Abstract

Interest in the nutritional value and pharmacological activities of blue-green algae has gradually increased. Spirulina extracts show protective effects against apoptosis and inflammatory damage in various cell types. Here, we investigated the protective effects of extracts from Spirulina maxima in a cytokine-mediated type 1 diabetes model in vitro and in streptozotocin-induced diabetic Wistar rats in vivo. Interleukin-1β and interferon-gamma induced substantial cytotoxicity to RINm5F rat insulinoma cells, increasing nitric oxide (NO) production, nuclear factor-kappa B (NF-κB) activity, the expression of endoplasmic reticulum (ER) stress genes, and activation of mitogen-activated protein kinases and key genes related apoptosis. However, the cytotoxicity of cytokines was significantly attenuated by Spirulina extract, which effectively prevented NO production by inhibiting the synthesis of cytokine-activated NO synthase (iNOS), and apoptosis was suppressed. These results suggest that Spirulina extract might be effective to preserve the viability and function of pancreatic β-cells against cytotoxic conditions. Moreover, diabetic mice orally administered Spirulina extract showed decreased glucose levels, increased insulin, and improvement in liver enzyme markers. The antioxidant effect of Spirulina extract may be helpful in treating type 1 diabetes by enhancing the survival, and reducing or delaying cytokine-mediated β-cells destruction.

Highlights

  • Spirulina maxima is a planktonic filamentous cyanobacterium with characteristic morphological features such as the arrangement of multicellular cylindrical trichomas in a helix along the entire body length

  • The present study demonstrates that Spirulina extract inhibits cell apoptosis through cytokine-mediated cytotoxicity in RINm5F pancreatic β-cells

  • Activation of cytokine-mediated caspase-3, Jun N-terminal kinase (JNK), and p38 Mitogen-activated protein kinases (MAPKs) were attenuated by treatment with Spirulina extract

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Summary

Introduction

Spirulina maxima is a planktonic filamentous cyanobacterium with characteristic morphological features such as the arrangement of multicellular cylindrical trichomas in a helix along the entire body length. Spirulina has an antioxidant defense system, which removes reactive oxygen species (ROS) that can damage cells by inducing oxidative stress [9,10]. Because this antioxidant system reduces most oxidized forms by photosynthesis, the antioxidant property in Spirulina extract is associated with some phycobiliproteins, such as C-phycocyanin and allophycocyanin [11,12]. Despite these pharmacological benefits, the molecular mechanisms related to the anti-oxidant effects of Spirulina are mostly unknown. We sought to determine the effects of Spirulina extract on cytokine-induced cytotoxicity in diabetes models, as well as the underlying mechanism, in order to establish its potential in the protection against pancreatic β-cell death

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