Ganoderic acid is a class of lanostane-type triterpenoids found in Ganoderma species, and is one of the most important pharmacologically active components in G. lucidum, exhibiting antioxidant, anti-neuropsychiatric, anti-tumor, and immune-enhancing properties. The content of ganoderic acid in G. lucidum is very low, and the traditional extraction process is complex, yielding minimal amounts at high cost. The biosynthetic pathway of G. lucidum triterpenoids(GLTs), including the synthesis of different structural forms of ganoderic acid from lanosterol, as well as the molecular regulatory mechanisms involving key regulatory enzyme genes and their functions, are not yet fully understood. With the continuous development of synthetic biology technologies, there has been a deeper understanding of the biosynthesis and metabolic regulation pathways of ganoderic acid and its derivatives at the molecular level. Research has explored the key regulatory enzyme genes related to ganoderic acid biosynthesis and their functions. Moreover, through the optimization of synthetic biology and culture conditions, large-scale production and preparation of GLTs at the cellular level have been achieved. This paper reviews and analyzes the latest research progress on the biosynthesis pathways and metabolic regulation of GLTs, focusing on the configuration of ganoderic acid and its derivatives, the biosynthetic pathways, key enzyme genes, transcription factors related to ganoderic acid biosynthesis, signal transduction mechanisms, and factors affecting triterpenoid biotransformation. This review is expected to provide a theoretical basis and technical reference for improving the efficient production of triterpenoid pharmacological components and the exploitation and utilization of G. lucidum resources.
Triterpenes/chemistry* ; Reishi/chemistry* ; Biosynthetic Pathways ; Lanosterol

This research investigated the impact of Ganoderma lucidum polysaccharides(GLP) on hepatoblastoma HepG2 and Huh6 cell models, as well as KM mouse model with in situ transplanted tumors, so as to provide a theoretical basis for the clinical application of GLP. Cell viability was assessed through the CCK-8 assay, whereas cell proliferation was evaluated by using the BeyoClick~(TM)EdU-488 test. Cell apoptosis was visualized via Hochest 33258 staining, and autophagy was detected through Mrfp-GFP-LC3 dual fluorescence staining. An in situ tumor transplantation model was created by using HepG2 cells in mice, and mice were treated with normal saline and GLP of 100, 200, and 300 mg·kg~(-1) for tumor count calculation and size assessment. Hematoxylin-eosin(HE) staining was used to observe pathological changes in tumor tissue and vital organs(liver, kidney, lung, spleen, and heart). Western blot analysis was conducted to measure the protein expressions of tumor protein P53(P53), B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cleaved-caspase-3, Beclin-1, autophagy related protein-5(Atg-5), microtubule-associated protein-light chain-3Ⅰ(LC3Ⅰ)/LC3Ⅱ, autophagy adapter protein 62(P62), protein kinase B(Akt), p-Akt, mammalian target of rapamycin(mTOR), and p-mTOR. The in vitro experiment revealed that compared with the control group, after GLP treatment, tumor cell viability decreased significantly; apoptosis rate increased in a dose-dependent manner, and autophagic flux was inhibited. The in vivo experiments showed that compared with the model group, mice treated with GLP exhibited significantly fewer and smaller tumors. Western blot results showed that compared with the control group or model group, levels of P53, Bax, cleaved-caspase-3, Beclin-1, Atg-5, and LC3-Ⅱ/LC3-Ⅰ were significantly increased after GLP treatment, and the levels of Bcl-2, P62, p-Akt/Akt, and p-mTOR/mTOR were significantly decreased. These outcomes suggest that GLP promotes apoptosis and autophagy in hepatoblastoma cells by regulating the Akt/mTOR pathway.
Animals ; Humans ; Autophagy/drug effects* ; Reishi/chemistry* ; Mice ; Apoptosis/drug effects* ; TOR Serine-Threonine Kinases/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Liver Neoplasms/genetics* ; Hepatoblastoma/genetics* ; Polysaccharides/pharmacology* ; Cell Line, Tumor ; Signal Transduction/drug effects* ; Male ; Cell Proliferation/drug effects* ; Hep G2 Cells

Originating from sporoderm-broken Ganoderma lucidum spores, Ganoderma lucidum spore oil(GLSO) is prepared by supercritical fluid extraction. Chemical composition studies show that GLSO mainly contains nonpolar substances, such as fatty acids, triglycerides, and steroids. GLSO is also famous for its edible and medical functions. It possesses various pharmacological effects, including anti-tumor, immune boosting, anti-fatigue, antioxidant property, and organ protection. This paper systematically summarizes the chemical constituents and pharmacological effects of GLSO, aiming to provide a reference for its future research and application.
Reishi/chemistry* ; Spores, Fungal/chemistry* ; Humans ; Animals ; Oils/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification*

Eight previously undescribed lanostane triterpenoids, including five nortriterpenoids with 26 carbons, ganothenoids A-E (1-5), and three lanostanoids, ganothenoids F-H (6-8), along with 24 known ones (9-32), were isolated from the fruiting bodies of Ganodrma theaecolum. The structures of the novel compounds were elucidated using comprehensive spectroscopic methods, including electronic circular dichroism (ECD) and nuclear magnetic resonance (NMR) calculations. Compounds 1-32 were assessed for their neuroprotective effects against H₂O₂-induced damage in human neuroblastoma SH-SY5Y cells, as well as their inhibitory activities against protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase. Compound 4 demonstrated the most potent neuroprotective activity against H₂O₂-induced oxidative stress by suppressing G₀/G₁ phase cell cycle arrest, reducing reactive oxygen species (ROS) levels, and inhibiting cell apoptosis through modulation of B-cell lymphoma 2 protein (Bcl-2) and Bcl-2 associated X-protein (Bax) protein expression. Compounds 26, 12, and 28 exhibited PTP1B inhibitory activities with IC₅₀ values ranging from 13.92 to 56.94 μmol·L^-1, while compound 12 alone displayed significant inhibitory effects on α-glucosidase with an IC₅₀ value of 43.56 μmol·L^-1. Additionally, enzyme kinetic analyses and molecular docking simulations were conducted for compounds 26 and 12 with PTP1B and α-glucosidase, respectively.
Humans ; Fruiting Bodies, Fungal/chemistry* ; Triterpenes/isolation & purification* ; Neuroprotective Agents/isolation & purification* ; Protein Tyrosine Phosphatase, Non-Receptor Type 1/metabolism* ; Ganoderma/chemistry* ; Apoptosis/drug effects* ; Hypoglycemic Agents/isolation & purification* ; Molecular Structure ; alpha-Glucosidases/metabolism* ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Oxidative Stress/drug effects* ; Hydrogen Peroxide/toxicity* ; Molecular Docking Simulation

In the digital transformation of Chinese pharmaceutical industry, how to efficiently govern and analyze industrial data and excavate the valuable information contained therein to guide the production of drug products has always been a research hotspot and application difficulty. Generally, the Chinese pharmaceutical technique is relatively extensive, and the consistency of drug quality needs to be improved. To address this problem, we proposed an optimization method combining advanced calculation tools(e.g., Bayesian network, convolutional neural network, and Pareto multi-objective optimization algorithm) with lean six sigma tools(e.g., Shewhart control chart and process performance index) to dig deeply into historical industrial data and guide the continuous improvement of pharmaceutical processes. Further, we employed this strategy to optimize the manufacturing process of sporoderm-removal Ganoderma lucidum spore powder. After optimization, we preliminarily obtained the possible interval combination of critical parameters to ensure the P_(pk) values of the critical quality properties including moisture, fineness, crude polysaccharide, and total triterpenes of the sporoderm-removal G. lucidum spore powder to be no less than 1.33. The results indicate that the proposed strategy has an industrial application value.
Bayes Theorem ; Data Mining ; Drug Industry ; Powders ; Reishi ; Spores, Fungal

Aims: This study was designed to examine the enzyme activity of selected virulent isolates of Ganoderma boninense against oil palm. In a separate in vitro assessment, the effect of macronutrients on the mycelial growth of four selected Ganoderma spp. was also tested. Methodology and results: The study involved a comparison of ligninolytic enzymes; lignin peroxidase (LiP), manganese peroxidase (MnP) and laccase (Lac) profiling of eight isolates of G. boninense, categorized into three levels of aggressiveness, with two control isolates (G. boninense PER71 and G. tornatum NPG1) using solid-state fermentation (SSF). The Principal Component Analysis (PCA) revealed that the isolates had a significant production of ligninolytic enzymes on day 80. The most aggressive isolate, ET61 had the highest Lac production. As for the macronutrient test, mycelial growth for all the Ganoderma spp. was highly affected by potassium (K). Conclusion, significance and impact of study The findings of this study elucidated the characteristics of G. boninense in relation to enzyme production for the degradation of oil palm lignin and the identification of essential nutrients involved in the survival and growth of Ganoderma spp. The study provides vital information on the pathogenic characteristics of G. boninense isolates involved in biomass degradation along with the role of nutrient on the growth of Ganoderma spp. that may influence basal stem rot (BSR) management in the field.
Enzymes ; Ganoderma ; Palm Oil

Ganoderma lucidum is a mushroom widely used for its edible and medicinal properties. Primary bioactive constituents of G. lucidum are ganoderic triterpenoids (GTs), which exhibit important pharmacological activity. Abscisic acid (ABA), a plant hormone, is associated with plant growth, development, and stress responses. ABA can also affect the growth, metabolism, and physiological activities of different fungi and participates in the regulation of the tetracyclic triterpenes of some plants. Our findings indicated that ABA treatment promoted GT accumulation by regulating the gene expression levels (squalene synthase (sqs), 3-hydroxy-3-methylglutaryl-CoA reductase (hmgr), and lanosterol synthase (ls)), and also activated cytosolic Ca²⁺ channels. Furthermore, under ABA mediation, exogenous Ca²⁺ donors and inhibitors directly affected the cytosolic Ca²⁺ concentration and related gene expression in Ca²⁺ signaling. Our study also revealed that ABA-mediated cytosolic Ca²⁺ played a crucial regulatory role in GT biosynthesis, accompanied by antioxidant defense modulation with increasing superoxide dismutase (SOD) activity and ascorbate peroxidase (APX) activity, and the resistance ability of O₂^•- and glutathione (GSH) contents.
Reishi/metabolism* ; Triterpenes/metabolism* ; Abscisic Acid/metabolism* ; Antioxidants/metabolism*

Aims: The basal stem rot disease in oil palm is caused by the pathogenic Ganoderma boninense, which is infectious after mating and forming dikaryotic hyphae. This study was aimed to generate a mating-type biomarker for the detection of pathogenic Ganoderma species. Methodology and results: Mating-type region of Ganoderma was amplified using polymerase chain reaction (PCR) and primers flanking the mating-type region of other basidiomycetes. Amplified fragments were sequenced and were identified as the Ganoderma pheromone receptor gene of matB locus called the gprb2 gene. Using this biomarker, the pheromone receptor gene was detected in a total of 107 pathogenic Ganoderma spp. while the gene was not detected in the non-pathogenic Ganoderma lucidum. Phylogenetic tree analyses of the gene fragment encoding the partial amino acid sequence of gprb2 showed clades of close evolutionary relationship among the 107 pathogenic Ganoderma spp. Phylogenetic analyses using deduced amino acid sequences of the Ganoderma pheromone receptor b2 gene, gprb2 with homologous pheromone receptors of other basidiomycetous fungi revealed high conservation of this pheromone receptor within their respective taxonomy. Conclusion, significance and impact of study A potential mating-type biomarker was successfully identified that could detect pathogenic Ganoderma spp. The research findings will be helpful in oil palm screening to detect pathogenic Ganoderma spp. and gain further insight into the role of the mating-type loci of Ganoderma towards its pathogenesis in causing the basal stem rot disease of oil palm.
Genes, Mating Type, Fungal ; Ganoderma

This study aims to explore the molecular mechanism of Ganoderma against gastric cancer based on network pharmacology, molecular docking, and cell experiment. The active components and targets of Ganoderma were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and gastric cancer-related targets from GeneCards and Online Mendelian Inheritance in Man(OMIM). The protein-protein interaction(PPI) network of the common targets was constructed with STRING, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of the common genes based on Bioconductor and R language. The medicinal-disease-component-target network and medicinal-disease-component-target-pathway network were established by Cytoscape. Molecular docking was performed between β-sitosterol(the key component in Ganoderma) and the top 15 targets in the PPI network. Cell experiment was performed to verify the findings. A total of 14 active components and 28 targets of Ganoderma were retrieved, and the medicinal and the disease shared 25 targets, including caspase-3(CASP3), caspase-8(CASP8), caspase-9(CASP9), and B-cell lymphoma-2(BCL2). The common targets involved 72 signaling pathways and apoptosis and p53 signaling pathway may play a crucial role in the effect of Ganoderma against gastric cancer. β-sitosterol had strong binding activity to the top 15 targets in the PPI network. The in vitro cell experiment demonstrated that β-sitosterol inhibited gastric cancer AGS cell proliferation by inducing cell apoptosis and cell cycle arrest in the S phase, which might be related to the regulation of the p53 pathway. This study shows the multi-component, multi-target, and multi-pathway characteristics of Ganoderma against gastric cancer, which lays a scientific basis for further research on the molecular mechanism.
Ganoderma ; Humans ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Network Pharmacology ; Stomach Neoplasms/genetics*

Aims: The development of an effective biocontrol formulation for inhibition of Ganoderma boninense, a well-known destructive pathogen in oil palm plantation is important to prolong the palm’s lifespan and reduce the losses due to this disease. In this paper, we present some new bioformulations with combination of different types of biocontrol agents in managing basal stem rot (BSR) disease. Methodology: The effectiveness of the treatments designed as T1 (Trichoderma harzianum + Lecanicillium spp. + Streptomyces sundarbansensis + Pseudomonas aeruginosa), T2 (Penicillium simplicissimum + Lecanicillium sp. + S. sundarbansensis + P. aeruginosa), T3 (P. simplicissimum + P. aeruginosa) and T4 (LEStani®) was evaluated through treatment on the oil palm seedlings artificial infected by G. boninense and the results were expressed in disease severity index (DSI), bole severity index (BSI) and ergosterol content. Conclusion, significance and impact of study All tested treatments (T1-T4) managed to control the severity of the Ganoderma infection from continuously increasing when the treatments were applied either one month before or after artificial inoculation. The disease severity of infected seedlings without treatments had increased for almost 2-fold at the end of the trial. Moreover, T1 had the greatest inhibition of G. boninense with the lowest ergosterol content (a bioindicator of Ganoderma colonization) detected (676.67 g/mL), which is about 1.9-fold lower than control (1273.33 ug/mL) without treatments and a BSI score of 1. Based on the effectiveness among the four tested biocontrol formulations, T1 is the most promising formulation to be further evaluated in the field for control of BSR disease. However, more research is needed in the future to estimate the effective amount for application in open environment.
Palm Oil ; Biological Control Agents ; Ganoderma