ling zhi preparation could reduce spontaneous activity of mice, strengthen the inhibitory effects of reserpine and chlorpromazine on nerve center, antagonize the excitatory function of benzedrine on nerve center, prolong the pentobarbital sodium induced sleep time, strengthen hypnogenesis effect of pentobarbital sodium at sub-threshold dose, antagonize electrical convulsion. Besides, it also had analgesic effect.

ling zhi had obvious antitussive effect, it could prolong the latent period of cough induced by ammonia stimulation, or decrease the times of cough significantly. chi zhi preparation had spasmolytic effect on smooth muscle contract of isolated trachea induced by histamine, and the effect was directly proportional to the medicine concentration.

ling zhi could significantly increase the cardiac contraction, decrease the heart rate in isolated toad heart, increase the contraction force of in situ rabbit heart. chi zhi liquid (3g/kg) could antagonize acute myocardial ischemia caused by hypophysin, significantly lower the high T wave in ECG.

Hot water extract of ling zhi could lower blood pressure, this effect was the most obvious 3 hours after oral administration. Initial clinic test also proved its blood pressure lowering effect and fat lowering effect. The blood pressure lowering effect of mycelin extracted from the mycelium of ling zhi had the characteristics of taking effect quickly, short action time, and dosage dependence.

ling zhi could also antagonize blood coagulation, prevent the thrombus formation, inhibit the platelet aggregation, and increase the deformability of aged RBC.

chi zhi preparation could increase the anoxia tolerance of normal mice and mice pre-treated isoprenaline under lower pressure and normal pressure circumstance. Dried powder of fermented ling zhi could also increase the anoxia tolerance ability of mice, particularly the ability of cardiac muscle, and lower the oxygen consumption whole animal, improve the cardiac metabolism of anoxic animals.

Ethanol extract of chi zhi had no influence over the increase of insulin secretion 10 minutes after oral administration of glucose, but had inhibitory effect on the continuous decrease of plasma insulin 30 minutes after the administration. It could also inhibit the increase of blood sugar induced by injection of adrenalin or oral administration of glucose. Polysaccharides of ganoderans A, B, C and heteroglycan isolated from ling zhi were injected intraperitoneally to mice at the dosage of 100mg/kg, the results showed that it could blood sugar.

The increase of serum GPT and accumulation of liver triglyceride in mice induced by CCl4 injection could be obviously improved by oral administration of ethanol and ether extract of fruit body onload="highlight();" of zi zhi and chi zhi. Besides, the extract could also relieve fatty liver caused by ethionine, promote the liver regeneration and strengthen the detoxifying function.

Immune hepatic injury was markedly induced by BCG or BCG plus inflammatory cytokines in BALB/c mice in vivo and in vitro. Under BCG-stimulated condition, augment of the liver weight and increase of the serum/supernatant ALT level were observed, as well as granuloma forming and inflammatory cells soakage were observed by microscopic analysis within liver tissues. Moreover, NO production was also increased by BCG or/and CM stimuli in the culture supernatant, and a lot of iNOS positive staining was observed in BCG-prestimulated hepatic sections. Application of Ganoderma lucidum polysaccharide (GLP)significantly mitigated hepatic tumefaction, decreased ALT enzyme release and NO production in serum/supernatant, improved the pathological changes of chronic and acute inflammation induced by BCG-stimuli in mice. Moreover, the immunohistochemical result showed that GLP inhibited iNOS protein expression in BCG-immune hepatic damage model. The study indicates that NO participates in immune liver injury induced by Mycobacterium bovis BCG infection. The mechanisms of protective roles by GLP for BCG-induced immune liver injury may be due to influence NO production in mice.

chi zhi preparation could inhibit the smooth muscle activity of isolated rabbit intestines and isolated ileum of Guinea pig, and the effect increased with the increase of medicine concentration. Concentrated solution of fermented chi zhi could also obviously inhibit the contraction of isolated rat uterine.

Extract of mycelium of bo gai ling zhi could significantly promote the phagocytosis rate of celiac macrophages and activity of lysosome in mice, obviously inhibit DNA synthesis in lymphocytes and T and B lymphocyte transformation induced by ConA and bacillus coli endotoxin. ling zhi polysaccharide had certain immunoenhancing effect.

The polysaccharide component with a branched (1-->3)-beta-D-glucan moiety from G. lucidum (PS-G) has shown evidence of enhancement of immune responses and of eliciting anti-tumor effects. Annexin V staining and MTT assays reveal that PS-G is able to inhibit spontaneous and Fas-induced neutrophil apoptosis, and this effect of PS-G is enhanced by the presence of zVAD (a caspase inhibitor) and GM-CSF. The antiapoptotic effect of PS-G is diminished by the presence of wortmannin and LY294002 (two PI-3K inhibitors), but is not altered by PD98059 (a MEK inhibitor). Western blotting indicates the stimulating effect of PS-G on Akt phosphorylation and its inhibition of procaspase 3 degradation, which occurs in neutrophils undergoing spontaneous apoptosis or triggered death by Fas. Taken together, PS-G elicitation of antiapoptotic effects on neutrophils primarily relies on activation of Akt-regulated signaling pathways.

A fucose-containing glycoprotein fraction which stimulates spleen cell proliferation and cytokine expression has been identified from the water-soluble extract of Ganoderma lucidum. Proteomic analysis of mouse spleen cells treated with this glycoprotein fraction showed approximately 50% change of the proteome. Further studies on the activities of this glycoprotein fraction through selective proteolysis and glycosidic cleavage indicate that a fucose containing polysaccharide fraction is responsible for stimulating the expression of cytokines, especially IL-1, IL-2 and INF-gamma.

Anti-allergic effect

ling zhi could obviously inhibit the allergic reaction of Guinea pig passively sensitized by egg albumen antiserum, tetanus toxoid antiserum on antigen attack, it could also significantly inhibit the release of allergic mediators such as histamine and SRS-A by lung tissue of Guinea pig actively sensitized by egg albumen antiserum or tetanaus toxoid antiserum on antigen attack. This effect would strengthen with the increase the dosage of ling zhi.

Water decoction of ling zhi could inhibit the growth of tumor. Hot water extract of mycelia of artificially cultured chi zhi had inhibitory effect on the growth of fibrosarcoma and metastasized focus of lung. Ganodenic acid, a kind of triterpene isolated from chi zhi, had cell toxicant on cultured liver carcoma in vitro.

The triterpene-enriched fraction, WEES-G6, was prepared from mycelia of G. lucidum by sequential hot water extraction, removal of ethanol-insoluble polysaccharides and then gel-filtration chromatography. It's found that WEES-G6 inhibited growth of human hepatoma Huh-7 cells, but not Chang liver cells, a normal human liver cell line. Treatment with WEES-G6 caused a rapid decrease in the activity of cell growth regulative protein, PKC, and the activation of JNK and p38 MAP kinases. The changes in these molecules resulted in a prolonged G2 cell cycle phase and strong growth inhibition. None of these effects were seen in the normal liver cells. This findings suggest that the triterpenes contained in G. lucidum are potential anticancer agents.

A study was designed to investigate the protective effect of a dietary water-soluble extract from cultured medium of Ganoderma lucidum (Rei-shi or Mannentake) mycelia (designated as MAK) on the induction and development of azoxymethane (AOM)-induced colon tumors in male F344/Du Crj rats. A total of 80 animals were divided into five groups at six weeks of age, groups 2, 3 and 4 being given weekly subcutaneous injections of AOM (15 mg/kg body onload="highlight();" weight) for the initial 3 weeks to induce colon tumors. Rats in group 1 and 5 were injected with the vehicle, 0.9% (w/v) saline, following the same schedule. Rats in groups 1, 2, 3, 4 and 5 were fed MF, MF, 1.25% MAK, 2.5% MAK and 2.5% MAK diets, respectively, starting 1 week before AOM treatment and throughout the six-month experimental period. There were no significant differences in number of ACF, total AC and AC per site among groups 2 to 4, but the tumor incidence was significantly lower, and tumor size was smaller in group 4 (AOM + 2.5% MAK) than in group 2 (AOM + MF). Additionally, beta-catenin positive tumor cell nuclei were significantly decreased in the MAK-fed rats (groups 3 and 4), which also demonstrated lowering of the PCNA labeling index and a shortened germinal region in the colon. The present results thus indicate that dietary MAK could act as a potent chemopreventive agent for colon carcinogenesis.

Spores or dried fruiting body onload="highlight();" of G. lucidum inhibit constitutively active transcription factors AP-1 and NF-kappaB in breast MDA-MB-231 and prostate PC-3 cancer cells. Furthermore, Ganoderma inhibition of expression of uPA and uPA receptor (uPAR), as well secretion of uPA, resulted in the suppression of the migration of MDA-MB-231 and PC-3 cells. The data suggest that spores and unpurified fruiting body onload="highlight();" of G. lucidum inhibit invasion of breast and prostate cancer cells by a common mechanism and could have potential therapeutic use for cancer treatment.

Different concentrations of Ganoderma lucidum(Leyss ex Fr) Karst Compound(GLC) (from 4 mg/ml to 12 mg/ml) could promote human bone marrow granulocyte-macrophage colony forming unit (CFU-GM) proliferation, but suppressed the growth of K562 leukemic cell colonies, and IC50 was 9.2 mg/.ml. The data from liquid culture demonstrated that GLC could suppress K562 cells proliferation in a dose-dependent(from 4 mg.ml-1 to 20 mg.ml-1) and time-dependent(from 1-5 days) manner. K562 cells could be induced to differentiate into more mature erythrocytic cells by 4 mg/.ml and 8 mg/ml GLC. It is concluded that GLC may be a good medicine for leukemia therapy.

Water extract of chi zhi could prolong the average life span of drosophilas, but it could neither lengthen the maximum life time, nor inhibit the brain MAO-B activity in mice.

To investigate antiherpetic substances from Ganoderma lucidum, various protein bound polysaccharides, GLhw, GLhw-01, GLhw-02, GLhw-03, were isolated by activity-guided isolation from water soluble substances of the carpophores. These substances were examined for their antiviral activities against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) by plaque reduction assay in vitro. Among them, the acidic protein bound polysaccharide, GLhw-02 of a brownish substance, exhibited the most potent antiherpetic activity with 50% effective concentrations (EC50) of 300 approximately 520 microg/ml in Vero and HEp-2 cells, and its selectivity indices (SI) were more than 20. GLhw-02 was identified to consist mainly of polysaccharide (approximately 40.6%) and protein (approximately 7.80%) by anthrone test and Lowry-Folin test, and showed the usual molar ratio (C:H:O = 1:2:1) of carbohydrates by elemental analysis. These results suggest that GLhw-02 possesses the possibility of being developed from a new antiherpetic agent.

A new highly oxygenated triterpene named ganoderic acid alpha has been isolated from a methanol extract of the fruiting bodies of Ganoderma lucidum together with twelve known compounds. The structures of the isolated compounds were determined by spectroscopic means including 2D-NMR. Ganoderiol F and ganodermanontriol were found to be active as anti-HIV-1 agents with an inhibitory concentration of 7.8 micrograms ml-1 for both, and ganoderic acid B, ganoderiol B, ganoderic acid C1, 3 beta-5 alpha-dihydroxy-6 beta-methoxyergosta-7,22-diene, ganoderic acid alpha, ganoderic acid H and ganoderiol A were moderately active inhibitors against HIV-1 PR with a 50% inhibitory concentration of 0.17-0.23 mM.

Fruiting bodies of Ganoderma lucidum (GLPS) at 250 and 500 mg/kg by intragastric input caused ulcer-healing effect in the rat; this was accompanied with a significant suppression of tumor necrosis factor (TNF)-alpha gene expression, but with an increased ornithine decarboxylase (ODC) activity. In RGM-1 cells, GLPS at 0.05, 0.25 and 1.0 mg/ml significantly enhanced [3H]thymidine incorporation and ODC activity in a concentration-dependent manner. However, these effects were abrogated by the addition of the ODC inhibitor, DL-alpha-difluoromethyl-ornithine (DFMO). GLPS at 0.25-1.0 mg/ml also increased mucus synthesis, as indicated by the increased D-[6-3H]glucosamine incorporation in RGM-1 cells. Furthermore, GLPS at 0.05-1.0 mg/ml increased the c-Myc protein expression. These findings indicated that GLPS produced a mucosal healing effect in the rat model, perhaps due partly to the suppression of TNF-alpha and induction of c-myc and ODC gene.

The ethanol extract of the mycelium of Ganoderma lucidum occurring in south India showed significant inhibition of Fe²⁺-induced peroxidation of lipid in rat liver (IC(50) 510 +/- 22 micro g/ml) and 37% inhibition of croton oil-induced peroxidation on the mouse skin at 20 mg/0.1 ml/skin. Carrageenan-induced acute and formalin-induced chronic inflammatory edema were inhibited by 56 and 60%, respectively, by the extract at 1,000 mg/kg body onload="highlight();" wt (i.p). The extract at a concentration of 5 mg/plate showed inhibition of mutagenicity elicited by direct acting mutagens, NaN(3) (55.5 and 75.7%) and MNNG (50.0 and 57.5%) for S. typhymurium strains TA100 and TA102, respectively. The extract at the same concentration also inhibited mutagenicity elicited by NPD (52.4 and 64.2%) and B[a]P (60.7 and 59.6%) for TA98 and TA100 strains, respectively. The B[a]P was activated in the presence of rat liver microsomal (S9) fraction. The results revealed that ethanol extract of Ganoderma lucidum mycelium possessed significant antiperoxidative, antiinflammatory, and antimutagenic activities. The findings suggest a medicinal use for the ethanol extract of the mycelium of G. lucidum occurring in South India.

Mice peritoneal macrophages were injured by reactive oxygen species (ROS), derived from tert-butylhydroperoxide (tBOOH). The survival rate of macrophages was measured by MTT assay, and the morphological changes of macrophages were observed under light and electron microscopes. It was found Ganoderma lucidum polysaccharides peptide (GLPP) (50, 100, 200 mg/kg, ip for 5 d) could inhibit the foam cell formation and necrosis of macrophages. The survival rate of macrophages was increased. GLPP (3.125, 12.5, 50, 200 mg/L) given to the cultured macrophages brought the same protective effects. Under the electron microscope it was found that GLPP (100 mg/kg, ip, for 5 d) could protect the organelle such as mitochondria against injury by tBOOH. The results indicated that GLPP had significant scavenging ROS and antioxidant effects.

Hot water extract of Ganoderma lucidum dose-dependently exhibited antioxidative effect on mouse liver and kidney lipid peroxidation; this indicated that hepatic and renal homogenates have a higher malonic dialdehyde level in an ethanol administered group than in the Ganoderma lucidum treated group. It was concluded that the hepatic and renal protective mechanism of Ganoderma lucidum, might be due at least in part to its prominent superoxide scavenging effect. Ganoderma extract could protect the liver and kidney from superoxide induced hepatic and renal damages.

The amino-polysaccharide fraction (designated as 'G009') from Ganoderma lucidum was tested for the ability to protect against oxidative damage induced by reactive oxygen species (ROS). G009 significantly inhibited iron-induced lipid peroxidation in rat brain homogenates and showed a dose-dependent inactivation of hydroxyl radicals and superoxide anions. It also reduced strand breakage in phiX174 supercoiled DNA caused by UV-induced photolysis of hydrogen peroxide and attenuated phorbol ester-induced generation of superoxide anions in differentiated human promyelocytic leukaemia (HL-60) cells. These findings suggest that G009 from Ganoderma lucidum possesses chemopreventive potential.

Hot-water extract of Ganoderma lucidum had good radioprotective ability, as well as protection against DNA damage induced by metal-catalyzed Fenton reactions and UV irradiation. Water-soluble polysaccharide isolated from the fruit body onload="highlight();" of Ganoderma lucidum was as effective as the hot-water extract in protecting against hydroxyl radical-induced DNA strand breaks, indicating that the polysaccharide compound is associated with the protective properties.

ling zhi preparation had therapeutic effects on angina pectoris and increased blood fat in coronary heart disease to a certain degree, it could lower serum cholesterol, triglyceride and b-lipoprotein. 20% Ling Zhi Tincture, 10ml tid was used to treat 30 cases of angina pectoris for consecutive more than half a year, the results were 17 markedly effective, 18 effective, 4 ineffective.

Ling Zhi Injection was used to treat 53 cases of various types of arrhythmia, the results showed that arrhythmia disappeared completely in 20 cases, 13 improved, 7 had a relapse, and 13 were ineffective.

ling zhi preparation had quite good therapeutic effect on chronic bronthitis, but it took effect slowly, usually 1~2 week after administration. It also had good long-term therapeutic effect.

Infantile patients with bronchial asthma were treated with Ling Zhi Injection im 1~2 ml for consecutive 1 month. 27 cases were treated, and 9 were markedly effective, 14 effective, and 4 ineffective.

ling zhi preparation was used to treat hepatitis of various types, the total effective rates were 73.07%~97%, markedly effect rates were 44%~76.4%. Generally speaking, it had better effects on acute hepatitis than on chronic hepatitis.

Artificially cultured ling zhi was used to treat 52 cases of leukopenia caused by various reasons, the results: 11 cases were markedly effective, 12 effective, 21 improved, the near-term effective rate was 84.6%, the total number of WBC increased by 1088/mm3.

Lao Jun Xian (ling zhi) Oral Liquid combining chemotherapy was used to treat 26 cases of malignant hemopathy, the total effect rate was 88.9%.

Sliced ling zhi, 6g per day, was decocted with water to get concentrated juice. The juice was taken when getting up early with empty stomach, or 1 hour before meals. 36 cases were treated, the total effective rate was 93.94%.

Ling Zhi Syrup (each ml contained 0.175g raw drug), 10~15mg, tid, a course of treatment consisted of 2 weeks ~ 2 months. 30 cases were treated, and 27 cases had an over half year follow-up survey, among them, 19 markedly effective, 3 effective, 1 improved, and 4 ineffective. The increase of platelet increase by more than 100,000/mm3 in 12 cases, 6~90,000/mm3 in 6 cases, 4~50,000/mm3 in 8 cases and 2~30,000/mm3 in 1 cases.

Except those noted, all references come from Weng Weiliang, et al., Clinical Chinese materia medica, Henan Science & Technology Press, 1998