Ganoderma lucidum and its pharmaceutically active compounds
Introduction
Ganoderma is a white rot wood-degrading basidiomycete with hard fruiting bodies. G. lucidum (W.Curt.:Fr.) Lloyd and Ganoderma applanatum (Pers.) Pat. (Aphyllophoromycetideae) are two species most often reported as a source of medicinal compounds. In Asian traditional medicine, the fruiting body of G. lucidum (Fig. 1), called Ling-Zhi in Chinese and Reishi in Japanese language, has been used for treatment of several diseases for thousands of years, as reported in Shen Nong's Materia Medica 1., 2.. However, an increasing systematic research (Fig. 2) into the Ganoderma active compounds elucidates its numerous pharmacological effects, such as antitumor, immunomodulatory, cardiovascular, respiratory, antihepatotoxic and central nervous system effects. Modern uses of Ganoderma therefore include treatment of coronary heart diseases, arteriosclerosis, hepatitis, arthritis, nephritis, bronchitis, asthma, hypertension, cancer and gastric ulcer 1., 3.. Publications also report on Ganoderma antiallergenic constituents [4], immunomodulatory action 5., 6., antitumor activity [7], cardiovascular effects [8], liver protection and detoxification, and effects on nervous system [9]. New reports emphasize its potential in treatment of viral, especially HIV infections 10., 11., 12., 13., 14., 15..
G. lucidum is very scarce in nature. As the demands of international markets for G. lucidum fruiting bodies and/or mycelium biomass are in constant increase, an artificial cultivation has become essential. Successful farming on wood logs and in bags filled with wood or straw substrates has been known for decades, especially in China. Biotechnological cultivation in bioreactors on solid substrates, or with submerged liquid substrate cultivation has been developed and introduced for small and pilot-plant production 16., 17., 18., 19., 20.. The quality and content of physiologically active substances vary from strain to strain, and also depend on location, culture conditions [21], the growth stage of the fungus [22], the processing procedures, and formulation preparation [23].
Diverse groups of chemical compounds with pharmacological activity have been isolated from the mycelium and fruiting body of Ganoderma species: triterpenoids, polysaccharides, proteins, amino acids, nucleosides, alkaloids, steroids, lactones, fatty acids and enzymes 1., 3.. The most important pharmacologically active constituents of Ganoderma mushrooms are triterpenoids and polysaccharides.
Section snippets
G. lucidum cultivation methods
As G. lucidum is very scarce in nature, artificial cultivation has become essential to meet the demands of international markets (Fig. 3).
The main traditional G. lucidum fruiting body cultivation methods remain sawdust cultivation in bags or bottles and cultivation on natural logs. Both cultivation technologies depend on the same essential environmental factors, including temperature, humidity and oxygen [24]. During the spawn run, mycelia grow at 10–38°C, with the optimum mycelial incubation
Cultivation on long unsterilized logs
In the past, natural logs as long as one meter were used without sterilization in growing Ganoderma species in China. Fruiting body cultivation on long wood logs took much labor. Long incubation periods (2–3 years) were required to obtain mature fruiting bodies on such substrates 24., 26..
Cultivation on short sterilized logs
Since the late 1980s, new trends have been developed using short logs. Almost all Ganoderma spp. natural log growers adopted the short-log cultivation in China, Japan, the United States and elsewhere. High
Sawdust substrates in sterilizable bags (synthetic log cultivation)
According to Royse [29], most cultivation of G. lucidum is on supplemented sawdust contained in heat-resistant polypropylene bottles or bags. Sawdust of hardwoods is usually supplemented with rice bran (10%) and CaCO3 (3%), moistened with water and filled (700 g) into plastic bags. A plastic collar then is fitted onto each bag and closed with a cotton plug. After heat treatment (95–100°C for 5 h) the substrate is allowed to cool overnight and then inoculated with grain or sawdust spawn. The
Solid-state cultivation
A Slovenian patent [40] claimed a process of growing G. lucidum on a solid cultivation substrate using the solid-state cultivation in a horizontal stirred bioreactor. Beech sawdust was used as a solid cultivation substrate. The process enabled a precise leading and monitoring of the fungal growth at sterile conditions. Large quantities of biomass could be prepared according to the process to yield products applicable to pharmacy. The biomass could also be used as a solid inoculum for the
Main pharmacologically active compounds in G. lucidum
The most important pharmacologically active constituents of Ganoderma mushrooms are triterpenoids and polysaccharides (Fig. 4).
Triterpenoids from Ganoderma mushrooms
Over 150 triterpenoids were found in Ganoderma spp., such as ganoderic (highly oxygenated C30 lanostane-type triterpenoids), lucidenic, ganodermic, ganoderenic, ganolucidic and applanoxidic acids, lucidones, ganoderals and ganoderols 5., 6., 7., 8., 9., 10., 11., 12., 13., 14., 15., 16., 17., 18., 19., 20., 21., 22., 23., 24., 25., 26., 27., 28., 29., 30., 31., 32., 33., 34., 35., 36., 37., 38., 39., 40., 41., 42., 43., 44., 45., 46., 47., 48., 49., 50., 51., 52., 53., 54., 55., 56., 57., 58.,
Polysaccharides from Ganoderma fruit bodies and mycelia
In recent years, a lot of scientific attention has been focussed on Ganoderma polysaccharides, which represent a structurally diverse class of biological macromolecules with a wide range of physicochemical properties. Studies have shown that the most active immunomodulatory polysaccharides are water-soluble β-1-3-d and β-1-6-d glucans, that can be precipitated by ethanol. Their prevailing structure is β-1-3 d-glucopyronan with 1–15 units of β-1-6 monoglucosyl side chains. Their 1,3-linked
Regulation and protection of cells
Several works suggested that G. lucidum also positively affects and protects living cells. Cao and Lin 106., 109. found out that G. lucidum polysaccharides had an effect on regulation of maturation and function of dendritic cells. You and Lin et al.[134] reported on protective effects of G. lucidum glycopeptides on injury of macrophages induced by reactive oxygen species. Shi et al.[135] studied aqueous extracts of eight mushroom species and found out that G. lucidum had a potential for
Peptidoglycanes and proteins
One of the oldest known proteins isolated from G. lucidum is LZ-8, for which immunomodulatory and immunosuppressive activities were reported [138]. From G. lucidum mycelia produced by submerged fermentation, Tian and Zhang [139] purified and characterized a proteinase A inhibitor with a molecular mass of 38 kDa. The purification was carried out by ethanol precipitation (50–80%), ACA44 gel filtration and Source 30Q anion exchange. Its carbohydrate content was about 70%. The linkage between the
Other compounds
Polysaccharides and triterpenes have been most thoroughly investigated from G. lucidum and related species. However, other active compounds have also been described, such as adenosine with anti-platelet aggregation effect, lectins with mitogenic effect, alkaloids, fatty acids, vitamins and essential minerals. A structured list of chemical constituents of G. lucidum was given in [87].
Formulations, market products and clinical trials
Several formulations have been developed, patented and used as nutraceuticals, nutriceuticals and pharmaceuticals [143], mainly with Ganoderma fruiting bodies, spores and their water or ethanol extracts, rarely with purified active compounds.
Several products have undergone clinical trials and became available commercially as a syrup, injection, tablet, tincture, or bolus of powdered medicine and additives [144]. For example, Zhang and Li [145] reported on a clinical investigation of Green
Conclusion
Reports on isolated compounds from G. lucidum are very convincing; there is abundant evidence that triterpenoids, polysaccharides and proteoglycans are effective. In most cases, extracts of partly-purified preparations have been used for in vitro or in vivo testing. Synergistic effects of mixtures of active components have been known; however, their biological activities need further assessment before they can be accepted not only by the traditional Asian medicine, but also by the Western
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