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Int. J. Mol. Sci. 2015, 16(10), 24139-24158; doi:10.3390/ijms161024139

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

1
Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan, Jeonbuk 570-749, Korea
2
College of Pharmacy, Chungbuk National University, Cheongju 361-763, Korea
3
Institute of Zoonosis Research Center and Department Infection Biology, College of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Korea
*
Author to whom correspondence should be addressed.
Academic Editor: Ge Zhang
Received: 3 September 2015 / Revised: 23 September 2015 / Accepted: 7 October 2015 / Published: 13 October 2015
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Abstract

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. View Full-Text
Keywords: Morus alba fruits; immune response; TLR; 5-fluorouracil (5-FU); chemotherapeutic activity Morus alba fruits; immune response; TLR; 5-fluorouracil (5-FU); chemotherapeutic activity
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Chang, B.Y.; Kim, S.B.; Lee, M.K.; Park, H.; Kim, S.Y. Improved Chemotherapeutic Activity by Morus alba Fruits through Immune Response of Toll-Like Receptor 4. Int. J. Mol. Sci. 2015, 16, 24139-24158.

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