Randa A. Zaghloul

Natural bioactive compounds with anti-neoplastic effects, such as celastrol (CLS), have attracted considerable interest in recent years. The present study aimed to investigate the effect of CLS on wnt/β-catenin signaling, and its potential combination with doxorubicin (Dox) to enhance chemotherapeutic effects. After intramuscular inoculation of Ehrlich tumor cells, tumor-bearing mice received CLS (2 mg/kg, i.p), Dox (5 mg/kg, once/week, i.p), and their combination for 21 days. Treatment with CLS showed showing antioxidant and anti-inflammatory, as evidenced by a significant increase in glutathione content and a significant decrease in the malondialdehyde, interleukin 6, and interleukin 1β concentrations. CLS also inhibited VEGF-mediated angiogenesis. The current study revealed that CLS downregulated β‐catenin gene expression with subsequent downstream target genes, such as cyclin-D1, and survivin, which dampens tumor cell proliferation and triggers cell cycle arrest as well as induces apoptosis as indicated by the increased expression of p53, caspase‐3. The current study concludes that CLS exerted its anti-neoplastic activity by suppressing the wnt/β-catenin signaling pathway, and opens a new perspective for combining CLS with Dox to enhance its chemotherapeutic effects and reduce the oxidative imbalance and inflammatory responses associated with Dox treatment.

Lung inflammation is a hallmark of several respiratory diseases. Despite the great effectiveness of the synthetic antiinflammatory agents, they cause potential side effects. Polydatin (PD), a natural phytomedicine, has antioxidant and antiinflammatory effects. Its clinical applications are hindered due to poor aqueous solubility, low bioavailability, and rapid metabolism by first-pass effect. Herein, we report the development of a novel chitosan oligosaccharide-coated PD-loaded Poly dl-lactide-co-glycolide nanoparticles (COS-coated PD/PLGA NPs) against a bleomycin-induced pulmonary inflammation in a rat model. The NPs exhibited a small particle size of 188.57 ± 5.68 nm and a high zeta potential of + 18.13 ± 2.75 mV with spherical architecture and sustained release pattern of PD. In vivo studies in bleomycin-induced lung inflammation in a rat model revealed the superior prophylactic activity of COS-coated PD/PLGA NPs over the free drug (PD) as demonstrated by histopathological and immunohistochemical analyses, alongside biochemical assays evaluating oxidative stress biomarkers and inflammatory cytokine levels. Overall, the optimized COS-coated PD/PLGA NPs formulation offers a promising prophylactic platform against many respiratory diseases. Graphical Abstract

Sitagliptin (STG) is a highly selective dipeptidyl peptidase-4 inhibitor recently used in the treatment of type 2 diabetes. The current study aimed to investigate the anti-neoplastic effect of STG alone and in combination with Doxorubicin (Dox), a known chemotherapeutic agent but with ominous side effects. After intramuscular inoculation of 2 × 10⁶ Ehrlich tumor cells, Female Swiss mice were divided into tumor-bearing control, STG-treated, Dox-treated, and a combination of STG and Dox-treated groups. The results showed a significant reduction in the tumor growth of the treated animals in comparison with those of the positive control group with a more prominent effect in the co-treated group. Where, the anti-proliferative and apoptotic effect of STG, and its chemo-sensitizing ability, when used in combination with Dox, was mediated by modulation of oxidative stress (MDA and GSH), attenuation of tumor inflammation (IL-6 and IL-1β), and angiogenesis (VEGF), suppressing proliferation (β-catenin and cyclin-D1) and enhancement of apoptosis (survivin, p53, caspase 3). Thus, in conclusion, STG as adjunctive therapy for Dox could be a strategy for the treatment of breast cancer patients, by their ability in hindering cell proliferation and minimizing the associated oxidative and inflammatory adverse reactions.