The mushroom Ganoderma lucidum (G. lucidum) has been consumed in China as a medicine for promoting health and longevity for thousands of years. Due to its paramount and multiple pharmaceutical effects, G. lucidum has received considerable attention from researchers and its chemical constituents as well as their respective functions were gradually unveiled by using modern research methods. Herein, we reported the isolation of a protein (Ganoderma lucidum ribonuclease, GLR) with anti-colorectal cancer activities from G. lucidum. This protein is a 17.4-kDa RNA degrading enzyme (ribonuclease) and was purified by using liquid chromatography procedures. GLR manifested potent anti-proliferative and anti-colony formation activities on HT29 and HCT116 colorectal cancer cells by inducing cell cycle arrest in G1 phase through the regulation of cyclin D1 and P53 expression. GLR was demonstrated to induce cell apoptosis in HCT116 cells by activating unfolded protein response and caspase-9 regulated pathways. Besides, the ability to undergo autophagy which is a stress adaption mechanism to cope with metabolic crisis was significantly suppressed by GLR treatment in HCT116 cells. The activation of apoptosis in GLR-treated HT29 cells was, however, independent of caspase-9 and the suppression of autophagy was also relatively minor. Thus the apoptosis of HT29 cells triggered by GLR was much milder than that in HCT116 cells. Our findings show that the RNase from G. lucidum may be one of the bioactive components that contribute to the anti-colorectal cancer activity of G. lucidum.

The 30% EtOH extracts of Ganoderma lucidum Fr. Karst (Ganodermateceae) showed weak 5alpha-reductase inhibitory activity and binding ability to androgen receptor. When LNCaP (lymph-node carcinoma of the prostate) cells were treated with the EtOH extracts, cell proliferation was inhibited. Treatment with the extracts significantly inhibited the testosterone-induced growth of the ventral prostate in castrated rats. These results showed that G. lucidum might be a useful ingredient in the treatment of androgen-induced diseases, such as benign prostatic hyperplasia or prostate cancer. From the 30% EtOH extracts, we isolated ganoderiol F, which showed binding activity to androgen receptor and inhibited LNCaP cell proliferation, as one of the active compounds in the 30% EtOH extracts 

A series of lanostane-type triterpene acids, including eleven lucidenic acids (3, 4, 9, 10, 13-19) and six ganoderic acids (20-22, 24, 26, 27), as well as six sterols (28-33), all isolated from the fruiting bodies of the fungus Ganoderma lucidum, were examined for their inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, a known primary screening test for anti-tumor promoters. All of the compounds tested, except for ganolactone (27) and three sterols (29-31), showed potent inhibitory effects on EBV-EA induction, with IC(50) values of 235-370 mol ratio/32 pmol TPA. In addition, nine lucidenic acids (1, 2, 5-8, 11, 12, 18) and four ganoderic acids (20, 23-25) were found to inhibit TPA-induced inflammation (1 microg/ear) in mice, with ID(50) values of 0.07-0.39 mg per ear. Further, 20-hydroxylucidenic acid N (18) exhibited inhibitory effects on skin-tumor promotion in an in vivo two-stage mouse-skin carcinogenesis test based on 7,12-dimethylbenz[a]anthracene (DMBA) as initiator, and with TPA as promoter.

INTRODUCTION:Protease enzyme is considered one of the most serious virulence factors produced by extended-spectrumβ-lactamase-producing and multidrug-resistant Pseudomonas aeruginosa (ESβLMDRPA) clinical isolates.

METHODOLOGY:The antibacterial activity of methanol extract of Ganoderma lucidum fruiting bodies was tested against a protease-producing ESβLMDRPA clinical isolate, showing its mode of action.

RESULTS:The extract showed high antibacterial activity. Its effect on purified protease indicated a reversible non-competitive protease inhibition (kis= 0.45 mg/mL).

CONCLUSIONS:The G. lucidum extract could be a promising anti-proteolytic active against ESβLMDRPA. It may form a primary platform for further phytochemical studies and development of new drugs for therapy of skin burn infections.

BACKGROUND:Dengue is a mosquito-borne viral infection that has become a major public health concern worldwide. Presently, there is no specific vaccine or treatment available for dengue viral infection.

METHODS:Lignosus rhinocerotis, Pleurotus giganteus, Hericium erinaceus, Schizophyllum commune and Ganoderma lucidium were selected for evaluation of their in-vitro anti-dengue virus serotype 2 (DENV-2) activities. Hot aqueous extracts (HAEs), ethanol extracts (EEs), hexane soluble extracts (HSEs), ethyl acetate soluble extracts (ESEs) and aqueous soluble extracts (ASEs) were prepared from the selected mushrooms. The cytotoxic effects of the extracts were evaluated by the MTT assay. The anti-DENV-2 activities of the extracts were evaluated in three different assays: simultaneous, attachment and penetration assays were perfomed using plaque reduction assays and RT-qPCR assays. The effect of the addition time on viral replication was assessed by the time of addition assay, and a virucidal assay was carried out to evaluate the direct effect of each mushroom extract on DENV-2. The chemical composition of glucans, and the protein and phenolic acid contents in the extracts were estimated.

RESULTS:We found that the HAEs and ASEs of L. rhinocerotis, P. giganteus, H. erinaceus and S. commune were the least toxic to Vero cells and showed very prominent anti-DENV2 activity. The 50% inhibitory concentration (IC) values of the ASEs ranged between 399.2-637.9 μg/ml, while for the HAEs the range was 312.9-680.6 μg/ml during simultaneous treatment. Significant anti-dengue activity was also detected in the penetration assay of ASEs (IC: 226.3-315.4 μg/ml) and HAEs (IC: 943.1-2080.2 μg/ml). Similarly, we observed a marked reduction in the expression levels of the ENV and NS5 genes in the simultaneous and penetration assays of the ASEs and HAEs. Time-of-addition experiments showed that the highest percent of anti-DENV2 activity was observed when the mushroom extracts were added immediately after virus adsorption. None of the extracts exhibited virucidal effect. Chemical composition analysis showed that the major components in the mushroom HAEs and ASEs were glucan (beta D-glucan) and proteins, however, there was no significant correlation between the anti-dengue activity and the concentration of glucans and proteins.

CONCLUSION:These findings demonstrated the potential of mushroom extracts as anti-dengue therapeutic agents with less toxic effects.

Among the most important traditional medicinal fungi, Ganoderma lucidum has been used as a therapeutic agent for the treatment of numerous diseases, including cancer, in Oriental countries. The aim of this study is to investigate the anti-inflammatory, anticancer and anti-metastatic activities of Ganoderma lucidum extracts in melanoma and triple-negative breast cancer cells. Ganoderma lucidum extracts were prepared by using common organic solvents; MDA-MB 231 and B16-F10 cell lines were adopted as cellular models for triple-negative breast cancer and melanoma and characterized for cell viability, wound-healing assay and measurement of cytokines secreted by cancer cells under pro-inflammatory conditions (incubation with lipopolysaccharide, LPS) and pretreatment with Ganoderma lucidum extract at different concentrations. Our study demonstrates, for the first time, how Ganoderma lucidum extracts can significantly inhibit the release of IL-8, IL-6, MMP-2 and MMP-9 in cancer cells under pro-inflammatory condition. Interestingly, Ganoderma lucidum extracts significantly also decrease the viability of both cancer cells in a time- and concentration-dependent manner, with abilities to reduce cell migration over time, which is correlated with a lower release of matrix metalloproteases. Taken together, these results indicate the possible use of Ganoderma lucidum extract for the therapeutic management of melanoma and human triple-negative breast cancer.

, within the Polyporaceae family of Basidiomycota, is a popular traditional remedy medicine used in Asia to promote health and longevity. Compounds extracted fromhave revealed anticancer, antioxidant and liver protective effects.has been associated with prostate cancer cells.extracts contain numerous bioactive components; however, the exact functional monomer is unknown and the role of triterpenes from(GLT) in prostate cancer remain obscure. The present study investigated the effects of GLT on cell viability, migration, invasion and apoptosis in DU-145 human prostate cancer cells. The results demonstrated that a high dose (2 mg/ml) of GLT inhibits cell viability in a dose- and time-dependent manner by the regulation of matrix metalloproteases. Furthermore, GLT induced apoptosis of DU-145 cells. In general, GLT exerts its effect on cancer cells via numerous mechanisms and may have potential therapeutic use for the prevention and treatment of cancer.

Immune Assist (IA) is produced from extract of six species of medical mushrooms: Agaricus blazei - Cordyceps sinensis - Grifola frondosa - Ganoderma lucidum - Coriolus versicolor - Lentinula edodes. The genoprotective potential of IA was evaluated for the first time. Significant antigenotoxic effects were detected in human peripheral blood cells against HOinduced DNA damage, in the pretreatment and in the posttreatment. The most efficient concentration of IA in pretreatment was 500 μg/mL, while in posttreatment it was the concentration of 250 μg/mL. Kinetics of attenuation of HOinduced DNA damage in posttreatment with the optimal concentration of IA showed significant decrease in the number of damaged cells at all time periods (15-60 min), reaching the greatest reduction after 15 and 45 min. Remarkable ·OH scavenging properties and moderate reducing power, together with the modest DPPH scavenging activity, could be responsible for the great attenuation of DNA damage after 15 min of exposure to IA, while reduction of DNAdamage after 45 min could be the result in additional stimulation of the cell's repair machinery. Our results suggest that IA displayed antigenotoxic and antioxidant properties. A broader investigation of its profile in biological systems is needed.

Crude proteins of cultured mycelia and fruiting bodies of Ganoderma lucidum were investigated for antioxidant, antibacterial and DNA protective activities. It was found that the half maximal inhibitory concentration (IC50) of the mycelia protein and fruiting bodies protein extracts against 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) radical (ABTS(•+)) were 2.47 ± 0.01 and 2.77 ± 0.11 μg protein/ml and against 2,2-diphenylpicrylhydrazyl radical (DPPH(•)) were 2.5 ± 0.01 and 3.42 ± 0.01 μg protein/ml, respectively. The ferric reducing-antioxidant power (FRAP) values of those samples were 1.73 ± 0.01 and 2.62 ± 0.01 μmole trolox/μg protein respectively. Protein hydrolysates prepared by pronase exhibited a weaker antioxidant activity. Both crude proteins showed antibacterial activity, whereas only the mycelia protein extract could protect DNA damage by hydroxyl ((•)OH) radicals. This protein extract was partial purified by Diethyl amino ethyl (DEAE)-Sepharose column and Sulfopropyl (SP)-Sepharose column, obtained major protein with molecular weight about 45 kilo Dalton (kDa). In conclusion, G. lucidum protein extracts have promise potential for applications as antioxidant and antibacterialagents.

Ganoderma lucidum, a mushroom that has been used to treat disease in East Asia for centuries, has been shown to be effective against many types of tumors, but the exact cellular mechanism of action is unknown. In this study we examined proliferation of a lung cancer cell line after treatment with 12 concentrations of powdered G. lucidum for 24, 48, and 120 hours. Based on half-maximal inhibitory concentrations values, proliferation of the H1793 cell line seemed to be sensitive to the extract in a time- and dose-dependent manner. We used immunoblot analysis to examine the amounts of cell cycle proteins (cyclin D, Cdk4, and Cdc2) and apoptotic proteins (Bcl-xL and Bax) after treatment with a range of G. lucidum concentrations. Changes in amounts of proteins that regulate the cell cycle were consistent with longer G1 and G2 phases. Proapoptotic protein (Bax) levels increased 6.5-fold, with a commensurate increase in the Bax-to-Bcl ratio, especially at 48 and 120 hours. These results suggest that the decrease in cellular proliferation correlated with a change in both cell cycle progression and apoptosis, and that the triterpenoid in G. lucidum is the bioactive component. Further biochemical characterization of this ancient herbal remedy could hold promise for treating lung cancer.

Aqueous extracts from the vegetative submerged mycelia of cultivated Basidiomycetes Ganoderma lucidum, Lentinus edodes, and Grifola frondosa, as well as from the fruiting bodies of G. lucidum, were found to have antitumor activity. The antitumor effect of the mycelial extracts from all 3 fungal species was ascertained in vivo in rats with implanted kidney cancer. Dystrophic changes in tumor cells and tumor necrosis (up to 90%) were noted. In vitro cytotoxicity studies of the A549 human lung adenocarcinoma cell line and HEp-2 human laryngeal epidermoid carcinoma cells showed that the extracts from the G. lucidum fruiting bodies and from the L. edodes vegetative mycelium were the most effective. The animals' immune systems were activated, and the fungal extracts displayed no toxicity when administered orally.

OBJECTIVE:To study the inhibitory effect of Ganoderma lucidum, the extract of chloroform, the extract of ethyl acetate and the remains after two-time extraction on BEL-7402 and MGC-803 cells and their protective effects on HL-7702 cells pre-and post-exposed to cisplatin (DDP) and various doses of 60Co gamma irradiation.

METHOD:The antitumor activity and protective effects on damaged HL-7702 cells induced by radiotherapy and chemotherapy of ganoderma lucidum were determined by MTT technique.

RESULT:The anticancer activity of the extract of chloroform Ganoderma lucidum was the best: at the concentration of 0.125 mg x mL(-1), the inhibitory rate was over 50%. To the HL-7702 cells damaged by DDP, four kinds of extracts didn't exert restoring effect, but the pretreatment with the extract of chloroform reduced the damaged degree significantly. To the 60Co gamma irradiated HL-7702 cells, only the extract of chloroform exerted restoring effect to some extent when exposed to middle or high dose of irradiation. The pre-administration of four kinds of extracts reduced the damaged degree by radiation.

CONCLUSION:The extract of chloroform exerts notable antitumor effects on cancer cells and protective effects on damaged normal cells induced by radiotherapy and chemotherapy.

Five new aromatic compounds, designed as lucidumins A-D (1-4) and lucidimine E (9), along with seven known aromatic compounds (5-8, 10-12) were isolated from Ganoderma lucidum. Their structures were determined by spectroscopic method. Bioactive evaluation showed that compounds 2-4 and 6-10 displayed remarkable neuroprotective activities against corticosterone-induced PC12 cell damage, with the cell viability ranging from 69.99% to 126.00%; and compounds 1-4, 9 and 10 exhibited significant anti-inflammatory activities against LPS-induced nitric oxide (NO) production in RAW264.7 macrophages, with ICvalues ranging from 4.68 to 15.49 μM. In particular, compound 10 showed remarkable neuroprotection with ECvalue of 2.49 ± 0.12 μM, and potent anti-inflammation with ICvalue of 4.68 ± 0.09 μM.

Targeting autophagy may serve as a promising strategy for cancer therapy. Ganoderma lucidum polysaccharide (GLP) has been shown to exert promising anti-cancer effects. However, the underlying mechanisms remain elusive. Whether GLP regulates autophagy in cancer has never been reported. In this study, GLP induced the initiation of autophagy in colorectal cancer (CRC) HT-29 and HCT116 cells, as evidenced by enhanced level of LC3-II protein, GFP-LC3 puncta, and increased formation of double membrane vacuoles. However, GLP treatment caused marked increase of p62 expression. Addition of late stage autophagy inhibitor, chloroquine (CQ), further enhanced LC3-II and p62 level, as well as increased autophagosome accumulation, suggesting a blockage of autophagic flux by GLP in CRC cells. We then found GLP blocked autophagosome and lysosome fusion as determined by mRFP-GFP-LC3 colocalization analysis. Mechanistic study revealed that GLP-induced disruption of autophagosome-lysosome fusion is due to reduced lysosome acidification and lysosomal cathepsin activities. Cell viability and flow cytometry assays revealed that GLP-induced autophagosome accumulation is responsible for GLP-induced apoptosis in CRC cells. In line with this, inhibition of autophagy initiation by 3-methyladenine (3-MA), an early stage autophagy inhibitor, attenuated GLP-induced apoptosis. In contrast, suppression of autophagy at late stage by CQ enhanced the anti-cancer effect of GLP. Furthermore, we demonstrated that GLP-induced autophagosome accumulation and apoptosis is mediated via MAPK/ERK activation. Finally, GLP inhibited tumor growth and also inhibited autophagic flux in vivo. These results unveil new molecular mechanism underlying anti-cancer effects of GLP, suggesting that GLP is a potent autophagy inhibitor and might be useful in anticancer therapy.

The aim of this work is to characterize the primary structure and physicochemical properties of natural polysaccharides (GLP) and degraded polysaccharides (GLP) from Ganoderma lucidum, and evaluate their hypolipidemic and antioxidant activities. The results of particle size distribution and scanning electron microscopy (SEM) showed that Ganoderma lucidum polysaccharides were effectively degraded by ultrasonic method. GLPwas composed of the same monosaccharide units as GLP but with different molar ratios. Infrared spectra and NMR showed that the primary structure of polysaccharides had not been changed by ultrasonic degradation. Meanwhile, the thermal stability of polysaccharides increased after ultrasonic treatment. After administration by GLP and GLPfour weeks, body weight, visceral index, atherosclerosis index (AI) and biochemical indicators in serum and in liver were determined. The results showed that GLPhad stronger hypolipidemic and antioxidant activities than GLP. GLPwas more effective than the GLP for reducing AI, total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C), raising high density lipoprotein (HDL-C) (p < 0.01), reducing malondialdehyde (MDA) content, as well as increasing the glutathione peroxidase (GSH-Px) in mice serum, increasing superoxide dismutase (SOD) activity and reducing MDA content in liver (p < 0.05 or p < 0.01). In addition, the histopathological observations of mice livers showed that GLPcould significantly improve lipid metabolism disorder in hepatocytes. Thus, GLPmight be tested as a more effective hypolipidemic drug.

The objective of this study was to compare the mycochemical profiles, antioxidant activities, and antidiabetic effects of 2 species of genus Ganoderma, the red lingzhi (G. lucidum) and purple lingzhi (G. sinense) mushrooms. In Chinese medicinal practice, hot water and ethanol are used as solvents to extract samples. In this study, a total of 4 extracts (ethanol and hot water extracts from G. lucidum and G. sinense) were prepared for further assays. Hot water extracts presented much higher values for total phenolic content and ferric-reducing antioxidant power than the ethanol extracts. Ethanol (70%) extract of G. lucidum had the strongestα-glycosidase inhibitory capacity, but the lingzhi polysaccharides showed no inhibitory effect. It also had the largest amount of total ganoderic acids. The results indicated that ethanol extracts from both G. lucidum and G. sinense showed better antidiabetic effects than the hot water extracts. Ganoderic acids, rather than polysaccharides, may contribute the antidiabetic effects of both the Ganoderma species.

Dengue virus (DENV) infection causes serious health problems in humans for which no drug is currently available. Recently, DENV NS2B-NS3 protease has been proposed as a primary target for anti-dengue drug discovery due to its important role in new virus particle formation by conducting DENV polyprotein cleavage. Triterpenoids from the medicinal fungus Ganoderma lucidum have been suggested as pharmacologically bioactive compounds and tested as anti-viral agents against various viral pathogens including human immunodeficiency virus. However, no reports are available concerning the anti-viral activity of triterpenoids from Ganoderma lucidum against DENV. Therefore, we employed a virtual screening approach to predict the functional triterpenoids from Ganoderma lucidum as potential inhibitors of DENV NS2B-NS3 protease, followed by an in vitro assay. From in silico analysis of twenty-two triterpenoids of Ganoderma lucidum, four triterpenoids, viz. Ganodermanontriol (-6.291 kcal/mol), Lucidumol A (-5.993 kcal/mol), Ganoderic acid C2 (-5.948 kcal/mol) and Ganosporeric acid A (-5.983 kcal/mol) were predicted to be viral protease inhibitors by comparison to reference inhibitor 1,8-Dihydroxy-4,5-dinitroanthraquinone (-5.377 kcal/mol). These results were furtherstudied for binding affinity and stability using the molecular mechanics/generalized Born surface area method and Molecular Dynamics simulations, respectively. Also, in vitro viral infection inhibition suggested that Ganodermanontriol is a potent bioactive triterpenoid.

Multidrug resistance is a major problem in small-cell lung cancer (SCLC). Ganoderma lucidum is a widely used herb in traditional Chinese medicine. We tested the effects of Ganoderma on drug-sensitive (H69) and multi-drug resistant (VPA) human SCLC cells. Both cells showed equal cytotoxicity when incubated with extracts of mycelia of 9 species of Ganoderma, including G. lucidum. Cells treated with the IC(50) of cytotoxic Ganoderma and analyzed by flow cytometry-PI staining showed increases in S phase. When compared untreated controls or SCLC cells treated with extracts of non-cytotoxic Ganoderma species, cells treated with extracts of cytotoxic Ganoderma species responded with an induction of apoptosis similar to cells treated with the chemotherapeutic drugs etoposide and doxorubicin. This was shown by four criteria: increased DNA fragmentation within cells as measured by ELISA; increased TUNEL staining for DNA breaks; increased specific activities of caspases 3 and 9, but not caspase 8 by colorimetric assays, indicating the endogenous pathway; and similar patterns changes in the expressions of 9 genes involved in the cell cycle/apoptosis, as measured by RT-PCR and capillary electrophoresis. Pre-incubation of drug-resistant SCLC cells with cytotoxic Ganoderma reduced the IC(50) for etoposide (3.4-0.21 microM) and doxorubicin (0.19-0.04 microM). These results show that extracts of several species of Ganoderma are cytotoxic to both drug-sensitive and drug-resistant SCLC cells, are pro-apoptotic, induce gene expression patterns that are similar to SCLC cells treated with chemotherapeutic drugs, and can reverse resistance to chemotherapeutic drugs.

Diabetes mellitus (DM) is the third most common non-infectious disease leading to early disability and high mortality. Moreover, the number of patients is growing every year. The main symptom of DM is hyperglycemia. Increased levels of blood glucose activate polyol, hexosamine, and protein kinase metabolic pathways cause the intensification of non-enzymatic glycosylation and nitration of macromolecules. This, in turn, leads to the development of oxidative and nitrative stresses and secondary complications, such as different kinds of micro- and macroangiopathies. Metabolic disorders caused by insulin deficiency in diabetes significantly impede the functioning of a homeostasis system, which change the physical, biochemical, morphological, and functional properties of blood cells. As a result, the oxygen-transport function of red blood cells (RBCs), rheological properties of the blood, and functions of immunocompetent cells as well as the process of apoptosis are primarily affected. Modern pharmacotherapy focuses on the search for new preparations that aim to decrease blood glucose levels. Undesirable side effects and adverse reactions caused by synthetic medicines led to the search and investigation of new preparations of natural origin. Medicinal mushrooms play an important role among such new preparations. They are a source of a large number of high- and low-molecular compounds with pronounced biological effects. Our investigations show pronounced hypoglycemic and anti-anemic action of submerged cultivated mycelium powder of medicinal mushrooms Agaricus brasiliensis (A. brasiliensis) and Ganoderma lucidum (G. lucidum) on streptozotocin-induced DM in rats. Also, we showed that mycelium powders have membrane protective properties as evidenced by the redistribution of RBC populations towards the growth of full functional cell numbers. Normalization of parameters of leukocyte formula and suppression of apoptosis of white blood cells in diabetic rats treated with A. brasiliensis and G. lucidum mycelia indicates pronounced positive effects of these strains of mushrooms. Thus, the use of medicinal mushrooms for treatment of DM and in prevention development of its secondary complications might be a new effective approach of this disease's cure. This article is aimed at summarizing and analyzing the literature data and basic achievements concerning DM type 1 treatment using medicinal mushrooms and showing the results obtained in our research.