especially in Egypt.Aim. This study evaluated the antibacterial activities of five antimicrobials [apramycin, propolis, chitosan nanoparticles (CNPs), chitosan propolis nanocomposite (CPNP) and CPNP +apramycin] against ten virulent and multidrug-resistant (MDR) S. Typhimurium field strains recovered from diarrheic rabbits through in vitro and in vivo study.Methodology. The expression levels of three virulence genes of S. Typhimurium strains were determined by quantitative reverse-transcription PCR (RT-qPCR) after exposure to sub-inhibitory concentrations of apramycin, propolis, CNPs, CPNP alone, and CPNP +apramycin. Additionally, 90 New Zealand rabbits were divided into control and experimentally S. Typhimurium-infected groups. The infected rabbits were orally administered saline solution (infected-untreated); 10 mg apramycin/kg (infected-apramycin-treated); 50 mg propolis/kg (infected-propolis-treated); 15 mg CPNP/kg (infected-CPNP-treated) and 15 mg CPNP +10 mg apramycin/kg (infected-CPNP +apramycin-treated) for 5 days.Results. The RT-qPCR analysis revealed different degrees of downregulation of all screened genes. Furthermore, the treatment of infected rabbits with CPNP or CPNP +apramycin significantly improved performance parameters, and total bacterial and Salmonella species counts, while also modulating both oxidative stress and altered liver and kidney parameters.Conclusion. This work demonstrates the use of CPNP alone or in combination with apramycin in the treatment of S. Typhimurium in rabbits.

Anti-arthritic effect of ß-caryophyllene and its ameliorative role on methotrexate and/or leflunomide-induced side effects in arthritic rats.

AIM: Rheumatoid arthritis (RA) is the most widespread inflammatory arthropathy, which causes severe disability. It is highly important to ameliorate the side effects caused by different drugs used to treat RA. Therefore, this study assessed the potential role of ß-caryophyllene (BCP) in treating adjuvant-induced arthritis (AIA), increasing the efficacy of methotrexate (MTX) and/or leflunomide (LEF), and ameliorating their side effects. MATERIAL AND METHODS: AIA was induced in rats by injecting complete Freund's adjuvant. The rats were divided into different groups such as sham group; control group; monotherapy groups, including BCP (300 mg/kg), MTX (1 mg/kg), and LEF (10 mg/kg); and combined groups, including MTX + BCP, LEF + BCP, MTX + LEF, and MTX + LEF + BCP groups. KEY FINDINGS: Monotherapy with BCP or MTX or LEF as well as MTX + LEF significantly reduced paw thickness and arthritic index; the histopathological changes in hind paw joints were recovered; and oxidative stress and tumor necrosis factor-alpha (TNF-α) levels in arthritic rats were reduced. The co-administration of BCP and MTX and/or LEF significantly improved the therapeutic efficacy of MTX and/or LEF and significantly reduced the myelosuppressive and hepatotoxic effects of MTX and/or LEF. Taken together, BCP could be used with MTX and/or LEF for the treatment of RA to reduce the side effects of the drugs and increase their efficacy.