Antrodia cinnamomea Galactomannan Elicits Immuno-stimulatory Activity Through Toll-like Receptor 4.

Antrodia cinnamomea (A. cinnamomea) is a medicinal fungus used in traditional Chinese medicine to treat different kinds of ailments, including liver diseases, abdominal pain, drug intoxication, diarrhea, itchy skin, hypertension, and cancer. Polysaccharides have been identified as one of the major pharmacologically active ingredients present in A. cinnamomea. The present study aims to investigate the immunoenhancing activity of galactomannan isolated from A. cinnamomea. The cold water-soluble polysaccharide (galactomannan-repeated; MW>70 kDa; named ACP) of A. cinnamomea was isolated, and immunostimulatory properties were studied through different immune cell models including mouse macrophages and human dendritic cells. Through Toll-like receptor 4, ACP stimulated tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in J774A.1 mouse macrophages, mouse peritoneal macrophages and human dendritic cells. It was further identified that ACP elicited its immunostimulatory activity through protein kinase C-α (PKC-α) and mitogen activated protein kinases (MAPK) phosphorylation. Furthermore, ACP exerted the endotoxin tolerance-like effect through NF-κB inhibition. These findings demonstrate the potential of A. cinnamomea galactomannan as an immunostimulator or an adjuvant in immunotherapy and vaccination.

Dioscorea phytocompounds enhance murine splenocyte proliferation ex vivo and improve regeneration of bone marrow cells in vivo.

Specific cytokines have been tested clinically for immunotherapy of cancers; however, cytotoxicity has often impaired their usefulness. Consequently, alternative approaches are increasingly desirable. Dioscorea spp. tuber is a widely used traditional Chinese medicinal herb claimed to confer immunostimulatory activity. In this study, we evaluated Dioscorea as an adjuvant therapy for use alongside chemotherapy for cancer. Phytocompounds from Dioscorea tubers were ethanol fractioned and used for ex vivo splenocyte proliferation assay or in vivo force-feeding of mice pre-treated with the chemotherapy agent 5-fluorouracil. Co-treatment with a 50-75% ethanol-partitioned fraction of the tuber extract of D. batatas (DsCE-II) and interleukin (IL)-2 resulted in a significantly higher rate of murine splenocyte cell proliferation ex vivo than treatment with DsCE-II or IL-2 alone. This DsCE-II fraction, which contains a polysaccharide with a high proportion of ß-1,4-linkage mannose (≥64%), also promoted the regeneration of specific progenitor cell populations in damaged bone marrow tissues of 5-fluorouracil-treated mice. Colony-forming unit (CFU) analyses demonstrated that the population of CFU-GM cells, but not CFU-GEMM or BFU-E cells, preferentially recovered to ~67% in the bone marrow of immune-suppressed mice fed with DsCE-II. DsCE-II efficacy level was ~85% of that obtained by subcutaneous administration of recombinant G-CSF proteins (5 µg kg(-1)) in mice tested in parallel. This study suggests that the DsCE-II fraction of D. batatas extract may be considered for further development as a dietary supplement for use alongside chemotherapy during cancer treatment.

Chemical composition and bioactivities of the marine alga Isochrysis galbana from Taiwan.

The present study investigated the chemical composition of Isochrysis galbana Parke, a marine microalga which is widely used as a feedstock in aquaculture. From gas chromatography/mass spectrometric analysis the mono-sugar compositions of I. galbana were 2.1% fucose, 2.5% rhamnose, 2.7% arabinose, 8.5% xylose, 15.7% mannose, 32.7% galactose and 35.8% glucose. The polysaccharides of I. galbana were able to induce prointerleukin-1beta (pro-IL-1beta) protein expression within murine macrophages. Furthermore, five kinds of chlorophyll and one sterol were separated from the ethanolic extracts, including pheophorbide-a, ethyl pheophorbide-a, 10S-10-hydroxypheophytin-a, 10R-10-hydroxypheophytin-a, (132-R)-pheophytin-a, and brassicasterol. In addition, the major soluble components of the ethanol/n-hexane extract were 9-octadecenoic acid (E) (38.4%), hexadecanoic acid (23.3%), tetradecanoic acid (15.7%), and octadecanoic acid (7.2%), but only a few polyunsaturated fatty acids were found, such as 9,12,15-octadecatrienoic acid (1.9%), 9,12-octadecadienoic acid (Z,Z) (3.4%), and docosahexaenoic acid (0.2%). This is the first occasion that polysaccharides from I. galbana have been demonstrated to exert immunomodulatory properties by the induction of IL-1 within macrophages.

Polysaccharides from Dioscorea batatas induce tumor necrosis factor-alpha secretion via Toll-like receptor 4-mediated protein kinase signaling pathways.

The bioactive polysaccharides (named ZPF1) from yam ( Dioscorea batatas) were chemically determined, suggesting repeating beta-1,4-mannan as mainly having a feature of acetylation on C2-OH and C3-OH, around 28%. The ZPF1 participated in the stimulation of murine wild-type macrophages predominantly in tumor necrosis factor-alpha (TNFalpha). Toll-like receptor 4 is proved to be one of the cellular receptors in ZPF1-mediated TNFalpha secretion. Reactive oxygen species transmission and PI3-kinase are found necessary for regulating TNFalpha secretion by ZPF1 stimulation. Moreover, we found that extracellular signal-regulated kinase 1/2, Jun N-terminal kinase 1/2, and p38 mitogen-activated protein kinase play important roles in the regulation of TNFalpha secretion in ZPF1-stimulated macrophages.