Cited by 29Fungal Biology and ApplicationsDrug-Induced Hepatotoxicity and ProtectionMedicinal plant effects and applications

Hepatoprotective Bioactivity of the Glycoprotein, Antrodan, Isolated from Antrodia cinnamomea Mycelia

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Ker, Yaw-Bee, Peng, Chiung-Chi, Chang, Wan-Lin, Chyau, Charng-Cherng, Peng, Robert Y.·2014·PLoS ONE

Abstract

Antrodan, a protein-bound polysaccharide isolated from Antrodia cinnamomea mycelia, was demonstrated to exhibit significant anti-inflammatory bioactivity in vitro. However, its role in hepatic injury in vivo still remains unclear. We hypothesized that antrodan may have beneficial hepatoprotective effects. To verify this, a lipopolysaccharide (LPS)-Sprague-Dawley rat model was used. Antrodan protected against liver damage by suppressing LPS-stimulated serum glutamine-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), interleukin (IL)-6, hepatic thiobarbituric acid reactive substances (TBARS), nitric oxide (NO), inducible NO synthase (iNOS) and nuclear factor (NF)-κB, and by effectively alleviating the downregulated hepatic superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px). Hematoxylin-eosin staining revealed that antrodan at a dosage of 40 mg/kg was able to alleviate LPS-induced liver damage to a normal status. In addition, we identified the partial main architectural backbone of antrodan to have a 1 → 3 linear β-glycosidic backbone of mannan linked by β-1 → 3 glucosidic branches. Conclusively, antrodan can potentially ameliorate liver damage in vivo by suppressing oxidative stress induced by LPS.

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Crossref · 10.1371/journal.pone.0093191

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  • H&E staining of Day 30 iHLOs revealed epithelial luminal structures.

    “Hematoxylin and eosin (H&E) staining revealed epithelial luminal structures, further substantiating epithelial maturation (Fig. 1G and Supplementary Fig. 1A)27.”

    From ​Temporal proteomic profiling of iPSC-derived human liver organoids reveals optimal maturation for drug metabolism and toxicology (2026) · cites this paper as [27]

    The Materials and Methods section describes H&E staining of liver tissue collected after LPS administration, while the Results section discusses hepatic injury. Our copy does not address Day 30 iHLOs, epithelial luminal structures, or their maturation (searched: iHLOs, epithelial lumen, organoids). (LLM, conf=0.75)

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Research works printed but not linked: 44

  1. [1]Chen J, Seviour R (2007) Medicinal importance of fungal beta-(1→3), (1→6)-glucans. Mycol Res 111: 635– 652. 17590323
  2. [2]Bohn JA, BeMiller JN (1995) (1→3)-β-D-glucans as biological response modifiers: a review of structure-functional activity relationships. Carbohydr Polym 28: 3– 14.
  3. [3]Tsukagoshi S, Hashimoto Y, Fujii G, Kobayashi H, Nomoto K, et al (1984) Krestin (PSK). Cancer Treat Rev 11: 31– 55. 6238674
  4. [4]Chan GCF, Chan WK, Sze DMY (2009) The effects of β-glucan on human immune and cancer cells (review). J Hematol Oncol 2: 25. 19515245 PMC2704234
  5. [5]Jedinak A, Dudhgaonkar S, Wu QL, Simon J, Sliva D (2011) Anti-inflammatory activity of edible oyster mushroom is mediated through the inhibition of NFκB and AP-1 signaling. Nutri J 10: 52. PMC3120742 21575254
  6. [6]Song KS, Li G, Kim JS, Jing K, Kim TD, et al (2011) Protein-bound polysaccharide from Phellinus linteus inhibits tumor growth, invasion, and angiogenesis and alters Wnt/b-catenin in SW480 human colon cancer cells. BMC Cancer 11: 307. 21781302 PMC3154178
  7. [7]Hong F, Yan J, Baran JT, Allendorf DJ, Hansen RD, et al (2004) Mechanism by which orally administered (beta)-1→3-glucans enhance the tumoricidal activity of antitumor monoclonal antibodies in murine tumor models. J Immunol 173: 797– 806. 15240666
  8. [8]Takimoto H, Wakita D, Kawaguchi K, Kumazawa Y (2004) Potentiation of cytotoxic activity in naive and tumor-bearing mice by oral administration of hot-water extracts from Agaricus blazei fruiting bodies. Biol Pharm Bull 27: 404– 406. 14993810
  9. [9]Yun CH, Estrada A, Van KA, Park BC, Laarveld B (2003) Beta-glucan, extracted from oat, enhances disease resistance against bacterial and parasitic infections. FEMS Immunol Med Microbiol 35: 67– 75. 12589959
  10. [10]Chen J, Raymond K (2008) Beta-glucans in the treatment of diabetes and associated cardiovascular risks. Vasc Health Risk Manag 4: 1265– 1272. 19337540 PMC2663451
  11. [11]Torkelson CJ, Sweet E, Martzen MR, Sasagawa M, Wenner CA, et al. (2012) Phase 1 clinical trial of Trametes versicolor in women with breast cancer. ISRN Oncol doi: 10.5402/2012/251632 PMC3369477 22701186 · DOI
  12. [12]Akagi J, Baba H (2010) PSK may suppress CD57+ T cells to improve survival of advanced gastric cancer patients. Int J Clin Oncol 15: 145– 152. 20229169
  13. [13]Maehara Y, Tsujitani S, Saeki H, Oki E, Yoshinaga K, et al (2012) Biological mechanism and clinical effect of protein-bound polysaccharide K (KRESTIN): review of development and future perspectives. Surg Today 42: 8– 28. 22139128 PMC3253283
  14. [14]Geethangili M, Tzeng YM (2011) Review of pharmacological effects of Antrodia camphorata and its bioactive compounds. Evid Based Complement Alternat Med doi: 10.1093/ecam/nep108 PMC3095428 19687189 · DOI
  15. [16]Lee SB, Jeon HW, Lee YW, Lee YML, Song KW, et al (2003) Bio-artificial skin composed of gelatin and (1,3), (1,6)-glucan. Biomaterials 24: 2503– 2511. 12695077
  16. [17]Moradali MF, Mostafavi H, Ghods S, Hedjaroude GA (2007) Immunomodulating and anticancer agents in the realm of macromycetes fungi (macrofungi). Int Immunopharmacol (7) 701– 724. 17466905
  17. [18]Chiu CH, Peng CC, Ker YB, Chen CC, Lee A, et al (2014) Physicochemical characteristics and anti-inflammatory activities of a novel glycoprotein, antrodan, isolated from Antrodia cinnamomea mycelia. Molecules 19: 22– 40. PMC6271056 24451244
  18. [19]Carbonero ER, Sassaki GL, Gorin PAG, Iacomini M (2002) A (1→6)-linked β-mannopyrananan, pseudonigeran, and a (1→4)-linked β-xylan, isolated from the lichenised basidiomycete Dictyonema glabratum. FEMS Microbiol Lett 206: 175– 178. 11814659
  19. [20]Wang CL, Pi CC, Kuo CW, Zhuang YJ, Khoo KH, et al (2011) Polysaccharides purified from the submerged culture of Ganoderma formosanum stimulate macrophage activation and protect mice against Listeria monocytogenes infection. Biotechnol Lett 33: 2271– 2278. 21744272
  20. [21]Miranda KM, Espey MG, Wink DA (2001) A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide 1: 62– 71. 11178938
  21. [22]Bradford MM (1976) A rapid and sensitive method for the quantitation of micro quantities of protein utilizing the principle of protein-dye binding. Anal Chem 72: 248– 254. 942051
  22. [23]Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47: 469– 474. 4215654
  23. [24]Aebi H (1984) Catalase in vitro. Methods Enzymol 105: 121– 126. 6727660
  24. [25]Lawrence RA, Burk RF (1976) Glutathione peroxidase activity in selenium- deficient rat liver. Biochem Biophys Res Commun 71: 952– 958. 971321
  25. [26]Buege JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52: 302– 310. 672633
  26. [27]Chen H, Zhang M, Xie B (2004) Quantification of uronic acids in tea polysaccharide conjugates and their antioxidant properties. J Agric Food Chem 52: 3333– 3336. 15161193
  27. [28]Lindequist U, Niedermeyer TH, Jülich WD (2005) The pharmacological potential of mushrooms. Evid Based Complement Alternat Med 2: 285– 299. 16136207 PMC1193547
  28. [30]Liu F, Ooi VEC, Chang ST (1997) Free radical scavenging activities of mushroom polysaccharide extracts. Life Sci 60: 763– 771. 9064481
  29. [32]Akira S, Taga T, Kishimoto T (1993) Interleukin-6 in biology and medicine. Adv Immunol 54: 1– 78. 8379461
  30. [33]Gao B (2012) Hepatoprotective and anti-inflammatory cytokines in alcoholic liver disease. J Gastroenterol Hepatol 27S2: 89– 93. PMC3281557 22320924
  31. [34]Damas P, Ledoux D, Nys M, Vrindts Y, De Groote D, et al (1992) Cytokine serum levels during severe sepsis in human: IL-6 as a marker of severity. Ann Surg 215: 362– 365. PMC1242452 1558416
  32. [35]Neveu WA, Bernardo E, Allard JL, Nagaleekar V, Wargo MJ, et al. (2011) Fungal allergen β-glucans trigger p38 mitogen-activated protein kinase–mediated IL-6 translation in lung epithelial cells. Am J Respir Cell Mol Biol 45: 1133–1141. PMC3262672 21642586
  33. [36]Mohamadin AM, Elberry AA, Elkablawy MA, Gawad HS, Al-Abbasi FA (2011) Montelukast, a leukotriene receptor antagonist abrogates lipopolysaccharide-induced toxicity and oxidative stress in rat liver. Pathophysiology 18: 235– 242. 21419608
  34. [37]Yokoyama H, Mizukami T, Kamegaya Y, Fukuda M, Okamura Y, et al (1998) Formation of superoxide anion in the hepatic sinusoid after lipopolysaccharide challenge. Alcohol Clin Exp Res 22(3S): 133S– 136S. 9622390
  35. [38]Sebai H, Sani M, Yacoubi MT, Aouani E, Ghanem-Boughanmi N, et al (2010) Resveratrol, a red wine polyphenol, attenuates lipopolysaccharide-induced oxidative stress in rat liver. Ecotoxicol Environ Saf 73: 1078– 1083. 20089305
  36. [39]Boveris A, Alvarez S, Navarro A (2002) The role of mitochondrial nitric oxide synthase in inflammation and septic shock. Free Radic Biol Med 33: 1186– 1193. 12398926
  37. [40]Yazar E, Er A, Uney K, Bulbul A, Avci GE, et al (2010) Effects of drugs used in endotoxic shock on oxidative stress and organ damage markers. Free Radic Res 44: 397– 402. 20102316
  38. [41]Green SJ, Scheller LF, Marletta MA, Seguin MC, Klotz FW, et al (1994) Nitric oxide: cytokine-regulation of nitric oxide in host resistance to intracellular pathogens. Immunol Lett 43: 87– 94. 7537721
  39. [42]Mungrue IN, Husain M, Stewart DJ (2002) The role of NOS in heart failure: lessons from murine genetic models. Heart Fail Rev 7 407–422: 39. 12379825
  40. [43]Fujimiya Y, Suzuki Y, Oshiman K, Kobori H, Moriguchi K, et al. (1998) Selective tumoricidal effect of soluble proteoglucan extracted from the Basidiomycete, Agaricus blazei Murill, mediated via natural killer cell activation and apoptosis. Cancer Immunol Immunother 46: 147–59 1998. PMC11037308 9625538
  41. [44]Yoshimura M, Nishikawa A, Ihara Y, Taniguchi S, Taniguchi T (1995) Suppression of lung metastasis of B16 mouse melanoma by N-acetylglucosaminyltransferase III gene transfection. Proc Natl Acad Sci U S A 92: 8754– 8758. 7568011 PMC41045
  42. [45]Fuster MM, Esko JD (2005) The sweet and sour of cancer: glycans as novel therapeutic targets. Nat Rev Cancer 5: 526– 542. 16069816
  43. [46]Dennis JW, Pawling J, Cheung P, Parttridge E, Demetriou M (2002) UDP-N-acetylglucosamine: alpha-6-D-mannoside beta1,6 N-acetylglucosaminyl transferase V (Mgat5) deficient mice. Biochim Biophys Acta 1573: 414–422. 12417426
  44. [47]Tsuboi S, Hatakeyama S, Ohyama C, Fukuda M (2012) Two opposing roles of O-glycans in tumor metastasis. Trends Mol Med 18: 224–232. PMC3356160 22425488

Cited by

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Authors
Ker, Y.-B., Peng, C.-C., Chang, W.-L., Chyau, C.-C., & Peng, R. Y.
Affiliations
  • Hungkuang University (TW)
  • Taipei Medical University (TW)
Corresponding author
  • Ker, Yaw-Bee
  • Chyau, Charng-Cherng
Venue
PLoS ONE
Published
2014-04-01
Volume
9
Issue
4
Pages
e93191
ISSN
1932-6203 (ISSN-L)
OpenAlex
W2037850871
Cited by
29
References
0
Citations by year
2026: 2 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 3 · 2020: 3 · 2019: 1 · 2018: 6 · 2017: 3 · 2016: 2 · 2015: 4 · 2014: 1
FWCI
2.43
Type
journal article
Language
en
Open access
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
National Science Council
Topics
  • Health Sciences › Medicine › Pharmacology › Fungal Biology and Applications
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
  • Health Sciences › Medicine › Complementary and alternative medicine › Medicinal plant effects and applications
Keywords
Antrodia cinnamomea, hepatoprotection, protein-bound polysaccharide, mycelium, lipopolysaccharide-induced liver injury, oxidative stress, anti-inflammatory activity, mannan, β-1,3-glucan, antioxidant enzymes, NF-κB, nitric oxide, interleukin-6
MeSH terms
Animals, Antioxidants, Fungal Proteins, Glycoproteins, Liver, Liver Function Tests, Male, Nitric Oxide, Oxidation-Reduction, Interleukin-6, NF-kappa B, Thiobarbituric Acid Reactive Substances, Protective Agents, Mycelium, Rats, Nitric Oxide Synthase Type II, Antrodia

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