Structural variety of glucans from Ganoderma lucidum fruiting bodies.

Ganoderma lucidum, widely used in traditional medicine, has several biological properties. Polysaccharides, mainly glucans, are known as one of its main bioactive compounds. Consequently, the achievement and chemical investigation of such molecules are of pharmaceutical interest. Herein, we obtained water-insoluble and water-soluble polysaccharides from G. lucidum by alkaline extraction. Fractionation process yielded three fractions (GLC-1, GLC-2, and GLC-3). All samples showed to be composed mainly of glucans. GLC-1 is a linear (1 â†’ 3)-linked ß-glucan; GLC-2 is a mixture of three different linear polysaccharides: (1 â†’ 3)-ß-glucan, (1 â†’ 3)-α-glucan, and (1 â†’ 4)-α-mannan; while GLC-3 is a branched ß-glucan with a (1 â†’ 4)-linked main chain, which is branched at O-3 or O-6 by (1 â†’ 3)- or (1 â†’ 6)-linked side chains. This research reports the variability of glucans in Ganoderma lucidum fruiting bodies and applicable methodologies to obtain such molecules. These polysaccharides can be further applied in biological studies aiming to investigate how their chemical differences may affect their biological properties.

Structural characterization of a galactoglucomannan with anti-neuroinflammatory activity from Ganoderma lucidum.

According to traditional Chinese medicine theory, Ganoderma lucidum (G. lucidum) presents certain effects for nourishing nerves and calming the mind. G. lucidum polysaccharides (GLPs) have various biological activities; however, the structural characterization and the structure-activity relationship in anti-neuroinflammation of GLPs needs to be further investigated. In this work, the crude polysaccharide GL70 exhibited a remarkable impact on enhancing the spatial learning and memory function, as well as reducing the anxiety symptoms of the lipopolysaccharide (LPS)-induced rat model of Alzheimer's disease (AD). A galactoglucomannan (GLP70-1-2) was isolated from GL70, and characterized by monosaccharide composition, partial acid hydrolysis, methylation, and NMR analysis. The backbone of GLP70-1-2 was →6)-α-D-glcp-(1 â†’ 6)-ß-D-galp-(1 â†’ [6)-ß-D-manp-(1]3 â†’ 4)-α-D-Glcp-(1 â†’ 6)-α-D-glcp-(1 â†’ 2)-ß-D-galp-(1 â†’ [4)-α-D-glcp-(1 â†’ 6)-ß-D-manp-(1 â†’ 2)-ß-D-galp-(1]2 â†’ 6)-ß-D-glcp-(1 â†’ 6)-ß-D-glcp-(1→ with two side chains attached to O-4 of →6)-ß-D-galp-(1→ and O-3 of →6)-ß-D-glcp-(1→, respectively. In addition, GLP70-1-2 exhibited remarkable efficacy in decreasing the level of pro-inflammatory factors in LPS-activated BV2 cells through the TLR4/MyD88/NF-κB pathway. Collectively, GLP70-1-2 exhibited significant anti-neuroinflammatory activity and may have the potential for developing as a drug for AD.

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.

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.

Structural characterization and anti-oxidative activity for a glycopeptide from Ganoderma lucidum fruiting body.

A water-soluble glycopeptide (named GL-PWQ3) with a molecular weight (Mw) of 2.40 × 104 g/mol was isolated from Ganoderma lucidum fruiting body by hot water extraction, membrane ultrafiltration, and gel column chromatography, which mainly consisted of glucose and galactose. Based on the methylation, FT-IR, 1D, and 2D NMR analysis, the polysaccharide portion of GL-PWQ3 was identified as a glucogalactan, which was comprised of unsubstituted (1,6-α-Galp, 1,6-ß-Glcp, 1,4-ß-Glcp) and monosubstituted (1,2,6-α-Galp and 1,3,6-ß-Glcp) in the backbone and possible branches that at the O-3 position of 1,3-Glcp and T-Glcp, and the O-2 position of T-Fucp, T-Manp or T-Glcp. The chain conformational study by SEC-MALLS-RI and AFM revealed that GL-PWQ3 was identified as a highly branched polysaccharide with a polydispersity index of 1.25, and might have compact sphere structures caused by stacked multiple chains. Moreover, the GL-PWQ3 shows strong anti-oxidative activity in NRK-52E cells. This study provides a theoretical basis for further elucidating the structure-functionality relationships of GL-PWQ3 and its potential application as a natural antioxidant in pharmacotherapy as well as functional food additives.

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.

PRMT5 regulates the polysaccharide content by controlling the splicing of thaumatin-like protein in Ganoderma lucidum.

IMPORTANCE: PRMT5 contributes to secondary metabolite biosynthesis in Ganoderma lucidum. However, the mechanism through which PRMT5 regulates the biosynthesis of secondary metabolites remains unclear. In the current study, PRMT5 silencing led to a significant decrease in the biosynthesis of polysaccharides from G. lucidum through the action of the alternative splicing of TLP. A shorter TLP2 isoform can directly bind to PGI and regulated polysaccharide biosynthesis. These results suggest that PRMT5 enhances PGI activity by regulating TLP binding to PGI. The results of the current study reveal a novel target gene for PRMT5-mediated alternative splicing and provide a reference for the identification of PRMT5 regulatory target genes.

Differential Analysis of Korean and Chinese Lingzhi or Reishi Medicinal Mushroom Ganoderma lucidum (Agaricomycetes) Spore Powder by Infrared Spectroscopy with Stoichiometry.

To investigate the differences between Korean Ganoderma lucidum spore powder (KP), broken-spo-roderm KP (BSKP), Chinese traditional G. lucidum spore powder (CP), and broken-sporoderm CP (BSCP), they were identified by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), second derivative infrared spectroscopy (SD-IR), dual-index sequence analysis (DISA) and X-ray diffraction (XRD). SEM showed that there were no significant differences in microstructure between the two kinds of spore powders. FT-IR spectra showed that the four spore powders appeared with characteristic peaks of 3400, 3006, 2925, 1745, 1535, 1454, 1249, 1074, 1049, and 896 cm-1, respectively, they were contained the characteristic peaks of total triterpenes, polysaccharides and fatty acids. DISA showed that the same species of spore powders, the overall similarity of before and broken the sporoderm was high with minor differences and there were no differences between the different kinds of spore powders. Similarity analysis showed that the four spore powders were in high agreement and were no differences. The polysaccharide, total triterpene, spore oil and protein content of the four spore powders were determined separately. The results showed that the active ingredients content of the batch of KP were lower than that of CP, that of BSKP were lower than that of BSCP, while the active ingredients content of both broken-sporoderm spore powders were higher than that of before broken-sporoderm. It is inferred that the structure of the main chemical and component of KP is the same as that of CP. This study provides a reference for the future development and application of G. lucidum.

Modifications of Ganoderma lucidum spores into digestive-tissue highly adherent porous carriers with selective affinity to hydrophilic or hydrophobic drugs.

Ganoderma lucidum spores (GLSs) have been suggested to provide optimal structures for transporting orally bioavailable drugs. However, the double-layer wall and cavities of GLSs are naturally closed. This study aimed to modify GLSs into porous carriers by opening the layers and internal cavity with iturin A (IA) followed by potassium hydroxide (KOH) or hydrochloric acid (HCl). The (IA + KOH)- and (IA + HCl)-treated GLS carriers exhibited a high loading rate of 301.50 ± 2.33 and 268.18 ± 7.72 mg/g for the hydrophilic methylene blue (MB) and hydrophobic rifampicin (RF), respectively. The mechanisms underlying the modification involved the enhancement of the specific surface area with IA and the exposure of hydrophilic groups or hydrophobic groups of the GLSs with KOH or HCl. The sustained 48-h molecule-release profiles of the MB- and RF-loaded GLS carriers were best fitted using a first-order kinetics model in simulated gastric (or intestinal) fluid compared with other models. In mice, the designed GLS carriers had high adhesion capacities onto the mucosa of the digestive tract and long retention times (120 h), and even promoted the secretion of mucus and expression of several key intestinal barrier proteins. This study provided a new method to modify GLSs into oral carriers with selective drug affinity, high loading capacity, sustained drug release, and high adhesion to the digestive tract.

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.

A review of Ganoderma lucidum polysaccharides: Health benefit, structure-activity relationship, modification, and nanoparticle encapsulation.

Ganoderma lucidum polysaccharides possess unique functional properties. Various processing technologies have been used to produce and modify G. lucidum polysaccharides to improve their yield and utilization. In this review, the structure and health benefits were summarized, and the factors that may affect the quality of G. lucidum polysaccharides were discussed, including the use of chemical modifications such as sulfation, carboxymethylation, and selenization. Those modifications improved the physicochemical characteristics and utilization of G. lucidum polysaccharides, and made them more stable that could be used as functional biomaterials to encapsulate active substances. Ultimate, G. lucidum polysaccharide-based nanoparticles were designed to deliver various functional ingredients to achieve better health-promoting effects. Overall, this review presents an in-depth summary of current modification strategies and offers new insights into the effective processing techniques to develop G. lucidum polysaccharide-rich functional foods or nutraceuticals.

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.

Neuroprotective, neurogenic, and anticholinergic evidence of Ganoderma lucidum cognitive effects: Crucial knowledge is still lacking.

Ganoderma lucidum is a mushroom that has been widely used for centuries in Asian countries for its antiaging properties. It is popularly known as "Ling Zhi," "Reishi," and "Youngzhi," and because of its benefits, it is known as the "immortality mushroom." Pharmacological assays have revealed that G. lucidum ameliorates cognitive impairments through inhibition of ß-amyloid and neurofibrillary tangle formation, antioxidant effect, reduction of inflammatory cytokine release and apoptosis, genic expression modulation, among other activities. Chemical investigations on G. lucidum have revealed the presence of metabolites such as triterpenes, which are the most explored in this field, as well as flavonoids, steroids, benzofurans, and alkaloids; in the literature, these have also been reported to have mnemonic activity. These properties of the mushroom make it a potential source of new drugs to prevent or reverse memory disorders, as actual medications are able to only alleviate some symptoms but are unable to stop the progress of cognitive impairments, with no impact on social, familiar, and personal relevance. In this review, we discuss the cognitive findings of G. lucidum reported in the literature, converging the proposed mechanisms through the several pathways that underlie memory and cognition processes. In addition, we highlight the gaps that deserve particular attention to support future studies.

Modeling and optimization of the protocol of complex chromatography separation of cyclooxygenase-2 inhibitors from Ganoderma lucidum spore.

INTRODUCTION: The spores of the medicinal fungus Ganoderma lucidum possess hepatoprotective properties. The main components, triterpenes, are particularly beneficial, making the screening and preparation of active triterpenes from Ganoderma lucidum significant. OBJECTIVES: We aimed to screen and verify cyclooxygenase-2 inhibitors from G. lucidum spores, establish a rapid online hyphenated technique for the preparation of active ingredients, and analyze the structures of the active ingredients. METHODS: Ultrafiltration LC combined with an enzyme inhibition assay and molecular docking was employed to screen and evaluate cyclooxygenase-2 ligands, which were prepared by pressurized liquid extraction coupled online with countercurrent chromatography and semi-preparative LC. The structures of the compounds were identified by nuclear magnetic resonance spectroscopy. RESULTS: Six cyclooxygenase-2 inhibitors, namely, ganoderic acids I, C2 , G, B, and A and ganoderenic acid A, were screened and evaluated. They were prepared using the online hyphenated technique, following which their structures were identified. CONCLUSION: This study provides opportunities for the discovery and development of new therapeutic drugs from other natural resources, as the present instrumental setup achieved efficient and systematic extraction and isolation of natural products compared with reference separation methods, thus exhibiting significant potential for industrial applications.

Determination on Tree Species Selection for Lingzhi or Reishi Medicinal Mushroom Ganoderma lucidum (Agaricomycetes) Cultivation by Fourier Transform Infrared and Two-Dimensional Infrared Correlation Spectroscopy.

As a wood-degrading Agaricomycetes mushroom, Ganoderma lucidum can be cultivated on broad-leaf hardwoods. Generally, producers care about the yield, but not the quality of G. lucidum cultivated by different tree species. In this study, five broad-leaf hardwood tree species-Quercus variabilis Bl. (Qv), Castanea mollissima Bl. (Cm), Liquidambar formosana Hance (Lf), Dalbergia hupeana Hance (Dh), and Platycarya strobilacea Sieb. et Zucc. (Ps)-were selected for cultivating of G. lucidum. The chemical compositions of G. lucidum fruiting bodies produced by these tree species were determined by Fourier transform infrared and two-dimensional infrared correlation spectroscopy in order to select the most suitable tree species for cultivation. The overall spectra showed less discrimination of each peak variation detected and properly kept most of the primary metabolites. The second derivative unfolded the stagnation of the first spectrum and more base peaks were detected especially in the range of the first two sections. The protein content contained in G. lucidum cultivated on Ps was 92%, like that on Dh. On the other hand, only 27% similarity was determined in G. lucidum cultivated on Ps and Qv. Therefore, the correlation of this range for the protein content can help in tree species selection. The active sequence of 2DIR spectral could be determined by the active bonding of the component reacted to the perturbation. The result could provide a scientific basis for the selection of tree species and the comprehensive utilization of broad-leaf tree resources on G. lucidum cultivation.

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.

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.

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.