Anti-Inflammatory Ergostanes from the Basidiomata of <i>Antrodia salmonea</i>

Shen, Chien‐Chang; Wang, Yea‐Hwey; Chang, Tun-Tschu; Lin, Lie‐Chwen; Don, Ming‐Jaw; Hou, Yanan; Liou, Kuo-Tong; Chang, Shiou; Wang, Wen-Yen; Ko, Han-Chieh; Shen, Yung Kang

doi:10.1055/s-2007-981591

Cited by 36 publications

(24 citation statements)

References 11 publications

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“…Activation of DC by a triterpenoid me-Ant K We have identified some unique triterpenoids isolated from the fruiting bodies of Ac and As and evaluated their biological effects [23,[35][36][37][38]. However, their immunomodulatory activity is not known.…”

Section: Resultsmentioning

confidence: 99%

“…All triterpenoids were isolated from fruiting bodies of Ac or As by a series of chromatographic cycles and HPLC, and the structures were determined by various spectrometers and NMR [23,[35][36][37][38]. Briefly, the chipped fruiting bodies were extracted with water, and then the residue of the fruiting bodies was refluxed with ethanol.…”

Section: Preparation Of Triterpenoids From Ac and Asmentioning

confidence: 99%

“…In this study, we tested the effect of these triterpenoids on mouse bone marrow-derived DC (BMDC). Methyl antcinate K (me-AntK), a recently identified triterpenoid isolated from Ac (unpublished data) or another mushroom Antrodia salmonea (As) [38], was shown to display potent stimulating activity on DC. …”

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confidence: 99%

“…1A). To determine the effect of these triterpenoids on DC, we first examined the BMDC cultures by microscopy after treatment of these compounds for 16 h. All compounds had 490-95% purity and were used at 50 mM as the maximal bioactivity was shown at this concentration for some compounds [23,36,38]. In addition, all compounds had no significant cytotoxicity at this dose as measured by PI staining (data not shown).…”

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confidence: 99%

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A triterpenoid methyl antcinate K isolated from Antrodia cinnamomea promotes dendritic cell activation and Th2 differentiation

Chen

Shen

et al. 2009

Eur J Immunol

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Dendritic cells (DC) play a central role in the initiation and regulation of immune responses.Increasing evidence has indicated that manipulation of DC can serve as a therapeutic mechanism for immunomodulation. In this study we tested some unique compounds isolated from Antrodia cinnamomea, a medicinal fungus in Taiwan, on mouse bone marrowderived DC activation. A triterpenoid methyl antcinate K (me-AntK) promoted DC maturation by enhancing the expression of MHC class II, CD86, and reducing the endocytosis. TNF-a, MCP-1, and MIP-1b were secreted by DC after me-AntK treatment, indicating augmentation of innate immunity by me-AntK. Interestingly, the me-AntK-activated DC induced Ag-specific T-cell proliferation and facilitated Th2 differentiation. Examining signaling responses, we found that me-AntK treatment uniquely activated JNK and ERK in DC. Our results demonstrate that me-AntK is the first natural triterpenoid to promote the ability of DC to prime Th2 responses. This suggests that me-AntK can potentially be applied to enhance immune responses and modulate DC function in immunotherapy.Key words: DC . Immunomodulation . Th2 . Triterpenoid Supporting Information available online Introduction DC are specialized leukocytes which take up and process Ag in peripheral tissues and then transport and present Ag to activate T cells in secondary lymphoid organs [1,2]. DC are heterogeneous but all subsets have intrinsic and cooperative Ag-presenting function [3,4]. Exposure of DC to pathogen products or pro-inflammatory stimuli induces DC maturation, which dramatically enhances the ability of DC to activate Ag-specific T cells [5]. TLR are important receptors involved in detection of PAMP in DC. TLR ligation induces the activation of NF-kB and MAP kinase pathways, resulting in DC maturation, which is characterized by upregulation of MHC class II and costimulatory molecule expression as well as cytokine and chemokine production [6]. Befitting the key regulatory role of DC in 2482immune responses, DC are being developed for the treatment of cancers, allergies, and viral infections, and as adjuvants for potent new vaccines to prevent or treat cancers and infectious diseases [7,8]. Thus, DC are manipulated as pharmacological targets for discovering novel biological modifiers of immune responses [9][10][11].Natural products and their derivatives have historically been a rich source of therapeutic agents and lead molecules in drug discovery [12]. A number of biologically active natural products have been isolated from Aphyllophorales, many of which are known as polypores. Polypores are a large group of terrestrial fungi of the phylum Basidiomycota (basidiomycetes), and they are a major source of pharmacologically active substances [13]. For example, Ganoderma lucidum (Ling Zhi or Reishi), a wellknown fungus that has been used for medicinal purposes for centuries, has been studied extensively [14,15]. A precious basidiomycete Antrodia cinnamomea [syn. A. camphorata] (Ac) restrictively grows in a unique host, the endemic and en...

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Section: Resultsmentioning

confidence: 99%

Section: Preparation Of Triterpenoids From Ac and Asmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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A triterpenoid methyl antcinate K isolated from Antrodia cinnamomea promotes dendritic cell activation and Th2 differentiation

Chen

Shen

et al. 2009

Eur J Immunol

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“…Among these steroid-like compounds, antcins, a unique group having ergostane skeletons, are only found in Niuchangchih to date. Anti-inflammatory, anti-insecticidal and cytotoxic activities have been observed in various antcins and their derivatives [10][11][12][13][14][15][16] .…”

Section: Introductionmentioning

confidence: 99%

Antcin A, a steroid-like compound from Antrodia camphorata, exerts anti-inflammatory effect via mimicking glucocorticoids

Chen¹,

Liu

et al. 2011

Acta Pharmacol Sin

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Aim: To determine the active ingredient of Niuchangchih (Antrodia camphorata) responsible for its anti-inflammatory effects and the relevant molecular mechanisms. Methods: Five major antcins (A, B, C, H, and K) were isolated from fruiting bodies of Niuchangchih. Structural similarity between the antcins and 2 glucocorticoids (cortisone and dexamethasone) was compared. After incubation with each compound, the cytosolic glucocorticoid receptor (GR) was examined for its migration into the nucleus. Mo lecular docking was performed to model the tertiary structure of GR associated with antcins. Results: Incubation with cortisone, dexamethasone or antcin A (but not antcins B, C, H, and K) led to the migration of glucocorticoid receptor into the nucleus. The minimal concentration of antcin A, cortisone and dexamethasone to induce nuclear migration of glucocorticoid receptor was 10, 1, and 0.1 mol/L, respectively. The results are in agreement with the simulated binding affinity scores of these three ligands docking to the glucocorticoid receptor. Molecular modeling indicates that C-7 of antcin A or glucocorticoids is exposed to a hydrophobic region in the binding cavity of the glucocorticoid receptor, and the attachment of a hydrophilic group to C-7 of the other four antcins presumably results in their being expelled when docking to the cavity. Conclusion: The anti-inflammatory effect of Niuchangchih is, at least, partly attributed to antcin A that mimics glucocorticoids and triggers translocation of glucocorticoid receptor into nucleus to initiate the suppressing inflammation.

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Antrodia salmonea‐induced oxidative stress abrogates HER‐2 signaling cascade and enhanced apoptosis in ovarian carcinoma cells

Yang

Lin

Rajendran

et al. 2018

Journal Cellular Physiology

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Antrodia salmonea is well known in Taiwan as a traditional Chinese medicinal fungus and has demonstrated antioxidant, anti-inflammatory, and anticancer effects. However, the anticancer activity of A. salmonea against human ovarian cancer is still elusive. Therefore, we investigated the antiovarian tumor activity of a fermented culture broth of A. salmonea and exhibits its underlying molecular mechanism. A. salmonea shows a significant effect on cell viability in human ovarian carcinoma (SKOV-3 or A2780) cell lines with an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Increased terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells and annexin V-propidium iodide stained cells indicate that A. salmonea induces late apoptosis in SKOV-3 cells. Notably, treatment with A. salmonea induced the following events: Apoptosis; caspase-3, -8, -9 and poly(ADP-ribose) polymerase activation; first apoptosis signal (Fas) and Fas ligand activation; Bid cleavage; and Bax2-B-cell lymphoma 2 dysregulation. The results show that A. salmonea-induced apoptosis was mediated by both mitochondrial and death receptor pathways. An increase in intracellular reactive oxygen species (ROS) was also observed in A. salmonea-treated cells, whereas the antioxidant N-acetylcysteine (NAC) prevented A. salmonea-induced cell death and DNA fragmentation, indicating that A. salmonea-induced apoptosis was mediated by ROS generation. Interestingly, A. salmonea-induced apoptosis is associated with the suppression of human epidermal growth factor receptor-2 (HER-2/neu) and phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) expression in HER-2/neu overexpressing SKOV-3 cells. NAC significantly prevented A. salmonea-induced HER-2/neu depletion and PI3K/AKT inactivation, indicating that A. salmonea-triggered apoptosis is mediated by ROS-inhibited HER-2/neu signaling cascades. To our knowledge, this is the first report describing the anticancer activity of this potentially beneficial mushroom against human ovarian carcinoma.

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Anti-Inflammatory Ergostanes from the Basidiomata of Antrodia salmonea

Cited by 36 publications

References 11 publications

A triterpenoid methyl antcinate K isolated from Antrodia cinnamomea promotes dendritic cell activation and Th2 differentiation

A triterpenoid methyl antcinate K isolated from Antrodia cinnamomea promotes dendritic cell activation and Th2 differentiation

Antcin A, a steroid-like compound from Antrodia camphorata, exerts anti-inflammatory effect via mimicking glucocorticoids

Antrodia salmonea‐induced oxidative stress abrogates HER‐2 signaling cascade and enhanced apoptosis in ovarian carcinoma cells

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