Chemical Constituents and Pharmacological Properties of Poria cocos

 

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Abstract

Poria cocos (Polyporaceae) is a saprophytic fungus that grows in diverse species of Pinus. Its sclerotium, called fu-ling or hoelen, is used in traditional Chinese and Japanese medicine for its diuretic, sedative, and tonic effects. Various studies of this fungus have demonstrated its marked anti-inflammatory activity in different experimental models of acute and chronic inflammation. It is widely used as a constituent of many preparations in Asian medicine, but the number of research papers on its clinical properties is insufficient for establishing its efficacy and safety from a scientific point of view. In this review, we have compiled all the published data concerning the chemistry, pharmacology, and clinical uses of this drug in order to evaluate its clinical interest for future use against various pathologies in which inflammation and immunodepression are implicated. We selected the papers for review on the basis of their ethnopharmacological relevance, using the most relevant databases for the biomedical sciences. Studies on various fungus extracts as well as on the major phytochemical compounds (polysaccharides and triterpenoids) present in Poria cocos comprised the principal objectives of this review. In several of the studies reviewed, the inhibitory effects of triterpenes on phospholipase A₂ (PLA₂) have been clearly demonstrated. In addition, the inhibitory effects of Poria cocos on the secretion of different cytokines from human peripheral blood monocytes have also been described. Triterpenoids are known to have a pivotal influence on certain diseases such as rheumatoid arthritis, psoriasis, autoimmune uveitis, septic shock, and possibly bronchial asthma, while polysaccharides can potentiate the immune response. Reviewing the literature, we found that polysaccharides from Poria cocos enhanced the secretion of immune stimulators and suppressed the secretion of immune suppressors, thus potentiating the immune response. In addition, they showed antitumor activity against different cancer cell lines. This activity is associated with their capacity to inhibit angiogenesis by downregulating both NF-κB and the induction of NF-κB/Rel translocation.

References

• 1 Lindner D L, Banik M T. Molecular phylogeny of Laetiporus and other brown rot polypore genera in North America.  Mycologia. 2008;  100 417-430
  CrossrefPubMedGoogle Scholar
• 2 Binder M, Hibbett D S, Larsson K H, Larsson E, Langer E, Langer G. The phylogenetic distribution of resupinate forms across the major clades of mushroom-forming fungi (Homobasidiomycetes).  Syst Biodivers. 2005;  3 113-157
  CrossrefPubMedGoogle Scholar
• 3 Ryvarden L. Genera of polypores: nomenclature and taxonomy. Synopsis fungorum 5. Oslo; Fungiflora 1991: 363
  Google Scholar
• 4 Giner-Larza E M, Máñez S, Giner-Pons R M, Carmen Recio M, Ríos J L. On the anti-inflammatory and anti-phospholipase A₂ activity of extracts from lanostane-rich species.  J Ethnopharmacol. 2000;  73 61-69
  CrossrefPubMedGoogle Scholar
• 5 Illana-Esteban C. Interés medicinal de Poria cocos (= Wolfiporia extensa).  Rev Iberoam Micol. 2009;  26 103-107
  CrossrefPubMedGoogle Scholar
• 6 Hsu H Y, Chen Y P, Shen S J, Hsu C S, Chen C C, Chang H C. Oriental Materia Medica. A concise guide. Long Beach; Oriental Healing Arts Institute 1986: 305-306
  Google Scholar
• 7 Chang H M, But P P H. Pharmacology and applications of Chinese Materia Medica. Singapore; World Scientific 1987: 875-877
  Google Scholar
• 8 Tai T, Akahori A, Shingu T. Triterpenoids from Poria cocos.  Phytochemistry. 1991;  30 2796-2797
  CrossrefPubMedGoogle Scholar
• 9 Tai T, Akahori A, Shingu T. A lanostane triterpenoid from Poria cocos.  Phytochemistry. 1992;  31 2548-2549
  CrossrefPubMedGoogle Scholar
• 10 Tai T, Akahori A, Shingu T. Triterpenes of Poria cocos.  Phytochemistry. 1993;  32 1239-1244
  CrossrefPubMedGoogle Scholar
• 11 Tai T, Shingu T, Kikuchi T, Tezuka Y, Akahori A. Triterpenes from the surface layer of Poria cocos.  Phytochemistry. 1995;  39 1165-1169
  CrossrefPubMedGoogle Scholar
• 12 Tai T, Shingu T, Kikuchi T, Tezuka Y, Akahori A. Isolation of lanostane-type triterpene acids having an acetoxyl group from sclerotia of Poria cocos.  Phytochemistry. 1995;  40 225-231
  CrossrefPubMedGoogle Scholar
• 13 Tai T, Akita Y, Konoshita K, Koyama K, Takahashi K, Watanabe K. Anti-emetic principles of Poria cocos.  Planta Med. 1995;  61 527-530
  Article in Thieme ConnectPubMedGoogle Scholar
• 14 Akihisa T, Nakamura Y, Tokuda H, Uchiyama E, Suzuki T, Kimura Y, Uchikura K, Nishi H. Triterpene acids from Poria cocos and their anti-tumor-promoting effects.  J Nat Prod. 2007;  70 948-953
  CrossrefPubMedGoogle Scholar
• 15 Akihisa T, Uchiyama E, Kikuchi T, Tokuda H, Suzuki T, Kimura Y. Anti-tumor-promoting effects of 25-methoxyporicoic acid A and other triterpene acids from Poria cocos.  J Nat Prod. 2009;  72 1786-1792
  CrossrefPubMedGoogle Scholar
• 16 Zheng Y, Yang X W. Two new lanostane triterpenoids from Poria cocos.  J Asian Nat Prod Res. 2008;  10 323-328
  CrossrefPubMedGoogle Scholar
• 17 Zheng Y, Yang X W. Poriacosones A and B: two new lanostane triterpenoids from Poria cocos.  J Asian Nat Prod Res. 2008;  10 645-651
  PubMedGoogle Scholar
• 18 Yasukawa K, Kaminaga T, Kitanaka S, Tai T, Nunoura Y, Natori S, Takido M. 3β-p-hydroxybenzoyldehydrotumulosic acid from Poria cocos, and its anti-inflammatory effects.  Phytochemistry. 1998;  48 1357-1360
  CrossrefPubMedGoogle Scholar
• 19 Nukaya H, Yamashiro H, Fuzakawa H, Ishida H, Tsuji K. Isolation of inhibitors of TPA-induced mouse ear edema from hoelen, Poria cocos.  Chem Pharm Bull. 1996;  44 847-849
  CrossrefPubMedGoogle Scholar
• 20 Akihisa T, Mizushina Y, Ukiya M, Oshikubo M, Kondo S, Kimura Y, Suzuki T, Tai T. Dehydrotrametenonic acid and dehydroeburiconic acid from Poria cocos and their inhibitory effects on eukaryotic DNA polymerase α and β.  Biosci Biotechnol Biochem. 2004;  68 448-450
  CrossrefPubMedGoogle Scholar
• 21 Yokoyama A, Natori S, Aoshima K. Distribution of tetracyclic triterpenoids of lanostane group and sterols in the higher fungi especially of the Polyporaceae and related families.  Phytochemistry. 1975;  14 487-497
  CrossrefPubMedGoogle Scholar
• 22 Zheng Y, Yang X W. Absorption of triterpenoid compounds from Indian bread (Poria cocos) across human intestinal epithelial (Caco-2) cells in vitro.  Zhongguo Zhong Yao Za Zhi. 2008;  33 1596-1601
  PubMedGoogle Scholar
• 23 Ukiya M, Akihisa T, Tokuda H, Hirano M, Oshikubo M, Nobukuni Y, Kimura Y, Tai T, Kondo S, Nishino H. Inhibition of tumor-promoting effects by poricoic acids G and H and other lanostane-type triterpenes and cytotoxic activity of poricoic acids A and G from Poria cocos.  J Nat Prod. 2002;  65 462-465
  CrossrefPubMedGoogle Scholar
• 24 Chihara G, Hamuro J, Maeda Y, Arai Y, Fukuoka F. Antitumor polysaccharide derived chemically from natural glucan (pachyman).  Nature. 1970;  225 943-944
  CrossrefPubMedGoogle Scholar
• 25 Kanayama H, Adechi N, Togami M. A new antitumor polysaccharide from the mycelia of Poria cocos Wolf.  Chem Pharm Bull. 1983;  31 1115-1118
  CrossrefPubMedGoogle Scholar
• 26 Jin Y, Zhang L, Chen L, Chen Y, Cheung P C, Chen L. Effect of culture media on the chemical and physical characteristics of polysaccharides isolated from Poria cocos mycelia.  Carbohydr Res. 2003;  338 1507-1515
  CrossrefPubMedGoogle Scholar
• 27 Wang Y, Zhang M, Ruan D, Shashkov A S, Kilcoyne M, Savage A V, Zhang L. Chemical components and molecular mass of six polysaccharides isolated from the sclerotium of Poria cocos.  Carbohydr Res. 2004;  339 327-334
  CrossrefPubMedGoogle Scholar
• 28 Huang Q, Zhang L. Solution properties of (1 → 3)-α-D-glucan and its sulfated derivative from Poria cocos mycelia via fermentation tank.  Biopolymers. 2005;  79 28-38
  CrossrefPubMedGoogle Scholar
• 29 Li G, Xu M L, Lee C S, Woo M H, Chang H W, Son J K. Cytotoxicity and DNA topoisomerases inhibitory activity of constituents from the sclerotium of Poria cocos.  Arch Pharm Res. 2004;  27 829-833
  CrossrefPubMedGoogle Scholar
• 30 Cuéllar M J, Giner R M, Recio M C, Just M J, Máñez S, Ríos J L. Effect of the basidiomycete Poria cocos on experimental dermatitis and other inflammatory conditions.  Chem Pharm Bull (Tokyo). 1997;  45 492-494
  CrossrefPubMedGoogle Scholar
• 31 Giner E M, Máñez S, Recio M C, Giner R M, Cerdá-Nicolás M, Ríos J L. In vivo studies on the anti-inflammatory activity of pachymic and dehydrotumulosic acids.  Planta Med. 2000;  66 221-227
  Article in Thieme ConnectPubMedGoogle Scholar
• 32 Cuéllar M J, Giner R M, Recio M C, Just M J, Máñez S, Ríos J L. Two fungal lanostane derivatives as phospholipase A2 inhibitors.  J Nat Prod. 1996;  59 977-979
  CrossrefPubMedGoogle Scholar
• 33 Jain M K, Yu B, Rogers J M, Smith A E, Boger E T A, Ostrander R L, Rheingold A L. Specific competitive inhibitor of secreted phospholipase A₂ from berries of Schinus terebinthifolius.  Phytochemistry. 1995;  39 537-547
  CrossrefPubMedGoogle Scholar
• 34 Scott D L, White S P, Otwinowski Z, Yuan W, Gelb M H, Sigler P B. Interfacial catalysis: the mechanism of phospholipase A₂.  Science. 1990;  250 1541-1546
  CrossrefPubMedGoogle Scholar
• 35 Kaminaga T, Yasukawa K, Takido M, Tai T, Nunoura Y. Inhibitory effects of Poria cocos on 12-O-tetradecanoylphorbol-13-acetate-induced eat oedema and tumour promotion in mouse skin.  Phytother Res. 1996;  10 581-584
  CrossrefPubMedGoogle Scholar
• 36 Prieto J M, Recio M C, Giner R M, Máñez S, Giner-Larza E M, Ríos J L. Influence of traditional Chinese anti-inflammatory medicinal plants on leukocyte and platelet functions.  J Pharm Pharmacol. 2003;  55 1275-1282
  CrossrefPubMedGoogle Scholar
• 37 Fuchs S M, Heinemann C, Schliemann-Willers S, Härtl H, Fluhr J W, Elsner P. Assessment of anti-inflammatory activity of Poria cocos in sodium lauryl sulphate-induced irritant contact dermatitis.  Skin Res Technol. 2006;  12 223-227
  CrossrefPubMedGoogle Scholar
• 38 Spelman K, Burns J J, Nichols D, Winters N, Ottersberg S, Tenborg M. Modulation of cytokine expression by traditional medicines: a review of herbal immunomodulators.  Altern Med Rev. 2006;  11 128-150
  PubMedGoogle Scholar
• 39 Yu S J, Tseng J. Fu-Ling, a Chinese herbal drug, modulates cytokine secretion by human peripheral blood monocytes.  Int J Immunopharmacol. 1996;  18 37-44
  CrossrefPubMedGoogle Scholar
• 40 Tseng J, Chang J G. Suppression of tumor necrosis factor-α, interleukin-1β, interleukin-6 and granulocyte-monocyte colony stimulating factor secretion from human monocytes by an extract of Poria cocos.  Chin J Microbiol Immunol. 1992;  1 1-10
  PubMedGoogle Scholar
• 41 Chang H H, Yeh C H, Sheu F. A novel immunomodulatory protein from Poria cocos induces Toll-like receptor 4-dependent activation within mouse peritoneal macrophages.  J Agric Food Chem. 2009;  57 6129-6139
  CrossrefPubMedGoogle Scholar
• 42 Chen X, Zhang L, Cheung P C. Immunopotentiation and anti-tumor activity of carboxymethylated-sulfated β-(1 → 3)-D-glucan from Poria cocos.  Int Immunopharmacol. 2010;  10 398-405
  CrossrefPubMedGoogle Scholar
• 43 Kaminaga T, Yasukawa K, Kanno T, Nunoura Y, Takido M. Inhibitory effects of lanostane-type triterpene acids, the components of Poria cocos, on tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin.  Oncology. 1996;  53 382-385
  CrossrefPubMedGoogle Scholar
• 44 Mizushina Y, Akihisa T, Ukiya M, Murakami C, Kuriyama I, Xu X, Yoshida H, Sakaguchi K. A novel DNA topoisomerase inhibitor: dehydroebriconic acid; one of the lanostane-type triterpene acids from Poria cocos.  Cancer Sci. 2004;  95 354-360
  CrossrefPubMedGoogle Scholar
• 45 Kang H M, Lee S K, Shin D S, Lee M Y, Han D C, Baek N I, Son K H, Kwon B M. Dehydrotrametenolic acid selectively inhibits the growth of H-ras transformed rat2 cells and induces apoptosis through caspase-3 pathway.  Life Sci. 2006;  78 607-613
  CrossrefPubMedGoogle Scholar
• 46 Gapter L, Wang Z, Glinski J, Ng K Y. Induction of apoptosis in prostate cancer cells by pachymic acid from Poria cocos.  Biochem Biophys Res Commun. 2005;  332 1153-1161
  CrossrefPubMedGoogle Scholar
• 47 Ling H, Zhou L, Jia X, Gapter L A, Agarwal R, Ng K Y. Polyporenic acid C induces caspase-8-mediated apoptosis in human lung cancer A549 cells.  Mol Carcinogen. 2009;  48 498-507
  CrossrefPubMedGoogle Scholar
• 48 Wu S J, Ng L T, Lin C C. Antioxidant activities of some common ingredients of traditional Chinese medicine, Angelica sinensis, Lycium barbarum and Poria cocos.  Phytother Res. 2004;  18 1008-1012
  CrossrefPubMedGoogle Scholar
• 49 Schinella G R, Tournier H A, Prieto J M, Mordujovich de Buschiazzo P, Ríos J L. Antioxidant activity of anti-inflammatory plant extracts.  Life Sci. 2002;  70 1023-1033
  CrossrefPubMedGoogle Scholar
• 50 Zhou L, Zhang Y, Gapter L A, Ling H, Agarwal R, Ng K Y. Cytotoxic and anti-oxidant activities of lanostane-type triterpenes isolated from Poria cocos.  Chem Pharm Bull (Tokyo). 2008;  56 1459-1462
  CrossrefPubMedGoogle Scholar
• 51 Yance D R, Sagar S M. Targeting angiogenesis with integrative cancer therapies.  Integr Cancer Ther. 2006;  5 9-29
  CrossrefPubMedGoogle Scholar
• 52 Lee K Y, Jeon Y J. Polysaccharide isolated from Poria cocos sclerotium induces NF-κB/Rel activation and iNOS expression in murine macrophages.  Int Immunopharmacol. 2003;  3 1353-1362
  CrossrefPubMedGoogle Scholar
• 53 Lee K Y, You H J, Jeong H G, Kang J S, Kim H M, Rhee S D, Jeon Y J. Polysaccharide isolated from Poria cocos sclerotium induces NF-κB/Rel activation and iNOS expression through the activation of p 38 kinase in murine macrophages.  Int Immunopharmacol. 2004;  4 1029-1038
  CrossrefPubMedGoogle Scholar
• 54 Jin Y, Zhang L, Zhang M, Chen L, Cheung P C, Oi V E, Lin Y. Antitumor activities of heteropolysaccharides of Poria cocos mycelia from different strains and culture media.  Carbohydr Res. 2003;  338 1517-1521
  CrossrefPubMedGoogle Scholar
• 55 Zhang M, Chiu L C, Cheung P C, Oi V E. Growth-inhibitory effects of a β-glucan from the mycelium of Poria cocos on human breast carcinoma MCF-7 cells: cell-cycle arrest and apoptosis induction.  Oncol Rep. 2006;  15 637-643
  PubMedGoogle Scholar
• 56 Wang Y, Zhang L, Li Y, Hou X, Zeng F. Correlation of structure to antitumor activities of five derivatives of a β-glucan from Poria cocos sclerotium.  Carbohydr Res. 2004;  339 2567-2574
  CrossrefPubMedGoogle Scholar
• 57 Zhang L, Chen L, Xu X, Zeng F, Cheung P C. Effect of molecular mass on antitumor activity of heteropolysaccharide from Poria cocos.  Biosci Biotechnol Biochem. 2005;  69 631-634
  CrossrefPubMedGoogle Scholar
• 58 Lin Y, Zhang L, Chen L, Jin Y, Zeng F, Jin J, Wan B, Cheung P C. Molecular mass and antitumor activities of sulfated derivatives of α-glucan from Poria cocos mycelia.  Int J Biol Macromol. 2004;  34 289-294
  PubMedGoogle Scholar
• 59 Chen Y Y, Chang H M. Antiproliferative and differentiating effects of polysaccharide fraction from fu-ling (Poria cocos) on human leukemic U937 and HL-60 cells.  Food Chem Toxicol. 2004;  42 759-769
  PubMedGoogle Scholar
• 60 Li T H, Hou C C, Chang C L T, Yang W C. Anti-hyperglycemic properties of crude extract and triterpenes from Poria cocos.  Evid Based Complement Alternat Med. DOI: 10.1155/2011/128402 , advance online publication 16 September 2010;
  
  PubMedGoogle Scholar
• 61 Sato M, Tai T, Nunoura Y, Yajima Y, Kawashima S, Tanaka K. Dehydrotrametenolic acid induces preadipocyte differentiation and sensitizes animal models of noninsulin-dependent diabetes mellitus to insulin.  Biol Pharm Bull. 2002;  25 81-86
  CrossrefPubMedGoogle Scholar
• 62 Su Y B, Huang Y T. Poria cocos inhibited the activation of hepatic stellate cells.  Planta Med. 2009;  75 1034-1035
  PubMedGoogle Scholar
• 63 Huang Y C, Chang W L, Huang S F, Lin C Y, Lin H C, Chang T C. Pachymic acid stimulates glucose uptake through enhanced GLUT4 expression and translocation.  Eur J Pharmacol. 2010;  648 39-49
  CrossrefPubMedGoogle Scholar
• 64 Hattori T, Hayashi K, Nagao T, Furuta K, Ito M, Suzuki Y. Studies on antinephritic effects of plant components (3): effect of pachyman, a main component of Poria cocos Wolf on original-type anti-GBM nephritis in rats and its mechanisms.  Jpn J Pharmacol. 1992;  59 89-96
  CrossrefPubMedGoogle Scholar
• 65 Dhan H P, Hou A J, Lu F E, Huang J L. Experimental study on the inhibitory effect of carboxymethyl pachymaram on hepatitis B virus expression from transfected cells.  Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2005;  19 290-292
  PubMedGoogle Scholar
• 66 Schinella G R, Tournier H A, Prieto J M, Ríos J L, Buschiazzo H, Zaidenberg A. Inhibition of Trypanosoma cruzi growth by medical plant extracts.  Fitoterapia. 2002;  73 569-575
  CrossrefPubMedGoogle Scholar
• 67 Li G H, Shen Y M, Zhang K Q. Nematicidal activity and chemical component of Poria cocos.  J Microbiol. 2005;  43 17-20
  PubMedGoogle Scholar
• 68 Zhang G W, Liu H Y, Xia Q M, Li J Q, Lü H, Zhang Q H, Yao Z F. Anti-rejection effect of ethanol extract of Poria cocos Wolf in rats after cardiac allograft implantation.  Chin Med J (Engl). 2004;  117 932-935
  PubMedGoogle Scholar
• 69 Sekiya N, Goto H, Shimada Y, Endo Y, Sakakibara I, Terasawa K. Inhibitory effects of triterpenes isolated from Hoelen on free radical-induced lysis of red blood cells.  Phytother Res. 2003;  17 160-162
  CrossrefPubMedGoogle Scholar
• 70 Chen W, An W, Chu J. Effect of water extract of Poria on cytosolic free calcium concentration in brain nerve cells of neonatal rats.  Zhongguo Zhong Xi Yi Jie He Za Zhi. 1998;  18 293-295
  PubMedGoogle Scholar
• 71 Liu Y C, Liu G Y, Liu R L. Effects of Poria cocos on ototoxicity induced by kanamycin in guinea-pigs.  Zhongguo Zhong Xi Yi Jie He Za Zhi. 1995;  15 422-423
  PubMedGoogle Scholar
• 72 Lee J H, Lee Y J, Shin J K, Nam J W, Nah S Y, Kim S H, Jeong J H, Kim Y, Shin M, Hong M, Seo E K, Bae H. Effects of triterpenoids from Poria cocos Wolf on the serotonin type 3A receptor-mediated ion current in Xenopus oocytes.  Eur J Pharmacol. 2009;  615 27-32
  CrossrefPubMedGoogle Scholar
• 73 Wang Y, Yu Y, Mao J. Carboxymethylated β-glucan derived from Poria cocos with biological activities.  J Agric Food Chem. 2009;  57 10913-10915
  CrossrefPubMedGoogle Scholar
• 74 Park Y H, Son I H, Kim B, Lyu Y S, Moon H I, Kang H W. Poria cocos water extract (PCW) protects PC12 neuronal cells from beta-amyloid-induced cell death through antioxidant and antiapoptotic functions.  Pharmazie. 2009;  64 760-764
  PubMedGoogle Scholar
• 75 Zheng Y, Yang X W. Absorption of triterpenoid compounds from Indian bread (Poria cocos) across human intestinal epithelial (Caco-2) cells in vitro.  Zhongguo Zhong Yao Za Zhi. 2008;  33 1596-1601
  PubMedGoogle Scholar
• 76 Zheng Y, Yang X W. Absorption and transport of pachymic acid in the human intestinal cell line Caco-2 monolayers.  Zhong Xi Yi Jie He Xue Bao. 2008;  6 704-710
  CrossrefPubMedGoogle Scholar
• 77 Chang T T, Huang C C, Hsu C H. Clinical evaluation of the Chinese herbal medicine formula STA-1 in the treatment of allergic asthma.  Phytother Res. 2006;  20 342-347
  CrossrefPubMedGoogle Scholar
• 78 Jia W, Gao W, Tang L. Antidiabetic herbal drugs officially approved in China.  Phytother Res. 2003;  17 1127-1134
  CrossrefPubMedGoogle Scholar
• 79 Manual Práctico de Farmacopea y Prescripción en Medicina Tradicional China. Amposta; AISVI 1993: 67
  Google Scholar

Prof. Dr. José-Luis Ríos

Department of Pharmacology
University of Valencia

Av. Vicent Andres Estelles s/n

46100 Burjassot

Valencia

Spain

Phone: +34 9 63 54 49 73

Fax: +34 9 63 54 49 98

Email: riosjl@uv.es