AIM: To investigate the effects of filtrate of fermented mycelia from Antrodia camphorata (FMAC) on liver fibrosis induced by carbon tetrachloride (CCI4) in rats. METHODS: Forty Wistar rats were divided randomly...AIM: To investigate the effects of filtrate of fermented mycelia from Antrodia camphorata (FMAC) on liver fibrosis induced by carbon tetrachloride (CCI4) in rats. METHODS: Forty Wistar rats were divided randomly into control group and model group. All model rats were given 200 mL/L CCI4 (2 mL/Kg, po) twice a week for 8 wk. Four weeks after CCh treatment, thirty model rats were further divided randomly into 3 subgroups: CCh and two FMAC subgroups. Rats in CCI4 and 2 FMAC subgroups were treated with FMAC 0, 0.5 and 1.0 g/kg, daily via gastrogavage beginning at the fitch week and the end of the eighth week. Spleen weight, blood synthetic markers (albumin and prothrombin time) and hepatic malondialdehyde (MDA) and hydroxyproline (HP) concentrations were determined. Expression of collagen I, tissue inhibitor of metalloproteinases (TIMP)-1 and transforming growth factor β1 (TGF-β1) mRNA were detected by RTPCR. Histochemical staining of Masson's trichrome was performed. RESULTS: CCI4 caused liver fibrosis, featuring increased prothrombin time, hepatic MDA and HP contents, and spleen weight and decreased plasma albumin level. Compared with CCh subgroup, FMAC subgroup (1 g/kg) significantly decreased the prothrombin time (36.7±7.2 and 25.1±10.2 in CCh and FMAC groups, respectively, P〈 0.05) and increased plasma albumin concentration (22.7± 1.0 and 30.7±2.5 in CCk and FMAC groups, respectively, P 〈 0.05). Spleen weight was significantly lower in rats treated with CCh and FMAC (1 g/kg) compared to CCh treated rats only (2.7±0.1 and 2.4±0.2 in CCk and FMAC groups, respectively, P〈0.05). The amounts of hepatic MDA and HP in CCI4± FAMC (1 g/kg) subgroup were also lower thanthose in CCh subgroup (MDA: 3.9±0.1 and 2.4±0.6 in CCh and CCI4 + FMAC groups, respectively, P〈 0.01; HP: 1730.7±258.0 and 1311.5±238.8 in CCI4 and CCI4+FMAC groups, respectively, P〈0.01). Histologic examinations showed that CCI4+FMAC subgroups had thinner or less fibrotic septa than CCh group. RT-PCR analysis indicated that FMAC (1 g/kg) reduced mRNA levels of collagen I, TIMP-1 and TGF-β1 (collagen I: 5.63±2.08 and 1.78±0.48 in CCh and CCI4+FMAC groups, respectively, P〈0.01; TIMP-1: 1.70±0.82 and 0.34±0.02 in CCh and CCI4 + FMAC groups, respectively, P〈0.01; TGF-β1:38.03±11.9 and 4.26±2.17 in CCh and CCI4+FMAC groups, respectively, P〈0.01) in the CCI4-treated liver. CONCLUSION: It demonstrates that FMAC can retard the progression of liver fibrosis induced by CCh in rats.展开更多
The increased vascular infl ammation is a key event in the development of atherosclerotic lesions.Antrodia cinnamomea has been shown to promote anticancerogenic activity through decreasing infl ammation.However,the po...The increased vascular infl ammation is a key event in the development of atherosclerotic lesions.Antrodia cinnamomea has been shown to promote anticancerogenic activity through decreasing infl ammation.However,the potential role of A.cinnamomea in cardiovascular diseases remains unexplored.Herein,using carotid arterial ligation models,we found that ethanol extract from A.cinnamomea(EEAC)signifi cantly inhibited neointimal hyperplasia in a dose-dependent manner,accompanied with the reduced expression of activated p65 and infl ammatory cytokines.We also show that EEAC ameliorated TNF-α-induced phosphorylation of p65 and pro-infl ammatory cytokine expression in both vascular smooth muscle cells(VSMCs)and macrophages in vitro.Mechanistically,EEAC suppressed expression levels of intercellular adhesion molecule-1(ICAM-1)and vascular cell adhesion molecule(VCAM-1)in VSMCs,which attenuates the ability of monocytes/macrophages adhesion to VSMCs.Furthermore,the expression level of these adhesion molecules and infi ltration of monocytes/macrophages were also decreased in neointimal VSMCs of arteries pretreated with EEAC.Altogether,our results reveal a novel function of A.cinnamomea in suppressing vascular infl ammation upon ligation injury during neointimal formation,likely through inhibition of infl ammatory cell infi ltration via downregulating the adhesion molecules in VSMCs.Thus,A.cinnamomea may offer a pharmacological therapy to slow down disease progression in patients with vascular injury.展开更多
Antrodia cinnamomea is a precious medicinal mushroom.It exhibits promising therapeutic effects on cancer,intoxication,hypertension,hepatitis,and inflammation.Its major bioactive constituents are ergostane and lanostan...Antrodia cinnamomea is a precious medicinal mushroom.It exhibits promising therapeutic effects on cancer,intoxication,hypertension,hepatitis,and inflammation.Its major bioactive constituents are ergostane and lanostane triterpenoids.In this study,we used intestinal Caco-2 cell monolayer model to reveal the intestinal absorption property of 14 representative triterpenoids from A.cinnamomea.The bidirectional transport through the monolayer at different time points was monitored by a fully validated LC/MS/MS method.In the case of pure compounds,ergostanes 5(25R-antcin H),6(25Santcin H)and 10(25R-antcin B)could readily pass through the Caco-2 cell layer,whereas lanostanes 13(dehydroeburicoic acid)and 14(eburicoic acid)could hardly pass through.When the cells were treated with A.cinnamomea extract,antcins A,B,C,H and K(1–6 and 9–11)were absorbed via passive transcellular diffusion,and showed high PAB and PBA values(>2.5×10^(-5) cm/s).Meanwhile,the lanostanes dehydrosulphurenic acid(8),15a-acetyldehydrosulphurenic acid(12),13 and 14 exhibited poor permeability.Transport features of these compounds were consistent with their pharmacokinetic behaviors in rats.This study could also be helpful in predicting the intestinal absorption of A.cinnamomea in human.展开更多
This study generated two fused protoplasts of Antrodia cinnamomea and Cordyceps militaris in two ways.The protoplasts of A.cinnamomea were inactivated by heat to inactivate biochemical processes and enzymatic activiti...This study generated two fused protoplasts of Antrodia cinnamomea and Cordyceps militaris in two ways.The protoplasts of A.cinnamomea were inactivated by heat to inactivate biochemical processes and enzymatic activities in the cytoplasm,and the protoplasts of C.militaris were inactivated by UV radiation to invalidate their genome function,then they were fused under optimal conditions to get a fusion rate as(7.42±0.8)×10^(-6) fusants/mL;the new fusants were abbreviated as Ac-Cm.On the other hand,when A.cinnamomea and C.militaris were treated with heat and UV oppositely using similar experiments,the fusion rate was(9.70±0.68)×10^(-5) fusants/mL,and the new fusants were abbreviated as Cm-Ac.We selected each of two best-growing fused colonies Ac-Cm-1,Ac-Cm-2,Cm-Ac-1,and Cm-Ac-2,together with parental A.cinnamomea and C.militaris,and studied their morphology,growth antagonism tests,and genetic relationships by 18 S rRNA sequencing.In comparison with the initial cultures of 4 fusants,the yields of adenosine,biomass,cordycepic acid,cordycepin,total polysaccharide,and total triterpenoids were increased up 1.305-50.1563 times in the optimal medium conditions.For gene stability tests,those of the four fusants and their outputs were stabilized within 10 generations.展开更多
Extensive in vitro and in vivo research reveals multiple intracellular molecular targets of Antrodia camphorata,and these targets affect growth,apoptosis,angiogenesis,invasion and metastasis of cells.These targets inc...Extensive in vitro and in vivo research reveals multiple intracellular molecular targets of Antrodia camphorata,and these targets affect growth,apoptosis,angiogenesis,invasion and metastasis of cells.These targets include tumor suppressor,cell cycle regulator,transcription factor,angiogenesis and metastasis factor,apoptosis and survival regulator,etc.Additionally,more and more attention has been paid to the molecular mechanism of A.camphorata on the regulation of tumor stem cells.Meanwhile,there is evidence that the immunoregulation of A.camphorata is enhanced,which may lead cell cycle arrest or apoptosis.In this paper,molecular mechanism of tumor cells and tumor stem cells regulated at multiple targets by A.camphorata in vitro and in vivo in the past decade is summarized.展开更多
Objective: Antrodia camphorata (AC), a precious medicinal mushroom in Taiwan, is popularly used for adjuvant cancer therapy. This paper aims to clarify the metabolites which are present in tumor tissues after oral ...Objective: Antrodia camphorata (AC), a precious medicinal mushroom in Taiwan, is popularly used for adjuvant cancer therapy. This paper aims to clarify the metabolites which are present in tumor tissues after oral administration of AC in Sarcoma-180 tumor-bearing mice, as well as their contents in tumors. Methods: Tumors of Sarcoma-180 tumor-bearing mice were obtained at 1 h and 4 h after oral administration of AC extract, and the metabolites in the tumor homogenate samples were characterized using UHPLC-orbitrap/MS analysis. Then, a fully validated LC-MS/MS method was developed for quantitative analysis of the most abundant compounds in tumor tissues, namely (25R/S)-antcin H. Results: A total of 33 compounds were characterized in tumor homogenate samples including 28 prototypes of triterpenoids and 5 metabolites. Among them, (25R)-antcin H and (25S)-antcin H had the highest contents of 2.03 and 0.66 μg/g tumor tissues for the 1 h group, and 2.04 and 0.59 μg/g tumor tissues for the 4 h group, respectively. It was obvious that (25R)-antcin H had higher tumor affinity than (25S)-antcin H, since the content of (25R)-antcin H was lower than that of (25S)-antcin H in AC extract (P 〈 0.01). Conclusion: Triterpenoids can enter tumor tissues after oral administration of AC. Particularly, (25R)-antcin H showed higher exposure to tumor than (25S)-antcin H. These compounds could contribute to the anticancer activities of AC.展开更多
The galactomannan from Antrodia cinnamomea(AC)is characterized as one of the important bioactive components that exhibits potential immunostimulatory propriety.The biological function of its corresponding oligosacchar...The galactomannan from Antrodia cinnamomea(AC)is characterized as one of the important bioactive components that exhibits potential immunostimulatory propriety.The biological function of its corresponding oligosaccharide fragments has not been revealed yet.In this study,we reported the first chemical synthesis of the series of oligosaccharide fragments related to AC galactomannan via the convergent glycosylation strategy.The preliminary immunological evaluation of these synthesized AC oligosaccharides disclosed that the backbone tetrasaccharide 1d showed the best immunomodulatory ability on enhancing proliferation,phagocytosis and cytokines secretion of Raw264.7 macrophages in vitro,indicating its immense potential as an immunostimulant candidate.展开更多
Antrodia camphorata, a well-known and highly valued edible medicinal mushroom with intriguing activities like liver protection, has been traditionally used for the treatment of alcoholic liver disease. A. camphorata s...Antrodia camphorata, a well-known and highly valued edible medicinal mushroom with intriguing activities like liver protection, has been traditionally used for the treatment of alcoholic liver disease. A. camphorata shows highly medicinal and commercial values with the demand far exceeds the available supply. Thus, the petri-dish cultured A. camphorata(PDCA) is expected to develope as a substitute. In this paper, nineteen triterpenes were isolated from PDCA, and thirteen of them were the unique anthroic acids in A. camphorata, including the main content antcin K, which suggested that PDCA produced a large array of the same anthroic acids as the wild one. Furthermore, no obvious acute toxicity was found suggesting the edible safety of PDCA. In mice alcohol-induced liver injury model, triglyceride(TG), aspartate aminotransferase(AST), alanine aminotransferase(ALT), and malondialdehyde(MDA) had been reduced by the PDCA powder as well as the main content antcin K, which indicated that the PDCA could protect alcoholic liver injury in mice model and antcin K could be the effective component responsible for the hepatoprotective activities of PDCA against alcoholic liver diseases.展开更多
Antrodia cinnamomea is extensively used as a traditional medicine to prevention and treatment of liver cancer.However,its comprehensive chemical fingerprint is uncertain,and the mechanisms,especially the potential the...Antrodia cinnamomea is extensively used as a traditional medicine to prevention and treatment of liver cancer.However,its comprehensive chemical fingerprint is uncertain,and the mechanisms,especially the potential therapeutic target for anti-hepatocellular carcinoma(HCC)are still unclear.Using UPLC-Q-TOF/MS,139 chemical components were identified in A.cinnamomea dropping pills(ACDPs).Based on these chemical components,network pharmacology demonstrated that the targets of active components were significantly enriched in the pathways in cancer,which were closely related with cell proliferation regulation.Next,HCC data was downloaded from Gene Expression Omnibus database(GEO).The Cancer Genome Atlas(TCGA)and Dis Ge NET were analyzed by bioinformatics,and 79 biomarkers were obtained.Furtherly,nine targets of ACDP active components were revealed,and they were significantly enriched in PI3 K/AKT and cell cycle signaling pathways.The affinity between these targets and their corresponding active ingredients was predicted by molecular docking.Finally,in vivo and in vitro experiments showed that ACDPs could reduce the activity of PI3 K/AKT signaling pathway and downregulate the expression of cell cycle-related proteins,contributing to the decreased growth of liver cancer.Altogether,PI3 K/AKT-cell cycle appears as the significant central node in anti-liver cancer of A.Cinnamomea.展开更多
This study investigated hypolipidemic,weight-reducing,and hepatoprotective effects of Antrodia cinnamomea mycelial extract obtained from solid-state culture(ACME)in an HFr D-induced obese/hyperlipidemic mouse model.Fo...This study investigated hypolipidemic,weight-reducing,and hepatoprotective effects of Antrodia cinnamomea mycelial extract obtained from solid-state culture(ACME)in an HFr D-induced obese/hyperlipidemic mouse model.Following 4-week ACME treatment,body weight,epididymal fat index,and some serum biochemical indices were measured.Expression levels of some related genes involved in cholesterol and lipid metabolism were analyzed by q RT-PCR.Moreover,histological studies of hepatic tissues were also conducted.After ACME treatment,body weight and epididymal fat index were significantly lower than that in model control group.ACME and simvastatin significantly reduced serum total cholesterol(T-CHO)and low-density lipoprotein cholesterol(LDL-C)levels,and increased high-density lipoprotein cholesterol(HDL-C)level.Subsequent experiments showed that:(i)ACME regulated transcriptional expression of 3-hydroxy-3-methylglutaryl-Co A reductase(HMGR),low-density lipoprotein receptor(LDLR),adipose triglyceride lipase(ATGL),and fatty acid synthase(FAS),with consequent reduction of blood lipid levels and body weight;(ii)ACME enhanced total antioxidant capacity(T-AOC)and superoxide dismutase(SOD)activity in hepatic tissues;(iii)ACME reduced malondialdehyde(MDA)level and ameliorated lipid oxidative damage in liver.Our findings indicate that ACME is a strong candidate for development as a novel anti-hyperlipidemia and anti-obesity health product.展开更多
Antrodia cinnamomea is an important edible and medicinal mushroom,and it exhibits multiple biological activities,such as hepatoprotection,antitumor,antivirus,and immunoregulation.Polysaccharides are the main products ...Antrodia cinnamomea is an important edible and medicinal mushroom,and it exhibits multiple biological activities,such as hepatoprotection,antitumor,antivirus,and immunoregulation.Polysaccharides are the main products of A.cinnamomea in submerged fermentation.In this work,exopolysaccharides from A.cinnamomea(AEPS)were extracted and purified by alcohol precipitation and Sevag method.Composition analysis revealed that AEPS were primarily composed of three distinct polysaccharides with mean molecular weights of 1,013,233,and 28,743 kDa,accounting for 78%,18%,and 4%of AEPS,respectively.The AEPS haveβ-type glycosidic bonds and relatively strong resistance to digestion.In vivo experiments showed that the intragastric administration of AEPS in mice with medium dose(0.25 g/kg body weight of mice)has the following effects:remarkably alleviate lincomycin hydrochloride(LIH)-induced injuries to immune organs;enhance the relative abundance of beneficial microorganisms such as Lactobacillus,Roseburia,Ligilactobacillus,and Lachnospiraceae_NK4A136_group in the intestinal tract;greatly reduce the levels of inflammatory cytokines IL-6 and TNF-αin serum and the relative abundances of harmful microbes such as Enterococcus and Shigella;regulate the balance of the gut microflora;and relieve LIH-induced symptoms such as diarrhea,inflammation,and weight loss.These findings might represent a new alternative to develop novel multifunctional carbohydrate prebiotics.展开更多
基金Supported by Department of Health, Executive Yuan of our country, No. DOH90-TD-1027
文摘AIM: To investigate the effects of filtrate of fermented mycelia from Antrodia camphorata (FMAC) on liver fibrosis induced by carbon tetrachloride (CCI4) in rats. METHODS: Forty Wistar rats were divided randomly into control group and model group. All model rats were given 200 mL/L CCI4 (2 mL/Kg, po) twice a week for 8 wk. Four weeks after CCh treatment, thirty model rats were further divided randomly into 3 subgroups: CCh and two FMAC subgroups. Rats in CCI4 and 2 FMAC subgroups were treated with FMAC 0, 0.5 and 1.0 g/kg, daily via gastrogavage beginning at the fitch week and the end of the eighth week. Spleen weight, blood synthetic markers (albumin and prothrombin time) and hepatic malondialdehyde (MDA) and hydroxyproline (HP) concentrations were determined. Expression of collagen I, tissue inhibitor of metalloproteinases (TIMP)-1 and transforming growth factor β1 (TGF-β1) mRNA were detected by RTPCR. Histochemical staining of Masson's trichrome was performed. RESULTS: CCI4 caused liver fibrosis, featuring increased prothrombin time, hepatic MDA and HP contents, and spleen weight and decreased plasma albumin level. Compared with CCh subgroup, FMAC subgroup (1 g/kg) significantly decreased the prothrombin time (36.7±7.2 and 25.1±10.2 in CCh and FMAC groups, respectively, P〈 0.05) and increased plasma albumin concentration (22.7± 1.0 and 30.7±2.5 in CCk and FMAC groups, respectively, P 〈 0.05). Spleen weight was significantly lower in rats treated with CCh and FMAC (1 g/kg) compared to CCh treated rats only (2.7±0.1 and 2.4±0.2 in CCk and FMAC groups, respectively, P〈0.05). The amounts of hepatic MDA and HP in CCI4± FAMC (1 g/kg) subgroup were also lower thanthose in CCh subgroup (MDA: 3.9±0.1 and 2.4±0.6 in CCh and CCI4 + FMAC groups, respectively, P〈 0.01; HP: 1730.7±258.0 and 1311.5±238.8 in CCI4 and CCI4+FMAC groups, respectively, P〈0.01). Histologic examinations showed that CCI4+FMAC subgroups had thinner or less fibrotic septa than CCh group. RT-PCR analysis indicated that FMAC (1 g/kg) reduced mRNA levels of collagen I, TIMP-1 and TGF-β1 (collagen I: 5.63±2.08 and 1.78±0.48 in CCh and CCI4+FMAC groups, respectively, P〈0.01; TIMP-1: 1.70±0.82 and 0.34±0.02 in CCh and CCI4 + FMAC groups, respectively, P〈0.01; TGF-β1:38.03±11.9 and 4.26±2.17 in CCh and CCI4+FMAC groups, respectively, P〈0.01) in the CCI4-treated liver. CONCLUSION: It demonstrates that FMAC can retard the progression of liver fibrosis induced by CCh in rats.
基金This work was supported by the National Key Research Project of China(2019YFC1606400)Major Public Welfare Projects in Henan Province(201300110200)+4 种基金National Key Research Project of Hebei Province(20375502D)Natural Science Foundation of Hebei Province(H2019206212)High-level Talent Funding Project of Hebei Province(A201905006)Fund of National R&D Center for Edible Fungus Processing Technology,Henan University(20200109)the Open Fund from Beijing Advanced Innovation Center for Food Nutrition and Human Health(20182025).
文摘The increased vascular infl ammation is a key event in the development of atherosclerotic lesions.Antrodia cinnamomea has been shown to promote anticancerogenic activity through decreasing infl ammation.However,the potential role of A.cinnamomea in cardiovascular diseases remains unexplored.Herein,using carotid arterial ligation models,we found that ethanol extract from A.cinnamomea(EEAC)signifi cantly inhibited neointimal hyperplasia in a dose-dependent manner,accompanied with the reduced expression of activated p65 and infl ammatory cytokines.We also show that EEAC ameliorated TNF-α-induced phosphorylation of p65 and pro-infl ammatory cytokine expression in both vascular smooth muscle cells(VSMCs)and macrophages in vitro.Mechanistically,EEAC suppressed expression levels of intercellular adhesion molecule-1(ICAM-1)and vascular cell adhesion molecule(VCAM-1)in VSMCs,which attenuates the ability of monocytes/macrophages adhesion to VSMCs.Furthermore,the expression level of these adhesion molecules and infi ltration of monocytes/macrophages were also decreased in neointimal VSMCs of arteries pretreated with EEAC.Altogether,our results reveal a novel function of A.cinnamomea in suppressing vascular infl ammation upon ligation injury during neointimal formation,likely through inhibition of infl ammatory cell infi ltration via downregulating the adhesion molecules in VSMCs.Thus,A.cinnamomea may offer a pharmacological therapy to slow down disease progression in patients with vascular injury.
基金This work was supported by National Natural Science Foundation of China(Nos.81222054,81303294)the Program for New Century Excellent Talents in University from Chinese Ministry of Education(No.NCET-11-0019).
文摘Antrodia cinnamomea is a precious medicinal mushroom.It exhibits promising therapeutic effects on cancer,intoxication,hypertension,hepatitis,and inflammation.Its major bioactive constituents are ergostane and lanostane triterpenoids.In this study,we used intestinal Caco-2 cell monolayer model to reveal the intestinal absorption property of 14 representative triterpenoids from A.cinnamomea.The bidirectional transport through the monolayer at different time points was monitored by a fully validated LC/MS/MS method.In the case of pure compounds,ergostanes 5(25R-antcin H),6(25Santcin H)and 10(25R-antcin B)could readily pass through the Caco-2 cell layer,whereas lanostanes 13(dehydroeburicoic acid)and 14(eburicoic acid)could hardly pass through.When the cells were treated with A.cinnamomea extract,antcins A,B,C,H and K(1–6 and 9–11)were absorbed via passive transcellular diffusion,and showed high PAB and PBA values(>2.5×10^(-5) cm/s).Meanwhile,the lanostanes dehydrosulphurenic acid(8),15a-acetyldehydrosulphurenic acid(12),13 and 14 exhibited poor permeability.Transport features of these compounds were consistent with their pharmacokinetic behaviors in rats.This study could also be helpful in predicting the intestinal absorption of A.cinnamomea in human.
基金supported by grants from the Ministry of Science and Technology of Taiwan(Grant number:MOST 106-2320-B-037008-MY2,MOST 108-2320-B-037-022-MY3,108-2811-B-037-511,and 109-2927-I-037-502)funded by the Drug Development and Value Creation Research Center,Kaohsiung Medical UniversityDepartment of Medical Research,Kaohsiung Medical University Hospital(Grant number:KMU-TC108A03-11)。
文摘This study generated two fused protoplasts of Antrodia cinnamomea and Cordyceps militaris in two ways.The protoplasts of A.cinnamomea were inactivated by heat to inactivate biochemical processes and enzymatic activities in the cytoplasm,and the protoplasts of C.militaris were inactivated by UV radiation to invalidate their genome function,then they were fused under optimal conditions to get a fusion rate as(7.42±0.8)×10^(-6) fusants/mL;the new fusants were abbreviated as Ac-Cm.On the other hand,when A.cinnamomea and C.militaris were treated with heat and UV oppositely using similar experiments,the fusion rate was(9.70±0.68)×10^(-5) fusants/mL,and the new fusants were abbreviated as Cm-Ac.We selected each of two best-growing fused colonies Ac-Cm-1,Ac-Cm-2,Cm-Ac-1,and Cm-Ac-2,together with parental A.cinnamomea and C.militaris,and studied their morphology,growth antagonism tests,and genetic relationships by 18 S rRNA sequencing.In comparison with the initial cultures of 4 fusants,the yields of adenosine,biomass,cordycepic acid,cordycepin,total polysaccharide,and total triterpenoids were increased up 1.305-50.1563 times in the optimal medium conditions.For gene stability tests,those of the four fusants and their outputs were stabilized within 10 generations.
基金Shandong Medical and Health Development Plan(2018WS423).
文摘Extensive in vitro and in vivo research reveals multiple intracellular molecular targets of Antrodia camphorata,and these targets affect growth,apoptosis,angiogenesis,invasion and metastasis of cells.These targets include tumor suppressor,cell cycle regulator,transcription factor,angiogenesis and metastasis factor,apoptosis and survival regulator,etc.Additionally,more and more attention has been paid to the molecular mechanism of A.camphorata on the regulation of tumor stem cells.Meanwhile,there is evidence that the immunoregulation of A.camphorata is enhanced,which may lead cell cycle arrest or apoptosis.In this paper,molecular mechanism of tumor cells and tumor stem cells regulated at multiple targets by A.camphorata in vitro and in vivo in the past decade is summarized.
基金This work was supported by National Natural Science Foundation of China (No. 81303294), the National Key Research and Development Program of China (No. 2017YFC1700405), and Young Elite Scientists Sponsorship Program by CAST (2016QNRC001).
文摘Objective: Antrodia camphorata (AC), a precious medicinal mushroom in Taiwan, is popularly used for adjuvant cancer therapy. This paper aims to clarify the metabolites which are present in tumor tissues after oral administration of AC in Sarcoma-180 tumor-bearing mice, as well as their contents in tumors. Methods: Tumors of Sarcoma-180 tumor-bearing mice were obtained at 1 h and 4 h after oral administration of AC extract, and the metabolites in the tumor homogenate samples were characterized using UHPLC-orbitrap/MS analysis. Then, a fully validated LC-MS/MS method was developed for quantitative analysis of the most abundant compounds in tumor tissues, namely (25R/S)-antcin H. Results: A total of 33 compounds were characterized in tumor homogenate samples including 28 prototypes of triterpenoids and 5 metabolites. Among them, (25R)-antcin H and (25S)-antcin H had the highest contents of 2.03 and 0.66 μg/g tumor tissues for the 1 h group, and 2.04 and 0.59 μg/g tumor tissues for the 4 h group, respectively. It was obvious that (25R)-antcin H had higher tumor affinity than (25S)-antcin H, since the content of (25R)-antcin H was lower than that of (25S)-antcin H in AC extract (P 〈 0.01). Conclusion: Triterpenoids can enter tumor tissues after oral administration of AC. Particularly, (25R)-antcin H showed higher exposure to tumor than (25S)-antcin H. These compounds could contribute to the anticancer activities of AC.
基金supported by grants from the National Key Research and Development Program of China(No.2018YFA0902000)the National Natural Science Foundation of China(No.21877074).
文摘The galactomannan from Antrodia cinnamomea(AC)is characterized as one of the important bioactive components that exhibits potential immunostimulatory propriety.The biological function of its corresponding oligosaccharide fragments has not been revealed yet.In this study,we reported the first chemical synthesis of the series of oligosaccharide fragments related to AC galactomannan via the convergent glycosylation strategy.The preliminary immunological evaluation of these synthesized AC oligosaccharides disclosed that the backbone tetrasaccharide 1d showed the best immunomodulatory ability on enhancing proliferation,phagocytosis and cytokines secretion of Raw264.7 macrophages in vitro,indicating its immense potential as an immunostimulant candidate.
基金supported by Fundamental Research Funds for the Central Universities(Nos.20720160117 and 20720150204)Xiamen Science and Technology program grant(Nos.3502Z20161235 and 3502Z20173021)
文摘Antrodia camphorata, a well-known and highly valued edible medicinal mushroom with intriguing activities like liver protection, has been traditionally used for the treatment of alcoholic liver disease. A. camphorata shows highly medicinal and commercial values with the demand far exceeds the available supply. Thus, the petri-dish cultured A. camphorata(PDCA) is expected to develope as a substitute. In this paper, nineteen triterpenes were isolated from PDCA, and thirteen of them were the unique anthroic acids in A. camphorata, including the main content antcin K, which suggested that PDCA produced a large array of the same anthroic acids as the wild one. Furthermore, no obvious acute toxicity was found suggesting the edible safety of PDCA. In mice alcohol-induced liver injury model, triglyceride(TG), aspartate aminotransferase(AST), alanine aminotransferase(ALT), and malondialdehyde(MDA) had been reduced by the PDCA powder as well as the main content antcin K, which indicated that the PDCA could protect alcoholic liver injury in mice model and antcin K could be the effective component responsible for the hepatoprotective activities of PDCA against alcoholic liver diseases.
基金supported by the National Key Research Project of China(2019YFC1606400)CAMS Innovation Fund for Medical Sciences(2019-I2M-5-055,China)+4 种基金Major Public Welfare Projects in Henan Province(201300110200,China)National Key Research Project of Hebei Province(20375502D,China)Natural Science Foundation of Hebei Province(H2019206212,China)High-level Talent Funding Project of Hebei Province(A201905006,China)Fund of National R&D Center for Edible Fungus Processing Technology,Henan University(20200109,China)。
文摘Antrodia cinnamomea is extensively used as a traditional medicine to prevention and treatment of liver cancer.However,its comprehensive chemical fingerprint is uncertain,and the mechanisms,especially the potential therapeutic target for anti-hepatocellular carcinoma(HCC)are still unclear.Using UPLC-Q-TOF/MS,139 chemical components were identified in A.cinnamomea dropping pills(ACDPs).Based on these chemical components,network pharmacology demonstrated that the targets of active components were significantly enriched in the pathways in cancer,which were closely related with cell proliferation regulation.Next,HCC data was downloaded from Gene Expression Omnibus database(GEO).The Cancer Genome Atlas(TCGA)and Dis Ge NET were analyzed by bioinformatics,and 79 biomarkers were obtained.Furtherly,nine targets of ACDP active components were revealed,and they were significantly enriched in PI3 K/AKT and cell cycle signaling pathways.The affinity between these targets and their corresponding active ingredients was predicted by molecular docking.Finally,in vivo and in vitro experiments showed that ACDPs could reduce the activity of PI3 K/AKT signaling pathway and downregulate the expression of cell cycle-related proteins,contributing to the decreased growth of liver cancer.Altogether,PI3 K/AKT-cell cycle appears as the significant central node in anti-liver cancer of A.Cinnamomea.
基金Fundamental Research Funds for the Central Universities of China(2662019PY066,2662016PY132)。
文摘This study investigated hypolipidemic,weight-reducing,and hepatoprotective effects of Antrodia cinnamomea mycelial extract obtained from solid-state culture(ACME)in an HFr D-induced obese/hyperlipidemic mouse model.Following 4-week ACME treatment,body weight,epididymal fat index,and some serum biochemical indices were measured.Expression levels of some related genes involved in cholesterol and lipid metabolism were analyzed by q RT-PCR.Moreover,histological studies of hepatic tissues were also conducted.After ACME treatment,body weight and epididymal fat index were significantly lower than that in model control group.ACME and simvastatin significantly reduced serum total cholesterol(T-CHO)and low-density lipoprotein cholesterol(LDL-C)levels,and increased high-density lipoprotein cholesterol(HDL-C)level.Subsequent experiments showed that:(i)ACME regulated transcriptional expression of 3-hydroxy-3-methylglutaryl-Co A reductase(HMGR),low-density lipoprotein receptor(LDLR),adipose triglyceride lipase(ATGL),and fatty acid synthase(FAS),with consequent reduction of blood lipid levels and body weight;(ii)ACME enhanced total antioxidant capacity(T-AOC)and superoxide dismutase(SOD)activity in hepatic tissues;(iii)ACME reduced malondialdehyde(MDA)level and ameliorated lipid oxidative damage in liver.Our findings indicate that ACME is a strong candidate for development as a novel anti-hyperlipidemia and anti-obesity health product.
基金financially supported by the National Natural Science Foundation of China(Grant numbers:32001661 and 32101964)the Natural Science Foundation of Jiangsu Province,China(Grant number:BK20190890).
文摘Antrodia cinnamomea is an important edible and medicinal mushroom,and it exhibits multiple biological activities,such as hepatoprotection,antitumor,antivirus,and immunoregulation.Polysaccharides are the main products of A.cinnamomea in submerged fermentation.In this work,exopolysaccharides from A.cinnamomea(AEPS)were extracted and purified by alcohol precipitation and Sevag method.Composition analysis revealed that AEPS were primarily composed of three distinct polysaccharides with mean molecular weights of 1,013,233,and 28,743 kDa,accounting for 78%,18%,and 4%of AEPS,respectively.The AEPS haveβ-type glycosidic bonds and relatively strong resistance to digestion.In vivo experiments showed that the intragastric administration of AEPS in mice with medium dose(0.25 g/kg body weight of mice)has the following effects:remarkably alleviate lincomycin hydrochloride(LIH)-induced injuries to immune organs;enhance the relative abundance of beneficial microorganisms such as Lactobacillus,Roseburia,Ligilactobacillus,and Lachnospiraceae_NK4A136_group in the intestinal tract;greatly reduce the levels of inflammatory cytokines IL-6 and TNF-αin serum and the relative abundances of harmful microbes such as Enterococcus and Shigella;regulate the balance of the gut microflora;and relieve LIH-induced symptoms such as diarrhea,inflammation,and weight loss.These findings might represent a new alternative to develop novel multifunctional carbohydrate prebiotics.