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The Scientific Rediscovery of an Ancient Chinese Herbal Medicine: Cordyceps sinensis Part I
Abstract
This review presents Cordyceps sinensis (Berk.) Sacc., a fungus highly valued in China as a tonic food and herbal medicine. The extant records show the continued use of C. sinensis is now centuries old. The major chemical, pharmacological, and toxicological studies on C. sinensis and the various derived, cultured, fermented mycelial products currently in use are reviewed from the English and Chinese literature. Preclinical in vitro and in vivo studies and clinical blinded or open-label trials in to date over 2000 patients are reviewed. These studies show the main activities of the fungus in oxygen-free radical scavenging, antisenescence, endocrine, hypolipidemic, antiatherosclerotic, and sexual function-restorative activities. The safety of the fungus, its effects on the nervous system, glucose metabolism, the respiratory, hepatic, cardiovascular, and immune systems, immunologic disease, inflammatory conditions, cancer, and diseases of the kidney will be reviewed in the second part of this article to be published in the winter issue of this journal.
... Natural Cordyceps sinensis is one of the most highly valued therapeutic agents in traditional Chinese medicine (TCM), with a centuries-long history of clinical use as a folk medicine administered for "Yin-Yang" double invigoration, health maintenance, disease amelioration, and post-disease and post-surgery recovery [1,2]. The therapeutic profiles of Cordyceps sinensis for respiratory, cardiovascular, endocrine, kidney, and liver systems, etc., have been studied using modern pharmacological approaches and summarized [2,3]. ...
... Natural Cordyceps sinensis is one of the most highly valued therapeutic agents in traditional Chinese medicine (TCM), with a centuries-long history of clinical use as a folk medicine administered for "Yin-Yang" double invigoration, health maintenance, disease amelioration, and post-disease and post-surgery recovery [1,2]. The therapeutic profiles of Cordyceps sinensis for respiratory, cardiovascular, endocrine, kidney, and liver systems, etc., have been studied using modern pharmacological approaches and summarized [2,3]. The lifespan-extending properties of natural Cordyceps sinensis and its mycelial fermentation products were validated in mice in a 4-year pharmacology study, and the molecular mechanisms have been explored using a whole-gene expression biochip technique [4,5]. ...
... Table). Peak A (a transversion point mutation genotype of unknown upstream and downstream sequences) was attenuated in S3. 2 Table). Fig 1 for the location). ...
Objective:
To examine multiple genotypes of Ophiocordyceps sinensis in a semi-quantitative manner in the stromal fertile portion (SFP) densely covered with numerous ascocarps and ascospores of natural Cordyceps sinensis and to outline the dynamic alterations of the coexisting O. sinensis genotypes in different developmental phases.
Methods:
Mature Cordyceps sinensis specimens were harvested and continuously cultivated in our laboratory (altitude 2,254 m). The SFPs (with ascocarps) and fully and semi-ejected ascospores were collected for histological and molecular examinations. Biochip-based single nucleotide polymorphism (SNP) MALDI-TOF mass spectrometry (MS) was used to genotype multiple O. sinensis mutants in the SFPs and ascospores.
Results:
Microscopic analysis revealed distinct morphologies of the SFPs (with ascocarps) before and after ascospore ejection and SFP of developmental failure, which, along with the fully and semi-ejected ascospores, were subjected to SNP MS genotyping analysis. Mass spectra showed the coexistence of GC- and AT-biased genotypes of O. sinensis that were genetically and phylogenetically distinct in the SFPs before and after ejection and of developmental failure and in fully and semi-ejected ascospores. The intensity ratios of MS peaks were dynamically altered in the SFPs and the fully and semi-ejected ascospores. Mass spectra also showed transversion mutation alleles of unknown upstream and downstream sequences with altered intensities in the SFPs and ascospores. Genotype #5 of AT-biased Cluster-A maintained a high intensity in all SFPs and ascospores. An MS peak with a high intensity containing AT-biased Genotypes #6 and #15 in pre-ejection SFPs was significantly attenuated after ascospore ejection. The abundance of Genotypes #5‒6 and #16 of AT-biased Cluster-A was differentially altered in the fully and semi-ejected ascospores that were collected from the same Cordyceps sinensis specimens.
Conclusion:
Multiple O. sinensis genotypes coexisted in different combinations with altered abundances in the SFPs prior to and after ejection, the SFP of developmental failure, and the two types of ascospores of Cordyceps sinensis, demonstrating their genomic independence. Metagenomic fungal members present in different combinations and with dynamic alterations play symbiotic roles in different compartments of natural Cordyceps sinensis.
... Cordyceps militaris, a model parasitic fungus species of the family Cordycipitaceae and genus Cordyceps, has been a traditional Chinese medicine for centuries (Zhu et al. 1998). In Asia, because of a wide range of biological effects, including immune regulation, antitumor, antioxidation, antiinflammatory, and antimicrobial properties (Tuli et al. 2014;Zhang et al. 2019;Qin et al. 2019;Jędrejko et al. 2021;Kontogiannatos et al. 2021), C. militaris has been used as an exhaustion remedy and treatment for numerous diseases. ...
... In 2009, the Ministry of Health, People's Republic of China, officially proclaimed the fruiting body of C. militaris to be edible (Ministry of Health of the People's Republic of China 2009), which promoted further research of the fungus. Cordyceps militaryis contains many bioactive substances, such as cordycepin, adenosine, cordyceps polysaccharide, amino acids, ergosterol, and polycystin (Zhu et al. 1998;Jędrejko et al. 2021;Quy et al. 2019). Among these substances, cordycepin is the most important and the standard by which to measure the quality of C. militaris (Qin et al. 2019). ...
We determined whether there exists a complementary pathway of cordycepin biosynthesis in wild-type Cordyceps militaris, high-cordycepin-producing strain C. militaris GYS60, and low-cordycepin-producing strain C. militaris GYS80. Differentially expressed genes were identified from the transcriptomes of the three strains. Compared with C. militaris, in GYS60 and GYS80, we identified 145 and 470 upregulated and 96 and 594 downregulated genes. Compared with GYS80, in GYS60, we identified 306 upregulated and 207 downregulated genes. Gene Ontology analysis revealed that upregulated genes were mostly involved in detoxification, antioxidant, and molecular transducer in GYS60. By Clusters of Orthologous Groups of Proteins and Kyoto Encyclopedia of Genes and Genomes analyses, eight genes were significantly upregulated: five genes related to purine metabolism, one to ATP production, one to secondary metabolite transport, and one to RNA degradation. In GYS60, cordycepin was significantly increased by upregulation of ATP production, which promoted 3′,5′-cyclic AMP production. Cyclic AMP accelerated 3′-AMP accumulation, and cordycepin continued to be synthesized and exported. We verified the novel complementary pathway by adding the precursor adenosine and analyzing the expression of four key genes involved in the main pathway of cordycepin biosynthesis. Adenosine addition increased cordycepin production by 51.2% and 10.1%, respectively, in C. militaris and GYS60. Four genes in the main pathway in GYS60 were not upregulated.
... Clinical trial findings indicate that this caterpillar fungus could include substances that prevent apoptosis (Zhu et al., 1998) [10] . In order to evaluate Cordyceps sinensis capacity to prevent apoptosis in vitro, these clinical outcomes have produced mixed results. ...
... Clinical trial findings indicate that this caterpillar fungus could include substances that prevent apoptosis (Zhu et al., 1998) [10] . In order to evaluate Cordyceps sinensis capacity to prevent apoptosis in vitro, these clinical outcomes have produced mixed results. ...
... Ophiocordyceps sinensis (Ascomycota: Ophiocordycipitaceae) (Berk.) Sung, Sung, Hywel-Jones and Spatafora, is a typical entomogenous fungus that mainly parasitizes Hepialidae caterpillars, forming a complex containing fungal sexual stroma and the caterpillar body (Zhu et al. 1998;Sung et al. 2007). It has been used for centuries as a traditional Chinese medicine to treat asthma, bronchial/ lung infection, and kidney disease (Zhu et al. 1998). ...
... Sung, Sung, Hywel-Jones and Spatafora, is a typical entomogenous fungus that mainly parasitizes Hepialidae caterpillars, forming a complex containing fungal sexual stroma and the caterpillar body (Zhu et al. 1998;Sung et al. 2007). It has been used for centuries as a traditional Chinese medicine to treat asthma, bronchial/ lung infection, and kidney disease (Zhu et al. 1998). Over 30 bioactivities, such as immunomodulatory, antitumor, anti-inflammatory, and antioxidant activities, derive from over 20 bioactive ingredients of O. sinensis (Lo et al. 2013). ...
Ophiocordyceps sinensis Berk. is a fungal parasite that parasitizes the larvae of Hepialidae and is endemic to the Qinghai–Tibet Plateau (QTP). The phylogeny and divergence time of O. sinensis and its host insects were analyzed for 137 individuals from 48 O. sinensis populations based on the elongation factor 1 alpha (EF-1α) gene. Lower nucleotide variation, with only 7 and 16 EF-1α haplotypes, was detected in O. sinensis and its host insects, respectively. The isolated and broad distribution patterns coexisted in both O. sinensis and its host insects on the QTP. The divergence time estimates show that O. sinensis and its host insects originated later than 14.33 million years (Myr) and earlier than 23.60 Myr in the Miocene period, and the major differentiation occurred later than 4 Myr. Their origin and differentiation match well with the second and third uplifts of the QTP, respectively. The host insects from the O. sinensis populations distributed around Qinghai Lake are inferred as an ancient and relict species that has survived various geological events of the QTP. It is suitable to estimate the divergence times of both O. sinensis and its host insects from the same individuals using one gene: EF-1α. Our findings of the origin, phylogeny, and evolution of the endemic species also support the epoch of geological events on the QTP.
... C. sinensis (now identified as Ophiocordyceps sinensis due to the reassignment of the species to the family Ophiocordycipitaceae) (Figure 1a), C. militaris (Figure 1b), C. sobolifera, C. subssesilus, C. ophioglossoides, and other Cordyceps species are currently being cultivated for medical uses and usage in health supplements. They comprise a variety of bioactive compounds, such as: nucleotides, amino acids, polysaccharides, flavonoids, proteins, and sterols, which endow it with a variety of health-improving properties, such as: antioxidant, anti-aging, immunoenhancer, neuro-cardioprotective, anti-metastatic, hepatoprotective, tonic effect, and so on [11,12]. This review is focused on providing up-to-date information on the wide range of bioactive compounds produced by various Cordyceps spp. ...
The Clavicipitaceae family’s largest and most diverse genus is Cordyceps. They are most abundant and diverse in humid temperate and tropical forests and have a wide distribution in: Europe, North America, and East and Southeast Asian countries, particularly: Bhutan, China, Japan, Nepal, Korea, Thailand, Vietnam, Tibet, and the Himalayan region of India, and Sikkim. It is a well-known parasitic fungus that feeds on insects and other arthropods belonging to 10 different orders. Over 200 bioactive metabolites, that include: nucleotides and nucleosides, polysaccharides, proteins, polypeptides, amino acids, sterols, and fatty acids, among others have been extracted from Cordyceps spp. demonstrating the phytochemical richness of this genus. These components have been associated with a variety of pharmacological effects, including: anti-microbial, anti-apoptotic, anti-cancer, anti-inflammatory, antioxidant, and immunomodulatory activities. In this paper, the bioactivity of various classes of metabolites produced by Cordyceps spp., and their therapeutic properties have been reviewed in an attempt to update the existing literature. Furthermore, one of its nucleoside and a key bioactive compound, cordycepin has been critically elaborated with regard to its biosynthesis pathway and the recently proposed protector-protégé mechanism as well as various biological and pharmacological effects, such as: suppression of purine and nucleic acid biosynthesis, induction of apoptosis, and cell cycle regulation with their mechanism of action. This review provides current knowledge on the bioactive potential of Cordyceps spp.
... parasitic on moth larvae and the moth larval bodies. It has protective effects on cardiovascular, liver and endocrine system [7][8][9]. However, highly specific natural habitat requirements, a high degree of host specificity for moth larvae and long-standing large scale excessive harvesting, have collectively made the naturally grown CS sorely deficient near extinction. ...
Background
Diabetic kidney disease (DKD) has mainly been considered as a glomerular disease. Our previous study showed that the progression of DKD was highly correlated with the dysfunction of renal proximal tubular cells. Fermented Cordyceps sinensis (CS), a substitute for natural CS, is a prominent herb widely used in China, and has exhibited excellent efficacy on DKD. However, the underlying mechanisms remain poorly understood.
Methods
The database analysis was used to identify the main therapeutic targets and pathways of CS involved in DKD treatment. Next, the protective effects of fermented CS on high glucose (HG, 30 mM) induced HK-2 cell injury was validated through cell proliferation and apoptosis assay, including CCK-8, EdU and TUNEL. Finally, quantitative real‑time PCR (qRT-PCR) and western blotting were used to verify key target genes.
Results
Our results revealed that 9 main targets (RELA, JNK1, PTEN, VEGFA, EGF, ERK2, CASP3, AKT1, MMP9) were recognized as key therapeutic targets with excellent binding affinity screened by database analysis and molecular docking. The biological processes were identified by Gene Ontology (GO) enrichment, which appeared mainly involved in the positive regulation of cell proliferation as well as the negative regulation of apoptosis. The verification experiments in vitro revealed that fermented CS significantly attenuated the HG-induced cytotoxicity and apoptosis, and promoted the proliferation of HK-2 cells. Moreover, fermented CS significantly downregulated the expressions of Bax, Caspase-3, VEGFA, P-AKT and P-ERK, and upregulated the expression of PTEN compared with that of HG group.
Conclusion
Our results demonstrate that the fermented CS has nephroprotective effects significantly, which functions via promoting proliferation and inhibiting apoptosis of renal proximal tubular cells, likely by targeting Caspase-3, Bax, VEGFA and PTEN. Furthermore, AKT and ERK signaling pathway may be the critical mechanisms underlying the efficacy of fermented CS in DKD treatment.
Fungi provide ecological and environmental services to humans, as well as health and nutritional benefits, and are vital to numerous industries. Fermented food and beverage products from fungi are circulating in the market, generating billions of USD.
However, the highest potential monetary value of fungi is their role in blue carbon trading because of their ability to sequester
large amounts of carbon in the soil. There are no conclusive estimates available on the global monetary value of fungi, primarily because there are limited data for extrapolation. This study outlines the contribution of fungi to the global economy and provides a first attempt at quantifying the global monetary value of fungi. Our estimate of USD 54.57 trillion provides a starting point that can be analysed and improved, highlighting the significance of fungi and providing an appreciation of their value. This paper identifies the different economically valuable products and services provided by fungi. By giving a monetary value to all important fungal products, services, and industrial applications underscores their significance in biodiversity and conservation. Furthermore, if the value of fungi is well established, they will be considered in future policies for effective ecosystem management.
Paecilomyces tenuipes is a popular medicinal mushroom, and has received extensive attention for medical application because of its various physiological activities. However, there is limited information about the anticancer and immunomodulatory activities of Paecilomyces tenuipes. This study attempted to evaluate the effect of an extract from the cultured fruiting bodies of Paecilomyces tenuipes (PTE) on the expression of the interleukin- 18 (IL-18) gene in rat pheochromocytoma (PC) 12 cells and rat brain. Related mRNA levels were determined by reverse transcription-polymerase chain reaction (RT-PCR). Protein levels were measured by Western blot and immunohistochemistry. Our results demonstrated that PTE induced IL-18 gene expression both in vitro and in vivo. Treatment of PC12 cells and rat brain cells with 10 μg/ml and 20 mg/kg PTE, respectively, yielded significant increases of IL-18 levels. Significantly, IL-18-immunoreactive neurons were detected in the Purkinje cells of the cerebellum. IL18-immunohistochemical staining was markedly enhanced in animals treated with PTE compared to findings in the untreated controls. These results suggest that PTE could be a potential candidate as an immune activator or anticancer drug.
Herbal drugs are manufactured from the leaves, roots, seeds, bark, fruit, stems, or flowers of various plants that have medical characteristics or are assumed to have medicinal benefits. The usage of herbal supplements by athletes has skyrocketed in the last decade. Athletes and non-athletes are increasingly using herbal medicines to boost endurance and strength performance. Herbal adaptogens are used to improve attention, increase endurance in scenarios where fatigue is present, reduce the number of stress-related diseases and impairments in the body, improve physical stamina, strength, and energy levels, improve sexual dysfunction, restore cognitive performance that has been affected by stress, and maintain cortisol.The research method involved a preliminary search on Google Search, PubMed, OVID Medline, Embase, ScienceDirect, Web of Science, and Google Scholar databases where keywords such as “Herbal adaptogens, Endurance, Athletes, Ashwagandha, Tulsi, Turmeric, Muscle strength” were used.In this article, we have reviewed the top 8 global market frontrunners of herbal adaptogens based on source, namely ashwagandha, astragalus, cordyceps, ginseng, holy basil, Rhodiola roseas, schisandra, and turmeric, and their effect on the improvement in the performance of athletes like increase in the muscle mass, endurance, and recovery of the athlete and their possible side effects.
Cordycepin (3'-deoxyadenosine), 2'-deoxyadenosine and the crystalline extracted from Cordyceps sinensis prepared by the authors have been characterized by NMR and IR studies.
Cordyceps militaris (Linn.) Link has been promoted on various nitrogenous media, yielding solutions which inhibit the growth of many strains of Bacillus subtilis. From the culture solutions a crystalline metabolic product, cordycepin, C10H13O3N5, has been isolated; it appears to be responsible for the total antibacterial activity of the culture solutions.
Alzheimer's disease (AD) and Pick's disease (PD) are dementing disorders of unknown origin. Monoamine oxidase (MAO) is important in the metabolism of a number of monoamine neurotransmitters. This study investigates MAO activity in aging, AD, and PD in frontal and temporal poles, nucleus basalis of Meynert (nbM), and hypothalamus. Regional variations in the activity of the two MAO forms (A and B) were found in aging, AD, and PD. Age-related increase of MAO-B was found in all four areas of the brain, and MAO-A was increased in the nbM and temporal pole. In AD, MAO-B was decreased in the nbM and increased in the temporal pole, while MAO-A was increased in the hypothalamus and frontal pole. In PD, MAO-B was decreased in the nbM and increased in the hypothalamus, while MAO-A was increased in the hypothalamus and decreased in the nbM and temporal pole. These data indicate that with regard to MAO activity, AD and PD are dissimilar diseases and neither strictly follows age-related changes.
This paper indicates that Paecilomyces sinensis ig 3g/kg/dx14 increases the amount of superoxide dismutase in the liver tissues of mice; that Paecilomyces sinensis is similar to natural Cordyceps sinensis in inhibiting the production of Lpo and increasing the amount of superoxide dismutase in the liver homogenates of mice in vitro. In addition Paecilomyces sinensis can also increase the amount of glutathione peroxidase in the liver homogenates of mice in vitro.