한국에서 개발된 곤충유래 약용버섯인 누에동충하초의 생산기술개발 및 약리학적 특성

이상몽(Sang Mong Lee),김용균(Yong Gyun Kim),박현철(Hyean Cheal Park),김근기(Keun Ki Kim),손홍주(Hong Joo Son),홍창오(Chang Oh Hong),박남숙(Nam Sook Park) 한국생명과학회 2017 생명과학회지 Vol.27 No.2

동충하초(Cordyceps)는 B.C. 2,000년 이후로부터 지금까지 중국, 한국, 일본 등 아시아 국가에서 잘 알려진 전통적인 불로장생의 비약으로 사용되어져 왔다. 곤충기생 곰팡이균으로서 원조 동충하초로 불리는 Cordyceps속에 속하는 Cordyceps sinensis는 우리나라 한반도에서는 발견되지 않고 있다. 그 이유는 해당 곰팡이균에 특정적인 기주곤충인 박쥐나방(Hepialus armonicanus)이 우리나라에는 존재하지 않기 때문으로 보인다. 따라서 차선책으로서 한국형의 동충하초, 즉 Paecilomyces tenuipes 동충하초균에 대한 곤충생체배지로서 누에(Silkworm, Bombyx mori)를 기주곤충으로 사용하는 누에동충하초의 인공적인 생산방법을 세계 최초로 개발하게 된 것이다. 따라서 본 총설은 누에동충하초를 개발하게 된 역사적 배경과 생산방법 및 약리학적 효능과, 비곤충유래 동충하초인 인공배지 배양동충하초(밀리타리스동충하초: Cordyceps militaris, 붉은자루동충하초: Cordyceps pruinosa 등)의 배양조건과 동충하초 품종육성, 배지배양조건, 동충하초의 식품에의 응용 가능성, 화학적 구성성분 및 약리적 효능 등에 대해 고찰하였다. 곤충유래의 누에동충하초 및 비곤충유래동충하초균사체 및 자실체동충하초의 주요 약리작용은 항종양, 면역증강, 항피로, 항스트레스, 항산화, 항노화, 항당뇨, 항염증, 항혈전, 항지질 및 해충방제 효능으로 요약된다. 동충하초의 주요 생리활성물질들은 단백다당체(헥소스, 헥소사민), 코디세핀, 만니톨, 산성다당체 등이다. 단백다당체와 부타놀 추출물은 매우 강한 항종양 효과를 보이나 세포독성은 나타내지 않았다. 만니톨은 종양유발쥐의 수명을 유의성 있게 연장하였다. 에르고스테롤은 항종양 활성은 보이지 않았으나 왕성한 식세포활성을 보였다. 따라서 우리가 높은 관심을 가지고 있는 누에동충하초의 항종양 활성은 세포독성효과보다는 면역력증강효과에 기인하는 것으로 사료된다[164]. Cordyceps is a traditional Chinese medicinal herb well-known in China, Korea and Japan since B.C. 2,000. The original entomopathogenic fungus, Cordyceps sinensis belonging to the genus Cordyceps could not be found inside Korean peninsula due to the absence of the host insect for the corresponding entomogenous fungus. The development of artificial production methods of Korean type Cordyceps using the silkworm Bombyx mori as in vivo culture medium for the the entomopathogenic fungus Paecilomyces tenuipes is the first, and wonderful occasion in the research history of insect industry of this global world. The aim of this article is to review the historical research background, mass-production methods, and pharmacological effects of the silkworm-dongchunghacho (Paecilomyces tenuipes) which is a newly developed Korean medicinal insect-borne mushroom, and another non-insect-borne medicinal mushroom (Cordyceps militaris and Cordyceps pruinosa). Their biological actions include anti-tumor, immunostimulating, anti-fatigue, anti-stress, anti-oxidant, anti-aging, anti-diabetic, anti-inflammatory, anti-thrombosis, hypolipidaemic and insecticidal effects. The bioactive principles are protein-bound polysaccharides (hexose, hexosamin), cordycepin, D-manitol, acidic polysaccharide etc. Protein-bound polysaccharides and n-butanol fractions were demonstrated to show a significant anti-tumor activities but did not show a cytotoxicities. D-mannitol exhibited a significant prolongation of the life span in tumor bearing mice. Ergosterol did not show an efficient anti-tumor activity, but showed a significant phagocytosis enhancing activity. Anti-tumor activity of silkworm-dongchunghacho might be attributed to immuno-stimulating activities rather than cytotoxic effects [164]. Also this review comprises the breeding of Dongchunghacho varieties, optimization of culture conditions, improvement of learning and memory by Dongchunghacho, application of them as foods and chemical constituents.

동충하초속균의 균사생장최적화

홍인표 외 한국버섯학회 2004 한국버섯학회지 Vol.2 No.3

This study was carried out to obtain basic data on physiological characteristics for an artificial cultivation of fruiting body of Cordyceps. Specimens such as Cordyceps longissima, C. militaris and C. prvinosa were collected at Mt. Halla of Cheju island in July, 2003. Among four different culture media which have been used for culture of mushrooms, MCM medium was selected for the favorable culture medium of the Cordyceps tested. The initial pH of solid medium for mycelial growth of Cordyceps was good in the range of pH 5.0~7.0 lower than 8.0. The mycelial growth of C. longissima was most favorable on culture media supplemented with glucose, one of monosaccharides. In C. militaris, nine carbon sources were favorable to the mycelial growth as compared with control among 11 carbon sources. Six nitrogen sources were favorable to the mycelial growth of C. longissima as compared with control among 9 carbon sources; namely, the mycelial growth of C. longissima was most favorable on culture media contained potassium nitrate, and followed in order by ammonium citrate and sodium nitrate in 4 weeks incubation. 본 연구는 동충하초속균의 자실체 인공 재배를 위한 기초 자료를 얻고자 제주도 한라산에서 채집한 Cordyceps longissima, C. militaris, C. pruinosa 등 야생 동충하초의 형태적, 생리적 특성조사를 수행하였다. Cordyceps longissima : 지좌는 숙주에서 1~2개 발생하며 곤봉형 또는 불규칙형으로 표면이 다소 거칠고 적갈색을 띤다. 두부는 23~59×6~8 mm이며, 병부는 원통형으로 37~151×2.5~4.0 mm이다. 자낭각은 묻힌형으로 553~600×215~270 ㎛. 자낭은 가는 원통형으로 330~510×5~6㎛이며, 자낭포자는 11~13×1.4~1.8 ㎛이다. 자실체는 매미목 매미과의 곤충에서 발생하였다. 균사 생장은 MCM 배지에서 25℃, 4주 배양시 73 mm이며, 균사의 색택은 진황색을 나타내었다. 탄소원으로는 단당류인 glucose, 질소원으로는 potassium nitrate를 가장 잘 이용하였다. C. militaris : 지좌는 숙주에서 1~3개 발생하며 곤봉형으로 주황색을 띤다. 두부는 9~23×6~8mm이며, 병부는 원통형으로 27~30×6~7 mm이다. 자낭각은 반묻힌형으로 465~510×260~310 ㎛. 자낭은 가는 원통형으로 320~385×4.2~4.8 ㎛이며, 자낭포자는 2.2~4.5×1.2~1.4 ㎛이다. 자실체는 나비목 곤충의 번데기에서 발생하였다. 균사 생장은 PDA 배지에서 25℃, 4주 배양시 71 mm이며, 균사의 색택은 연노랑색을 나타내었다. 탄소원으로는 단당류인 frucose, 질소원으로는 potassium nitrate를 가장 잘 이용하였다. C. pruinosa : 지좌는 숙주에서 1개 발생하며 곤봉형으로 주홍색을 띤다. 두부는 7~9×3~4이며, 병부는 원통형으로 13~22× 2~3 mm이다. 자낭각은 반묻힌형으로 350~520×130~310 ㎛. 자낭은 원통형으로 256~270×5~6㎛이며, 자낭포자는 3.2~5.1×0.8~1.3 ㎛이다. 자실체는 나비목 곤충의 번데기에서 발생하였다. 균사 생장은 PDA 배지에서 25℃, 4주 배양시 60 mm이며, 균사의 색택은 연붉은색을 나타내었다. 탄소원으로는 단당류인 arabinose와 mannose, 질소원으로는 sodium nitrite를 가장 잘 이용하였다.

Authentication and quality control of Cordyceps sinensis, a traditional Chinese medicine known as winter-worm summer-grass

Cheung, Jerry KH,Li, Shao P,Tsim, Karl WK Kyung Hee Oriental Medicine Research Center 2005 Oriental pharmacy and experimental medicine Vol.5 No.4

Cordyceps, one of the most valued traditional Chinese medicines, consists of the dried fungus Cordyceps sinensis growing on the larva of caterpillar. It is also known as 'winter-worm and summer-grass' because of its appearance during different seasons. The parasitic complex of the fungus and the caterpillar is found in soil of a prairie at an elevation of 3,500 to 5,000 meters in northwestern part of China. According to Chinese medicinal theory, Cordyceps is used to replenish the kidney and soothe the lung, and indeed many clinical applications have been reported. The natural Cordyceps is rare and expensive on the local market, and therefore, several mycelial strains have been isolated from natural Cordyceps and manufactured in large quantities by fermentation technology, and they are commonly sold as health food products in Orient. The adulterants of Cordyceps are commonly found on the market, and therefore the authentication of these products has to be defined. Having the urgent need from current market, different chemical markers such as nucleoside, ergosterol, mannitol and polysaccharide are being used for quality control of Cordyceps. Unfortunately, these markers are far from optimization, and therefore extensive works are needed to define the pharmacological efficiency of these markers.

Optimization of Mycelial Growth of Entomogenous fungi of the Genus Cordyceps

홍인표,남성희,정이연,성규병,남학우,강석우,허현,이민웅,곽순성,Hong, In-Pyo,Nam, Sung-Hee,Jung, I-Yeon,Sung, Gyoo-Byung,Nam, Hack-Woo,Kang, Seok-Woo,Hur, Hyeon,Lee, Min-Woong,Guo, Shun-Xing The Korean Society of Mushroom Science 2004 한국버섯학회지 Vol.2 No.3

본 연구는 동충하초속균의 자실체 인공 재배를 위한 기초자료를 얻고자 제주도 한라산에서 채집한 Cordyceps longissima, C. militaris, C. pruinosa 등 야생 동충하초의 형태적, 생리적 특성조사를 수행하였다. Cordyceps longissima : 지좌는 숙주에서 1~2개 발생하며 곤봉형 또는 불규칙형으로 표면이 다소 거칠고 적갈색을 띤다. 두부는 $23{\sim}59{\times}6{\sim}8mm$이며, 병부는 원통형으로 $37{\sim}151{\times}2.5{\sim}4.0mm$이다. 자낭각은 묻힌형으로 $553{\sim}600{\times}215{\sim}270{\mu}m$. 자낭은 가는 원통형으로 $330{\sim}510{\times}5{\sim}6{\mu}m$이며, 자낭포자는 $11{\sim}13{\times}1.4{\sim}1.8{\mu}m$이다. 자실체는 매미목 매미과의 곤충에서 발생하였다. 균사 생장은 MCM 배지에서 $25^{\circ}C$, 4주 배양시 73 mm이며, 균사의 색택은 진황색을 나타내었다. 탄소원으로는 단당류인 glucose, 질소원으로는 potassium nitrate를 가장 잘 이용하였다. C. militaris : 지좌는 숙주에서 1~3개 발생하며 곤봉형으로 주황색을 띤다. 두부는 $9{\sim}23{\times}6{\sim}8mm$이며, 병부는 원통형으로 $27{\sim}30{\times}6{\sim}7mm$이다. 자낭각은 반묻힌형으로 $465{\sim}510{\times}260{\sim}310{\mu}m$. 자낭은 가는 원통형으로 $320{\sim}385{\times}4.2{\sim}4.8{\mu}m$이며, 자낭포자는 $2.2{\sim}4.5{\times}1.2{\sim}1.4{\mu}m$이다. 자실체는 나비목 곤충의 번데기에서 발생하였다. 균사 생장은 PDA 배지에서 $25^{\circ}C$, 4주 배양시 71 mm이며, 균사의 색택은 연노랑색을 나타내었다. 탄소원으로는 단당류인 frucose, 질소원으로는 potassium nitrate를 가장 잘 이용하였다. C. pruinosa : 지좌는 숙주에서 1개 발생하며 곤봉형으로 주홍색을 띤다. 두부는 $7{\sim}9{\times}3{\sim}4$이며, 병부는 원통형으로 $13{\sim}22{\times}2{\sim}3mm$이다. 자낭각은 반묻힌형으로 $350{\sim}520{\times}130{\sim}310{\mu}m$. 자낭은 원통형으로 $256{\sim}270{\times}5{\sim}6{\mu}m$이며, 자낭포자는 $3.2{\sim}5.1{\times}0.8{\sim}1.3{\mu}m$이다. 자실체는 나비목 곤충의 번데기에서 발생하였다. 균사 생장은 PDA 배지에서 $25^{\circ}C$, 4주 배양시 60 mm이며, 균사의 색택은 연붉은색을 나타내었다. 탄소원으로는 단당류인 arabinose와 mannose, 질소원으로는 sodium nitrite를 가장 잘 이용하였다. This study was carried out to obtain basic data on physiological characteristics for an artificial cultivation of fruiting body of Cordyceps. Specimens such as Cordyceps longissima, C. militaris and C. pruinosa were collected at Mt. Halla of Cheju island in July, 2003. Among four different culture media which have been used for culture of mushrooms, MCM medium was selected for the favorable culture medium of the Cordyceps tested. The initial pH of solid medium for mycelial growth of Cordyceps was good in the range of pH 5.0~7.0 lower than 8.0. The mycelial growth of C. longissima was most favorable on culture media supplemented with glucose, one of monosaccharides. In C. militaris, nine carbon sources were favorable to the mycelial growth as compared with control among 11 carbon sources. Six nitrogen sources were favorable to the mycelial growth of C. longissima as compared with control among 9 carbon sources; namely, the mycelial growth of C. longissima was most favorable on culture media contained potassium nitrate, and followed in order by ammonium citrate and sodium nitrate in 4 weeks incubation.

Optimization of Mycelial Growth of Entomogenous fungi of the Genus Cordyceps

In-Pyo Hong,Sung-Hee Nam,I-Yeon Jung,Gyoo-Byung Sung,Hack-Woo Nam,Seok-Woo Kang,Hyeon Hur,Min-Woong Lee,Shun-Xing Guo 한국버섯학회 2004 한국버섯학회지 Vol.2 No.3

This study was carried out to obtain basic data on physiological characteristics for an artificial cultivation of fruiting body of Cordyceps. Specimens such as Cordyceps longissima, C. militaris and C. pruinosa were collected at Mt. Halla of Cheju island in July, 2003. Among four different culture media which have been used for culture of mushrooms, MCM medium was selected for the favorable culture medium of the Cordyceps tested. The initial pH of solid medium for mycelial growth of Cordyceps was good in the range of pH 5.0~7.0 lower than 8.0. The mycelial growth of C. longissima was most favorable on culture media supplemented with glucose, one of monosaccharides. In C. militaris, nine carbon sources were favorable to the mycelial growth as compared with control among 11 carbon sources. Six nitrogen sources were favorable to the mycelial growth of C. longissima as compared with control among 9 carbon sources; namely, the mycelial growth of C. longissima was most favorable on culture media contained potassium nitrate, and followed in order by ammonium citrate and sodium nitrate in 4 weeks incubation.

In vitro에서 큰번데기 동충하초 자실체형성의 불안정성

부샨 쓰레스타 외 한국버섯학회 2004 한국버섯학회지 Vol.2 No.3

Traditionally, Cordyceps species have been used as a part of herbal medicine in Oriental countries, including Korea for internal health, vigor and to cure different diseases related to heart, lung etc. In recent years, research on artificial fruiting of some species of the genus Cordyceps including C. militaris has been carried out extensively because of their medicinal value. Instability observed in the in vitro fruiting of C. militaris is reported in the present study. 전통적으로 Cordyceps종은 한국을 포함한 동양에서 건강증진과 심장과 폐에 관련된 질환을 치료하는 약용식물의 하나로 사용되어왔다. 최근에 동충하초의 약리적 가치 때문에 큰번데기 동충하초를 포함한 몇가지 Cordyceps종의 인공재배에 관한 연구가 활발하게 이루어지고 있다. 본 연구에서는 큰번데기 동충하초를 in vitro에서 인공재배한 결과 자실체 형성이 불안정한 것을 관찰하였기에 보고하고자 한다.

Instability in in vitro fruiting of Cordyceps militaris

부샨쓰레스타,박영진,한상국,최성근,성재모,Shrestha, Bhushan,Park, Young-Jin,Han, Sang-Kuk,Choi, Sung-Keun,Sung, Jae-Mo The Korean Society of Mushroom Science 2004 한국버섯학회지 Vol.2 No.3

전통적으로 Cordyceps종은 한국을 포함한 동양에서 건강증진과 심장과 폐에 관련된 질환을 치료하는 약용식물의 하나로 사용되어왔다. 최근에 동충하초의 약리적 가치때문에 큰번데기 동충하초를 포함한 몇가지 Cordyceps 종의 인공재배에 관한 연구가 활발하게 이루어지고 있다. 본 연구에서는 큰번데기 동충하초를 in vitro에서 인공재배한 결과 자실체 형성이 불안정한 것을 관찰하였기에 보고하고자 한다. Traditionally, Cordyceps species have been used as a part of herbal medicine in Oriental countries, including Korea for internal health, vigor and to cure different diseases related to heart, lung etc. In recent years, research on artificial fruiting of some species of the genus Cordyceps including C. militaris has been carried out extensively because of their medicinal value. Instability observed in the in vitro fruiting of C. militaris is reported in the present study.

Biochemical Characterization of Protease Produced by Cordyceps nutans

( Seon Ah Kim ),( Mi-kyung Kim ) 대한임상검사과학회 2012 대한임상검사과학회지(KJCLS) Vol.44 No.4

The fruiting body of Cordyceps is derived from the pupa or larva of insects infected by the entomopathogenic fungi Cordyceps. The fruiting body has been used as an anti-cancer and anti-inflammatory ingredient in traditional Chinese medicine. The biochemical characteristics of protease isolated from Cordyceps nutans were investigated in this study. The culturing period for production of protease by C. nutans was 10days. The acidity was pH 7.0, and the temperature was 25℃. The carbon and nitrogen sources for the production of the protease were glucose and yeast extract, respectively. The ratio of C/N was 2% glucose and 0.6% yeast extract. 0.06% CuSO4 was used as the inorganic salt. The investigation into the acidity of the protease produced by C. nutans revealed that the optimal pH and temperature were pH 7.0 and 30℃. The stability of the protease was shown as pH 6.0∼9.0 and 30∼50℃. The investigation into the influence of the metal ions on the enzyme activation of C. nutans revealed that it was inhibited in ZnSO4 and activated in FeSO4.

Biochemical Characterization of Protease Produced by Cordyceps nutans

Kim, Seon Ah,Kim, Mi-Kyung 대한임상검사과학회 2012 대한임상검사과학회지(KJCLS) Vol.44 No.4

The fruiting body of Cordyceps is derived from the pupa or larva of insects infected by the entomopathogenic fungi Cordyceps. The fruiting body has been used as an anti-cancer and anti-inflammatory ingredient in traditional Chinese medicine. The biochemical characteristics of protease isolated from Cordyceps nutans were investigated in this study. The culturing period for production of protease by C. nutans was 10days. The acidity was pH 7.0, and the temperature was $25^{\circ}C$. The carbon and nitrogen sources for the production of the protease were glucose and yeast extract, respectively. The ratio of C/N was 2% glucose and 0.6% yeast extract. 0.06% $CuSO_4$ was used as the inorganic salt. The investigation into the acidity of the protease produced by C. nutans revealed that the optimal pH and temperature were pH 7.0 and $30^{\circ}C$. The stability of the protease was shown as pH 6.0~9.0 and $30{\sim}50^{\circ}C$. The investigation into the influence of the metal ions on the enzyme activation of C. nutans revealed that it was inhibited in $ZnSO_4$ and activated in $FeSO_4$.

동충하초 nutans에 의해 생산 된 Protease의 생화학 적 Characterization

김선아,김미경 대한임상검사과학회 2012 대한임상검사과학회지(KJCLS) Vol.44 No.4

The fruiting body of Cordyceps is derived from the pupa or larva of insects infected by the entomopathogenic fungi Cordyceps. The fruiting body has been used as an anti-cancer and anti-inflammatory ingredient in traditional Chinese medicine. The biochemical characteristics of protease isolated from Cordyceps nutans were investigated in this study. The culturing period for production of protease by C. nutans was 10days. The acidity was pH 7.0, and the temperature was 25℃. The carbon and nitrogen sources for the production of the protease were glucose and yeast extract, respectively. The ratio of C/N was 2% glucose and 0.6% yeast extract. 0.06% CuSO4 was used as the inorganic salt. The investigation into the acidity of the protease produced by C. nutans revealed that the optimal pH and temperature were pH 7.0 and 30℃. The stability of the protease was shown as pH 6.0∼9.0 and 30∼50℃. The investigation into the influence of the metal ions on the enzyme activation of C. nutans revealed that it was inhibited in ZnSO4 and activated in FeSO4. .