Ganoderma lucidum-Derived Meroterpenoids Show Anti-Inflammatory Activity In Vitro.

Ganoderma lucidum, known as the "herb of spiritual potency", is used for the treatment and prevention of various diseases, but the responsible constituents for its therapeutic effects are largely unknown. For the purpose of obtaining insight into the chemical and biological profiling of meroterpenoids in G. lucidum, various chromatographic approaches were utilized for the title fungus. As a result, six undescribed meroterpenoids, chizhienes A-F (1-6), containing two pairs of enantiomers (4 and 5), were isolated. Their structures were identified using spectroscopic and computational methods. In addition, the anti-inflammatory activities of all the isolates were evaluated by Western blot analysis in LPS-induced macrophage cells (RAW264.7), showing that 1 and 3 could dose dependently inhibit iNOS but not COX-2 expression. Further, 1 and 3 were found to inhibit nitric oxide (NO) production using the Greiss reagent test. The current study will aid in enriching the structural and biological diversity of Ganoderma-derived meroterpenoids.

Identification of sedative-hypnotic compounds shared by five medicinal Polyporales mushrooms using UPLC-Q-TOF-MS/MS-based untargeted metabolomics.

BACKGROUND: Five Polyporales mushrooms, namely Amauroderma rugosum, Ganoderma lucidum, G. resinaceum, G. sinense and Trametes versicolor, are commonly used in China for managing insomnia. However, their active components for this application are not fully understood, restricting their universal recognition. PURPOSE: In this study, we aimed to identify sedative-hypnotic compounds shared by these five Polyporales mushrooms. STUDY DESIGN AND METHODS: A UPLC-Q-TOF-MS/MS-based untargeted metabolomics, including OPLS-DA (orthogonal projection of potential structure discriminant analysis) and OPLS (orthogonal projections to latent structures) analysis together with mouse assays, were used to identify the main sedative-hypnotic compounds shared by the five Polyporales mushrooms. A pentobarbital sodium-induced sleeping model was used to investigate the sedative-hypnotic effects of the five mushrooms and their sedative-hypnotic compounds. RESULTS: Ninety-two shared compounds in the five mushrooms were identified. Mouse assays showed that these mushrooms exerted sedative-hypnotic effects, with different potencies. Six triterpenes [four ganoderic acids (B, C1, F and H) and two ganoderenic acids (A and D)] were found to be the main sedative-hypnotic compounds shared by the five mushrooms. CONCLUSION: We for the first time found that these six triterpenes contribute to the sedative-hypnotic ability of the five mushrooms. Our novel findings provide pharmacological and chemical justifications for the use of the five medicinal mushrooms in managing insomnia.

Combined NMR and MS-based metabonomics and real-time PCR analyses reveal dynamic metabolic changes of Ganoderma lucidum during fruiting body growing.

Ganoderma lucidum (G. lucidum) is a rare medicinal fungus with various beneficial properties. One of its main components, ganoderic acids (GAs), are important triterpenoids known for their sedative and analgesic, hepatoprotective, and anti-tumor activities. Understanding the growth and development of the G. lucidum fruiting body is crucial for determining the optimal time to harvest them. In this study, we used nuclear magnetic resonance (NMR) spectroscopy to systematically characterize the metabolites of G. lucidum at seven distinct developmental stages. We also measured the contents of seven kinds of GAs using LC-MS/MS. A total of 49 metabolites were detected in G. lucidum, including amino acids, sugars, organic acids and GAs. During the transition from the bud development period (I) to the budding period (II), we observed a rapid accumulation of glucose, tyrosine, nicotinamide ribotide, inosine and GAs. After the budding period, the contents of most metabolites decreased until the mature period (VII). In addition, the contents of GAs showed an initial raising, followed by a decline during the elongation period, except for GAF, which exhibited a rapid raise during the mature stage. We also detected the expression of several genes involved in GA synthesis, finding that most genes including 16 cytochrome P450 monooxygenase were all down-regulated during periods IV and VII compared to period I. These findings provide valuable insights into the dynamic metabolic profiles of G. lucidum throughout its growth stage, and it is recommended to harvest G. lucidum at period IV.

A Comprehensive Review on the Chemical Composition, Pharmacology and Clinical Applications of Ganoderma.

Ganoderma is the dried fruiting bodiy of Ganoderma lucidum (Leyss.ex Fr.) Karst. or Ganoderma sinense Zhao, Xu et Zhang, belonging to the family Polyporaceae, which grows mainly in tropical, subtropical, and temperate regions. As a traditional Chinese medicine, Ganoderma has been used in China for more than 2000 years because of its medicinal properties, such as relieving cough and asthma, providing nourishment, and strengthening. Currently, more than 470 natural compounds have been obtained from the fungus, mainly including terpenoids, steroids, alkaloids, phenols, and other types of compounds. Modern pharmacological studies have shown that Ganoderma has antitumor, anti-inflammatory, hypoglycemic, hypolipidemic, and immunomodulatory effects. It is mainly used in clinical practice for the treatment of Diabetic Nephropathy and malignant tumors, with few side effects and high safety. This paper reviews the progress of research on its chemical composition, pharmacological effects, and clinical applications, with the goal of providing a basis for the better development and utilization of Ganoderma.

Inhibition of intrarenal PRR-RAS pathway by Ganoderma lucidum polysaccharide peptides in proteinuric nephropathy.

Excessive proteinuria leads to renal dysfunction and damage. Ganoderma lucidum polysaccharide peptide (GL-PP) and Ganoderma lucidum polysaccharide peptide 2 (GL-PP2) are biologically active compounds extracted from Ganoderma lucidum. GL-PP has a relative molecular weight of 37,121 with 76.39 % polysaccharides and 16.35 % polypeptides, while GL-PP2 has a relative molecular weight of 31,130, composed of 64.14 % polysaccharides and 17.73 % polypeptides. The xylose: mannose: glucose monosaccharide ratios in GL-PP and GL-PP2 were 4.83:1:7.03 and 2.35:1:9.38, respectively. In this study, we investigated the protective effects of GL-PP and GL-PP2 on proteinuria-induced renal dysfunction and damage using rat and cell models. Both compounds reduced kidney injury, proteinuria, and inhibited the (pro)renin receptor (PRR)-renin-angiotensin system (RAS) pathway, inflammatory cell infiltration, oxidative stress, and fibrosis. GL-PP2 showed stronger inhibition of cyclooxygenase-2 and inducible nitric oxide synthase proteins compared to GL-PP. In cell models, both compounds displayed anti-inflammatory properties and improved cellular viability by inhibiting the PRR-RAS pathway. GL-PP2 has higher feasibility and productivity than GL-PP in pharmacology and industrial production. It shows promise in treating proteinuria-induced renal disease with superior anti-inflammatory effects and economic, safe industrial application prospects. Further research is needed to compare efficacy, mechanisms, clinical applications, and commercial feasibility of GL-PP and GL-PP2.

Significance of culture period on the physiochemistry and anti-cancer potentials of polysaccharides from mycelia of Ganoderma lucidum.

Ganoderma lucidum polysaccharides (GPS) have many functions. Polysaccharides are abundant in G. lucidum mycelia, but it is unclear whether the production and chemical characteristics of polysaccharides are related to the liquid cultural periods of mycelia. This study harvests G. lucidum mycelia at different cultural stages and isolates GPS and sulfated polysaccharides (GSPS) separately to determine an optimum cultural duration. After 42 and 49 days of mycelia are found to be the best times to harvest GPS and GSPS. Characteristic studies show that glucose and galactose are the main sugars in GPS and GSPS. The molecular weights of various GPS and GSPS are mainly distributed at >1000 kDa and from 101 to 1000 kDa. The sulfate content of GSPS at Day 49 is greater than that at Day 7. GPS and GSPS at 49 days exhibits a good anticancer effect but does not affect normal fibroblasts. GPS and GSPS that is isolated on day 49 inhibits lung cancer by suppressing epidermal growth factor receptor (EGFR) and transforming growth factor beta receptor (TGFßR)-mediated signaling networks. These results show that the mycelia of G. lucidum that are cultured for 49 days exhibit the best biological characteristics.

Ganoderma lucidum polysaccharide peptides GL-PPSQ2 alleviate intestinal ischemia-reperfusion injury via inhibiting cytotoxic neutrophil extracellular traps.

Ganoderma lucidum polysaccharides peptides (GLPP) are the main effective ingredients from G. lucidum (Leyss. ex Fr.) Karst with anti-inflammatory, antioxidant, and immunoregulatory activities. We extracted and characterized a novel GLPP, named GL-PPSQ2, which were found to have 18 amino acids and 48 proteins, connected by O-glycosidic bonds. The monosaccharide composition of GL-PPSQ2 was determined to be composed of fucose, mannose, galactose and glucose with a molar ratio of 1:1.45:2.37:16.46. By using asymmetric field-flow separation technique, GL-PPSQ2 were found to have a highly branched structure. Moreover, in an intestinal ischemia-reperfusion (I/R) mouse model, GL-PPSQ2 significantly increased the survival rate and alleviated intestinal mucosal hemorrhage, pulmonary permeability, and pulmonary edema. Meanwhile, GL-PPSQ2 significantly promoted intestinal tight junction, decreased inflammation, oxidative stress and cellular apoptosis in the ileum and lung. Analysis with Gene Expression Omnibus series indicates that neutrophil extracellular trap (NET) formation plays an important role in intestinal I/R injury. GL-PPSQ2 remarkedly inhibited NETs-related protein myeloperoxidase (MPO) and citrulline-Histone H3 (citH3) expression. GL-PPSQ2 could alleviate intestinal I/R and its induced lung injury via inhibiting oxidative stress, inflammation, cellular apoptosis, and cytotoxic NETs formation. This study proves that GL-PPSQ2 is a novel drug candidate for preventing and treating intestinal I/R injury.

Effects of Mexican Ganoderma lucidum extracts on liver, kidney, and the gut microbiota of Wistar rats: A repeated dose oral toxicity study.

Well-characterized and standardized extracts of a Mexican genotype of Ganoderma lucidum (Gl), a medicinal mushroom, cultivated on oak sawdust (Gl-1) or oak sawdust plus acetylsalicylic acid (Gl-2, ASA), have been shown to exert antioxidant, hypocholesterolemic, anti-inflammatory, prebiotic, and anticancer properties. However, toxicity analyses still need to be carried out. Different doses of these Gl-1 or Gl-2 extracts were administered to Wistar rats for 14 days in a repeated dose oral toxicity study. We assessed the external clinical signs, biochemical parameters, liver and kidney tissues, injury and inflammation biomarkers, gene expression, inflammatory responses, proinflammatory mediators, and gut microbiota. Gl extracts had no significant adverse, toxic or harmful effects on male and female rats compared to the control groups. No injury or dysfunction were recorded in the kidney or liver, as there were no significant abnormal variations in organ weight, tissue histopathology, serum biochemical parameters (C-reactive protein, creatinine, urea, glucose, ALT and AST transaminases, TC, LDL-c, TG, HDL-c), urinary parameters (creatinine, urea nitrogen, albumin, the albumin-to-creatinine ratio, glucose), injury and inflammatory biomarkers (KIM-1/TIM-1, TLR4, and NF-кB protein expression; IL-1ß, TNF-α and IL-6 gene expression), or the expression of genes linked to cholesterol metabolism (HMG-CoA, Srebp2, Ldlr). Gl-1 and Gl-2 extracts showed prebiotic effects on the gut microbiota of male and female Wistar rats. Bacterial diversity and relative bacterial abundance (BRA) increased, positively modulating the Firmicutes/Bacteroidetes ratio. The ASA (10 mM) added to the substrate used for mushroom cultivation changed properties and effects of the Gl-2 extract on Wistar rats. The no-observed-adverse-effect-level (NOAEL) was 1000 mg/kg body weight/day of Gl-1 or Gl-2 extracts. Clinical trials are recommended for further exploring the potential therapeutic applications of studied extracts.

A Review on the Sources, Structures, and Pharmacological Activities of Lucidenic Acids.

Ganoderma lucidum has long been used as a multi-purpose plant and functional food. The pharmacological properties of G. lucidum are primarily attributed to its polysaccharides and triterpenoids. Ganoderic and lucidenic acids are the two major triterpenoids groups in G. lucidum. Despite the discovery of 22 types of lucidenic acids, research on lucidenic acids is significantly less extensive compared to that on ganoderic acid. To the best of our knowledge, for the first time, in this review, we aimed to summarize the sources, contents, chemical structures, and pharmacological effects, including anti-cancer, anti-inflammatory, antioxidant, anti-viral, neuroprotective, anti-hyperlipidemic, anti-hypercholesterolemic, and anti-diabetic properties, of lucidenic acids. Studies on lucidenic acids are still preliminary and have several limitations. Therefore, more in-depth studies with optimal designs are essential for the development of lucidenic acids as medicines, functional foods, and nutraceuticals.

A novel promising neuroprotective agent: Ganoderma lucidum polysaccharide.

Nervous system diseases (NSDs) are characterized by a wide range of symptoms, a complex pathophysiology, an unclear etiology, a great deal of variation in treatment response, and lengthy therapy cycles, all of which pose considerable hurdles to clinical treatment. A traditional valuable medicine known as Ganoderma lucidum (GL) has a significant role to play in preserving health and treating diseases. Ganoderma lucidum polysaccharides (GLP) is one of the cardinal effective active ingredients of GL, which has a number of pharmacological actions, including liver protection, immune regulation, antioxidant activity, anticancer activity, antibacterial activity, and antiviral activity. Recently, studies on the structural characterization and biological functions of GLP were presented in this article to review the progress of researches about GLP on NSDs and summarize the potential mechanisms of action. These studies were anticipated to provide new research ideas for GLP as a novel promising neuroprotective agent and provide a reference for better development and utilization of GLP.

The role of post-transcriptional modification on a new tRNAIle(GAU) identified from Ganoderma lucidum in its fragments' cytotoxicity on cancer cells.

Ganoderma lucidum (Ganoderma) is a famous Chinese herbal medicine which has been used clinically for thousands of years in China. Despite numerous studies on triterpenes and polysaccharides, the bioactivity of RNAs abundant in Ganoderma remains unknown. Here, based on LC-MS techniques, dihydrouracil, 5-methyluridine (m5U) and pseudouridine were identified at position 19, 52 and 53 of a new tRNAIle(GAU) which was isolated as the most abundant tRNA species in Ganoderma, and is the first purified tRNA from fungus. Cytotoxic screening of tRNA-half (t-half) and tRNA fragment (tRF) derived from this tRNA, as well as their mimics (t-half or tRF as antisense strand), demonstrated that the double-stranded form, i.e., tRF and t-halve mimics, exhibited stronger cytotoxicity than their single-stranded form, and the cytotoxicity of t-half mimic is significantly stronger than that of tRF mimic. Notably, the cytotoxicity of 3'-t-half mimic is not only much more potent than that of taxol, but also is much more potent than that of ganoderic acids, the major bioactive components in Ganoderma. Furthermore, 3'-t-half mimic_M2 (m5U modified) exhibited significantly stronger cytotoxicity than unmodified 3'-t-half mimic, which is consistent with the computational simulation showing that m5U modification enhances the stability of the tertiary structure of 3'-t-half mimic. Overall, the present study not only indicates t-halves are bioactive components in Ganoderma which should not be neglected, but also reveals an important role of post-transcriptional modification on tRNA in its fragments' cytotoxicity against cancer cells, which benefits the design and development of RNAi drugs from natural resource.

Nor-triterpenoids from the fruiting bodies of Ganoderma lucidum and their inhibitory activity against FAAH.

Two new nor-triterpenoids ganodrenol A (1), B (2), and a new natural product ganodrenol C (3), along with three known nor-triterpenoids (4-6) were isolated from the fruiting bodies of Ganoderma lucidum. The chemical structures of these isolates were determined by 1 D and 2 D NMR, HRESIMS, and X-ray crystallography analysis. The inhibitory effects of isolated triterpenoids (1-6) against FAAH were evaluated by an in vitro assay, and compound 4 showed an inhibition rate of 70.27%. In addition, the cytotoxic effect of compounds (1-6) was evaluated against LOVO, MCF-7, and RAW264.7 cells, which displayed no significant cytotoxicity.

Ganoderma lucidum polysaccharides ameliorate lipopolysaccharide-induced acute pneumonia via inhibiting NRP1-mediated inflammation.

CONTEXT: Ganoderma lucidum polysaccharides (GLP), from Ganoderma lucidum (Leyss. ex Fr.) Karst. (Ganodermataceae), are reported to have anti-inflammatory effects, including anti-neuroinflammation and anti-colitis. Nevertheless, the role of GLP in acute pneumonia is unknown. OBJECTIVE: To explore the protective role of GLP against LPS-induced acute pneumonia and investigate possible mechanisms. MATERIALS AND METHODS: GLP were extracted and used for high-performance liquid chromatography (HPLC) analysis after acid hydrolysis and PMP derivatization. Sixty C57BL/6N male mice were randomly divided into six groups: Sham, Model, LPS + GLP (25, 50 and 100 mg/kg/d administered intragastrically for two weeks) and LPS + dexamethasone (6 mg/kg/d injected intraperitoneally for one week). Acute pneumonia mouse models were established by intratracheal injection of LPS. Haematoxylin and eosin (H&E) staining was examined to evaluate lung lesions. ELISA and quantitative real-time PCR were employed to assess inflammatory factors expression. Western blots were carried out to measure Neuropilin-1 expression and proteins related to apoptosis and autophagy. RESULTS: GLP suppressed inflammatory cell infiltration. In BALF, cell counts were 1.1 × 106 (model) and 7.1 × 105 (100 mg/kg). Release of GM-CSF and IL-6 was reduced with GLP (25, 50 and 100 mg/kg) treatment. The expression of genes IL-1ß, IL-6, TNF-α and Saa3 was reduced. GLP treatment also suppressed the activation of Neuropilin-1 (NRP1), upregulated the levels of Bcl2/Bax and LC3 and led to downregulation of the ratio C-Caspase 3/Caspase 3 and P62 expression. DISCUSSION AND CONCLUSIONS: GLP could protect against LPS-induced acute pneumonia through multiple mechanisms: blocking the infiltration of inflammatory cells, inhibiting cytokine secretion, suppressing NRP1 activation and regulating pneumonocyte apoptosis and autophagy.

Ganoderma lucidum polysaccharide peptide alleviates hyperuricemia by regulating adenosine deaminase and urate transporters.

Hyperuricemia (HUA) affects human health and is involved in the pathogenesis of common chronic diseases. Previous studies showed that Ganoderma lucidum extract lowered HUA in animals. However, the active ingredient and pharmacological mechanism of Ganoderma lucidum extract in the improvement of HUA are unknown. The purpose of this study was to determine the anti-HUA efficacy and related mechanism of Ganoderma lucidum polysaccharide peptide (GLPP) using a potassium oxonate (PO)-induced mouse model and an adenosine-induced cell model. The experimental results showed that blood uric acid (UA) was decreased up to 40.6% by GLPP in HUA mice in a dose-dependent manner. Additionally, GLPP significantly reduced UA production by inhibiting the hepatic and blood adenosine deaminase (ADA) activity and increased UA excretion by decreasing the expression of glucose transporter 9 (GLUT9) and increasing the expression of organic anion transporter 1 (OAT1) in kidney. The adenosine-induced cell model showed that the inhibitory effect of GLPP on ADA activity may be the main reason for the alleviation of HUA by GLPP. Furthermore, PO-induced renal histopathological damage was also alleviated by GLPP in a dose-dependent manner. The experimental results in this study indicated that GLPP exerted anti-HUA effects via regulating the UA production and excretion, suggesting that GLPP could be developed into a therapeutic agent for HUA.

Immunomodulatory Effects of Extract of Lingzhi or Reishi Medicinal Mushroom Ganoderma lucidum (Agaricomycetes) Basidiocarps Cultivated on Alternative Substrate.

Ganoderma lucidum is a medicinal mushroom exhibiting numerous health benefits primarily based on strong immunostimulatory effects. The study aimed to investigate if there were differences in effects of extracts of commercially (GC) and alternatively (wheat straw) (GA) cultivated G. lucidum basidiocarps on properties of peritoneal macrophages (PM) and monocyte-derived dendritic cells (MoDCs). Differences in immunomodulatory effects of GC/GA extracts were studied. The viability of treated PMs, their adhesive and phagocytic capability, and their capacity to produce reactive oxygen species (ROS) and NO were tested. Immature MoDCs generated from human monocytes were treated with poly I:C (10.0 µg/ml) and loxoribine (34.0 µg/ml), a selective TLR3 and TLR7 agonists, respectively, and with/without GC/GA extract (100.0 µg/ml). The effect of each combination on phenotypic properties, cytokines production by MoDCs, and their proliferation and Th polarizing capacity was studied. GA extract stimulated the metabolic and phagocytic activity of PMs, their adhesion capability, and ability to produce ROS and NO more strongly compared to GC. Both tested extracts significantly increased allostimulatory and Th1 polarization capacity of simultaneous TLR3 and TLR7-activated MoDCs, but GA extract was more effective. The extract of alternatively cultivated G. lucidum basidiocarps increased production of ROS and NO by TLR4 stimulated PMs and upregulated production of certain cytokines as well as allostimulatory and Th1 polarization capacity of MoDCs. GA extract could be a potent immunostimulatory agent for activation of MoDCs with the simultaneous engagement of TLRs, which seems to be a promising strategy for the preparation of DC-based anti-tumor vaccines.

Lanostane triterpenoids from Ganoderma lucidum and their inhibitory effects against FAAH.

Ganoderma lucidum is a famous edible and medicinal fungus. Through a bioactive phytochemical investigation of the ethanolic extracts of the fruiting bodies of G. lucidum, twenty-nine triterpenoids, including eleven previously undescribed triterpenoids, were isolated and characterized based on spectroscopic data. The inhibitory effects of all the triterpenes against fatty acid amide hydrolase (FAAH) were found to be in the range of 30-60% at 100 µM. Methyl ganoderate A displayed the strongest inhibitory activity (61%) against FAAH. Furthermore, all compounds displayed no cytotoxicity against LOVO and MCF-7 human cancer cells. Hence, our present study provides information about G. lucidum as a functional food or pharmaceutical supplement for the treatment of neuroinflammation.

Production Ganoderma lucidum extract nanoparticles by expansion of supercritical fluid solution and evaluation of the antioxidant ability.

Due to the growing human tendency to treat with natural substances, fungi such as Ganoderma lucidum can be a good source to meet this need. Effectiveness, ease of use and a rich source of active ingredients such as ganoderic acids have caused G. lucidum to be considered in the pharmaceutical and food industries. In this project, G. lucidum was applied to extraction using supercritical carbon dioxide. Then expansion of supercritical fluid solution (ESS) was used as, novel, repeatable and green method to yield nanoparticles from G.lucidum extract. The response surface method was used to improve the Extraction efficiency, antioxidant activity, and improving the nanoparticles production status. Optimal conditions were observed at the extraction step by setting pressure at 27.5 MPa, dynamic time of 46 min, and modifier volume of 162 µL. The optimum point for the production of nanoparticles was obtained as follows: pressure drop at 25 MPa, 20 min for collection time, and 40° C for temperature. Under these conditions, the size and count were 86.13 nm, and 98, respectively. Nanoparticles were analyzed by FESM and, the DPPH was used for antioxidant activity evaluation. The LC-MS identified various ganoderic acids from G.lucidum that are famous to be highly oxygenated triterpenoids.

Ganoderma lucidum polysaccharide inhibits the proliferation of leukemic cells through apoptosis.

OBJECTIVE: To investigate the cytotoxic effect of polysaccharides derived from Ganoderma lucidum on T lymphocyte leukemia cells. METHODS: Water-soluble polysaccharides were extracted from the fruit bodies of G. lucidum, purified, and characterized using HPGPC-MALLS and NMR. The cytotoxicity of G. lucidum polysaccharide fraction 5 (GLP5) to T lymphocyte leukemia cell line Jurkat and human immortalized epidermal cell line HaCat was assessed using MTT assay. Apoptosis was assessed using flow cytometry. Expressions of apoptosis-related genes in the cells after being exposed to GLP5 were detected using Western blot assay. RESULTS: GLP5 was a ß-(1→3) and ß-(1→6) linked glucan. It inhibited the proliferation of Jurkat cells in a concentration-dependent manner and the half-maximal inhibitory concentration (IC50) was 34.5 mg/L but did not suppress the growth of HaCat cells. Apoptotic cells in Jurkat cells were detected to increase with increasing GLP5 concentrations. The expression levels of cleaved caspase-3 were significantly higher after the cells were exposed to 25 and 50 mg/L GLP5 when compared to non-exposed cells (Control). In addition, the expression levels of BAX and Bcl2 were significantly up- and down-regulated after treatment with GLP5 at 25 and 50 mg/L when compared with control (P<0.05), respectively. CONCLUSIONS: GLP5 has antiproliferative activity against Jurkat cells and the activity is likely mediated through the activation of apoptosis pathways.

Investigation of HER-3 gene expression under the influence of carbohydrate biopolymers extract of shiitake and reishi in MCF-7 cell line.

INTRODUCTION: Edible-medicinal fungi are mainly used in Asian countries to prevent various diseases. These mushrooms are also used to treat lung diseases and cancer. Ganoderma lucidum and Lentinula edodes are the most important edible-medicinal fungi. The polysaccharides of these fungi are one of the bioactive compounds with anti-cancer properties. OBJECTIVE: Evaluation of anti-cancer effects of Shiitake and Reishi polysaccharides. METHODS: In this study, fungal polysaccharides were extracted using the hot water method and were purified by Diethylaminoethyl Sephadex A-25 (DEAE-Sephadex A-25) chromatography column and their concentration was measured by phenolic sulfuric acid method. The biological effects of the extracted polysaccharides from Ganoderma lucidum and Lentinula edodes on the MCF-7 cell line were investigated using an MTT assay and then its effects on the expression of the P53 cancer regulatory gene and HER-3 gene were investigated. RESULTS: Based on the results, the concentration of Ganoderma lucidum and Lentinula edodes extracted polysaccharides were 0.024 and 0.103 mg/ml, respectively. Polysaccharides of these two fungi increased the expression of the P53 gene and decreased the expression of the HER-3 gene in a dose and time-dependent manner. DISCUSSION: Natural biocompatible polysaccharides with anti-cancer properties that are native, are available, and inexpensive, so they can be used as dietary supplements to prevent and help treat cancer.

Sterols and triterpenoids from Ganoderma lucidum and their reversal activities of tumor multidrug resistance.

Two sterols and seven triterpenoids were isolated and identified from Ganoderma lucidum by silica gel column chromatography, preparative high-performance liquid chromatography and spectra analysis. Then, the multidrug resistance reversal activities of these compounds were assessed using MTT assay. Among these compounds, ganoderol B (3), ganoderone A (4), ganodermanondiol (6) and ganoderiol F (8) were shown to reverse the resistance of human oral epidermoid carcinoma cell line KBv200 to doxorubicin, and the reversal folds were 6.59, 4.70, 4.01 and 7.09, respectively. Ganoderiol F could increase the intracellular accumulation of doxorubicin in KBv200 cells through inhibiting P-glycoprotein transport function. Further mechanistic investigation found that ganoderiol F did not alter P-glycoprotein expression. In conclusion, ganoderiol F has potent effect in reversing P-glycoprotein mediated tumor multidrug resistance. Potential reversal agents against multidrug resistance in tumor may be found in triterpenoids from Ganoderma lucidum.[Formula: see text].