The anti-leukemia and anti-inflammatory effects and their molecular mechanisms of methanol extract of Antrodia cinnamomea mycelia

• Main Authors: Chi-Luan Wen, 文紀鑾
• Other Authors: Chao-LinKuo
• Format: Others
• Language: en_US
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/88224418522945601725

博士 === 中國醫藥大學 === 中國藥學暨中藥資源學系博士班 === 100 === Antrodia cinnamomea (named as Niu-chang-chih), a well-known Taiwanese folk medicinal mushroom, has a broad-spectrum of pharmacological effects, especially with anti-tumor and anti-inflammatory properties. In this study, we attempted to assess the anti-leukemia and anti-inflammatory activities and mode of action of the methanol extract from liquid cultured mycelia of A. cinnamomea (MEMAC). In part 1, we examined the potential role and the underlying mechanisms of MEMAC in the cell growth and differentiation of human acute myeloid leukemia HL60 cells. We found firstly that MEMAC inhibited proliferation and induced G1 cell cycle arrest in HL60 cells. Moreover, MEMAC could induce differentiation of HL60 cells into the monocytic lineage. In addition, MEMAC activated the extracellular signal-regulated kinase (ERK) pathway and increased CCAAT/enhancer-binding protein β (C/EBPβ) expression. These findings demonstrate that MEMAC-induced HL60 cell monocytic differentiation might be via the activating ERK signaling pathway, and upregulating the downstream transcription factor C/EBPβ, consequently enhancing the differentiation marker CD14 gene expression. These observations suggest that MEMAC might be a potential differentiation-inducing agent for treatment of leukemia. In part 2, we evaluated the anti-inflammatory effect of MEMAC in both in vitro and in vivo systems. The in vitro anti-inflammatory activity of MEMAC was judged by the measurement of the levels of pro-inflammatory cytokines and mediators in lipopolysaccharide (LPS)-, palmitoyl-3-cysteine-serine-lysine-4 (Pam3CSK4)-, polyinosine–polycytidylic acid (PolyIC)-stimulated RAW264.7 cells, respectively. The results showed that MEMAC inhibited the production of LPS, Pam3CSK4, PolyIC-induced pro-inflammatory cytokines(TNF-α and IL-6), and mediators (NO and PGE2). Moreover, MEMAC decreased the levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) protein expression in LPS-stimulated RAW264.7 macrophages. The in vivo anti-inflammatory activity of MEMAC was carried out using carrageenan-induced hind paw edema in mice. The data indicated that MEMAC exhibited significant (p < 0.05) anti-inflammatory activity by reducing the edema volume in carrageenan-induced paw edema in mice. MEMAC (400 mg/kg) also reduced the carrageenan-induced leukocyte migration (50.92 ± 5.71%). Furthermore, MEMAC also increased the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the liver tissue and decreased the levels of serum NO and TNF-α after carrageenan administration. Taken together, our findings reveal that MEMAC has the anti-AML and anti-inflammatory properties.