2. NuLiv Operates on 6 Interconnected Business Platforms
1. Focused RESEARCH on METABOLISM (slides 3- 16)
2. Discovery of novel, safe, and BIOACTIVE botanical FRACTIONS &
COMPOUNDS (slides 17 - 25)
3. Development of PRODUCTION PROCESS for NuLiv’s proprietary
bioactive fractions and compounds (slides 26 – 28)
4. Development of safe and effective SUPPLEMENT products (slides
29)
5. SOURCING and QC of botanical ingredients (slides 30 – 31)
6. Futuristic WELLNESS products and services platform (A NuLiv
experimental model) (slides 32)
3. Focused Research on Metabolism
For close to a decade, NuLiv has centered its research around
metabolism, the biological functions that sustain life, at cellular
and systemic levels
1. Research initiatives (slides 4 – 6)
1.1 Central belief
1.2 Hypothesis
1.3 Strategy
2. Life Science and Clinical Research platforms (slides 7 –14)
2.1 Facility
2.2 Staff & advisors
2.3 Validation platform
2.4 Supporting framework
3. Patents (slide 15)
4. Papers (slide 16)
4. The Central Belief that laid down
the Foundation for Our Research
TCM offers the best organized and time tested holistic
and systemic health wisdom.
NuLiv’s research idea, discovery of novel bioactive
ingredients, and development of nutritional products
should germinate from this knowledge base
5. The Hypothesis Our Research Strategy is Built Upon
• “Qi” (breathing, life force, energy) and “Xue” (circulation),
the foundation of TCM principle, are the metaphysical
transformation and final manifestation and distribution
of nutrients in human body.
• The biological pathway of this manifestation and distribution,
i.e., nutrient absorption, transportation of nutrients through
bodily fluids (blood included), metabolic and catabolic
functions, regulation of haemopoiesis & angiogenic functions,
even its effect on immune functions, are all integral to this
final manifestation.
• “Qi” and “Xue” herbs must be bioactively involved in the
various biological pathways and functions. Study of these
herbs should offer better odds of novel discoveries and
understanding of their benefits toward human health.
.
6. Our Strategy is to Build a Research Platform that
Allow us to Discover Novel Bioactive Compounds
from Chinese “Qi” and “Xue” Herbs
1. Select safe and widely used TCM herbs as research subjects.
2. Extract, separate, fractionate, and purify these herbs to fraction
and/or compound levels.
3. Develop bioassays to identify purity and concentration level of
these fractions and compounds.
4. Formulate application specific functional ingredients composed
of these fractions and/or compounds and assay for their
efficacies.
5. Test ingredient efficacy and safety to the technical or financial
level that is feasible; cell, animal and human.
6. Develop and test for ingredient reproducibility and stability.
7. NuLiv’s Advanced and Integrated
Life Science and Clinical Research Platform
Component Description
Facility NuLiv Taipei Laboratory
NuLiv Shanghai Laboratory
Management, Staff and
Advisors
Highly educated and trained in business, multi
scientific & clinical disciplines, and work closely
in a truly interdisciplinary manner
Discovery and Validation In-house and 3rd
party in vitro, in vivo, and
human use study platforms
Supporting
Framework/Network
Supported by NuLiv’s own subsidiaries and
affiliates, and long term strategic partners and
alliances in many distinguished academic and
research institutions
8. Research Facilities
Taipei and Shanghai Laboratories
• NuLiv Taipei (NDMC) Laboratory
1. Research initiatives
2. Research: Chemistry, cell assay, animal and human study
on plant derived bioactive fractions/compounds
3. Product design and development
4. Production process development
• NuLiv Shanghai Laboratory
1. Extraction, fractionation, purification of botanicals
2. Production process, MOA, and CMC development
3. Sourcing and Procurement
4. QA and QC
11. NuLiv Management /Business & Research Executives
Founder & CEO
Austin Wang, M.S. NuLiv Holdings, Inc. (World Headquarters) Taipei City,
Taiwan
Executive Director
Y.H. Lee, M.D. Vice Chancellor, China Medical Univ. (Taiwan), Previously
Dean, Chang Kung Medical School, Dep. Director, Chang Kung Hospital
System (10,000+ beds)
Principle Scientific Advisor
H.C. Lin, Ph.D. Univ. of North Carolina. Taught TCM at NDMC for over 20
years. Pioneered the hypothesis that “Qi” herbs regulate absorption and
other metabolic functions
President
Americas, Europe, Asia, Africa
Business Development
Sales & Marketing Representative
Americas, Europe, Asia, Africa
Michael Wang, M.S. NuLiv Science USA, Walnut, CA
David Allen, Ph.D. World Wellness, LLC., San Diego, CA
President
Greater China
David Wu, Ph.D. Business Administration, Univ. of South Australia,
Director
Research & Development
NuLiv Taipei Laboratory
Thomas Yang, Ph.D., Molecular Microbiology, Univ. of Texas, Southwestern
Medical Center
Director
NuLiv Shanghai Laboratory
Sunnie Sun, Ph.D., Pharm. Analysis, Sheng Yang Pharm. Univ.
Director
Clinical Research
Rose Chen, M.D., Ph.D., Shanghai TCM University
12. NuLiv’s Scientific Advisors
Chang, T.C., Ph.D. Biochemistry, Univ. of Illinois, Professor, Dept. of Biochemistry, National Defense
Medical Center,Taiwan
Chang, W.L., Ph.D. Pharmacy, National Taiwan Univ., Professor, School. of Pharmacy, National Defense
Medical Center, Taiwan
Kuo, C.H., Ph.D. Physiokinetics, Univ. of Texas, Professor and Chair, Department of Exercise Science,
National Taipei Physical Education College, Taiwan
Chen, C.X., Professor Director, Department of Pharmacology, TCM Univ., Shanghai, China.
Serves as our toxicity and safety advisor on TCM and other herbs
Komatsu, Yasuhiro,
Ph.D.
Medical science, Juntendo University, Prior Dean of R&D department, Tsumura &
Co.
Chu, C. H, Ph.D. Food engineering, University of Tokyo, expert in pre-clinical pharmacology tests
Fan, David, Ph.D. Senior Lecturer, Trinity College, Cambridge Univ., Editor-in-chief, Angiogenesis
Hsieh, Steve, Ph.D. Nutritional Biochemistry, Univ. of Wisconsin, Ex Vice Chairman, National Science
Council, R.O.C. Government
Looi Hwang, Ph.D. Industrial & Environmental Pharmacy Ph.D. from Purdue, previously G.M. of MSD,
Hanzhou, China & and Merck of Singapore
J.K. Luo, Ph.D. Editor (acting), Journal of Heterocyclic Chemistry, Professor at University of S.
Florida
Funfack, Wolf, M.D. Metabolic Balance founder.
Peng, C.K., Ph.D. Statistical Physics, Boston Univ., Assoc. Professor/Co-director, Rey Institute for
Nonlinear Dynamics in Physiology and Medicine, Harvard Medical School.
13. Our In vitro, In vivo, and
Human Research Platforms
In vitro Assay
Systems
• Establish any cell assay system in 2 to 4 months
• Currently available cell assay systems: HaCaT and HDF cell,
Caco-2, 3T3-L1, HSMMT,HepG2, HCH & SW 1353, and etc
In vivo Assay for
efficacy and
safety Systems
• Nude mice for cancer and cosmetic studies
• db/db mice for diabetes and wound healing studies
• SD rat for ergogenic and diabetes studies
• absorption model (portal vein)
• Acute and Sub-acute Toxicity
Human use
Study
• Topical skin care test
• Ergogenic test
• Cancer adjuvant therapy
14. Our Supporting Framework & Network
Facility, equipment,
interdisciplinary consultation
National Defense Medical Center
Industrial Technology Research institute,
Taiwan
Yang Ming University, Taiwan
Taipei Medical University, Taiwan
In vivo and human study China Pharmaceutical University, Nanjing,
China Taipei Physical Education College
I-Shou University Hospital
NuLiv Wellness Clinic
Consultation, Cellular science
Metabolic health
TCM pharmacology &
toxicology
angiogenesis
Yang Ming Univ. Stem Cell Research Center
Taipei Medical Univ. Stem Cell Research Center
Dr. Wolfgang Funfack, Metabolic Balance, De.
Shanghai TCM university
China Medical University, Taiwan
Trinity college, Cambridge University, UK
15. Title Country/Region Patent NO. Application NO.
Method for Regulating Nutrient
Absorption with Astragalosides
USA US11/426,029
China CN200610090113.0
Taiwan I271195
Method for Regulating Nutrient
Absorption with Ginsenosides
USA US11/426,06
China
CN200610090114.5
CN200910178493.7
CN200910178492.2
Taiwan I317280
Method for Skin Care PCT PCT/US07/77326
USA US11/469,659
China CN200710089586.3
Taiwan TW095132614
Use of Cycloartane compounds for
treating arthritis
USA US12/353,779
China N/A yet
Taiwan TW098135306
Patents from NuLiv’s Research
16. • Effect of ginsenosides on glucose uptake in human Caco-2 cells is mediated through altered Na+/glucose cotransporter 1 expression.
Chang TC, Huang SF, Yang TC, Chan FN, Lin HC, Chang WL. J Agric Food Chem. 2007 ;55(5):1993-8.
• Effect and mechanism of ginsenosides CK and Rg1 on stimulation of glucose uptake in 3T3-L1 adipocytes. Huang YC, Lin CY,
Huang SF, Lin HC, Chang WL, Chang TC. J Agric Food Chem. 2010 ;58(10):6039-47.
• Glycogen overload by postexercise insulin administration abolished the exercise-induced increase in GLUT4 protein. Chou CH,
Tsai YL, Hou CW, Lee HH, Chang WH, Lin TW, Hsu TH, Huang YJ, Kuo CH. J Biomed Sci. 2005 ;12(6):991-8.
• The induction of orphan nuclear receptor Nur77 expression by n-butylenephthalide as pharmaceuticals on hepatocellular
carcinoma cell therapy. Chen YL, Jian MH, Lin CC, Kang JC, Chen SP, Lin PC, Hung PJ, Chen JR, Chang WL, Lin SZ, Harn HJ.Mol
Pharmacol. 2008 ;74(4):1046-58.
• The natural compound n-butylidenephthalide derived from Angelica sinensis inhibits malignant brain tumor growth in vitro and
in vivo. Tsai NM, Chen YL, Lee CC, Lin PC, Cheng YL, Chang WL, Lin SZ, Harn HJ. J Neurochem. 2006;99(4):1251-62.
• The antitumor effects of Angelica sinensis on malignant brain tumors in vitro and in vivo. Tsai NM, Lin SZ, Lee CC, Chen SP, Su HC,
Chang WL, Harn HJ. Clin Cancer Res. 2005;11(9):3475-84.
• Acetone extract of Angelica sinensis inhibits proliferation of human cancer cells via inducing cell cycle arrest and apoptosis. Cheng
YL, Chang WL, Lee SC, Liu YG, Chen CJ, Lin SZ, Tsai NM, Yu DS, Yen CY, Harn HJ. Life Sci. 2004;75(13):1579-94.
• Ginsenoside Rb1 inhibits tube-like structure formation of endothelial cells by regulating pigment epithelium-derived factor
through the oestrogen beta receptor.
• Leung KW, Cheung LW, Pon YL, Wong RN, Mak NK, Fan TP, Au SC, Tombran-Tink J, Wong AS. Br J Pharmacol. 2007;152(2):207-15.
• Metabolites of ginsenosides as novel BCRP inhibitors. Jin J, Shahi S, Kang HK, van Veen HW, Fan TP. Biochem Biophys Res
Commun. 2006;345(4):1308-14.
• Signaling pathway of ginsenoside-Rg1 leading to nitric oxide production in endothelial cells. Leung KW, Cheng YK, Mak NK, Chan
KK, Fan TP, Wong RN.FEBS Lett. 2006 ;580(13):3211-6
• Modulating angiogenesis: the yin and the yang in ginseng. Sengupta S, Toh SA, Sellers LA, Skepper JN, Koolwijk P, Leung HW,
Yeung HW, Wong RN, Sasisekharan R, Fan TP. Circulation. 2004;110(10):1219-25.
• S.-F. Huang, Y.-C. Huang, J.-Y. Lin, W.-L. Chang and T.-C. Chang (2010) Effect of Ginsenoside Rb1 on Glucose Uptake and Expression
of Glucose Transporters in Animal Cells, Adaptation Biology and Medicine, Volume 6: Cell Adaptations and Challenges, 2010 (In
Press).
• Yu-Chuan Huang, Cheng-Yu Lin, Su-Fen Huang, Wen-Liang Chang, and Tsu-Chung Chang (2010) Differential effect of oleanolic and
ursolic acid on GLUT4 expression and membrane translocation in 3T3-L1 adipocytes, Manuscript in preparation.
Published Papers and papers in Press
17. Discovery of Novel, Safe, and Bioactive
Botanical Fractions and Compounds
After a decade of following our research central belief, hypothesis, and strategy,
and by subjecting dozen “Qi” and “Xue” herbs through our in vitro, in vivo, and
human studies, we have discovered 6 bioactive fractions and compounds in
these herbs that have shown dose-dependent benefit toward specific human
functions
1. 6 bioactive fractions / compounds discovered (slide 18)
2. Functional ingredients formulated with our bioactive fractions/compounds
2.1 Brief descriptions of the 6 functional ingredients (slide 19)
2.2 ActiGinTM
, for optimum exercise energy, endurance, and recovery (slide 20)
2.3 AstraGinTM
, for enhanced nutrients absorption at the cellular level (slide 21)
2,4 AstrionTM
, for youthful and radiant skin (slide 22)
2.5 ImmunoAGTM
, for adjuvant therapy (slide 23)
2.6 OsteoSineTM
, for reversing bone loss (slide 24)
2.7 Slim&FitTM
, for weight control and metabolic syndrome (slide 25)
18. 6 Fractions / Compounds from our
Research and Their Biological Functions
Fractions/Compounds Discovered Functions
NL-F001 Anti-angiogeneis
NL-F002 Enhance amino acids, vitamins, and
glucose absorption at the cellular level;
anti-angiogenesis
NL-F003 Increase Adiponectin secretion
Ergogenic/recovery
NL-F004 Enhance amino acids, vitamins, and
glucose absorption at the cellular level
NL-F006 Enhance amino acids, vitamins, and
glucose absorption at the cellular level ;
Increase Adiponectin secretion
NL-F007 Increase collagen and hyaluronic acid
secretion; decrease MMP-1 secretion
19. Proprietary Nutraceutical Ingredients Formulated with
NuLiv Bioactive Fractions and Compounds
AstraGinTM
An all natural nutrient uptake enhancing complex that improves amino acids, glucose,
vitamins absorption by 62%, 57%, 50% through regulation and parallel alteration on both
the protein and mRNA expression levels of the nutrient transporter genes
AstrionTM
Reduces the number and appearance of fine lines & wrinkles, skin discoloration due to
sun damage, and firms, tones, and hydrates skin through increased dermal genesis and
UV protection. Dermal genesis promotes the synthesis of new collagen and hyaluronic
acid and, at the same time, reduces the breakdown of existing collagen due to UV light
destruction
ActiGinTM
Increased delivery of glucose to muscle cells; Protect against free radical attack after
exercise; Anti-inflammation; Minimize muscle cell damage; Increased glycogen
replenishment after Intensive workout
ImmunoAGTM
ImmunoAGTM
promotes nutrient absorption and metabolism in intestinal cells, Inhibits
abnormal cell proliferation and angiogenesis, induces abnormal cell mitotic arrest and
apoptosis through the activation of multiple signal pathways. In an in vivo study,
ImmunoAGTM
demonstrated to inhibit abnormal cell growth by 44% and prolonged the
life of subcutaneous abnormal cell bearing rats by 33% when compared to a control
group.
OsteoSineTM
Promotes bone mineral density and structural strength by enhancing bone formation
and reducing bone resorption. This dual action has been confirmed by NuLiv’s PO (post-
ovariectomized) female rats (equivalent to menopausal women) and RA (retinoic Acid-
induced acute osteoporosis) rats (Equivalent to none gender or age-related osteoporosis
persons) models.
Slim&FitTM Decreases the intestinal absorption of glucose through the regulation and parallel
alteration on both the protein and mRNA expression levels of the nutrient transporter
genes while increases the glucose absorption in muscle and adipocyte cells through
insulin independent pathway.
24. OsteoSineTM
In vivo Study
Normal bone treated with retinoic
acid to simulate osteoporosis
conditions
Treated with 400 mg of
OsteoSine daily for 5 weeks
26. Development of Production Process
for
NuLiv’s Proprietary Bioactive Fractions and Compounds
We develop production process, reference standard, MOA,
bioassay, and QA Programs for the production of our
proprietary active fractions and compounds so that they
have the same purity and concentration level as in those
used in our research.
1. Extraction, Fractionation, Separation, and Purification of
Raw Herbs to the Fraction and Compound Levels (slide
27)
2. Purity and concentration level of our proprietary
bioactive fractions / compounds are identified and
measured by specific bioassays (slide 28)
28. The Purity and Concentration Level of our Bioactive Fractions
and Compounds are Identified and Measured by Specific Bioassays
Active constituentsMedicinal
plants
Crude
extracts
Fraction 1
Fraction 2
Fraction 3
Fraction 4
Fraction 5
Fraction 6
…
fractionationextraction
Formulation
Depend on function
Products & Marketing
Structure
elucidation
UV
MS
NMR
IR
CD
1
H NMR
13
C NMR
2D NMR
separation
Absorption
Anti-cancer
Skin care, etc
Active
constituents
QC systems
-LC/UV
-GC/MS
Bioassay
QC
29. Our Supplements are Highly Effective and Safe
in Supporting Critical Human Health Functions
30. Our Sourcing Operations Guarantees Premier Quality Products with
Competitive Prices and Timely Delivery to our Customers
NuLiv/Customer specifications/requirements
Vendor
Vendor Survey for Certificates, Qualifications, MOA, COA, sample
Onsite Vendor Survey
Disqualified
Qualified
Contract/Agreement
Primary
suppliers
Secondary
Supplier
31. Our Quality Control on Sourcing Operations
Closely Follows Pharmaceutical Protocols
• Follow USP/NF, AOAC, ChP, GB, In-house developed MOA
• PhytoMonitorTM
Double QC Checking
– First tested at the manufacturing sites or production sample tested at
NuLiv shanghai Laboratory
– Production order samples tested at NuLiv Shanghai laboratory before
order can be shipped.
– Samples can be tested by independent 3rd party laboratories in the U.S.
for additional quality control.
– Alkemists Pharmaceuticals, CA
– Michelson Lab, CA
– Oregon Department of Agriculture (heavy metals)
32. Futuristic Wellness Product and Service Platform
(A NuLiv Experimental Model)
Wellness Advisors
Interactive and personal
wellness information exchange
and virtual community management
NuLiv Wellness Management Inc.
Device
HRM Meridian
Blood analysis
CD/Biochips
Nutritional Sciences
NuLiv Laboratories
(Slides 1 – 42)
System complexity analysis
DynaDx – Harvard Reylab
Evidence based wellness
know-how
NuLiv Wellness Clinic
Wellness/Sub-clinical Primary Care Clinic
Cellular sciences
Steminent Therapeutic Inc.
33. Whether its research capability,
cutting edge proprietary botanical fractions,
highly effective nutritional supplement products,
premium quality botanical ingredients,
or even Futuristic Wellness Model,
NuLiv Science is the company that you can trust.
Thank you