CELLMetrix

Benefits | Cell Health | Stem Cell | FAQ | The Science | Label Facts

CELLMetrix beneficial effects based on the literature of its components:

• Adult stem cell rejuvenation [1-4, 48-49]
• Promotes stem cell self-renewal [55]
• Healthy cardiovascular system [5-8]
• Healthy blood glucose levels [9-13] 
• Healthy blood pressure levels [14-15] 
• Healthy cholesterol levels [9,16-17] 
• Younger looking skin [18-24]
• Better learning and focus [25-30]     
• More endurance with exercise [31-35]     
• Healthy immune system [31-32, 36-39]     
• Healthy breasts, colon, pancreas 
  and prostate [40-46]

See References

Slash years off your biological age while looking younger, feeling stronger and aging gracefully.

Support Cellular Microenvironments to Nourish Telomeres and Protect DNA

As part of its multi-pathway activity, the ingredients in CELLMetrix can also help to detoxify the body and lower inflammation that promotes imbalance and inhibits stem cell function. 

Quick Science and History

In the nucleus of each cell, the DNA molecule is packaged into thread-like structures called chromosomes. Each chromosome is made up of DNA, tightly coiled many times around proteins called histones that support its structure. At the end of each chromosome are telomeres. Telomeres are the caps at the end of each strand of DNA that protect it, like the plastic tips at the end of shoelaces. Telomeres shorten each time a cell divides and act as a clock that signals cells to age. Eventually telomeres become so short that the DNA is unprotected and cells stop functioning or die.

Telomeres are supported in their microenvironment by an enzyme called telomerase.

In fact, the three scientists who discovered how telomerase impacts telomere length won the 2009, the Nobel Prize for Physiology/Medicine. This discovery has been termed, “the single greatest longevity development in our lifetime.” Their papers explained how the ends of DNA strands are protected by telomeres, and that telomeres are supported by telomerase. When human cells are exposed to telomerase the telomerase slows cell aging and allows cells to begin copying again.

By changing gene expression to a younger phenotype you can have older cells function as they did when they were younger.

The BENEFITS

CELLMetrix is a one of a kind cellular support supplement formulated to positively affect many of the biomarkers that are involved with vitality and aging. CELLMetrix works on multiple levels to support cellular health throughout the body. This product was formulated using the latest scientific breakthroughs as well as ingredients that have a long history of evidence for their cellular benefits.

CELLMetrix™ Ingredient Benefits

•       Look & Feel Younger
•       Increased Learning & Focus
•       Strength & Endurance
•       Harnesses the Power of Your Own Stem Cell Rejuvenation
•       Ingredients DOUBLED Simple Lab Animals Lifespan
•       Helps Support Healthy Cardiovascular, Immune, Metabolic and Neural Health
•       Helps Support Healthy Blood Pressure, Blood Glucose and Cholesterol Levels

Stem Cells and Aging

Children are protected from the ravages of aging and can rapidly recover from injury or illness. It is because the young have regenerative stem cells, which have a superior ability to repair and regenerate most damaged tissues. As we age, our stem cell populations become depleted and/or slowly lose their capacity to repair. Moreover, the micro-environment (i.e. niches) around stem cells becomes less nurturing with age, so cell turnover and repair are further reduced. This natural progression occurs so slowly that we are barely aware of the decline, hence aging. Unfortunately, we typically start noticing our body aging as early as our 30s and 40s, and especially after 50 years of age.

CELLMetrix™ works differently than other products on the market

You may have seen a number of products advertised as stimulating or enhancing stem cells. Each person only has a limited number, so using them up faster may not be a good strategy. CELLMetrix is about improving the effectiveness and longevity of your stem cells as well as preserving the stem cell micro-environment. The micro-environment declines with age due to a decline in capillary density and increases in basal inflammation, fibrosis, toxic waste products, and fat cells.

An effective stem cell therapy must address the declines in micro-environments, as stem cells will not respond well in a harmful or toxic environment. That is exactly what CELLMetrix is designed for!

CELLMetrix™ Beneficial Effects Based on the Literature of its Components 

Astragalus Root Extract and Complex

Astragalus compounds are shown to have the ability to inhibit chromosomal instability by supporting the chromosomes micro-environment. Scientific breakthroughs in the last five years have observed this to be a key factor to healthy aging.

One compound in Astragalus in a laboratory study on mice was shown to reduce of DNA damage and an improvement of DNA repair ability. Another similar study showed two Astragalus compounds delayed aging. In one paper a team of researchers from the UCLA AIDS Institute described how their work with a new drug derived from astragalus root not only reduces the aging process of immune cells, but also enhances how these cells respond to viral infections.

Astragalus root has a long history of use increase metabolism, stamina, strength and vitality. Scientist are now able to test and study in detail the compounds and the mechanisms of action for these benefits.

Scientists now believe that astragalus also works by stimulating several factors of the immune system. In laboratory studies, astragalus extracts increase the activity of monocytes, natural killer cells, and lymphocytes, In addition, astragalus has been shown to reverse immune suppression. In other studies Astragalus was shown to suppress airway hyper reactivity associated with allergic asthma in vivo and increase M-cholinergic receptor density in senile rats, which suggests that it may have a role in combating senility.  

Oligomeric Proanthocyanidins (OPCs) from Pine Bark

OPC is the acronym for “oligomeric proanthocyanidins,” a class of polyphenolic bioflavonoids. OPCs are nature's most powerful antioxidants. In fact, their usefulness in fighting free radicals and helping people lead a longer, healthier life is well established in scientific literature.

OPCs are a unique class of highly bioavailable flavanol compounds that protect and strengthen collagen, which make up skin, connective tissues and vascular walls by delaying aging in human vascular endothelial cells. By supporting the vascular walls you can enhance nutrient delivery to all parts of our body. OPCs also scavenge oxygen free radicals at a greater rate than vitamins C or E.

Pterostilbene Extract and Complex

Pterostilbene is a dimethylated derivative of resveratrol and for some mechanisms, is more potent. It is also much better absorbed and is commonly referred to as a 'better resveratrol'. While most of the actions of the two are comparable, pterostilbene is much more absorbable following oral ingestion and may be a more potent antioxidant and anticancer molecule.

A study in 2012 stated, “Importantly, markers of cellular stress, inflammation and AD pathology were positively modulated by pterostilbene but not resveratrol and were associated with upregulation of peroxisome proliferator-activated receptor (PPAR) alpha expression.”

Additional clinical studies on Pterostilbene show positive effects and in many cases it’s superiority to resveratrol in these areas, blood sugar circulation, immune function, lowering body fat, controlling asthma, controlling inflammation and colon health.

Pterocarpus Marsupium Extract and Complex

Pterocarpus marsupium demonstrates some very unique features, which include beta cell protective and regenerative properties. These effects have been reproduced in numerous animal and human trials for over half a century.

From the Indian Kino Tree, the flavonoid constituents marsupin, pterosupin and liquiritigenin, reduce serum triglycerides, total cholesterol and low-density lipoprotein in the blood. These and other flavonoids of Pterocarpus Marsupium have been studied and shown to have strong anti-oxidant properties and have a positive effect on cataracts in small animal studies.

Milk Thistle

Silybin and dehydrosilybin, two polyphenolic compounds, display a plethora of biological effects generally ascribed to their known antioxidant capacity. The fruit of the milk thistle plant contains flavonoids that are proven liver protectants. The standardized extract known as silymarin contains three flavonoids of the flavonol subclass. Silybin predominates, followed by silydianin and silychristin.

Endothelial progenitor cells (or EPC) is a term that has been applied to multiple different cell types that play roles in the regeneration of the endothelial lining of blood vessels. Clinical findings suggest that silymarin counteracts the inhibitory effects of rapamycin in EPCs. This protects EPCs against the antiproliferative effects of rapamycin and restore their reconstructive ability.

L-Theanine

L-Theanine is an amino acid (a building block for proteins) found in green tea. Evidence from human electroencephalograph (EEG) studies show that it has a direct effect on the brain. L-theanine significantly increases activity in the alpha frequency band which indicates that it relaxes the mind without inducing drowsiness.

A study published in 2012 stated: Compounds that delay aging in model organisms may be of significant interest to anti-aging medicine, since these substances potentially provide pharmaceutical approaches to promote healthy lifespan in humans. In the model organism C. elegans, L-theanine is capable of promoting paraquat resistance and longevity suggesting that this compound may as well promote healthy lifespan in mammals and possibly humans.

Bioperine

Bioperine is the only source of piperine to obtain patented status for its ability to increase the bioavailability of nutritional compounds. Bioperine is also the only source of piperine to undergo clinical studies in the U.S. to substantiate its safety and efficacy for nutritional use. When Bioperine was administered orally to healthy humans in a dose of 5 mg per person per day, the serum levels of different tested nutrients significantly increased by up to 60%.

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CELL HEALTH

Overall health starts with the health of your cells. Your cells replicate daily and the DNA inside cells is susceptible to damage simply from normal cell reproduction as well as a lack of quality nutrients. When DNA is damaged, the cells then replicate with errors, creating problems with your genetic code. The body experiences millions of DNA incidents per day that can contribute to damage. As we age, generations of these damaged cells diminish the function of your organ systems and tissues, reducing vitality, leading to aging and ultimately illness.

Now, with CELLMetrix you can add support to your cellular health. As part of its multi-pathway activity, the ingredients in CELLMetrix are able to support cell microenvironments protecting DNA and ensuring healthy cell reproduction as we age.

Cells

The human body is comprised of around 100 trillion cells. Billions of these cells die every day. Cells are being replicated daily from existing cells to replace the cells that are worn out, damaged or dying. Every seven years almost all of your cells will be replaced. By keeping your cells healthy now, you can promote future generations of healthy cells.
Nutrition has a very important role in sustaining cellular health overtime. Nutrients provide the raw materials for the creation of new cells and allow your existing cells to function properly.

Telomeres and DNA Replication

Telomeres

Telomeres are the caps at the end of the DNA strand that prevents the DNA from unraveling or breaking. Unfortunately, the telomeres shorten every time a cell divides. There eventually comes a point where the telomeres become so disintegrated that the DNA can no longer replicate.

Without telomeres, chromosome ends could fuse together and degrade the cell's genetic blueprint, making the cell malfunction, become cancerous or die. Because broken DNA is dangerous, a cell has the ability to sense and repair chromosome damage. Without telomeres, the ends of chromosomes would look like broken DNA, and the cell would try to fix something that wasn't broken. That also would make them stop dividing and eventually die.

In fact, the three scientists who discovered how a healthy telomere microenvironment impacts telomere length won the 2009, the Nobel Prize for Physiology/Medicine. This discovery has been termed, “the single greatest longevity development in our lifetime.” Their papers explained how the ends of DNA strands are protected by telomeres and how a healthy telomere microenvironment slows cell aging and allows cells to begin copying again.
Now this is not the whole answer to the disease known as Aging but certainly a very big one.

Stem Cells

While CELLMetrix supports a healthy microenvironment for all cells, the stem cells are probably the most important.

Stem cells are in all the organs and tissues of the body and are responsible for regenerating cells in case of injury or disease. Through aging, adult stem cells slowly lose the ability to differentiate into functional tissue-specific cells.

Stem cells are undifferentiated cells that are able to differentiate into specialized cells and can divide (when healthy) to produce more stem cells. They have no specific chosen function until further directed. Stem cells are your body’s reserve, replacing cells that become damaged and cells that die. Stem cells, as with all cells, need the proper nutrition to stay healthy.

An example of adult stem cells and aging is that your skin is continually losing dead cells, so that adult stem cells must continuously replenish the dying skin cells. As we age there are progressively fewer functional skin stem cells. Skin cell turnover slows, leading to thinner, dryer, less elastic skin that loses its youthful vitality. Hair thins and turns grey when hair follicle stem cells decline. Hearing, vision, taste, smell and touch all slowly decline with age, as the declining stem cell populations required to maintain these functions are unable to fully rejuvenate.

This is also true with all the organs within the body responsible for all bodily functions.

CELLMetrix is a dietary supplement designed to improve the function of your existing stem cells. When an organ or tissue is damaged, the stem cell emits natural signals that new cells are needed to replace old or damaged cells. CELLMetrix supports the adult stem cells that respond to provide new replacement cells.

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STEM CELL

A stem cell is a “blank” cell that has not yet made up its mind as to what it is going to be. “Stem cells have the remarkable potential to develop into many different cell types in the body. Serving as a sort of repair system for the body, they can theoretically divide without limit to replenish other cells as long as the person is still alive. When a stem cell divides, each new cell has the potential to either remain a stem cell or become another type of cell with a more specialized function, such as a muscle cell, a red blood cell, or a brain cell.”

Adult Stem Cells

Adult stem cells are predominantly formed in the bone marrow. And, just as in the beginnings of life, adult stem cells can literally change into any type of cell in the body throughout life. These adult stem cells are released from the bone marrow into the circulation of the bloodstream to seek out problem areas, then renew and restore those areas.

Adult stem cells have been identified in many organs and tissues, including brain, bone marrow, peripheral blood, blood vessels, skeletal muscle, skin, teeth, heart, gut, liver, ovarian epithelium, and testis. They are thought to reside in a specific area of each tissue (called a "stem cell niche”). Stem cells may remain quiescent (non-dividing) for long periods of time until they are activated by a normal need for more cells to maintain tissues, or by disease or tissue injury.
Adult Stem Cells therapy holds the key to unlocking the anti-aging fountain of youth we’ve all been wishing for. You can turn back the clock with their own adult stem cells therapies naturally.

Distinguishing Features of Progenitor/Precursor Cells and Stem Cells.

A stem cell is an unspecialized cell that is capable of replicating or self renewing itself and developing into specialized cells of a variety of cell types. The product of a stem cell undergoing division is at least one additional stem cell that has the same capabilities of the originating cell. Shown here is an example of a hematopoietic stem cell producing a second generation stem cell and a neuron. A progenitor cell (also known as a precursor cell) is unspecialized or has partial characteristics of a specialized cell that is capable of undergoing cell division and yielding two specialized cells. Shown here is an example of a myeloid progenitor/precursor undergoing cell division to yield two specialized cells (a neutrophil and a red blood cell).

Adult Stem Cell Plasticity

It was not until recently that anyone seriously considered the possibility that stem cells in adult tissues could generate the specialized cell types of another type of tissue from which they normally reside—either a tissue derived from the same embryonic germ layer or from a different germ layer. For example, studies have shown that blood stem cells (derived from mesoderm) may be able to generate both skeletal muscle (also derived from mesoderm) and neurons (derived from ectoderm). That realization has been triggered by a flurry of papers reporting that stem cells derived from one adult tissue can change their appearance and assume characteristics that resemble those of differentiated cells from other tissues.

The term plasticity, as used in this report, means that a stem cell from one adult tissue can generate the differentiated cell types of another tissue. At this time, there is no formally accepted name for this phenomenon in the scientific literature. It is variously referred to as "plasticity", "unorthodox differentiation" or "transdifferentiation".

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The SCIENCE

CELLMetrix works by protecting and nourishing your cells and stem cells which is the key to cell renewal, recovery and longevity. It does so by supplying synergistic herbal ingredients to stimulate your cells, including stem cells at the molecular level.

CELLMetrix supplies the nutrients necessary for a healthy cell microenvironment, which includes telomerase. This can effectively protect the telomeres that are the tips of the chromosomes. Healthy telomeres assist the DNA within the cell to replicate more effectively thus resulting in more vibrant healthy new cells.
Based on the 2009, the Nobel Prize for Physiology/Medicine and leading anti-aging scientists CELLMetrix is designed to create cellular health for a more vibrant and healthy aging process.

This page will allow you easy access to news articles, medical journal abstracts (and links) and information about telomeres and telomerase and ingredients found in CELLMetrix. You will find all the referenced material found on this entire website at the bottom of this page.

The studies are on ingredients found in CELLMetrix: Pine bark OPCs, Pterocarpus marsupium extract, Astragalus root extract, Milk thistle liposome, L-Theanine, Pterostilbene. You will find pertinent information in bold.

Aging by telomere loss can be reversed.

Bernardes de Jesus B1, Blasco MA.
1Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3, Madrid E-28029, Spain.
Abstract
Recently in Nature, Jaskelioff et al. (2010) demonstrated that multiple aging phenotypes in a mouse model of accelerated telomere loss can be reversed within 4 weeks of reactivating telomerase. This raises the major question of whether physiological aging, likely caused by a combination of molecular defects, may also be reversible.

Beyond average: potential for measurement of short telomeres.

Vera E1, Blasco MA.
1Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Madrid, E-28029, Spain
Abstract
The length of telomeres, and in particular the abundance of short telomeres, has been proposed as a biomarker of aging and of general health status. A wide variety of studies show the association of short telomeres with age related pathologies and cancer, as well as with lifespan and mortality. These facts highlight the importance of measuring telomere length in human populations and by using reliable methods to uncover the association between telomere length and human disease. This review discusses the advantages and drawbacks of current telomere length measurement methods. Most of these methods provide mean telomere length values per cell or per sample and very few of them are able to measure the abundance of short telomeres, which are the ones indicative of telomere dysfunction. The information provided by each method and their suitability for different studies is discussed here.
PMID:22683684 [PubMed - indexed for MEDLINE]  PMCID: PMC3409675

The two isomers of HDTIC compounds from Astragali Radix slow down telomere shortening rate via attenuating oxidative stress and increasing DNA repair ability in human fetal lung diploid fibroblast cells.

Wang P1, Zhang Z, Sun Y, Liu X, Tong T.
4-Hydroxy-5-hydroxymethyl-[1,3]dioxolan-2,6'-spirane-5',6',7',8'-tetrahydro-indolizine-3'-carbaldehyde (HDTIC)-1 and HDTIC-2 are two isomers extracted from Astragalus membranaceus (Fisch) Bunge Var. mongholicus (Bge) Hsiao. Our previous study had demonstrated that they could extend the lifespan of human fetal lung diploid fibroblasts (2BS). To investigate the mechanisms of the HDTIC-induced delay of replicative senescence, in this study, we assessed the effects of these two compounds on telomere shortening rate and DNA repair ability in 2BS cells. The telomere shortening rates of the cells cultured with HDTIC-1 or HDTIC-2 were 31.5 and 41.1 bp with each division, respectively, which were much less than that of the control cells (71.1 bp/PD). We also found that 2BS cells pretreated with HDTIC-1 or HDTIC-2 had a significant reduction in DNA damage after exposure to 200 microM H(2)O(2) for 5 min. Moreover, the 100 microM H(2)O(2)-induced DNA damage was significantly repaired after the damaged cells were continually cultured with HDTIC for 1 h. These results suggest that HDTIC compounds slow down the telomere shortening rate of 2BS cells, which is mainly due to the biological properties of the compounds including the reduction of DNA damage and the improvement of DNA repair ability. In addition, the slow down of telomere shortening rate, the reduction of DNA damage, and the improvement of DNA repair ability induced by HDTIC may be responsible for their delay of replicative senescence.
PMID:19839736 Planta Med. 2012 Jan;78(2):115-21.

Astragaloside IV and cycloastragenol stimulate the phosphorylation of extracellular signal-regulated protein kinase in multiple cell types.

Yung LY1, Lam WS, Ho MK, Hu Y, Ip FC, Pang H, Chin AC, Harley CB, Ip NY, Wong YH.
Two Chinese herb-derived small molecule telomerase activators, astragaloside IV (AG-IV) and cycloastragenol (CAG), have recently been shown to improve the proliferative response of CD8+ T lymphocytes from HIV-infected patients by upregulating telomerase activity. Here, we examined the signaling mechanism of AG-IV and CAG. Telomerase activity in human embryonic kidney HEK293 fibroblasts was increased upon treatment with increasing concentrations of AG-IV or CAG. Both compounds induced the phosphorylation of extracellular signal-regulated protein kinase (ERK) in a time- and dose-dependent manner in HEK293 cells and HEK-neo keratinocytes. AG-IV and CAG also stimulated ERK phosphorylation in other cell lines of lung, brain, mammary, endothelial, and hematopoietic origins. Use of selective inhibitors and dominant negative mutants revealed the involvement of c-Src, MEK (ERK kinase), and epidermal growth factor receptor in CAG-induced ERK phosphorylation. Our data indicate that AG-IV and CAG may exert their cellular effects through the activation of the Src/MEK/ERK pathway.© Georg Thieme Verlag KG Stuttgart New York. 22083896

Anti-aging effect of astragalosides and its mechanism of action.

Lei H, Wang B, Li WP, Yang Y, Zhou AW, Chen MZ.
Institute of Clinical Pharmacology, Anhui Medical University, Hefei 230032, China. keerfood@mail.hf.ah.cn
Rotating rod test and step-down type passive avoidance test were performed to determine the effects of AST on motor and memory of D-galactose (D-gal)-induced senescent mice and the middle-aged mice. The proliferative response of splenocytes induced by Con A or LPS, IL-2 production of splenocytes induced by ConA of D-gal-treated mice and the middle-aged mice were also measured.
AST (40 mg.kg(-1).d(-1), ig, for 10 weeks) was found to ameliorate age-related alternations in both motor response and memory, enhance the deteriorated cellular immunity in D-gal-treated mice and the pre-aged (17-month-old) mice.
CONCLUSION:
AST has an anti-aging effect on D-gal-induced senescent mice and has the effect of delaying senility of the middle-aged mice, which was related to its improvement of brain function and immunomodulatory effects.
PMID: 12617771 Zhongguo Zhong Yao Za Zhi. 2007 Dec;32(23):2539-42.

Enhanced oral bioavailability of Astragaloside IV in rats through complexation with 2-hydroxypropyl-beta-cyclodextrin

Zhenhua Chen, Bing Gu*
School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China
Received 12 May 2008.
Purpose: Astragaloside IV (AGS-IV), the main active constituent of the Chinese medical herb, Astragalus membranaceus, is reported to exhibit a variety of cardiovascular pharmacological actions. However its poor aqueous solubility affects its oral absorption which limits its development as a treatment and its preclinical investigation. The effect of 2-hydroxypropyl-beta-cyclodextrin (HPCD), a novel solubility enhancer, on the oral bioavailability of AGS-IV in Sprague Dawley rats was evaluated with the aim of preparing a stable and effective oral formulation suitable for clinical application. Methods: Inclusion compounds in aqueous solution were prepared by solution-agitating technique, and identified by observation under a microscope, differential scanning calorimetry, solubility and phase solubility diagrams. The concentrations of AGS-IV in rat plasma were determined by liquid chromatograph-mass spectrometry/mass spectrometry. Results: Both methods involving novel optical rotation continuous variation plotting and the analysis of phase solubility diagrams consistently proved that AGS-IV and HPCD can form an inclusion compound with a molar ratio of 1: 1. The solubility of
AGS-IV in neutral aqueous solution at 25˚C was increased from 22.2 µg/ml to 286.8 µg/ml. The concentration-time profiles in plasma samples after oral administration of AGS-IV and the inclusion compound both fitted a two-compartment model. The t1/2 of the inclusion compound was 12.88 h, and the AUC was 5275.49 ng·h/ml, whereas the t1/2 of AGS-IV was 4.54 h, and the AUC was 1184.32 ng·h/ml.  (4.55 times greater bioavailability)
Conclusion: Complexation with HPCD can significantly increase AGS-IV oral bioavailability in rats, reducing the variability in its systemic concentration and pharmacological effects. The continuous variation plot based on the optical rotation increment is a reliable addition to the classical continuous variation method used widely in the pharmaceutical sciences.

Effects of AST and ASI on metabolism of free radical insenescent rats treated by Hydrocortisone.

Li WZ1, Li WP, Yin YY.
To study the effects of Astragaloside (AST) and Astragalus Saponin I (ASI) on metabolism of free radical and immune function in senescent rats treated by HC.
METHOD:
Hydrocorisone (HC) was used to estabilsh the aging model in rats. The content of molondialdehyde (MDA), glutathoine (GSH) and oxidized glutathoine (GSSG) in liver and brain was detected according to kit. The activity of Mn superoride dismulase (Mn-SOD) and catalase (CAT) was also surveyed by kit. Concanavalin (ConA) was used to detect the proliferation and interleukin-2 (IL-2) production of splenocytes.
Compared with HC control, AST and ASI could decrease the content of MDA, GSH and GSSG in liver and brain, increase the activity of Mn-SOD and CAT, and promote the proliferation and interleukin-2 (IL-2) activity of splenocytes.
AST and ASI could delay the aging effect in rats treated by HC, and its mechanism maybe the antioxidant and regulating immunity.
PMID:18330253

Protective effects of AST and ASI on memory impairment and its mechanism in senescent rats treated by GC

Li W1, Li W, Yin Y, Gong H, Wu G, Zhu F.
To study the protective effects and mechanisms of astragaloside (AST) and astragalus saponin I (ASI) on the memory impairment in senescent rats treated by glucocorticoid (GC).
METHOD:
Y maze test was performed to determine the effects of AST and ASI on memory impairment of hydrocortisone(HC)-induced senescent rats. Using Ca2+ sensitive fluorescent indicator (Furo-2), free intracellular calcium concentration ([Ca2+]i) was measured by double wavelength fluorescence sepectrophotometer in thymocytes and hippocampal neurons induced dexamethasone (DEX). And apoptosis was detected by DNA gel electrophoresis and flow cytometry.
RESULT:
Compared with HC control, AST and ASI can improve the memory of the senescent rats treated by HC, lower [Ca2+]i and suppress apoptosis of thymocytes and hippocampal neurons induced by DEX.
CONCLUSION:
AST and ASI can delay the aging in rats treated by HC, and its mechanism may include lowering[Ca2+]i and suppressing the apoptosis of thymocytes and hippocampal neurons.
PMID:19385186

Pterocarpus marsupium extract reveals strong in vitro antioxidant activity.

Mohammadi M1, Khole S, Devasagayam TP, Ghaskadbi SS.

Diabetes mellitus is a complex chronic disease characterized by hyperglycemia, which via several mechanism leads to an increase in production of reactive oxygen species (ROS) leading to various secondary complications. Thus, a drug having both antidiabetic and antioxidant properties would have great therapeutic value for overcoming the oxidative load in diabetes. The present study was aimed at extensively evaluating the antioxidant properties of an anti-diabetic plant extract of stem bark ofPterocarpus marsupium using various in vitro radical scavenging assays as well as by using liver slice cultures as a model system. Our results demonstrate that the whole aqueous extract showed high antioxidant activity in all different assays used and also protected mitochondria against oxidative damage. Ethanol was used as an inducer of oxidative stress in liver slice culture and cytotoxicity was estimated by quantitating release of cytotoxicity marker enzymes such as lactate dehydrogenase (LDH). Additionally, levels of antioxidant enzymes (AOEs) namely superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were also estimated. The whole aqueous extract significantly reduced LDH release along with reduction of lipid peroxidation compared to ethanol treated slices. These results indicate that the P. marsupium extract may serve as a potential source of natural antioxidant for treatment of diabetes.
PMID: 22495601
Pterocarpus marsupium (Pterostilbene)
Diabetes Obes Metab. 2005 Jul;7(4):414-20.

Pterocarpus marsupium extract (Vijayasar) prevented the alteration in metabolic patterns induced in the normal rat by feeding an adequate diet containing fructose as sole carbohydrate.

Grover JK1, Vats V, Yadav SS.
Insulin resistance (hyperinsulinaemia) is now recognized as a major contributor to the development of glucose intolerance, dyslipidaemia and hypertension in non-insulin-dependent diabetes mellitus (NIDDM) patients. Sedentary lifestyle, consumption of energy-rich diet, obesity, longer lifespan, etc., are important reasons for this rise (J. R. Turtle, Int J Clin Prac 2000; 113: 23). Aqueous extracts of Pterocarpus marsupium Linn bark (PM), Ocimum sanctum Linn leaves (OS) and Trigonella foenumgraecum Linn seeds (FG) have been shown to exert hypoglycaemic/antihyperglycaemic effect in experimental as well as clinical setting. As no work has been carried out so far to assess the effect of PM, OS and FG on fructose-induced hyperglycaemia, hyperinsulinaemia and hypertriglyceridaemia, we undertook this study to assess whether these extracts attenuate the metabolic alteration induced by fructose-rich diet in rats. Five groups of rats (eight each) were fed chow diet, 66% fructose diet, 66% fructose diet + PM leaves extract (1 g/kg/day), 66% fructose diet + OS leaves extract (200 mg/kg/day) and 66% fructose diet + FG seeds extract (2 g/kg/day) for 30 days. Fructose feeding to normal rats for 30 days significantly increased serum glucose, insulin and triglyceride levels in comparison with control. Treatment with all the three plants extract for 30 days significantly lowered the serum glucose levels in comparison with control group. However, only PM extract substantially prevented hypertriglyceridaemia and hyperinsulinaemia, while OS and FG had no significant effect on these parameters. Results of this study, in addition to previous clinical benefits of PM seen in NIDDM subjects, are suggestive of usefulness of PM bark (Vijayasar) in insulin resistance, the associated disorder of type 2 diabetes; however, OS and FG may not be useful. Though several antidiabetic principles (-epicatechin, pterosupin, marsupin and pterostilbene) have been identified in the PM, yet future studies are required to certify their efficacy and safety before clinical scenario.

Anti-cataract activity of Pterocarpus marsupium bark and Trigonella foenum-graecum seeds extract in alloxan diabetic rats.

Vats V1, Yadav SP, Biswas NR, Grover JK.
Long-term complications are frequently encountered in diabetes mellitus and are difficult to treat. This study was undertaken to assess the effect of three antidiabetic plants on the development of cataract in rats. An aqueous extract of Pterocarpusmarsupium Linn bark (PM, Hindi name: Vijaysar) (1 g kg(-1) day(-1)), Ocimum sanctum Linn leaves (OS, Hindi name, Tulsi) (200 mg kg(-1) day(-1)) and alcoholic extract of Trigonella foenum-graecum Linn seeds (FG, Hindi name, Methi) (2 g kg(-1) day(-1)) were given to alloxan (120 mg kg(-1)) diabetic rats until the development of cataract. Serum glucose and body weight were monitored at regular intervals while cataract was examined through naked eye as well as slit lamp at 75, 100 and 115 days after alloxan administration. Administration of all the three plant extracts exerted a favorable effect on body weight and blood glucose, the effects were best with PM followed by FG and OS. On the course of cataract development, PM followed by FG exerted anti-cataract effect evident from decreased opacity index while OS failed to produce any anti-cataract effect in spite of significant antihyperglycemic activity.
PMID: 15234767

L-Theanine extends lifespan of adult Caenorhabditis elegans.

Zarse K1, Jabin S, Ristow M.
Compounds that delay aging in model organisms may be of significant interest to anti-aging medicine, since these substances potentially provide pharmaceutical approaches to promote healthy lifespan in humans. We here aimed to test whether pharmaceutical concentrations of L-theanine, a putative anti-cancer, anti-obesity, blood pressure-lowering, and neuroprotective compound contained in green tea (Camellia sinensis), are capable of extending lifespan in a nematodal model organism for aging processes, the roundworm Caenorhabditis elegans.
Adult C. elegans roundworms were maintained on agar plates, were fed E. coli strain OP50 bacteria, and L-theanine was applied to agar to test (1) whether it may increase survival upon paraquat exposure and (2) whether it may promote longevity by quantifying survival in the presence and absence of the compound.
RESULTS:
L-Theanine increases survival of C. elegans in the presence of paraquat at a concentration of 1 micromolar. L-theanine extends C. elegans lifespan when applied at concentrations of 100 nM, as well as 1 and 10 micromolar.
CONCLUSIONS:
In the model organism C. elegans, L-theanine is capable of promoting paraquat resistance and longevity suggesting that this compound may as well promote healthy lifespan in mammals and possibly humans.
PMID: 22422488

Silymarin from Milk Thistle (Siliphos)

Altern Med Rev. 2005 Sep;10(3):193-203.
A review of the bioavailability and clinical efficacy of milk thistle phytosome: a silybin-phosphatidylcholine complex (Siliphos).
Kidd P1, Head K.
Certain of the water-soluble flavonoid molecules can be converted into lipid-compatible molecular complexes, aptly called phytosomes. Phytosomes are better able to transition from a hydrophilic environment into the lipid-friendly environment of the outer cell membrane, and from there into the cell, finally reaching the blood. The fruit of the milk thistle plant (Silybum marianum, Family Asteraceae) contains flavonoids that are proven liver protectants. The standardized extract known as silymarin contains three flavonoids of the flavonol subclass. Silybin predominates, followed by silydianin and silychristin. Although silybin is the most potent of the flavonoids in milk thistle, similar to other flavonoids it is not well-absorbed. Silybin-phosphatidylcholine complexed as a phytosome provides significant liver protection and enhanced bioavailability over conventional silymarin.
PMID:16164374

Silymarin inhibits endothelial progenitor cells' senescence and protects against the antiproliferative activity of rapamycin: preliminary study.

Parzonko A1, Naruszewicz M
Rapamycin, an antiproliferative agent used on drug-eluting stents, induces endothelial progenitor cells (EPCs) senescence through telomerase inactivation and may impair the reendothelization of an injured arterial wall, leading to thrombosis. We examined whether silymarin, a complex of flavonolignans with hepatoprotective and antioxidative properties, can protect EPCs against rapamycin-induced senescence. Mononuclear cells were isolated from peripheral blood of healthy volunteers. EPCs were cultured in endothelial cell growth medium-2 in the presence or absence of rapamycin (0.1 ng/mL) and/or silymarin (12.5–50 μg/mL). EPCs senescence–associated b-galactosidase activity, telomerase activity, and prolifertive activity were measured. The influence on tubular-like structure formation in vitro was investigated, and colony-forming assay on methylcellulose plates was performed. Silymarin increased telomerase activity 3-fold, reduced the number of senescent cells, and increased EPC proliferative activity (up to 64%) in comparison with cells cultured with rapamycin alone. Moreover, silymarin partially prevented impairment of tubular-like structure formation in Matrigel by rapamycin. These findings suggest that silymarin counteracts the inhibitory effects of rapamycin in EPCs. Silymarin may protect EPCs against the antiproliferative effects of rapamycin and restore their reconstructive ability.
PMID:20838231

Low-dose pterostilbene, but not resveratrol, is a potent neuromodulator in aging and Alzheimer's disease.

Chang J1, Rimando A, Pallas M, Camins A, Porquet D, Reeves J, Shukitt-Hale B, Smith MA, Joseph JA, Casadesus G.
Recent studies have implicated resveratrol and pterostilbene, a resveratrol derivative, in the protection against age-related diseases including Alzheimer's disease (AD). However, the mechanism for the favorable effects of resveratrol in the brain remains unclear and information about direct cross-comparisons between these analogs is rare. As such, the purpose of this study was to compare the effectiveness of diet-achievable supplementation of resveratrol to that of pterostilbene at improving functional deficits and AD pathology in the SAMP8 mouse, a model of accelerated aging that is increasingly being validated as a model of sporadic and age-related AD. Furthermore we sought to determine the mechanism of action responsible for functional improvements observed by studying cellular stress, inflammation, and pathology markers known to be altered in AD. Two months of pterostilbene diet but not resveratrol significantly improved radial arm water maze function in SAMP8 compared with control-fed animals. Neither resveratrol nor pterostilbene increased sirtuin 1 (SIRT1) expression or downstream markers of sirtuin 1 activation. Importantly, markers of cellular stress, inflammation, and AD pathology were positively modulated bypterostilbene but not resveratrol and were associated with upregulation of peroxisome proliferator-activated receptor (PPAR) alpha expression. Taken together our findings indicate that at equivalent and diet-achievable doses pterostilbene is a more potent modulator of cognition and cellular stress than resveratrol, likely driven by increased peroxisome proliferator-activated receptor alpha expression and increased lipophilicity due to substitution of hydroxy with methoxy group in pterostilbene.
PMID: 21982274

A Review of Pterostilbene Antioxidant Activity and Disease Modification

Denise McCormack 1 ,* and David McFadden 2
Abstract:
Pterostilbene (trans-3,5-dimethoxy-4-hydroxystilbene) is a natural dietary compound and the primary antioxidant component of blueberries. It has increased bioavailability in comparison to other stilbene compounds, which may enhance its dietary benefit and possibly contribute to a valuable clinical effect. Multiple studies have demonstrated the antioxidant activity of pterostilbene in both in vitro and in vivo models illustrating both preventative and therapeutic benefits. The antioxidant activity of pterostilbene has been implicated in anticarcinogenesis, modulation of neurological disease, anti-inflammation, attenuation of vascular disease, and amelioration of diabetes. In this review, we explore the antioxidant properties of pterostilbene and its relationship to common disease pathways and give a summary of the clinical potential of pterostilbene in the prevention and treatment of various medical conditions.
Dehydrosilybin attenuates the production of ROS in rat cardiomyocyte mitochondria with an uncoupler-like mechanism.Gabrielová E1
Jabůrek M, Gažák R, Vostálová J, Ježek J, Křen V, Modrianský M.
Reactive oxygen species (ROS) originating from mitochondria are perceived as a factor contributing to cell aging and means have been sought to attenuate ROS formation with the aim of extending the cell lifespan. Silybin and dehydrosilybin, two polyphenolic compounds, display a plethora of biological effects generally ascribed to their known antioxidant capacity. When investigating the cytoprotective effects of these two compounds in the primary cell cultures of neonatal rat cardiomyocytes, we noted the ability of dehydrosilybin to de-energize the cells by monitoring JC-1 fluorescence. Experiments evaluating oxygen consumption and membrane potential revealed that dehydrosilybin uncouples the respiration of isolated rat heart mitochondria albeit with a much lower potency than synthetic uncouplers. Furthermore, dehydrosilybin revealed a very high potency in suppressing ROS formation in isolated rat heart mitochondria with IC(50) = 0.15 μM. It is far more effective than its effect in a purely chemical system generating superoxide or in cells capable of oxidative burst, where the IC(50) for dehydrosilybin exceeds 50 μM. Dehydrosilybin also attenuated ROS formation caused by rotenone in the primary cultures of neonatal rat cardiomyocytes. We infer that the apparent uncoupler-like activity of dehydrosilybin is the basis of its ROS modulation effect in neonatal rat cardiomyocytes and leads us to propose a hypothesis on natural ischemia preconditioning by dietary polyphenols.
PMID:21153691

Determination of pterostilbene in rat plasma by a simple HPLC-UV method and its application in pre-clinical pharmacokinetic study.

Lin HS1, Yue BD, Ho
A simple HPLC-UV method was developed and validated for the quantification of pterostilbene (3,5-dimethoxy-4'-hydroxy-trans-stilbene), a pharmacologically active phytoalexin in rat plasma. The assay was carried out by measuring the UV absorbance at 320 nm. Pterostilbene and the internal standard, 3,5,4'-trimethoxy-trans-stilbene eluted at 5.7 and 9.2 min, respectively. The calibration curve (20-2000 ng/mL) was linear (R(2)> 0.997). The lower limits of detection and of quantification were 6.7 and 20 ng/mL, respectively. The intra- and inter-day precisions in terms of RSD were all lower than 6%. The analytical recovery ranged from 95.5 +/- 3.7 to 103.2 +/- 0.7% while the absolute recovery ranged from 101.9 +/- 1.1 to 104.9 +/- 4.4%. This simple HPLC method was subsequently applied in a pharmacokinetic study carried out in Sprague-Dawley rats. The terminal elimination half-life and clearance of pterostilbene were 96.6 +/- 23.7 min and 37.0 +/- 2.5 mL/min/kg, respectively, while its absolute oral bioavailability was 12.5 +/- 4.7%. Pterostilbene appeared to have better pharmacokinetic characteristics than its natural occurring analog, resveratrol.

References
1. Yu, Q., Y.S. Bai, and J. Lin, [Effect of astragalus injection combined with mesenchymal stem cells transplantation for repairing the Spinal cord injury in rats]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 2010. 30(4): p. 393-7.
2. Xu, C.J., et al., [Effect of astragalus polysaccharides on the proliferation and ultrastructure of dog bone marrow stem cells induced into osteoblasts in vitro]. Hua Xi Kou Qiang Yi Xue Za Zhi, 2007. 25(5): p. 432-6.
3. Xu, C.J., et al., [Effects of astragalus polysaccharides-chitosan/polylactic acid scaffolds and bone marrow stem cells on repairing supra-alveolar periodontal defects in dogs]. Zhong Nan Da Xue Xue Bao Yi Xue Ban, 2006. 31(4): p. 512-7.
4. Zhu, X. and B. Zhu, [Effect of Astragalus membranaceus injection on megakaryocyte hematopoiesis in anemic mice]. Hua Xi Yi Ke Da Xue Xue Bao, 2001. 32(4): p. 590-2.
5. Qiu, L.H., X.J. Xie, and B.Q. Zhang, Astragaloside IV improves homocysteine-induced acute phase endothelial dysfunction via antioxidation. Biol Pharm Bull, 2010. 33(4): p. 641-6.
6. Araghi-Niknam, M., et al., Pine bark extract reduces platelet aggregation. Integr Med, 2000. 2(2): p. 73-77.
7. Rohdewald, P., A review of the French maritime pine bark extract (Pycnogenol), a herbal medication with a diverse clinical pharmacology. Int J Clin Pharmacol Ther, 2002. 40(4): p. 158-68.
8. Koch, R., Comparative study of Venostasin and Pycnogenol in chronic venous insufficiency. Phytother Res, 2002. 16 Suppl 1: p. S1-5.
9. Rimando, A.M., et al., Pterostilbene, a new agonist for the peroxisome proliferator-activated receptor alpha-isoform, lowers plasma lipoproteins and cholesterol in hypercholesterolemic hamsters. J Agric Food Chem, 2005. 53(9): p. 3403-7.
10. Manickam, M., et al., Antihyperglycemic activity of phenolics from Pterocarpus marsupium. J Nat Prod, 1997. 60(6): p. 609-10.
11. Grover, J.K., V. Vats, and S.S. Yadav, Pterocarpus marsupium extract (Vijayasar) prevented the alteration in metabolic patterns induced in the normal rat by feeding an adequate diet containing fructose as sole carbohydrate. Diabetes Obes Metab, 2005. 7(4): p. 414-20.
12. Mao, X.Q., et al., Astragalus polysaccharide reduces hepatic endoplasmic reticulum stress and restores glucose homeostasis in a diabetic KKAy mouse model. Acta Pharmacol Sin, 2007. 28(12): p. 1947-56.
13. Schafer, A. and P. Hogger, Oligomeric procyanidins of French maritime pine bark extract (Pycnogenol) effectively inhibit alpha-glucosidase. Diabetes Res Clin Pract, 2007. 77(1): p. 41-6.
14. Kwak, C.J., et al., Antihypertensive effect of French maritime pine bark extract (Flavangenol): possible involvement of endothelial nitric oxide-dependent vasorelaxation. J Hypertens, 2009. 27(1): p. 92-101.
15. Xue, B., et al., Effect of total flavonoid fraction of Astragalus complanatus R.Brown on angiotensin II-induced portal-vein contraction in hypertensive rats. Phytomedicine, 2008.
16. Mizuno, C.S., et al., Design, synthesis, biological evaluation and docking studies of pterostilbene analogs inside PPARalpha. Bioorg Med Chem, 2008. 16(7): p. 3800-8.
17. Sato, M., et al., Dietary pine bark extract reduces atherosclerotic lesion development in male ApoE-deficient mice by lowering the serum cholesterol level. Biosci Biotechnol Biochem, 2009. 73(6): p. 1314-7.
18. Kimura, Y. and M. Sumiyoshi, French Maritime Pine Bark (Pinus maritima Lam.) Extract (Flavangenol) Prevents Chronic UVB Radiation-induced Skin Damage and Carcinogenesis in Melanin-possessing Hairless Mice. Photochem Photobiol, 2010.
19. Pavlou, P., et al., In-vivo data on the influence of tobacco smoke and UV light on murine skin. Toxicol Ind Health, 2009. 25(4-5): p. 231-9.
20. Ni, Z., Y. Mu, and O. Gulati, Treatment of melasma with Pycnogenol. Phytother Res, 2002. 16(6): p. 567-71.
21. Bito, T., et al., Pine bark extract pycnogenol downregulates IFN-gamma-induced adhesion of T cells to human keratinocytes by inhibiting inducible ICAM-1 expression. Free Radic Biol Med, 2000. 28(2): p. 219-27.
22. Rihn, B., et al., From ancient remedies to modern therapeutics: pine bark uses in skin disorders revisited. Phytother Res, 2001. 15(1): p. 76-8.
23. Saliou, C., et al., Solar ultraviolet-induced erythema in human skin and nuclear factor-kappa-B-dependent gene expression in keratinocytes are modulated by a French maritime pine bark extract. Free Radic Biol Med, 2001. 30(2): p. 154-60.
24. Van Wijk, E.P., R. Van Wijk, and S. Bosman, Using ultra-weak photon emission to determine the effect of oligomeric proanthocyanidins on oxidative stress of human skin. J Photochem Photobiol B, 2010. 98(3): p. 199-206.
25. Haskell, C.F., et al., The effects of L-theanine, caffeine and their combination on cognition and mood. Biol Psychol, 2008. 77(2): p. 113-22.
26. Owen, G.N., et al., The combined effects of L-theanine and caffeine on cognitive performance and mood. Nutr Neurosci, 2008. 11(4): p. 193-8.
27. Yamada, T., et al., Effects of theanine, a unique amino acid in tea leaves, on memory in a rat behavioral test. Biosci Biotechnol Biochem, 2008. 72(5): p. 1356-9.
28. Jia, R.Z., et al., [Neuroprotective effects of Astragulus membranaceus on hypoxia-ischemia brain damage in neonatal rat hippocampus]. Zhongguo Zhong Yao Za Zhi, 2003. 28(12): p. 1174-7.
29. Nathan, P.J., et al., The neuropharmacology of L-theanine(N-ethyl-L-glutamine): a possible neuroprotective and cognitive enhancing agent. J Herb Pharmacother, 2006. 6(2): p. 21-30.
30. Nobre, A.C., A. Rao, and G.N. Owen, L-theanine, a natural constituent in tea, and its effect on mental state. Asia Pac J Clin Nutr, 2008. 17 Suppl 1: p. 167-8.
31. Murakami, S., et al., Effects of oral supplementation with cystine and theanine on the immune function of athletes in endurance exercise: randomized, double-blind, placebo-controlled trial. Biosci Biotechnol Biochem, 2009. 73(4): p. 817-21.
32. Kawada, S., et al., Cystine and theanine supplementation restores high-intensity resistance exercise-induced attenuation of natural killer cell activity in well-trained men. J Strength Cond Res, 2010. 24(3): p. 846-51.
33. Hu, Y.C. and J.Y. Hou, [Effect of zhimu and huangqi on cardiac hypertrophy and response to stimulation in mice]. Zhongguo Zhong Yao Za Zhi, 2003. 28(4): p. 369-74.
34. Chen, K.T., et al., Reducing fatigue of athletes following oral administration of huangqi jianzhong tang. Acta Pharmacol Sin, 2002. 23(8): p. 757-61.
35. Luo, H.M., R.H. Dai, and Y. Li, [Nuclear cardiology study on effective ingredients of Astragalus membranaceus in treating heart failure]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 1995. 15(12): p. 707-9.
36. Sugiura, H., et al., [Effects of exercise in the growing stage in mice and of Astragalus membranaceus on immune functions]. Nippon Eiseigaku Zasshi, 1993. 47(6): p. 1021-31.
37. Cho, W.C. and K.N. Leung, In vitro and in vivo anti-tumor effects of Astragalus membranaceus. Cancer Lett, 2007. 252(1): p. 43-54.
38. Kong, X., et al., Effects of Chinese herbal medicinal ingredients on peripheral lymphocyte proliferation and serum antibody titer after vaccination in chicken. Int Immunopharmacol, 2004. 4(7): p. 975-82.
39. Takagi, Y., et al., Combined administration of (L)-cystine and (L)-theanine enhances immune functions and protects against influenza virus infection in aged mice. J Vet Med Sci, 2010. 72(2): p. 157-65.
40. Tin, M.M., et al., Astragalus saponins induce growth inhibition and apoptosis in human colon cancer cells and tumor xenograft. Carcinogenesis, 2007. 28(6): p. 1347-55.
41. Mannal, P.W., et al., Pterostilbene inhibits pancreatic cancer in vitro. J Gastrointest Surg, 2010. 14(5): p. 873-9.
42. Paul, S., et al., Dietary intake of pterostilbene, a constituent of blueberries, inhibits the {beta}-catenin/p65 downstream signaling pathway and colon carcinogenesis in rats. Carcinogenesis, 2010.
43. Paul, S., et al., Anti-inflammatory action of pterostilbene is mediated through the p38 mitogen-activated protein kinase pathway in colon cancer cells. Cancer Prev Res (Phila Pa), 2009. 2(7): p. 650-7.
44. Suh, N., et al., Pterostilbene, an active constituent of blueberries, suppresses aberrant crypt foci formation in the azoxymethane-induced colon carcinogenesis model in rats. Clin Cancer Res, 2007. 13(1): p. 350-5.
45. Chakraborty, A., et al., In vitro evaluation of the cytotoxic, anti-proliferative and anti-oxidant properties of pterostilbene isolated from Pterocarpus marsupium. Toxicol In Vitro, 2010. 24(4): p. 1215-28.
46. Alosi, J.A., et al., Pterostilbene inhibits breast cancer in vitro through mitochondrial depolarization and induction of caspase-dependent apoptosis. J Surg Res, 2010. 161(2): p. 195-201.
47. Ly, Y., et al., Study on effect of Astragalus membranaceus injection on hematopoiesis in anemic mice with myelosuppression. Zhong Yao Cai, 2005. 28(9): p791-3. http://www.ncbi.nlm.nih.gov/pubmed/16447871
48. Shen, B. et al., Effects of astragalus and angelica on bone marrow stem cells proliferation and VEGF protein expression in vitro. 2011. 24(8): p 652-5. http://www.ncbi.nlm.nih.gov/pubmed/21928670
49. Zhang WJ, Wojta J, Binder BR. Regulation of the fibrinolytic potential of cultured human umbilical vein endothelial cells: astragaloside IV downregulates plasminogen activator inhibitor-1 and upregulates tissue-type plasminogen activator expression. J Vasc Res. 1997. 34(4):p. 273-80.
50. Shi R, He L, Hu Y, et al. The regulatory action of radix astragali on M-cholinergic receptor of the brain of senile rats. J Tradit Chin Med 2001;21:p. 232-5.
51. Wang, Y., et al. Pterostilbene simultaneously induces apoptosis, cell cycle arrest and cyto-protective autophagy in breast cancer cells. Am J Transl Res. 2012; 4(1): p. 44–51. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3276376/
52. Kakuda T. Neuroprotective effects of the green tea components L-theanine and catechins. Biol Pharm Bull. 2002; 25(12): p. 1513-8.
53. Egashira et al. Theanine prevents memory impairment induced by repeated cerebral ischemia in rats. Phytother.Res. 2008; 22: p. 65-8. http://www.ncbi.nlm.nih.gov/pubmed/17705146
54. Kakuda T., Neuroprotective effects of theanine and its preventive effects on cognitive dysfunction.
Pharmacol Res. 201; 64(2): p162-8. http://www.ncbi.nlm.nih.gov/pubmed/21477654
55. Desbordes, S.C., High-Throughput Screening Assay For The Identification Of Compounds Regulating Self-Renewal And Differentiation In Human Embryonic Stem Cells. Cell Stem Cell. 2008; 2(6): p. 602–12. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756729/

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Frequently Asked Questions (FAQ’s)

1. What is the preferred dose of CELLMetrix™ and when should it be taken?

If you are 125 pounds or less or in your 20s, then it may be best to only take one capsule of CELLMetrix per day preferably with a meal. For those over 125 pounds and over 30 years of age, we recommend two capsules per day preferably taken one at breakfast and one at dinner. Note that the recommendation to take CELLMetrix at meals is not due to any problems with taking the supplement on an empty stomach. Rather, the pterostilbene in CELLMetrix acts as an insulin sensitizer to help glucose cross into your cells and thus reduces the spike in glucose and insulin that routinely occurs after a meal. It is also best to take the two capsules at different meals, as the 105 minute half-life of pterostilbene in the blood stream means that less of the insulin sensitizer is around after 4 hours and even less after 8 hours. That said, if you are one of the many people who can only remember to take your pills once per day, then it is best to take two capsules at the same time, preferably at one of your meals.

2. What improvements might I experience taking CELLMetrix™?

Some of the benefits of CELLMetrix such as a slowing of the aging process may not be immediately apparent, natural supplementation may take 3 to 6 months. There have been many quicker beneficial effects from our beta formulation version including:

• Younger looking, smoother and more elastic skin.
• General mood elevation.
• Sinus clearing and better breathing.
• Improvement in gum health.
• Improvement in eyesight.
• More endurance during vigorous workouts.
• Loss of belly fat that was resistant to other efforts.

We do not make any medical claims for CELLMetrix, however, you might find it interesting to do before and after blood tests with your doctor and monitor LDL and HDL cholesterol, fasting glucose, fasting insulin and C-Reactive Protein (CRP) which is an indicator of chronic inflammation. Another test you may want to periodically check yourself is blood pressure.

Note that CELLMetrix is not meant as a treatment or preventive for hypertension, cholesterol problems, diabetes, or inflammation. However, CELLMetrix can help with keeping these blood parameters at more healthful levels for those already in the normal range.

If you experience one or more of these benefits and/or some other benefit that is not listed, please let us know by using the Contact Us page.

3. I read that many herbs are not well absorbed, and therefore do little good. Is that true for the ingredients in CELLMetrix?

What you are referring to is “bioavailability,” or how well compounds are taken up into and absorbed by your cells. Standard versions of three of our key ingredients; milk thistle, astragalus root extract and Pterocarpus marsupium which contains pterostilbene among other important compounds are not very bioavailable.

Recognizing how critical bioavailability is to your optimal health (and to your pocketbook), those key ingredients were made 3-10 times more effective through the use of two patent-pending processes.

4. How does CELLMetrix™ compare to the more popular telomere products?

We believe CELLMetrix is one of the, if not the most effective telomere health products on the market. To the best of our knowledge, there have been no clinical studies comparing any of the products to one another.

We do know that even though our manufacturing costs compare with the higher priced products, we have kept our prices much lower in order to make CELLMetrix affordable to nearly everyone interested in optimal health and longevity.

5. How does CELLMetrix™ compare to the widely available anti-aging supplement resveratrol?

Much research has been done on Resveratrol and it has been in the news during the past few years. While the original experiment treating mice with resveratrol did generate somewhat longer-lived mice, later experiments have given mixed results in extending mouse lifespan, as is also the case with longevity experiments in worms and fruit flies.

One likely reason for these variable results is that resveratrol is a very unstable compound with only a 14-minute half-life in the blood stream. In contrast, pterostilbene, a close resveratrol analog, has a half-life of 105 minutes (7.5 fold higher) and is one of the principle components found in CELLMetrix. This means that by the time you have lost 50% of pterostilbene, you have lost more than 99% of resveratrol. Moreover, neither resveratrol nor pterostilbene are very bioavailable without the proprietary technology used in CELLMetrix. While the pterostilbene is the most prevalent resveratrol analog in CELLMetrix, there is another potent resveratrol analog in CELLMetrix called marsupsin, which acts synergistically with pterostilbene.

6. In picking the herbal extracts for CELLMetrix™, were ingredients chosen that affect the same genes that differed in the Methuselah flies?

The Methuselah flies are fruit fly colonies that were selectively bred for over 20 years for healthy longevity. They live 4X longer than normal flies due to selectively bred changes in gene expression. The reason this is important is that fruit flies are a surprisingly good model for human longevity genes. The genes attributed to longevity are approximately 90% similar between humans and fruit flies. The method used to pick the ingredients chosen for CELLMetrix is described in Fine-Tuning Your Longevity Genes. The gene expression changes in Methuselah flies did give many targets for intervention into the aging process. The surprise was that there were so many genes that changed in Methuselah flies. This naturally led to the idea that many targets would have to be hit simultaneously if one were to succeed in inducing a major change in the rate of aging. That was the genesis of the wide spectrum CELLMetrix, which may finally have the potential to target a critical threshold of the genes involved in aging. While the selection of ingredients for CELLMetrix had many constraints beyond targeting Methuselah genes, the final product was found to alter many of the highest scoring Methuselah genes using our licensed proprietary AI software. This fact plus the fly longevity data gives us high confidence that we are on the right track. A third party’s subsequent human Field Trial showed many positive results, which are all independent, measures of long health span and lifespan.

7. What are the potential interactions between CELLMetrix™ and medications?

Remember; always consult your physician before starting any supplement regiment.

 If you are taking any of the following drugs, then you should consult your physician before taking herbal, vitamin or other nutritional supplements. It may be necessary to monitor and adjust some of the medications as needed.

•Cholesterol lowering drugs

•Blood thinners (Plavix, Coumadin, etc.)

•Blood pressure lowering drugs (Beta Blockers, ACE inhibitors, ARB drugs, and/or diuretics)

•Anti-depressants

8. How safe is CELLMetrix™ and what are the side effects?

All of the individual herbal extracts in CELLMetrix have 40 years or longer history of human use without significant reported side effects. Moreover, both animal and human trials have been published on the safety and effectiveness of the individual herbal extracts. If you believe you have experienced any side effects while using CELLMetrix please report them to us using our Contact page.

9. Why is Astragalus and Pterocarpus listed twice on your label?

The concentrated Astragalus and Pterocarpus ingredients were complexed with cyclodextrins to increase bioavailability but the concentrated ones leave behind many other beneficial compounds. The un-concentrated plant extracts of Astragalus and Pterocarpus marsupium were added to include the other >1000 compounds other than Astragaloside IV and Pterostilbene. Both plants in their complete form bring properties that have been used for over 1000 years for healing.  

 10. Pterostilbene is is a main component of Pterocarpus marsupium extract. Why is it listed separately?

 Same idea as above. Plus you should know that we use a 99% standardization (for maximum purity) of that single compound. It is differentiated from the whole pterocarpus marsupium root extract.

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LABEL FACTS

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