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.
Key words
Poria cocos
- Polyporaceae - polysaccharides - triterpenes - anti‐inflammatory activity - anticancer activity - immunomodulatory activity
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
-
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
-
3 Ryvarden L. Genera of polypores: nomenclature and taxonomy. Synopsis fungorum 5. Oslo; Fungiflora 1991: 363
-
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
-
5
Illana-Esteban C.
Interés medicinal de Poria cocos (= Wolfiporia extensa).
Rev Iberoam Micol.
2009;
26
103-107
-
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
-
7 Chang H M, But P P H. Pharmacology and applications of Chinese Materia Medica. Singapore; World Scientific 1987: 875-877
-
8
Tai T, Akahori A, Shingu T.
Triterpenoids from Poria cocos.
Phytochemistry.
1991;
30
2796-2797
-
9
Tai T, Akahori A, Shingu T.
A lanostane triterpenoid from Poria cocos.
Phytochemistry.
1992;
31
2548-2549
-
10
Tai T, Akahori A, Shingu T.
Triterpenes of Poria cocos.
Phytochemistry.
1993;
32
1239-1244
-
11
Tai T, Shingu T, Kikuchi T, Tezuka Y, Akahori A.
Triterpenes from the surface layer of Poria cocos.
Phytochemistry.
1995;
39
1165-1169
-
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
-
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
-
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
-
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
-
16
Zheng Y, Yang X W.
Two new lanostane triterpenoids from Poria cocos.
J Asian Nat Prod Res.
2008;
10
323-328
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
24
Chihara G, Hamuro J, Maeda Y, Arai Y, Fukuoka F.
Antitumor polysaccharide derived chemically from natural glucan (pachyman).
Nature.
1970;
225
943-944
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
51
Yance D R, Sagar S M.
Targeting angiogenesis with integrative cancer therapies.
Integr Cancer Ther.
2006;
5
9-29
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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;
-
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
-
62
Su Y B, Huang Y T.
Poria cocos inhibited the activation of hepatic stellate cells.
Planta Med.
2009;
75
1034-1035
-
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
-
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
-
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
-
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
-
67
Li G H, Shen Y M, Zhang K Q.
Nematicidal activity and chemical component of Poria cocos.
J Microbiol.
2005;
43
17-20
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
78
Jia W, Gao W, Tang L.
Antidiabetic herbal drugs officially approved in China.
Phytother Res.
2003;
17
1127-1134
-
79 Manual Práctico de Farmacopea y Prescripción en Medicina Tradicional China. Amposta; AISVI 1993: 67
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
