Crouching Fungus, Hidden Caterpillar

Crouching Fungus, Hidden Caterpillar

Using STN to explore World Traditional Medicine

6/28/2010

CAS is a division of the American Chemical Society. Copyright 2010 American Chemical Society. All rights reserved.2

In the 1990s, a team of unknown Chinese female track and field athletes stunned the world by annihilating long-standing records

•

1993 Stuttgart World Championship (August)

–

Took gold and silver medals in the Woman’s 10,000m

–

Swept all three medals in the Women’s 3,000m

6/28/2010


Wang Junxia

•

Stuttgart (August 1993)–

Took gold medal in the Woman’s 10,000m

•

Beijing National Championship (September 1993)

–

Broke three world records in three days

–

Took 16.5 seconds off Woman’s 3,000m

–

Took 42.0 seconds off Woman’s 10,000m

•

End of 1993–

Won the World Cup Marathon Championship

6/28/2010


•

Stuttgart (August 1993)–

Won gold medal for Woman’s 3,000m

•

Beijing (September 1993)–

Captured world record in the Woman’s 1,500m

–

Went from 73rd in the world to world record holder within a year

Qu

Yunxia

6/28/2010


First Asians to win gold medals in such world sports events

Track & Field News

: "They [the Chinese] appear to have come up with the greatest quantum leap in human performance in history.“

How did they do it?

Coach Ma Junren

attributed success to: “Hard work and ancient Chinese secrets—turtle’s blood and caterpillar milkshakes.”

Caterpillar milkshakes? Dong Chong Xia Cio

6/28/2010


Using STN to explore World Traditional Medicine (WTM)

•

What is Dong Chong Xia Cio?•

What is WTM?•

Why is WTM inaccessible?•

What makes STN a rich source of WTM information?

•

What can WTM tell us about Dong Chong Xia Cio?

•

What does CAS REGISTRYSM

tell us about WTM?

What is Dong Chong Xia Cio?

6/28/2010


On grasslands of Himalayan Plateau lives a small, enigmatic creature

Only at altitudes of 9,800 to 16,000 feet •

Tibet •

Nepal•

Bhutan•

Sichuan, China•

Yunnan, China

6/28/2010


According to legend, this creature can transform itself from animal to plant, then back again

“Winter worm, summer grass”•

Yartsa

Gunba

(Tibetan)•

Dong Chong Xia Cio

(Chinese) Caterpillar fungus

6/28/2010


Tibetan herders discovered Yartsa

Gunba

thousands of years ago while observing invigorated behavior of yaks that ate fruiting bodies

6/28/2010


Caterpillar fungus (Cordyceps

sinensis) is the rarest, most expensive, and most celebrated herbal remedy in the world

6/28/2010


Herbal remedies are one component of World Traditional Medicine (WTM)

What is Traditional Medicine*?•

Knowledge, skills, and practices of maintaining health and treating physical and mental illness

•

Based on observations, beliefs, and experiences indigenous to different cultures

•

Serves as primary health care for 80% of the population in some Asian and African countries

*Definition according to WHO (United

Nations World Health Organization)

6/28/2010


Why is information on WTM inaccessible to many searchers?

•

Western scientists distrust and discount “folk remedies”

•

Asian WTM not available to Western scientists until recently

•

WTM not part of patenting tradition until 1990s

•

Often overlooked•

Unique, one-of-a-kind inventions

•

Small Asian patent authorities not covered by many database producers

•

Literature published in Asian languages not translated into English

6/28/2010


What makes STN a rich source of WTM?

•

Robust coverage of WTM content (patent, medicinal, food, and life science databases)

•

Continual enhancement of Asian coverage in STN‘s major value-added patent databases

•

English translations of many “obscure”

Asian-language patents and journal articles

•

CAplusSM

–

60 patent authorities, many smaller patent offices not always covered by others

–

50,000 WTM patents added earlier this year

•

CAS REGISTRY–

Links WTM to published substance information through CAS Registry Numbers®

6/28/2010


What can STN tell us about Dong Chong Xia Cio?

•

Search STN cluster 2Anavist•

Search terms –

Caterpillar fungus–

Cordyceps

sinensis•

2,248 total answers for all six databases

=> file 2Anavist => search caterpillar fungusL8 95 FILE CAPLUS L9 3 FILE EPFULL L10 4 FILE PCTFULL L11 2 FILE USPAT2 L12 12 FILE USPATFULL L13 306 FILE WPINDEX TOTAL FOR ALL FILESL14 422 CATERPILLAR FUNGUS

=> search cordyceps

sinensisL16 1672 FILE CAPLUS L17 35 FILE EPFULL L18 72 FILE PCTFULL L19 25 FILE USPAT2 L20 150 FILE USPATFULL L21 413 FILE WPINDEX TOTAL FOR ALL FILESL22 2367 CORDYCEPS SINENSIS

=> search L15 or L23TOTAL FOR ALL FILESL43 2248 DUPLICATE REMOVE L42

Let’s import these answers into STN®

AnaVistTM

for analysis of trends

6/28/2010


Patents 1185

Non-patents 512

Interest in this topic has exploded over the last 20 years.

Powerful analytical capabilities of STN AnaVist allow you to view many trends, such as publication years

6/28/2010


Patents 1185

Non-patents 512

People’s Republic of China dominates caterpillar fungus research

6/28/2010


STN AnaVist shows that China’s patent publication in caterpillar fungus began in 1987

6/28/2010


Earlier this year, 50,000 WTM patents were added to CAplus

•

Let’s see what they have to say about the magical properties of caterpillar fungus

6/28/2010


Chinese-language patent from CAplus:

Cordyceps

provides many curative effects

TI

A health tea

prepared from Chinese medicinal materials of Yigong

tea, Cordyceps, and Fructus

Lycii, and its preparation method

IN

He, Xingyou

PA Peop. Rep. China

SO

Faming Zhuanli

Shenqing

Gongkai

Shuomingshu, No pp. given

DT

Patent

LA Chinese

AB A health tea, chong

caocha

(Cordyceps

health tea), having effects in tonifying

lung, invigorating kidney, stopping bleeding, resolving phlegm, improving eyesight, resisting aging, resisting radiation, and protecting health, is prepd. by oven drying Yigong

tea, Cordyceps, and Fructus

Lycii

resp.; pulverizing; sieving; mixing; sterilizing; and packaging. The health tea can be used for treating chronic cough, dyspnea

due to deficiency, neurasthenia, spermatorrhea, soreness of waist and knee joints, liver diseases, and diabetes.

6/28/2010



Cordyceps

offers mental health benefits

AN 2005:1214021 CAPLUS

TI A health food

IN Yu, Hong

PA Peop. Rep. China

SO Faming Zhuanli

Shenqing

Gongkai

Shuomingshu

DT Patent

LA Chinese

AB

The product has effects in calming nerves

and strengthening brain, resisting radiation, relieving hypoxic, relieving body fatigue,

improving sleep, resisting aging, improving immunity, promoting metab.; and can overcome anxiety and depression, improve phys. strength and intelligence.

6/28/2010



Cordyceps

removes speckles and wrinkles, improves intelligence, prevents myopiaAN 2005:896079 CAPLUS

TI A series of Cordyceps

milks and Cordyceps

milk products, and their preparation methods

IN LI, Jiang

PA Peop. Rep. China

SO Faming Zhuanli

Shenqing

Gongkai

Shuomingshu, No pp. given

DT Patent

LA Chinese

AB A series of functional Cordyceps

milk products has anticancer, cardiovascular and cerebrovascular

diseases preventing, renal failure reliving, antiviral, speckle and wrinkle removing, intelligence improving, yang supporting, fat reducing, hair and skin caring, and myopia preventing effects.

6/28/2010


Chinese-language patent from CAplus: Cordyceps

inhibits tumor cells and relieves effects of chemotherapy

AN 1997:208475 CAPLUS

TI Capsule made from fermented cordyceps

sinensis

powder, rhodiola

sacra and dioscorea

opposite, and its preparation method

AU Liang, Shan

CS ASSIGNEE: Sichuan Huichuntang

Biotechnology Co., Ltd.

SO (2008) Faming Zhuanli

Shenqing

Gongkai

Shuomingshu.

LA Chinese

AB

...It has yang supporting, spleen, stomach, lung and kidney invigorating, salivation promoting, seminal emission arresting, blood circulation promoting, blood stasis dispelling, anti-inflammatory, antibacterial, antifatigue, anti-anoxia, antiaging, immunity enhancing, and tumor cells inhibiting effects;

and can be used for treating spleen diseases, lung diseases, stomach diseases, kidney diseases, hypertension, hypotension, hyperthyroidism, hypothyroidism, and diabetes.

It can also relieve the adverse side effects of chemotherapy

6/28/2010



Cordyceps

is “Antisenile

medicine”

AN 2006:144722

TI Antisenile

medicine

IN Zhao, Heng

PA Zhao Heng, Peop. Rep. China

SO Faming Zhuanli

Shenqing

Gongkai

Shuomingshu, 26 pp.

AB The medicine primarily consists of .alpha.-

mannatide

15%-45%, melatonin 0.5%-5% and Chinese medicine for removing free radical 50-

80% The medicine also consists of Chinese medicine for enhancing body immunity, Chinese medicine for adjusting neuroendocrine

function,

Chinese medicine for adjusting body metab.,

Chinese medicine for prolong cell life, and Chinese medicine for antigene

mutation.

6/28/2010


Chinese-language journal article from CAplus:

Cordyceps

protects against genetic damage from cigarette smoke

AN 1997:208475 CAPLUS

TI Protective effects of Cordyceps

sinensis

(Berk) Sacc, artificial pypha

on genetic damage induced by cigarette smoke

AU Ma, Jixia; Bi, Shixiu

CS Sch. Life Sci., Beijing Univ., Beijing, 100871, Peop. Rep. China

SO Beijing Daxue

Xuebao, Ziran

Kexueban

(1996), 32(4), 521-526

LA Chinese

AB The protective effects of cordyceps

sinensis


against genetic damage induced by cigarette smoke in Kunming mice strain were studied with the micronucleus test of bone marrow cell and sperm malformation test. Mutagenic potential in groups treated with cigarette smoke for 1, 2 and 4 wk was noticed. The anti-mutation function of the cordyceps

sinensis


was very evident in groups for 2 wk. The rate of suppression of micronucleus formation was 55%.

6/28/2010


How is it possible that one small fungus can exhibit so many health benefits? What are its bioactive constituents?

AN 2006:226491 CAPLUS

TI Pharmacological actions of Cordyceps, a prized folk medicine

AU Ng, T. B.; Wang, H. X.

CS Department of Biochemistry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, Peop. Rep. China

SO Journal of Pharmacy and Pharmacology (2005), 57(12), 1509-1519

DT Journal; General Review

LA English

AB A review. Cordyceps

species, including C. sinensis,

C. militaris,

C. pruinosa,

and C. ophioglossoides,

are prized traditional medicinal materials. The aim of this article is to review the chem. constituents and pharmacol. actions of Cordyceps

species.

The chem. constituents include

–

cordycepin

(3'-deoxyadenosine) and its derivs.

–

ergosterol

–

polysaccharides

–

glycoprotein

–

peptides contg. α-aminoisobutyric

acid.

(continued)

6/28/2010


What are the pharmacological effects?

AB They include antitumor, antimetastatic

immunomodulatory, antioxidant, anti-inflammatory, insecticidal, antimicrobial, hypolipidemic, hypoglycemic, antiaging, neuroprotective, and renoprotective

effects.

Polysaccharide accounts for the anti-inflammatory, antioxidant, antitumor, antimetastatic, immunomodulatory, hypoglycemic, steroidogenic, and hypolipidemic

effects.

Cordycepin

contributes to the antitumor, insecticidal, and antibacterial activity.

Ergosterol

exhibits antitumor and immunomodulatory

activity.

A DNase

has been characterized.

What can we learn about these substances from CAS REGISTRY?

6/28/2010


CAS REGISTRY: Cordycepin

(3′-deoxy-adenosine)

~1,100 references in CAplus (1907 to date)

HO

N ON

N

OH

NH 2

N

RR S

RN 73-03-0 REGISTRYCN Adenosine, 3'-deoxy-

(CA INDEX NAME)OTHER CA INDEX NAMES:CN Cordycepin

(6CI, 7CI) OTHER NAMES:CN .beta.-D-erythro-Pentofuranoside, adenine-

9 3-deoxy-CN 3'-DeoxyadenosineCN 9-(3-Deoxy-.beta.-D-ribofuranosyl)adenineCN 9-CordyceposidoadenineCN 9H-Purin-6-amine, 9-(3-deoxy-.beta.-D-

erythro-pentofuranosyl)-CN CordycepineCN NSC 401022CN NSC 63984MF C10 H13 N5 O3

6/28/2010


Cordycepin

was isolated and its structure elucidated in 1951

AN 1952:48370 CAPLUSTI Cordycepin, a metabolic product from cultures of Cordyceps

militaris. I. Isolation and characterization

AU Cunningham, K. G.; Hutchinson, S. A.; Manson, William; Spring, F. S.CS Roy. Tech. Coll., Glasgow, UKSO Journal of the Chemical Society

(1951)

2299-300

AN 1952:48371 CAPLUSTI Cordycepin, a metabolic product from cultures of Cordyceps

militaris. II. Structure of cordycepin

AU Bentley, H. R.; Cunningham, K. G.; Spring, F. S.CS Roy. Tech. Coll., Glasgow, UKSO Journal of the Chemical Society

(1951)

2301-5

6/28/2010


What are the mechanisms behind cordycepin’s

potent bioactivities?

HO

N ON

N

OH

NH 2

N

RR S

HO

N O

OH

N

N

OH

NH 2

N

RR

SR

Cordycepin, 3′-deoxy-adinosine Adenosine

6/28/2010


Antiviral effects of adenosine analog noted in 1974

Cordycepin

inhibits action of viral mRNA in synthesizing peptides

AN 1974:421592 CAPLUS

TI Inhibition of herpes simplex virus replication by cordycepin

AU Becker, Yechiel; Olshevsky, Udy

CS Hadassah Med. Sch., Hebrew Univ., Jerusalem, Israel

SO Israel Journal of Medical Sciences

(1973), 9(11-12), 1581-5

AB Cordycepin

[73-03-0] inhibited the synthesis of herpes simplex virus in infected cells, although viral DNA replication was not affected and the synthesis of structural peptides was only partially inhibited. Cordycepin

has been reported to inhibit the synthesis of adenylate-rich sequences of mRNA, suggesting that the assembly of the virons

may require the synthesis of peptides translated from mRNA species rendered nonfunctional by cordycepin.

HO

N ON

N

OH

NH 2

N

RR S

6/28/2010


Scientists discover how cordycepin

fights cancer (2010)

Inhibits tumor cell mRNA protein synthesis

AN 2010:59472 CAPLUS TI Cordycepin

Inhibits Protein Synthesis and Cell Adhesion through Effects onSignal Transduction

AU Wong, Ying Ying; Moon, Alice; Duffin, Ruth; Barthet-Barateig, Adeline;Meijer, Hedda

A.; Clemens, Michael J.; de Moor, Cornelia H.CS School of Pharmacy, Centre for Biomolecular

Sciences, University ofNottingham, Nottingham, NG7 2RD, UK

SO Journal of Biological Chemistry (2010), 285(4), 2610-2621AB 3'-Deoxyadenosine, also known as cordycepin, is a known polyadenylation

inhibitor with a large spectrum of biol. activities, includinganti-proliferative, pro-apoptotic and anti-inflammatory effects.

In thisstudy we confirm that cordycepin

reduces the length of poly(A) tails, withsome mRNAs being much more sensitive than others.

The low doses of cordycepin

that cause poly(A) changes also reduce the proliferation of NIH3T3 fibroblasts. At higher doses of the drug we obsd. inhibition of cell attachment and a redn. of focal adhesions.

Furthermore, we obsd. a strong inhibition of total protein synthesis that correlates with an inhibition of mammalian target of rapamycin

(mTOR) signaling, as obsd. by redns. in Akt

kinase

and 4E-binding protein (4EBP) phosphorylation. In 4EBP knock-out cells, the effect of cordycepin

on translation is strongly reduced, confirming the role of this modification. In addn., the AMP-activated kinase

(AMPK) was shown to be activated.

Inhibition of AMPK prevented translation repression by cordycepin

and abolished 4EBP1 dephosphorylation, indicating that the effect of cordycepin

on mTOR

signaling and protein synthesis is mediated by AMPK activation. We conclude that many of the reported biol. effects of cordycepin

are likely to be due to its effects on mTOR

and AMPK signaling.

6/28/2010


STN instantly links to full-text sources—

Scientists discover how cordycepin

fights cancer

6/28/2010


CAS REGISTRY: α-Aminoisobutyric

acid ~3,075 references in CAplus (1907 to date)

RN 62-57-7 REGISTRYED Entered STN: 16 Nov 1984CN Alanine, 2-methyl-

(CA INDEX NAME)OTHER NAMES:CN .alpha.,.alpha.-DimethylglycineCN .alpha.-Aminoisobutanoic

acidCN .alpha.-Aminoisobutyric

acidCN .alpha.-MethylalanineCN 2,2-DimethylglycineCN 2-Amino-2-methylpropanoic acidCN 2-Amino-2-methylpropionic acidCN 2-Aminoisobutyric acidCN 2-MethylalanineCN 21: PN: WO2005055994 PAGE: 50 claimed sequenceCN AIBCN Aminoisobutyric

acid CN NSC 16590

6/28/2010


CAS REGISTRY: Cordycepic

acid (D-mannitol)


RN 69-65-8 REGISTRYED Entered STN: 16 Nov 1984CN D-Mannitol

(CA INDEX NAME)OTHER CA INDEX NAMES:CN Cordycepic

acid (6CI, 7CI) CN Mannitol, D-

(8CI)OTHER NAMES:CN Cerestar

16700CN D-(-)-MannitolCN D-MannitCN DiosmolCN E 421CN Isotol...

6/28/2010


CAS REGISTRY: Ergosterol

(Provitamin

D)


RN 57-87-4 REGISTRY ED Entered STN: 16 Nov 1984CN Ergosta-5,7,22-trien-3-ol, (3.beta.,22E)-

(CA INDEX NAME)OTHER CA INDEX NAMES:CN Ergosterol

(8CI)OTHER NAMES:CN (22E,24R)-Ergosta-5,7,22-trien-3.beta.-olCN (24R)-Ergosta-5,7,22-trien-3.beta.-olCN 24-Methylcholesta-5,7,22-trien-3.beta.-olCN 24.alpha.-Methyl-22E-dehydrocholesterolCN 24R-Methylcholesta-5,7,22E-trien-3.beta.-olCN 3.beta.-Hydroxyergosta-5,7,22-trieneCN ErgosterinCN Provitamin DCN Provitamin

D2

6/28/2010


Are the same bioactive constituents available in the fungal fruiting body as in the host caterpillar?

AN 2007:359436 EMBASE TI Simultaneous determination of free ergosterol

and ergosteryl

esters in Cordyceps

sinensis

by HPLC.AU Yuan, Jian-Ping (correspondence); Wang, Jiang-Hai; Liu,

Xin; Kuang, Hui-Cong; Zhao, Shu-YanCS Food Engineering Research Center, State Education Ministry,

College of Life Sciences, Guangzhou, 510275, China. SO Food Chemistry, (2007) Vol. 105, No. 4, pp. 1755-1759.

Refs: 24LA EnglishAB The caterpillar-shaped Chinese medicinal mushroom Cordyceps

sinensis

consists of the fruiting body (CsA) and the host caterpillar (CsB).

Ergosterol

is a principal sterol in fungi and can indicate the level of mycelia of C. sinensis.

Ergosterol

is present in two forms, as free ergosterol

and esterified

ergosterol, which have different physiological functions.

The relative abundances of free to esterified

ergosterol

are different among the various species. ...

The results showed that CsA

and CsB

had similar ergosterol

compositions, but the level of ergosteryl

esters in CsB

was much higher than that in CsA, indicating that CsA

and CsB

might be in different growth phase or have different physiological functions for the growth and multiplication of C. sinensis.

6/28/2010


Full-text journal article from CAplus:

Two newly identified anti-tumor metabolites (gliocladicillins)

AN

2009:1592059 CAPLUS

TI Ecology-based screen identifies new metabolites from a Cordyceps-colonizing fungus as cancer cell proliferation inhibitors and apoptosis inducers

AU Chen, Y.; Guo, H.; Du, Z.; Liu, X.-Z.;

CS Center for Molecular Immunology, Chinese Academy of Sciences, Beijing, Peop. Rep. China

SO Cell Proliferation

(2009), 42(6), 838-847

AB Objectives: To identify new anti-cancer agents from Cordyceps-colonizing fungi...to explore their anti-cell proliferative mechanisms, and to evaluate their anti-

tumor effects in vivo.

... two new epipolythio-dioxopiperazines, named gliocladicillins

A (1) and B (2)...[that] inhibited growth of HeLa, HepG2 and MCF-7 tumor cells.

Conclusions: Gliocladicillins

A (1) and B (2) are effective anti-tumor agents in vitro and in vivo and should be further evaluated for their potential in clin. use.

6/28/2010


With STN, you can explore novel bioactive substances revealed from

ancient WTM secrets

Thank you for your kind attention!

Crouching fungus, hidden caterpillar

Dong Chong Xia Cio

Crouching Fungus, Hidden Caterpillar

Technology

Transcript of Crouching Fungus, Hidden Caterpillar