Associate editor: I. KimuraRecent research and development of Antrodia cinnamomea
Introduction
Fungi form the second largest group of living organisms after insects and it is believed that over 1.5 million fungal species exist in nature (Mueller & Bills, 2004). They have attracted scientists from different disciplines owing to their fascinating nature and capability to survive in hostile environments in the midst of decay at the harshest layer of the ecosystem. This survival mechanism has been evolved over millennia through producing an arsenal of secondary metabolites to fight array of different pathogens in such environments. These secondary metabolites have been utilized in the health care system over the past two centuries with astonishing success in reducing mortality rate and diseases burden (Halpern, 2007). Fungi can be subdivided into two main categories, microfungi and macrofungi or mushrooms. Mushrooms are not a taxonomic group but do include well over 12,000 species possessing macroscopic fruiting-bodies, the mushrooms or sporocarps, which are visible to the naked eye.
Medicinal mushrooms have emerged as integral ingredients of dietary supplements in the last few decades. It is estimated that between 80 and 85% of all medicinal mushrooms products are derived from the fruiting bodies, which have been either artificially cultured or collected from nature. However, due to the increased in market demand, mycelial products are considered the wave of the future (Cheung, 2008). Dietary supplements or functional foods or nutraceuticals are food components which affect one or more identified functions in the body in a positive manner and contain higher doses of food bioactive agents exceeding the levels obtained from normal food (Chang & Miles, 2004). The concept of functional food aroused from the prevailing fact that food and medicine have a common origin. Dietary supplements play a major role in global health system through curtailing health expenditure and offering superior health habits. It is estimated that the global market for dietary supplement reached $187 billion in 2010 (S.-H. Liu et al., 2010). Self-selected dietary supplements offer a unique opportunity for citizens to participate actively in the management of their own health issues instead of being on the passive side accepting whatever treatment the health professional decides to administer (Webb, 2006). Of course the health care team members participating in treatment should be fully aware with the patient's functional food intake to adjust therapeutic regimen and avoid any undesirable interactions. In a recent survey conducted in USA, it was found that 60% of patients who use dietary supplements never informed their physicians fearing of their disapproval or lack of understanding of complementary alternative medicine concept (Morris & Murray, 2006). Moreover, some physicians lack solid knowledge on dietary supplements biological activity and their interactions with prescribed drugs. However, with the proper knowledge from both sides, this sort of democratizing treatment is believed to improve patient compliance and mutual trust between patient and other health care team members.
Currently there are several important medicinal mushrooms used worldwide as dietary supplements including: Antrodia cinnamomea (AC), Cordyceps sinensis, Ganoderma lucidum, Phellinus igniarius, Polystictus versicolori, and Poria cocos (Halpern, 2007). In this review we focus on summarizing the recent milestones in AC research, especially the published work after 2008. We discuss in a chronological order the pharmacological activities of AC purified components and crude extracts as well as the biological effects of AC mycelia and fruiting bodies. We also state the recent findings in AC quality control protocols, synthetic methodologies for the preparation of its active components, developed culture techniques, phylogenetic analysis and gene cloning. For the research published before 2008, the reader is advised to refer to the following reviews (Ao et al., 2009, Chen et al., 2010, Geethangili and Tzeng, 2011, Rios et al., 2012).
Section snippets
A. cinnamomea and its host tree (Cinnamomum kanehirai)
A. cinnamomea (AC) is a treasured endemic Taiwanese medicinal mushroom, known in Chinese as “Niu-Chang-Chih”. The fungus has yellowish orange to brownish orange fruiting bodies possessing irregular shapes such as plate-type, horse's hoof, or tower shape (Cherng et al., 1995). Wild AC grows tightly attached by a broad lateral base in the rotting empty trunk of C. kanehirai, which is the only host tree for this mushroom. The growth rate of wild AC is extremely slow, as it takes one year for the
Challenges in A. cinnamomea research
Scientific research on AC has started in the early nineties of the last century with the taxonomic identification and binomial naming of the mushroom. One of the first obstacles emerged in studying A. cinnamomea was the scientific debate on its legitimate name. Four different names have been associated with this fungus including: Ganoderma camphoratum, A. cinnamomea, A. camphorata, and Taiwanofungus camphoratus. These names are used interchangeably in literature to indicate A. cinnamomea;
Pharmacological activity
A plethora of research has been conducted on AC extracts and its active components in vitro and in vivo in the last five years. In the coming section we summarize these findings according to the published reports, however, the reader may find some discrepancies in the results, such as different IC50 values against similar cell lines in different studies, which may be attributed to the experiment settings, source of the extract, or the use of unpurified samples. We state the reported results by
Extraction process of A. cinnamomea
It is believed that over 60% of the marketed herbal products and dietary supplements would fail most analytical tests required for pharmaceutical entities including quality, identity and quantity of the active components. FDA records showed that in the last thirteen years, 7 out of every 10 applications for new dietary supplements approval were rejected (Noonan & Noonan, 2008). Interestingly, the number of rejected applications has increased over time reaching 8 out of 10 in 2002. Safety
Synthesis
The promising biological activities of several classes of secondary metabolites isolated from AC jolted the development of different synthetic methodologies for the preparation of these active ingredients. Cross coupling reactions catalyzed by transition metals proved efficiency in the synthesis of AC secondary metabolites in high yielding protocols. Synthesis of maleic anhydride derivative and antrodimides were accomplished starting from succinic anhydride (41) which was converted to
Culture conditions
Different culturing techniques were developed to grow AC aiming to meet the increasing demand for this treasured mushroom. Of course culture conditions significantly affect AC growth rate and secondary metabolites composition. These effects have been studied by several research groups and their key findings are summarized in this section (Table 2). The effect of four different essential oils on the growth of cultured AC mycelia and basidiomes (fruiting bodies) grown on potato dextrose agar
Phylogenetic analysis
The difference in the D2 sequences of the large subunit (LSU) ribosomal DNA (rDNA) among different AC strains and related fungal taxa was investigated aiming to find similar genetic sequences between different fungal strains (Chiu et al., 2009). Matrix analysis of six different strains (B85, B86, B71 BCRC35396, BCRC35398, and BCRC35716) revealed 100% sequence identity. However, less similarity was observed upon comparing AC to similar fungal taxa such as A. malicola, Trametes versicolori or
Conclusion and future perspectives
In this review we introduced the recent findings in AC research done mainly by several research groups in Taiwan, Japan, and China. The recent introduction of this mushroom as a dietary supplement to the European and American markets is calling for the involvement of research groups from other countries and regulatory authorities to provide a clear biological and safety profile, as a crucial step in the process of including AC in the global complementary alternative system.
In the last five
Acknowledgment
This work was supported by grants from the Department of Health, Executive Yuan, Taiwan (DOH100-TD-C-111-002) and the National Science Council, Taiwan awarded to Yang-Chang Wu and Fang-Rong Chang. Part of this work has been conducted under the scientific agreement between the Department of Pharmacognosy and Natural products Chemistry, Faculty of Pharmacy, Ain-Shams University, Cairo, Egypt and the Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University,
References (211)
- et al.
Niuchangchih (Antrodia camphorata) and its potential in treating liver diseases
J Ethnopharmacol
(2009) The effects and challenges of bladder outlet obstruction
J Urol
(2000)- et al.
Unified route to asymmetrically substituted butenolide, maleic anhydride, and maleimide constituents of Antrodia camphorata
Tetrahedron
(2012) - et al.
Apoptotic effects of a high performance liquid chromatography (HPLC) fraction of Antrodia camphorata mycelia are mediated by down-regulation of the expressions of four tumor-related genes in human non-small cell lung carcinoma A549 cell
J Ethnopharmacol
(2010) - et al.
The adjuvant effects of Antrodia camphorata extracts combined with anti-tumor agents on multidrug resistant human hepatoma cells
J Ethnopharmacol
(2008) - et al.
A 90-day subchronic toxicological assessment of Antrodia cinnamomea in Sprague–Dawley rats
Food Chem Toxicol
(2011) - et al.
Polysaccharides from Antrodia camphorata mycelia extracts possess immunomodulatory activity and inhibits infection of Schistosoma mansoni
Int Immunopharmacol
(2008) - et al.
Compound MMH01 possesses toxicity against human leukemia and pancreatic cancer cells
Toxicol In Vitro
(2009) - et al.
Ethanol extracts of fruiting bodies of Antrodia cinnamomea exhibit anti-migration action in human adenocarcinoma CL1-0 cells through the MAPK and PI3K/AKT signaling pathways
Phytomedicine
(2012) - et al.
Anticancer effects of Taiwanofungus camphoratus extracts, isolated compounds and its combinational use
J Exp Clin Med
(2010)