Search Results (162)

Agricultural by-products are increasingly recognized as sustainable resources for mushroom cultivation and biomass valorization. This study evaluated pineapple stubble and coffee pulp as functional substrate supplements for Cordyceps militaris cultivation. Fruiting bodies were successfully produced on brown rice substrates supplemented with 5–15% pineapple stubble or coffee pulp, either alone or in combination. Substrate composition markedly influenced fungal morphology, biological efficiency (BE), and cordycepin production. Moderate supplementation improved cultivation performance, whereas excessive supplementation reduced BE. Cordycepin accumulation was generally higher in the substrate than in the fruiting bodies. The highest cordycepin content was observed in the substrate supplemented with 15% coffee pulp, reaching 3.93%, approximately twofold higher than that of the brown rice control. Correlation analysis revealed that carbon content and the carbon-to-nitrogen (C/N) ratio were positively associated with BE, while nitrogen content was positively correlated with cordycepin accumulation in the substrate. In addition, coffee pulp extract exhibited notable adenosine deaminase inhibitory activity, suggesting that substrate-derived bioactive compounds may contribute to enhanced cordycepin accumulation during cultivation. After cultivation, the spent mushroom substrate showed reduced C/N ratios and increased nitrogen content, indicating active fungal metabolism-mediated substrate transformation. These findings demonstrate that coffee and pineapple by-products can serve as sustainable supplements to improve cordycepin production in C. militaris. Furthermore, the resulting spent substrate, enriched in nitrogen and bioactive compounds, may represent a valuable secondary resource for agricultural and industrial applications. Full article

Background/Objectives: Exposure to particulate matter (PM) containing bacterial endotoxins triggers inflammation and oxidative stress in the respiratory epithelium. In this study, we investigated chitosan nanoparticle-loaded Cordyceps militaris grown on germinated Rhynchosia nulubilis (GCN) as a potential functional food-derived ingredient against PM- and lipopolysaccharide (LPS)-induced cellular damage in human lung epithelial cells. Methods: This study employed an integrative approach combining GCN analysis with bioinformatics methods using a PM- and LPS-induced pulmonary cellular inflammation model. Gene Expression Omnibus (GEO) transcriptomic datasets and Cytoscape-based network analysis were utilized to identify key hub genes and signaling pathways associated with PM- and LPS-induced pulmonary inflammation, which were subsequently validated by RT-PCR and Western blotting. Results: Nano-encapsulation significantly improved the antioxidant capacity and storage stability of the extract compared with non-encapsulated Cordyceps militaris grown on germinated Rhynchosia nulubilis (GRC). GCN markedly attenuated PM- and LPS-induced cytotoxicity and intracellular reactive oxygen species (ROS) production in a dose-dependent manner, resulting in a therapeutic index approximately 4.5-fold higher than that of GRC under PM and LPS co-exposure. Bioinformatics analysis identified inflammation-related genes and pathways associated with PM- and LPS-induced pulmonary responses, primarily enriched in tumor necrosis factor (TNF)-related inflammatory pathways, Toll-like receptor signaling, and cytokine signaling. Consistent with these findings, GCN suppressed the expression of C-X-C motif chemokine ligand 2 (CXCL-2) and tumor necrosis factor-alpha (TNF-α) mRNA and inhibited mitogen-activated protein kinase (MAPK)-mediated activator protein-1 (AP-1) and nuclear factor-kappa B (NF-κB) signaling pathways in human type II alveolar epithelial cells (A549). Conclusions: Collectively, nano-encapsulation enhanced the stability and bioactivity of Cordyceps militaris-based extracts, suggesting that GCN may have potential as a functional food-derived candidate ingredient to protect airway epithelial cells against inflammation and oxidative stress induced by PM and LPS. As this study was conducted using an in vitro A549 epithelial cell model, further validation in physiologically relevant systems is needed to confirm its translational applicability. Full article

Cordyceps militaris is a high-value medicinal mushroom with growing demand in functional-food and nutraceutical markets, yet practical frameworks for small-scale, family-operated cultivation remain limited. This study presents an integrated technical and economic feasibility analysis of small-scale Cordyceps production under two scenarios: a one-room setup (Scenario 1) and a two-room configuration with a shared processing area and staggered scheduling (Scenario 2). Both use consistent biological, operational, and market assumptions with no hired labor, and the analysis covers capital expenditure (CapEx), operating costs (OpEx), profitability, payback, and break-even thresholds, complemented by sensitivity analysis of parameters such as biological efficiency and contamination rates. Both scenarios were technically and financially viable. Scenario 1 achieved a net present value (NPV) of $1761, an internal rate of return (IRR) of 10%, a 4.7-year discounted payback, and a 133% five-year return on investment (ROI); Scenario 2 attained an NPV of $85,437, a 66% IRR, a 1.6-year payback, and a 366% ROI. Because gross margins were consistent across scales, the expansion’s advantage stemmed from more efficient CapEx amortization rather than improved unit profitability. Cordyceps cultivation emerges as a viable family-operated, small-scale enterprise that can diversify family income, generate supplementary or primary earnings, and support urban and rural livelihoods. Full article

Cordyceps militaris, a medicinal and edible mushroom, is renowned for its bioactive constituents and health-promoting effects. This study investigated the effects of vacuum freeze drying (VF), vacuum drying (VD), oven drying (OV), and sun drying (SU) on the metabolite profiles and antioxidant activities of C. militaris. VF showed the highest levels of total phenolics, total carotenoids, cordycepin, and N⁶-(2-hydroxyethyl)-adenosine, whereas VD better preserved total flavonoids. VF- and VD-treated samples also exhibited stronger antioxidant capacities than those processed by OV and SU in 1,1-diphenyl-2-picrylhydrazyl radical (DPPH•), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS^•+), hydroxyl radical (•OH), and ferric reducing antioxidant power (FRAP) assays. Metabolomics analysis identified 193 significantly altered metabolites after drying treatments. VF, VD, and SU increased carbohydrates, vitamins, and phenolic acids, while leading to reductions in amino acids, nucleotides, and fatty acids. KEGG analysis revealed that drying significantly affected pathways related to purine and pyrimidine metabolism, amino acid biosynthesis, and phenylpropanoid biosynthesis. Network pharmacology further identified 8 key compounds potentially associated with antioxidant effects through interactions with 37 core targets. These findings highlight the importance of selecting appropriate drying methods to preserve the bioactive compounds and functional quality of C. militaris. Full article

Cordyceps militaris is a well-known edible and medicinal entomopathogenic fungus that can be cultivated using silkworm larvae as hosts. However, no reports have been found regarding the gut microbiota of silkworms (Bombyx mori) following C. militaris injection. Based on three biological replicates, illumina 16S rRNA gene sequencing was used to investigate the changes over time in the gut bacteria and fungi of silkworms injected with C. militaris. The results indicated that following inoculation with C. militaris, the abundance of Bacillales and Basidiomycetes increased, while that of Pseudomonadales and Ascomycetes decreased. The abundance of Mammaliicoccus increased by 78% and 26% in dying silkworms compared to their pre-inoculated counterparts and blank control group, respectively. The relative abundance of Rhodotorula in dying silkworms was 2.89-fold and 80.51-fold higher than that in the pre-inoculation group and blank control group, respectively. After inoculation with C. militaris, fungi showed the greatest community variations at day 2, while bacteria displayed the most distinct differences at day 4. Under C. militaris infection, the abundance of all four pathways of Genetic Information Processing in silkworm larvae’s gut microbiota significantly increased. Taken together, the results demonstrate that inoculation with C. militaris induced significant alterations in the composition, structure, assembly, and predictive functional profiles of gut bacteria and fungi in silkworms. This study provides a theoretical basis for exploring the production of C. militaris using silkworm larvae as insect hosts. 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

Morphological control in submerged fermentation is a well-established method for enhancing bioactive metabolite production in filamentous fungi. However, the molecular mechanisms linking morphology to fermentation efficiency remain insufficiently understood. In this study, supplementing 1.5% Tween 80 (P80) at the seed culture stage of Cordyceps militaris consistently induced the formation of compact, uniform mycelial pellets. This morphological induction at the seed stage enhanced fermentation performance, increasing exopolysaccharide (EPS) titer by 71.1% and reducing the production cycle by 24 h. Transcriptomic analysis revealed that pelletized cultures exhibited transcriptional patterns associated with MAPK signaling related to cell wall integrity and upregulation of genes involved in cell wall remodeling. Additionally, pelletized cultures displayed a reduced oxidative burden and were associated with enhanced antioxidant capacity. These findings link morphology induction to cell wall remodeling and oxidative stress defense, offering a potentially scalable strategy for industrial polysaccharide production in medicinal fungi. Full article

Background: Probiotics and medicine food homology are known to offer gentle approaches to prevent obesity, although it is difficult with such approaches to satisfy consumers’ requirements to lose weight quickly. The probiotic strain Bifidobacterium animalis ssp. lactis 420 (B420) and Cordyceps militaris synergistically prevented obesity and related disorders in high-fat diet (HFD)-fed mice. Methods: The synergistic effects correlated with improved gut integrity, diminished systemic inflammation, and enhanced glucose homeostasis. Gut microbiota analysis revealed that the bloom of the commensal Akkermansia muciniphila contributed to the synergistic effects by inducing a profound shift in HFD-induced gut microbiota disorder. Results: The bloom of A. muciniphila was significantly correlated with a boost in mucin 2 within the colon, achieved through increased goblet cell quantity and elevated mucin 2 expression. To reveal the collaborating pathway, we found that Cordyceps militaris did not promote the propagation of B420 in vitro or in vivo. Moreover, heat-killed B420 could not enhance the preventive efficacy of Cordyceps militaris against obesity caused by the HFD. Conclusions: The metabolites of live B420 and Cordyceps militaris-derived metabolites in the gut microbiota collaboratively promoted the production of mucin 2. Thus, our results reveal a mechanism by which a combination of probiotics and medicine food homology enhance their therapeutic effects against obesity. Full article

The growth–specialized metabolism trade-off limits fungal natural product production. Here, we investigated cordycepin overproduction in Cordyceps militaris high-yield GYS60 and low-yield GYS80 via comparative proteomics, Post-Translational Modification (PTM) mapping, and metabolomics. We identified an acetyl-CoA-gated checkpoint centered on O-methyltransferase CCM_06472, whose activity is modulated by Lys123 acetylation and Ser34 phosphorylation in a manner consistent with activation and inhibition. GYS60 hyperactivates the tricarboxylic acid (TCA) cycle and β-oxidation to generate a 4.1-fold acetyl-CoA surplus, 62% of which is channeled into cordycepin synthesis. A single K123Q acetylation-mimetic mutation boosted cordycepin titers by >4-fold in wild-type strains. This acetyl-CoA checkpoint reveals PTM-gated flux allocation as a key regulatory mechanism, providing a minimal-intervention strategy for engineering fungal cell factories. Full article

Background/Objectives: The medical mushroom Ophiocordyceps sinensis (Caterpillar Fungus), known for its ability to enhance “vitality,” is one of the most popular medicines in Asian traditional medical systems. According to the Chinese Pharmacopeia, O. sinensis is standardized for its adenosine content, the precursor of ATP, which mediates numerous physiological and pathological processes in many diseases. The related fungus of order Hypocreales, Cordyceps militaris, and its major bioactive constituents, 3′-deoxyadenosine (cordycepin), also exhibit pleiotropic biological activities. This review aims to provide a rationale for the adaptogenic and resilience-supporting effects of these medicinal fungi and to align food and drug regulation in Western countries. Methods: In this narrative review, we integrated results from chemical, pharmacokinetic, network pharmacology, preclinical, and clinical studies of O. sinensis, C. militaris, and cordycepin using network pharmacology and bioinformatics tools. Results: Across studies, recurrent mechanistic hubs included PI3K–Akt, AMPK–mTOR, MAPK, NF-κB, apoptosis, and adaptive stress-response signaling pathways, linking immune regulation and metabolic homeostasis. Experimental studies confirmed modulation of cytokine production, kinase signaling, and mitochondrial regulators. Clinical meta-analyses demonstrate consistent adjunctive benefits in renal and pulmonary disorders, although heterogeneity in preparation and methodological limitations remains significant. The review reveals controversy regarding the bioavailability of cordycepin in vivo and its concentration in vitro studies, raising the hypothesis that cordycepin may act as a driver, triggering the organism’s adaptive stress response in stress-induced and aging-related diseases. Pharmacokinetic data indicate that systemic cordycepin concentrations after oral administration remain in the nanomolar range, suggesting that some predicted molecular interactions may occur indirectly or through systems-level mechanisms. The review, for the first time, suggests establishing a regulatory category for resilience-supporting physiological modulators to align food and drug regulation in the EU with contemporary systems biology, thereby complementing the work of EFSA, EMA, FDA, and Asian authorities. Conclusions:O. sinensis, C. militaris, and 3-deoxyadenosine share a common adaptogenic mechanism for maintaining homeostasis of cellular and integrated biological system functions. The systems-level network analysis and reductionistic molecular ligand preceptor pharmacology provide complementary approaches for understanding the multi-target bioactivity of these fungi. This review clarifies conceptual and regulatory barriers to recognizing resilience-supporting interventions and informs future regulatory innovation. Full article

WIB-801CE, a standardized Cordyceps militaris extract containing 7.0% cordycepin, suppresses platelet activation induced by thrombin, collagen, and adenosine diphosphate (ADP). As these agonists generate thromboxane A₂ (TXA₂), which amplifies platelet activation via a self-propagating feedback loop, blockade of TXA₂-mediated signaling offers strong antithrombotic potential. TXA₂-antagonistic effects were evaluated using U46619, a stable TXA₂ analog. Platelet activation was assessed by fibrinogen binding to integrin αIIbβ₃, aggregation, and phosphorylation of platelet-activating proteins—PI3K (Tyr458), Akt (Ser473), p38 MAPK (Thr180/Tyr182), ERK1 (Thr202/Tyr204), JNK1 (Thr183/Tyr185)—and inhibitory proteins—VASP (Ser157) and IP₃RI (Ser1756)—via immunoblotting. Thrombin-induced fibrin clot retraction, cytotoxicity, coagulation parameters, and antioxidant capacity were also examined. WIB-801CE significantly inhibited U46619-induced fibrinogen binding to integrin αIIbβ₃ and platelet aggregation, without inducing cytotoxicity or impairing hemostatic function. It also significantly downregulated the phosphorylation of platelet-activating proteins and upregulated the phosphorylation of platelet-inhibiting proteins. Additionally, WIB-801CE abolished thrombin-induced fibrin clot retraction and demonstrated antioxidant capacity. WIB-801CE disrupts TXA₂-driven platelet activation and thrombus stabilization by selectively modulating phosphorylation of key signaling proteins at defined regulatory sites. These properties highlight its promise as a therapeutic candidate for thrombotic disorders with platelet hyperreactivity. Full article

Cordyceps militaris is an entomopathogenic fungus traditionally used in Asian ethnomedicine and increasingly investigated for its potential health-promoting properties, including immunomodulatory and anti-inflammatory activities. In recent years, it has gained attention as a dietary supplement with possible applications in sports nutrition. This narrative review summarizes and critically evaluates the current human evidence regarding the ergogenic and post-exercise recovery effects of C. militaris supplementation in healthy individuals. A structured database search was conducted using predefined eligibility criteria, and the methodological quality of included studies was appraised through domain-based risk-of-bias assessment. Five intervention studies published between 2017 and 2024, comprising 321 participants aged 16–35 years, were identified. Supplementation protocols ranged from 1 to 16 weeks, with daily doses of 1–12 g administered either as isolated fungal material or as a part of multi-ingredient formulations. Assessed outcomes included indices of aerobic performance and exercise capacity, such as maximal or peak oxygen uptake (VO₂max/VO₂peak), time to exhaustion, power output, running performance, and maintenance of peripheral oxygen saturation during high-intensity exercise. Several studies also evaluated biochemical markers related to muscle damage and inflammatory responses, including creatine kinase, blood urea nitrogen, and white blood cell counts. Although some studies reported improvements in selected performance and recovery parameters, the findings were inconsistent. The certainty of the evidence is limited by small sample sizes, heterogeneity of participants and exercise protocols, insufficient reporting of randomization, lack of trial registration in most studies, absence of standardized preparations with quantified bioactive constituents, and the use of multi-ingredient supplements. Well-designed randomized controlled trials using chemically characterized preparations and homogeneous athletic populations are required to clarify the efficacy and practical relevance of C. militaris in sports nutrition. Full article

Cordyceps militaris is an important medicinal and edible fungus that contains a wide range of bioactive ingredients, including cordycepin, polysaccharides, ergosterol, mannitol, proteins, and carotenoids, which collectively confer tonic, anti-fatigue, immunopotentiating, antioxidant, anti-inflammatory, and metabolic-regulating properties. Notably, the culture residue of C. militaris, which remains rich in bioactive compounds, is mostly discarded during production, resulting in resource waste and potential environmental pollution. In this study, C. militaris culture residue extract (CME) was prepared by ultrasonic extraction, and its antiviral activity was evaluated using Nicotiana benthamiana via foliar spraying. The results showed that CME treatment significantly upregulated the expression of defense-related genes PR1, PR2, and ICS1, with PR1 showing the most pronounced induction (13.20-fold before and 11.89-fold after TMV inoculation), thereby conferring strong antiviral activity. In addition, root irrigation with 10 mg/mL CME significantly increased plant height, stem diameter, dry weight, fresh weight, chlorophyll content, and carotenoid content in tomato plants. Taken together, these findings indicate that CME functions as a plant immune inducer capable of effectively suppressing tobacco viral diseases while promoting plant growth. This study not only provides a new strategy for the value-added reutilization of C. militaris culture residues but also offers a scientific basis for the green control of tobacco mosaic disease. Full article

Cordycepin is a key active component of Cordyceps militaris, but the molecular mechanism underlying temperature-regulated biosynthesis remains unclear. In this study, Cordyceps militaris strain KN-1 was used as experimental material, with low-temperature (15 °C), control (20 °C), and high-temperature (25 °C) treatments applied during the fruiting body stage. Transcriptomics, untargeted metabolomics, weighted gene co-expression network analysis (WGCNA), and Reverse Transcription quantitative PCR (RT-qPCR) validation were integrated to elucidate the molecular mechanism of temperature-mediated cordycepin biosynthesis. The results showed that 25 °C increased fruiting body cordycepin content by 84%, while 15 °C reduced it. Transcriptomic analysis identified differentially expressed genes (DEGs) enriched in transmembrane transport and fatty acid metabolism, and untargeted metabolomics revealed differential metabolites (DAMs) enriched in lipids and organic acids, indicating that temperature primarily affects Cordyceps militaris membrane function. WGCNA showed that the MEblue module was positively correlated with cordycepin (r = 0.93), with Major Facilitator Superfamily (MFS) members accounting for the highest proportion (47.1%) that may affect cordycepin transmembrane transport. Multi-omics analysis indicated that high temperature promotes cordycepin accumulation through the synergistic regulation of multiple pathways: upregulating genes in the pentose phosphate pathway, purine metabolism, and cordycepin biosynthetic gene cluster (Cns1–Cns3), increasing protective agent pentostatin content, downregulating cordycepin-degrading genes, and enhancing cordycepin transmembrane transport. This study clarifies the molecular mechanism of temperature-mediated cordycepin accumulation, providing a theoretical basis for improving cordycepin production via temperature regulation, optimizing Cordyceps militaris strain quality, and facilitating efficient industrial production. Full article

Chronic diabetic wounds are characterized by persistent inflammation, impaired angiogenesis, oxidative stress, and defective tissue remodeling, leading to delayed healing. Cordyceps militaris, a medicinal fungus with known anti-inflammatory and antioxidant properties, has shown therapeutic potential in metabolic disorders; however, its role in diabetic wound repair remains unclear. In this study, we evaluated the wound-healing effects of an aqueous extract of C. militaris using in vitro keratinocyte models and a streptozotocin-induced diabetic mouse model. C. militaris treatment significantly accelerated wound closure, improved epidermal regeneration, and enhanced skin barrier integrity. Mechanistically, C. militaris restored HIF-1α and TGF-β1 expression, promoted cell proliferation and fibroblast activation, and increased the expression of matrix metalloproteinases MMP-1 and MMP-2, indicating enhanced extracellular matrix remodeling. In parallel, excessive inflammatory responses were attenuated, as evidenced by reduced IL-6 and TNF-α levels, along with activation of SIRT1/Nrf2/HO-1 antioxidant signaling pathways. Collectively, these findings demonstrate that C. militaris promotes a balanced wound-healing microenvironment and represents a promising natural therapeutic candidate for the treatment of diabetic wounds. Full article