Effect of Agmatine on a mouse model of allergic airway inflammation: A comparative study.

INTRODUCTION: Asthma is a chronic lung disease that injures and constricts the airways. This study evaluates the effects of agmatine on ovalbumin (OVA)-induced allergic inflammation of the airways. METHODS: OVA sensitization by intraperitoneal injection was used to induce airway inflammation in mice on days 0 and 7; then the mice were challenged using beclomethasone (150 µg/kg, inhalation), a standard anti-asthmatic drug, from day 14 to day 16. Furthermore, agmatine (200 mg/kg) was intraperitoneally injected on day 0 and then daily for 16 days, followed by OVA challenge. The lung weight ratio, total and differential cell counts, TNF-α, interleukin-5 (IL-5) and IL-13 in bronchoalveolar lavage fluid (BALF), lung nitrite/nitrate (NO), and oxidative parameters were determined. Moreover, histopathological and immunohistochemical staining was employed. RESULTS: Injection of agmatine (200 mg/kg) for 16 days significantly attenuated inflammation of the airways. The levels of BALF inflammatory cells, TNF-α, IL-5, IL-13, lung NO, and malondialdehyde (MDA), significantly decreased with concomitant elevation of superoxide dismutase (SOD) levels. Histological and immunohistochemical analyses of mast cells paralleled to biochemical improvements. CONCLUSION: Finally, this study illustrated that agmatine attenuates the allergic inflammation of airways caused by OVA by mitigating cytokines release, NO expression, and oxidative stress.

Nifuroxazide Mitigates Angiogenesis in Ehlrich's Solid Carcinoma: Molecular Docking, Bioinformatic and Experimental Studies on Inhibition of Il-6/Jak2/Stat3 Signaling.

Nifuroxazide is an antidiarrheal medication that has promising anticancer activity against diverse types of tumors. The present study tested the anticancer activity of nifuroxazide against Ehrlich's mammary carcinoma grown in vivo. Furthermore, we investigated the effect of nifuroxazide on IL-6/jak2/STAT3 signaling and the possible impact on tumor angiogenesis. The biological study was supported by molecular docking and bioinformatic predictions for the possible effect of nifuroxazide on this signaling pathway. Female albino mice were injected with Ehrlich carcinoma cells to produce Ehrlich's solid tumors (ESTs). The experimental groups were as follows: EST control, EST + nifuroxazide (5 mg/kg), and EST + nifuroxazide (10 mg/kg). Nifuroxazide was found to reduce tumor masses (730.83 ± 73.19 and 381.42 ± 109.69 mg vs. 1099.5 ± 310.83) and lessen tumor pathologies. Furthermore, nifuroxazide downregulated IL-6, TNF-α, NFk-ß, angiostatin, and Jak2 proteins, and it also reduced tumoral VEGF, as indicated by ELISA and immunohistochemical analysis. Furthermore, nifuroxazide dose-dependently downregulated STAT3 phosphorylation (60% and 30% reductions, respectively). Collectively, the current experiment shed light on the antitumor activity of nifuroxazide against mammary solid carcinoma grown in vivo. The antitumor activity was at least partly mediated by inhibition of IL-6/Jak2/STAT3 signaling that affected angiogenesis (low VEGF and high angiostatin) in the EST. Therefore, nifuroxazide might be a promising antitumor medication if appropriate human studies will be conducted.

Chemopreventive effect of α-hederin/carboplatin combination against experimental colon hyperplasia and impact on JNK signaling.

Colon cancer is the commonest cancer worldwide. α-Hederin is a monodesmosidic triterpenoid saponin possessing diverse pharmacological activities. The running experiment was designed to test the chemopreventive activity of α-hederin when used as an adjuvant to carboplatin in an experimental model of mouse colon hyperplasia induced by 1,2-dimethylhydrazine (DMH). Fifty male Swiss albino mice were classified into five groups: group (I): saline group, group (II): DMH-induced colon hyperplasia control group, group (III): DMH + carboplatin (5 mg/kg) group, group (IV): DMH + α-hederin (80 mg/kg) group, and group (V): DMH + carboplatin (5 mg/kg)+α-hederin (80 mg/kg) group. Analyzing of colonic tissue indicated that the disease control group showed higher colon levels of phospho-PI3K to total-PI3K, phospho-AKT to total-AKT and cyclin D1 concurrent with lower phospho-JNK/total JNK ratio and caspase 3. However, treatment with α-hederin, in combination with carboplatin, favorably ameliorated phosphorylation of PI3K/AKT/JNK proteins, increased colon caspase 3 and downregulated cyclin D1. Microscopically, α-hederin, in combination with carboplatin, produced the most reduction in the histologic hyperplasia score, enhanced the goblet cell survival in periodic acid Schiff staining and reduced proliferation (Ki-67 immunostaining) in the current colon hyperplasia model. Collectively, the current study highlighted for the first time that using α-hederin as an adjuvant to carboplatin enhanced its chemopreventive activity, improved JNK signaling and increased apoptosis. Hence, further studies are warranted to test α-hederin as a promising candidate with chemotherapeutic agents in treating colon cancer.