Combined Use of Ganoderma lucidum ReishiMax and Tea Polyphenols

Tegreen Inhibits Tumor Growth Synergistically in Cancer-Bearing Mice

Yan Zhang, Li Zhang, Ningzhi Tan, Ying Qi, Ling Gao, Jia-Shi Zhu
Pharmanex Beijing Clinical Pharmacology Center, Beijing, China; Pharmanex Shanghai
R&D Center, Shanghai, China; Pharmanex Research Institute, Provo, UT, USA
Abstract Comparing Market Reishi Products ReishiMax Increases IL-2 in Mice Inhibition of Adhesion (%) of MDA-MB-231 Inhibition of Proliferation (%) of MDA-MB-231
5 p<0.001 by ANOVA Cells by ReishiMax (GLE) and Tegreen Cells by ReishiMax (GLE) and Tegreen

Two Urn Reishi

Ganoderma lucidum (Reishi) and green tea Tegreen (GT polyphenols, mg/ml) Tegreen (GT polyphenols, mg/ml)

Zhongke Spores
4

IL-2 (ng/ml)
are commonly used in China for cancer +822%
0 0.03 0.06 0.125 0 0.03 0.06 0.125

Beijing Spores
3

Double Bridge
prevention and adjuvant therapy. A screening +799%

Jilin Spores
revealed superior anti-malignancy activities of 2 0 100 ± 4.8 24 ± 1.1 7 ± 1.7 2.7 ± 0.1 0 100 ± 5 100 ± 6 95 ± 2 51 ± 3

ReishiMax
ReishiMax (RM) among commercial Reishi +405% GLE GLE
1 p=0.12 0.125 55 ± 4.8 20 ± 3.7 2 ± 1.1 - 0.125 77 ± 2 49 ± 3 40 ± 1 -
(mg/ml) (mg/ml)
products (JACM 9:491, 2003). Synergy of RM and
0
0.25 45 ± 2.4 13 ± 9.2 1.5 ± 0.6 - 0.25 46 ± 2 32 ± 1 27 ± 0.2 -
Tegreen (TG; containing >98% tea polyphenols) Placebo 0.585 1.170 2.925 0.585 (g/kg)
was found in anti-cancer in human breast and Other Reishi 0.5 27 ± 9.8 10 ± 6.2 0.3 ± 0.2 - 0.5 43 ± 3 30 ± 2 23 ± 0.2 -
Placeo ReishiMax
prostate cancer cells (Intl J Oncol 30:963, 2007). Sliva,et al., J. Altern. Compl. Medicine 2003, 9(4):491-497 Thyagarajan, Zhu, Sliva. Combined effect of green tea and Ganoderma lucidum Thyagarajan, Zhu, Sliva. Combined effect of green tea and Ganoderma lucidum
By Prof. Chiang of National Taiwan University on invasive behavior of breast cancer cells. Itn J Oncol 2007, 30:963-969 on invasive behavior of breast cancer cells. Itn J Oncol 2007, 30:963-969
Further screening showed that fucose-containing
polysaccharides are highly enriched in RM Reishi Triterpenes ReishiMax Enhances To Examine the Anti-Cancer ↑ Survival of S180 Sarcoma-Bearing Mice
DAD1 D, Sig=252,16 Ref=off (E:\REISHI\03011309.D)
NK Cell Activity in Mice
(0.34%), the class of polysaccharides mAU
ReishiMax Effects of RM+TG Combo and Delayed the Death of the Mice
demonstrating high immune enhancing activities 0 90 p<0.01 by ANOVA Placebo (n=20) Kaplan-Meier Ln Cum. Hazard Plot for timeRM Kaplan-Meier Ln Cum. Hazard Plot for timeRTM
0 10 20 30 40 50 min

NK Cell Activity
DAD1 D, Sig=252,16 Ref=off (E:\HP1100~5\DATA\REISHI\02092903.D) Censor Variable: <None> Censor Variable: <None>

(Bioorg Med Chem 10:1050, 2002). They are much mAU

Product A from Hongkong
85 Grouping Variable: groupRM
0
Grouping Variable: groupRTM
0

less (0.04-0.20%) in other Reishi products. In 0

0 10 20 30 40 50 min
80 +17.3% +17.4% +17.7% ReishiMax 666 mg/kg (n=20)
-.5 Placebo -.5
Placebo
DAD1 D, Sig=252,16 Ref=off (E:\HP1100~5\REISHI-1\03102102.D)
addition to the survival studies in cancer mice mAU Product B from China
75 -1 -1

70 RM 333mg/kg + TG 333mg/kg (n=20)

(FASEB J 21:A1100, 2007), we tested synergy of 0
0 10 20 30 40 50 min +13.1%
-1.5 -1.5

RM and TG in inhibiting tumor growth in sarcoma- mAU

DAD1 D, Sig=252,16 Ref=off (E:\HP1100~5\DATA\REISHI\02051607.D) 65
0 (days) 14 28
-2
ReishiMax -2

Product C from Taiwan RM 333mg/kg

bearing mice. After 28-day treatment, RM+TG 60 (Examine deaths of mice) -2.5 666 mg/kg -2.5

0
0 10 20 30 40 50 min Placebo 0.585 1.170
2.925 0.585(g/kg) -3 -3
TG 333mg/kg
significantly decreased tumor weight by 45% in mAU
DAD1 D, Sig=252,16 Ref=off (E:\REISHI\02122612.D)
Product D from Japan ReishiMax Other Reishi Inject S180 sarcoma cells 1.4 1.65 1.9 2.15 2.4 2.65 1.4 1.65 1.9 2.15 2.4 2.65

S180-innoculated mice, compared to controls 0.2 ml into peritoneal cavity Ln Time Ln Time
0
0 10 20 30 40 50 min By Prof. Chiang of National Taiwan University
(p<0.05). The data further confirmed the previous
finding of synergy of RM and TG in anti- Fucose-Containing Reishi Glycoproteins ReishiMax Increases Secretion To Examine the Anti-Cancer RM+TG Reduces Size of S180
malignancy, indicating their therapeutic values in Lot Fucose % 2000
of Interferon-γ in Mice Effects of RM+TG Combo 2.8
Sarcoma in Mice
Interferon-γ (pg/ml)

cancer prevention and adjuvant treatment. ReishiMax MG 23931 0.34 Placebo (n=20)

Weight of Tumor (g)

2.6
1500 p<0.05 by ANOVA
Product 1 050803 0.15 ReishiMax 0.2 g/kg (n=20) 2.4

p=0.024
Scientific Background Product 2 (TW) 31127 0.089
1000 +745% +886% +726% ReishiMax 0.8 g/kg (n=20)
2.2
2.0
Product 2 renew (TW) LAK 1128 0.10 p=0.167
♦Ganoderma lucidum (GL) and Green Tea are Product 3 (SH) 030520 0.068
500
RM 0.1g/kg + TG 0.1g/kg (n=20) 1.8
RM 0.4g/kg + TG 0.4g/kg (n=20) 1.6
precious medicinal herbs and have broad Product 4 060209 0.142

p=0.145
p=0.257

p=0.077
1.4
Product 5 021206 0.148
nutritional and health benefits. They have Product 6 (spores) 20061010 0.20
0 0 (days) 14 28 1.2
Placebo 0.585 1.170 2.925 0.585 (g/kg)
Examine 1.0
been used in china for >2000 years, Product 7 (spores) 800190 0.06 Other Reishi 0.8
ReishiMax Subcutaneous injection of Size of Tumor
including for anti-cancer adjuvant treatment. Product 8 (spores) 0QN1027 0.043 Placebo 0.2 0.8 0.1+0.1 0.4+0.4 (g/kg)
By Prof. Chiang of National Taiwan University 0.2 ml S180 sarcoma cells ReishiMax RM + TG
♦ReishiMax (RM), an extract of GL, contains
high concentrations of active chemicals: Tegreen (TG) Promotes Cancer Catechins (EGCg) Inhibits Cancer Summary and Conclusions
triterpenes (Ma et al. J Nat Prod 2002, 65:72) Cell Apoptosis Growth in Mice ♦ ReishiMax maintains the healthy ♦ Synergy of ReishiMax and Tegreen in
and Fucose-containing glycoproteins (Wang Blank Add TG immune functions: anti-cancer in vitro
et al. Bioorg Med Chem 2002, 10:1057).
Placebo ↑the activity of macrophages ↓Cancer cell proliferation
♦Tegreen (TG) contains >98% tea MCF-10A cells
↑ proliferation of B cells, and T cells ↓Cancer cell invasive behaviors
polyphenols, ~70% tea catechins, the major ↑ T cell functions (↑ Th1,↓ Th2) ↓Cancer cell migration
anti-cancer chemicals (Cooper and Morre BT-20 cells EGCG
↑ the NK cell functions ↓Angiogenesis
2005, 11:521). ↑ secretion of Interferon-γ ♦ Synergy of ReishiMax and Tegreen in
♦Synergy of RM and TG in anti-cancer was ♦ Tegreen keeps the normal cell health: anti-malignancy in vivo
shown in vitro (Thyagarajan, Zhu, Sliva Itn J HeLa cells ↑ Apoptosis of mutant cells ↑Survival time
Oncol 2007, 30:963). (Prof. J. Morre, Purdue University) Naasani, et al., Cancer Res. 2003, 63: 824-830 ↓ Angiogenesis ↓Cancer death risks