Antrodia camphorata

Taiwanese nameNiu Chang Chih

This native Taiwanese mushroom is starting to attract interest because of the exceptionally high concentration of its triterpenoid compounds and their structural diversity. Other important bioactive compounds include polysaccharides, maleic/succinic acid derivatives, benzenoids and benzoquinone derivatives1-4.
In the wild Taiwanofungus camphoratus, syn.: Antrodia camphorata grows solely on the tree Cinnamomum kanehirai, a species of cinnamon that grows at altitudes of between 450 and 2,000m in the mountains of Taiwan.
As the fruiting body only develops fully once the tree is dead, in the past many trees were felled to supply demand for this unique and extremely lucrative mushroom (wild A. camphorata fetches up to US$15,000/kg) and this, coupled with the fact that C. kanehirai itself is highly sought for furniture manufacture, has led to over-exploitation, with the result that C. kanehirai is now protected by the Taiwanese government5.
To replace the wild-collected material, commercial cultivation of A. camphorata has been developed using a variety of techniques to produce either cultivated fruiting body, pure mycelium (grown by liquid fermentation), or mycelial biomass (mycelium and residual substrate). Levels of triterpenes are highest in the fruiting body products, which are also the most expensive, and lowest in the mycelial biomass products, with liquid fermentation mycelial products offering a cost-effective intermediate option.
A. camphorata has a wide range of traditional indications, including alcohol intoxication, cancer, hypertension, fatigue, viral infection and liver disease1.

HEPATOPROTECTIVE – The use of A. camphorata by Taiwanese natives to counter the adverse effects of excessive alcohol consumption was first reported by a traditional Chinese medicine doctor, Wu-Sha in 1773. In animal experiments both the fruiting body and mycelium have been shown to protect against alcohol-induced hepatitis and liver steatosis (fatty liver), as well as CCl4 and cytokine induced liver damage, ameliorating increases in AST, ALT and ALP levels and histopathological changes in a dose-dependent manner with no observed lesions5-9.
A. camphorata fruiting bodies also inhibited alcohol-induced rises in cholesterol, hepatic lipids and liver enzymes in rats with moderate effect at a dose of 0.025g/kg and increased efficacy at a dose of 0.1g/kg10-12.
Separately it has been shown that A. camphorata possesses strong antioxidant activity and it has been suggested that this is a major contributor to its hepatoprotective properties13,14. Its antioxidant activity is correlated with the presence of total polyphenols, crude triterpenoids and the protein/polysaccharide ratio of the polysaccharide extract15. A. camphorata polysaccharides also showhepatoprotective and anti-hepatitis B activity16,17, while a number of maleic/succinic acid derivatives showed potent inhibitory activity against hepatitis C protease through competitive inhibition18.
In addition A. camphorata has been shown to suppress the invasive potential of liver cancer cells through inhibition of NF-kappaB19 and to induce apoptosis in human hepatoma cells20-23.

CANCER – As well as its effects on liver cancer, multiple in vitro and in vivo studies show inhibition of cancer cell growth and migration, together with increase in apoptosis, in various cancer cell lines including breast, prostate, liver, bladder, cervical and oral carcinoma1,24-29.

ASTHMA – The immune modulating and anti-inflammatory actions of A. camphorata offer potential in asthma treatment with animal experiments showing that A. camphorata polysaccharides dose-dependently inhibited the development of airway hyperresponsiveness, airway eosinophilia and Th2 immune status30.

SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) – A mycelial extract of A. camphorata reduced urine protein and creatinine levels and suppressed changes in the kidney glomerular basement membrane (a histological hallmark of SLE) at a dose of 400mg/kg in a mouse model of SLE, suggesting ability to protect the kidney from autoimmune disease31,32.

CARDIOVASCULAR DISEASEA. camphorata has traditionally been used to treat a variety of heart conditions, including hypertension and atherosclerosis, and A. camphorata extracts have been reported to inhibit thickening of blood vessel walls and to promote vasodilation33,34.

CLINICAL SUMMARY
Main Therapeutic Application – Liver disease.
Key Component – Triterpenes, Polysaccharides.
Dose – While the more expensive fruiting body contains the highest level of triterpenes and is preferred in Taiwan for cancer treatment, mycelium produced by liquid fermentation is increasingly available and has been shown to offer a cost effective alternative for treatment of liver conditions, with a recommended dose of 1-3g/day.
Caution – Patients on anti-coagulant medication.

REFERENCES
1. Review of pharmacological effects of Antrodia camphorata and its bioactive compounds. Geethangili M, Tzeng YM. Evid Based Complement Alternat Med. 2011;2011:212641.
2. Analysis of Taiwan patents for the medicinal mushroom ‘Niu-Chang-Chih’. Chen YF, Lu WL, Wu MD, Yuan GF. Recent Pat Food Nutr Agric. 2013;5(1):62–69.
3. Immunomodulatory effect of polysaccharides extracted from the medicinal mushroom Antrodia camphorata (higher Basidiomycetes) in specific pathogen-free chickens. Song AR, Qin D, Zhao C, Sun XL, Huang F, Kong C, Yang S. Int J Med Mushrooms. 2014;16(1):95–103.
4. New anti-inflammatory aromatic components from Antrodia camphorata. Chen YC, Chiu HL, Chao CY, Lin WH, Chao LK, Huang GJ, Kuo YH. Int J Mol Sci. 2013;14(3):4629–4639.
5. Niuchangchih (Antrodia camphorata) and its potential in treating liver diseases. Ao ZH, Xu ZH, Lu ZM, Xu HY, Zhang XM, Dou WF. J Ethnopharmacol. 2009;121(2):194–212.
6. Further studies on the hepatoprotective effect of Antrodia camphorata in submerged culture on ethanol-induced acute liver injury in rats. Lu ZM, Tao WY, Xu HY, Ao ZH, Zhang XM, Xu ZH. Nat Prod Res. 2011;25(7):684–695.
7. Protective effects of Antrodia cinnamomea against liver injury. Liu YW, Lu KH, Ho CT, Sheen LY. J Tradit Complement Med. 2012;2(4):284–294.
8. Current evidence for the hepatoprotective activities of the medicinal mushroom Antrodia cinnamomea. Yue PY, Wong YY, Wong KY, Tsoi YK, Leung KS. Chin Med. 2013;8(1):21.
9. Hepatoprotective effects of eburicoic acid and dehydroeburicoic acid from Antrodia camphorata in a mouse model of acute hepatic injury. Huang GJ, Deng JS, Huang SS, Lee CY, Hou WC, Wang SY, Sung PJ, Kuo YH. Food Chem. 2013;141(3):3020–3027.
10. Fruiting body of Niuchangchih (Antrodia camphorata) protects livers against chronic alcohol consumption damage. Huang CH, Chang YY, Liu CW, Kang WY, Lin YL, Chang HC, Chen YC. J Agric Food Chem. 2010;58(6):3859–3866.
11. Effects of Antrodia camphorata on alcohol clearance and antifibrosis in livers of rats continuously fed alcohol. Wu MT, Tzang BS, Chang YY, Chiu CH, Kang WY, Huang CH, Chen YC. J Agric Food Chem. 2011;59(8):4248–4254.
12. Further studies on the hepatoprotective effect of Antrodia camphorata in submerged culture on ethanol-induced acute liver injury in rats. Lu ZM, Tao WY, Xu HY, Ao ZH, Zhang XM, Xu ZH. Nat Prod Res. 2011;25(7):684–695.
13. Antioxidative and hepatoprotective effects of Antrodia camphorata extract. Hsiao G, Shen MY, Lin KH, Lan MH, Wu LY, Chou DS, Lin CH, Su CH, Sheu JR. J Agric Food Chem. 2003;51(11):3302–3308.
14. Protection of oxidative damage by aqueous extract from Antrodia camphorata mycelia in normal human erythrocytes. Hseu YC, Chang WC, Hseu YT, Lee CY, Yech YJ, Chen PC, Chen JY, Yang HL. Life Sci. 2002;71(4):469–482.
15. Antioxidant properties of Antrodia camphorata in submerged culture. Song TY, Yen GC. J Agric Food Chem. 2002;50(11):3322–3327.
16. Protective effects of a neutral polysaccharide isolated from the mycelium of Antrodia cinnamomea on Propionibacterium acnes and lipopolysaccharide induced hepatic injury in mice. Han HF, Nakamura N, Zuo F, Hirakawa A, Yokozawa T, Hattori M. Chem Pharm Bull. 2006;54(4):496–500.
17. Antrodia camporata polysaccharides exhibit anti-hepatitis B virus effects. Lee IH, Huang RL, Chen CT, Chen HC, Hsu WC, Lu MK. FEMS Microbiol Lett. 2002;209(1):63–67.
18.  Inhibitory effects of antrodins A-E from Antrodia cinnamomea and their metabolites on hepatitis C virus protease. Phuong do T, Ma CM, Hattori M, Jin JS. Phytother Res. 2009;23(4):582–584.
19. Antrodia cinnamomea fruiting bodies extract suppresses the invasive potential of human liver cancer cell line PLC/PRF/5 through inhibition of nuclear factor κB pathway. Hsu YL, Kuo PL, Cho CY, Ni WC, Tzeng TF, Ng LT, Kuo YH, Lin CC. Food Chem Toxicol. 2007;45(7):1249–1257.
20. Induction of apoptosis in human hepatoma cells by mycelia of Antrodia camphorata in submerged culture. Song TY, Hsu SL, Yen GC. J Ethnopharmacol. 2005;100(1-2):158–167.
21. Mycelia from Antrodia camphorata in submerged culture induce apoptosis of human hepatoma HepG2 cells possibly through regulation of Fas pathway. Song TY, Hsu SL, Yeh CT, Yen GC. J Agric Food Chem. 2005;53(14):5559–5564.
22. Methyl antcinate A from Antrodia camphorata induces apoptosis in human liver cancer cells through oxidant-mediated cofilin- and Bax-triggered mitochondrial pathway. Hsieh YC, Rao YK, Wu CC, Huang CY, Geethangili M, Hsu SL, Tzeng YM. Chem Res Toxicol. 2010;23(7):1256–1267.
23. Medicinal fungus Antrodia cinnamomea inhibits growth and cancer stem cell characteristics of hepatocellular carcinoma. Liu YM, Liu YK, Lan KL, Lee YW, Tsai TH, Chen YJ. Evid Based Complement Alternat Med. 2013;2013:569737.
24. Antrodia camphorata extract induces replicative senescence in superficial TCC, and inhibits the absolute migration capability in invasive bladder carcinoma cells. Peng CC, Chen KC, Peng RY, Chyau CC, Su CH, Hsieh-Li HM. J Ethnopharmacol. 2007;109(1):93–103.
25. Inhibition of cyclooxygenase-2 and induction of apoptosis in estrogen-nonresponsive breast cancer cells by Antrodia camphorata. Hseu YC, Chen SC, Tsai PC, Chen CS, Lu FJ, Chang NW, Yang HL. Food Chem Toxicol. 2007;45(7):1107–1115.
26. Unique Formosan mushroom Antrodia camphorata differentially inhibits androgen-responsive LNCaP and -independent PC-3 prostate cancer cell. Chen KC, Peng CC, Peng RY, Su CH, Chiang HS, Yan JH, Hsieh-Li HM. Nutr Cancer. 2007;57(1):111–121.
27. Anti-metastatic activities of Antrodia camphorata against human breast cancer cells mediated through suppression of the MAPK signaling pathway. Yang HL, Kuo YH, Tsai CT, Huang YT, Chen SC, Chang HW, Lin E, Lin WH, Hseu YC. Food Chem Toxicol. 2011;49(1):290–298.
28. Cytotoxic effect and induction of apoptosis in human cervical cancer cells by Antrodia camphorata. Yang PY, Hu DN, Liu FS. Am J Chin Med. 2013;41(5):1169–1180.
29. Anticancer effects of eleven triterpenoids derived from Antrodia camphorata. Lee YP, Tsai WC, Ko CJ, Rao YK, Yang CR, Chen DR, Yang MH, Yang CC, Tzeng YM. Anticancer Res. 2012;32(7):2727–2734.
30. Administration of polysaccharides from Antrodia camphorata modulates dendritic cell function and alleviates allergen-induced T helper type 2 responses in a mouse model of asthma. Liu KJ, Leu SJ, Su CH, Chiang BL, Chen YL, Lee YL. Immunology. 2010;129(3):351–362.
31. An extract of Antrodia camphorata mycelia attenuates the progression of nephritis in systemic lupus erythematosus-prone NZB/W F1 mice. Chang JM, Lee YR, Hung LM, Liu SY, Kuo MT, Wen WC, Chen P. Evid Based Complement Alternat Med. 2011;2011:465894.
32. Review of biological and pharmacological activities of the endemic Taiwanese bitter medicinal mushroom, Antrodia camphorata (M. Zang et CH. Su) Sh. H. Wu et al. (higher Basidiomycetes). Yue PY, Wong YY, Chan TY, Law CK, Tsoi YK, Leung KS. Int J Med Mushrooms. 2012;14(3):241–256.
33. A novel inhibitory effect of Antrodia camphorata extract on vascular smooth muscle cell migration and neointima formation in mice. Li YH, Chung HC, Liu SL, Chao TH, Chen JC. Int Heart J. 2009;50(2):207–220.
34. The vasorelaxation of Antrodia camphorata mycelia: involvement of endothelial Ca(2+)-NO-cGMP pathway. Wang GJ, Tseng HW, Chou CJ, Tsai TH, Chen CT, Lu MK. Life Sci. 2003;73(21):2769–2783.