Taiwanofungus camphoratus is a precious medicinal fungus endemic to Taiwan and has been used as traditional medicine for a long time. Many pharmacological studies have revealed that T. camphoratus ...possessed various biological activities, such as immunomodulatory effects, anticancer activity and liver protective function. The aim of this study is to investigate the non-specific and antigen (ovalbumin OVA)-specific immunomodulation effects of solid-state cultivated powder of T. camphoratus (Leader Antrodia cinnamomea LAC) in BABL/c male mice. In non-specific and antigen-specific immune function studies, 8-week-old mice were orally administered with LAC for 6 and 8 weeks, respectively. The results have shown that the proliferation of splenic immune cells, phagocytic activity of macrophages and cytolytic activity of natural killer cells were enhanced by LAC. Additionally, LAC increased the levels of IL-2, TNF-α, INF-γ, GM-CSF and serum OVA-IgG and OVA-IgM. These findings provided evidences that LAC had the immunomodulation effects on both antigen-specific and non-specific immune responses in mice.
In this study, we investigated the cytoprotective effects of antcin C, a steroid-like compound isolated from Antrodia cinnamaomea against AAPH-induced oxidative stress and apoptosis in human hepatic ...HepG2 cells. Pretreatment with antcin C significantly protects hepatic cells from AAPH-induced cell death through the inhibition of ROS generation. Furthermore, AAPH-induced lipid peroxidation, ALT/AST secretion and GSH depletion was significantly inhibited by antcin C. The antioxidant potential of antcin C was correlated with induction of antioxidant genes including, HO-1, NQO-1, γ-GCLC, and SOD via transcriptional activation of Nrf2. The Nrf2 activation by antcin C is mediated by JNK1/2 and PI3K activation, whereas pharmacologic inhibition of JNK1/2 and PI3K abolished antcin C-induced Nrf2 activity. In addition, AAPH-induced apoptosis was significantly inhibited by antcin C through the down-regulation of pro-apoptotic factors including, Bax, cytochrome c, capase 9, -4, -12, -3, and PARP. In vivo studies also show that antcin C significantly protected mice liver from AAPH-induced hepatic injury as evidenced by reduction in hepatic enzymes in circulation. Further, immunocytochemistry analyses showed that antcin C significantly increased HO-1 and Nrf2 expression in mice liver tissues. These results strongly suggest that antcin C could protect liver cells from oxidative stress and cell death via Nrf2/ARE activation.
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•Ag-APS nanoparticles identify and quantify aristolochic acid I (AAI) in herbal extracts.•This method is applicable to traditional Chinese herbal extracts.•Detection limit of AAI ...using SERS is 40 nM.
Herbs containing aristolochic acids (AAs) have already been proven to be highly carcinogenic and nephrotoxic. In this study, a novel surface-enhanced Raman scattering (SERS) identification method was developed. Ag-APS nanoparticles with a particle size of 3.53 ± 0.92 nm were produced by combining silver nitrate and 3-aminopropylsilatrane. The reaction between the carboxylic acid group of aristolochic acid I (AAI) and amine group of Ag-APS NPs was used to form amide bonds, and thus, concentrate AAI, rendering it easy to detect via SERS and amplified to obtain the best SERS enhancement effect. Detection limit was calculated to be approximately 40 nM. Using the SERS method, AAI was successfully detected in the samples of four Chinese herbal medicines containing AAI. Therefore, this method has a high potential to be applied in the future development of AAI analysis and rapid qualitative and quantitative analysis of AAI in dietary supplements and edible herbs.
Evidence has accumulated that berberine is able to induce cell cycle arrest and apoptosis in many human cancer cell lines. However, there is no available information on the effects of berberine on ...human oral squamous cell carcinoma. In this study, the effects of berberine on cell growth, apoptosis and cell cycle regulation in human oral squamous carcinoma HSC-3 cells were examined. Berberine induced dose- and time-dependent irreversible inhibition of cell growth and cellular DNA synthesis. This was also confirmed by phase-contrast microscopy which showed that berberine induced morphological changes in HSC-3 cells. Propidium iodide/annexin V staining for flow cytometric analysis showed that berberine-induced apoptosis correlated with caspase-3 activation. Flow cytometric studies of the cell cycle distribution showed that berberine induced mainly G0/G1-phase arrest. Flow cytometric examinations also showed that berberine induced reactive oxygen species (ROS) and Ca2+ production, as well as the dysfunction of mitochondrial membrane potential (MMP), which were correlated with apoptosis. In conclusion, our data support that berberine initially induces an endoplasmic reticulum stress response based on ROS and Ca2+ production which is followed by dysfunctions of the mitochondria, resulting in apoptosis of these oral cancer HSC-3 cells. Prolonged exposure of the HSC-3 cells to berberine causes increased apoptosis through reduced levels of MMP, release of cytochrome c and activation of caspase-3.
Berberine has a wide range of biological actions that suggest it may be of use in cancer prevention. It was previously reported that berberine induced cell cycle arrest, not only at the G0/G1-phase, ...but also at the G2/M-phase in a dose-dependent manner. However, the mechanism of berberine-induced G2/M-phase arrest in leukemia cells is not fully understood. In the present study, the effects of the naturally occurring berberine (the major constituent of Coptis chinensis) on the cell cycle, as well as on CDK1, cyclin B1, 14-3-3sigma, Wee1 and Cdc25c expressions, were investigated in the human promyelocytic leukemia HL-60 cells and in the murine myelomonocytic leukemia WEHI-3 cells. The flow cytometry assays indicated that berberine induced G2/M-phase arrest in both examined cell lines. The berberine-induced G2/M-phase arrest in both examined cell lines was accompanied by increased levels of Wee1 and 14-3-3sigma, but decreased levels of Cdc25c, CDK1 and cyclin B1. However, CDK2 expression was not affected as revealed by Western blotting assay. Berberine induced G2/M arrest in both the examined cells via the inhibition of cyclin B1 and the promotion of Wee1.
Taiwanofungus camphoratus is a unique medicinal mushroom endemic to Taiwan, and it is used as a folk medicine in East Asian countries. The aim of the present study was to investigate the ...immunomodulatory effects of "leader Antrodia cinnamomea capsule" (LAC), a health food product containing solid-state cultivated mycelial powder of T. camphoratus. For the in vivo studies, mice were orally administered LAC (76, 250, and 760 mg/kg b.w.) for 30 days, and its effects on cell-mediated humoral immune function were examined. The results of the concanavalin A-induced splenic lymphocyte proliferation test showed that LAC significantly increased splenic lymphocyte proliferation compared with the control. In addition, serum hemolysin analysis showed that LAC treatment significantly increased the half value of serum hemolysin (HC50) in mice compared with the control. Moreover, treatment with LAC significantly increased the phagocytic index as measured by carbon clearance and natural killer cell activity. Taken together, these findings provide strong evidence that LAC can modulate immune function.
Abstract
Therapeutic administration of glucocorticoids (GCs) is frequently used as add-on chemotherapy for palliative purposes during breast cancer treatment. Recent studies have shown that GC ...treatment induces microRNA-708 in ovarian cancer cells, resulting in impaired tumor cell proliferation and metastasis. However, the regulatory functions of GCs on miR-708 and its downstream target genes in human breast cancer cells (BCCs) are poorly understood. In this study, we found that treatment with either the synthetic GC dexamethasone (DEX) or the natural GC mimic, antcin A (ATA) significantly increased miR-708 expression by transactivation of glucocorticoid receptor alpha (GRα) in MCF-7 and MDA-MB-231 human BCCs. Induction of miR-708 by GR agonists resulted in inhibition of cell proliferation, cell-cycle progression, cancer stem cell (CSC)-like phenotype and metastasis of BCCs. In addition, GR agonist treatment or miR-708 mimic transfection remarkably inhibited IKKβ expression and suppressed nuclear factor-kappaB (NF-κB) activity and its downstream target genes, including COX-2, cMYC, cyclin D1, Matrix metalloproteinase (MMP)-2, MMP-9, CD24, CD44 and increased p21CIP1 and p27KIP1 that are known to be involved in proliferation, cell-cycle progression, metastasis and CSC marker protein. BCCs xenograft models indicate that treatment with GR agonists significantly reduced tumor growth, weight and volume. Overall, our data strongly suggest that GR agonists induced miR-708 and downstream suppression of NF-κB signaling, which may be applicable as a novel therapeutic intervention in breast cancer treatment.
Chloroplast genetic engineering is an environmentally friendly approach, where the foreign integrated gene is often expressed at a higher level than nuclear transformation. The cry1Ab gene was ...successfully transferred into the cabbage chloroplast genome in this study. The aadA and cry1Ab genes were inserted into the pASCC201 vector and driven by the prrn promoter. The cabbage-specific plastid vectors were transferred into the chloroplasts of cabbage via particle gun mediated transformation. Regenerated plantlets were selected by their resistance to spectinomycin and streptomycin. According to antibiotic selection, the regeneration percentage of the two cabbage cultivars was 4-5%. The results of PCR, Southern, Northern hybridization and western analyses indicated that the aadA and cry1Ab genes were not only successfully integrated into the chloroplast genome, but functionally expressed at the mRNA and protein level. Expression of Cry1Ab protein was detected in the range of 4.8-11.1% of total soluble protein in transgenic mature leaves of the two species. Insecticidal effects on Plutella xylostella were also demonstrated in cry1Ab transformed cabbage. The objectives of this study were to establish a gene transformation system for Brassica chloroplasts, and to study the possibility for insect-resistance in dicot vegetables using chloroplast gene transformation.
Antrodia cinnamomea is a valuable and unique edible fungus originating from the forests of Taiwan. In this study, an anti-metastatic compound, 2,3,5-trimethoxy-4-cresol (TMC), was isolated from the ...solid-state cultured mycelium of A. cinnamomea. According to the results obtained from cell wound healing, cell migration and invasion assays, TMC effectively suppressed movement, migration and invasion of lung cancer cells at the dosage of 5–40 μM, which was non-toxic to A549 cells. In addition, TMC reduced protein expression of Akt, MMP-2 and MMP-9 and enhanced E-cadherin and TIMP-1 protein expression, which are known to regulate cell adhesion, migration and invasion. Taken together, TMC effectively suppresses movement, migration and invasion of lung cancer cells, and achieves an anti-cancer metastasis effect.
is a rare and endemic medicinal mushroom native to Taiwan. The pharmacological effects of
have been extensively studied. The aim of the present study was to assess the genotoxic, oral toxic and ...teratotoxic effects of
health food product ⿿Leader Deluxe
(LDAC)⿿⿿ using in vitro and
tests. The Ames test with 5 strains of Salmonella typhimurium showed no signs of increased reverse mutation upon exposure to LDAC up to concentration of 5 mg/plate. Exposure of Chinese Hamster Ovary cells (CHO-K1) to LDAC did not produce an increase in the frequency of chromosomal aberration in vitro. In addition, LDAC treatment did not affect the proportions of immature to total erythrocytes and the number of micronuclei in the immature erythrocytes of ICR mice. Moreover, 14-days single-dose acute toxicity and 90-days repeated oral dose toxicity tests with rats showed that no observable adverse effects were found. Furthermore, after treatment with LDAC (700⿿2800 mg/kg/day) there was no evidence of observable segment II reproductive and developmental toxic effects in pregnant SD rats and their fetuses. These toxicological assessments support the safety of LDAC for human consumption.
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