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Sharika R, Mongkolpobsin K, Rangsinth P, Prasanth MI, Nilkhet S, Pradniwat P, Tencomnao T, Chuchawankul S. Experimental Models in Unraveling the Biological Mechanisms of Mushroom-Derived Bioactives against Aging- and Lifestyle-Related Diseases: A Review. Nutrients 2024; 16:2682. [PMID: 39203820 PMCID: PMC11357205 DOI: 10.3390/nu16162682] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2024] [Revised: 07/29/2024] [Accepted: 08/10/2024] [Indexed: 09/03/2024] Open
Abstract
Mushrooms have garnered considerable interest among researchers due to their immense nutritional and therapeutic properties. The presence of biologically active primary and secondary metabolites, which includes several micronutrients, including vitamins, essential minerals, and other dietary fibers, makes them an excellent functional food. Moreover, the dietary inclusion of mushrooms has been reported to reduce the incidence of aging- and lifestyle-related diseases, such as cancer, obesity, and stroke, as well as to provide overall health benefits by promoting immunomodulation, antioxidant activity, and enhancement of gut microbial flora. The multifunctional activities of several mushroom extracts have been evaluated by both in vitro and in vivo studies using cell lines along with invertebrate and vertebrate model systems to address human diseases and disorders at functional and molecular levels. Although each model has its own strengths as well as lacunas, various studies have generated a plethora of data regarding the regulating players that are modulated in order to provide various protective activities; hence, this review intends to compile and provide an overview of the plausible mechanism of action of mushroom-derived bioactives, which will be helpful in future medicinal explorations.
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Affiliation(s)
- Rajasekharan Sharika
- Immunomodulation of Natural Products Research Unit, Chulalongkorn University, Bangkok 10330, Thailand; (R.S.); (K.M.); (S.N.); (P.P.)
- Department of Transfusion Medicine and Clinical Microbiology, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand
| | - Kuljira Mongkolpobsin
- Immunomodulation of Natural Products Research Unit, Chulalongkorn University, Bangkok 10330, Thailand; (R.S.); (K.M.); (S.N.); (P.P.)
- Department of Transfusion Medicine and Clinical Microbiology, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand
| | - Panthakarn Rangsinth
- Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China;
| | - Mani Iyer Prasanth
- Natural Products for Neuroprotection and Anti-Ageing Research Unit, Chulalongkorn University, Bangkok 10330, Thailand; (M.I.P.); (T.T.)
- Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand
| | - Sunita Nilkhet
- Immunomodulation of Natural Products Research Unit, Chulalongkorn University, Bangkok 10330, Thailand; (R.S.); (K.M.); (S.N.); (P.P.)
- Department of Transfusion Medicine and Clinical Microbiology, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand
| | - Paweena Pradniwat
- Immunomodulation of Natural Products Research Unit, Chulalongkorn University, Bangkok 10330, Thailand; (R.S.); (K.M.); (S.N.); (P.P.)
- Department of Clinical Microscopy, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand
| | - Tewin Tencomnao
- Natural Products for Neuroprotection and Anti-Ageing Research Unit, Chulalongkorn University, Bangkok 10330, Thailand; (M.I.P.); (T.T.)
- Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand
| | - Siriporn Chuchawankul
- Immunomodulation of Natural Products Research Unit, Chulalongkorn University, Bangkok 10330, Thailand; (R.S.); (K.M.); (S.N.); (P.P.)
- Department of Transfusion Medicine and Clinical Microbiology, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand
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Ji BR, Huang CW, Chen YI, Ho WJ, Chang SW, Chang SL, Chang CH. Non-Insulin Secretion Relative Hypoglycemic Effect of Neonatal Streptozotocin-induced Diabetic Rats by Gavage Feeding Antrodia cinnamomea (Agaricomycetes). INT J PHARMACOL 2022. [DOI: 10.3923/ijp.2022.1605.1612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Ruan S, Yang Y, Li W. Antrodia Camphorata Polysaccharide activates autophagy and regulates NLRP3 degradation to improve liver injury-related inflammatory response. Aging (Albany NY) 2022; 14:8970-8981. [PMID: 36227135 PMCID: PMC9740354 DOI: 10.18632/aging.204330] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 09/26/2022] [Indexed: 12/14/2022]
Abstract
This study illustrated the liver protection mechanism of ACP from the perspective of autophagy activation. ACP suppressed the inflammatory injury of KCs, and decreased the cell apoptosis rate. After LTG and LC3 staining, ACP promoted lysosomal production, increased LC3 expression, activated autophagy, and suppressed the expression of NLRP3 and inflammatory factors. Under the electron microscope, ACP accelerated the production of autophagosomes. After simultaneous treatment with 3-MA and ACP, the effect of ACP on resisting KC injury decreased, the expression of NLRP3 was up-regulated, and autophagy was suppressed. As discovered in the mouse model of liver injury, ACP inhibited the ALT and AST levels, promoted the occurrence of autophagy, reduced NLRP3 expression and alleviated liver injury. ACP activates autophagy to induce NLRP3 degradation, thus suppressing inflammatory response in liver injury and exerting the liver protection effect, which is one of the mechanisms of action of ACP.
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Affiliation(s)
- Shuiliang Ruan
- Department of Gastroenterology, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314001, Zhejiang Province, China
| | - Yi Yang
- Department of Pharmacy, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314001, Zhejiang Province, China
| | - Wenyan Li
- Department of Pharmacy, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314001, Zhejiang Province, China
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Liu SC, Wu TY, Hsu TH, Lai MN, Wu YC, Ng LT. Chemical Composition and Chronic Toxicity of Disc-Cultured Antrodia cinnamomea Fruiting Bodies. TOXICS 2022; 10:587. [PMID: 36287867 PMCID: PMC9610047 DOI: 10.3390/toxics10100587] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 09/30/2022] [Accepted: 09/30/2022] [Indexed: 06/16/2023]
Abstract
Antrodia cinnamomea (AC) is a popular fungus for use as folk medicine in health maintenance and disease prevention and treatment. Disc culture is a novel technique for producing AC fruiting bodies. This study aimed to investigate the bioactive components and toxicological properties of disc-cultured AC fruiting body powders (ACP) in rats. The HPLC technique was used to quantify the composition of bioactive triterpenoids in ACP. Toxicological properties were evaluated on male and female Sprague-Dawley rats receiving ACP orally at 200, 600, and 1000 mg/kg body weight for 90 days; the control group received only distilled water. The results show that ACP contained seven important AC index compounds, namely antcins A, B, C, K, and H, dehydrosulphurenic acid, and dehydroeburicoic acid. At the tested doses, oral ACP administration for 90 days caused no mortality, adverse effects on general health, body and organ weights, and food intake. Furthermore, no significant variations were observed in hematological and biochemical parameters among either sex of ACP-treated and control animals. An histopathological examination of vital organs showed no significant structural changes in organs, even in high-dose ACP-treated animals. This study indicated that ACP contained the major bioactive triterpenoids of AC fruiting bodies, and its no-observed-adverse-effect level (NOAEL) was 1000 mg/kg/day, about 20 times the recommended daily intake.
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Affiliation(s)
- Shou-Chou Liu
- College of Biotechnology and Bioresources, Da-Yeh University, Changhua County 51591, Taiwan
| | - Tung-Ying Wu
- Department of Food Science and Nutrition, Meiho University, Pingtung 912009, Taiwan
| | - Tai-Hao Hsu
- Department of Medicinal Botanicals and Foods on Health Applications, Da-Yeh University, Changhua County 51591, Taiwan
| | - Ming-Nan Lai
- Kang Jian Biotech Co., Ltd., Nantou 54245, Taiwan
| | - Yang-Chang Wu
- College of Chinese Medicine, China Medical University, Taichung 406040, Taiwan
| | - Lean-Teik Ng
- Department of Agricultural Chemistry, National Taiwan University, No.1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan
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Mameri A, Bournine L, Mouni L, Bensalem S, Iguer-Ouada M. Oxidative stress as an underlying mechanism of anticancer drugs cytotoxicity on human red blood cells' membrane. Toxicol In Vitro 2021; 72:105106. [PMID: 33539984 DOI: 10.1016/j.tiv.2021.105106] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 01/17/2021] [Accepted: 01/30/2021] [Indexed: 11/29/2022]
Abstract
The aim of this study is to investigate the direct in vitro effects of anticancer drugs on red blood cells (RBCs) and to explore the underlying mechanism, mainly by measuring RBCs oxidative stress (OS) status. After RBCs direct contact with fourteen (14) anticancer drugs, several parameters were assessed including: cellular turbidity, methemoglobin (metHb) generation, released Hb and Hb stability. Moreover, intracellular Hb, considered as new molecular target of anticancer drugs, was quantified inside RBCs. MDA level, the main biomarker of OS, was simultaneously measured. The cellular turbidity reveled severe (docetaxel "TXT", 0.03 ± 0.002), moderate (methotrexate "MTX", 0.49 ± 0.009), or none (5-fluorouracil "5-FU", 0.76 ± 0.029) membrane cytotoxicity (MC). An inverse relationship between cell concentration, released Hb and metHb content was obtained. High metHb generation, revealing intense OS, was also mostly expressed in paclitaxel "TXL" and etoposide "VP16". Further, epirubicin "EPI" and "TXT" induced important oxidation of membrane lipids with 0.32 ± 0.014 and 0.26 ± 0.004, respectively. Also, MTX (0.17 ± 0.006) and doxorubicin "DOX" (0.32 ± 0.034) affected significantly Hb stability by a direct contact with molecule. These findings demonstrated that anticancer drugs have the ability to induce membrane damages by the exacerbation of OS through membrane lipid peroxidation and Hb oxidation even inside RBCs.
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Affiliation(s)
- Amal Mameri
- Laboratoire de Gestion et Valorisation des Ressources Naturelles et Assurances Qualités (LGVRNAQ), Faculté des Sciences de la Nature et de la Vie et des Sciences de la Terre, Université de Bouira, 10000 Bouira, Algeria
| | - Lamine Bournine
- Département des Sciences Biologiques, Faculté des Sciences de la Nature et de la Vie et des Sciences de la Terre, Université de Bouira, 10000 Bouira, Algeria; Laboratoire de Biotechnologie Végétales et Ethnobotanique (LBVEB), Faculté des Sciences de la Nature et de la Vie, Université de Bejaia, 06000 Bejaia, Algeria.
| | - Lotfi Mouni
- Laboratoire de Gestion et Valorisation des Ressources Naturelles et Assurances Qualités (LGVRNAQ), Faculté des Sciences de la Nature et de la Vie et des Sciences de la Terre, Université de Bouira, 10000 Bouira, Algeria; Département des Sciences Biologiques, Faculté des Sciences de la Nature et de la Vie et des Sciences de la Terre, Université de Bouira, 10000 Bouira, Algeria
| | - Sihem Bensalem
- Laboratoire de Biotechnologie Végétales et Ethnobotanique (LBVEB), Faculté des Sciences de la Nature et de la Vie, Université de Bejaia, 06000 Bejaia, Algeria
| | - Mokrane Iguer-Ouada
- Laboratoire Associé en Ecosystèmes Marins et Aquacoles (LAEMA), Faculté des Sciences de la Nature et de la Vie, Université de Bejaia, 06000 Bejaia, Algeria
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Wu JD, Chou JC. Optimization of Protoplast Preparation and Regeneration of a Medicinal Fungus Antrodia cinnamomea. MYCOBIOLOGY 2019; 47:483-493. [PMID: 32010470 PMCID: PMC6968695 DOI: 10.1080/12298093.2019.1687252] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/19/2019] [Revised: 10/23/2019] [Accepted: 10/27/2019] [Indexed: 06/10/2023]
Abstract
Antrodia cinnamomea is a unique medicinal fungus in Taiwan. It has been found rich in some pharmacologically active compounds for anti-cancer, hangover, and immune regulation etc. With the in-depth study of these components, it would be interesting and important to establish a molecular system for basic studies of A. cinnamomea. Thus, we would like to set up a foundation for this purpose by studying the A. cinnamomea protoplast preparation and regeneration. Firstly, we studied the optimization method of protoplast preparation of A. cinnamomea, and found various factors that may affect the yield during protoplast preparation, such as mycelial ages, pH values, and osmotic stabilizers. Secondly, in the regeneration of protoplasts, we explored the effects of various conditions on the regeneration of protoplasts, including different media and osmotic pressure. In addition, we found that citrate buffer with pH value around 3 dramatically increased the regeneration of protoplasts of A. cinnamomea, and provided a set of regeneration methodology for A. cinnamomea.
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Affiliation(s)
- Jyun-De Wu
- Department of Life Science, National Dong Hwa University, Hualien, Taiwan
| | - Jyh-Ching Chou
- Department of Natural Resources and Environmental Studies, National Dong Hwa University, Hualien, Taiwan
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Wang C, Zhang W, Wong JH, Ng T, Ye X. Diversity of potentially exploitable pharmacological activities of the highly prized edible medicinal fungus Antrodia camphorata. Appl Microbiol Biotechnol 2019; 103:7843-7867. [PMID: 31407039 DOI: 10.1007/s00253-019-10016-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Revised: 07/08/2019] [Accepted: 07/09/2019] [Indexed: 12/14/2022]
Abstract
Antrodia camphorata, also known as A. cinnamomea, is a precious medicinal basidiomycete fungus endemic to Taiwan. This article summarizes the recent advances in research on the multifarious pharmacological effects of A. camphorata. The mushroom exhibits anticancer activity toward a large variety of cancers including breast, cervical, ovarian, prostate, bladder, colorectal, pancreatic, liver, and lung cancers; melanoma; leukemia; lymphoma; neuroblastoma; and glioblastoma. Other activities encompass antiinflammatory, antiatopic dermatitis, anticachexia, immunoregulatory, antiobesity, antidiabetic, antihyperlipidemic, antiatherosclerotic, antihypertensive, antiplatelet, antioxidative, antiphotodamaging, hepatoprotective, renoprotective, neuroprotective, testis protecting, antiasthmatic, osteogenic, osteoprotective, antiviral, antibacterial, and wound healing activities. This review aims to provide a reference for further development and utilization of this highly prized mushroom.
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Affiliation(s)
- Caicheng Wang
- State Key Laboratory of Ecological Pest Control for Fujian and Taiwan Crops, Fujian Agriculture and Forestry University, Fuzhou, 350002, Fujian, China.,Key Laboratory of Biopesticide and Chemical Biology, Ministry of Education, Fujian Agriculture and Forestry University, Fuzhou, 350002, Fujian, China.,Fujian Key Laboratory of Plant Virology, Institute of Plant Virology, Fujian Agriculture and Forestry University, Fuzhou, 350002, Fujian, China
| | - Weiwei Zhang
- State Key Laboratory of Ecological Pest Control for Fujian and Taiwan Crops, Fujian Agriculture and Forestry University, Fuzhou, 350002, Fujian, China.,Key Laboratory of Biopesticide and Chemical Biology, Ministry of Education, Fujian Agriculture and Forestry University, Fuzhou, 350002, Fujian, China.,Fujian Key Laboratory of Plant Virology, Institute of Plant Virology, Fujian Agriculture and Forestry University, Fuzhou, 350002, Fujian, China
| | - Jack Ho Wong
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Tzibun Ng
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Xiujuan Ye
- State Key Laboratory of Ecological Pest Control for Fujian and Taiwan Crops, Fujian Agriculture and Forestry University, Fuzhou, 350002, Fujian, China. .,Key Laboratory of Biopesticide and Chemical Biology, Ministry of Education, Fujian Agriculture and Forestry University, Fuzhou, 350002, Fujian, China. .,Fujian Key Laboratory of Plant Virology, Institute of Plant Virology, Fujian Agriculture and Forestry University, Fuzhou, 350002, Fujian, China.
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Lin MH, Lee KM, Hsu CY, Peng SY, Lin CN, Chen CC, Fan CK, Cheng PC. Immunopathological effects of Agaricus blazei Murill polysaccharides against Schistosoma mansoni infection by Th1 and NK1 cells differentiation. Int Immunopharmacol 2019; 73:502-514. [DOI: 10.1016/j.intimp.2019.05.045] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2018] [Revised: 01/24/2019] [Accepted: 05/14/2019] [Indexed: 11/27/2022]
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Protective effect of a 3 kDa peptide obtained from beef myofibrillar protein using alkaline-AK on neuronal cells. Neurochem Int 2019; 129:104459. [PMID: 31077759 DOI: 10.1016/j.neuint.2019.05.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 04/29/2019] [Accepted: 05/05/2019] [Indexed: 01/02/2023]
Abstract
The protective effect of two 3 kDa peptide fractions (AK3KF1 and AK3KF2), obtained from beef myofibrillar protein using an inexpensive enzyme (alkaline-AK) on human neuronal cells (SH-SY5Y) against H2O2-induced apoptosis was investigated. These peptides were isolated and further separated by fast protein liquid chromatography (FPLC), and their protective effect against H2O2-mediated cell death was measured by determining cell viability, nitric oxide (NO) production, mitochondrial membrane potential (MMP), apoptosis, morphological changes in cell nuclei, and in vitro antioxidant assays. The results indicated that treatment with peptide fractions increased cell viability and MMP, and decreased NO production, fragmentation of cell nuclei, and apoptosis in H2O2-treated SH-SY5Y cells. This is the first study to report neuroprotective effects of a peptide obtained from beef myofibrillar protein. The peptide sequence was identified as Thr-Gln-Lys-Lys-Val-Ile-Phe-Cys (TQKKVIFC). Thus, these findings suggest that TQKKVIFC can prevent neuronal cell death and could be useful in preventing neurodegenerative diseases.
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Abstract
We report the total synthesis of (±)-antroquinonol based on a concise and efficient route.
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Affiliation(s)
- Xiaoming Wang
- Beijing National Laboratory for Molecular Sciences
- Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education
- Department of Chemical Biology
- College of Chemistry and Molecular Engineering
- Synthetic and Functional Biomolecules Center
| | - Chao Du
- Beijing National Laboratory for Molecular Sciences
- Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education
- Department of Chemical Biology
- College of Chemistry and Molecular Engineering
- Synthetic and Functional Biomolecules Center
| | - Benke Hong
- Beijing National Laboratory for Molecular Sciences
- Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education
- Department of Chemical Biology
- College of Chemistry and Molecular Engineering
- Synthetic and Functional Biomolecules Center
| | - Xiaoguang Lei
- Beijing National Laboratory for Molecular Sciences
- Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education
- Department of Chemical Biology
- College of Chemistry and Molecular Engineering
- Synthetic and Functional Biomolecules Center
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Antroquinonol Exerts Immunosuppressive Effect on CD8 + T Cell Proliferation and Activation to Resist Depigmentation Induced by H 2O 2. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2017; 2017:9303054. [PMID: 29456788 PMCID: PMC5804328 DOI: 10.1155/2017/9303054] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/17/2017] [Revised: 09/17/2017] [Accepted: 10/10/2017] [Indexed: 01/01/2023]
Abstract
Antroquinonol was investigated as antioxidant and inhibition of inflammatory responses. Our study was to evaluate its immunosuppressive effect on CD8+ T cells and protective effect on depigmentation. CD8+ T cells were treated with antroquinonol in vitro, and C57BL/6 mice were treated with antroquinonol with or without H2O2in vivo for 50 consecutive days. We found antroquinonol could inhibit proliferation of CD8+ T cells and suppress the production of cytokines IL-2 and IFN-γ and T cell activation markers CD69 and CD137 in vitro. H2O2 treatment induced depigmentation and reduced hair follicle length, skin thickness, and tyrosinase expression in vivo. Whereas, antroquinonol obviously ameliorated depigmentation of mice skin and resisted the reduction of hair follicle length, skin thickness, and tyrosinase expression induced by H2O2. Antroquinonol decreased CD8+ T cell infiltration in mice skin, inhibited the production of IL-2 and IFN-γ, and decreased the expression of CXCL10 and CXCR3. Summarily, our data shows antroquinonol inhibits CD8+ T cell proliferation in vitro. It also reduces CD8+ T cell infiltration and proinflammatory cytokine secretion and suppresses the thinning of epidermal layer in vivo. Our findings suggest that antroquinonol exerts immunosuppressive effects on CD8+ T cell proliferation and activation to resist depigmentation induced by H2O2.
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Prevention of TGF-β-induced early liver fibrosis by a maleic acid derivative anti-oxidant through suppression of ROS, inflammation and hepatic stellate cells activation. PLoS One 2017; 12:e0174008. [PMID: 28384213 PMCID: PMC5383026 DOI: 10.1371/journal.pone.0174008] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2016] [Accepted: 03/01/2017] [Indexed: 11/19/2022] Open
Abstract
Current anti-fibrotic effect of antioxidants in vivo is disappointing due probably to the fact that once liver fibrogenesis is established it is too advanced to be reversed by anti-oxidation mechanism. We consider antioxidant may only act on the early phase of fibrogenesis. Thus, we had previously established an early liver fibrosis animal model using an inducible expression vector (pPK9a), which contains TGF-β gene and was hydro-dynamically transferred into mice to induce a transient liver fibrosis. TGF-β1 has been well documented to up-regulate the expression of α2(1) collagen (Col 1A2) gene in the liver via the reactive oxygen species (ROS); the process triggers inflammation, leading to hepatic stellate cells (HSC) activation and liver fibrogenesis. Using our animal model and ROS, cyclooxygenase-2 (Cox-2) and Col 1A2 promoter assays as screening targets, we report here that a maleic acid derivative isolated from the Antrodia camphorata mycelium strongly decreases ROS production, promoter activity of Cox-2 and Col 1A2, intracellular calcium, expression of alpha-smooth muscle actin (α-SMA), Smad4-p-Smad2/3 co-localization in cell nucleus and the DNA binding activity of Sp1. Our results suggest that the maleic acid derivative prevents liver fibrosis at an early phase both in vitro and in vivo through the inhibition of ROS, inflammation and the activation of HSC.
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Kumar KJS, Wang SY. Antioxidant Properties of Antrodia cinnamomea: An Extremely Rare and Coveted Medicinal Mushroom Endemic to Taiwan. MEDICINAL AND AROMATIC PLANTS OF THE WORLD 2017. [DOI: 10.1007/978-981-10-5978-0_6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Chen WL, Ho YP, Chou JC. Phenologic variation of major triterpenoids in regular and white Antrodia cinnamomea. BOTANICAL STUDIES 2016; 57:33. [PMID: 28597443 PMCID: PMC5432900 DOI: 10.1186/s40529-016-0148-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/23/2016] [Accepted: 10/20/2016] [Indexed: 06/07/2023]
Abstract
BACKGROUND Antrodia cinnamomea and its host Cinnamomum kanehirae are both endemic species unique to Taiwan. Many studies have confirmed that A. cinnamomea is rich in polysaccharides and triterpenoids that may carry medicinal effects in anti-cancer, anti-inflammation, anti-hypertension, and anti-oxidation. Therefore it is of interest to study the chemical variation of regular orange-red strains and white strains, which included naturally occurring and blue-light induced white A. cinnamomea. RESULTS The chemical profiles of A. cinnamomea extracts at different growth stages were compared using thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). The TLC and HPLC profiles indicated that specific triterpenoids varied between white and regular strains. Moreover, the compounds of blue-light induced white strain were similar to those of naturally occurring white strain but retained specific chemical characteristics in more polar region of the HPLC chromatogram of regular strain. CONCLUSIONS Blue-light radiation could change color of the regular A. cinnamomea from orange-red to white by changing its secondary metabolism and growth condition. Naturally occurring white strain did not show a significantly different composition of triterpenoid profiles up to eight weeks old when compared with the triterpenoid profiles of the regular strain at the same age. The ergostane-type triterpenoids were found existing in both young mycelia and old mycelia with fruiting body in artificial agar-plate medium culture, suggesting a more diversified biosynthetic pathway in artificial agar-plate culture rather than wild or submerged culture.
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Affiliation(s)
- Wei-Lun Chen
- Department of Natural Resources and Environmental Studies, National Dong Hwa University, Shou-feng, Hualien, 97401 Taiwan
| | - Yen-Peng Ho
- Department of Chemistry, National Dong Hwa University, Shou-feng, Hualien, 97401 Taiwan
| | - Jyh-Ching Chou
- Department of Natural Resources and Environmental Studies, National Dong Hwa University, Shou-feng, Hualien, 97401 Taiwan
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Tsai MY, Hung YC, Chen YH, Chen YH, Huang YC, Kao CW, Su YL, Chiu HHE, Rau KM. A preliminary randomised controlled study of short-term Antrodia cinnamomea treatment combined with chemotherapy for patients with advanced cancer. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2016; 16:322. [PMID: 27565426 PMCID: PMC5002173 DOI: 10.1186/s12906-016-1312-9] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/11/2015] [Accepted: 08/23/2016] [Indexed: 01/19/2023]
Abstract
Background Antrodia cinnamomea (AC) is a popular medicinal mushroom in Taiwan that has been widely used for treatment of various cancers. Few clinical studies have reported its application and efficiency in therapeutic chemotherapy strategies. We performed a double-blind, randomized clinical study to investigate whether AC given for 30 days had acceptable safety and efficacy in advanced cancer patients receiving chemotherapy. Methods Patients with advanced and/or metastatic adenocarcinoma, performance status (PS) 0–2, and adequate organ function who had previously been treated with standard chemotherapy were randomly assigned to receive routine chemotherapy regimens with AC (20 ml twice daily) orally for 30 days or placebo. The primary endpoint was 6-month overall survival (OS); the secondary endpoints were disease control rate (DCR), quality of life (QoL), adverse event (AE), and biochemical features within 30 days of treatment. Results From August 2010 to July 2012, 37 subjects with gastric, lung, liver, breast, and colorectal cancer (17 in the AC group, 20 in the placebo group) were enrolled in the study. Disease progression was the primary cause of death in 4 (33.3 %) AC and 8 (66.7 %) placebo recipients. Mean OSs were 5.4 months for the AC group and 5.0 months for the placebo group (p = 0.340), and the DCRs were 41.2 and 55 %, respectively (p = 0.33). Most hematologic, liver, or kidney functions did not differ significantly between the two groups, but platelet counts were lower in the AC group than in the placebo group (p = 0.02). QoL assessments were similar in the two groups, except that the AC group showed significant improvements in quality of sleep (p = 0.04). Conclusions Although we found a lower mortality rate and longer mean OS in the AC group than in the control group, A. cinnamomea combined with chemotherapy was not shown to improve the outcome of advanced cancer patients, possibly due to the small sample size. In fact, the combination may present a potential risk of lowered platelet counts. Adequately powered clinical trials will be necessary to address this question. Trial registration ClinicalTrials.gov NCT01287286.
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Correlation between liver cirrhosis and risk of death from oral cancer: Taiwan cohort study. The Journal of Laryngology & Otology 2016; 130:565-70. [PMID: 27160281 DOI: 10.1017/s002221511600791x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND A nationwide population-based cohort was used to examine the severity of liver cirrhosis and risk of mortality from oral cancer. METHODS The cohort consisted of 3583 patients with oral cancer treated by surgery between 2008 and 2011 in Taiwan. They were grouped on the basis of normal liver function (n = 3471), cirrhosis without decompensation (n = 72) and cirrhosis with decompensation (n = 40). The primary endpoint was mortality. Hazard ratios of death were also determined. RESULTS The mortality rates in the respective groups were 14.8 per cent, 20.8 per cent and 37.5 per cent at one year (p < 0.001). The adjusted hazard ratios of death at one year for each group compared to the normal group were 2.01 (p = 0.021) for cirrhotic patients without decompensation, 4.84 (p < 0.001) for those with decompensation and 2.65 (p < 0.001) for those receiving chemotherapy. CONCLUSION Liver cirrhosis can be used to predict one-year mortality in oral cancer patients. Chemotherapy should be used with caution and underlying co-morbidities should be managed in cirrhotic patients to reduce mortality risk.
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Application of Antrodia camphorata Promotes Rat's Wound Healing In Vivo and Facilitates Fibroblast Cell Proliferation In Vitro. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2015; 2015:317693. [PMID: 26557855 PMCID: PMC4617886 DOI: 10.1155/2015/317693] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/21/2015] [Revised: 08/15/2015] [Accepted: 08/23/2015] [Indexed: 01/26/2023]
Abstract
Antrodia camphorata is a parasitic fungus from Taiwan, it has been documented to possess a variety of pharmacological and biological activities. The present study was undertaken to evaluate the potential of Antrodia camphorata ethanol extract to accelerate the rate of wound healing closure and histology of wound area in experimental rats. The safety of Antrodia camphorata was determined in vivo by the acute toxicity test and in vitro by fibroblast cell proliferation assay. The scratch assay was used to evaluate the in vitro wound healing in fibroblast cells and the excision model of wound healing was tested in vivo using four groups of adult Sprague Dawley rats. Our results showed that wound treated with Antrodia camphorata extract and intrasite gel significantly accelerates the rate of wound healing closure than those treated with the vehicle. Wounds dressed with Antrodia camphorata extract showed remarkably less scar width at wound closure and granulation tissue contained less inflammatory cell and more fibroblast compared to wounds treated with the vehicle. Masson's trichrom stain showed granulation tissue containing more collagen and less inflammatory cell in Antrodia camphorata treated wounds. In conclusion, Antrodia camphorata extract significantly enhanced the rate of the wound enclosure in rats and promotes the in vitro healing through fibroblast cell proliferation.
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Protection against oxidative damage in human erythrocytes and preliminary photosafety assessment of Punica granatum seed oil nanoemulsions entrapping polyphenol-rich ethyl acetate fraction. Toxicol In Vitro 2015; 30:421-8. [PMID: 26407526 DOI: 10.1016/j.tiv.2015.09.020] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2015] [Revised: 09/18/2015] [Accepted: 09/20/2015] [Indexed: 11/21/2022]
Abstract
The main purpose of the present study is to evaluate the ability of nanoemulsion entrapping pomegranate peel polyphenol-rich ethyl acetate fraction (EAF) prepared from pomegranate seed oil and medium chain triglyceride to protect human erythrocyte membrane from oxidative damage and to assess preliminary in vitro photosafety. In order to evaluate the phototoxic effect of nanoemulsions, human red blood cells (RBCs) are used as a biological model and the rate of haemolysis and photohaemolysis (5 J cm(-2) UVA) is assessed in vitro. The level of protection against oxidative damage caused by the peroxyl radical generator AAPH in human RBCs as well as its effects on bilayer membrane characteristics such as fluidity, protein profile and RBCs morphology are determined. EAF-loaded nanoemulsions do not promote haemolysis or photohaemolysis. Anisotropy measurements show that nanoemulsions significantly retrain the increase in membrane fluidity caused by AAPH. SDS-PAGE analysis reveals that AAPH induced degradation of membrane proteins, but that nanoemulsions reduce the extension of degradation. Scanning electron microscopy examinations corroborate the interaction between AAPH, nanoemulsions and the RBC membrane bilayer. Our work demonstrates that Punica granatum nanoemulsions are photosafe and protect RBCs against oxidative damage and possible disturbance of the lipid bilayer of biomembranes. Moreover it suggests that these nanoemulsions could be promising new topical products to reduce the effects of sunlight on skin.
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Lee YC, Ho CL, Kao WY, Chen YM. A phase I multicenter study of antroquinonol in patients with metastatic non-small-cell lung cancer who have received at least two prior systemic treatment regimens, including one platinum-based chemotherapy regimen. Mol Clin Oncol 2015; 3:1375-1380. [PMID: 26807250 DOI: 10.3892/mco.2015.642] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2015] [Accepted: 09/08/2015] [Indexed: 12/31/2022] Open
Abstract
Antroquinonol is isolated from Antrodia camphorata, a camphor tree mushroom, and is a valuable traditional Chinese herbal medicine that exhibits pharmacological activities against several diseases, including cancer. This first-in-human phase I study of antroquinonol included patients with metastatic non-small-cell lung cancer who had received at least two prior systemic treatment regimens. An open-label, dose escalation, pharmacokinetic (PK) study was conducted to determine the maximum tolerable dose (MTD), dose-limiting toxicities (DLTs), and safety/tolerability and preliminary efficacy profiles of antroquinonol. The patients received escalating doses of once-daily antroquinonol in 4-week cycles (up to 3 cycles). The escalated doses were 50-600 mg. PKs were evaluated on day 1 and 28 of cycle 1. Between January, 2011 and October, 2012, 13 patients with metastatic adenocarcinoma were enrolled. No DLTs occurred in any patient at any dose level. Tmax was observed between 1.00 and 3.70 h under single-dose conditions, and at 1.92-4.05 h under multiple-dose conditions. The mean elimination half-life ranged between 1.30 and 4.33 h, independent of the treatment dose. Antroquinonol at all dose levels had a mild toxicity profile, with no reported treatment-related mortality. The most common treatment-related adverse events were diarrhea, vomiting and nausea. The best tumor response was stable disease in 3 patients. In conclusion, antroquinonol at all dose levels, administered daily for 4 weeks, was generally safe and well tolerated, without DLTs. The recommended dose level for a phase II study is ≥600 mg daily.
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Affiliation(s)
- Yu-Chin Lee
- Sijhih Cathay General Hospital, New Taipei 221, Taiwan, R.O.C.; School of Medicine, National Yang-Ming University, Taipei 112, Taiwan, R.O.C
| | - Ching-Liang Ho
- Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, R.O.C
| | - Woei-Yau Kao
- Taipei Tzu Chi General Hospital, Taipei 231, Taiwan, R.O.C
| | - Yuh-Min Chen
- School of Medicine, National Yang-Ming University, Taipei 112, Taiwan, R.O.C.; Department of Chest Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan, R.O.C.; College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan, R.O.C
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Kandikattu HK, Rachitha P, Krupashree K, Jayashree GV, Abhishek V, Khanum F. LC-ESI-MS/MS analysis of total oligomeric flavonoid fraction of Cyperus rotundus and its antioxidant, macromolecule damage protective and antihemolytic effects. ACTA ACUST UNITED AC 2015; 22:165-73. [PMID: 26319439 DOI: 10.1016/j.pathophys.2015.07.001] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2014] [Revised: 05/28/2015] [Accepted: 07/19/2015] [Indexed: 10/23/2022]
Abstract
In the present investigation, we identified the phytochemical constituents of total oligomeric flavonoid fraction (TOF) of Cyperus rotundus by LC-ESI-MS/MS and also demonstrated its antihemolytic effects against 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) induced hemolysis of rat erythrocytes. Our results of TOF extract exhibited DPPH, metal chelating, ABTS, NO and hydroxyl radical scavenging activities with an IC50 values of 23.72±1.6, 52.45±2.88, 9.8±0.42, 6.5±0.33 and 120±6.83μg/ml respectively, whereas total antioxidant and reducing power activities were 194±12.5μg GAE/mg extract and 145±8.3μg AAE/mg extract. The extract showed potent inhibitory activity against AAPH induced plasmid DNA damage, protein oxidation and lipid peroxidation. The TOF extract mitigates AAPH induced hemolysis and exhibits ∼50% antihemolytic activity. TOF pretreatment also preserved morphology of erythrocytes as observed and measured by light microscope and atomic force microscope analysis. Furthermore, the TOF fraction effectively inhibited AAPH induced LDH release, ROS generation and lipid peroxidation. Taken together, our data demonstrate the antihemolytic activity of C. rotundus against AAPH induced oxidative stress of erythrocytes, and was associated with the decrease in oxidative stress, cellular damage and protection of macromolecules. In conclusion, the effects might be correlated with high content of flavonoids and polyphenols identified in C. rotundus. This suggests the clinical application of TOF fraction of C. rotundus against ROS induced cell death.
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Affiliation(s)
- Hemanth Kumar Kandikattu
- Biochemistry and Nanosciences Discipline, Defence Food Research Laboratory, Mysore 570011, Karnataka, India
| | - P Rachitha
- Biochemistry and Nanosciences Discipline, Defence Food Research Laboratory, Mysore 570011, Karnataka, India
| | - K Krupashree
- Biochemistry and Nanosciences Discipline, Defence Food Research Laboratory, Mysore 570011, Karnataka, India
| | - G V Jayashree
- Biochemistry and Nanosciences Discipline, Defence Food Research Laboratory, Mysore 570011, Karnataka, India
| | - Virat Abhishek
- Food Engineering and Packaging Division, Defence Food Research Laboratory, Mysore 570011, Karnataka, India
| | - Farhath Khanum
- Biochemistry and Nanosciences Discipline, Defence Food Research Laboratory, Mysore 570011, Karnataka, India.
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Ribeiro AB, Berto A, Ribeiro D, Freitas M, Chisté RC, Visentainer JV, Fernandes E. Stem bark and flower extracts of Vismia cauliflora are highly effective antioxidants to human blood cells by preventing oxidative burst in neutrophils and oxidative damage in erythrocytes. PHARMACEUTICAL BIOLOGY 2015; 53:1691-1698. [PMID: 25868622 DOI: 10.3109/13880209.2014.1001407] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
CONTEXT Vismia cauliflora A.C.Sm. [Hypericaceae (Clusiaceae)] is an Amazonian plant traditionally used by indigenous population to treat dermatosis and inflammatory processes of the skin. Previous research on V. cauliflora extracts suggests its potential to neutralize cellular oxidative damages related to the production of reactive oxygen and nitrogen species. OBJECTIVE To determine the activity of stem bark and flower extracts of V. cauliflora on the modulation of oxidative burst in human neutrophils, as well as its potential to inhibit oxidative damage in human erythrocytes. MATERIALS AND METHODS The modulation of neutrophil's oxidative burst by the ethanolic extracts (0.3-1000 µg/mL) was determined by the oxidation of specific probes by reactive species. Additionally, the potential of these extracts to inhibit oxidative damage in human erythrocytes was evaluated by monitoring its biomarkers of oxidative stress. RESULTS Vismia cauliflora extracts presented remarkable capacity to prevent the oxidative burst in activated human neutrophils (IC50 < 15 µg/mL). However, the maximum percentage of inhibition achieved against hydrogen peroxide was 45%. Concerning the oxidative damage in human erythrocytes, the extracts were able to minimize the tert-butyl hydroperoxide-induced hemoglobin oxidation and lipid peroxidation in a very low concentration range (2.7-18 μg/mL). Furthermore, only stem bark extract (100 µg/mL) was able to inhibit the depletion of glutathione (13%). DISCUSSION AND CONCLUSION These results reinforce the therapeutic potential of stem bark and flower extracts of V. cauliflora to heal topical skin disease, namely in the treatment of neutrophil-related dermatosis and skin conditions related to oxidative stress, including skin aging.
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Affiliation(s)
- Rohidas S. Sulake
- Department
of Chemistry, National Dong Hwa University, Hualien 97401, Taiwan
| | - Chinpiao Chen
- Department
of Chemistry, National Dong Hwa University, Hualien 97401, Taiwan
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Yang HL, Lin SW, Lee CC, Lin KY, Liao CH, Yang TY, Wang HM, Huang HC, Wu CR, Hseu YC. Induction of Nrf2-mediated genes by Antrodia salmonea inhibits ROS generation and inflammatory effects in lipopolysaccharide-stimulated RAW264.7 macrophages. Food Funct 2014; 6:230-41. [PMID: 25380370 DOI: 10.1039/c4fo00869c] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
Antrodia salmonea (AS), a well-known medicinal mushroom in Taiwan, has been reported to exhibit anti-oxidant, anti-angiogenic, anti-atherogenic, and anti-inflammatory effects. In the present study, we investigated the activation of Nrf2-mediated antioxidant genes in RAW264.7 macrophages by the fermented culture broth of AS, studied the resulting protection against lipopolysaccharide (LPS)-stimulated inflammation, and revealed the molecular mechanisms underlying these protective effects. We found that non-cytotoxic concentrations of AS (25-100 μg mL⁻¹) protected macrophages from LPS-induced cell death and ROS generation in a dose-dependent manner. The antioxidant potential of AS was directly correlated with the increased expression of the antioxidant genes HO-1, NQO-1, and γ-GCLC, as well as the level of intracellular GSH followed by an increase in the nuclear translocation and transcriptional activation of the Nrf2-ARE pathway. Furthermore, Nrf2 knockdown diminished the protective effects of AS, as evidenced by the increased production of pro-inflammatory cytokines and chemokines, including PGE₂, NO, TNF-α, and IL-1β, in LPS-stimulated macrophages. Notably, AS treatment significantly inhibited LPS-induced ICAM-1 expression in macrophages. Our data suggest that the anti-inflammatory potential of Antrodia salmonea is mediated by the activation of Nrf2-dependent antioxidant defense mechanisms. Results support the traditional usage of this beneficial mushroom for the treatment of free radical-related diseases and inflammation.
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Affiliation(s)
- Hsin-Ling Yang
- Institute of Nutrition, China Medical University, Taichung 40402, Taiwan
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Tung YT, Tsai TC, Kuo YH, Yen CC, Sun JY, Chang WH, Chen HL, Chen CM. Comparison of solid-state-cultured and wood-cultured Antrodia camphorata in anti-inflammatory effects using NF-κB/luciferase inducible transgenic mice. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2014; 21:1708-1716. [PMID: 25442281 DOI: 10.1016/j.phymed.2014.08.011] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/01/2014] [Revised: 07/28/2014] [Accepted: 08/24/2014] [Indexed: 06/04/2023]
Abstract
PURPOSE Antrodia camphorata (AC), a highly valued polypore mushroom native only to Taiwan, has been traditionally used as a medicine for the treatment of food and drug intoxication, diarrhea, abdominal pain, hypertension, skin itching, and cancer. In this study, both of solid-state-cultured AC (S-AC) and wood-cultured AC (W-AC) were evaluated the anti-inflammatory effects on hyperoxia-induced lung injury in NF-κB-luciferase(+/+) transgenic mice. METHODS The homozygous transgenic mice (NF-κB-luciferase(+/+)) were randomly assigned to four groups for treatment (n = 6) including Normoxia/DMSO group, Hyperoxia/DMSO group, Hyperoxia/S-AC group, and Hyperoxia/W-AC group. After 72 h of hyperoxia, we examined the bioluminescence images, reactive oxygen species (ROS), the mRNA and protein expression levels of inflammation factors, and histopathological analyses of the lung tissues. RESULTS Hyperoxia-induced lung injury significantly increased the generation of ROS, the mRNA levels of IL-6, TNF-α, IL-1β and IL-8, and the protein expression levels of IKKα/β, iNOS and IL-6. Pulmonary edema and alveolar infiltration of neutrophils was also observed in the hyperoxia-induced lung tissue. However, treatment with either S-AC or W-AC obviously decreased hyperoxia-induced generation of ROS and the expression of IL-6, TNF-α, IL-1β, IL-8, IKKα/β and iNOS compared to hyperoxia treatment alone. Lung histopathology also showed that treatment with either S-AC or W-AC significantly reduced neutrophil infiltration and lung edema compared to treatment with hyperoxia treated alone. To find out their major compounds, eburicoic acid and dehydroeburicoic acid were both isolated and identified from S-AC and W-AC by using HPLC, MS, and NMR spectrometry. CONCLUSIONS These results demonstrated that methanolic extracts both of S-AC and W-AC have excellent anti-inflammatory activities and thus have great potential as a source for natural health products.
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Affiliation(s)
- Yu-Tang Tung
- Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan
| | - Tung-Chou Tsai
- Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan
| | - Yueh-Hsiung Kuo
- Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 404, Taiwan; Department of Biotechnology, Asia University, Taichung 413, Taiwan
| | - Chih-Ching Yen
- China Medical University Hospital, and China Medical University, Taichung 404, Taiwan
| | - Jheng-Yue Sun
- Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan
| | - Wen-Hui Chang
- Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan
| | - Hsiao-Ling Chen
- Department of Bioresources, Da-Yeh University, Changhwa 515, Taiwan
| | - Chuan-Mu Chen
- Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan; Rong Hsing Research Center for Translational Medicine and iEGG Center, National Chung Hsing University, Taichung 402, Taiwan.
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Effect of Antrodia camphorata on inflammatory arterial thrombosis-mediated platelet activation: the pivotal role of protein kinase C. ScientificWorldJournal 2014; 2014:745802. [PMID: 25541625 PMCID: PMC4212544 DOI: 10.1155/2014/745802] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2014] [Accepted: 09/11/2014] [Indexed: 01/31/2023] Open
Abstract
Antrodia camphorata is a rare Taiwanese medicinal mushroom. Antrodia camphorata extract has been reported to exhibit antioxidant, anti-inflammation, antimetastasis, and anticancer activities and plays a role in liver fibrosis, vasorelaxation, and immunomodulation. Critical vascular inflammation leads to vascular dysfunction and cardiovascular diseases, including abdominal aortic aneurysms, hypertension, and atherosclerosis. Platelet activation plays a crucial role in intravascular thrombosis, which is involved in a wide variety of cardiovascular diseases. However, the effect of Antrodia camphorata on platelet activation remains unclear. We examined the effects of Antrodia camphorata on platelet activation. In the present study, Antrodia camphorata treatment (56-224 μg/mL) inhibited platelet aggregation induced by collagen, but not U46619, an analogue of thromboxane A2, thrombin, and arachidonic acid. Antrodia camphorata inhibited collagen-induced calcium (Ca(2+)) mobilization and phosphorylation of protein kinase C (PKC) and Akt. In addition, Antrodia camphorata significantly reduced the aggregation and phosphorylation of PKC in phorbol-12, 13-dibutyrate (PDBu) activated platelets. In conclusion, Antrodia camphorata may inhibit platelet activation by inhibiting of Ca(2+) and PKC cascade and the Akt pathway. Our study suggests that Antrodia camphorata may be a potential therapeutic agent for preventing or treating thromboembolic disorders.
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Antimicrobial activity of Antrodia camphorata extracts against oral bacteria. PLoS One 2014; 9:e105286. [PMID: 25144619 PMCID: PMC4140745 DOI: 10.1371/journal.pone.0105286] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2014] [Accepted: 07/21/2014] [Indexed: 11/19/2022] Open
Abstract
Antrodia camphorata (A. camphorata) is a unique, endemic and extremely rare mushroom species native to Taiwan, and both crude extracts of and purified chemical compounds from A. camphorata have been reported to have a variety of significant beneficial effects, such as anti-tumor and anti-inflammatory activity. However, reports on the effects of A. camphorata against dental pathogens have been limited. Oral health is now recognized as important for overall general health, including conditions such as dental caries, periodontal disease and rheumatoid arthritis. Streptococcus mutans (S. mutans) and Porphyromonas gingivalis (P. gingivalis) are the most common bacteria associated with dental plaque and periodontopathic diseases, respectively. Thus, our study examined the ability of five various crude extracts of A. camphorata to inhibit the growth of dental bacteria and anti-adherence in vitro. Among the extracts, the ethanol, ethyl acetate and chloroform extracts exhibited the lowest MICs against P. gingivalis and S. mutans (MIC = 4∼16 µg/mL). The MIC of the aqueous extract was greater than 2048 µg/mL against both P. gingivalis and S. mutans. In vitro adherence of S. mutans was significantly inhibited by the addition of either the ethyl acetate extract or chloroform extract (MIC = 16∼24 µg/mL), while the ethanol extract (MIC = 32∼64 µg/mL) exhibited moderate inhibitory activity. Based on the result of this study, the ethyl acetate and chloroform extracts of A. camphorata may be good candidates for oral hygiene agents to control dental caries and periodontopathic conditions.
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Cheng PC, Huang CC, Chiang PF, Lin CN, Li LL, Lee TW, Lin B, Chen IC, Chang KW, Fan CK, Luo TY. Radioprotective effects ofAntrodia cinnamomeaare enhanced on immune cells and inhibited on cancer cells. Int J Radiat Biol 2014; 90:841-52. [DOI: 10.3109/09553002.2014.911989] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
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Liu DZ, Liang YC, Lin SY, Lin YS, Wu WC, Hou WC, Su CH. Antihypertensive Activities of a Solid-State Culture ofTaiwanofungus camphoratus(Chang-Chih) in Spontaneously Hypertensive Rats. Biosci Biotechnol Biochem 2014; 71:23-30. [PMID: 17213674 DOI: 10.1271/bbb.60268] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Wild and solid-state cultures (SSC) of Taiwanofungus camphoratus (aka Antrodia camphorata and Chang-chih [CC]) were sequentially extracted with cold water, methanol, and hot water to get cold-water-soluble (CWS), methanol-soluble (MS), and hot-water-soluble (HWS) extracts, respectively. Only the MS extract exhibited angiotensin-converting enzyme (ACE) inhibitory activities. The antihypertensive effects of the MS extract (10 mg/kg BW) were measured in spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats. MS extract of the SSC type was able to effectively lower the systolic blood pressure (SBP) and diastolic blood pressure (DBP) of SHR, but not of WKY rats, the results being significantly different from those for distilled water only (the blank). However, wild CC and its MS extract were not as effective as the SSC type in reducing SHR blood pressure and had no effect on WKY rats. SSC-type CC might be developed into a health food with the ability to regulate blood pressure.
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Affiliation(s)
- Der-Zen Liu
- Graduate Institute of Biomedical Materials and Engineering, Taipei Medical University, Taiwan
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Chen YR, Chang KT, Tsai MJ, Lee CH, Huang KJ, Cheng H, Ho YP, Chen JC, Yang HH, Weng CF. Antrodia cinnamomea profoundly exalted the reversion of activated hepatic stellate cells by the alteration of cellular proteins. Food Chem Toxicol 2014; 69:150-62. [PMID: 24751970 DOI: 10.1016/j.fct.2014.04.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2013] [Revised: 03/24/2014] [Accepted: 04/04/2014] [Indexed: 01/05/2023]
Abstract
The direct modulation of Antrodia cinnamomea (AC) on the prominent role of liver fibrosis-hepatic stellate cells (HSCs) in situ remains unclear. Firstly, the administration of A. cinnamomea mycelial extract (ACME) could improve liver morphology and histological changes including collagen formation and GPT activity in the liver of thioacetamide (TAA)-injured rats. The morphology and fatty acid restore of TAA-induced HSCs (THSCs) returned to the non-chemical induced HSCs (NHSCs) type as measured by immunofluorescence and Oil Red O staining. PPARγ was upregulated associated with the lowering of α-SMA protein in NHSC-ACME. ACME inhibited the MMP-2 activity in NHSCs by gelatin Zymography. After LC-MS/MS, the cytoskeleton (tubulin, lamin A) and heat shock protein 8 in NHSC-ACME, and guanylate kinase, brain-specific kinase, SG-II and p55 proteins were downregulated in THSC-ACME. Whereas MHC class II, SMC6 protein, and phospholipase D were upregulated in NHSC-ACME. Furthermore, PKG-1 was downregulated in NHSC-ACME and upregulated in THSC-ACME. SG-II and p55 proteins were downregulated in NHSC-ACME and THSC-ACME by Western blotting. Taken together, the beneficial effect of A. cinnamomea on the induction of HSC cellular proteins is potentially applied as an alternative and complementary medicine for the prevention and amelioration of a liver injury.
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Affiliation(s)
- Yi-Ren Chen
- Institute of Biotechnology, National Dong Hwa University, Hualien 974, Taiwan
| | - Kai-Ting Chang
- Institute of Biotechnology, National Dong Hwa University, Hualien 974, Taiwan
| | - May-Jywan Tsai
- Neural Regeneration Laboratory, Neurological Institute, Taipei Veterans General Hospital, Taipei 112, Taiwan
| | - Chia-Hung Lee
- Institute of Biotechnology, National Dong Hwa University, Hualien 974, Taiwan
| | - Kao-Jean Huang
- Institute of Biotechnology, National Dong Hwa University, Hualien 974, Taiwan
| | - Henrich Cheng
- Neural Regeneration Laboratory, Neurological Institute, Taipei Veterans General Hospital, Taipei 112, Taiwan
| | - Yen-Peng Ho
- Department of Chemistry, National Dong Hwa University, Hualien 974, Taiwan
| | - Jian-Chyi Chen
- Department of Biotechnology, Southern Taiwan University, Tainan 710, Taiwan
| | - Hsueh-Hui Yang
- Department of Research, Buddhist Tzu Chi General Hospital, General Education Center, Tzu Chi College of Technology, Hualien 970, Taiwan
| | - Ching-Feng Weng
- Institute of Biotechnology, National Dong Hwa University, Hualien 974, Taiwan.
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Hseu YC, Lee CC, Chen YC, Senthil Kumar K, Chen CS, Tsai CT, Huang HC, Wang HM, Yang HL. Antrodia salmonea in submerged culture exhibits antioxidant activities in vitro and protects human erythrocytes and low-density lipoproteins from oxidative modification. Food Chem Toxicol 2014; 66:150-7. [DOI: 10.1016/j.fct.2014.01.035] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2013] [Revised: 01/13/2014] [Accepted: 01/20/2014] [Indexed: 02/02/2023]
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Park DK, Lim YH, Park HJ. Antrodia camphorata grown on germinated brown rice inhibits HT-29 human colon carcinoma proliferation through inducing G0/G1 phase arrest and apoptosis by targeting the β-catenin signaling. J Med Food 2014; 16:681-91. [PMID: 23957353 DOI: 10.1089/jmf.2012.2605] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
Antrodia camphorata (AC) has been used as a traditional medicine to treat food and drug intoxication, diarrhea, abdominal pain, hypertension, pruritis (skin itch), and liver cancer in East Asia. In this study, we investigated anticancer activities of AC grown on germinated brown rice (CBR) in HT-29 human colon cancer cells. We found that the inhibitory efficacy of CBR 80% ethanol (EtOH) extract on HT-29 and CT-26 cell proliferation was more effective than ordinary AC EtOH 80% extract. Next, 80% EtOH extract of CBR was further separated into four fractions; hexane, ethyl acetate (EtOAc), butanol (BuOH), and water. Among them, CBR EtOAc fraction showed the strongest inhibitory activity against HT-29 cell proliferation. Therefore, CBR EtOAc fraction was chosen for further studies. Annexin V-fluorescein isothiocyanate staining data indicated that CBR EtOAc fraction induced apoptosis. Induction of G0/G1 cell cycle arrest on human colon carcinoma cell was observed in CBR EtOAc fraction-treated cells. We found that CBR decreased the level of proteins involved in G0/G1 cell cycle arrest and apoptosis. CBR EtOAc fraction inhibited the β-catenin signaling pathway, supporting its suppressive activity on the level of cyclin D1. High performance liquid chromatography analysis data indicated that CBR EtOAc fraction contained adenosine. This is the first investigation that CBR has a greater potential as a novel chemopreventive agent than AC against colon cancer. These data suggest that CBR might be useful as a chemopreventive agent against colorectal cancer.
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Affiliation(s)
- Dong Ki Park
- Cell Activation Research Institute, Konkuk University, Seoul, Korea
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Chisté RC, Freitas M, Mercadante AZ, Fernandes E. Carotenoids inhibit lipid peroxidation and hemoglobin oxidation, but not the depletion of glutathione induced by ROS in human erythrocytes. Life Sci 2014; 99:52-60. [DOI: 10.1016/j.lfs.2014.01.059] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2013] [Revised: 12/10/2013] [Accepted: 01/17/2014] [Indexed: 11/29/2022]
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Yang HL, Kumar KJS, Kuo YT, Chang HC, Liao JW, Hsu LS, Hseu YC. Antrodia camphorata induces G1 cell-cycle arrest in human premyelocytic leukemia (HL-60) cells and suppresses tumor growth in athymic nude mice. Food Funct 2014; 5:2278-88. [DOI: 10.1039/c4fo00423j] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Antrodia camphorata is a well-known medicinal mushroom in Taiwan.
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Affiliation(s)
- Hsin-Ling Yang
- Institute of Nutrition
- China Medical University
- Taichung 40402, Taiwan
| | | | - Ya-Ting Kuo
- Institute of Nutrition
- China Medical University
- Taichung 40402, Taiwan
| | - Hebron C. Chang
- Institute of Biotechnology and Bioinformatics
- Asia University
- Taichung 41354, Taiwan
| | - Jiunn-Wang Liao
- Graduate Institute of Veterinary Pathology
- National Chung Hsing University
- Taichung 402, Taiwan
| | - Li-Sung Hsu
- Institute of Biochemistry and Biotechnology
- Chung Shan Medical University
- Taichung 40401, Taiwan
| | - You-Cheng Hseu
- Department of Health and Nutrition Biotechnology
- Asia University
- Taichung 41354, Taiwan
- Department of Cosmeceutics
- College of Pharmacy
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Yang FC, Yang YH, Lu HC. Enhanced antioxidant and antitumor activities of Antrodia cinnamomea cultured with cereal substrates in solid state fermentation. Biochem Eng J 2013. [DOI: 10.1016/j.bej.2013.04.020] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
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Yang SM, Ka SM, Hua KF, Wu TH, Chuang YP, Lin YW, Yang FL, Wu SH, Yang SS, Lin SH, Chang JM, Chen A. Antroquinonol mitigates an accelerated and progressive IgA nephropathy model in mice by activating the Nrf2 pathway and inhibiting T cells and NLRP3 inflammasome. Free Radic Biol Med 2013; 61:285-97. [PMID: 23567192 DOI: 10.1016/j.freeradbiomed.2013.03.024] [Citation(s) in RCA: 67] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2012] [Revised: 02/25/2013] [Accepted: 03/28/2013] [Indexed: 12/12/2022]
Abstract
High levels of reactive oxygen species (ROS), systemic T cell activation, and macrophage infiltration in the kidney are implicated in the acceleration and progression of IgA nephropathy (IgAN), the most frequent type of primary glomerulonephritis. However, the pathogenic mechanism of IgAN is still little understood, and it remains a challenge to establish a specific therapeutic strategy for this type of glomerular disorder. Recently, we showed that antroquinonol (Antroq), a pure active compound from Antrodia camphorata mycelium, inhibits renal inflammation and reduces oxidative stress in a mouse model of renal fibrosis. But the anti-inflammatory and immune-regulatory effects of Antroq on the acceleration and progression of primary glomerular disorders have not been determined. In this study, we show that Antroq administration substantially impeded the development of severe renal lesions, such as intense glomerular proliferation, crescents, sclerosis, and periglomerular interstitial inflammation, in mice with induced accelerated and progressive IgAN (AcP-IgAN). Further mechanistic analysis in AcP-IgAN mice showed that, early in the developmental stage of the AcP-IgAN model, Antroq promoted the Nrf2 antioxidant pathway and inhibited the activation of T cells and NLRP3 inflammasome. Significantly improved proteinuria/renal function and histopathology in AcP-IgAN mice of an established stage supported potential therapeutic effects of Antroq on the disease. In addition, Antroq was shown to inhibit activation of NLRP3 inflammasome in vitro by an IgA immune complex (IC) partly involving a reduced ROS production in IgA-IC-primed macrophages, and this finding may be helpful in the understanding of the mode of action of Antroq in the treated AcP-IgAN mice.
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Affiliation(s)
- Shun-Min Yang
- Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC
| | - Shuk-Man Ka
- Graduate Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei, Taiwan, ROC.
| | - Kuo-Feng Hua
- Department of Biotechnology and Animal Science, National Ilan University, Ilan, Taiwan, ROC
| | - Tzu-Hua Wu
- Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC
| | - Yi-Ping Chuang
- Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan, ROC
| | - Ya-Wen Lin
- Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan, ROC
| | - Feng-Ling Yang
- Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan, ROC
| | - Shih-Hsiung Wu
- Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan, ROC
| | - Sung-Sen Yang
- Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC
| | - Shih-Hua Lin
- Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC
| | - Jia-Ming Chang
- Department of Pharmacology, Institute for Drug Evaluation Platform, Development Center for Biotechnology, Taipei, Taiwan, ROC
| | - Ann Chen
- Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC; Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
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Yang HL, Lin KY, Juan YC, Kumar KJS, Way TD, Shen PC, Chen SC, Hseu YC. The anti-cancer activity of Antrodia camphorata against human ovarian carcinoma (SKOV-3) cells via modulation of HER-2/neu signaling pathway. JOURNAL OF ETHNOPHARMACOLOGY 2013; 148:254-265. [PMID: 23619020 DOI: 10.1016/j.jep.2013.04.023] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/21/2012] [Revised: 03/09/2013] [Accepted: 04/08/2013] [Indexed: 06/02/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Antrodia camphorata (AC) is well known in Taiwan as a traditional Chinese medicinal fungus. However, the anticancer activity of AC against human HER-2/neu-overexpressing ovarian cancers is poorly understood. MATERIALS AND METHODS The aim of this study is to investigate whether a submerged fermentation culture of AC can inhibit human ovarian carcinoma cell (SKOV-3) proliferation by suppressing the HER-2/neu signaling pathway. Cell viability, colony formation, DCFH-DA fluorescence microscopy, western blotting, HER-2/neu immunofluorescence imaging, flow cytometry, and TUNEL assays were carried out to determine the anti-cancer effects of AC. RESULTS MTT and colony formation assays showed that AC induced a dose-dependent reduction in SKOV-3 cell growth. Immunoblot analysis demonstrated that HER-2/neu activity and tyrosine phosphorylation were significantly inhibited by AC. Furthermore, AC treatment significantly inhibited the activation of PI3K/Akt and their downstream effector β-catenin. We also observed that AC caused G2/M arrest mediated by down-regulation of cyclin D1, cyclin A, cyclin B1, and Cdk1 and increased p27 expression. Notably, AC induced apoptosis, which was associated with DNA fragmentation, cytochrome c release, caspase-9/-3 activation, PARP degradation, and Bcl-2/Bax dysregulation. An increase in intracellular reactive oxygen species (ROS) was observed in AC-treated cells, whereas the antioxidant N-acetylcysteine (NAC) prevented AC-induced cell death, HER-2/neu depletion, PI3K/Akt inactivation, and Bcl-2/Bax dysregulation, indicating that AC-induced cell death was mediated by ROS generation. CONCLUSIONS These results suggest that AC may exert anti-tumor activity against human ovarian carcinoma by suppressing HER-2/neu signaling pathways.
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Affiliation(s)
- Hsin-Ling Yang
- Institute of Nutrition, China Medical University, Taichung, Taiwan
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Antioxidant effect of astragalin isolated from the leaves of Morus alba L. against free radical-induced oxidative hemolysis of human red blood cells. Arch Pharm Res 2013; 36:912-7. [PMID: 23512775 DOI: 10.1007/s12272-013-0090-x] [Citation(s) in RCA: 61] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2013] [Revised: 03/02/2013] [Accepted: 03/05/2013] [Indexed: 12/12/2022]
Abstract
We evaluated the antioxidant properties of mulberry leaves extract (MLE) and flavonoids isolated from MLE. MLE was prepared by extraction with methanol. Flavonoids were analyzed by high-performance liquid chromatography. Oxidative hemolysis of normal human red blood cells (RBCs) was induced by the aqueous peroxyl radical [2,2'-Azobis (2-amidinopropane) dihydrochloride, AAPH]. MLE contained three flavonoids in the order quercetin (QC) > kaempferol (KF) > astragalin (AG). Oxidative hemolysis of RBCs induced by AAPH was suppressed by MLE, AG, KF, and QC in a time- and dose-dependent manner. MLE and these three flavonoids prevented the depletion of cystosolic antioxidant glutathione (GSH) in RBCs. AG had the greatest protective effect against AAPH-induced oxidative hemolysis and GSH depletion in RBCs.
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Wu MD, Cheng MJ, Yech YJ, Yuan GF, Chen JJ. Inhibitory Effects of Maleimide Derivatives from the Mycelia of the FungusAntrodia cinnamomeaBCRC 36799 on Nitric Oxide Production in Lipopolysaccharide (LPS)-Activated RAW264.7 Macrophages. Chem Biodivers 2013; 10:434-41. [DOI: 10.1002/cbdv.201200258] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2012] [Indexed: 11/08/2022]
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Medicinal Fungus Antrodia cinnamomea Inhibits Growth and Cancer Stem Cell Characteristics of Hepatocellular Carcinoma. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2013; 2013:569737. [PMID: 23533499 PMCID: PMC3606723 DOI: 10.1155/2013/569737] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/01/2013] [Accepted: 01/16/2013] [Indexed: 01/19/2023]
Abstract
Background. Antrodia cinnamomea is an edible fungus commonly used in Asia as a well-known medicinal herb capable of treating drug intoxication and liver cancer. Methods. This study evaluated the anticancer activity of its biotechnological product, mycelial fermentation broth (AC-MFB) on hepatocellular carcinoma (HCC) by tetrazolium-based colorimetric assay in vitro and syngeneic Balb/c 1MEA.7R.1 tumor implantation model in vivo. Given that cancer stem cell characteristics, such as angiogenesis, invasiveness, and migration, are known to cause recurrence, we further evaluated the effect of AC-MFB on cellular viability inhibition of HCC cells, angiogenic activity and migration of endothelial cells, and the release of proangiogenic factors from HCC cells. Results. We found that AC-MFB markedly inhibited the growth of HCC without hepatic enzyme abnormality. This anti-HCC activity was validated by growth-inhibitory effects on both cultured murine 1MEA.7R.1 and human HA22T/VGH HCC cells. For cancer stem cell characteristics, AC-MFB inhibited the cellular viability, migration, and tube formation activity of EA. hy926 and SVEC4-10 endothelial cells. Production of extracellular vascular endothelial growth factor and intracellular hypoxia-inducible factor-1 alpha from HCC cells was suppressed by AC-MFB. Conclusion. Antrodia cinnamomea could inhibit the growth and cancer stem cell characteristics of HCC cells.
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Adesanoye OA, Molehin OR, Delima AA, Adefegha AS, Farombi EO. Modulatory effect of methanolic extract ofVernonia amygdalina(MEVA) on tert-butyl hydroperoxide-induced erythrocyte haemolysis. Cell Biochem Funct 2012. [DOI: 10.1002/cbf.2933] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Affiliation(s)
- Omolola A. Adesanoye
- Drug Metabolism & Toxicology Research Laboratories, Department of Biochemistry, College of Medicine; University of Ibadan; Ibadan; Nigeria
| | - Olorunfemi R. Molehin
- Drug Metabolism & Toxicology Research Laboratories, Department of Biochemistry, College of Medicine; University of Ibadan; Ibadan; Nigeria
| | - Adetutu A. Delima
- Drug Metabolism & Toxicology Research Laboratories, Department of Biochemistry, College of Medicine; University of Ibadan; Ibadan; Nigeria
| | - Adeniyi S. Adefegha
- Drug Metabolism & Toxicology Research Laboratories, Department of Biochemistry, College of Medicine; University of Ibadan; Ibadan; Nigeria
| | - Ebenezer O. Farombi
- Drug Metabolism & Toxicology Research Laboratories, Department of Biochemistry, College of Medicine; University of Ibadan; Ibadan; Nigeria
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The Antitumor Activity of Antrodia camphorata in Melanoma Cells: Modulation of Wnt/β-Catenin Signaling Pathways. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2012; 2012:197309. [PMID: 23049605 PMCID: PMC3463817 DOI: 10.1155/2012/197309] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/06/2012] [Accepted: 08/14/2012] [Indexed: 12/16/2022]
Abstract
Antrodia camphorata (AC) is well known in Taiwan as a traditional Chinese medicine. The aim of this study was to investigate whether a fermented culture broth of AC could inhibit melanoma proliferation and progression via suppression of the Wnt/β-catenin signaling pathway. In this study, we observed that AC treatment resulted in decreased cell viability and disturbed Wnt/β-catenin cascade in B16F10 and/or B16F1 melanoma cells. This result was accompanied by a decrease in the expression of Wnt/β-catenin transcriptional targets, including c-Myc and survivin. Furthermore, treatment of melanoma cells with AC resulted in a significant increase in apoptosis, which was associated with DNA fragmentation, cytochrome c release, caspase-9 and -3 activation, PARP degradation, Bcl-2/Bax dysregulation, and p53 expression. We also observed that AC caused G1 phase arrest mediated by a downregulation of cyclin D1 and CDK4 and increased p21 and p27 expression. In addition, we demonstrated that non- and subcytotoxic concentrations of AC markedly inhibited migration and invasion of highly metastatic B16F10 cells. The antimetastatic effect of AC was further confirmed by reductions in the levels of MMP-2, MMP-9, and VEGF expression. These results suggest that Antrodia camphorata may exert antitumor activity by downregulating the Wnt/β-catenin pathways.
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Wen CL, Teng CL, Chiang CH, Chang CC, Hwang WL, Kuo CL, Hsu SL. Methanol extract of Antrodia cinnamomea mycelia induces phenotypic and functional differentiation of HL60 into monocyte-like cells via an ERK/CEBP-β signaling pathway. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2012; 19:424-435. [PMID: 22293124 DOI: 10.1016/j.phymed.2011.11.003] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/07/2011] [Revised: 10/05/2011] [Accepted: 11/02/2011] [Indexed: 05/31/2023]
Abstract
Antrodia cinnamomea (named as Niu-chang-chih), a well-known Taiwanese folk medicinal mushroom, has a spectrum of biological activities, especially with anti-tumor property. This study was carried out for the first time to examine the potential role and the underlying mechanisms of A. cinnamomea in the differentiation of human leukemia HL60 cells. We found that the methanol extract of liquid cultured mycelia of A. cinnamomea (MEMAC) inhibited proliferation and induced G1-phase cell cycle arrest in HL60 cells. MEMAC could induce differentiation of HL60 cells into the monocytic lineage, as evaluated by the morphological change, nitroblue tetrazolium reduction assay, non-specific esterase assay, and expression of CD14 and CD11b surface antigens. In addition, MEMAC activated the extracellular signal-regulated kinase (ERK) pathway and increased CCAAT/enhancer-binding protein β (C/EBPβ) expression. Reverse transcriptase polymerase chain reaction analysis showed that MEMAC upregulated the expression of C/EBPβ and CD14 mRNA in HL60 cells. DNA affinity precipitation assay and chromatin immunoprecipitation analyses indicated that MEMAC enhanced the direct binding of C/EBPβ to its response element located at upstream of the CD14 promoter. Furthermore, inhibiting ERK pathway activation with PD98059 markedly blocked MEMAC-induced HL60 monocytic differentiation. Consistently, the MEMAC-mediated upregulation of C/EBPβ and CD14 was also suppressed by PD98059. These findings demonstrate that MEMAC-induced HL60 cell monocytic differentiation is via the activating ERK signaling pathway, and downstream upregulating the transcription factor C/EBPβ and differentiation marker CD14 gene, suggesting that MEMAC might be a potential differentiation-inducing agent for treatment of leukemia.
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Affiliation(s)
- Chi-Luan Wen
- Taiwan Seed Improvement and Propagation Station, Council of Agriculture, Propagation Technology Section, Taichung, Taiwan
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Wang LC, Wang SE, Wang JJ, Tsai TY, Lin CH, Pan TM, Lee CL. In vitro and in vivo comparisons of the effects of the fruiting body and mycelium of Antrodia camphorata against amyloid β-protein-induced neurotoxicity and memory impairment. Appl Microbiol Biotechnol 2012; 94:1505-19. [PMID: 22350319 DOI: 10.1007/s00253-012-3941-3] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2011] [Revised: 02/01/2012] [Accepted: 02/02/2012] [Indexed: 11/30/2022]
Abstract
Antrodia camphorata is a particular and precious medicinal mushroom, and its fruiting body was found to provide more efficient protection from oxidative stress and inflammation than its mycelium because of its higher content of triterpenoids, total phenols, and so on. In the previous in vitro studies, the mycelium of A. camphorata is proven to provide strong neuroprotection in neuron cells and suggested to have the potential of protection against neurotoxicity of amyloid β-protein (Aβ) known as the risk factor toward Alzheimer's disease (AD) development. However, the in vivo study and the comparison study with the fruiting body have not yet been investigated. This study compared the effect of the fruiting body and mycelium of A. camphorata on alleviating the Aβ40-induced neurocytotoxicity in the in vitro Aβ-damaged neuron cell model (PC-12 cell treated with Aβ40) and memory impairment in the in vivo AD animal model induced with a continuous brain infusion of Aβ40. In the results of in vitro and in vivo studies, the fruiting body possessed stronger anti-oxidative and anti-inflammatory abilities for inhibiting neurocytotoxicity in Aβ40-treated PC-12 cells and Aβ40 accumulation in Aβ40-infused brain than mycelium. Moreover, hyperphosphorylated tau (p-tau) protein expression, known as an important AD risk factor, was suppressed by the treatment of fruiting body rather than that of mycelium in the in vitro and in vivo studies. These comparisons supported the reasons why the fruiting body resulted in a more significant improvement effect on working memory ability than mycelium in the AD rats.
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Affiliation(s)
- Li-Chun Wang
- Continuing Education School, National Taitung Junior College, Taitung, Taiwan, Republic of China
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Tsai PY, Ka SM, Chang JM, Lai JH, Dai MS, Jheng HL, Kuo MT, Chen P, Chen A. Antroquinonol differentially modulates T cell activity and reduces interleukin-18 production, but enhances Nrf2 activation, in murine accelerated severe lupus nephritis. ACTA ACUST UNITED AC 2012; 64:232-42. [PMID: 21905011 DOI: 10.1002/art.33328] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
OBJECTIVE Accelerated severe lupus nephritis (ASLN), with an acute onset of severe clinical manifestations and histopathologic renal lesions, may represent transformation of mild LN to a severe form of glomerulonephritis. Abnormal activation of T and B cells and/or oxidative stress may play a major role in the pathogenesis of ASLN. This study tested the hypothesis that antroquinonol, a purified compound and major effective component of Antrodia camphorata with antiinflammatory and antioxidant activities, might prevent the transformation of mild LN into higher-grade (severe) nephritis in a murine lupus model. METHODS Experimental ASLN was induced in (NZB×NZW)F1 mice by twice weekly intraperitoneal injections of Salmonella-type lipopolysaccharide (LPS). Starting 2 days after the first dose of LPS, mice were treated daily with antroquinonol, administered by gavage, for different durations up to 5 weeks. RESULTS Antroquinonol administration significantly ameliorated the proteinuria, hematuria, impairment of renal function, and development of severe renal lesions, especially cellular crescent formation, neutrophil infiltration, fibrinoid necrosis, and T cell proliferation in the glomerulus, as well as periglomerular interstitial inflammation. Mechanistic analyses revealed that antroquinonol 1) inhibited T cell activation/proliferation, but enhanced Treg cell suppression and reduced renal production of interleukin-18 (IL-18); 2) inhibited production of reactive oxygen species and nitric oxide, but increased activation of Nrf2 in the kidney; and 3) suppressed renal inflammation via blocking of NF-κB activation. CONCLUSION Antroquinonol may have therapeutic potential for the early treatment of ASLN via its differential regulation of T cell function and lowering of IL-18 production, but also via the promotion of Nrf2 activation.
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Affiliation(s)
- Pei-Yi Tsai
- Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, and Development Center for Biotechnology, Taipei, Taiwan, Republic of China
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LAI MINNAN, KO HUEYJIUN, NG LEANTEIK. HYPOLIPIDEMIC EFFECTS OF ANTRODIA CINNAMOMEA EXTRACTS IN HIGH-FAT DIET-FED HAMSTERS. J Food Biochem 2011. [DOI: 10.1111/j.1745-4514.2010.00530.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
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Lin YW, Chiang BH. 4-acetylantroquinonol B isolated from Antrodia cinnamomea arrests proliferation of human hepatocellular carcinoma HepG2 cell by affecting p53, p21 and p27 levels. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2011; 59:8625-8631. [PMID: 21739974 DOI: 10.1021/jf2011326] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/31/2023]
Abstract
The 4-acetylantroquinonol B isolated from the mycelium of Antrodia cinnamomea could inhibit proliferation of hepatocellular carcinoma cells HepG2 with IC(50) 0.1 μg/mL. When the HepG2 cells were treated with 4-acetylantroquinonol B for 72 h, the proportion of cells in the G1 phase of the cell cycle increased and that in the S phase decreased significantly, and the proportion of G2/M phase cells were not obviously changed. In addition, the 4-acetylantroquinonol B treatment resulted in the decreases of CDK2 and CDK4, and an increase of p27 in a dose-dependent manner. The protein levels of p53 and p21 proteins were also increased when the cells were treated with low dosage (0.1 μg/mL) of 4-acetylantroquinonol B. Higher dosages, however, decreased the expression of p53 and p21 proteins. Assay of RT-PCR indicated that, corresponding to the increases of p53 and p21 proteins at the dosage of 0.1 μg/mL, the mRNAs of p53 and p21 showed 1.66- and 1.61-fold upregulations, respectively. Corresponding to the decreases of CDK2 and CDK4 proteins, the mRNAs of CDK2 and CDK4 showed -1.02- and -1.13-fold downregulations, respectively. However, level of p27 mRNA showed -1.2-fold downregulation in spite of the increase in p27 protein. This observation, again, confirms the fact that the p27 gene rarely undergoes homozygous inactivation in cancer cells. Our finding suggested that the 4-acetylantroquinonol B inhibits proliferation of HepG2 cells via affecting p53, p21 and p27 proteins, and can be considered as a potential cancer drug.
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Affiliation(s)
- Yu-Wei Lin
- Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan
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Wu MD, Cheng MJ, Wang WY, Huang HC, Yuan GF, Chen JJ, Chen IS, Wang BC. Antioxidant activities of extracts and metabolites isolated from the fungus Antrodia cinnamomea. Nat Prod Res 2011; 25:1488-96. [PMID: 21337253 DOI: 10.1080/14786410903132563] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Three different solvent partitions (n-hexane, ethyl acetate [EtOAc] and n-BuOH) of the culture broth from Antrodia cinnamomea were assayed with two different radical scavenging methods: 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and superoxide radical scavenging (SOD) assay. The EtOAc layer exhibited the best antioxidant activity. Two major antioxidant metabolites were isolated from the active EtOAc layer. The antioxidant activities of compounds 1-6 were further evaluated by DPPH, SOD and trolox equivalent antioxidant capacity (TEAC) assays. Compounds 3 and 5 showed stronger free radical scavenging than the reference BHA, ED₅₀ = 1.36 and 34.24 µM. Compound 5 displayed moderate SOD activity (ED₅₀ = 310.0 µM), and its antioxidant capacity of TEAC value was 2.2 mM trolox equivalency.
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Affiliation(s)
- Ming-Der Wu
- Bioresource Collection and Research Center (BCRC), Food Industry Research and Development Institute (FIRDI), Hsinchu 300, Taiwan.
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Marouf BH, Zalzala MH, Al-Khalifa II, Aziz TA, Hussain SA. Free radical scavenging activity of silibinin in nitrite-induced hemoglobin oxidation and membrane fragility models. Saudi Pharm J 2011; 19:177-83. [PMID: 23960757 PMCID: PMC3745080 DOI: 10.1016/j.jsps.2011.03.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2011] [Accepted: 03/13/2011] [Indexed: 01/23/2023] Open
Abstract
Free radical formation in heme proteins is recognized as a factor in mediating the toxicity of many drugs. Xenobiotics and drug therapy-related toxicity, due to oxidative modification of hemoglobin (Hb), has been attributed in part to the uncontrolled oxidative reactions. A variety of antioxidant strategies to ameliorate potential oxidative damage in vivo have been suggested. The present study was designed to evaluate the dose-response relationship of the free radical scavenging properties of silibinin dihemisuccinate (SDH) in nitrite-induced Hb oxidation in vitro and in vivo. Different concentrations of SDH were added, before and after different intervals of inducing Hb oxidation in erythrocytes lysate, and formation of methemoglobin (MetHb) was monitored spectrophotometrically; the same approach was utilized to evaluate the effect of the same doses of SDH on the integrity of erythrocytes after induction of hemolysis. Moreover, the most effective dose of SDH was administered in rats before challenge with toxic dose of sodium nitrite, and MetHb formation was monitored as mentioned before. The results showed that in both in vitro and in vivo models, SDH successfully attenuates Hb oxidation after challenge with sodium nitrite; this protective effect was not related to the stage of the catalytic stage of Hb oxidation, though the effect was more prominent when the compound was administered before nitrite. In conclusion, SDH can effectively, in concentration-dependent pattern, attenuate sodium nitrite-induced Hb oxidation and maintain integrity of red blood cells both in vitro and in vivo.
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Affiliation(s)
- Bushra H. Marouf
- Department of Pharmacology, College of Pharmacy, University of Sulaimani, Kurdistan, Iraq
| | - Munaf H. Zalzala
- Department of Pharmacology and Toxicology, College of Pharmacy, University of Baghdad, Baghdad, Iraq
| | - Ihab I. Al-Khalifa
- Department of Pharmacology and Toxicology, College of Pharmacy, University of Baghdad, Baghdad, Iraq
| | - Tavga A. Aziz
- Department of Pharmacology, College of Pharmacy, University of Sulaimani, Kurdistan, Iraq
| | - Saad A. Hussain
- Department of Pharmacology and Toxicology, College of Pharmacy, University of Baghdad, Baghdad, Iraq
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Tsai PY, Ka SM, Chao TK, Chang JM, Lin SH, Li CY, Kuo MT, Chen P, Chen A. Antroquinonol reduces oxidative stress by enhancing the Nrf2 signaling pathway and inhibits inflammation and sclerosis in focal segmental glomerulosclerosis mice. Free Radic Biol Med 2011; 50:1503-16. [PMID: 21376112 DOI: 10.1016/j.freeradbiomed.2011.02.029] [Citation(s) in RCA: 63] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2010] [Accepted: 02/24/2011] [Indexed: 12/24/2022]
Abstract
Oxidative stress, inflammation, and fibrosis are involved in the development and progression of focal segmental glomerulosclerosis (FSGS), a common form of idiopathic nephrotic syndrome that represents a therapeutic challenge because it has a poor response to steroids. Antroquinonol (Antroq), a purified compound, is a major active component of a mushroom, namely Antrodia camphorata, that grows in the camphor tree in Taiwan, and it has inhibitory effects on nitric oxide production and inflammatory reactions. We hypothesized that Antroq might ameliorate FSGS renal lesions by modulating the pathogenic pathways of oxidative stress, inflammation, and glomerular sclerosis in the kidney. We demonstrate that Antroq significantly (1) attenuates proteinuria, renal dysfunction, and glomerulopathy, including epithelial hyperplasia lesions and podocyte injury; (2) reduces oxidative stress, leukocyte infiltration, and expression of fibrosis-related proteins in the kidney; (3) increases renal nuclear factor E2-related factor 2 (Nrf2) and glutathione peroxidase activity; and (4) inhibits renal nuclear factor-κB (NF-κB) activation and decreases levels of transforming growth factor (TGF)-β1 in serum and kidney tissue in a mouse FSGS model. Our data suggest that Antroq might be a potential therapeutic agent for FSGS, acting by boosting Nrf2 activation and suppressing NF-κB-dependent inflammatory and TGF-β1-mediated fibrosis pathways in the kidney.
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Affiliation(s)
- Pei-Yi Tsai
- Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China
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Nutritional Composition, Antioxidant Activities, and Antiulcer Potential of Lentinus squarrosulus (Mont.) Mycelia Extract. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2011; 2011:539356. [PMID: 21423634 PMCID: PMC3057541 DOI: 10.1155/2011/539356] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/20/2010] [Revised: 12/24/2010] [Accepted: 01/12/2011] [Indexed: 11/30/2022]
Abstract
Water extract of Lentinus squarrosulus mycelia was analysed for nutritional content, antioxidant capacity, and antiulcer ability. The extract contains high protein (57.6 g/100 g) and low total fat (0.5 g/100 g) and is rich in magnesium (0.4 g/100 g), potassium (3.8 g/100 g), vitamins B1 (1.42 mg/100 g), and B3 (194.29 mg/100 g) with total phenolic content of 39.16 mg/100 g. The cupric reducing antioxidant capacity and 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity of the extract were A450 of 0.20 ± 0.03 at 0.5 mg/ml and IC50 of 14.29 mg/ml, respectively. Oral feeding of L. squarrosulus extract (250 mg/kg) offered significant gastric mucosal protection of Sprague-Dawley rats compared to cimetidine (50 mg/kg). The ulcer healing rate of ulcerated rats after 24, 48, and 72 hours of treatment was 82%, 90%, and 100%, respectively. The IL-1β level in the serum and the NF-κB level in the tissues indicate that the healing potential was associated with attenuation of proinflammatory cytokines.
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