Search Results (120)

This study presents the development and optimization of a functional soy sauce fermented with Cordyceps militaris (C. militaris), a medicinal fungus known for its high cordycepin and polysaccharide content. Using C. militaris as the sole starter culture, the process aimed to improve both nutritional and functional properties. Response surface methodology was employed to optimize the entire fermentation process. During the koji stage, temperature, aeration, and inoculum concentration were adjusted to maximize protease activity and cordycepin production. In the fermentation stage, temperature, brine concentration, and water-to-material ratio were optimized to increase amino acid nitrogen and bioactive compound levels. Under optimal conditions (24 °C, 679.60 LPM aeration, 9.6% inoculum for koji; 32 °C, 12% brine, 1.53:1 water-to-material ratio for fermentation), the resulting soy sauce contained 1.14 ± 0.05 g/100 mL amino acid nitrogen and 16.88 ± 0.47 mg/100 mL cordycepin. Compared with traditionally fermented soy sauce, the C. militaris product exhibited a darker color, enhanced umami taste, and a distinct volatile profile featuring linoleic acid, methyl palmitate, and niacinamide. These results demonstrate the feasibility of using C. militaris in soy sauce fermentation and its potential as a novel functional condiment with improved bioactivity and sensory quality. Full article

Cordyceps sinensis (C. sinensis) is widely recognized for its bioactive compounds and associated health benefits. However, due to its delicate nature, conventional chilled storage often results in the rapid degradation of valuable compounds, leading to loss of nutritional value and overall quality. This study integrated and evaluated comprehensive strategies: three gas-conditioning and two light-based preservation methods for maintaining both quality and nutritional integrity during 12-day chilled storage at 4 °C. The results revealed that vacuum packaging significantly inhibited weight loss (3.49%) compared to in the control group (10.77%) and preserved sensory quality (p < 0.05). UV-based interventions notably suppressed polyphenol oxidase and tyrosinase activities by 36.4% and 29.7%, respectively (p < 0.05). Modified atmosphere packaging (MAP) with 80% N₂ and 20% CO₂ (MAP-N₂CO₂) maintained higher levels of cordycepin (1.77 µg/g) and preserved energy charge above 0.7 throughout storage. The results suggest that MAP-based treatments are superior methods for the chilled storage of C. sinensis, with diverse advantages and their corresponding shelf lives associated with different gas compositions. Full article

Cordycepin, a bioactive adenosine analog, holds promise in pharmaceutical and health product development. However, large-scale production remains constrained by the limitations of natural producers, Cordyceps spp. Herein, we report the reconstruction of the first genome-scale metabolic model (GSMM) for a cordycepin-producing strain of recombinant Aspergillus oryzae. The model, iNR1684, incorporated 1684 genes and 1947 reactions with 93% gene-protein-reaction coverage, which was validated by the experimental biomass composition and growth rate. In silico analyses identified key gene amplification targets in the pentose phosphate and one-carbon metabolism pathways, indicating that folate metabolism is crucial for enhancing cordycepin production. Nutrient optimization simulations revealed that chitosan, D-glucosamine, and L-aspartate preferentially supported cordycepin biosynthesis. Additionally, a carbon-to-nitrogen ratio of 11.6:1 was identified and experimentally validated to maximize production, higher than that reported for Cordyceps militaris. These findings correspond to a faster growth rate, enhanced carbon assimilation, and broader substrate utilization by A. oryzae. This study demonstrates the significant role of GSMM in uncovering rational engineering strategies and provides a quantitative framework for precision fermentation, offering scalable and sustainable solutions for industrial cordycepin production. Full article

This study employs advanced numerical simulation to investigate the influence of shelf temperature on the freeze-drying kinetics and product quality of Cordyceps militaris. Emphasis is placed on the glass transition and structural collapse mechanisms during the primary drying stage. A detailed computational model was developed to predict temperature profiles, glass transition temperature, collapse temperature, and moisture distribution under varying process conditions. Simulation results indicate that maintaining the shelf temperature below 10 °C minimizes the risk of structural collapse and volume shrinkage while improving drying efficiency and product stability. Based on the model, an optimal freeze-drying protocol is proposed: shelf heating at 0 °C, condenser plate at −32 °C, and chamber pressure at 35 Pa. Experimental validation confirmed the feasibility of this regime, yielding a shrinkage of 9.52%, a color difference (ΔE) of 4.86, water activity of 0.364 ± 0.018, and a rehydration ratio of 55.14 ± 0.789%. Key bioactive compounds, including adenosine and cordycepin, were well preserved. These findings underscore the critical role of simulation in process design and optimization, contributing to the development of efficient and high-quality freeze-dried functional food products. Full article

Cordyceps militaris, a model species in the genus Cordyceps, is widely distributed globally and is known for its significant medicinal value. It has been traditionally used in Chinese medicine to enhance immunity, alleviate fatigue, and treat tumors, among other therapeutic purposes. Here, we successfully assembled a telomere-to-telomere (T2T) level genome of C. militaris CH1 using PacBio HiFi and Hi-C technologies. The assembled genome is 32.67 Mb in size, with an N50 of 4.70 Mb. Gene prediction revealed a total of 10,749 predicted genes in the C. militaris CH1 genome, with a gene completeness of 99.20%. Phylogenetic analysis showed the evolutionary relationship between C. militaris CH1 and other Cordyceps species, suggesting that the divergence between this strain and C. militaris ATCC 34164 occurred approximately 1.36 Mya. Combined transcriptomic and metabolomic analyses identified 842 differentially expressed genes and 2052 metabolites that were significantly altered under light stress, primarily involving key pathways related to amino acid metabolism, purine metabolism, and secondary metabolite biosynthesis. Joint analysis of genes and metabolites revealed 79 genes coding for enzymes associated with the synthesis of adenine and adenosine, with the expression of 52 genes being upregulated, consistent with the accumulation trends of adenine and adenosine. Four gene clusters related to the synthesis of cordycepin were identified, with a significant upregulation of cns3 (FUN_003263), suggesting that light stress may promote cordycepin biosynthesis. This comprehensive analysis not only provides new insights into the genomics, metabolomics, and functional gene research of C. militaris CH1 but also offers a potential biological foundation for understanding the synthesis mechanisms of cordycepin and its efficient production. Full article

Air pollutants are significant environmental factors that contribute to the exacerbation of respiratory, cardiopulmonary, and skin diseases in East Asia, and their impact is based on particle size. Natural products represent a promising and sustainable strategy for reducing the adverse effects of air pollutants on health. Cordyceps spp. have been integral to traditional Chinese medicine. Recently, their fruiting bodies and related supplements have gained popularity. The physiological effects of Cordyceps species are well documented and attributed to their chemical constituents, such as cordycepin, polysaccharides, cordymin, glycoprotein, ergosterol, and other bioactive extracts. Cordyceps supplementation may support lung health and enhance respiratory function. Although further clinical data are necessary, many preclinical studies have found a connection between Cordyceps and improved lung health. In addition, preclinical and clinical studies have indicated that Cordyceps and its derivatives (e.g., Ningxinbao, Corbrin, and Jinshuibao capsules) protect against vascular diseases by modulating key molecular pathways. This review provides insights into the potential of Cordyceps for clinical application in the management of air pollutant-related respiratory and vascular diseases. Full article

Alzheimer’s disease (AD) is considered one of the main pathologies of our time, whose incidence and prevalence are suggested to be strongly underestimated. AD presents as a complex neurodegenerative condition characterized by marked neuroinflammation and a significant decline in the cognitive and mnemonic functions of affected patients. Recognized AD pathological hallmarks include amyloid beta plaque and neurofibrillary tangle formation, synaptic dysfunction with considerable apoptosis of cholinergic and dopaminergic neurons, and high levels of oxidative stress and neuroinflammation. The available pharmacological treatments are represented by acetylcholinesterase inhibitors to treat the mild to moderate form of the disease and N-methyl-D-aspartate inhibitors alone or in combination with the previously cited ones in the late stage of the neurodegenerative condition. Furthermore, emerging drug therapies such as monoclonal antibodies are promising agents in AD management. Although scientific evidence highlights these chemicals as effective in slowing down disease progression, significant limitations behind their employment derive from the notable dose-dependent side effects and the single-target mechanism of action. In this context, two well-studied phytotherapeutics, W. somnifera (W. somnifera) and fungi belonging to the genus Cordyceps, have gained attention for their chemical composition regarding their neuroprotective and anti-inflammatory effects. Ashwagandha (obtained principally from the roots of W. somnifera) is an adaptogen that relieves stress and anxiety. It contains several ergostane-type steroidal lactones—such as withanolides and withaferin A—and various alkaloids, contributing to its antioxidant and neuroprotective effects. Likewise, cordycepin is the main bioactive principle found in Cordyceps fungi. This natural nucleoside has been reported to possess therapeutic potential as an anti-cancer, immunomodulatory, and anti-inflammatory agent, with some studies suggesting a beneficial role in AD treatment. The purpose of the present review is to investigate the pharmacological properties of W. somnifera and Cordyceps species in the context of AD treatment and explore the therapeutic potential of the constitutive bioactive molecules in preclinical models mimicking this neurodegenerative condition. Full article

The anticancer activity of 3′-deoxyadenosine (Cordycepin, or dCor) is known to be linked to the inhibition of the MAPK/ERK signalling and Hedgehog pathways, as well as the termination of primer elongation by primase in DNA lagging-strand synthesis. In this study, the electronic properties of dCor, 7,8-dihydro-8-oxo-3′-deoxyadenosine (^OXOdCor), and 8-hydroxy-3′deoxyadenosie (^HOdCor), together with their spin densities, charge distributions, and global reactive descriptors, have been taken into consideration at the M06-2x/6-31++G** level of theory in the aqueous phase. It was found that dCor predominantly adopts a 3′-endo,anti conformation, while ^OXOdCor and ^HOdCor adopt a 2′-endo,syn conformation. Also, the keto form of oxidised dCor was found to be energetically preferred to its enolic form. The adiabatic ionisation potentials (AIPs) were noted as follows (in eV): 6.29 for dCor, 6.21 for ^OXOdCor, and 6.17 for ^HOdCor. The lowest adiabatic electron affinity among all the discussed adenine nucleosides analogues was assigned for ^OXOdCor at 1.12 eV. A thorough analysis of the spin density distribution of the adiabatic radical cation reveals that it has a higher accumulation at N6 > C5 > C8 > 3 of dCor, C5 > N6 > N7 > O8 of ^OXOdCor, and N6 > C5 > C8 > C2 of ^HOdCor. The results suggest that Cordycepin is more easily converted to ^OXOdCor and ^HOdCor than canonical adenine nucleosides. Much like typical drugs, after its administration and release, Cordycepin is exposed to various physiological factors and can be exposed to ionisation radiation during combined therapy. These factors can influence the therapeutic potential of Cordycepin. Therefore, further studies on its stability are of utmost importance. Full article

Microbial protein represents a sustainable alternative to conventional animal protein, yet optimizing substrates for fungal cultivation remains critical. This study demonstrates the successful upcycling of chitin waste and aged rice into fungal protein through fermentation with Cordyceps militaris. Substrate formulations (0–20% chitin waste mixed with aged rice) were evaluated for their effects on fungal growth, yield, and metabolite profiles. Results revealed that aged rice alone supported fruiting body yields comparable to fresh rice (9.8 g vs. 9.8 g), with no significant differences in the morphology or growth rate. The addition of 5% chitin waste led to a 17% improvement in yield compared to the control, increasing the average fresh weight of fruiting bodies from 9.8 g to 11.5 g per bottle, while higher chitin levels (20%, T4) suppressed mycelial growth entirely. Fourier-transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) confirmed chitin’s structural complexity and nitrogen-rich composition, which slowed the substrate utilization but enriched secondary metabolites. Liquid chromatography–mass spectrometry (LC-MS) identified 1025 metabolites, including up-regulated bioactive compounds (e.g., cordycepin and piplartine) in chitin-amended substrates, linked to amino acid and lipid metabolism pathways. Safety assessments confirmed the absence of toxins, validating the substrates’ suitability for food applications. These findings highlight chitin waste (≤5%) as a viable nitrogen supplement to aged rice, improving the fungal protein yield and bioactive compound synthesis. This approach advances sustainable biomass valorization, offering a scalable strategy to reduce agricultural waste while producing nutrient-dense fungal protein. Full article

An optimal culture medium and highly stable biometabolites are important in industrial production processes. The response surface methodology with a Box–Behnken design was performed to determine the optimal culture medium of an engineered Aspergillus oryzae strain for cordycepin production by submerged fermentation. The influences of glucose, yeast extract, and adenine concentrations on cordycepin production were explored, and their concentrations were used for experimental design. The results reveal that the optimal culture components involved 30.0 g/L of glucose, 9.8 g/L of yeast extract, and 1.5 g/L of adenine. As predicted, the maximum cordycepin concentration (1724.53 ± 18.30 mg/L) was obtained with a short fermentation time (2 days). A significant increase in cordycepin yield (>50% increase) was observed in the culture grown in the optimized culture medium compared to that grown in the basal medium. A xanthine oxidase inhibitory activity assay demonstrated that the cordycepin product had a pharmacological function. It exhibited strong stability under high thermal and acidic conditions, with over 95% product recovery. The findings of this study are valuable for developing cost-effective processes for producing health-benefiting products. Full article

Cordyceps militaris is a medicinal mushroom widely utilized in traditional East Asian medicine, recognized for its diverse therapeutic properties. This review explores the potential of C. militaris-derived bioactive gels for applications in dermatology and skincare, with a particular focus on their therapeutic and anti-aging benefits. In response to the rising incidence of skin cancers and the growing demand for natural bioactive ingredients, C. militaris has emerged as a valuable source of functional compounds, including cordycepin, polysaccharides, and adenosine. These compounds exhibit multiple bioactivities, including apoptosis induction, cell cycle arrest, and anti-inflammatory effects, which have been shown to be particularly effective against melanoma and other skin cancers. Additionally, the antioxidant properties of C. militaris enhance skin resilience by scavenging reactive oxygen species, reducing oxidative stress, and promoting collagen synthesis, thereby addressing skin health and anti-aging requirements. The potential for incorporating C. militaris compounds into gel-based formulations for skincare is also examined, either as standalone bioactives or in combination with synergistic ingredients. Emphasis is placed on the necessity of clinical trials and standardization to establish the safety, efficacy, and reproducibility of such applications. By providing a safer alternative to synthetic agents, C. militaris-derived bioactive gels represent a promising advancement in dermatology and skincare. Full article

Douchi is a kind of soybean-fermented food in China. To explore the common and differential compounds in different Douchi, Douchi was fermented by Aspergillus niger, Rhizopus arrhizus, and Bacillus circulans, respectively, and co-fermented by the three strains in this study. The common and characteristic flavor compounds and common and characteristic non-volatile components of different strains of fermented Douchi were explored through GC×GC-TOFMS and UPLC–Q-TOFMS omics analysis. The result suggested that Pyrazines, ketones, and alkenes such as tetramethyl-pyrazine, 2,5-dimethyl pyrazine, furaneol, 2,3-butanedione, gamma-terpinene might contribute to the basic flavor of the Douchi fermented by A. niger, R. arrhizus, and B. circulans. Peptides, amines, and flavonoids, such as N–acetylhistamine, 7,3′,4′–trihydroxyflavone, (3S,8As)-3-isobutylhexahydropyrrolo[1,2-a]pyrazine-1,4-dione might contribute to the basic function of the above three Douchi. The common metabolic pathways involved in the fermentation were isoflavonoid biosynthesis, flavonoid biosynthesis, etc. Ketones and esters such as 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one, 3-octanone, 5-methylfurfural and nonanal contributed to the unique flavor, while betaine, oleanolic acid, saikosaponin D and leucine might contribute to the unique function of A. niger fermented Douchi. Alkenes, pyrazine, and ketones such as α-terpinene, ethyl-pyrazine, dihydro-3-methyl-2(3H)-furanone, and linalool might contribute to unique flavor, while cordycepin, 2-Phenylacetamide might contributed to the unique function of R. arrhizus fermented Douchi. The unique flavor of B. circulans fermented Douchi might derived from ketones and esters such as 3-acetyl-2-butanone, 2-tridecanone, propionic acid-2-phenylethyl ester, while vitexin, astragalin, and phenethylamine might contribute to the unique function. Compared with single-strain fermented Douchi, the flavor substances and non-volatile components in multi-strain fermented Douchi were more abundant, such as hexadecanoic acid methyl ester, benzeneacetic acid ethyl ester, 9,12-octadecadienoic acid ethyl ester, nuciferine, and erucamide. It was speculated that there were common and differential substances in Douchi fermented by Aspergillus niger, Rhizopus arrhizus, and Bacillus circulans, which might contribute to the basic and unique flavor and function. Compared with single-strain fermented Douchi, the flavor substances and metabolites in multi-strain fermented Douchi were more abundant. This study provided a reference for the research of flavor and functional substances of Douchi. Full article

Cordyceps primarily consists of ascomycetes, a parasitic fungus that infects insects and arthropods. Recently, Cordyceps has been shown to manifest a diverse range of pharmacological activities, rendering it applicable for the treatment and mitigation of various diseases, such as diabetes, acute liver injury, and colitis. Many active constituents have been identified from Cordyceps sinensis, including cordycepin, adenosine, sterols, and polysaccharides. Polysaccharides constitute a primary active component of Cordyceps, exhibiting immunomodulatory effects. We searched the Web of Science database with the keywords of cordyceps, polysaccharide, and immune modulation; collected related studies from 2004 to 2024; and eliminated articles with low influence and workload. A review of the research advancements regarding the immunomodulatory effects of Cordyceps polysaccharides was conducted with the aim of furnishing valuable reference information. Research indicates that polysaccharides exhibiting immunomodulatory activity are predominantly sourced from Cordyceps sinensis and Cordyceps militaris. Immunological experimental results demonstrate that Cordyceps polysaccharides can augment the activities of macrophages, lymphocytes, and dendritic cells while fostering the expression of immune-active substances such as cytokines and chemokines. Furthermore, animal experiments have substantiated the immunomodulatory effects of Cordyceps polysaccharides. These effects encompass ameliorating immune suppression induced by drugs or radiation, enhancing immune organ indices, elevating the expression of immunoreactive substances, and mitigating immune evasion prompted by tumors. In conclusion, Cordyceps polysaccharides exhibit significant immunomodulatory activity and merit further investigation. Full article

Cordyceps militaris extract (CME) contains many bioactive compounds, mainly cordycepin (CPN). This study aimed to investigate the possible mechanisms underlying the amelioration of LPS-induced acute liver injury in piglets by CME or CPN supplementation using multi-omics analysis. Twenty-four weaned piglets were randomly distributed into 4 groups (n = 6): the control and LPS groups were fed basal diets; the CPN + LPS (CPN-LPS) and CME + LPS (CME-LPS) groups were fed the basal diets supplemented with CME or CPN. The results showed that CPN or CME supplementation significantly decreased the C-reactive protein level (p < 0.05) and improved liver tissue pathology to prevent acute liver injury after LPS treatment. Compared with LPS, the transcriptomic analysis indicated that CPN supplementation significantly downregulated cell adhesion molecules, while CME supplementation significantly downregulated inflammatory mediator regulation of TRP channels, complement and coagulation cascades and cytokine-cytokine receptor interaction. The metabolomic results showed that CPN or CME supplementation significantly reduced disease biomarker of bicyclo-prostaglandin E2, and increased levels of deoxyinosine and 3-hydroxyanthranilic acid (p < 0.05). The combined transcriptome and metabolome helped identify two metabolites PC 34:2 and PC 36:0, which may be associated with the restoration of liver cell morphology. In conclusion, CPN and CME could attenuate LPS-induced acute liver injury by regulating immune-related genes and metabolites. This study elucidates the potential protective mechanism of CPN or CME supplementation against acute liver injury. Full article

Cordyceps militaris, a fungus widely used in traditional Chinese medicine and pharmacology, is recognized for its abundant bioactive compounds, including cordycepin and carotenoids. The growth, development, and metabolite production in various fungi are influenced by the complex interactions between regulatory cascades and light-signaling pathways. However, the mechanisms of gene regulation in response to light exposure in C. militaris remain largely unexplored. This study aimed to identify light-responsive genes and potential transcription factors (TFs) in C. militaris through an integrative transcriptome analysis. To achieve this, we reconstructed an expanded gene regulatory network (eGRN) comprising 507 TFs and 8662 regulated genes using both interolog-based and homolog-based methods to build the protein–protein interaction network. Aspergillus nidulans and Neurospora crassa were chosen as templates due to their relevance as fungal models and the extensive study of their light-responsive mechanisms. By utilizing the eGRN as a framework for comparing transcriptomic responses between light-exposure and dark conditions, we identified five key TFs—homeobox TF (CCM_07504), FlbC (CCM_04849), FlbB (CCM_01128), C6 zinc finger TF (CCM_05172), and mcrA (CCM_06477)—along with ten regulated genes within the light-responsive subnetwork. These TFs and regulated genes are likely crucial for the growth, development, and secondary metabolite production in C. militaris. Moreover, molecular docking analysis revealed that two novel TFs, CCM_05727 and CCM_06992, exhibit strong binding affinities and favorable docking scores with the primary light-responsive protein CmWC-1, suggesting their potential roles in light signaling pathways. This information provides an important functional interactive network for future studies on global transcriptional regulation in C. militaris and related fungi. Full article