Antihydatic and immunomodulatory effects of Algerian propolis ethanolic extract: In vitro and in vivo study

Objective: To evaluate the in vitro and in vivo effect of the Algerian propolis ethanolic extract (EEP) against Echinococcus granulosus (E. granulosus) infection. Methods: In vitro scolicidal activity of EEP was investigated on the protoscolices of hydatid cyst. This in vitro study was conducted by using an in vivo assay. BALB/c mice were inoculated with E. granulosus and treated with propolis for three months. Hydatid cysts development was assessed. Nitric oxide (NO), tumor necrosis factor alpha (TNF-α) production and inducible NO synthase, NF-κB, and TNF-α spleen expression were estimated by Griess method and immunofluorescence respectively. Results: Our study revealed that EEP has a high scolicidal activity against E. granulosus. Oral administration of EEP decreased TNF-α, NF-κB and inducible NO synthase expression in the spleen tissues in the CE+EEP group, in comparison with the CE group. Concomitantly, EEP treatment caused an important systemic decrease in NO and TNF-α levels. These findings are associated with the reduction of CE development. Conclusions: This is the first report demonstrating with interest the antihydatic and immunomodulatory effects of the Algerian EEP, suggesting its therapeutic potential for the hydatid disease treatment.

Propolis modulates NOS2/arginase-1 pathway in tropomyosin-induced experimental autoimmune uveitis.

In this study, we evaluated the preventive and curative effects of ethanolic extract of Propolis (EEP) during α-Tropomyosin-induced uveitis in an experimental model using Wistar rats, through the regulation of inducible nitric oxide synthase (NOS2) and arginase-1. In this context, rats received daily injection of EEP (100 mg/kg) for 5 days prior to immunization or for 9 days commencing 5 days post immunization with α-Tropomyosin extract, then were sacrificed at day 14. Histological examination, NOS2, arginase-1, and nuclear factor-κB (NF-κB) expression were evaluated in the retinas. Plasmatic production of nitric oxide (NO), urea, IL-4, and TNF-α was assessed. We have found that treatment with EEP substantially reduced the retinal histological damages induced by α-Tropomyosin. In the same context, a significant decrease of NO and TNF-α levels was noticed. Interestingly, EEP down-modulated NOS2 and NF-κB expression in retina. Also, an increase in urea and IL-4 levels was concomitant to an up-modulation of arginase-1 expression. Hence, it appears that EEP attenuated retinal damages through the induction of Th2 response and the inhibition of NF-κB/NOS2 pathway.

Ex vivo immunomodulatory effect of ethanolic extract of propolis during Celiac Disease: involvement of nitric oxide pathway.

Celiac Disease (CeD) is a chronic immune-mediated enteropathy, in which dietary gluten induces an inflammatory reaction, predominantly in the duodenum. Propolis is a resinous hive product, collected by honeybees from various plant sources. Propolis is well-known for its anti-inflammatory, anti-oxidant and immunomodulatory effects, due to its major compounds, polyphenols and flavonoids. The aim of our study was to assess the ex vivo effect of ethanolic extract of propolis (EEP) upon the activity and expression of iNOS, along with IFN-γ and IL-10 production in Algerian Celiac patients. In this context, PBMCs isolated from peripheral blood of Celiac patients and healthy controls were cultured with different concentrations of EEP. NO production was measured using the Griess method, whereas quantitation of IFN-γ and IL-10 levels was performed by ELISA. Inducible nitric oxide synthase (iNOS) expression, NFκB and pSTAT-3 activity were analyzed by immunofluorescence assay. Our results showed that PBMCs from Celiac patients produced high levels of NO and IFN-γ compared with healthy controls (HC). Interestingly, EEP reduced significantly, NO and IFN-γ levels and significantly increased IL-10 levels at a concentration of 50 µg/mL. Importantly, EEP downmodulated the iNOS expression as well as the activity of NFκB and pSTAT-3 transcription factors. Altogether, our results highlight the immunomodulatory effect of propolis on NO pathway and on pro-inflammatory cytokines. Therefore, we suggest that propolis may constitute a potential candidate to modulate inflammation during Celiac Disease and has a potential therapeutic value.