Research Article: Immune-enhancing effects of anionic macromolecules extracted from Codium fragile on cyclophosphamide-treated mice

Date Published: February 19, 2019

Publisher: Public Library of Science

Author(s): Chaiwat Monmai, SangGuan You, Woo Jung Park, David D. Roberts.


Immune-regulation and homeostasis are critical in cancer therapy and immunomodulatory biomaterials have been used to decrease side effects of immunosuppressant drugs. Anionic macromolecules (CFAMs) were isolated from the seaweed Codium fragile, and its immune-enhancing biological activities were examined in CY-induced immunosuppressed mice. CFAMs improved the splenic lymphocyte proliferation, NK cell activity, and spleen index. The expression of immune-associated genes was highly upregulated in splenic lymphocytes, and gene expression was differently regulated according to mitogens such as T-cell (Con A) and B-cell (LPS) mitogens. Additionally, CFAMs boosted the proliferation, NO production, and phagocytosis of peritoneal macrophages. CFAMs also considerably stimulated immune-associated gene expression in peritoneal macrophages. Moreover, our results showed CFAMs mediated its immune-enhancing effects via the MAPK pathway. These suggested CFAMs can be used as a potent immunomodulatory material under immune-suppressive condition. Furthermore, CFAMs may also be used as a bio-functional and pharmaceutical material for improving human health and immunity.

Partial Text

Immunomodulation, consisting of immune-stimulation and immunosuppression, is a sophisticated mechanism regulating the pathophysiology and etiology of various diseases affecting the immune system [1]. Immuno-regulation and homeostasis are crucial factors affecting cellular processes [2]. An immunomodulatory material can be used as an immune-stimulator to decrease the side effects of immunosuppressant drugs [3]. From ancient times, natural products with immune-regulatory properties have been considered to be important. They also act as important nutrients for improving human health and preventing chronic diseases and physiological problems, such as allergies, infections, and autoimmune diseases. Beta-glucan, a polysaccharide, is useful for treating respiratory tract infections [4]. Hemicellulose is known to possess immune-regulatory, antibacterial, and antitumor biological activities [5]. Chitin also enhances innate immunity and modulates inflammation in occupational allergies in humans [6]. Moreover, carbohydrates are known to be associated with the regulation of gut microbiota, which affect host immunity and health [7].

In humans, immune-regulation is important for protection against several diseases, including tumorigenesis [30]. CY, a well-known chemotherapeutic drug used for tumor treatment, induces adverse effects on the immune system and causes immunosuppression, which can be life threatening [31]. Therefore, many natural compounds having immune-modulation activities have been reported recently. These compounds alleviate the deleterious effects of chemotherapeutic drugs [1, 30–32]. Particularly, polysaccharides with low toxic side-effects have been used as adjuvant medications or immunomodulators for strengthening host defense responses [33, 34]. In the present study, we determined the efficacy of polysaccharides isolated from C. fragile in enhancing immunological functions in immunosuppressed BALB/c mice.

The present study demonstrated that CFAMs, anionic macromolecules from C. fragile, enhanced the immune responses in CY-treated immunosuppressed mice via peritoneal macrophage proliferation, NO production and phagocytosis by peritoneal macrophages, enhancing macrophage gene expression, increasing splenic lymphocyte proliferation and NK cell activity, spleen index, and splenic lymphocyte gene expression. Additionally, it was shown using macrophages and NF-κB- and MAPK-inhibited cells that CFAMs stimulated macrophages via the MAPK pathway. Consequently, our results might help in elucidating the immune-enhancing mechanisms of CFAMs under immune-suppressive conditions in cancer treatment. In conclusion, CFAMs may be used as a potent biofunctional and pharmaceutical material for enhancing immunity in humans.




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