Search Results (92)

The triterpenoid and polysaccharide constituents of Ganoderma lucidum (GL) are believed to influence key pathogenic pathways in Alzheimer’s disease (AD). This study first examined the molecular rationale for GL’s neuroprotective properties by subjecting its principal triterpenoids, Ganoderic Acid A&B, to computational profiling. Molecular docking was performed against human acetylcholinesterase (AChE), TNF-α, COX-2, IL-6, caspase-3, Bcl-2, and the Keap1–Nrf2 complex using CB-Dock2, alongside SwissADME-based physicochemical and ProTox-3.0-based toxicological screening. These targeted pathways were then biologically validated in an in vitro AD model induced by Aβ_1–42 toxicity in SH-SY5Y cells, assessing AChE activity, apoptosis, ROS levels, mitochondrial membrane potential (MMP), and cytokine expression (COX-2, TGF-β1, IL-6, TNF-α, IL-10). Docking revealed high binding affinities of both triterpenoids toward all seven targets (Vina scores: −7.3 to −10.4 kcal/mol), predicting strong modulation of cholinergic, inflammatory, apoptotic, and antioxidant pathways. Consistent with these predictions, GL extract significantly reduced TNF-α, COX-2, and IL-6 mRNA and protein levels, attenuated ROS accumulation, preserved MMP except at 500 µg/mL, and exerted a concentration-dependent antiapoptotic effect. IL-10 and TGF-β1 showed complex, dose-dependent patterns, reflecting indirect regulatory responses. Together, these findings support GL’s neuroprotective potential against Aβ-induced toxicity through direct engagement of cholinergic, inflammatory, apoptotic, and antioxidant regulatory proteins. Full article

Oxidative stress drives skin aging, barrier impairment, and inflammatory amplification, making dietary antioxidants potential systemic contributors to cutaneous redox homeostasis. Edible fungi are distinctive sources of redox-active metabolites, particularly ergothioneine, a stable sulfur-containing antioxidant whose cellular uptake is mediated by the ergothioneine transporter OCTN1 (SLC22A4). This review evaluates ergothioneine, polysaccharides and β-glucans, cordycepin, phenolics, and Ganoderma triterpenoids as processing-sensitive dietary bioactives with redox relevance rather than topical cosmetic ingredients. We examine how cultivation, drying, cooking, extraction, fermentation, and microbial biomanufacturing determine antioxidant formation, retention, oral bioaccessibility, and dose realism, and how antioxidant response, inflammatory, mitochondrial, and gut microbiota-mediated pathways connect intake to skin endpoints. The strongest oral evidence concerns biomarker-linked ergothioneine-rich Pleurotus. Smaller Flammulina velutipes and Sparassis crispa trials report hydration or transepidermal water loss signals without comparable exposure biomarkers, whereas purified ergothioneine provides provisional non-mushroom food evidence. Compared with better-established oral ingredients, edible fungi offer distinctive food technology advantages but a narrower human evidence base. Priorities include processing-aware quality and safety markers, contaminant control, standardized digestion models, dose-realistic exposure estimates, and biomarker-anchored randomized human trials. Full article

Ganoderma lucidum is a medicinal mushroom widely recognized as a source of bioactive metabolites, particularly triterpenoids. Although most studies have focused on fruiting bodies and spores, the potential of cultured mycelial biomass as a source of functional secondary metabolites remains less explored. In this study, we isolated and characterized polycarpol from the mycelia of G. lucidum and evaluated its anti-melanogenic activity in B16F10 murine melanoma cells. Dried mycelia obtained after liquid culture were extracted with 70% ethanol, partitioned with ethyl acetate, and purified by repeated chromatographic separation. The isolated compound was identified as polycarpol by LC–ESI–MS, HR-MS/MS, and NMR spectroscopy, together with comparison with previously reported spectroscopic data. The anti-melanogenic activity of polycarpol was evaluated in α-MSH-stimulated B16F10 murine melanoma cells, a commonly used cellular model of melanogenesis. Polycarpol reduced α-melanocyte-stimulating hormone-induced cellular tyrosinase activity and melanin production at concentrations that did not markedly affect cell viability. Notably, 2 μg/mL (4.54 μM) polycarpol showed a melanin-inhibitory effect comparable to that of arbutin. Western blot analysis showed that polycarpol decreased the expression of microphthalmia-associated transcription factor, tyrosinase, and tyrosinase-related protein-1. In addition, polycarpol suppressed CREB phosphorylation and modulated the MAPK signaling pathways. These findings suggest that polycarpol inhibits melanogenesis through regulation of MITF-associated melanogenic signaling. Overall, this study demonstrates that cultured G. lucidum mycelia can produce anti-melanogenic triterpenoids and highlights cultured mycelial biomass as a controllable fungal material for exploring anti-melanogenic triterpenoids, although further optimization is required to improve production efficiency. Full article

Medicinal fungi are important sources of natural medicines and are rich in a wide range of secondary metabolites with significant bioactivities, including terpenoids and alkaloids. As one of the core tools of systems biology, metabolomics has developed from simple metabolite detection into a key approach for understanding the complex life processes and medicinal value of medicinal fungi. This review summarizes recent advances in the application of metabolomics to the discovery of bioactive compounds from medicinal fungi, the optimization of cultivation and extraction processes, the analysis of pharmacological mechanisms, and the improvement of drug delivery strategies. The main methods used in metabolomics are outlined, with emphasis on the key steps of sample preparation, data acquisition, and data analysis. The review then describes how metabolomics can be used for the rapid discovery of bioactive compounds in medicinal fungi. It further explains how metabolomics can guide the precise optimization of fermentation parameters and the improvement of extraction processes by revealing the effects of environmental factors, such as light, temperature, pH, and inducers, as well as different extraction methods, on metabolic networks. In addition, this review summarizes the role of metabolomics in clarifying the molecular mechanisms by which bioactive compounds exert pharmacological effects through the modulation of specific metabolic pathways, as well as its application in optimizing dose, formulation, and route of administration. Representative studies have demonstrated that integrated metabolomic and proteomic analyses have revealed the preferential accumulation of triterpenoids, sterols, and polyphenolic compounds during the budding stage of Ganoderma lucidum. Finally, future studies should integrate metabolomics with genomics, transcriptomics, proteomics, and other omics approaches to link bioactive metabolites with their biosynthetic genes, regulatory networks, and molecular targets. In such an integrated framework, metabolomics can serve as a phenotype-oriented core for the discovery and functional characterization of therapeutic metabolites from medicinal fungi, although further experimental and clinical validation remains essential. Full article

Prior studies on Ganoderma lucidum spore oil (GLSO) rarely systematically explored its storage oxidative deterioration mechanism via multi-marker combined characterization. This study innovatively integrated the Schaal oven accelerated storage test and dual-NMR detection (LF-NMR and ¹H NMR) to evaluate the oxidative stability of GLSO over 60 d. Dynamic changes in routine oxidation indices, glycerol core aldehydes (GCAs), phytosterols and their triterpenoid biosynthetic precursors, fatty acids and volatile compounds were synchronously tracked. Results revealed complex fluctuating accumulation of primary and secondary oxidation products; non-volatile GCAs exhibited continuous monotonic growth and acted as reliable markers for severe GLSO oxidation. Unsaturated fatty acids and phytosterols and their triterpenoid biosynthetic precursors degraded in a structure-dependent pattern, with phytosterols and their triterpenoid biosynthetic precursors degradation sensitivity ranked as squalene > lanosterol > β-sitosterol. Correlation analysis clarified the intrinsic linkage between fatty acid substrates and oxidation derivatives. This work innovatively reveals the complete lipid oxidation pathway of GLSO, offering novel theoretical references and multi-index evaluation strategies for quality control and preservation of high-grade GLSO products. Full article

Background/Objectives: For over two millennia, Ganoderma lucidum has served as a traditional remedy, yet its translation into evidence-based therapy remains stymied by a persistent obstacle. Potent in vitro activities consistently fail to translate in vivo, a shortfall rooted in the poor systemic bioavailability of its signature triterpenoids and polysaccharides. We contend that the defining hurdle is no longer compound discovery but whether emerging formulation technologies genuinely overcome these barriers or merely sidestep them in ways that obscure the underlying physiology. Methods: We construct a structure–activity–formulation (SAF) prioritization framework. We critically survey a broad spectrum of delivery platforms—including lipid-based, polymeric, micellar, tellurium nanorod, and G. lucidum-derived vesicular systems—against their demonstrated capacity to improve oral exposure. Clinical assessments and regulatory considerations are integrated to anchor the analysis in translational reality. Results: Bioavailability has been systematically treated as a post hoc variable, even though the very structural features conferring bioactivity impose the steepest systemic barriers. To date, no G. lucidum nanoformulation has advanced to human trials, and the regulatory terrain for these complex natural-product nanomedicines remains uncharted. We distill three experimentally tractable propositions—testing lipid-mediated absorption, triple-helix conformational dependency, and co-delivery synergy—that offer discrete entry points for rigorous investigation. Conclusions: We argue that the field must pivot decisively from descriptive cataloging to hypothesis-driven, comparative investigation, anchored by reference-material standardization and proactive regulatory dialogue. Confronting the bioavailability bottleneck as a primary design parameter—rather than an ancillary nuisance—represents the most credible route from historical remedy to evidence-based therapeutic. Full article

Ganoderic acids (GAs) are bioactive lanostane-type triterpenoids produced by Ganoderma lucidum that accumulate predominantly in fruiting bodies, whose long cultivation period limits their practical production. Using Global Natural Products Social Molecular Networking (GNPS), we identified G. lucidum TM701, which accumulated 99 GA derivatives in mycelia and exhibited higher triterpenoid levels and greater chemical diversity than the commercial strain BCRC 36203. Four abundant GAs (GA-Mb/Mc, GA-S/Mf, GA-T, and GA-R) were selected as marker compounds for monitoring GA production. A modified two-stage cultivation strategy, combining submerged inoculum preparation with nutrient optimization during static cultivation, increased GA production to 1396 mg L⁻¹ GAs in potato dextrose broth supplemented with 2% glucose. Heat treatment revealed interconversion among GA-Mb/Mc, GA-Mh, and GA-P/Q, indicating a dehydration-driven stabilization of conjugated diene structures. G. lucidum TM701 mycelia not only provide a platform for triterpenoid production, but also serve as a promising model for elucidating GA biosynthesis and investigating their thermal transformation. Full article

Ganoderma leucocontextum, a fungus discovered by our group, is highly valued for its immune modulation and anti-tumor polysaccharides significantly. Thus, this research aims to select a substrate formulation to enhance its polysaccharides and reveal the underlying mechanism. Seven distinct substrate formulations, incorporating combinations of fruit-tree wood, bagasse, oak wood, and cottonseed hulls, were explored. Interesting, the fruiting bodies grown on GMTZ fruit-tree wood–bagasse formulation showed the highest polysaccharide content at 3.19 ± 0.56% (p < 0.01 or 0.05). Moreover, GMTZ efficiently channeled resources toward diterpenoids synthesis at the expense of flavonoid and most triterpenoid production. It also dramatically enhanced androgen synthesis, while showing no corresponding accumulation of storage lipids or certain hormone signals, reinforcing a specific metabolic commitment. Furthermore, PCA analysis of the metabolomics confirmed the profound impact of substrate formulations. Correlation analysis revealed that GMTZ promoted a growth-and-synthesis metabolic phenotype, which was characterized by metabolic signatures of supporting anabolism and cellular homeostasis. In contrast, formulations that induced the defense-and-stress phenotype were often rich in lignin, which diverted resources toward detoxification and stress responses and suppressed growth-oriented metabolite synthesis. Moreover, prostaglandin A1, deoxycholic acid, cucurbitacin E, and 1-hydroxy-2-naphthoic acid were found to be positively correlated with polysaccharide synthesis. In addition, networks for polysaccharide biosynthesis were mapped and it was proposed, accordingly, that prostaglandin A1-phosphoglucomutase may be a mechanism by which GMTZ enhances polysaccharides. This research provided a substrate formulation for elevating polysaccharides in G. leucocontextum. Full article

To address the lack of a comprehensive quality control system for Ganoderma lucidum, we developed an integrated evaluation strategy across four varieties and three growth stages. This system integrates the targeted screening of anti-benign prostatic hyperplasia (BPH) triterpenoids acting on 5α-reductase type 2 (SRD5A2) with a chemical consistency assessment utilizing systematic quantitative fingerprint method (SQFM) and chemometrics. UPLC-Q-TOF-MS/MS identified 85 triterpenoids in the samples. An orthogonal partial least squares (OPLS) regression was utilized to screen seven chromatographic peaks that positively correlated with SRD5A2 inhibitory activity. Three principal bioactives were structurally identified as ganoderic acids DM and B, and ganoderenic acid A, which demonstrated significant in vitro SRD5A2 inhibition rates of 61.16 ± 1.87%, 36.41 ± 1.10%, and 41.82 ± 2.09%, respectively. Molecular dynamics simulations and averaged weak interaction analysis revealed that these compounds exert potent enzyme inhibition via hydrogen bonds and hydrophobic interactions with distinct SRD5A2 amino acid residues. The SQFM-chemometrics quality system confirmed ten samples reached Grade 6 or above, identifying the H3 variety at the initial stage as possessing the highest active ingredient content and optimal overall quality. This integrated framework enables rapid bioactive discovery and robust standardization for G. lucidum-based functional foods, thereby facilitating their industrial development. Full article

Colitis is a global health challenge that severely impairs quality of life, necessitating effective dietary interventions. This study investigated the protective effects of Ganoderma lucidum triterpenoids (GLTs) on pathological symptoms, inflammatory responses, and gut microbiota dysbiosis in a dextran sulfate sodium (DSS)-induced murine model. Our results demonstrated that GLT intervention significantly attenuated the disease activity index (DAI), prevented colon shortening, and fortified gut barrier integrity through upregulating the transcription of tight junction proteins. GLT inhibited the secretion of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and bolstered antioxidant defenses (CAT) by controlling the TLR4/NF-κB pathway and upregulating the Nrf2 pathway. Furthermore, 16S rRNA sequencing and non-targeted metabolomics revealed that GLT reshaped the gut microbial landscape (enriching Enterorhabdus and Lachnospiraceae NK4A136 group) and reconfigured amino acid metabolism to restore colonic homeostasis. Collectively, these findings highlight the potential of GLT as a functional food ingredient to prevent colitis, potentially linked to the modulation of the microbiota–metabolite–immune interplay, offering a novel nutritional strategy for inflammatory bowel disease management. Full article

Medicinal mushrooms have become an important component of modern dietary supplementation and functional nutrition due to their diverse biological activities and long-standing use in traditional medicine. Among the most widely studied and utilized species are Ganoderma lucidum, Lentinula edodes, Grifola frondosa, Cordyceps militaris, Cordyceps sinensis, Trametes versicolor, and Inonotus obliquus. Their therapeutic potential is associated with a wide range of biologically active constituents, including polysaccharides, triterpenoids, phenolic compounds, and other secondary metabolites. Experimental and clinical studies indicate that extracts derived from these species may support immune function, modulate inflammatory responses, and exhibit antioxidant, antimicrobial, and anticancer properties. In addition to extensive in vitro and in vivo investigations, a growing number of clinical studies have evaluated the safety and potential therapeutic benefits of medicinal mushroom preparations in humans. In recent years, increasing attention has been directed toward their incorporation into nutraceutical formulations and functional foods aimed at supporting health and preventing chronic diseases. Advances in cultivation technologies and extraction methods have also contributed to improved availability and standardization of mushroom-derived products. This review provides a comprehensive overview of selected medicinal mushroom species commonly used in dietary supplements, focusing on their bioactive constituents, reported biological activities, and potential applications in contemporary medicine. Full article

Type 2 diabetes mellitus (T2DM) is a major global health challenge that has intensified interest in multi-target nutraceuticals with potential adjunctive benefits. Ganoderma lucidum (Lingzhi/Reishi) is a medicinal mushroom traditionally used in East Asia and is increasingly investigated for its role in glycemic regulation and metabolic disturbances. This review critically synthesizes current evidence on its hypoglycemic effects, focusing on bioactive compounds, molecular mechanisms, and translational limitations. Unlike broader reviews on Ganoderma bioactivity and health-related benefits, this review specifically evaluates the alignment between taxonomic authentication, chemical standardization, preclinical mechanisms, and human clinical evidence in the context of glycemic regulation. This narrative review was based on a targeted literature search conducted in PubMed/MEDLINE, Web of Science, and Scopus for studies published up to October 2025, supplemented by Google Scholar. The included studies comprised in vitro experiments, in vivo animal models, and human clinical trials evaluating glycemic and metabolic outcomes of Ganoderma preparations. In vitro and animal studies indicate that polysaccharides, including β-(1→3)/(1→6)-glucans and proteoglycans such as FYGL, may improve insulin sensitivity via AMPK (AMP-activated protein kinase) and PI3K/Akt pathways, promote GLUT4 (glucose transporter type 4) translocation, suppress hepatic gluconeogenesis, protect pancreatic β-cells, and modulate gut microbiota. In enzyme assays and preclinical models, lanostane-type triterpenoids act primarily by inhibiting α-glucosidase and α-amylase, thereby potentially reducing postprandial glucose excursions. Despite consistent preclinical evidence, clinical findings remain heterogeneous, with the largest randomized controlled trial reporting no significant glycemic benefit. Overall, Ganoderma lucidum shows strong mechanistic plausibility but insufficient clinical evidence for antidiabetic efficacy. Future research should prioritize species authentication, chemical standardization, and adequately powered clinical trials. Full article

Ganoderma lucidum is a medicinal fungus widely utilized in traditional medicine and functional foods. Its primary bioactive constituents are ganoderic acids (GAs), a group of triterpenoid compounds. While chemical-induced apoptosis has previously been shown to enhance GAs production, this study investigates the role of physical stress in this regulatory pathway. We demonstrate that heat-induced apoptosis significantly increases GAs production in G. lucidum. To determine whether apoptosis directly regulates this process, we overexpressed the human anti-apoptotic gene Bcl-2 in G. lucidum, confirming expression via RT-PCR and Western blot analysis. Upon heat-induced apoptosis, these Bcl-2 overexpression mutants exhibited increased mycelial cell viability, accompanied by reduced metacaspase activity and, notably, decreased GAs production. Furthermore, we identified a Type I metacaspase gene in G. lucidum, Glmca1, which contains highly conserved catalytic domains common across fungal species. Silencing of Glmca1 followed by heat-induced apoptosis led to results similar to Bcl-2 overexpression: enhanced cell viability, suppressed metacaspase activity, and a significant reduction in GAs yield. These findings provide compelling evidence that apoptosis functions as a critical regulatory mechanism for secondary metabolite production in G. lucidum. Consequently, modulating apoptotic pathways through physical induction offers a promising strategy for enhancing the production of bioactive ingredients in medicinal fungi. Full article

The liver is a critical organ in drug metabolism and detoxification. Ganoderma lingzhi triterpenoids, a major class of bioactive compounds in G. lingzhi extracts, exhibit liver protective effects with pharmaceutical potential. In this study, we established an acute liver injury model in mice via intraperitoneal injection of 0.25% Carbon tetrachloride(CCl₄) olive oil. Prophylactic and therapeutic administration of G. lingzhi triterpenoid extracts were evaluated using alanine aminotransferase (ALT), aspartate aminotransferase (AST), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and hepatic histopathology. Western blot analysis assessed protein expression of anti-inflammatory and antioxidant stress-related pathways (Nrf2/Keap1 and MyD88/NF-κB-p65). Intervention effects on acute liver injury were determined by measuring protein molecular weight following triterpenoid treatment. In summary, G. lingzhi triterpenoids significantly alleviate oxidative stress and inflammatory responses in mice with acute liver injury by activating the KEAP1-Nrf2 antioxidant pathway and inhibiting the NF-κB-p65 and MyD88-mediated inflammatory pathways. These triterpenoids reduced serum transaminase levels, improved hepatic histopathological damage, and exerted effective protective effect on liver tissue. This study provides experimental support for the comprehensive evaluation of G. lingzhi’s anti-inflammatory and antioxidant effects. Full article

Ganoderma lucidum spore powder is widely recognized as a high-grade Ganoderma product and is extensively consumed as a functional food and dietary supplement in China. To compare quality differences, nine batches of sporoderm-broken G. lucidum spore powders (DX, SD, FJ, JL, XZ, LQ, AH, LN, and GZ) were collected from representative producing regions across China. Their physicochemical properties, antioxidant activities, and enzyme inhibition capacities were analyzed in this work. The results revealed varying degrees of differences in color, chemical composition, antioxidant activity, and metabolic enzyme inhibitory effects among the samples. Notably, sample GZ contained the highest levels of total sugar, polysaccharides, lipids, protein, total phenolics, and total triterpenoids; sample XZ had the highest ergosterol content; and sample LN exhibited the highest levels of reducing sugar and nucleosides. GZ demonstrated the strongest radical scavenging activity, ferric-reducing antioxidant power (FRAP), cupric ion-reducing capacity, and inhibitory effects against α-glucosidase, α-amylase, lipase, acetylcholinesterase, and xanthine oxidase. Sample AH showed the greatest Fe²⁺-chelating capacity. Principal component analysis indicated that GZ, AH, and LN exhibited stronger antioxidant and metabolic enzyme inhibition activities, whereas LQ and FJ showed lower activities. These findings confirm significant quality differences among G. lucidum spore powders sourced from different geographical regions. Full article