ENHANCED BIO-ENERGY STATE IN MICE LIVER AFTER

ADMINISTRATION OF CORDYMAX
Wu ZM, Dai DW, Bao TT, Xu CF, Zhu J-S
Pharmanex Pharmacology Center Beijing , China; Institute of Materia Medica;
Peking Union Medical University, Beijing, China; Pharmanex Provo, USA

Abstract 31P NMR Spectroscopy Changes in Hepatic β-ATP

Natural Cordyceps sinensis and its mycelial fermentation product γ-ATP
α-ATP
4.2
CordyMax have been advocated for centuries to enhance human

P : Ref
+18.4%
4.0
vitality. This study was to evaluate the effect of CordyMax on tissue MDPA (Ref.)
PME
Pi β-ATP

energetics of male C57-BL/6 mice using non-invasive 31P NMR 38

3.8

Ratio of β-ATP
PC
PDE
spectroscopy. Mice were divided into 3 groups. Groups A and B 3.6 +12.3% 400 mg/kg
(n=5 each) received an extract of CordyMax , 200 or 400 mg/kg/day, 3.4
200 mg/kg

and Group C (n=6) received placebo. All treatments were given by Placebo

gavage for 7 days and then discontinued. Hepatic β-ATP and 3.2

inorganic phosphate were measured using a 31P NMR 3.0

Treatment

spectroscope [Bruker], after mice been anesthetized with Note: 0 7 14 (Days)

pentobarbitol (55 mg/kg, i.p.) and immobilized on shielding belt. An MDPA methylene diphosphonic acid
MDPA reference was placed on the back of the coil. Measurements PME phosphomonoesters
were made at baseline,
baseline after 7 days of treatment,
treatment and 7 days after Pi inorganic phosphate Decreases iin H
D Hepatic
ti
discontinuing treatment (washout phase). Tissue pH was calculated PDE phosphodiesters
Inorganic Phosphate
from chemical shift differences betweenα-ATP and Pi. At the end of PC phosphocreatine 1.2
the treatment phase, b-ATP was increased in relation to the MDPA Placebo
1.1

Ratio of Pi : Ref
reference in mice receiving CordyMax: Group A 3.81±0.03 31P NMR Spectroscopy on mouse liver: 400 mg/kg
(+12.3% on average); Group B 4.00±0.04 (+18.4%); compared
α-, β-, γ-ATP, other triphosphorate 1.0
-17.6%
with Group C 3.36±0.04 (p<0.001). Inorganic phosphate was 200 mg/kg
compounds, and inorganic phosphate;
decreased in Groups A and B, but not in Group C (p<0.001). 0.9
calculate cellular pH.
Consequently, the ratio β-ATP/Pi was also significantly increased in
0.8
mice receivingg CordyMax:
y Groupp A 4.81±0.05 (+47.7%
( on -24.5%

average); Group B 4.50±0.09 (+41.4%); compared with Group C 0.7

Treatment

3.10±0.04 (p<0.001). At the end of the washout phase, β-ATP had Increases in Hepatic β-ATP 0 7 14 (Days)
returned to baseline in Groups A and B. Hepatic tissue pH was In Response to Oral CordyMax
unchanged throughout the study. We conclude that CordyMax
3.8 CordyMax
Ratio of β-ATP : Ref

increased steady state levels of hepatic bio-energy when 400 mg/kg/d Increases in the Ratio of
administered to mice for 7 days. Our findings may explain the β-ATP : Pi
5.0
reported energizing effect of CordyMax in human subjects. 3.6
+13.7% +47.7%
p>0.20 p<0.001
Ratio of β-ATP : Pi

p>0.20
3.4
4.0
+41 4%
+41.4%
Placebo 200 mg/kg
3.2
400 mg/kg
0 1 2 3 4 5 6 7 (Days) 3.0
Placebo

Treatment
2.0
Experimental Design 0 7 14 (Days)
Cordyceps sinensis (Berk.) Sacc. Placebo group No treatment (n=6mice)

(Collected from Qinghai-Tibetan plateau of China) CordyMax 200 mg/kg
Isolation & Purification CordyMax 400 mg/kg
0 (days)
No treatment (n=5mice)
Changes in Hepatic Tissue pH
No treatment (n=5mice)
8
7 14

Cs-4 (A Paecilomyces hepiali 6

31P NMR spectroscopy 31P NMR spectroscopy
Chen strain) Pre-Rx
pH

4
At the time indicated, 7-day Rx
Industrial Fermentation •Anaesthetized mice with 7-day post-Rx
2
Pentobarbital
CordyMax •Preformed 31P NMR 0
Placebo
200 400 (mg/kg/d)
spectroscopy on mouse liver CordyMax
Introduction
♦ CordyMax improves aerobic capability Summary
and enhances endurance in older humans 7-day CordyMax Treatment:
(Chin J Integrat Med 2004; 10:187-192; SH J Prevent Med
2008, 20:367-369).
↑ Hepatic ATP
↑ VO2max, ↑ Anaerobic Threshold, ↓ Hepatic inorganic phosphate
↑ Maximal Ventilation, ↑ Hepatic ratio of ATP:Pi
↓ RER, ↓ Lactic acid
No ∆ in hepatic tissue pH
♦ CordyMax improves glucose and lipid
metabolisms (J Alternat Compl Med 2002; 8:309-314;
Chin J Clin Pharmacy 2007; 16:274-277; Proceedings 2008
Conclusion
Symposium Chin Asso Med Mycol. 2008, pp157-164). • CordyMax improved steady-state hepatic bio-energy status
 CordyMax Improves Glucose Metabolism in
Animals and in Humans
Wu ZM, Nicodemus K, Zhao CS, Zhu J-S
Pharmanex Pharmacology Center, Beijing, China; Fit Stop Human
Performance Lab, Encinitas, CA, USA, Pharmanex Provo, USA

Abstract
Preliminary reports demonstrated that supplementation with Experimental Design (1): Experimental Design (2):
a mycelia fermentation product of Cordyceps sinensis
Randomized, Double-Blind, Placebo Controlled
((CordyMax)
y ) increased maximal O2 uptake
p and anaerobic Placebo (n=12 rats)
threshold in mid-age to elderly humans, and enhanced in Placebo (n=15) (4.5 g/day)
vivo bio-energy metabolisms in animals (J Alternat CordyMax 250 mg/kg (n=12 rats)
Complement Med 7:231, 2001; Chin J Integrat Med 10:187, CordyMax (n=15) (4.5 g/day)
2004; Shanghai J Prevent Med 20:367, 2008). We further CordyMax 500 mg/kg (n=12 rats)
studied in a randomized, double-blind clinical trial the effect
0 (weeks) 6
of CordyMax (4.5 g/day, 6 weeks) in highly-fit athletes on
0 (days) 18
glucose metabolism. Male adventure racers and multi-sport
endurance athletes (age 32±4 yrs; VO2peak 63±8 Sub-maximal exercise-metabolism testing
ml/kg/min) were assigned to either a CordyMax or a control 8 Reduction of FBG
group (n=15 each). We found a 7% decrease in fast blood
mol/L)

glucose within normal ranges after the CordyMax therapy 6

Inclusion Criteria:
Blood Glucose (mm

(92±1 to 87±2 mg/dL; p<0.01), but no change in placebo 5

controls. During prolonged sub-maximal exercise (70% Healthy, highly fit, male endurance athletes
p=0.768

p=0.262

p<0.001
p<0.001
4

VO2peak, 60 min), reductions of respiratory exchange ratio 3 under the age of 40 years
Day 18

were found in the CordyMax vs. control group (p=0.02). In

Day 0
Day 8

2
mice given CordyMax for 4 weeks, responses of serum Training Training vol. Number of
1
insulin and C-peptide to an oral glucose load were 0
Background Hrs./wk. Subjects
diminished and recovered to the pre-load levels quickly vs. Vehicle 250 500 (mg/kg) Adventure Racers 11 ± 7 9
control group (p<0.01 or 0.05) with no change in the glucose Control CordyMax
tolerant curve. The glucose-insulin index was lower in the Pro/Competitive Triathletes 15 ± 7 10
CordyMax (7±1 x105 units) vs. control group (10±1 x105)
Improvement
p of oral Glu tolerance Active Military (Reco/SeALs) 11 ± 1 3
(p<00.01).
(p 01) Our data suggest that CordyMax (1) safely lowers
basal glucose in normal humans, (2) improves glucose 11 Vehicle Olympic Rower/Kayak 10 1
Blood Glucose (mmol/L)

metabolism by enhancing insulin receptor sensitivity, and (3) Control

10 Ultra-distance runner 14 1
enhances fat mobilization and beta-oxidation thereby CordyMax
sparing glycogen expenditure during prolonged endurance 9 250 mg/kg High Fit Multi-sport 9± 4 6
exercise. 8 AUC:
p=0.022 AUC:
7
p=0.005
6
Constant work-rate, Decrease in FBG
5
0 0.5 1 1.5 2 sub-maximal exercise 100
Time (hours)
90

(mg/dL)
Reduction of fasting serum insulin 80 p=0.006

Post-Rx
Pre-Rx
-7.22%
70
40
Insulin (mU/ml)

Cordyceps sinensis (Berk.) Sacc. 30

60 p=0.870
+0.89%
(Collected from Qinghai-Tibetan plateau) 50
p=0.225

p=0.012

20 Placebo CordyMax
Isolation & Purification
10

0
(A Paecilomyces Vehicle 250 500
Cs-4 Reduction of RER during sub-maximal exercise
hepiali Chen strain) Control CordyMax
1.05

Increase in insulin sensitivity Placebo CordyMax

Industrial Fermentation 1.00
0.24
n Sensitivity

0.95
0.22
RER

Pre-Rx
CordyMax 0.20 0.90
Post-Rx
008

p<0.001

0 18
0.18
Insulin

p=0.0

0.85 Post-Rx
Introduction 0.16
Pre-Rx
0.80
♦ CordyMax improves aerobic capability 0.14 0 10 20 30 40 50 60 0 10 20 30 40 50 60
Vehicle 250 500 (mg/kg)
and enhances endurance in older humans Control Exercise Time (min)
CordyMax
(Chin J Integrat Med 2004; 10:187-192; SH J
Prevent Med 2008, 20:367-369).
↑ VO2max, ↑ Anaerobic Threshold, Summary and Conclusion
↑ Maximal Ventilation,
CordyMax
y Treatment:
↓ RER,
RER ↓ Lactic acid
♦ Improves oral glucose tolerance, and reduces fasting blood
♦ CordyMax improves lipid metabolism glucose within normal ranges;
(Proceedings 2008 Symposium Chin Asso Med ♦ Increases insulin sensitivity, and reduces fasting serum insulin;
Mycol. 2008, pp157-164).
♦ Enhances fat mobilization and beta-oxidation thereby sparing
♦ CordyMax improves steady-state hepatic glycogen expenditure during prolonged submaximal exercise in
bio-energy status (J Alternat Compl Med highly-fit humans.
2001; 7:231-240).
CORDYMAX INCREASES SERUM HDL-CHOLESTEROL AND
REDUCES OXIDIZED LDL-CHOLESTROL IN HUMANS WITH
REDUCED SERUM HDL-CHOLESTEROL
Wu ZM, Wang BE, Pei Y, Liu CZ, Li SQ, Zhang W, Xu ZB,
Rippe J, Zhu JS
Pharmanex Clinical Center, Beijing; Beijing Friendship Hospital
and Beijing Association for Medico-Pharmaceutical Research &
Development; Rippe Lifestyle Institute, Shrewsbury, MA, USA;
Ph
Pharmanex Provo,
P UT,
UT USA

Abstract Study Aims Increases in Serum HDL-Cholesterol

Females Males
Literature reported CordyMax, a mycelial fermentation product 1. To examine the effect of CordyMax

Week 0
on serum HDL-cholesterol

Week 8
of Cordyceps sinensis, regulated the blood lipids in 55
p=0.023
43

Week 0

Week 8
41
hyperlipidemic patients and prevented the formation of

Serum HDL (mg/dl)

50
2. To examine the effect of CordyMax 39
atherosclerosis in animals and humans. (Administ Tradit Chin 45
on serum oxidized LDL-cholesterol 37
Med 1995;5:14-18). We tested the effect of CordyMax (3.0 g/day) 40 35
in 133 dyslipidemic
y p subjects
j on increasing g HDL cholesterol 33
35
(HDL-c) and reducing oxidized LDL cholesterol (ox-LDL). 31
Subjects with reduced serum HDL-c (<40 mg/dL for males or <45 Experimental Design 30
+14.7% +31.1% 29
p=0.261 +12.3%
p=0.015 p<0.001 p=0.003
mg/dL for females) were randomized to a CordyMax or placebo Randomized; Double-blind; 25
27
group (double-blind). Eight weeks of CordyMax did not change 20 25
total cholesterol and triglycerides significantly. At Week 8, LDL-c
Placebo Controlled Placebo CordyMax Placebo CordyMax
was reduced with CordyMax significantly by 5.4% (p=0.002). Placebo 3 g/day n=56
Lead-in
Most dramatically, ox-LDL was reduced by 22.9% in CordyMax
Phase Increases in Serum apoA1
group (p=0.001). Atherosclerosis Index [= (TC – HDL-c)/HDL-c] CordyMax 3 g/day n=77
1.8
reduced with CordyMax by 29% (p<0.001). HDL-c was increased
with CordyMax by 31.1% (p<0.001) in females and by 12.3% 1.6
-2 0 (weeks) 8

g/dl)
(p=0.003)) in males. Apolipoprotein
(p p p p A1 was increased with 1.4

Serum apoA1 (mg

CordyMax by 34.7% (p=0.005). The ratio of ox-LDL/HDL-c was 1.2

reduced by 10.5% (p=0.003). In conclusion, CordyMax　 Inclusion Criteria: 1.0

significantly lowers LDL-c, ox-LDL and Atherosclerosis Index, 0.8
p=0.934
+34.7%
and increases HDL-c and ApoA1, reducing the risk of Serum HDL-cholesterol 0.6 p=0.005
atherosclerosis and cardio- and cerebro-vascular diseases.
Males ≤ 40 mg/dl
0.4

0.2

females ≤ 45 mg/dl
Introduction 0.0
Placebo CordyMax
♦CordyMax increases activities of scavenging oxygen
free radicals in elderly senescent patients Reduction of Serum LDL-Cholesterol
LDL Cholesterol Reduction of Atherosclerosis Index
(Administ Tradit Chin. Med. 1995;5:14-18) 160
8

↑ Superoxide Dismutase (SOD) activity 7

Atherosclerosis Index

150
↓ Plasma malondialdehyde (MDA)
Serum LDL (mg/dl)

♦CordyMax interrupts the formation of atheromatous

140 5
p=0.446 -5.4%
p=0.002 4
p=0.309
plaque in the aorta and inhibits thrombosis on the 130 -29.0%
3 p<0.001
surface of experimentally injured endothelia of arteries 120
Week 0

Week 8

in rabbits (Administ Tradit Chin. Med. 1995;5:6; Chapter 4, in: 2

Week 0

Week 8

Advanced Study for TCM Herbs, Vol. 1. IMM, ed., 1995:91-113)

110
1

♦CordyMax decreases total and LDL-cholesterol in

100 0

CordyMax Placebo CordyMax

Placebo
hyperlipidemic patients (Intl J Orient Med 1990; 15:77-80)
♦CordyMax improves lipid-glucose metabolisms in elite
Reduction of Oxidized LDL-Cholesterol Reduction of Ratio of OxLDL:HDL
athletes (Chin J Clin Pharmacy 2007; 16:274-277)
30 0.8
Serum oxLDL (mg/dl)

o of oxLDL : HDL

0.7
25
0.6
20
0.5
p=0.852
15 p=0.549 0.4
-22.9% -10.5%
p=0.001 0.3 p=0.003
Week 0

Week 8

10
Ratio
Week 0

Week 8

0.2
5
0.1

0 0.0
Placebo CordyMax Placebo CordyMax

Cordyceps sinensis (Berk.) Sacc.

(Collected from Qinghai-Tibetan plateau of China) Summary Conclusion
Isolation & Purification CordyMax supplementation for 8 weeks
CordyMax treatment increases
In all patients
serum HDL-c and decreases oxidized
↑ Serum HDL-cholesterol
HDL cholesterol
Cs-4 (A Paecilomyces hepiali ↓ Serum oxLDL LDL-c in patients with reduced
Chen strain) ↓ Ratio of oxLDL:HDL baseline serum HDL-c, indicating
In patients with baseline serum LDL-c >130 mg/dL reduced risks of atherosclerosis, and
Industrial Fermentation ↓ Serum LDL-cholesterol ischemic cardio- and cerebro-
↑ Serum apoA1
vascular diseases.
↓ Atherosclerosis Index
CordyMax No ∆ serum triglycerides
 CordyMax Extends the Lifespan of Mice
— A preliminary report
Wu ZM, Zhang Y, Tan NZ, Zhao CS, Yang JY, Zhu J-S
Pharmanex Beijing Pharmacology Center, Beijing China;
Pharmanex Research Institute, Provo, USA
Abstract
Cordyceps sinensis and its mycelia fermentation product CordyMax have Deaths in Each Group
been used for Centuries for anti-fatigue and endurance enhancement. We Food intake of female mice
reported anti-fatigue and endurance enhancement properties, and Vehicle control
4.6
28 dead 20 Live
improvement of glucose, lipid and energy metabolisms by CordyMax in
CM 1000
4.2
CM 500 mg/kg 22 dead 26 Live

Food intake (g)

animals and humans in previous studies. In this study, we explored possible
Control
anti-aging effects of CordyMax in mice. A total of 192 healthy ICR mice (12 3.8

months of age, half males and half females) were randomized into 4
CM 1000 mg/kg 32 dead 16 Live
3.4
groups, receiving either vehicle or CordyMax at a dose of 500, 1000, or 1500 CM 1500 mg/kg 27 dead 21 Live
mg/kg.bw. All mice were fed with regular forage or forages contained 3.0

CordyMax in different concentrations. Body weight was monitored once a 2.6 CM 500
After 64 weeks of CM Treatment
CM 1500
week. Calorie intake was monitored twice per week and adjusted carefully to
2.2
match the average calorie intake levels for vehicle controls, males and 10 20 30 40 50 60 70
12 m-old (n=48)
females respectively. y CordyMax
y administration continues until all mice die.
27 m-old
Time ((weeks)) 8 m-old
Mice have been treated for 64 weeks thus far. The preliminary results show:
(1) no significant differences in body weight and calorie intake were observed
amongst 4 groups. (2) Compared to controls, the survival time of 75% Food intake of male mice Kaplan-Meier Cumulative Survival Plot
animals in the CordyMax groups (500, 1000, and 1500 mg/kg.bw) extends
4.9
over 14, 14, and 16 weeks respectively, and the survival time of 50% animals 1.0
CM 1500

Cumulative Survival Rate

in the CordyMax groups extends over 9, 1, and 5 weeks respectively. 4.5 CM 1000
Food intake (g)

CM 500 0.8
Analysis with use of Kaplan-Meier Cumuli Survivor Plot showed significantly
4.1 Control
extended lifespan of the mice and reduced death risks by CordyMax: p=0.049 CM 1000
0.6
(Week 36); p=0.036 (Week 40); p=0.059 (Week 48); p=0.027 (Week 64). The 3.7
Control
y
low dose CordyMax treatment ((equivalent
q to the human dose)) appeared
pp to 33
3.3
0.4
CM 500
show the best survivor curve. This study demonstrates the lifespan-extending
effects of CordyMax in mice, while the experiment is still ongoing. At the 2.9 0.2
CM 1500
meanwhile, additional studies demonstrated that CordyMax has anti-oxidation 2.5
p=0.027
10 20 30 40 50 60 70 0
activity, and improves glucose, lipid and energy metabolisms and aerobic
Time (weeks) 0 100 200 300 400 500
exercise capacity in animals and in humans (reported separately), all of which Time (days)
support the general anti-aging function of CordyMax.

Introduction BW of female mice Kaplan-Meier Cumulative Survival Plot

1. Cordyceps sinensis is traditionally believed as a medicinal 50
1.0
Cumulative Survival Rate

CM 500
herb with anti
anti-aging
aging activities and promoting longevity. 48
Body Weight (g)

2. Literature indicates the therapeutic functions of Cordyceps 46

0.8
44 Control
sinensis and its mycelia fermentation product CordyMax in 42
CM 500
0.6
improving energy, glucose, and lipid metabolisms and 40
CM 1500
benefiting to cardiovascular, the liver, the lungs and kidneys 38 0.4

health. (Zhu et al. J. Altern Compl Med. 1998; 4: 289-303, 36 CM 1000

Control
429-457) 34 0.2
p=0.013
3. We have reported anti-fatigue and vitality-endurance 32
0
30
enhancement properties of CordyMax, and improvement of 10 20 30 40 50 60 70
0 100 200 300 400 500
Time (weeks)
energy, glucose, and lipid metabolisms by CordyMax in Time (days)
animals and humans in previous studies.
4. The aim of this study is to test the lifespan extension effect
BW of male mice Lifespan Extended (Days) 
of CordyMax in mice.
at the % Survival 
160
47 CM 500 Control
Cordyceps sinensis (Berk.) Sacc.
Lifespaan (days) extended

140

(Collected from Qinghai-Tibetan plateau of China) 45

dy Weight (g)

120

Isolation & Purification 43 100

80
41
60
CM 1000
Cs-4 (A Paecilomyces hepiali 39 CM 1500
Bod

40
Chen strain) 20
37

Industrial Fermentation 35
0

10 20 30 40 50 60 70 ‐20
97. 95. 93. 91. 89. 87. 85. 83. 81. 79. 77. 75. 72. 70. 68. 66. 64. 62. 60. 58. 56. 54. 52. 50. 47. 45. 43.
9% 8% 8% 7% 6% 5% 4% 3% 3% 2% 1% 0% 9% 8% 8% 7% 6% 5% 4% 3% 3% 2% 1% 0% 9% 8% 8%
Time (weeks) 500mg/kg
CordyMax 23 35 85 76 50 85 98 94 85 12 10 98 60 80 80 78 82 82 74 45 42 75 65 66 69 72 57
1000mg/kg ‐6 49 44 46 35 43 25 87 92 10 84 94 63 59 56 35 35 35 25 ‐2 ‐6 13 3 10 14 25 15
1500mg/kg 75 87 88 95 78 13 13 12 12 13 12 10 74 63 60 35 35 32 28 ‐9 5 19 39 39 38 43 28

Experimental Design:
Lifespan studies in mice Summary
Vehicle control ((n=48 mice)) 1 Analysis with use of Kaplan
1. Kaplan-Meier
Meier Cumuli Survivor Plot showed significant
CM 500 mg/kg (n=48 mice) extension of mouse lifespan and reduced death risks by CordyMax: p=0.049
CM 1000 mg/kg (n=48 mice) (Week 36); p=0.036 (Week 40); p=0.059 (Week 48); p=0.027 (Week 64).
CM 1500 mg/kg (n=48 mice) 2. The low dose CordyMax treatment (equivalent to the human dose) appeared to
show the best survivor curve.
~ 3 years
Treatment starts 3. This study demonstrates the lifespan-extending effects of CordyMax in mice,
all mice
8m-o
at the age of 12 months
dead
while the experiment is still ongoing.
 Anti-oxidation activities of CordyMax:
a mechanism of its anti-aging property
Wu ZM, Yang JY, Tan NZ, Zhang Y, Zhao C, Zhu J-S
Pharmanex Beijing, China; Pharmanex Research Institute,
Provo Utah, USA
Abstract
Cordyceps sinensis and its mycelia fermentation product CordyMax have Increases in plasma thiol groups Increases in liver CAT
g and endurance enhancement. We
been used for Centuries for anti-fatigue 0.7
reported anti-fatigue and endurance enhancement properties, and

Thiol groups (mmol/L)

40
improvement of glucose, lipid and energy metabolisms by CordyMax in
animals and humans in previous studies. We also demonstrated the anti- 0.6

CAT (U/mg pro.)

aging effect of CordyMax in mice. To explore the mechanism of the anti- +22.6% 30
p<0.001 + 24.7%
aging actions, we tested anti-oxidation activity of CordyMax in mouse

+ 20.8%; p=0.001

+ 25.0%; p<0.001
+ 22.9%; p=0.001
p<0.001

+16%; p=0.001

+15%; p=0.002

+16% p<0.001
models with oxidative damage. Mice were randomized into 5 groups, 0.5
20
receiving vehicle or CordyMax at a dose of 500, 1000, or 1500 mg/kg.bw
for 60 days. Mice in vehicle and 3 CordyMax groups were given a single
0.4
dose of 11 Gry 60Co γ-rays radiation, and sacrificed in Day 4 after 10
radiation. We found that plasma glutathione (GSH) and the thiol groups,
and liver superoxide
p dismutase (SOD)
( ) and catalase (CAT)
( ) were 0
0.3
significantly reduced by 29.0%, 22.6%, 6.0% and 24.7%, and liver protein Normal Vehicle 500 1000 1500 (mg/kg)
Normal Vehicle 500 1000 1500(mg/kg)
carbonyl groups was significantly increased by 37.3% in vehicle controls, control control CordyMax
CordyMax
compared to normal mice. As compared to vehicle controls, CordyMax 60Co -11Gy
therapy at a dose of 500, 1000, or 1500 mg/kg.bw increased plasma thiol 60Co -11Gy
groups by 22.9%, 20.8%, and 25% respectively (p=0.001, 0.001, and
<0.001), and liver CAT by 16%, 14.8%, and 16.4% respectively (p=0.001,
0.002, and<0.001). CordyMax at a dose of 1000 or 1500 mg/kg.bw reduced
liver protein carbonyl groups by 8.7% and 13.5% respectively (p=0.035 Increases in plasma GSH
and 0.001), and increased plasma GSH by 26.3% and 26.5% (p=0.023 and
Increases in liver GSH-Rd
40
0.026). Liver SOD was increased with CordyMax (1000 and 1500 mg/kg.bw)
byy 9.4% and 5.7% ((both p<0.05).
p ) Liver GSH-reductase was increased with

o.)
35
8

(nmol/min/mg pro
Glutathione(mg/L)

CordyMax (500mg/kg) by 10.5% (p=0.039). The results indicate that

30
CordyMax improves antioxidant capacity in mice with radiation-induced

GSH-Rd
6 + 7.6%
oxidative injure, representing one of the mechanisms of anti-aging
+26.5%; p=0.026
+26.3%; p=0.023

+29% p=0.072

+11%; p=0.039
functions of CordyMax. p<0.001 20
4
Introduction
♦ Cordyceps sinensis is believed as an “Yin-Yang” double 2 10

invigorating and anti-aging TCM herb

♦ CordyMax, the mycelia fermentation product of Cordyceps 0 0
Normal 500 1000 1500 (mg/kg) Normal
sinensis, has the following functions: control
Vehicle
C
CordyMax control
Vehicle 500 1000 1500 (mg/kg)
CordyMax
o Anti-fatigue and endurance enhancement 60Co
60Co -11Gy -11Gy
o Improvement of glucose, lipid & energy metabolisms
♦ Oxidative stress and free radical damages are generally
believed as the most important cause of aging and induce
aging-related biochemical/molecular changes Decreases in liver protein 
♦ Isotope radiation induces production of large amount of free Increases in liver SOD carbonyl groups 
radicals and oxidative injury, causing acute aging and death 8.0
500
SOD (U/mg prro.)

Cordyceps
y p sinensis ((Berk.)) Sacc.
o.)
ps

60
6.0
(nmol/mg pro
Carbonyl group

400
(Collected from Qinghai-Tibetan plateau of China)
+6.0%
+ 9.4%; p<0.05

+ 5.7%; p<0.05

Isolation & Purification 300

- 8.7%; p=0.035

p=0.018
- 14%; p=0.001

4.0
- 37%
200 p<0.001

Cs-4 (A Paecilomyces hepiali 2.0

100
Chen strain)
0
0
Industrial Fermentation Normal
control
Vehicle 500 1000 1500 (mg/kg)
Normal Vehicle 500 1000 1500 (mg/kg)
CordyMax control
CordyMax
60Co -11Gy 60Co -11Gy
CordyMax

Experimental Design: Summary Conclusion

Non-radiation control (n=15) CordyMax Treatment for 60 days in ♦ CordyMax improves
Vehicle control (n=15) radiation-induced oxidative injured mice: antioxidant capacity in mice
with radiation-induced
CordyMax 500 mg/kg (n=15) ↑ Plasma thiol groups
oxidative injure.
j
CordyMax 1000 mg/kg (n=15) ↑ Plasma glutathione
♦ The results from this study
CordyMax 1500 mg/kg (n=15) ↑ Liver SOD supports the concept of
0 (days) 60 63 ↑ Liver CAT CordyMax as an anti-aging
↑ Liver GSH-Rd product that has been
60Co Collect demonstrated by the lifespan-
(11Gy) blood ↓ Liver protein carbonyl groups extending study.
& liver
 ANTI-FATIGUE AND ENDURANCE ENHANCEMENT
PROPERTIES OF CORDYMAX IN HUMANS
Zhu JS, Xiao Y, Li CL, Huang XZ, Hagan RD
Pharmanex Research Institute,
Institute Provo UT
UT, USA; Shihezi University,
University Xinjiang; Pharmanex
Clinical Center, Beijing; Peking Union University, Beijing; Peking University, Beijing; The
Fit Stop Human Performance & Health Enhancement Laboratory, Encinitas, CA, USA

Abstract
To Examine the Effects of CordyMax on Heart Rate during CWR

Average % Change in Heaart Rate

Cordyceps sinensis and a standardized mycelial fermentation product of C. Aerobic Capacity, Endurance +3%
sinensis, CordyMax, are known as medicinal herbal products for invigoration, Enhancement, and Exercise metabolism
h lth preservation,
health ti anti-aging,
ti i andd anti-fatigue.
ti f ti Th
Theiri anti-fatigue
ti f ti andd
+2% p=0.05
p 0.05
in Humans
endurance enhancement functions have been reported. By use of a traditional +1%
symptom-analysis method in a double-blind clinical trial, elderly patients with Randomized, Double-blind, Placebo-controlled 0%
senescence-related symptoms reported improvement of fatigue, dizziness,
Placebo -1%
intolerance to cold temperature, sexual dysfunction, etc. by CordyMax
-2%
supplementation in majority of patients (J Appl Tradit Chin Med 1993;1:32). CordyMax
Animal studies demonstrated that CordyMax improved steady state bio-energy -3%
ATP levels in mouse liver by use of in vivo serial 31P NMR spectroscopy (J 0 (weeks) 6 or 12 -4%
Alternat Compl Med 2001, 7:231), and promoted efficient use of limited oxygen CordyMax Placebo
supply to support body’s essential physiological activities and greater tolerance
to hypoxia-induced acidosis (Chin Tradit Herbal Drugs 1986;17: 209). We Exercise tests Exercise tests
examined
i d th
the anti-fatigue
ti f ti andd endurance
d enhancement
h t properties
ti off ‹Healthy
H lth older
ld subjects
bj t & athletes
thl t O2 Pulse
P l during
d i CWR

Average % Change of O2 Pulse

CordyMax with use of sports physiology methods. In double-blind clinical trials +12%
with use of an incremental work rate protocol on a cycle ergometer and/or
treadmill, we found that CordyMax increased VO2max by 7.0%, anaerobic
+10% p=0.05
threshold by 12.6%, maximal ventilation by 10.4% and maximal work rate by Peak Oxygen Uptake +8%
+6%
5.9%, indicating improvement of aerobic exercise capacity in healthy 2.2 +6.7%, p=0.05 +4%
sedentary adults of advance ages. In healthy young athletes and by use of a
constant work rate protocol, CordyMax therapy increased O2 pulse by 7.6% 2.0
+2%

and reduced heart rate (HR) by 2.2%, RER by 2.5%, and lactic acid by 10.5% 0%
(L/min)

during endurance exercise, indicating improvement of cardiovascular and -2%

1.8
metabolism functions during endurance exercise. CordyMax also accelerated
k6
k0

-4%
Week
Week

HR recovery 3 min post maximal exercise by 6.3%. In summary, CordyMax -0.05%

0 05% CordyMax Placebo
supplementation influences favorably aerobic capacity and cardiovascular, 1.6
p=0.80
pulmonary, and metabolic functions during maximal and endurance exercise,
improves fatigue and endurance performance, and facilitates recovery from
exercise.
1.4
CordyMax Placebo RER during CWR
+4%

Averagee % Change in RER

Introduction +3% p=0.025
♦ Cordyceps sinensis is traditionally believed as an anti- Anaerobic Threshold +2%
+1%
aging tonic herb
+12.6%, p=0.012
Anaerobic Threshold ((L/min)

0%
♦ CordyMax, the mycelia fermentation product of C. sinensis, 1.4
-1%
p
improves senescence-related symptoms,
y p , includingg fatigue,
g , 13
1.3
and increases activities of scavenging oxygen free radicals -2%

in elderly senescent patients (Administ Tradit Chin Med 1995; 1.2 -3%
5:14-18) 1.1 -4%
Week 0

Week 6

-2.4% CordyMax Placebo

♦ CordyMax extends lifespan and enhances body’s anti- 1.0 p=0.41
oxidant activities
0.9
♦ CordyMax improves energy, glucose and lipids
metabolisms in humans and animals (J Alternat Compl Med 0.8 Lactic Acid during CWR
Average % Change in Lactic Acid

CordyMax Placebo
2001; 7:231-240; J Alternat Compl Med 2002; 8:309-314; Chin J Clin +30%
Pharmacy 2007; 16:274-277; Proceedings 2008 Symposium Chin Asso p=0.031
Med Mycol. 2008, pp157-164) +20%

W k Output
Work O t t +10%
Incremental work-rate (IWR) exercise 1.5
on cycle ergometer +3.1%, p=0.033 0%
Work Output (KJ/kg)

1.4

1.3 -10%
VO2 (L/min)

1.2
Week 12

-20%
Week 0

-4.9% CordyMax Placebo

1.1
p=0.626
1.0
work rate: 0.9 Summary
y & Conclusion
+25 watt CordyMax Placebo
every 2 min CordyMax Treatment:
↑ Peak O2 uptake
↑ Anaerobic threshold
Time (min) ↑ Work output
1-Mile Walk Time ↑ O2 pulse
% Change in Timee for 1-Mile Walk

Constant Work Rate (CWR) 5%

↓ Peak heart rate
From Week 0 to Week 12

Sub-Maximal Exercise
4% p=0.05 ↓ RER
3%
2% ↓ Blood lactate
1% ↓ Time for 1-mile walk and for
VO2 (L/min)

0%
-1%
recovery
-2% CordyMax Treatment:
-3%
-4% In healthy subjects, improved
-5% aerobic exercise capacity,
Work Rate at 70% VO2max CordyMax Placebo
endurance, glucose-lipid
Time (min)
metabolisms during endurance
exercises
 Maturation of Cordyceps sinensis associates with
co-existence of Hirsutella sinensis and
Paecilomyces hepiali DNA
Zhu J-S, Guo Y, Yao YS, Zhou YJ, Zheng TY, Chen W
Pharmanex Research Institute, Provo UT, USA; Shihezi University, Xinjiang; Pharmanex
Clinical Center, Beijing; Institute of Microbiology, Chinese Academy of Sciences, Beijing
Abstract ITS PCR Products Nested PCR Products
A decades-long debate has not given a consensus on the
Using Phsp3/5Primers
Template: Fresh C. sinensis
anamorph-telemorph connection for Cordyceps sinensis
(Cs). Literature reported isolations of Paecilomyces hepiali 1 2 3 4 5 6 7 8 9 10 11
500
and Hirsutella sinensis from natural Cordyceps
y p sinensis,, 400
300
and evidence of molecular existence of H. sinensis in C. 200
sinensis. We tested a hypothesis in this study that P. hepiali 100
and H. sinensis co-exist in natural C. sinensis, and their
proliferation predominance changes during maturation of C.
sinensis. Mycological and molecular approaches were
ITS4/5 DNA segments by single-step PCR. rDNA was
employed to examine the growth of P. hepiali and H. sinensis extracted from P. hepiali (Lane 1), H. sinensis (Lane 2),

AccI

AccI

AccI

AccI
and C. sinensis (Lane 3) as the templates, and ITS4 &
(bp)
and their genes in freshly collected C. sinensis after
thorough prior cleaning and surface sterilization. A nested ITS5 primers were used.
PCR method with use of a touch-down program was used to
identify the genes of P. hepiali and H. sinensis in the DNA Sequences
caterpillar body and stroma of natural C. sinensis. We found 1 2 3 4 5 6 7 8 9

that P. hepiali and H. sinensis were detected simultaneously

PCR products were amplified from rDNA
in freshly collected C. sinensis by mycological and
molecular examinations. Maturation of C. sinensis after it is templates extracted from caterpillars and
visible above ground associates with a large decrease in the stromata of C. sinensis with use of a nested
ability of competitive growth of H. sinensis (p<0.001). P. PCR protocol (upper panel), and digested with
hepiali and H. sinensis genes were found in both caterpillar AccI (lower panel).
body and stroma of natural C. sinensis. We conclude that C.
sinensis is a complex traditional Chinese herb with multiple
fungi living in its caterpillar and stroma. Its maturation from Sequences of the Nested
early May to late June associates with dynamic changes in
proliferation predominance of the fungi.
PCR Products

Scientific Background
♦ Cordyceps sinensis (Berk.) Sacc. is a precious tonic
herb used in china for centuries, having broad
nutritional and health benefits (Zhu et al., J Alternat
Compli Med 4:289-303 & 429-457, 1998). Its life cycle
is complex and its natural supply is scarce.
♦ Although on the basis of DNA sequence Hirsutella
sinensis is hypothesized as the anamorph (asexual
stage) of C. sinensis, >10 fungi were isolated from
natural C. sinensis, possibly suggesting a multi-
fungi symbiosis in natural C. sinensis. Endonuclease Digestions of P. hepiali
♦ Through competitive proliferation, live Paecilomyces & H. sinensis ITS PCR Products
hepiali and Hirsutella sinensis were identified
BamHI
BamHI

Acc I
Acc I

Ava I
Ava I

Alu I
Alu I

simultaneously (Guo and Zhu, FASEB J. 19: A1033,

2005).

Experimental Methods
♦ 100 pieces of fresh C. sinensis were
collected from Qinghai-Tibetan Plateau in
early May, following by immediate on-site
clean, surface sterilized and freeze in liquid
nitrogen for transportation and further Lane: 1 2 3 4 5 6 7 8 9 10 11
process. DNA template: P. hepiali ITS4/5 H. sinensis ITS4/5
Summary
♦ Caterpillars and stromata of natural C. PCR Products Using Phsp3/5 Primers
sinensis were separately grounded into ♦ P. hepiali genes were amplified
P. hepiiali

DNA
powder
d iin li
liquid
id nitrogen.
it Rib
Ribosomal l DNA Template: Fresh C. sinensis from caterpillar and stroma of
was extracted. natural C. sinensis (GenBank
♦ A nested, dual-step PCR technique was used 600
500 #EF555097), in addition to the
400
(Guo and Zhu, FASEB J. 20: A431, 2006). 300
200 detections of H. sinensis genes.
100
1. A pair of primers, ITS4/5, were used for
Lane: 1 2 3 4 5 6 7 8 9 10
the 1st PCR: annealing at 40 Ԩ for 30
cycles. Discussions
2. A pair of Paecilomyces hepiali primers, ♦ We found simultaneous existence
AccI

AccI
AvaI

AvaI

Phsp3 and Phsp5, and a touch

touch-down
down PCR of live P.
P hepiali and H.
H sinensis
protocol were used for the 2nd PCR:
initially annealing at 70 Ԩ with 0.3 Ԩ
and their genes in nature C.
decrement for each cycle, for 35 cycles. sinensis.
3. DNA sequencing and restrictive
Lane: 1 2 3 4 5
♦ The multi-fungi existence in
PCR products were amplified from rDNA templates natural C. sinensis may suggest
endonuclease digestions with BamHI and
extracted from C. sinensis and P. hepiali with use of P. complex anamorph-telemorph
AccI specific for Paecilomyces hepiali and
hepiali “specific” primers Phsp3-Phsp5 (upper panel),
Aval and AluI for Hirsutella sinensis. connections to C. sinensis.
and digested with AccI and AvaI (lower panel).
 Maturational alterations of differential expressions of
GC:AT-biased Cordyceps sinensis mutants and
Paecilomyces hepiali in natural Cordyceps sinensis
Zhu J-S,
J-S Gao L,
L Yao YS,
YS Zhou YJ,
YJ Zheng TY,
TY Chen W
Pharmanex Research Institute, Provo, UT, USA; Shihezi University,
Xinjiang; Pharmanex Clinical Center, Beijing

Abstract rDNA preparation, Southern Restrictive digestions of

A decades-long debate has not given a consensus on the anamorph-telemorph connection blotting and PCR analysis Hsprp1/3 PCR products
for Cordyceps sinensis (Cs). Literature reported simultaneous detections of Paecilomyces
hepiali (Ph) and Hirsutella sinensis (Hs) and their DNA in freshly collected natural Cs and a
♦ Caterpillar and stroma of the sterilized C.
>50% decline of colony-forming ability of caterpillar Hs along with Cs maturation under sinensis were grounded separately into
competitive proliferation conditions. In this study, we tested the expressions of Ph and powder in liquid nitrogen for genomic
multiple Hs-related Cs genes during Cs maturation. Southern blotting analysis revealed
dramatic increases in expressions of Ph and Hs genes with Cs maturation, with use of Ph DNA extraction with DNeasy Plant Mini
(ITS5-179) and Hs (ITS5-162) specific probes. Two Hs-related species on Hs blot were seen Kit (Qiagen).
after the genomic Cs DNA was digested with EcoRI, probably representing the GC:AT-
biased mutants. They expressed differentially in stroma and caterpillar body at different ♦ AvaI, DraI, & EcoRI were used for the
stages of Cs maturation. The AT bias does not express in premature Cs caterpillar, but genomic DNA and PCR product
highly predominately in premature stroma; while the GC bias expresses oppositely in the
premature Cs compartments. The differential expressions altered non-proportionally in the
digestions
caterpillar body and stroma when Cs matures. The expression pattern of the AT-bias ♦ Probes:
species is highly similar to that for Ph. EcoRI digestions of PCR products in ITS1/5.8S rDNA
g
regions when Cs stroma ggenomic DNA used as the template p showed increased qquantityy of ― P. hepiali probe: 175 bp (ITS5-179)
digestible species in proportion to the increased length of stroma during Cs maturation. In ― H. sinensis probe: 158 bp (ITS5-162)
conclusion, Cs maturation associates with augmented expressions of both Ph and Hs ― Internal control probes: a 18S
genes and altered differential expressions of GC:AT-biased Cs mutants. These maturation-
related changes in the expressions of Cs-associated fungi represent the important fragment
elements in Cs life cycle, opening an avenue to unmask the anamorph-telemorph
connection of this precious Chinese herb.
♦ Probes were labeled with DIG High Prime
DNA Labeling and Detection Kit (Roche)

Scientific Background
Southern blots: P. hepiali (upper)
♦ Cordyceps sinensis (Berk.) Sacc. has been
used as a precious medicinal herb in china
& H. sinensis (lower) rDNA in
for centuries Type 1 or 2 C.
C sinensis
♦ It has broad nutritional and health benefits Caterpillar Stroma
(Zhu et al., J Alternat Compli Med 4:289-303
Collected in: May Jun May Jun
& 429-457, 1998)
Type of C. sinensis: 1 2 1 2
♦ Co-existence of fungi P. hepiali and H.
sinensis was found in fresh C. sinensis (Zhu P. hepiali
et al., J Mycol Res 5:214-224, 2007)
18S Internal Control

Maturation of C.
C sinensis and the C t ill Stroma
Caterpillar St
Temperature on Qinghai-Tibet Plateau Collected in: May Jun May Jun Reversely orientated rDNA
Less Matured Matured Type of C. sinensis: 1 2 1 2 sequences (GC-bias)
Harvest Season Early May Late June H. sinensis

Temperature on 0-10 Ԩ 10-20 Ԩ 18S Internal Control

the Plateau
Stroma Short Long GC and AT-biased
GC- AT biased mutants
A: “Type 1” B: “Type 2” of C. sinensis

A B

Summary & Conclusions

↑ Biomass of P. hepiali and C. sinensis mutants rDNA
with C. sinensis maturation
♦ Differential expressions of C. sinensis mutants:
¾ Premature caterpillar: only AB067721 (GC-bias)
¾ Premature stroma: predominated with AT-biased mutants
(AB067740 or AB067744)
¾ Mature caterpillar: still predominated by AT-biased
mutants (AB067740 or AB067744), but more GC-bias
Collection of fresh C. sinensis Restrictive digestions of expresses (AB067721)
¾ Mature stroma: equally express with AT-bias (AB067740
♦ Type 1 C. sinensis: 50 pieces Hsprp1/3 PCR products or AB067744) and GC-bias (AB067721)
♦ Type 2 C. sinensis: 50 pieces ¾ With C. sinensis Maturation:
ƒ In stroma: expression of GC-bias increases
♦ C. sinensis were collected from Qinghai- ƒ In caterpillar: expression of AT-biases increases
Tibet Plateau, followed by on-site ♦ C. sinensis exists reversely orientated GC-bias
cleaning, surface sterilizing and freezing rDNA, indicating reverse chromosome exchanges
in liquid nitrogen. ♦ Expressions of P. hepiali and AT-biased mutants
are synchronized with C. sinensis maturation
 MATURATION OF CORDYCEPS SINENSIS ASSOCIATES
WITH CHANGES IN PROFILES OF PROTEINS AND SMALL
MOLECULAR WEIGHT ORGANIC CHEMICALS
Zhu J-S,
S Zhang, LJ, Qi
Q Y, Liu XJ, Zhang L, Wu ZM, Zheng TY,
Chen W
Pharmanex Research Institute, Provo UT, USA; Shihezi University,
Xinjiang; Pharmanex Clinical Center, Beijing; Pharmanex R&D
Center, Shanghai; Fudan University, Shanghai

Abstract Collection of fresh C. sinensis

♦ Type 1 C. sinensis: 90 pieces
Background: Literature reported differential expressions of Paecilomyces
hepiali and Hirsutella sinensis DNA in the caterpillar body and stroma of ♦ Type 2 C. sinensis: 90 pieces
natural Cordyceps sinensis during C. sinensis maturation. ♦ Fresh C. sinensis were collected from Qinghai-Tibet Plateau in early May for Type 1 C. sinensis
Hypothesis: Differential expressions of P. hepiali and H. sinensis in natural and in late June for Type 2, followed by on-site cleaning, surface sterilizing and freezing in
C. sinensis may alter the profiles of proteins and other organic chemicals liquid nitrogen for further process.
during maturation of C. sinensis.
Designg and Methods: SELDI-TOF MS and HPLC analyses y were used to
profile proteins and small molecular weight organic chemicals in caterpillar
HPLC profiling of small molecule chemicals
body and stroma of natural C. sinensis and mycelia of P. hepiali and H. ♦Caterpillars and stromata of C. sinensis, and freeze-dried P. hepiali and H. sinensis mycelia were individually grinded into powder in
sinensis. liquid nitrogen. Small molecules were extracted in either methanol or water, and analyzed for total quality profiling on HPLC with an
ODS-C18 (262 nm).
Results: Maturation of C. sinensis after it is visible above ground associates
with altered profiles of proteins and small organic chemicals. The profiles for ♦The mobile phase was a linear gradient of Acetonitrile (A) and 0.1% H3PO4 with 5mM Sodium salt of 1-Hexanesulflonic Acid (B).
the mycelia of fungi do not completely match to those for the stroma or
caterpillar body of natural C. sinensis during its maturation. The profiles for
H. sinensis mycelia appear to be more distinct from those for natural C.
sinensis, than the profiles for P. hepiali mycelia.
Conclusions: The maturation of C. sinensis associates with significant
changes
g in the component
p organic
g chemicals. The compounds
p from all
component fungi may contribute jointly to the overall pharmacological
functions of natural C. sinensis.

Scientific Background
♦ Cordyceps sinensis (Berk.) Sacc. has been used
in china as a precious tonic herb for centuries
♦ It has broad nutritional and health benefits (Zhu
et al., J Alternat Compli Med 4:289-303 & 429-
457,, 1998).
)
♦ Co-existence of P. hepiali and H. sinensis was SELDI-TOF MS profiling of proteins
found in fresh C. sinensis (Zhu et al., J Mycol ♦ Caterpillars and stromata of C. sinensis and freeze-dried P. hepiali & H. sinensis mycelia were individually grinded
into powder in liquid nitrogen. The powder (0.5 g each) was dissolved in 600 ml Tris-Glycine (pH 8.3) & centrifuged at
Res 5:214-224, 2007) 14,000 rpm for 5 min at 4 Ԩ.
♦ Competitive proliferation abilities are altered ♦ Supernatants were diluted with PBS to about 200-300 nM, before being subjected to a normal-phase chip and
associated with unparallel alterations of gene analyzed on a PBS-II protein chip reader (Surface-enhanced laser desorption ionization – time of flight mass spectra,
or SELDI-TOF MS; Ciphergen Biosystems Inc.).
copies of the fungi (EB2008 Program #704.4, Apr.
6 Poster Board #C303)

Maturation of C. sinensis and the

Temperature on Qinghai-Tibet Plateau
Less Matured Matured

Harvest Season Early May Late June

Temperature on 0-10 Ԩ 10-20 Ԩ
the Plateau
Stroma Short Long
A: “Type 1” B: “Type 2”

A B

Summary & Conclusions

♦ Distinct profiles of proteins and small molecule chemicals were noted for
caterpillars and stromata during C.C sinensis maturation.
maturation The maturation
associates with dynamic changes in profiles of component chemicals,
supporting its superior function profiles.
♦ The profiles for P. hepiali and H. sinensis mycelia do not completely
match to those for C. sinensis.
♦ The profiles for P. hepiali mycelia appear to be closer to those for C.
sinensis, than those for H. sinensis.