GUÍA DE PROCEDIMIENTOS LABORALES: PROCEDIMIENTOS ADMINISTRATIVOS, JUDICIALES E INTERNACIONALES DE PROTECCIÓN DE LOS DERECHOS LABORALES Dr. Max PuigMinistro de Trabajo Equipo de coordinación Sandra Dueñas-PaschalGerente RegionalPact Andrés Valentín Herrera GonzálezDirector general de TrabajoMinisterio de Trabajo Rafael Arturo Mariano OviedoDirector de Asistencia JudicialMinisterio de Trabajo
Kutyaegeszseg.huReishi or Ling Zhi (Ganoderma lucidum) Solomon P. WasserInstitute of Evolution, University of Haifa, Mount Carmel, Haifa, Israel and locust (Quercus, Acer, Alnus, Betula, Castanea,Coryolus, Fagus, Fraxinus, Populus, Pyrus, Magnolia, Ganoderma lucidum (reishi mushroom, Ling Zhi) has Tilia). G. lucidum is less frequently found on conifer- been an economically important species, particularly ous trees (e.g., Larix, Picea, Pinus) in Europe, Asia, in the Far East countries (China, Japan, Korea, etc.), and North and South America (in temperate rather for over 4000 years. It is widely grown on a commercial than subtropical regions). In the Orient, it grows pri- scale and is commonly purchased for its medicinal and marily on plum trees. It is also found on stumps, generally near the soil surface, and occasionally onsoils arising from buried roots.
NAME AND GENERAL DESCRIPTION In Latin, lucidum means shiny or brilliant and aptly The mushroom is too tough to be edible.
describes this mushroom's fruiting body, which has amodeled, sculptured, varnished appearance. The Chi- RELATED SPECIES AND ARTIFICIAL nese and Koreans know it as Ling Zhi (mushroom of herb and immortality), whereas the Japanese call thismushroom reishi or mannentake (10,000 year mush- Ling Zhi encompasses several Ganoderma species, room). The virtues of G. lucidum extracts, handed which are widely used for medicinal purposes, e.g., down from generation to generation, include it as a G. lucidum, G. luteum Steyaert, G. atrum Zhao, Xu ‘‘cancer cure'' and a symbol of happy augury, good and Zhang, G. tsugae Murrill, G. applanatum (Pers.: fortune, good health, longevity, and even immortality.
Wallr.) Pat., G. australe (Fr.) Pat., G. capense (Lloyd) Beginning with the Yuan Dynasty (1280–1368 A.D.), Teng, G. tropicum (Jungh.) Bres., G. tenue Zhao, Xu G. lucidum has been endlessly represented in art—in and Zhang, and G. sinense Zhao, Xu and Zhang.
paintings, carvings of jade and deer's antlers, furniture According to two famous Chinese plant medical and carpet designs, balustrades, jewelry, women's hair books, Shen Nong Ben Cao Jing (25–220 A.D., Eastern combs, perfume bottles—in short, wherever an artistic Han Dynasty) and Ben Cao Gang Mil by Li Shi-Zhen urge found an outlet. The earliest mention of Ling Zhi (1590 A.D., Ming Dynasty), six Ling Zhi species= was in the era of the ﬁrst emperor of China, Shing- varieties were known in China at that time. World- huang of the Ch'in Dynasty (221–207 B.C.). Subse- wide, more than 250 Ganoderma species have been quently, depictions of this fungus proliferated through described.[2,3] However, in therapeutic practices and Chinese literature and art. The mushroom is known literature citations, Ganoderma usually refers to the by many in North America and Europe as one of species of G. lucidum.
the ‘‘artist's conk'' fungi (the true artist conk is Besides being treasured for its medicinal value in China for more than 1000 yr, the lack of availability A detailed description of the reishi mushroom and of G. lucidum was also largely responsible for it being its taxonomy can be found in Refs.[3,10] (Fig. 1).
so highly cherished and expensive. During ancienttimes in China, any person who picked the mushroom from the natural environment and presented it to ahigh-ranking ofﬁcial was usually well rewarded. Even This annual mushroom grows on a wide variety of in the early 1950s, it was presented to Chinese leaders dead or dying trees, e.g., deciduous trees especially in Mainland China and Taiwan, following the occa- oak, maple, elm, willow, sweet gum, magnolia, sional discovery in the wild. In the past, G. lucidumgrew in small quantities only in the wild; therefore, itwas very expensive.
Artiﬁcial cultivation of this valuable mushroom Solomon P. Wasser is at the Institute of Evolution, University of Haifa, Mount Carmel, Haifa, Israel.
was successfully achieved in the early 1970s, and since Encyclopedia of Dietary Supplements DOI: 10.1081/E-EDS-120022119Copyright # 2005 by Marcel Dekker. All rights reserved.
Reishi or Ling Zhi (Ganoderma lucidum) , nephritis, hypertension, arthritis,neurasthenia, insomnia, bronchitis, asthma, and gastriculcers.[6,8–11] In China, G. lucidum has been cherishedfor over 4000 yr as a longevity-promoting tonic.According to Hikino, ‘‘the most important elixirsin the Orient'' are ginseng (Paxax ginseng C.A. Meyer)and the fruit bodies of G. lucidum.
Fascination with Ganoderma began under the name of ling chih, later transliterated to reishi in Japanese.
The fungus ﬁrst appeared in Chinese literature duringthe Han Dynasty (206 B.C.–220 A.D.). Emperor Wuassociated growth of the fungus in an inner chamberof the Imperial Palace with a plant of immorality—known simply as the chih plant or chih fungus.The Han Dynasty chronicler, Pan Ku, wrote a poemusing the term ling chih. However, the associationbetween the original chih fungus and G. lucidum hadclearly derived from legends of an earlier mysteriouschih fungus or chih plant of immortality recorded inIndia. Indeed, versions of Indian legends concerningthis mushroom are found later, in almost identicalform in the Chinese literature, in reference to whatwould be ling chih (reishi), while the identity of thetrue chih plant or fungus of immortality remains indispute. In addition to its medicinal properties, reishihas been used in the Orient as a talisman to protect aperson or home against evil. Medicinal uses of G. lucidum in ancient Far East countries included the treatment of neurasthenia,debility from prolonged illness, insomnia, anorexia,dizziness, disease, hypertension, prevention of altitude sickness, Fig. 1 Ganoderma lucidum: (a) fruit body, (b) spores.
treatment of ‘‘deﬁciency fatigue,'' carcinoma, andbronchial cough in the elderly.[3,6,7,9–11] Chineseresearch during the past decade has focused on much 1980, production of G. lucidum has developed the same uses, whether in the ﬁelds of antiaging=life rapidly, particularly in China. The process of produ- cing G. lucidum fruiting bodies is the same as for chronic viral hepatitis, male sexual dysfunction, other cultivated edible mushrooms and can be divided hypercholesterolemia, immunological function in the into two major stages. The ﬁrst involves the prepara- tion of the fruiting culture, stock culture, mother induced immunosuppression, anticarcinogenic and spawn, and planting spawn, while the second entails antitumor activity, and immunostimulation.[6,8,13–18,55] the preparation of growth substrates for mushroom Different types of G. lucidum, according to Traditional cultivation. Currently, the methods most widely Chinese Medicine (TCM), have different tastes and adopted for commercial production are the wood thus affect different organs. Based on their color, six log, short wood segment, tree stump, sawdust bag, different types of G. lucidum have been classiﬁed, and bottle procedures (for cultivation details, see each with different uses (Table 1).
General Nutritional Components ofGanoderma lucidum HISTORY AND TRADITIONAL USES G. lucidum contains mainly protein, fat, carbohydrate, G. lucidum has been used in folk medicine of China and ﬁber. Artiﬁcially cultivated variety has similar and Japan, especially in the treatment of hepatopathy, contents of nutritional components compared with Reishi or Ling Zhi (Ganoderma lucidum) The six types of reishi Improves eyesight and liver function; calms nerves Aids internal organs; improves memory; enhances vitality Strengthens spleen function; calms the ‘‘spirit'' (shen) Improves lung function; gives courage and strong will Enhances function of ears, joints, muscles; helps complexion aThe red-colored variety of G. lucidum is generally regarded as the most potent and medicinal. wild types, and the extraction signiﬁcantly increases spores also contain triterpene lactones, and docu- the amounts of crude protein and carbohydrates mented triterpenoids have been divided into 10 groups and deleted crude ﬁber. Mizuno reported the based on the structural similarities and known bio- composition of G. lucidum extract (% of dry weight), logical and medicinal properties (Fig. 2).
which consisted of folin-positive material (68.9%),glucose (11.1%), protein (7.3%), and metals (10.2%)(K, Mg, and Ca are the major components with Ge 489 mg=g). These results generally agree with those reported by other authors.[4,5,10] However, there arequalitative and quantitative differences in the chemical More than 100 types of polysaccharides have been composition of G. lucidum products depending on the isolated from the fruiting body, spores, and mycelia, strain, origin, extracting process, and cultivation or separated from the broth of a submerged liquid culture of G. lucidum. Most have a molecular weightranging from 4 105 to 1 106 in the primarystructure. They comprise one of the major sources of Major Bioactive Constituents G. lucidum's pharmacologically active compounds.
G. lucidum polysaccharides such as b-D-glucans, Over 300 reports have been published concerning heteropolysaccharides, and glycoprotein have been the chemical constituents of G. lucidum and related isolated and characterized and are considered the species. The fruiting body, mycelia, and spores of G.
major contributors of bioactivity of the mushroom.
lucidum contain approximately 400 different bioactive b-D-glucans consist of a linear backbone of b-(1 ! 3)- compounds, which mainly include triterpenoids, poly- linked D-glucopyranosyl groups with varying degrees saccharides, nucleotides, sterols, steroids, fatty acids, of branching from the C6 position. In addition to proteins=peptides, and trace elements.[11,16,20,21,55] water-soluble b-D-glucans, b-D-glucans also exist withheteropolysaccharide chains of xylose, mannose, galac-tose, uronic acid, and b-D-glucans–protein complexes TERPENOID COMPOUNDS that are present at 10–50% in dry G. lucidum.[16,24–26]Some protein-bound polysaccharides and fucose- containing glycoprotein with bioactivity have beenisolated.[18,27,28] At least 140 different triterpenes have been identiﬁed inG. lucidum.[3,6,10,11,20,21] The majority are bitter tastingand largely occur as ganoderic acid. A new triterpe- noid, named ganosporeric acid A, was recently isolatedfrom the ether-soluble fraction of the spores. Min Some proteins with bioactivity have also been isolated et al. reported the isolation of six new lanostane- from G. lucidum. The LZ-8 is one such protein isolated type triterpenes, and also from the spores (ganoderic from G. lucidum, which was shown, by sequencing stu- acids g, d, e, z, Z, and y). Preliminary studies indicate dies, to be similar to the variable region of the immuno- that the spores contain considerably higher contents globulin heavy chain in its sequence and in its predicted of ganoderic acids than other parts of the fungus and secondary structure. Major biological activities of LZ-8 that triterpene composition of the fruit body varies resemble those of lectins, with mitogenic capacity toward according to the area in which it is grown. The mouse spleen cells and human peripheral lymphocytes Reishi or Ling Zhi (Ganoderma lucidum) Fig. 2 The lanostane-type triterpenoids of Ganoderma lucidum. These triterpenoids are divided into ten groups based onstructural similarity.
and agglutination of sheep red blood cells in vitro.
function as a potent suppressor of bovine serum Neither was inhibited by the mono- or dimeric sugars albumin-induced anaphylaxis in CFW mice in vitro.
examined, indicating that LZ-8 is not a lectin per se.
It appears to be related to an ancestral protein of the It did not agglutinate human red blood cells but could Reishi or Ling Zhi (Ganoderma lucidum) NITROGENOUS COMPOUNDS Triterpenoids, such asganoderic acids T–Z isolated from G. lucidum, showed Nucleotides and Nucleosides cytotoxic activity in vitro on hepatoma cells. Alanostanoid, 3b-hydroxyl-26-oxo-5a-lanosta-8,24-dien- Nucleosides include adenosine and 5-deoxy-50 methyl- 11-one, and a steroid, ergosta-7,22-diene-3b,3a,9a- triol, isolated from fruiting bodies of G. lucidum,demonstrated potent inhibitory effects on KB cellsand human PLC=PRF=5 cells in vitro. OTHER CONSTITUENTS immune function is thought to be the major mechan- Reishi also contains sterols, amino acids, soluble ism of antitumor action by G. lucidum. Among the proteins, oleic acid, cyclo-octasulfur, an ergosterol responsible for the antitumor effect.[3,10,11,13,20,28,30] This polysaccharide appears to act by binding to leukocyte surfaces or serum-speciﬁc proteins leading to activation of macrophages, T-helper, natural killer (NK) and other effector cells.[33–35] All of these Regarding the inorganic ions, the mushroom con- increase the production of cytokines such as tumor tains Mg, Ca, Zn, Mn, Fe, Cu, and Ge. The spores necrosis factor (TNF-a) interleukins (IL) and inter- themselves contain choline, betaine, tetracosanoic acid, feron (IFN), nitric oxide (NO), and antibodies by the stearic acid, palmitic acid, ergosta-7, 22-dien-3-ol, activated effector cells. Tumor regression in various nonadecanoic acid, behenic acid, tetracosane, hentri- animal models can be ascribed to vascular damage to acontane, ergosterol, and b-sitosterol. One of the tumor blood ﬂow and necrosis caused by T cells and lipids isolated from G. lucidum is pyrophosphatidic local TNF-a production.
In addition to host defense potentiation, other mechanisms are also involved in the antitumor effect.
THERAPEUTIC APPLICATIONS A compound from G. lucidum suppressed the growthof K562 leukemic cells in a dose- and time-dependent Preclinical and Clinical Studies manner and induced their differentiation into moremature erythrocytic cells. The conditioned medium G. lucidum has been reported to have a number of from PS-stimulated human blood mononuclear cells pharmacological effects including immunomodulating, (PSG-MNC-CM) signiﬁcantly inhibited the growth of U937 cells and induced their differentiation into chemopreventive, antitumor, radioprotective, sleep- mature monocytes=macrophages, which had functions promoting, antibacterial, antiviral (including anti-HIV), of phagocytosis and producing cytoplasmic super- hypolipidemic, antiﬁbrotic, hepatoprotective, diabetic, oxide. Inhibition of DNA polymerase and posttrans- antioxidative and radical-scavenging, anti-aging, hypo- lational modiﬁcation of oncoproteins may contribute glycemic, and anti-ulcer properties.[3,6,9–11,16,25,30,55] to the antitumor activity of reishi. The organic Reishi has now become recognized as an alternative germanium may also contribute to its antitumor adjuvant in the treatment of leukemia, carcinoma, activity. The mechanisms for tumor prevention hepatitis, and diabetes.[9–11,14–18,25,30,55] Clinical stu- and antitumor effect of G. lucidum are shown in Fig. 3.
dies, to date, lack the controls needed to make a scien- In clinical studies, G. lucidum products have been tiﬁc assessment of its efﬁcacy in a given application, a widely used as a single agent or in combination with situation expected to change with increasing interest other herbal medicines or chemotherapeutic drugs for from Western scientiﬁc communities. It was only many years, mainly in Asian countries. However, since the last decade that clinical trials on the use randomized, placebo-controlled and multicancer clini- of G. lucidum preparation used to treat cancer and cal studies using reishi alone have rarely been reported.
other diseases have been reported in internationalpeer-reviewed journals.
Ganoderma lucidum as a Single Agent In a randomized, placebo-controlled clinical study,143 cancer were given an oral G. lucidum polysaccharide and glycoproteins) isolated from G. lucidum demon- extract (Ganopoly) of 1800 mg three times daily for strated antitumor activity against Sarcoma 180 in 12 weeks. Twenty-seven patients were not assessable Reishi or Ling Zhi (Ganoderma lucidum) Fig. 3 The mechanisms for the tumor preventive and antitumor effect of G. lucidum. Active constituents from G. lucidum mayoperate through several mechanisms including enhancement of detoxiﬁcation of carcinogens (line 1), increased expression andactivity of Phase II enzymes (line 2), inhibition of organ exposure of carcinogens due to reduced absorption or increased excretion(line 3), decreased expression and activity of Phase I (e.g., CYPs) enzymes (line 4), decreased formation of toxic metabolites andadduct formation with macromolecules (line 5), enhanced host immune responses (e.g., activation of macrophages, T lymphocytes,and natural killers producing various cytokines such as TNF-a, IFNs, and ILs, which improve immunosurveillance and kill pre-neoplastic and cancer cells) (line 6), antioxidative and radical-scavenging effects (line 7), antipromotion effect (line 8),antiproliferation (line 9), apoptosis induction of tumor cells (line 10), induction of differentiation (line 11), direct cytotoxicity,induction of cell-cycle arrest, antiproliferation and modulation of signaling transduction molecules (line 12), antiprogressionand tumor growth inhibition (line 13), antimetastasis (line 14), and anti-angiogenesis (line 15). for response and toxicity, because they were lost in of 143 cases (26.6%) had stable disease for 12 weeks the follow-up or refused further therapy before the or more (range: 12–50 weeks). There was no signiﬁcant 12 weeks of treatment. Of the 100 fully assessable change in the Functional Assessment of Cancer patients, 46 (32.2%) had progressive disease before or Therapy-General (FACT-G) scores in 85 assessable at the 6-week evaluation point (range: 5 days–6 weeks).
patients. However, palliative effects on cancer-related Sixteen subjects (11.2%) developed progressive dis- symptoms, such as sweating and insomnia, have been ease between 6 and 12 weeks of therapy. No objective observed in many subjects. In the group with stable (partial or complete) responses were observed, but 38 disease, FACT-G scores improved in 23 patients, were Reishi or Ling Zhi (Ganoderma lucidum) unchanged in ﬁve, and declined in one. contributors to the anticancer effect of group, the median change from the baseline score to G. lucidum, but other constituents, such as proteins, the 6- and 12-week score was þ7.6 and þ10.3, both also play a role (Fig. 4). Several recently published statistically signiﬁcant (P < 0.05). For the 38 patients reports have found that G. lucidum or G. lucidum- with SD, the median change from the baseline score containing herbal mixtures (PC-SPES) had biological was 28.1 10.2 weeks. The prostate-speciﬁc antigen activities (e.g., cancer biomarker alteration) and (PSA) levels in the ﬁve prostate cancer patients were beneﬁcial effects (e.g., palliative effects in cancer reduced signiﬁcantly (P < 0.05) during SD. Ganopoly patients) although striking objective responses were was well tolerated with ﬁve moderate adverse events not observed.[16,47] recorded. The results indicate that Ganopoly may havean adjunct role in the treatment of patients withadvanced cancer although objective responses were CHEMO- AND RADIOPREVENTIVE EFFECTS not observed in this study.
The chemo- and radiopreventive effect of G. lucidummay result from its effects on the immune system.
polysaccharides restored the TNF-a Herbal Mixture: PC-SPES production inhibited by cyclophosphamide to normallevels in mice. Both the G. lucidum extract and krestin PC-SPES has been used as an alternative in the treat- ment of prostate cancer. Several clinical trials have versicolor) were beneﬁcially effective in the recovery been completed with patients having advanced pros- of cellular immunocompetence, measured by [3H] tate cancer.[48,49] Small et al. included 70 subjects thymidine incorporation with splenic cells stimulated with androgen-dependent (n ¼ 33) and androgen- independent (n ¼ 37) disease, which was refractory (PHA) and concanavalin A. The extract (400 mg=day= to surgery, radiotherapy, and hormone therapy. Treat- kg body weight) appears more effective than krestin ment of PC-SPES at a dose of 3 capsules (320 mg= (500 mg=day=kg body weight) in repairing the damage capsule) orally resulted in 80% decrease in PSA levels of subset T cells in the spleens of g-irradiated mice, as in all 32 patients with androgen-dependent cancer, the relative thymus weight and CD4 and CD8 spleno- while it was undetectable in 26 patients (81%). The cytes were higher in G. lucidum extract-treated mice median duration of PSA response was 57 weeks. In compared with krestin-treated mice. the 35 patients with androgen-independent cancer, 19 In morphine-dependent mice, a polysaccharide (54%) had a PSA decrease of 50% with median dura- peptide from G. lucidum could restore several immu- tion of PSA response of 18 weeks. The study by Pfeifer nologic parameters depressed by morphine treatment et al., which included only 16 patients with andro- to normal levels or even beyond. Both c-myb and gen-independent disease for just a 20-week follow-up, c-myc mRNA expression in splenocytes of repetitive showed an improvement in quality of life for the morphine-treated mice was signiﬁcantly decreased, patients. PC-SPES was generally well tolerated by and the polysaccharide peptide could induce the prostate cancer patients, but they exhibited a dose- expression of these genes indicating that the one from dependent toxicity similar to that of diethylstilboes- G. lucidum could be of a potential application in con- trol. Side effects include reduced libido, hot ﬂashes, trolling abuse of opiate-induced immunodeﬁciency.
diarrhea, dyspepsia, leg cramps, nipple tenderness, andgynecomastia.[48,49] events are pulmonary emboli in 4–5% of patients and deep vein thrombosis in 2% of patients. Overall, theclinical responses to PC-SPES compare favorably with Triterpenoids of G. lucidum have been reported to second-line hormonal therapy with agents, such as exert various enzyme inhibitory activities. Inhibitors estrogens and ketoconazole. However, it must be of farnesyl protein transferase (FTP) have been noted that the adulteration of PC-SPES products has demonstrated to inhibit Ras-dependent cell transfor- become a serious problem. Further details may be mation and thus represent a potential therapeutic obtained at the website of the NIH National Center strategy for the treatment of human cancers. Gano- for Complementary and Alternative Medicine at deric acids A and C were identiﬁed to be inhibitors of FTP. Ergosterol peroxide, 5,8-epidioxy-5a, 8b- In summary, animal studies have demonstrated the antitumor activity of G. lucidum administered reported to selectively enhance the inhibitory effect by different routes at different stages of tumor of linoleic acid on DNA polymerase-b, but not on growth.[3,10,16,20] Polysaccharides and triterpenoids the type a enzyme. Ergosterol peroxide itself was Reishi or Ling Zhi (Ganoderma lucidum) Fig. 4 Possible molecular targets of G. lucidum. G. lucidum constituents (e.g., b-D-glucan and triterpenoid) modulated Ras=Erk,c-myc, CREB protein and mitogen-activated protein kinases, which may provide an explanation for the cancer preventive andanticancer effect of G. lucidum. ineffective but completely blocked rat DNA poly- MITOGENIC ACTIVITY merase-b in the presence of linoleic acid. Inhibitorsof phospholipase A2(PLA2) can be developed as poten- Extracts from G. lucidum (e.g., polysaccharide frac- tial anti-inﬂammatory agents for the treatment of tions, methanolic extracts, and LZ-8) have mitogenic rheumatic arthritis, asthma, and psoriasis. Ganoderic effects on mouse splenocytes and human peripheral acid T was found to inhibit secreted PLA2 from blood mononuclear cells (PBMCs) in the presence of pig pancreas, human synovial ﬂuid, and bee venom, various immunostimulating or immunosuppressive but no such effect was observed with ganoderic acids agents (e.g., PHA and 12-O-tetradecanoylphorbol 13- AA, O, R, S, T-OH, and T-OH-H2. acetate).[42,43] Treatment of the PBMCs with cyclo-sporin A (CsA) led to blockage of the cell proliferation.
The methanolic fraction from G. lucidum recovered IMMUNOMODULATING EFFECTS the CsA-induced inhibition of the cell proliferation,which might be due to the inhibition of the protein The immunomodulating effects of G. lucidum are kinase C signal pathway and acceleration of the CsA shown in Fig. 5.
Reishi or Ling Zhi (Ganoderma lucidum) Fig. 5 The immune-modulating effects of G. lucidum. The major immunomodulating effects of active substances derived fromG. lucidum include mitogenecity and activation of immune effector cells such as T lymphocytes, macrophages, and NK cellsleading to the production of cytokines including ILs, TNF-a, and IFNs. Other effects, such as inhibition of mast cells, activationof B lymphocytes, and the complement system have also been reported. EFFECTS ON IMMUNE Extracts from G. lucidum are potent activators of T cells, inducing the production of a number of cyto-kines, in particular IL-2. In human PBMC (primarily In vitro and in vivo studies in mice indicated that G. luci- T cells) in vitro, the crude G. lucidum water extract dum water extract stimulates the production of IL-2 by splenocytes in the presence of hydrocortisone.[3,7,10,11] IL-10 and TNF-a, IL-1b, IL-6, and IL-2. Crude Reishi or Ling Zhi (Ganoderma lucidum) polysaccharide fractions isolated from fresh differentiated and apoptosis bodies potentiated the release of IFN-g from human inductive to the HL-60 and the U937 leukemic cells. T cells. A polysaccharide fraction (GL-B) promoted IFN-g and TNF-a released from macrophages act the production of IL-2 in a dose-dependent manner synergistically to inhibit the growth of leukemic cells and markedly enhanced the cytotoxicity of cytotoxic as shown by the antibody-neutralization studies.
T lymphocytes, which was increased by 100% at a GLB7, a G. lucidum polysaccharide, decreased the concentration of 200 mg=ml. GL-B also restored the production of oxygen-free radicals and antagonized mixed lymphocyte response to alloantigen, automatic the respiratory burst induced by PMA in murine proliferation, and IL-2 production of splenocytes in peritoneal macrophages. These observations suggest aged mice declined as compared with that in young adult mice in vitro.
radicals in murine peritoneal macrophages plays an LZ-8 is also a potent T-cell activator mediating its important role in the anti-aging effect of G. lucidum effects via cytokine regulation of integrin expression.
Stimulation of human peripheral blood lymphocytes Ganoderan (GAN), a b-D-glucan isolated from with LZ-8 resulted in the production of IL-2 and a G. lucidum, enhanced the production of NO in the corresponding upregulation of IL-2 receptor expres- RAW 264.7 macrophages. The ability of GANs to sion. In addition to T-cell proliferation, microscopic produce NO was based on differences in the chemical examination of LZ-8-stimulated peripheral blood lym- composition of GANs obtained from the mycelium phocytes revealed that LZ-8 induced cellular aggregate on various carbon sources and mycelial fractionation.
formation. This formation correlated with a dramatic The highest NO production was observed in the poly- rise in ICAM-1 expression and an increased produc- saccharide, which was extracted from the mycelial wall.
tion of IFN-g, TNF-a, and IL-1b, molecules associated Partial removal of the protein in the extracellular GAN with regulation of ICAM-1 expression. Both the aggre- by TCA treatment did appreciably reduce its capacity gate formation and the proliferative effects of LZ-8 to secrete NO. The cell proliferation of GAN-treated were blocked by the addition of a monoclonal anti- RAW 264.7 cell lines was inhibited compared to its body to either CD18 or CD11a, the counter–receptor control. Of the culture supernatant of macrophage complex components for ICAM-1. Furthermore, addi- activated by this glycan, the percentage of cytotoxicity tion of neutralizing antibodies to both IL-2 receptor against mouse leukemia L1210 cells was slightly depen- and TNF-a blocked aggregate formation, cellular dent on the amount of NO in the culture supernatants proliferation, and ICAM-1 expression.
of the activated macrophages. These results indicatethat the b-glucan-related polysaccharides of the higherfungus activate macrophages and release NO, which is Natural Killer (NK) Cells an important chemical messenger for the induction ofmany biological responses.
A protein–polysaccharide fraction (GLB) from the G. lucidum enhanced the cytotoxicity of splenic NK growing tips of G. lucidum is a strong stimulator to cells in tumor-bearing mice.[3,16,37] the macrophages. When analyzed using a ﬂowcytometer, GLB (100 mg=ml) increased the phagocyticactivity of the BALB=c mouse peritoneal macrophages as well as chicken macrophage BM2CL cells againstFITC-labeled Candida albicans by 55.2% and 21.2%, Macrophages are responsible for killing pathogens in respectively. It also enhanced the spreading and the body. Activation of macrophages by substances expression of MHC class II molecules of BM2CL cells from G. lucidum results in the release of cytokines, as well as the mouse peritoneal macrophages.
NO, and other mediators.[37,45] All of these responsesare associated with the antitumor, antimicrobial, andanti-inﬂammatory effects of G. lucidum.
Polysaccharides from G. lucidum, in particular b-D-glucans, are potent stimulators of murine and Some substances from G. lucidum can act on mast human macrophages in vitro and in vivo.[37,45] CR3 cells. A water extract of the fruit body had inhibitory receptors on macrophages are bound by b-D-glucans activity on histamine release from rat peritoneal mast and internalized, priming a series of molecular cells, induced by compound 48=80 or antigen (egg events. Crude water-extracted polysaccharides isolated white albumin)-antibody reaction and on passive cuta- from fresh fruiting bodies of G. lucidum potentiated neous anaphylaxis reaction in guinea pigs and rats.
the production of cytokines including IL-1b, IL-6, Two ganoderic acids (C and D) isolated from the fruit IFN-g, and TNF-a by human macrophages, which body by methanol inhibited the histamine release from Reishi or Ling Zhi (Ganoderma lucidum) rat mast cells, induced by compound 48=80 animal studies indicate that G. lucidum navalin A. A chloroform extract from G. lucidum extracts (mainly polysaccharides or triterpenoids) broth also signiﬁcantly inhibited histamine release from rat peritoneal mast cells induced by A-23187 induced by toxic chemicals (e.g., CCl4) and Bacillus and compound 48=80. The mechanism for the inhibi- tory activity on histamine release from mast cells was further studied. Palmitic acid, stearic acid, oleic acid, (HBV) activity in a duckling study. Recently, a rando- and linoleic acid were isolated from the active frac- mized placebo-controlled clinical study[15,17] showed tions. Of these, oleic acids induced membrane stabili- that treatment with G. lucidum polysaccharides for zation in model membrane systems. Cyclo-octasulfur 12 weeks reduced hepatitis B e antigen (HBeAg) and extracted from the culture medium of G. lucidum HBV DNA in 25% (13=52) patients with HBV infec- may decrease calcium uptake from the extracellular tion. The mechanisms of the hepatoprotective effects medium by a disulﬁde exchange reaction in the cell of G. lucidum have been largely undeﬁned. However, membrane leading to inhibition of histamine release from mast cells.[3,10,11,14,16] mechanisms. These include antioxidant and radical-scavenging activity, modulation of hepatic Phase Iand II enzymes, inhibition of b-glucuronidase, anti-ﬁbrotic and antiviral activity, modulation of NO COMPLEMENT SYSTEM production, maintenance of hepatocellular calciumhomeostasis, and immunomodulating effects (Fig. 6).
An alkali extract isolated from cultured mycelium of The mushroom could represent a promising approach G. lucidum activated classical and alternative path- for the management of various chronic hepatopathies.
ways of a complement system. Activated complement Further studies are needed to explore the kinetics C3 was observed by crossed immunoelectrophoresis and mechanisms of action of its constituents with in mice. This fraction also activated the reticulo- endothelial system of mice in the carbon clearance test and increased hemolytic plaque forming cells of the isolated from G. lucidum have shown protective effects spleen. The alkali extract consisted of 10% carbo- on the liver in animal and human studies. Ninety hydrate and 49% proteins. A clinical study in elderly patients with chronic hepatitis B, hepatitis B viral patients with insomnia and palpitations recently (HBV) DNA positivity, and aminotransferase eleva- showed that taking G. lucidum essence for 4–6 weeks tion were included in this multicenter prospective increased their serum C3 levels.[3,10,20] randomized Phase I=II study. Subjects were rando-mized to be given Ganopoly (n ¼ 60) or a placebo(n ¼ 30) for 12 weeks, then followed up for 13 weeks.
Effect of therapy on levels of HBV DNA and HISTAMINE RELEASE INHIBITION aminotransferase activities in serum and HBeAgstatus were investigated. There were 78 assessable The fruiting bodies have been traditionally used as patients who entered the trial for efﬁcacy and safety; anti-inﬂammatory agents for the treatment of asthma 13 of 52 (25%) receiving Ganopoly responded by or allergy. In the course of a screening test for the reducing HBeAg and HBV DNA compared to 10 of inhibition of histamine release from rat mast cells, it 26 (4%) patients in the control group (P < 0.05).
was found for the ﬁrst time that ganoderic acids Among those with serum aspartate aminotransferase C and D inhibited histamine release from rat mast (AST) values <100 U=L (n ¼ 29), 41% (12=29) cells (that were induced by compound 48=80 and responded, and among those with AST values concanavalin A). Other than the triterpenoid com- >100 U=L (n ¼ 23), 65% (15=23) responded. Within pounds, cyclo-octasulfur from this fungus also effec- the 6-mo study period, 33% (17=52) of treated tively inhibited histamine release from rat peritoneal patients had normal aminotransferase (ALT) values, mast cells and interacted with membrane proteins to and 13% (7=52) had cleared hepatitis B surface inhibit Ca uptake causing a blockade of histamine antigen (HBsAg) from serum, whereas none of the controls had normal ALT values or had lost HBsAg.
Eight of the 60 patients in the Ganopoly group and4 of the 30 in the controls were unable to be fol- lowed up due to loss or withdrawal. Our studyindicates that Ganopoly is well tolerated and appears G. lucidum has been widely used for the treatment of to be active against HBV patients with chronic chronic hepatopathy of various etiologies. Data from hepatitis B.[3,10,15,17] Reishi or Ling Zhi (Ganoderma lucidum) Fig. 6 Possible mechanisms for the hepatoprotective effects of G. lucidum. These include antioxidative and radical-scavengingeffects, downregulation of activating enzymes, and upregulation of detoxifying enzymes, antiviral activities, inhibition of b-glucuronidase, enhanced hepatic nucleic acid and protein synthesis, inhibition of hepatic collagen synthesis, immunomodulatingeffects, and modulation of nitric oxide (NO) production. GSH ¼ glutathione; GSSG ¼ oxidized glutathione; INOS ¼ indu-inducible NO synthase; SOD ¼ superoxide dismutase; CYP ¼ cytochrome P450; UGT ¼ uridine diphosphate glucuronosyl-transferases. (From Ref..) ANTIDIABETIC EFFECT type II DM of >3 mo duration during which patientsdid not receive insulin; age >18 yr; normal vital signs Animal studies have demonstrated that the poly- for age and disease state; normal electrocardiogram saccharide fractions of G. lucidum have potential (ECG); and fasting plasma glucose (FPG) level of hypoglycemic and hypolipidemic activities.
8.9–16.7 mmol=L in sulfonylurea-naive patients or an A water extract of reishi reduced the increase in FPG < 10 mmol=L before washout in sulfonylurea- blood glucose and blood insulin levels in rats (50 mg treated patients. They were randomly grouped and p.o.) following oral glucose test. Following adrenaline given either Ganopoly or an oral placebo of 1800 mg (i.v.) or oral glucose in rats, the mushroom inhibited three times daily for 12 weeks. The subjects underwent increases in blood glucose without raising blood 4 weeks of dose adjustment, followed by 8 weeks of insulin levels. Glycans (ganoderans B and D) have dose maintenance. Fasting and stimulated glycosylated shown signiﬁcant hypoglycemic activity in mice.
hemoglobin (HbA1c), plasma glucose, insulin, and A clinical study aimed at evaluating the efﬁcacy C-peptide were monitored at predetermined intervals.
and safety of polysaccharide fractions extracted from Adverse events and hypoglycemic episodes were G. lucidum (Ganopoly) by a patented technique in recorded. Treatment with Ganopoly signiﬁcantly 71 patients with conﬁrmed type II diabetes mellitus decreased the mean HbA1c from 8.4% at baseline to (DM) was carried out. Eligibility criteria included 7.6% at 12 weeks. Signiﬁcant changes in mean FPG Reishi or Ling Zhi (Ganoderma lucidum) and PPG levels at the last visit paralleled administrated G. lucidum extract tablets in mean HbA1clevels. At baseline, the mean FPG and (2 tablets b.i.d. or 220 mg=day), systemic blood PPG values for patients treated with Ganopoly were 12.0 and 13.6 mmol=L, respectively. At week 12, mean capillary and arterial blood pressure showing sig- PPG values had decreased to 11.8 mmol=L. However, niﬁcant improvements in as little as 14 days. No these parameters did not change or slightly increased changes of any signiﬁcance were found in the placebo for patients receiving placebos. The between-group group. According to Soo in treating hypertension, difference in PPG levels at week 12 was signiﬁcant G. lucidum was shown to be highly effective in a very (P < 0.05). Changes in fasting insulin, 2-hr postpran- large number of treated cases. In the more successful dial insulin, fasting C-peptide, and 2-hr postprandial cases, blood pressure was back to normal within C-peptide were consistent with the between-group 2 mo, and in some cases, within 2 weeks.
differences in these end points being signiﬁcant at thelast visit. Overall, Ganopoly was well tolerated. Thisstudy demonstrated that Ganopoly is efﬁcacious and ANTIBACTERIAL AND ANTIVIRAL VALUE safe in lowering blood glucose concentrations. A 2-mo open label comparative clinical study of a Antibacterial Effect of Ganoderma lucidum on reishi powder extract (1 g t.i.d.) for eight diabetic Gram-Positive and Gram-Negative Bacteria patients (four with NIDD and four with IDDM)found hypoglycemic effects comparable to those Recently, more studies demonstrated that G. lucidum found in controls who were administered insulin contained antibacterial constituents that are able (100 IU=ml for 60 days) or oral hypoglycemic agents (250 mg=day for 60 days).[3,10,11,18] bacteria.[3,5,10,11,17,55,56] The aqueous extract from thecarpophores of G. lucidum inhibited 15 types of gram-positive and gram-negative bacteria. Further studiesindicate that the antimicrobial combinations of G.
CARDIOVASCULAR AND CIRCULATORY lucidum extract with four antibiotics (ampicillin, cefa- zolin, oxytetracycline, and chloramphenicol) resultedin additive effects in most instances: synergism in two Cholesterol and Lipid Metabolism instances when combined with cefazolin againstBacillus and Klebsiella oxytoca, and The powdered mycelium of reishi, at 5% of the diet of antagonism in two instances.
spontaneously hypertensive rats for 4 weeks, causedplasma total cholesterol to decrease signiﬁcantly (by18.6%) compared to controls. Total liver triglyceride Helicobacter pylori and total liver cholesterol levels were also signiﬁcantlylower in the reishi-fed group (by approximately 46% Helicobacter pylori is associated with human gastro- and 56%, respectively).[51,52] duodenal diseases such as gastritis, peptic ulcer, andgastric carcinoma. The extracts of many mushroomsinhibited the growth of this bacterium.[17,58] The extract of G. lucidum and some other species of higherBasidiomycetes arrested the growth of this pathogen.
A water extract of the mycelium administered to rats When their extracts were fractionated, the ether frac- and rabbits (3–30 mg=kg i.v.) produced signiﬁcant tions of G. lucidum and Agaricus bisporus (J. Lge) hypotensive effects; an activity the researchers sug- Imbach were the most effective. Among seven compo- gested is secondary to the primary effect that sup- nents separated from the ether fraction of G. lucidum presses sympathetic outﬂow of the central nervous extract by silica gel column chromatography, P3 system. The powdered mycelium of reishi, at 5% was the most potent with a minimum inhibitory of the diet of spontaneously hypertensive rats for concentration of 200 mg=ml.
4 weeks, caused systolic blood pressure to be signiﬁ- It appears that some constituents such as gano- cantly lower (approximately 10 mmHg) without causing mycin, triterpenoids, and aqueous extracts from a signiﬁcant difference in the heart rate Jin et al. Ganoderma species have a broad spectrum of in vitro conducted a double-blind, placebo-controlled clinical antibacterial activity against gram-positive and gram- study of G. lucidum in 54 patients with primary negative bacteria and H. pylori. Thus, it is possible that stage-II hypertension who had not responded to the antibacterial activity of Ganoderma species may be previous drug treatment (captopril 25 mg t.i.d. or beneﬁcial for those patients with chronic infection (e.g., nomodipine 20 mg t.i.d.). In the group which was chronic bronchitis) and those with H. pylori-positive Reishi or Ling Zhi (Ganoderma lucidum) peptic ulcer diseases, though clinical lastoid cell line. The IC50 required to conﬁrm this.
and EC50 values were 125 and 11 mg=ml, respectively,resulting in a therapeutic index of 11.4. This aqueouslow-molecular-weight extract was further fractionated to eight subfractions by methanol: GLA (methanolic Virus (HIV) Activity extract), GLB (hexane soluble), GLC (acetic ethersoluble), GLD (water soluble), GLE (neutral), GLF HIV was isolated as an etiological agent of acquired (acidic), GLG (alkaline), and GLH (amphoteric). All subfractions except GLD, GLF, and GLH exhibited Acquired immunodeﬁciency syndrome caused by HIV anti-HIV activity with IC50 and EC50 values of infection has recently become an important social and 22–44 mg=ml and 14–44 mg=ml, respectively. GLC and medical problem. Anti-HIV therapy by nucleoside GLG inhibited HIV RT. Showing consistency, incuba- analogues, such as 30-azido-thymidine, is the major tion of GLC at 50 mg=ml or GLG (100 mg=ml) with effective approach for the treatment of acquired immu- Jurkat T cells gave a 75% and 66% inhibition of HIV nodeﬁciency syndrome. These agents are potent growth, respectively. However, the high-molecular- inhibitors of HIV reverse transcriptase (RT) and weight fraction did not inhibit any HIV-induced protease. However, the emergence of drug-resistant cytopathic effect. Both low-molecular-weight and variants of HIV and toxicities severely limits the high-molecular-weight fractions from G. lucidum had long-term effectiveness of these drugs. Recent studies negligible toxicities to CEM cells. The results indicate have indicated that many natural products are active that the aqueous low-molecular-weight fraction from as anti-HIV agents. These compounds belong to a wide the fruiting bodies of G. lucidum, and the neutral range of different structural classes, e.g., coumarins, and alkaline subfractions from the methanolic extract might contain small molecular weight polysaccharides.
naphtho- and anthraquinones, and polysaccharides. In vitro studies indicate that various triterpenoids from G. lucidum had potent inhibitory activity against Epstein-Barr Virus HIV. Lucidenic acid O and lucidenic lactone, isolatedfrom the fruiting body of G. lucidum, not only inhi- Virus-induced carcinogenesis is considered a compli- bited the activities of calf DNA polymerase-a and rat cated process with multiple steps involving a number DNA polymerase-b, but also those of HIV-1 RT. of cellular signaling pathways. A few polyoxygenated Ganoderiol F and ganodermanontriol isolated from lanostanoid triterpenes isolated from G. applanatus the fruiting bodies of G. lucidum are active against HIV-1 growth with an IC100 of 7.8 mg=ml.[10,11,17] induced Epstein–Barr virus early antigen in Raji cells.
Ganoderic acid B and ganoderiol B showed potent Similar effects have been observed with Zingiberaceae inhibitory effect on HIV protease with an IC50 value rhizomes, a commonly used traditional medicine in of 0.17 mM. Other triterpenoids including ganoderic Malaysia. These results indicate that herbal medicines, such as Ganoderma species, may behave as antitumor diene, ganoderic acid-a, ganoderic acid H, and gano- deriol A had moderate activity against HIV-1 proteasewith IC50 values of 0.17–0.23 mM.[10,11,17,50] In addi-tion, ganoderic acid-b, lucidumol B, ganodermanon- diol, ganodermanontriol, and ganolucidic acid Ashowed signiﬁcant anti-HIV-1 protease activity with The antiviral effects of two water-soluble substances IC50 values of 20, 59, 90, 70, and 70 mM, respec- (GLhw and GLlw) and eight methanol-soluble sub- tively. Ganoderic acid A, B, and C1 had minor inhi- stances (GLMe-1-8) isolated from the carpophores of bitory activity against HIV protease with IC50 values G. lucidum, were investigated on inﬂuenza A virus of 140–430 mM. It appears that there is a structure– strains and vesicular stomatitis virus Indiana and activity relationship for triterpenoid showing anti- New Jersey in vitro. These activities were evaluated HIV protease activity. The C3, C24, or C25 atoms by the cytopathic effect inhibition assay and plaque are vital for the anti-HIV activity. reduction assay using Vero and HEp-2 cells. Five sub- The aqueous low-molecular-weight fraction extrac- stances, GLhw, GLMe-1, -2, -4, and -7 signiﬁcantly ted from G. lucidum also exhibited anti-HIV activity inhibited the cytopathic effects of vesicular stomatitis using the XTT [2,3-bis (2-methoxy-4-nitro-5-sulfo- virus. GLMe-4 did not exhibit cytotoxicity up to 1000 mg=ml, while it displayed potent antiviral activity hydroxide] antiviral assay, which can quantitatively on the vesicular stomatitis virus New Jersey strain with measure cytopathic effects of HIV-1 on CEM cells, a therapeutic index of more than 5.43.[64,65] Reishi or Ling Zhi (Ganoderma lucidum) Mechanism Consideration hardly inﬂuenced the activities of DNApolymerase-b, prokaryotic DNA polymerases, terminal The mechanisms for the antibacterial and antiviral deoxynucleotidyl transferase, HIV RT, RNA polymer- activity of Ganoderma species are largely undeﬁned.
ase, deoxyribonuclease I, and ATPase. Linoleic acid Gao et al. suggest that multiple mechanisms may from G. lucidum inhibited the activities of mammalian be involved. For example, the Ganoderma species DNA polymerases.[38,66] constituents (e.g., polysaccharides and triterpenoids) Immunomodulating effects of G. lucidum are may inhibit viral replication of HSV, HBV, HIV, and considered to play a role in antimicrobial activity.[15,17] other types of viruses by interfering with their adsorp- Activation of immune effector cells (e.g., T cells, tion, virus–hepatocyte fusion and endocytosis, viral macrophages, and natural killer cells) by both patho- integration, assembly, and release (Fig. 7).
gen infection and G. lucidum administration caused Data from in vitro studies indicate that Ganoderma an enhanced production of cytokines, radicals, and polysaccharides have direct anti-HBV activity through NO facilitating the killing of viruses and bacteria.
inhibition of HBV DNA polymerase. The extract For example, activation of Kupffer cells by G. lucidum from G. lucidum inhibited the HBV DNA polymerase polysaccharides and triterpenoids within the liver faci- activity in PLC=PRF=5 cells by 80%, 70%, and 60%, litate the killing of HBV. In addition, a study of the respectively, with a 28–41% decrease in HBV DNA mouse indicates that a proteoglycan with a carbo- contents. Some constituents isolated from G. lucidum hydrate protein ratio of 11.5 : 1 isolated from G. lucidum showed inhibitory effect on eukaryotic DNA poly- stimulated the proliferation of mouse spleen lym- merase. For example, two cerebrosides from the phocytes, resulting in a three-to-four fold increase fruiting bodies selectively inhibited the activities of in the percentage of B cells. These B cells were replicative DNA polymerases (especially the a and enlarged, expressed CD71 and CD25 on the cell d type) with a IC50 of 12–57 mM. However, these surface, and showed an increase in the production of Fig. 7 Possible mechanisms for the antiviral effects of G. lucidum. Polysaccharides and triterpenoids may inhibit viral repli-cation of HSV, HBV, HIV, and other types of viruses by interfering with their adsorption, and virus–hepatocyte fusion andendocytosis, viral integration, assembly, and release. (From Ref..) Reishi or Ling Zhi (Ganoderma lucidum) immunoglobulins. Therefore, Ganoderma stimulate B cells in vivo, producing immunoglobulins,which can neutralize HBV.[15,17] Because reishi potentiates the immune system, caution Furthermore, the immunosuppressive activity of is advised for those receiving immunosuppressive G. lucidum constituents may decrease tissue and cellular damage following infection. Ling-Zhi-8 at 8and 12 mg=kg by intraperitoneal injection signiﬁcantlyblocked the production of antibody to HBsAg (83.3– 96.8% inhibition) in mice treated with twice the sensiti-zation of the antigen. As Ling-Zhi-8 did not alter the In oral dosages of 1.5–9 g=day, some patients, when mitogen responsibility of spleen cells and the T-cell initially taking a powder extract of reishi, have experi- subset population in mice, and prevented systemic enced temporary symptoms of sleepiness, thirst, rashes, anaphylaxis and Arthus reactions, these immuno- bloating, frequent suppressive activities may be ascribed to the blocking and loose stools. Large oral doses of vitamin C of antigen-speciﬁc antibody production. The immuno- (6–12 g=day) taken at the same time as reishi powder suppressive effect might ameliorate the immune extract (2–10 g=day) reportedly counteracted loose response to HBV infection.[15,17] The inhibition of platelet aggregation by G.
Potential role in the treatment of HBV infection in lucidum[3,10,11] may present an additive effect in those combination with antiviral nucleoside analogues taking blood thinning medications such as daily aspirinor warfarin.
Further studies are required to identify the molecular Synergistic antimicrobial activity was shown with targets of G. lucidum constituents for viruses and an aqueous extract of G. lucidum in combination with bacteria. Herbal medicines often contain multiple cefazolin against Klebsiella oxytoca ATCC 8724 and active substances with individual constituents possibly Bacillus subtilis ATCC 6603, Staphylococcus aureus contributing to the bioactivity observed in vitro and in ATCC 25923, Escherichia coli ATCC 25933, and vivo. Therefore, multiple important molecules might Salmonella typhi ATCC 6509. be the targets of a herbal medicine. The identiﬁcationof these targets may provide molecular evidence ofthe pharmacological activity and toxicity of herbs. G. lucidum may play an adjunct role in the manage-ment of infectious diseases. However, further exp- In animal experiments, G. lucidum extracts showed a erimental clinical studies are needed to identify very low toxicity.[3,5,10,11] There are few reported data mechanisms of action, optimal dosing, efﬁcacy, and on the long-term adverse effects on G. lucidum and safety, alone or in combination with chemotherapeutic its derivatives.
The aqueous extract of reishi administered to mice (5 g=kg p.o. for 30 days) produced no changes in bodyweight, organ weight, or hematological parameters.
The polysaccharide fraction at the same dosage pro- duced no lethal or serious effects. The mushroomproduced no changes in the estrus cycles of ovariecto- G. lucidum is usually prescribed in various forms. It mized mice from a dosage of 10 g=kg p.o. and no may be injected as a solution of powdered spore.
increase in the weight of levator cavernosa and testicles It may be ingested as a soup, syrup, tea, tablets, in male mice from the same dosage. The LD50 in mice capsules, tincture, or bolus (powdered medicine in of the reﬂux percolate was 38.3 1.048 g=kg i.g. No honey). The dose in tincture form (20%) is 10 ml three organ toxicity was found in rabbits taking a syrup times daily, that of tablet is 1 g tablets three times daily, and syrup is 4–6 ml=day. As an antidote for 4–140 ml=kg p.o. daily for 10 days), or in dogs (2 ml=kg ingestion of poisonous mushrooms, dried G. lucidum and 4 ml=kg p.o. daily for 10 days). An alcoholic (120–200 g) is decocted in water and given as a drink extract (1.2 and 12 g=kg i.g. daily for 30 days) produced 3–5 times daily.[3,5,10,11] no signs of toxicity in young rats in DCG, majororgans, hepatic function, growth, or development.
Toxic reactions were absent in dogs administered an alcoholic extract (12 g=kg i.g. daily for 15 days andat 24 g=kg i.g. daily for 13 days); however, they did Contraindications. None known.
display lethargy.[10,11] Reishi or Ling Zhi (Ganoderma lucidum) Current biomedical applications of A. Cosmonaut training in Russia 1. Improves work capacity 2. Rapid recovery of normal physiology B. Usage with conventional treatment in 1. Maintains leukocyte counts 2. Enhances the immune system 3. Reduces chemotherapy toxicity and elimination of induced leucopenia (low blood leukocytes) by chemotherapy and radiation 4. Accelerates postsurgical recovery 5. Sedation, pain relief and reduction of morphine dependence in terminal cancer patients 6. Usage during remission to prevent relapses C. Cardiovascular disorders including 1. Coronary dilation and increasing coronary circulation 2. Increases frequency and amplitude of heart contraction 3. Blood pressure regulation together with other medication 4. Antihyperlipidemic, antihypoglycemic and antiplatelet aggregation 5. Relief from oxygen deprivation D. Immunomodulation effects 2. Antiviral (e.g., anti-HIV) 4. Anti-inﬂammatory 5. Therapy of autoimmune disorders 6. Inhibition of histamine release in allergy and prevention of E. Usage during remission of cancer and hepatitis B treatment F. Enhancing oxygen utilization 1. Relief from discomfort of high-altitude stress, headaches, dizziness, nausea, and insomnia 2. Relief of oxygen deprivation caused by coronary arteries blocked by atheromas, spasms, or clots 3. Tolerance to hypobaric (low pressure) conditions G. Other examples 1. Usage in combination with other medication 2. Anti-aging, antioxidant free radical scavenger To test the toxicity of wild reishi, fruit bodies urea, GOT, or GPT signiﬁcantly different compared to harvested in a rural area of Hong Kong were pre- controls. No abnormalities were found in histological pared as a freeze-dried powder extract (yield: 1 g=20 g examinations of livers and kidneys, organ weights of freeze-dried fruit bodies and 50 ml of extract (liver, kidney, heart, lung, and spleen), or organ=body solution=100 g of freeze-dried fruit bodies). Examining weight ratios compared to the control. acute toxicity, the extract solution (0.9259=kg) was Summarized data about G. lucidum biomedical administered to male mice at a dosage equivalent to applications are shown in Table 2. The observed effects the one commonly recommended by manufacturers include both clinical and preclinical observations, and of commercial concentrated extracts. Neither evidence the reader should refer to the preceding discussion of of acute toxicity was found, nor was serum contents of the various applications for more details.
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International Journal of Obesity (2004) 28, 1124–1133 & 2004 Nature Publishing Group All rights reserved 0307-0565/04 $30.00 Pretreatment predictors of attrition and successfulweight management in women PJ Teixeira1*, SB Going3, LB Houtkooper3, EC Cussler2, LL Metcalfe2, RM Blew2, LB Sardinha1 andTG Lohman2 1Department of Exercise and Health, Faculty of Human Movement, Technical University of Lisbon, Lisbon, Portugal;