Characterization of Cinnamomum kanehirae Extract-Stimulated Triterpenoids Synthesis in Submerged Fermentation of Antrodia camphorata via Untargeted Metabolomics.

The underlying mechanisms of Cinnamomum kanehirae-stimulated growth and metabolism of Antrodia camphorata remain unknown. Herein, we first observed that the methanol extract of C. kanehirae trunk (MECK) (2 g/L) showed a potent stimulatory effect on A. camphorata triterpenoids production (115.6 mg/L). Second, MECK treatment considerably increased the category and abundance of many secondary metabolites in the mycelia. We identified 93 terpenoids (8 newly formed and 49 upregulated) in the MECK-treated mycelia, wherein 21 terpenoids were the same as those in the fruiting bodies. Third, 42 out of the 93 terpenoids were annotated in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, mainly involving monoterpenoids and diterpenoids syntheses. Finally, 27 monoterpenes and 16 sesquiterpenes were detected in the MECK, and the two terpenoids with the highest abundance (linalool and α-pinene) were selected for verification and found to considerably increase the terpenoids production of A. camphorata and demonstrate the regulation of mRNA expression levels of nine key genes in the mevalonate pathway via RT-qPCR. This study is beneficial for elucidating the terpenoids synthesis mechanism in A. camphorata.

Selenium Enrichment of the Edible Medicinal Mushroom Antrodia camphorata by Submerged Fermentation.

Selenium (Se) is an essential nutrient element in human physiological metabolism and immune function. Supplementation of bioavailable Se will confer benefit on human life, especially when intake of this nutrient is inadequate. The edible and medicinal mushroom Antrodia camphorata is a unique fungus endemic to Taiwan, which has shown high therapeutic and nutritive value. This study is the first to demonstrate that A. camphorata can assimilate and transform sodium selenite into organic selenium. With an initial concentration of Se (IV) at 10 mg/L in 100 mL of the medium at 25 °C, the total selenium content in Se-enriched A. camphorata mycelia was 1281.3 ± 79.2 µg/g, in which the organic selenium content accounted for 88.1%. Further analysis demonstrated that selenium-enriched polysaccharide was the main form of Se present in A. camphorata (61.5% of the organic selenium). Four water-soluble Se-polysaccharide fractions were separated from A. camphorata, and ACP II was the major fraction of Se-polysaccharide. The scavenging efficiency of Se-polysaccharides on DPPH and ABTS radicals was determined, proving that selenium enrichment dramatically improved the in vitro antioxidant capacity of A. camphorata polysaccharide. Therefore, the selenium accumulation and transformation ability of A. camphorata provides an opportunity for developing this beneficent fungus into a novel selenium-enriched dietary or medicinal supplement.

ZnF3, a sulfated polysaccharide from Antrodia cinnamomea, inhibits lung cancer cells via induction of apoptosis and activation of M1-like macrophage-induced cell death.

Sulfated polysaccharides (Ac-SPSs) of Antrodia cinnamomea present anti-cancer activity. However, the anti-cancer mechanism of Ac-SPSs is not fully understood and remains largely unexplored. In this study, we identify an Ac-SPS with 7.9 kDa, noted ZnF3, and aim to examine the dual anti-cancer functions of ZnF3 on inhibiting cancer cells and activating macrophages. A biological study shows that ZnF3 inhibits lung cancer cells by inducing subG1 population and apoptosis. ZnF3 downregulates the expression of TGFß receptor in lung cancer cells. In parallel, ZnF3 activates macrophages via induction of TNF-α and IL-6 secretion, NO production and phagocytosis. ZnF3 activates AKT/mTOR pathway and induces M1 type macrophage polarization. Cancer cells co-cultured with ZnF3-stimulated macrophages, leading to inhibition of lung cancer cells. This study demonstrates that ZnF3 not only directly inhibits cancer cells but also activates macrophages-mediated cytotoxic effect on cancer cells. Moreover, ZnF3 may be a supplement for suppressing lung cancer cells.

A review on the protective effect of active components in Antrodia camphorata against alcoholic liver injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Antrodia camphorata is a genus of wood-rot basidiomycete in the family Fomitopsidaceae. It is a valuable medicinal fungus in China that contains more than 78 kinds of active compounds. A. camphorata has good protection effects on the liver, especially on alcoholic liver injury (ALI). AIM: This paper summarizes the complex occurrence and development of alcoholic liver disease (ALD). In addition, the effect of ALD on the intestine through the gut-liver axis is summarized. The protective mechanism of A. camphorata on ALI is reviewed to reveal its therapeutic potential, offering insights into future research. MATERIALS AND METHODS: A comprehensive search in the literature was obtained from books and online databases such as Web of Science, Google Scholar, PubMed, Scopus, Science direct, ACS Publications and Baidu Scholar. RESULTS: The pathogenesis of ALD mainly includes oxidative stress injury, intestinal microflora imbalance, inflammatory mediator injury and nutritional imbalance. A. camphorata contains rich active components (e.g. polysaccharides, triterpenoids, maleic and succinic acid derivatives, amino acids, superoxide dismutase, vitamins, lignin and sterols). These components have good antioxidant, anti-inflammatory and intestinal protection activities. Therefore, A. camphorata has a wide application in the prevention and treatment of ALI. CONCLUSIONS: ALD develops from a mild disease to alcoholic hepatitis and cirrhosis, which is the main reason of global morbidity and mortality. At present, there is no effective drug for the treatment of ALD. A. camphorata, as a valuable medicinal fungus unique to Taiwan, has a great protective effect on the liver. It is expected to be an effective drug for ALI treatment. Although many studies have performed the protective effects of A. camphorata on ALI, its regulatory effects on the gut-liver axis of ALD patients need to be further explored.

A network pharmacology-based strategy to explore the pharmacological mechanisms of Antrodia camphorata and antcin K for treating type II diabetes mellitus.

BACKGROUND: Diabetes mellitus is a chronic carbohydrate metabolism disorder, which could develop a series of complications and thus lead to poor quality of life or even mortality. Antrodia camphorata is a rare parasitic fungus and has been proven to be effective for treating type II diabetes. PURPOSE: This study aims to evaluate the anti-diabetic activities of A. camphorata and its main compound antcin K, as well as to demonstrate the mechanisms. STUDY DESIGN AND METHODS: Network pharmacology was used to explore the potential targets of 12 major compounds of A. camphorata on diabetes. The core targets were analyzed by protein-protein interactions and the key pathways were enriched by Kyoto Encyclopedia of Genes and Genomes (KEGG). The anti-diabetic effects of A. camphorata and antcin K were evaluated using a high-fat diet (HFD)-induced diabetic mice model and oral glucose tolerance test (OGTT). The mRNA expressions were assessed using qPCR. RESULTS: Network pharmacology revealed 17 core targets between the 12 compounds and diabetes. The insulin resistance and NF-κB signaling pathways were enriched using KEGG. Five insulin resistance-related targets were focused on and antcin K (1/2) was discovered in the compound-target-pathway network. In vivo studies exhibited that A. camphorata and antcin K could dose-dependently reduce blood levels of glucose and lipids, decrease serum levels of insulin and leptin, and increase serum levels of adiponectin in HFD mice (p < 0.05). The mechanism could be through modulating the expressions of Tnfα, Il6, and Pparγ. The OGTT test also showed the down-regulatory effects of A. camphorata and antcin K on blood glucose. CONCLUSION: This study demonstrates that A. camphorata and its major compound antcin K possess potent anti-diabetic effects. The mechanism may be through the insulin resistance pathway.

Antrodin A from Antrodia camphorata modulates the gut microbiome and liver metabolome in mice exposed to acute alcohol intake.

This study aimed to investigate the protective effect of Antrodin A (AdA) from Antrodia camphorata (A. camphorata) mycelium on alcohol-induced gut microbiota and liver metabolomic disorders. In acute alcoholic liver injury mice, AdA ameliorated alcoholic exposure-induced hepatic lipid deposition (TC and TG), oxidative stress (MDA), inflammation (TNF-α, IL-1ß, IL-6, IL-17 and IFN-γ), and liver damage via modulating microbiome and metabolomic responses. AdA restored the composition of intestinal flora with an increase in the relative abundance of Lactobacillus and Dubosiella and a decrease in Clostridium_sensu_stricto_1, Lachnospiraceae_NK4A136_group, Prevotellaceae_NK3B31_group, and Prevotellaceae_UCG-001. Besides, AdA favorably regulated alcohol-induced metabolic disorders, including glutathione metabolism (S-(2-hydroxyethyl)glutathione and glutathione oxidized), ascorbate and aldarate metabolism (l-ascorbic acid), and taurine and hypotaurine metabolism (taurine). In conclusion, AdA in A. camphorata is a beneficial active ingredient to treat the microbiomic and metabolic disturbance induced by alcohol intake.

Antrodia cinnamomea Inhibits Growth and Migration of Lung Cancer Cells through Regulating p53-Bcl2 and MMPs Pathways.

Antrodia cinnamomea has been shown to possess antitumor activity. This study investigated the effects and mechanisms of Antrodia cinnamomea extract (ACE) on growth and migration of human non-small cell lung cancer A549 cells. The effect of ACE on cell viability was determined by MTT assay and fluorescent live-cell imaging. The apoptotic effect of ACE was determined by cell cycle distribution using flow cytometry. A P53-mediated apoptosis pathway was identified by measuring protein expression of p53 and Bcl-2 with Western blotting. Additionally, mRNA expression of p53 and Bcl-2 and Bax was detected by qRT-PCR. The effect of ACE on cancer cell migration was confirmed by a wound-healing assay. Expression of MMP-2 and MMP-9 at the protein and gene levels was determined by western blot and qRT-PCR analysis. This study demonstrates the inhibitory effect of ACE on A549 cell proliferation in a dose-response manner with an [Formula: see text]. It was determined that ACE concentration at [Formula: see text] induced cell cycle arrest at S phase in A549 cells. The apoptosis-regulating protein p53 expression was enhanced and also associated with the downregulation of Bcl-2 in ACE treatment cells. The mRNA expression of p53 and Bcl-2 associated with Bxa was consistent with protein expression. The inhibition of migration of cancer cells treated with ACE was clearly evident. At the same time, suppression of expression of MMP-2 and MMP-9 at protein and mRNA levels was observed. The findings of this study highlight ACE as a potential agent of adjuvant therapy for lung cancer.

4-Acetylantrocamol LT3, a New Ubiquinone from Antrodia cinnamomea, Inhibits Hepatocellular Carcinoma HepG2 Cell Growth by Targeting YAP/TAZ, mTOR, and WNT/ß-Catenin Signaling.

4-acetylantrocamol LT3 (4AALT3), a new ubiquinone from the mycelium of Antrodia cinnamomea (Polyporaceae), has been recently shown to possess anticancer activity. However, the detailed mechanisms of such action remain unclear. In this study, the molecular mechanisms of 4AALT3 on hepatocellular carcinoma cells (HCC) were investigated. Human hepatocellular carcinoma cell line HepG2 cells were treated with concentrations of 4AALT3. Cell viability, colony formation, and the underlying mechanisms were then analyzed by CCK-8, colony formation, qPCR, and Western blotting assays. We found that 4AALT3 significantly decreased cell viability and colony formation in a dose-dependent manner. Accordingly, 4AALT3 significantly decreased protein levels of cyclin B, E1, D1, and D3, thereby facilitating cell cycle arrest. In addition, 4AALT3 significantly suppressed the nuclear localization of Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ), mammalian target of rapamycin (mTOR), and WNT/[Formula: see text]-catenin signaling pathways, all of which are well-known signaling pathways that contribute to the malignant properties of HCC. These effects are associated with activation of 5' AMP-activated protein kinase (AMPK) and autophagy. Our findings indicate that 4AALT3 exerts inhibitory effects on HepG2 cell growth via multiple signaling pathways and may be a potential agent for HCC therapy.

Nanoparticles of Antroquinonol-Rich Extract from Solid-State-Cultured Antrodia cinnamomea Improve Reproductive Function in Diabetic Male Rats.

PURPOSE: To characterize the nanoparticle of antroquinonol from A. cinnamomea and its ameliorative effects on the reproductive dysfunction in the diabetic male rat. MATERIAL AND METHODS: The chitosan-silicate nanoparticle was used as the carrier for the delivery of antroquinonol from solid-state-cultured A. cinnamomea extract (AC). The rats were fed with a high-fat diet and intraperitoneally injected with streptozotocin to induce diabetes. The rats were daily oral gavage by water [Diabetes (DM) and Control groups], three different doses of chitosan-silicate nanoparticle of antroquinonol from solid-state-cultured A. cinnamomea (nano-SAC, NAC): (DM+NAC1x, 4 mg/kg of body weight; DM+NAC2x, 8 mg/kg; and DM+NAC5x, 20 mg/kg), solid-state-cultured AC (DM+AC5x, 20 mg/kg), or metformin (DM+Met, 200 mg/kg) for 7 weeks. RESULTS: The nano-SAC size was 37.68±5.91 nm, the zeta potential was 4.13±0.49 mV, encapsulation efficiency was 79.29±0.77%, and loading capacity was 32.45±0.02%. The nano-SAC can improve diabetes-induced reproductive dysfunction by regulating glucose, insulin, and oxidative enzyme and by increasing the level of testosterone, follicle-stimulating hormone, luteinizing hormone, and sperm count as well as sperm mobility. In testicular histopathology, the seminiferous tubules of A. cinnamomea-supplemented diabetic rats showed similar morphology with the control group. CONCLUSION: The nanoparticle of antroquinonol from Antrodia cinnamomea can be used as an effective strategy to improve diabetes-induced testicular dysfunction.

The Leaf Extracts of Toona sinensis and Fermented Culture Broths of Antrodia camphorata Synergistically Cause Apoptotic Cell Death in Promyelocytic Leukemia Cells.

Toona sinensis is a common edible vegetable that is used in certain Chinese dishes and has importance in folk medicine. The leaf extracts of T sinensis possess and exhibit anticancer efficacy against various cancer cell types. In Taiwanese folklore, Antrodia camphorata, also known as "Niu-Cheng-Zi," is used in traditional medicine to treat various illnesses. Its fruit and mycelium possess various potent antiproliferative properties. Two studies from our group have reported that T sinensis or A camphorata has the ability to cause apoptosis in various cancer cells. Conversely, underlying molecular mechanisms and any beneficial effects remain unknown. This study shows anticancer efficacy for both T sinensis and A camphorata co-treatments that target HL-60 cells. The combination index values indicate that 40 µg/mL of T sinensis and 25 µg/mL of A camphorata as a combined treatment shows a synergetic effect, which reduces HL-60 cell proliferation. Alternately, this treatment exhibited no cytotoxic effects for human umbilical vein endothelial cells. Western blot data showed that T sinensis and A camphorata as a combined treatment result in augmented expression of apoptosis, cytochrome c release, Bcl-2 inhibition, expression of Bax, Fas, and FasL, as well as the cleavage of Bid in HL-60 cells. Moreover, this combined treatment overshadowed monotherapy in its ability to inhibit uPAR, MMP-9, MMP-2, COX-2 expression, and PGE2 secretions. Our study strongly implies that this combined treatment offers more beneficial effects to suppress and treat leukemia due to apoptosis-mediated cell inhibition. Further in vivo studies related to the combined treatment could establish its future potential.

Antrodia cinnamomea is a potentially effective complementary medicine for adjuvant therapy against breast cancer with bone metastasis: A case report.

RATIONALE: Palbociclib (PAL) is a first-in-class selective inhibitor of the cyclin-dependent kinases 4 (CDK4) and CDK6 and is indicated for the treatment of hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) in combination with fulvestrant (FUL) in postmenopausal women. Antrodia cinnamomea (AC), a well-known Chinese folk medicine in Taiwan, possesses numerous biological capabilities, most notably an anti-tumor effect. However, the clinical use of AC as complementary medicine combined with adjuvant therapy is unexplored. In this case report, we evaluated AC combined with PAL plus FUL to reduce the tumor burden in an MBC patient. PATIENT CONCERNS: A Slovenian woman diagnosed with relapsed bone metastases of breast cancer (BC) was unable to undergo surgery and refused radiation therapy due to fear of side effects; she also feared the side effects of adjuvants. However, she was eager to live with a high quality of life. DIAGNOSIS: Stage IV, HR-positive/HER2-negative BC with relapse of bone metastases. INTERVENTIONS: After diagnosis of relapse of bone metastases, she received adjuvant with PAL plus FUL. Additionally, she chose to take AC orally (10 g/d). OUTCOMES: The pain was mostly relieved, and the side effects of adjuvant therapy reduced. Magnetic resonance imaging revealed reduction of tumor size at the fifth month of adjuvant therapy plus AC. After 14 months of adjuvant therapy plus AC, the tumors at the thoracic vertebrae T1 and T3 were found to have shrunk from 35.2 and 12.0 mm to 28.1 and 9.9 mm, respectively. Remarkably, no further metastases were observed. LESSONS: According to the circulating tumor cells (CTCs) test data, AC had better anti-tumor efficacy on active tumor cells than PAL plus FUL. Thus, AC could be an effective complementary medicine for adjuvant therapy in patients with HR-positive/HER2-negative MBC. Interestingly, continued elevation of carcinoma antigen 15-3 and lactate dehydrogenase levels but decreasing levels of alkaline phosphatase were observed, which may be indicative of the potent efficacy of treatment resulting in massive tumor cell death. The CTCs test may be a sensitive approach to monitor the progression of BC and subsequently evaluate the efficiency of therapy.

Oxidative Stress Induction Is a Rational Strategy to Enhance the Productivity of Antrodia cinnamomea Fermentations for the Antioxidant Secondary Metabolite Antrodin C.

Antioxidant metabolites contribute to alleviating oxidative stress caused by reactive oxygen species (ROS) in microorganisms. We utilized oxidative stressors such as hydrogen peroxide supplementation to increase the yield of the bioactive secondary metabolite antioxidant antrodin C in submerged fermentations of the medicinal mushroom Antrodia cinnamomea. Changes in the superoxide dismutase and catalase activities of the cells indicate that ROS are critical to promote antrodin C biosynthesis, while the ROS production inhibitor diphenyleneiodonium cancels the productivity-enhancing effects of H2O2. Transcriptomic analysis suggests that key enzymes in the mitochondrial electron transport chain are repressed during oxidative stress, leading to ROS accumulation and triggering the biosynthesis of antioxidants such as antrodin C. Accordingly, rotenone, an inhibitor of the electron transport chain complex I, mimics the antrodin C productivity-enhancing effects of H2O2. Delineating the steps connecting oxidative stress with increased antrodin C biosynthesis will facilitate the fine-tuning of strategies for rational fermentation process improvement.

Antrodin A from mycelium of Antrodia camphorata alleviates acute alcoholic liver injury and modulates intestinal flora dysbiosis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Antrodia camphorata (A. camphorata) is a rare functional fungus in Taiwan and contains a variety of biologically active ingredients. Antrodin A (AdA) is one of the main active ingredients in the solid-state fermented A. camphorata mycelium. It protects the liver from alcohol damage by improving the antioxidant and anti-inflammatory capacity of the liver and maintaining the stability of the intestinal flora. AIM OF THE STUDY: The aim of this study was to evaluate the hepatoprotective activities of ethyl acetate layer extract (EALE), AdA, and Antroquinonol (Aq) from mycelium of A. camphorata on alcoholic liver injury. MATERIALS AND METHODS: Mice were given with intragastrically vehicle (NC, 2% CMC-Na), alcohol (AL, 12 mL/kg bw), or different A. camphorata samples (EALE, AdA, Aq) at low (100 mg/kg bw) or high (200 mg/kg bw) dosages. The positive control (PC) group was given with silymarin (200 mg/kg bw). Except the NC group, each group of mice was fasted for 4 h after the last treatment and was intragastrically administrated with 50% alcohol (12 mL/kg bw). At the end of experiment, mouse serum was collected and the liver was excised. A portion of the liver was fixed in formalin and used for histopathological analysis, whereas the rest was used for biochemical analysis and real-time PCR analysis. The intestinal flora structure of feces was analyzed by determining the v3-v4 region sequence in 16S rDNA. RESULTS: The high-dose groups of the three samples (EALEH, AdAH, and AqH) significantly alleviated the alcohol-induced increases in liver index, serum ALT, AST, and AKP activities. Serum TG level was significantly reduced in all treatment groups. The increase of HDL-C content indicated that active ingredients of A. camphorata could reduce the lipid content in serum. Furthermore, MDA contents of the AdAH and AqH groups in liver were significantly reduced, accompanying with the levels of SOD, CAT, and GSH elevated to various extents. Antioxidant and anti-inflammatory capabilities in the liver were increased in the AdAH group, as evidenced by the mRNA expression levels of Nrf-2 and HO-1 were significantly increased; while those of CYP2e1, TNF-α, and TLR-4 were significantly decreased. Analysis of intestinal flora of feces showed that alcohol treatment significantly changed the composition of intestinal flora. Supplementation with AdA could mitigate dysbiosis of intestinal flora induced by alcohol. Flora of Faecalibaculum, Lactobacillus, and Coriobacteriaceae_UCG-002 showed significantly negative correlations with ALT, AST, AKP, and MDA levels. CONCLUSION: Antrodin A could improve the antioxidant and anti-inflammatory capacities of the liver and maintain the stability of intestinal flora. It is potentially a good candidate compound against acute alcoholic liver injury.

Antrodan Alleviates High-Fat and High-Fructose Diet-Induced Fatty Liver Disease in C57BL/6 Mice Model via AMPK/Sirt1/SREBP-1c/PPARγ Pathway.

Non-alcoholic fatty liver disease (NAFLD) and -steatohepatitis (NASH) imply a state of excessive fat built-up in livers with/or without inflammation and have led to serious medical concerns in recent years. Antrodan (Ant), a purified ß-glucan from A. cinnamomea has been shown to exhibit tremendous bioactivity, including hepatoprotective, antihyperlipidemic, antiliver cancer, and anti-inflammatory effects. Considering the already well-known alleviating bioactivity of A. cinnamomea for the alcoholic steatohepatitis (ASH), we propose that Ant can be beneficial to NAFLD, and that the AMPK/Sirt1/PPARγ/SREBP-1c pathways may be involved in such alleviations. To uncover this, we carried out this study with 60 male C57BL/6 mice fed high-fat high-fructose diet (HFD) for 60 days, in order to induce NAFLD/NASH. Mice were then grouped and treated (by oral administration) as: G1: control; G2: HFD (HFD control); G3: Ant, 40 mgkg (Ant control); G4: HFD+Orlistat (10 mg/kg) (as Orlistat control); G5: HFD+Ant L (20 mg/kg); and G6: HFD+Ant H (40 mg/kg) for 45 days. The results indicated Ant at 40 mg/kg effectively suppressed the plasma levels of malondialdehyde, total cholesterol, triglycerides, GOT, GPT, uric acid, glucose, and insulin; upregulated leptin, adiponectin, pAMPK, Sirt1, and down-regulated PPARγ and SREBP-1c. Conclusively, Ant effectively alleviates NAFLD via AMPK/Sirt1/CREBP-1c/PPARγ pathway.

Taiwanofungus camphoratus Combined With Amphotericin B for Metastatic Cancer Patients Unresponsive to or Unwilling to Undergo Chemotherapy: A Pilot Study.

CONTEXT: Taiwanofungus camphoratus is a parasitic mushroom found in the heartwood of Cinnamomum kanehirai and is used as a nutritional supplement. It has an anticancer action, both alone and synergistically with amphotericin B (AmB). OBJECTIVE: The study intended to assess the efficacy of a T camphoratus ethanol extract (TCEE) combined with AmB for patients with metastatic cancer whose cancer did not respond to multiline chemotherapy or who were unwilling to receive chemotherapy. DESIGN: The research team performed a retrospective analysis as a pilot study. SETTING: The study took place at a single hospital (Taipei Medical University Hospital, Taipei, Taiwan). PARTICIPANTS: Participants were 9 patients at the hospital who were terminally ill with metastatic cancer. INTERVENTIONS: The participants had received daily doses of 2-3 g of the TCEE in combination with a weekly dose of 20-25 mg of AmB in 500 cc of 5% glucose water, given intravenously in 4-6 h. OUTCOME MEASURES: Outcome measures included (1) a primary evaluation index measuring the efficacy of the treatment; (2) a measure of tumor burden that was estimated using the response evaluation criteria in solid tumors (RECIST 1.1), (3) a secondary evaluation index measuring survival duration, and (4) safety. RESULTS: The mean treatment time was 54.4 ± 18.3 wk. At the end of the study, 2 patients showed a continued complete response, 1 patient had a continued partial response, and 1 patient showed a stable disease. The other 5 participants had times to progression ranging from 24 to 48 wk, with a mean of 35.6 wk. The mean survival time was 57.8 ± 18.5 wk, and 5 patients were still alive at the end of the study. CONCLUSIONS: For patients whose metastatic cancer did not respond to multiline chemotherapy or who were unwilling to receive chemotherapy, the use of TCEE as an adjuvant therapy to AmB resulted in tumor suppression and a delay in time to disease progression. The preliminary results reported here can be used to guide a future, more extensive clinical study of the combination.

A mechanistic and empirical review of antcins, a new class of phytosterols of formosan fungi origin.

Antcins are unique phytosterols isolated from A. cinnamomea and A. salmomea, which are the endemic fungus of Taiwan. A. cinnamomea has long been highly valued medicinal mushroom in Taiwan and traditionally used as a folk remedy for various human illness. Recent scientific explorations claimed that the pharmacological activities of A. cinnamomea and A. salmomonea are gone beyond their original usage. The therapeutic efficacy of these medicinal mushrooms was attributed to their high content of unique bioactive secondary metabolites, including terpenoids, benzenoids, ubiquinol derivatives, polysaccharides, lignans, nucleic acids, steroids, and maleic/succinic acid derivatives. Antcins is a group of steroids in Antrodia spp. with ergostane skeleton received much attention in Taiwan's academic circle due to their broad-spectrum of biological activities. At present, twelve antcins, i.e. antcin A, B, C, D, E, F, G, H, I, K, M, and N along with twelve derivatives/epimers (25R/S-antcin A, B, C, H, I and K) and seven analogs (methyl antcinate A, B, G, H, K, L and N) were identified. Several studies have demonstrated that antcins possessed anti-cancer, anti-inflammation, anti-oxidant, anti-diabetic, anti-aging, immunomodulation, hepatoprotection, and hypolipedimic activities. The main goal of this review is to define the chemistry, isolation, advances in production, and biological activities of antcins and their derivatives/analogs. Special attention has been given to a detail view of their biological activities in vitro and in vivo and their pharmacological potentials.

Antcamphin M Inhibits TLR4-Mediated Inflammatory Responses by Upregulating the Nrf2/HO-1 Pathway and Suppressing the NLRP3 Inflammasome Pathway in Macrophages.

The medicinal mushroom Antrodia cinnamomea has been demonstrated to have anti-inflammatory properties. However, the bioactive compounds in A. cinnamomea need further investigation. The present study aimed to understand the mechanism of action of antcamphin M, an ergostanoid isolated from A. cinnamomea mycelium and to clarify its underlying mechanisms of action. RAW264.7 cells were pretreated with the indicated concentrations of antcamphin M, prior to stimulation with lipopolysaccharide (LPS). Cell viability, production of nitric oxide (NO), prostaglandin E2 (PGE2), cytokines, and chemokines, as well as the inflammation-related signaling pathways were investigated. The study revealed that antcamphin M significantly decreased the LPS-induced production of NO, PGE2, pro-inflammatory cytokines, and keratinocyte chemoattractant CXCL1 (KC), along with the levels of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins without significant cytotoxicity, indicating it had a better anti-inflammatory activity than that of gisenoside Rb1 and Rg1. Additionally, antcamphin M significantly inhibited the activation of MAPKs (p38, ERK, and JNK), NFκB, and components of the NLRP3 inflammasome (NLRP3, ASC, and caspase-1) signaling pathways and also increased the levels of nuclear factor erythroid-2-related factor (Nrf2) and heme oxygenase-1 (HO-1). These findings suggest that antcamphin M possesses potent anti-inflammatory activities and could be a potential candidate for the development of anti-inflammatory drugs.

Antrodia Cinnamomea Prolongs Survival in a Patient with Small Cell Lung Cancer.

Introduction: Antrodia cinnamomea (AC) is an extremely rare medicinal fungus native to forested regions of Taiwan. It possesses numerous biological activities, especially anti-tumor effects shown in various in vitro cancer cells and in vivo animal models. However, there are few clinical reports about AC as a treatment for cancer patients. This report attempts to demonstrate the therapeutic effect of dish-cultured AC (DAC) on a small cell lung cancer (SCLC) patient taken orally for an extended duration. Patient concerns: An 88-year-old male with a history of diabetes mellitus and hypertension visited the outpatient department with the symptoms of dyspnea and a cough for two weeks. After a diagnosis of SCLC, the patient declined both chemotherapy and radiotherapy because of the side effects and only accepted supportive care without additional therapy. Diagnosis: Limited-stage SCLC (T4N2M1a, stage IV) after the chest radiograph, computed tomography-guided biopsy, and pathological diagnosis. Interventions: The patient was prescribed DAC with an increasing dosage, from 5 g/d up to 10 g/d DAC, for six months, without radiation or chemotherapy treatment. Outcomes: DAC caused the tumor to shrink substantially. Surprisingly, the patient survived for 32 months without relapse after six months of DAC treatment. Laboratory examinations indicated that the patient's health had improved significantly, reverting to near normal levels. Notably, he had a good quality of life with a high Barthel index score. Unfortunately, this patient died of septic shock caused by acute cholangitis. Conclusion: DAC may exert an anti-cancer effect, which can lead to tumor regression. This is supposed to be achieved by the combined DAC's immunomodulatory, anti-angiogenic, anti-metastatic, anti-proliferative, and pro-apoptotic effects mediated through multiple signaling pathways. We propose that DAC can be used as a complementary medicine to prolong the life expectancy and improve the life quality of SCLC patients.

A Benzenoid 4,7-Dimethoxy-5-Methyl-L, 3-Benzodioxole from Antrodia cinnamomea Attenuates Dendritic Cell-Mediated Th2 Allergic Responses.

Dendritic cells (DCs) play a critical role in initiating immune responses; however, DCs also induce Th2-related allergic sensitivities. Thus, DCs become a target for therapeutic design in allergic diseases. In this study, we aim to investigate the anti-allergic effect of pure compounds from a medicinal mushroom Antrodia cinnamomea (Ac) on DC-induced allergic responses. We identified a benzenoid compound 4,7-dimethoxy-5-methyl-l,3-benzodioxole (DMB) which may modulate Th2 polarization in bone marrow-derived DCs (BMDCs) and in a murine food allergy model. DMB effectively reduced the Th2 adjuvant cholera toxin (CT)-induced BMDC maturation and cytokine production. In studying the mechanism, DMB blocked the molecular processes involved in Th2 induction, including cAMP activation, IL-33 production, and IRF4/Tim4 upregulation, in CT-activated BMDCs. Furthermore, DMB treatment attenuated the symptoms, clinical scores, and Th2 responses of CT-induced ovalbumin (OVA)-specific food allergy in mice at sensitization stage. These results indicated that DMB could suppress DC function for Th2 polarization and mitigate allergic responses. Thus, DMB may have potential to be a novel agent for preventing or treating food allergy.

Antrodia cinnamomea-An updated minireview of its bioactive components and biological activity.

Antrodia cinnamomea or Antrodia camphorata is a distinctive mushroom of Taiwan, which is being used as a traditional medicine to treat various health-related conditions. More than 78 compounds have been identified in A. cinnamomea. Large numbers of phytochemical studies have been carried out in A. cinnamomea due to the high amount of terpenoids. Besides that, the extracts and active components of A. cinnamomea were reported to have various biological activities including hepatoprotective, antihypertensive, antihyperlipidemic, anti-inflammatory, antioxidant, antitumor, and immunomodulatory activities. In this review article, we have summarized the recent findings of A. cinnamomea and its molecular mechanisms of action in various disease models. PRACTICAL APPLICATIONS: A. cinnamomea, medicinal fungus used in traditional medicine in Taiwan also possess high market value. Aim of the present review is to highlight the compounds present in A. cinnamomea and their different pharmacological activities in preventing/cure various diseases/disorders. A. cinnamomea can be potentially developed into health foods or drugs.