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Improved Chemotherapeutic Activity by Morus alba Fruits through Immune Response of Toll-Like Receptor 4

Morus alba L. fruits have long been used in traditional medicine by many cultures. Their medicinal attributes include cardiovascular, hepatoprotective, neuroprotective and immunomodulatory actions. However, their mechanism of macrophage activation and anti-cancer effects remain unclear. The present...

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Autores principales: Chang, Bo Yoon, Kim, Seon Beom, Lee, Mi Kyeong, Park, Hyun, Kim, Sung Yeon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632743/
https://www.ncbi.nlm.nih.gov/pubmed/26473845
http://dx.doi.org/10.3390/ijms161024139
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author Chang, Bo Yoon
Kim, Seon Beom
Lee, Mi Kyeong
Park, Hyun
Kim, Sung Yeon
author_facet Chang, Bo Yoon
Kim, Seon Beom
Lee, Mi Kyeong
Park, Hyun
Kim, Sung Yeon
author_sort Chang, Bo Yoon
collection PubMed
description Morus alba L. fruits have long been used in traditional medicine by many cultures. Their medicinal attributes include cardiovascular, hepatoprotective, neuroprotective and immunomodulatory actions. However, their mechanism of macrophage activation and anti-cancer effects remain unclear. The present study investigated the molecular mechanisms of immune stimulation and improved chemotherapeutic effect of M. alba L. fruit extract (MFE). MFE stimulated the production of cytokines, nitric oxide (NO) and tumor necrosis factor-α (TNF-α) and tumoricidal properties of macrophages. MFE activated macrophages through the mitogen-activated protein kinase (MAPKinase) and nuclear factor-κB (NF-κB) signaling pathways downstream from toll-like receptor (TLR) 4. MFE was shown to exhibit cytotoxicity of CT26 cells via the activated macrophages, even though MFE did not directly affect CT26 cells. In a xenograft mouse model, MFE significantly enhanced anti-cancer activity combined with 5-fluorouracil and markedly promoted splenocyte proliferation, natural killer (NK) cell activity, cytotoxic T lymphocyte (CTL) activity and IFN-γ production. Immunoglobulin G (IgG) antibody levels were significantly increased. These results indicate the indirect anti-cancer activity of MFE through improved immune response mediated by TLR4 signaling. M. alba L. fruit extract might be a potential anti-tumor immunomodulatory candidate chemotherapy agent.
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spelling pubmed-46327432015-11-23 Improved Chemotherapeutic Activity by Morus alba Fruits through Immune Response of Toll-Like Receptor 4 Chang, Bo Yoon Kim, Seon Beom Lee, Mi Kyeong Park, Hyun Kim, Sung Yeon Int J Mol Sci Article Morus alba L. fruits have long been used in traditional medicine by many cultures. Their medicinal attributes include cardiovascular, hepatoprotective, neuroprotective and immunomodulatory actions. However, their mechanism of macrophage activation and anti-cancer effects remain unclear. The present study investigated the molecular mechanisms of immune stimulation and improved chemotherapeutic effect of M. alba L. fruit extract (MFE). MFE stimulated the production of cytokines, nitric oxide (NO) and tumor necrosis factor-α (TNF-α) and tumoricidal properties of macrophages. MFE activated macrophages through the mitogen-activated protein kinase (MAPKinase) and nuclear factor-κB (NF-κB) signaling pathways downstream from toll-like receptor (TLR) 4. MFE was shown to exhibit cytotoxicity of CT26 cells via the activated macrophages, even though MFE did not directly affect CT26 cells. In a xenograft mouse model, MFE significantly enhanced anti-cancer activity combined with 5-fluorouracil and markedly promoted splenocyte proliferation, natural killer (NK) cell activity, cytotoxic T lymphocyte (CTL) activity and IFN-γ production. Immunoglobulin G (IgG) antibody levels were significantly increased. These results indicate the indirect anti-cancer activity of MFE through improved immune response mediated by TLR4 signaling. M. alba L. fruit extract might be a potential anti-tumor immunomodulatory candidate chemotherapy agent. MDPI 2015-10-13 /pmc/articles/PMC4632743/ /pubmed/26473845 http://dx.doi.org/10.3390/ijms161024139 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chang, Bo Yoon
Kim, Seon Beom
Lee, Mi Kyeong
Park, Hyun
Kim, Sung Yeon
Improved Chemotherapeutic Activity by Morus alba Fruits through Immune Response of Toll-Like Receptor 4
title Improved Chemotherapeutic Activity by Morus alba Fruits through Immune Response of Toll-Like Receptor 4
title_full Improved Chemotherapeutic Activity by Morus alba Fruits through Immune Response of Toll-Like Receptor 4
title_fullStr Improved Chemotherapeutic Activity by Morus alba Fruits through Immune Response of Toll-Like Receptor 4
title_full_unstemmed Improved Chemotherapeutic Activity by Morus alba Fruits through Immune Response of Toll-Like Receptor 4
title_short Improved Chemotherapeutic Activity by Morus alba Fruits through Immune Response of Toll-Like Receptor 4
title_sort improved chemotherapeutic activity by morus alba fruits through immune response of toll-like receptor 4
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632743/
https://www.ncbi.nlm.nih.gov/pubmed/26473845
http://dx.doi.org/10.3390/ijms161024139
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