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The Scientific Rediscovery of an Ancient Chinese Herbal Medicine: Cordyceps sinensis Part I

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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.
... Despite having potent efficacy in rodents, purified myriocin is not an approved drug for human consumption. However, extracts from Isaria sinclairii and Cordyceps sinesis have been an essential component of traditional Chinese medication that has been consumed for thousands of years for the treatment of numerous indications, including diabetes [30][31][32][33][34][35] . Cordyceps gained worldwide prominence after 1993 following admittance from world record breaking Chinese long-distance runners that they consumed Cordyceps tonic during their training periods 30,32,33,36 . ...
... However, extracts from Isaria sinclairii and Cordyceps sinesis have been an essential component of traditional Chinese medication that has been consumed for thousands of years for the treatment of numerous indications, including diabetes [30][31][32][33][34][35] . Cordyceps gained worldwide prominence after 1993 following admittance from world record breaking Chinese long-distance runners that they consumed Cordyceps tonic during their training periods 30,32,33,36 . Since then, Cordyceps extracts have been increasingly sold as nutritional supplements in numerous countries, including United States and are being consumed by a large population globally. ...
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Ectopic ceramide accumulation in insulin-responsive tissues contributes to the development of obesity and impairs insulin sensitivity. Moreover, pharmacological inhibition of serine palmitoyl transferase (SPT), the first enzyme essential for ceramide biosynthesis using myriocin in rodents reduces body weight and improves insulin sensitivity and associated metabolic indices. Myriocin was originally extracted from fruiting bodies of the fungus Isaria sinclairii and has been found abundant in a number of closely related fungal species such as the Cordyceps . Myriocin is not approved for human use but extracts from Cordyceps are routinely consumed as part of traditional Chinese medication for the treatment of numerous diseases including diabetes. Herein, we screened commercially available extracts of Cordyceps currently being consumed by humans, to identify Cordyceps containing myriocin and test the efficacy of Cordyceps extract containing myriocin in obese mice to improve energy and glucose homeostasis. We demonstrate that commercially available Cordyceps contain variable amounts of myriocin and treatment of mice with a human equivalent dose of Cordyceps extract containing myriocin, reduces ceramide accrual, increases energy expenditure, prevents diet-induced obesity, improves glucose homeostasis and resolves hepatic steatosis. Mechanistically, these beneficial effects were due to increased adipose tissue browning/beiging, improved brown adipose tissue function and hepatic insulin sensitivity as well as alterations in the abundance of gut microbes such as Clostridium and Bilophila . Collectively, our data provide proof-of-principle that myriocin containing Cordyceps extract inhibit ceramide biosynthesis and attenuate metabolic impairments associated with obesity. Moreover, these studies identify commercially available Cordyceps as a readily available supplement to treat obesity and associated metabolic diseases.
... al. 2002) [11] . Cordycepin has a broad spectrum of biological activity, plays an important role in the treatment of respiratory and cerebrovascular diseases, enhancement of body immunomodulatory function and regulation of liver and renal metabolism (Zhu et al., 1998a(Zhu et al., , 1998b [20,21] . Moreover, it also has been used as an anti-cancer, anti-tumor, anti-fungal (Kim, et al. 2002) [8] , anti-hyperlipidemia (Guo, et al. 2010) [7] , antioxidant (Ramesh, et al. 2012) [15] , and anti-leukemia (Thomadaki, et al. 2008) [19] . ...
... al. 2002) [11] . Cordycepin has a broad spectrum of biological activity, plays an important role in the treatment of respiratory and cerebrovascular diseases, enhancement of body immunomodulatory function and regulation of liver and renal metabolism (Zhu et al., 1998a(Zhu et al., , 1998b [20,21] . Moreover, it also has been used as an anti-cancer, anti-tumor, anti-fungal (Kim, et al. 2002) [8] , anti-hyperlipidemia (Guo, et al. 2010) [7] , antioxidant (Ramesh, et al. 2012) [15] , and anti-leukemia (Thomadaki, et al. 2008) [19] . ...
Article
Spawn is a fundamental element in mushroom production. Present study was conducted to determine the effect of different organic additive on spawn production of Cordyceps militaris, for this purpose cereals flour such as Maize, Rice, Sorghum, Barley and Oat flour were used while Chickpea, Pigeon pea, Pea, Black gram and Green gram flour were used as pulses flour for spawn improvement and were added in wheat grains. The results obtained from present investigation show that, in case of cereal flour, maximum spawn growth was found in maize flour while in case of pulse flour use as organic additives, pigeon pea flour was found best organic additive for spawn production.
... Its long history of medicinal use in China, dates back to the Qing dynasty in A.D.1694 (Wang, 1914). According to Chinese tradition and the Chinese Pharmacopoeia (Commission, 2005), Cordyceps sinensis can "tonify the lung, replenish the kidneys, arrest bleeding, dissolve phlegm, treat chronic coughs, treat spontaneous sweating and restore strength after an illness" (Commission, 2005;Li & Tsim, 2004;Liu, 1998;Zhu, Halpern, & Jones, 1998a, 1998b. More recent studies suggest that Cordyceps may have immunomodulatory (Jordan, Hirsch, & Lee, 2008), anti-proliferative (Yang, Huang, Hsieh, & Lin, 2003), pro-apoptotic (Zhang & Wu, 2007) and anti-fibrotic effects (Li, Liu, Xiong, & Xu, 2006;Wang, Bai, Wang, & Dai, 2007). ...
Article
It has been suggested that the Traditional Chinese herbal preparation Cordyceps sinensis (CS) may have a beneficial effect in renal disease. We have previously demonstrated bio-activity of naturally occurring CS. To satisfy increasing demand, CS derivatives have been produced by aseptic mycelia cultivation. The aim of this work was to compare and contrast the bio-activity of natural CS and two specific products derived from cultured Cordyceps mycelia, “Jinshuibao Capsule” (Paecilomyces sinensis) and “Corbrin Capsule” (Hirsutella sinensis). In addition using two different cell systems we examined the potential anti-fibrotic potential of these products beyond the kidney. All three preparations antagonised the activity of the pro-fibrotic cytokine TGF-β1 in renal epithelial cells. Activity was seen in the raw water-soluble components, and the hydrophilic and hydrophobic extracts from each preparation suggesting that the bio-activity is not confined to one component of the raw material. In addition to the effects in the renal cell line, similar effects of antagonism of phenotypic activation of pulmonary fibroblasts by TGF-β1 was also seen suggesting an applicability of these observations to solid organ fibrosis beyond the kidney. Mechanistically the data demonstrate antagonism of TGF-β1 activation of Smad signalling and specifically of induction of the hyaladherin TSG-6, which we have previously demonstrated to orchestrate the formation of a hyaluronan, peri-cellular coats driving phenotypic cellular activation. In summary the data support the claim that both naturally occurring and products derived from cultured Cordyceps mycelia have similar bio-activity which may have particular relevance for solid organ fibrosis and associated organ dysfunction.
... Natural C. sinensis is a precious therapeutic agent in traditional Chinese medicine with a rich history of clinical use for health maintenance, disease amelioration, postdisease and post-surgery recovery, and anti-aging therapy [47,[76][77]. The Chinese Pharmacopoeia defines natural C. sinensis as an insect-fungi complex containing a dead larva from the Hepialidae family and the O. sinensis fruiting body. ...
Conference Paper
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Ascomycete reproduction is controlled by the mating-type (MAT) locus. The existence of homothallic and pseudohomothallic reproduction types has been hypothesized based on genetic data obtained for Hirsutella sinensis, the GC-biased Genotype #1 of Ophiocordyceps sinensis. However, the inconsistent occurrence of the mating-type genes of MAT1-1 and MAT1-2 idiomorphs in numerous H. sinensis strains at the genome level contradicts the genetic-based capability of the fungus to undergo self-fertilization. In addition to the genetic regulation of the mating process, transcriptional regulation also occurs in H. sinensis strains that show differential transcription of the mating genes or that exhibit transcription of the MAT1-2-1 gene with unspliced intron I that contains stop codons, which contradicts the (pseudo)homothallism hypotheses. These findings suggest that H. sinensis (either monoecious or dioecious) needs a mating partner to achieve sexual outcrossing(physiological heterothallism or hybridization) for the development and maturation of the fruiting body, ascocarps, and ascospores of natural C. sinensis. The genome assemblies of five H. sinensis strains contain the genes for both a- and α-pheromone receptors, which are differentially transcribed in H. sinensis. However, consistent occurrence and transcription of the mating genes of both MAT1-1 and MAT1-2 idiomorphs have been reported in natural C. sinensis, which includes the GC- and AT-biased genotypes of O. sinensis fungi and other cocolonized fungi. The differential occurrence and transcription of the mating-type genes of MAT1-1 and MAT1-2 idiomorphs in Samsoniella hepiali might reciprocally participate in the reproduction processes of O. sinensis and the entire lifecycle of natural C. sinensis.
... In a clinical trial in 2009, Johnson et al. [62] confirmed that a daily oral dose of AndoSan (a mushroom extract mixture containing A. blazei mycelium 82%, Hericium erinaceum 15%, Grifola frondosa 3%) when administered to subjects for 12 days, led to significant in vivo reduction in interleukin-1 (IL-1). The genus Cordyceps includes C. sinensis and C. militaris which are the most valued species in Traditional Chinese Medicine [63]. These have been established for immuno-logical regulation, free radical scavenging, anticancer, antimicrobial, analgesic, antihyperlipidemic, antileukemic and lung improving attributes. ...
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Chapter
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