Cordyceps militaris is being studied and cultivated as a medicinal mushroom having many valuable biological andpharmaceutical activities. In the breeding of new C. militaris mushroom, single ascospores were isolated and examined theirmycelial growth, mycelial density, and production of stroma and perithecia. Among them selected isolates were crossed andhybrids were produced showing high quality fruiting bodies on artificial media. Mycelial growth rate of new strain‘Dowonhongcho’ was higher than that of better on ‘Yedang 3’ on SDAY at 10-25oC. The stromata of new strain were club-shaped and bright orange-red. Its height was 6.1 cm and the cordycepin content was 0.34% on average. The new strainshowed 9% higher yield than ‘Yedang 3’ with producing firmer fruit bodies. The optimum temperature for mycelial growthwas 22~25oC and the optimum temperature for stroma development was 18~22oC. Fruiting bodies were began to produce45 days later after inoculation. This new cultivar may serve as a valuable one for artificial cultivation and industrial-scaleproduction of C. militaris.

The inhibitory activities of the Cordyceps pruinosa butanol fraction (Cp-BF) were investigated by determining inflammatory responses of lipopolysaccharide (LPS)-treated RAW264.7 macrophage cells and by evaluating HCl/ethanol (EtOH)-triggered gastric ulcers in mice. The molecular mechanisms of the inhibitory effects of Cp-BF were investigated by identifying target enzymes using biochemical and molecular biological approaches. Cp-BF strongly inhibited the production of NO and TNF-α, release of reactive oxygen species (ROS), phagocytic uptake of FITC-dextran, and mRNA expression levels of interleukin (IL)-6, inducible NO synthase (iNOS), and tumour necrosis factor-alpha (TNF)-α in activated RAW264.7 cells. Cp-BF also strongly down regulated the NF-κB pathway by suppressing IKKβ according to luciferase reporter assays and immunoblot analysis. Furthermore, Cp-BF blocked both increased levels of NF-κB-mediated luciferase activities and phosphorylation of p65/p50 observed by IKKβ overexpression. Finally, orally administered Cp-BF was found to attenuate gastric ulcer and block the phosphorylation of IκBα induced by HCl/EtOH. Therefore, these results suggest that the anti-inflammatory activity of Cp-BF may be mediated by suppression of IKKα and its downstream NF-κB activation. Since our group has established the mass cultivation conditions by developing culture conditions for Cordyceps pruinosa, the information presented in this study may be useful for developing new anti-inflammatory agents.

4-isopropyl-2,6-bis(1-phenylethyl)aniline 1 (KTH13-AD1) is a metabolite of Cordyceps bassiana that has been traditionally used to treat various inflammatory disease. Even though it has the magnificent pharmaceutical potential, there was not much understanding on its anti-inflammatory actions. Therefore, this study was aimed to determine the anti-inflammatory effects of KTH13-AD1. We found that KTH13-AD1 suppressed nitric oxide (NO) and reactive oxygen species (ROS) production in lipopolysaccharide (LPS)- or sodium nitroprusside (SNP)-treated macrophages (RAW264.7 cells). Similarly, mRNA expression of inducible NO synthase (iNOS) and tumor necrosis factor-a (TNF-a) analyzed by RT-PCR and real-time PCR was also reduced by this compound. Interestingly, KTH13-AD1 also strongly diminished the levels of NF-kB-mediated luciferase activities and nuclear translocated NF-kB family proteins. In agreement with these, KTH13-AD1 suppressed the upstream signaling pathway for NF-kB activation including IkBa, IKKa/b, AKT, p85/PI3K and Src in time- and dose-dependent manners. Therefore, these results strongly suggest that KTH13-AD1 has a strong anti-inflammatory activity via suppression of the NF-kB signaling pathway.

In this study, we aimed to examine the cellular and molecular mechanisms of KTH-13 (4-isopropyl-2,6-bis(1-phenylethyl)phenol) which is derived from Cordyceps staphylindaecola in the cancer cells survival. The apoptotic effect of KTH-13 on various cancer cells, such as C6 glioma, MDA-MB-231 breast cancer, and A549 cells, was determined by MTT assay, and result showed that KTH-13 (0-100mM) dramatically inhibited the cancer cell survival. IC50 of KTH13 were 60.549, 53.512, >100, in C6, MDA-MB-231, and A549, respectively. DNA fragmentation result revealed that MDA-MB-231 cells treated with KTH-13 100mM undergoes apoptosis. To understand the action mechanism of KTH-13, the effect of KTH-13 on caspase which is key regulator of apoptosis was verified. The amount of cleaved capspase-3 and 7, executioner caspases, was increased by KTH-13 treatment, at time dependent (capspase-3 case) and dose dependent manner (caspase-7 case). And the cleavage of caspase-9 which is initiator caspase was also elevated in KTH-13 treated MDA-MB-231 cells showing time dependent manner. However, caspase-8 was not regulated by KTH-13, indicating KTH-13 specifically targets caspase-9 signal. As caspase-9 is closely associated with intrinsic pathway, the involvement of bcl-2 family was identified. Bax, pro-apoptotic molecule, was up-regulated whereas Bcl-2, anti-apoptotic protein, was down-regulated. And the Bax/Bcl-2 ratio was increased about 10 times. Then, the survival signal was also observed. The phosphorylation of Akt and p85 was diminished by KTH-13 treatment at 2,4,6 and 8 hour. Collectively, results suggest that KTH-13 induces cancer cells apoptosis via caspase3, 7, 8 and Bcl-2 family signaling pathway. And the Akt and p85 is also involved in KTH-13 action mechanism.

Cordyceps species, including C. sinensis, C. militaris, C. pruinosa and C. bassiana and C. staphylindaecola are prized traditional medicinal materials. From many Cordyceps species, Cordyceps militaris is well known and is ethopharmacologically known in Far East Asian countries such as Korea, China, and Japan. Continuous scientific studies have found that these preparations are capable of exhibiting numerous pharmacological activities as anti-oxidative, anti-viral, anti-cancer, anti-fibrotic, antiinflammatory, anti-nociceptive, anti-angiogenic, anti-diabetic, and anti-obesity drugs. Many species of Cordyceps (more than 600 types) have not yet been evaluated for their pharmacological activities. A preliminary study indicated that the biological activity varied between species and even between strains of the same species. But the chemical and functional properties and constituents of Cordyceps militaris have been studies extensively. The chemical constituents of Cordyceps militaris include cordycepin (3'-deoxyadenosine) and its derivatives, ergosterol, polysaccharides, a glycoprotein and peptides containing aminoisobutyric acid. They include anti-tumour, anti-metastatic, mmunomodulatory, antioxidant, anti-inflammatory, insecticidal, antimicrobial, hypolipidaemic, hypoglycaemic, anti-ageing, neuroprotective and renoprotective effects. Cordycepin is reported to possess many pharmacological activities including immunological stimulating, anti-cancer, anti-virus, insecticidal, antibacterial and anti-infection activities. Polysaccharide accounts for the anti-inflammatory, antioxidant, antitumour, anti-metastatic, immunomodulatory, hypoglycaemic, steroidogenic and hypolipidaemic effects. Ergosterol exhibits anti-tumour and immunomodulatory activity. The aim of this presentation is to review the chemical constituents and pharmacological actions of Cordyceps militaris.

Cordyceps species (Cordycipitaceae, Hypocreales) were previously mentioned under dominant genera such as basidiomycetous Clavaria Vaill. ex L. and ascomycetous Sphaeria Haller. Cordyceps Fr. was coined by Fries (1818) from a combination of a Greek word cordyle, meaning a club, and a Latin word caput, meaning a head. Cordyceps was, however, ranked at tribal level under Sphaeria by Fries (1823). Link (1833) later re-elevated Cordyceps to genus level. As a result, there was variation on author citation of Cordyceps in different botanical codes such as Cordyceps (E. M. Fries) Link (1833), Cordyceps E. M. Fries (1818) and Cordyceps Fr. (1824). In 19th and 20th centuries, more and more species were described, with necessity to divide Cordyceps into subgenera, sections and subsections based on morphological similarities. Recent molecular phylogenetic studies, however, showed that Cordyceps is polyphyletic and its members are dispersed in various clades within Hypocreales. As a consequence, Cordyceps was amended in strict sense by Sung et al. (2007) and distantly related clades were named under separate genera. Here, we review recent nomenclatural changes of Cordyceps-related fungi in light of recent changes in the International Code of Nomenclature for algae, fungi, and plants (ICN).

일반성분 중 조회분 함량은 버섯이 균사체 보다 높은 조회분 함량을 보였다. 조단백질은 모든 시험구에서 19% 내외로 나타났고, 조지방 함량은 동충하초 균사체에서 가장 높았으며, 조섬유는 팽이버섯에서 가장 높게 나타났다. 가용성물질소물은 팽이버섯균사체와 동충하초균사체에서 60% 이상의 함량을 나타내었다. 각 시료별 총단백질과 총당의 구성 비율은 팽이버섯과 팽이버섯 균사체의 단백다당류의 구성이 다름을 확인하였다. 시료별 핵산관련물질 함량은 팽이버섯에서 5'-GMP, 5'-XMP, 5'-IMP순으로 높게 나타났고, 팽이버섯 균사체는 5'-XMP, 5'-GMP, 5'-IMP, 동충하초 균사체는 5'-XMP, 5'-IMP, 5'-GMP순으로 높게 나타났다. 모든시료에서 각각 17종의 아미노산이 검출되었다. 각 시료의 총 아미노산 함량을 살펴보면 팽이버섯 18,980 mg%, 팽이버섯 균사체 17,604 mg%, 동충하초 균사체 18,429 mg%로 나타났고 모든 시료에서 glutamic acid 함량이 가장 높았다. 유리아미노산 함량도 구성아미노산과 유사하게 팽이버섯, 팽이버섯 균사체, 동충하초 균사체 순으로 높게 나타났다. 본 실험결과 팽이버섯, 팽이버섯 균사체 및 동충하초 균사체는 핵산관련 물질과 아미노산 함량이 높게 나타나, 아미노산 함유 식품 개발에 적합한 자원으로 활용도가 기대된다.

Cordyceps militaris is a entomopathogenic ascomycetous fungus and cultivated as a medicinal mushroom having many valuable biological and pharmaceutical activities. It was cultivated on five different grain media which were compared with silkworm pupa medium for the artificial fruiting body production. C/N ratio of pupa and bean media was low at 5.9 and 5.8 respectively, which was attribute to low nitrogen contents compared to others. The various media had a significant effect on mycelial growth, cordycepin contents, fruiting body production. The mycelial growth were greatest at barley and wheat media but least at pupa medium. The cordycepin contents were highest at bean and pupa media with 2.9 and 2.6 mg/g, respectively. This was followed by wheat, corn, barley and brown rice media. The yield of fruiting body was greatest at barley and wheat media but the yield and days to harvest were least at silkworm pupa medium.

Cordyceps sensu lato contains more than 400 entomopathogenic and mycoparasitic species. It was traditionally classified in Clavicipitaceae of Hypocreales and recently phylogenetically separated into several genera such as Cordyceps Fr. 1818 emend. G. H. Sung et al.(Cordycipitaceae Kreisel ex Sung et al.), Elaphocordyceps G. H. Sung & Spatafora and Ophiocordyceps Petch emend. G. H. Sung et al.(Ophiocordycipitaceae G. H. Sung et al.), and Metacordyceps G. H. Sung et al . and Tyrannicordyceps Kepler & Spatafora (Clavicipitaceae (Lindau) Earle ex Rogerson). Some species of Cordyceps sensu lato (e.g., C. militaris and C. pruinosa) are highly regarded as medicinal mushrooms in East Asia. Beauveria species, on the other hand, are widely used as potential biocontrol agents for insects in agriculture and forest due to their wide host range and global distribution. A recently described Beauveria species, Beauveria sungii S.A. Rehner & Humber 2011, is here shown as the anamorph of Cordyceps scarabaeicola Y. Kobayasi 1976 based on the teleomorphic material and phylogenetic analysis of the B.sungii isolate KACC 47482. In Cordyceps sensu stricto clade, Cordyceps Fr. 1818 is an older generic name than Beauveria Vuill. 1912 .Hence ,C. scarabaeicola is suggested to be adopted for B. sungii on the priority basis of both generic name and species epithet in view of the recent revision of Article 59 of the Melbourne Code (recently changed to the ‘International Code of Nomenclature for algae, fungi, and plant’orICN). Based on one fungus = one name principle, all legitimate Beauveria species are also proposed to be transferred to Cordyceps. The consequences of abandonment of dual nomenclature for pleomorphic fungi are also briefly discussed with reference to Cordyceps and Beauveria.

The effects of environmental and nutritional requirement such as temperature, pH, different media, carbon, nitrogen, and carbon-to-nitrogen ratio on the mycelial growth of Cordyceps militaris strain ‘Yedang 3’ were studied. The optimum temperature and pH for the growth of mycelium were 20-25oC and pH 6-7, respectively. Out of ten media tested, mushroom complete media (MCM) was the best medium for fast mycelial growth, and Sabouraud’s dextrose agar yeast extract (SDAY), malt extract yeast extract agar (YMA) also were favored. The color and shape of colonies varied in different media. The best carbon sources for mycelial growth were fructose, mannitol, and sucrose, whereas the best nitrogen sources were tryptone and peptone. However, mycelia grew slowly in inorganic nitrogen compounds such as NH4Cl, (NH4)2SO4, NH4NO3, and NaNO3. The optimum C:N ratio observed on the culture media was 30-40 range. These results provided basic information on cultural characteristics of vegetative growth and might be useful for spawn production in Cordyceps militaris.

Cordyceps militar is (Clavicipitales) is an edible mushroom which is widely distributed in China, Japan and Korea. Various phytochemical constituents, cordycepin, homocitrully laminoadenosine and sterols have been reported from this source and a wide range of biological activities, including antimicrobial, macrophage activation, anticancer, immune modulatory effects were studied. In a continuing search for bioactive constituents from Korean mushrooms, we performed a phytochemical investigation of the MeOH extract from the fruiting bodies of C. militaris. By repeated column chromatographic separation of the extract, fourteen compounds, were isolated. The identification and structural elucidation of the compound was based on NMR spectral data. anti-aging activities were performed on adriamycin-induced cellular senescence model. Human dermal fibroblasts(HDFs) and human umbilical endothelial cells(HUVECs) treated with adriamycin for inducing aging were used for cytotoxicity and senescence-associated beta-galactosidase(SA-β-gal) activity assay.

밀리타리스 동충하초 추출물은 체내 염증반응을 유도하는 peroxinitrite를 밀리타리스 동충하초 추출물 128 μg/ml 처리로 peroxinitrite를 60.77±1.67% 저해시켜 뛰어난 저해능을 가지는 것으로 free radical의 생성을 억제하며, Raw 264.7 세포에 LPS 1 μg/ml을 처리하여 NO 생성이 3.75 ± 0.20 μM까지 증가하였으나 밀리타리스 동충하초 추출물 32 μg/ml 처리군에서 3.21 ± 0.10 μM, 64 μg/ml 처리군에서 3.07 ± 0.13 μM로 농도 의존적, 유의적으로 감소 시켰다. 또한, 이로 인해 발현되는 염증 유전자 COX-2의 발현을 유의적으로 저해 한 것을 Western blot으로 확인 하였다. 그러므로, 밀리타리스 동충하초 추출물은 항염증소재로의 가능성이 충분하다고 사료된다.

The average life expectancy has continuously increased with the development of medicine. However, Some of men have been suffered from the insufficient secretion of testosterone causing by physical factors, social and psychological factors. Testosterone is an essential steroid hormone controlling male reproductive function. Alternative medicines in plants, fungi, and insects have been studied to enhance sexuality. In the present study, we determined the effect of an acorn pollen and Cordyceps militaris fruiting body on testosterone concentration in Sprague-Dawley rats. Eighteen rats per group were housed to regular diet or diet supplemented with acorn pollen powder or fruiting body power for 4 weeks. Serum was collected from 6 rats per group. Results showed that changes of the body weight, food and water intake of the rats were not observed in this study. However, acorn pollen powder and Cordyceps militaris fruiting body significantly stimulated testosterone production (p < 0.05) compared to the control, respectively. Hence, it suggests that acorn pollen or Cordyceps militaris fruiting body might be developed as a complementary medicine to improve sexual hormones.

This study was carried out to investigate anticancer activities fruiting body extracts and fractions of Cordyceps militaris. Fruiting body of this mushroom was extracted using by 80% MeOH. Fractionations of these extracts were performed by n-hexane, methylene chloride, ethyl acetate, n-BuOH. AGS(human gastric cancer line) was cultured in media conditions (10% FBS, 1% Penicillin-Streptomycin in RPMI). Anticancer activities of each fractions of Cordyceps militaris were examined by using MTT, Cell titer Glo.

 ,  , Cordyceps (vegetable wasp and plant worm), an entomopathogenic fungi, has been used as a herbal medicine in Asian countries since ancient times. Cordyceps nutans is common but there is little research on this species. This study investigated the optimal culture conditions of C. nutans and the inhibitory effect on nitric oxide (NO) production in RAW 264.7 cell treated culture broth. The optimal conditions for the mycelial growth were 25℃ and pH 7.0-8.0. Mycelial growth was highest on mushroom complete medium (MCM), V8 juice agar (V8A), and yeast malt dextrose (YMD) medium. Mycelial growth on mushroom minimal medium (MMM) did not occur, so nutrient source was essential. Dextrose and sucrose as carbon sources, and ammonium citrate as a nitrogen source were satisfactory for mycelial growth. Cytotoxicity of C. nutans culture broth was not found in RAW 264.7 cells. C. nutans culture broth suppressed NO production of lipopolysaccharide (LPS)-stimulated RAW 264.7 cell in a dose-dependent manner. Thus, our results provided the optimal conditions for cultivation of C. nutans and showed that C. nutans may have excellent physiological activities.

Cordyceps militaris (CM) has been used as a traditional folk medicine to strengthen the immune system and regain energy in Far East Asian countries. Some of men have been suffered from the insufficient secretion of testosterone causing by physical factors, social and psychological factors. Testosterone is an essential steroid hormone controlling male reproductive function. Alternative medicines in plants, fungi, and insects have been studied to enhance sexuality. Cordyceps species including Cordyceps sinensis and C. militaris has been used as for the enhancement of sexual function for hundreds of years. In the present study, we determined the effect of fruiting bodies of C. militaris which cultured on bee drone medium (DCM) on testosterone concentration in Sprague-Dawley rats. Eighteen rats per group were housed to regular diet or diet supplemented with DCM for 4 weeks. Serum was collected from 6 rats per group. Results showed that changes of the body weight, food and water intake of the rats were not observed in this study. However, DCM significantly stimulated testosterone production (p < 0.05) compared to the control. Hence, it suggests that fruiting bodies of C. militaris grown on the bee drone medium might be developed as a complementary medicine to improve sexual hormones.

This study was carried to investigate the antidiabetic metabolism effect of water extract Cordyceps Militalis(C.M.) in Streptozotocin(STZ) induced diabetic rats. Diabetes were induced by intravenous injection of STZ at a dose of 42mg/kg,b.w. dissolved in citrate buffer. The water extract of C.M. was orally administrated once a day for 7 days at a dose of 500mg/kg,b.w(body weight). or 1,000mg/kg.b.w. The content serum glucose was significantly decreased in C.M. treated group compared to the those of STZ-control group. The content of hepatic glycogen and activities of glucose-6-phosphate dehydrogenase(G-6-PDH), glucokinase(GK) were significantly increased, but activity of glucose-6-phoshatase(G-6-Pase) was significantly decreased in C.M. treated group compared to the those of STZ-control group. These results indicated that water extract of C.M. would have antidiabetic metabolism effect in STZ-induced diabetic rats.

The objective of this study was to determine the feeding effect of a diet containing Cordyceps with fly pupa on the changes in blood lipid profile from broiler chickens, fatty acids and thiobarbituric acid reactive substances (TBARS) in chicken meat. A total of 360 chicks (Ross strain 308) were divided on hatch day into four treated groups with respect to a 35-day feeding regimen: T1 (control group), T2 (2.0% Cordyceps with fly pupa), T3 (3.5% Corceps with fly pupa) and T3 (5.0% Cordyceps with fly pupa). Blood triacylglyceride and total cholesterol level was significantly decreased by 5.32-10.63% and 9.23-12.62%, respectively, in groups T2, T3 and T4 when compared to T1 (p<0.05). Water holding capacity was significantly highest in T2 (p<0.05), while there were no significant differences among groups T2, T3 and T. In chicken meat, the ratio of saturated fatty acid to unsaturated fatty acid was high in the T3 and T4 groups, the ratio of n-6 to n-3 fatty acid was low in the T2, T3 and T4 groups and oleic acid (18:1n-9) was high in the T2, T3 and T4 groups, when compared to T1 (p<0.05). TBARS tended to increase according to the storage time (in days), and was significantly lower in the chicken thigh muscles with skin in groups T2, T3 and T4 as compared to T1 (p<0.05). These results suggest that a diet containing 2.0-3.5% of Cordyceps with fly pupa may decrease blood lipid and improve both the shelf-life and quality of broiler chicken meat.