Korean J Gastroenterol.  2020 Sep;76(3):150-158. 10.4166/kjg.2020.76.3.150.

Arthrospira (Spirulina) platensis Attenuates Dextran Sulfate Sodium-induced Colitis in Mice by Suppressing Key Pro-inflammatory Cytokines

• Garcia FAdO
• Sales-Campos H
• Yuen VG
• Machado JR
• Viana GSdB
• Oliveira CJF
• McNeill JH

• KMID: 2506671
• DOI: http://doi.org/10.4166/kjg.2020.76.3.150

Abstract

Background/Aims
Therapies aimed at modulating cytokines have been used to treat inflammatory illnesses, such as inflammatory bowel disease. On the other hand, patients may become intolerant, refractory, or present with several side effects. Arthrospira (Spirulina) platensis (SPI) is a blue-green microalga with bioactive molecules that have been evaluated to treat inflammatory diseases. On the other hand, few studies have examined their effects on the production of specific cytokines and the intestinal architecture in dextran sulfate sodium (DSS)-induced colitis. Therefore, this study examined the effects of a treatment using SPI in a murine model of intestinal inflammation.
Methods
All mice (C57BL/6 male) were evaluated daily for their food and water intake, bodyweight variations, and clinical signs of disease. Colon inflammation was induced by exposure to DSS for 6 consecutive days. SPI was given orally at 50, 100, and 250 mg/kg/day. ELISA was performed to assess the production of cytokines. Myeloperoxidase and nitric oxide were also investigated. The level of microscopic damage was assessed by staining colon sections with hematoxylin and eosin.
Results
SPI attenuated the DSS-induced inflammation, with improvements in the clinical signs and a decrease in the production of inflammatory cytokines, such as tumor necrosis factor-α and interferon-γ. In addition, particularly at 250 mg/kg, SPI attenuated the severity of colitis by modulating the level of mucosal and submucosal cell infiltration, which preserved the epithelial barrier.
Conclusions
SPI may be an alternative source of bioactive molecules with immunomodulatory properties, and has great potential to be used in the treatment of inflammatory diseases.

Keyword

Spirulina; Inflammatory bowel diseases; Cytokines; Immunomodulation; Inflammation

Figure

• 

  Fig. 1 SPI appears to control the colitis outcome in a dose-dependent manner. C57BL/6 male mice were exposed to DSS 3% in their drinking water for six days. The mice were treated by gavage once per day with 50, 100, or 250 mg/kg of SPI extract or saline, and euthanized on day 6. The black arrows in (A) and (B) indicate the days of treatment. Healthy: mice treated with saline only; DSS+Vei - mice exposed to DSS and treated with saline; DSS+50 or 100 or 250 mg/kg – mice exposed to DSS and treated with different concentrations of SPI. (A) weight variation; (B) clinical disease score; (C) overall clinical score; (D) post mortem score; (E) accumulated score; (F) intestinal length. The experiments were conducted with six mice/group. The results are representative of two independent experiments. DSS, dextran sulfate sodium; SPI, Arthrospira (Spirulina) platensis. ap <0.05.

• 

  Fig. 2 SPI does not appear to affect the production MPO and NO. C57BL/6 male mice were exposed to DSS 3% in their drinking water for six days. The mice were treated by gavage with 50, 100, or 250 mg/kg of SPI extract or saline, and euthanized on day 6. (A) MPO. (B) NO. DSS+Vehicle: mice exposed to DSS and treated with saline; DSS+50 or 100 or 250 mg/kg–mice exposed to DSS 3% and treated with different concentrations of SPI. The experiments were conducted with six mice/group. The results are representative of two independent experiments. MPO, myeloperoxidase; NO, nitric oxide; DSS, dextran sulfate sodium; SPI, Arthrospira (Spirulina) platensis.

• 

  Fig. 3 Treatment with SPI attenuated DSS-induced injury in the colon. C57BL/6 male mice were exposed to DSS 3% in the drinking water for six days. The mice were treated by gavage with 50, 100, or 250 mg/kg of SPI extract or saline, and euthanized on day 6. In (A), the mice exposed to DSS without treatment showed moderate edema (arrow), moderate mononuclear cell infiltration (arrowhead), and intense destroyed crypts (asterisk) (H&E, ×40). (B-D) Mice treated with A. platensis at 50, 100, or 250 mg/kg, respectively, showed mild edema (arrow), mild mononuclear cell infiltration (arrowhead), and mild destroyed crypts (asterisk) (H&E, ×40). The experiments were conducted with six mice/group. The results are representative of two independent experiments. SPI, Arthrospira (Spirulina) platensis; DSS, dextran sulfate sodium.

• 

  Fig. 4 SPI reduces key inflammatory cytokines to the progression of intestinal inflammation. C57BL/6 male mice were exposed to DSS 3% in their drinking water for six days. The mice were treated by gavage with 50, 100, or 250 mg/kg of SPI extract or saline, and euthanized on day 6. (A) TNF-α; (B) IFN-γ; (C) IL-4; (D) IL-6; (E) IL-17; (F) IL-10 and (G) IL-27. Dashed line: control mice, not exposed to DSS. DSS+vehicle: mice exposed to DSS and treated with saline; DSS+50 or 100 or 250 mg/kg–mice exposed to DSS 3% and treated with different concentrations of SPI extract. The experiments were conducted with six mice/group. The results are representative of two independent experiments. SPI, Arthrospira (Spirulina) platensis; DSS, dextran sulfate sodium; TNF, tumor necrosis factor; IFN, interferon; IL, interleukin.ap<0.05.

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