Monthly Archives: June 2016

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Polygala teniufolia and its neuroprotective benefits

Polygala tenuifolia (Yuan Zhi) is an herb in the family Polygalaceae.

Polygala tenuifolia has demonstrated potent and extensive neuroprotection benefits. Studies have concluded that Polygala teniufolia tested in healthy adults produced:

  • Memory-enhancing effects [1]
  • Cognitive improvement [2]
  • Increases NGF secretion in astrocytes [3]
  • Potent antidepressant-like effects [4]
  • Inhibited MAO-A and MAO-B activity,
  • Blocked stress-induced elevations of plasma cortisol [5]
  • Improved hippocampal-dependent learning and memory [6]
  • Rescued stress-induced deficits in hippocampal neuronal plasticity and neurogenesis [[7]
  • Displays anti-inflammatory activity towards microglia [8]

References:

[1] Lee J.-Y., Kim K.Y., Shin K.Y., Won B.Y., Jung H.Y., Suh Y.H. (2009). “Effects of BT-11 on memory in healthy humans”. Neuroscience Letters 454 (2): 111–114. doi:10.1016/j.neulet.2009.03.024. PMID 19429065.

[2] Shin K.Y., Lee J.-Y., Won B.Y., Jung H.Y., Chang K.-A., Koppula S., Suh Y.-H. (2009). “BT-11 is effective for enhancing cognitive functions in the elderly humans”. Neuroscience Letters 465 (2): 157–159. doi:10.1016/j.neulet.2009.08.033.

[3] Yabe T., Tuchida H., Kiyohara H., Takeda T., Yamada H. (2003). “Induction of NGF synthesis in astrocytes by onjisaponins of Polygala tenuifolia, constituents of kampo (Japanese herbal) medicine, Ninjin-yoei-to.”. Phytomedicine 10 (2-3): 106–14. doi:10.1078/094471103321659799. PMID 12725562.

[4] Jin Zeng-liang L., Gao Nana, Zhang Jian-rui R., et al (2014). “The discovery of Yuanzhi-1, a triterpenoid saponin derived from the traditional Chinese medicine, has antidepressant-like activity”. Progress in neuro-psychopharmacology & biological psychiatry. 53: 9–14. doi:10.1016/j.pnpbp.2014.02.013.

[5] Hu Yuan, Liu Ming, Liu Ping, Guo Dai-Hong H., Wei Ri-Bao B., Rahman Khalid. (2011). “Possible mechanism of the antidepressant effect of 3,6′-disinapoyl sucrose from Polygala tenuifolia Willd”. The Journal of pharmacy and pharmacology 63: 869–874. doi:10.1111/j.2042-7158.2011.01281.x.

[6] Xue Wei, Hu Jin-feng, Yuan Yu-he, et al. (2009). “Polygalasaponin XXXII from Polygala tenuifolia root improves hippocampal-dependent learning and memory”. Acta Pharmacologica 30: 1211–1219. doi:10.1038/aps.2009.112.

[7] Hu Yuan, Liao Hong-Bo, Liu Ping, Dai-Hong Guo, Wang Yu-Yu, Rahman Khalid. (2009). “Antidepressant-like effects of 3,6′-disinapoyl sucrose on hippocampal neuronal plasticity and neurotrophic signal pathway in chronically mild stressed rats”. Neurochemistry International. doi:10.1016/j.neuint.2009.12.004

[8] Cheong Myung-Hee H., Lee Sang-Ryong R., Yoo Hwa-Seung S., et al. (2011). “Anti-inflammatory effects of Polygala tenuifolia root through inhibition of NF-κB activation in lipopolysaccharide-induced BV2 microglial cells.”. Journal of Ethnopharmacology. doi:10.1016/j.jep.2011.08.008


Resources:

BioFoundations.net – Yuan Zhi


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Natural Substances that are Recognized as Geroprotectors

Gerontology is the study of all aspects of aging, including:

  • biological
  • cognitive
  • psychological
  • social

A branch of gerontology, called biogerontology, studies the biological aging process and the various potential means to intervene in the process.   The biological aging process primarily focuses on senescence which is the gradual deterioration of function in humans and other animals.  Senescence can refer either to cellular senescence or to senescence of the whole body.

Researchers have used the term “geroprotector” to describe the various agents and strategies which prevent or reverse senescence and in particular preventing the triggers of cellular senescence.  The purpose of a geroprotector is to affect the root cause of aging and prolong lifespan as well as reduce, delay or impede the onset of age-related pathologies.   This is hopefully accomplished by mitigating the aging process and repairing certain damage caused by the aging process.  1

The geroprotectors that have been identified to date have been treatments by substances (both natural and pharmaceutical) that are researched in the laboratory on:

  • flies
  • rodents
  • yeast

The results of these geroprotectors is that these organisms have lived significantly longer.   2  

A number of the compounds identified as geroprotectors are approved for human use.

This article provides a list of natural substances and compounds that are recognized as geroprotectors.  The source of this list is obtained from Geroprotectors.org and The JenAge Ageing Factor Database AgeFactDB.

The Table below lists those natural substances that are recognized as geroptrotectors.  With most of the substances, the list of studies are references to clinical trials for these substances.

Natural Substances as Geroprotectors

CategorySubstanceDescriptionStudies
Alkaloids
BerberineBerberine is a quaternary ammonium salt from the protoberberine group of isoquinoline alkaloids. It is found in such plants as Berberis [e.g. Berberis aquifolium (Oregon grape), Berberis vulgaris (barberry), Berberis aristata (tree turmeric)], Hydrastis canadensis (goldenseal)1
Amines
D-GlucosamineGlucosamine is an amino sugar and a prominent precursor in the biochemical synthesis of glycosylated proteins and lipids. Glucosamine is part of the structure of the polysaccharides chitosan and chitin2
SpermidineSpermidine is a polyamine compound found in ribosomes and living tissues, and having various metabolic functions within organisms. It was originally isolated from semen.3
Amino Acids
CreatineCreatine is a nitrogenous organic acid that occurs naturally in vertebrates and helps to supply energy to all cells in the body, primarily muscle. 4
L-theanineTheanine is an amino acid analogue of the proteinogenic amino acids L-glutamate and L-glutamine and is found primarily in particular plant and fungal species. It was discovered as a constituent of green tea in 1949 and in 1950 was isolated from gyokuro leaves, which have high theanine content.5
N-Acetyl-L-Cysteine (NAC)N-Acetyl-Cysteine is an endogenous form of Cysteine produced from Cysteine within the body.6
Disaccharide
TrehaloseTrehalose, also known as mycose or tremalose, is a natural alpha-linked disaccharide formed by an α,α-1,1-glucoside bond between two α-glucose units.7
Hormones
MelatoninMelatonin is a Neurohormone (regarded as a Neuropeptide) produced by the Pineal Gland. It is a hormone that anticipates the daily onset of darkness.8
Hydroquinone
Nordihydroguaiaretic AcidNordihydroguaiaretic acid (NDGA) is an antioxidant compound found in the creosote bush (Larrea tridentata).9
Lipids
Sodium ButyrateSodium butyrate is a compound with formula Na(C3H7COO). It is the sodium salt of butyric acid. It has various effects on cultured mammalian cells including inhibition of proliferation, induction of differentiation and induction or repression of gene expression.10
Minerals
MagnesiumMagnesium is an alkaline macromineral that functions as an electrolyte. 11
Nicotinamide Adenine Dinucleotides
Nicotinamide Adenine DinucleotideNicotinamide adenine dinucleotide (NAD) is a coenzyme found in all living cells. The compound is a dinucleotide, because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an adenine base and the other nicotinamide. Nicotinamide adenine dinucleotide exists in two forms, an oxidized and reduced form abbreviated as NAD+ and NADH respectively.12
Nootropic
VinpocetineVinpocetine is a semisynthetic derivative of the vinca alkaloid vincamine, an extract from the lesser periwinkle plant.13
Organic Acids
Alpha-ketoglutarateα-Ketoglutaric acid is one of two ketone derivatives of glutaric acid. α-Ketoglutarate is a key intermediate in the Krebs cycle, coming after isocitrate and before succinyl CoA.14
FumerateFumaric acid or trans-butenedioic acid is the chemical compound with the formula HO2CCH=CHCO2H. The salts and esters are known as fumarates. Fumaric Acid participates as an intermediate compound in the Krebs cycle of energy production within the mitochondria of cells15
MalateMalic acid is an organic compound with the molecular formula C4H6O5. It is a dicarboxylic acid that is made by all living organisms. The salts and esters of malic acid are known as malates. The malate anion is an intermediate in the citric acid cycle.16
Peptides
CarnosineCarnosine (beta-alanyl-L-histidine) is a dipeptide of the amino acids beta-alanine and histidine. It is highly concentrated in muscle and brain tissues.17
GlutathioneGlutathione (GSH) is an important antioxidant in plants, animals, fungi, and some bacteria and archaea, preventing damage to important cellular components caused by reactive oxygen species such as free radicals, peroxides, lipid peroxides and heavy metals. It is a tripeptide with a gamma peptide linkage between the carboxyl group of the glutamate side-chain and the amine group of cysteine (which is attached by normal peptide linkage to a glycine).18
Polyphenol
BaicaleinBaicalein is a cell-permeable flavone, originally isolated from the roots of Scutellaria baicalensis19
Blueberry polyphenolsBlueberries are perennial flowering plants with indigo-colored berries from the section Cyanococcus within the genus Vaccinium.20
Caffeic AcidCaffeic acid is an organic compound that is classified as hydroxycinnamic acid. This yellow solid consists of both phenolic and acrylic functional groups. It is found in all plants because it is a key intermediate in the biosynthesis of lignin.21
CatechinCatechin is a flavan-3-ol, a type of natural phenol and antioxidant. It is a plant secondary metabolite. It belongs to the group of flavan-3-ols (or simply flavanols), part of the chemical family of flavonoids.22
CurcuminCurcumin is a bright yellow chemical produced by some plants. It is the principal curcuminoid of turmeric, which is a member of the ginger family (Zingiberaceae). 23
Ellagic AcidEllagic acid is a natural phenol antioxidant found in numerous fruits and vegetables. Ellagic acid is the dilactone of hexahydroxydiphenic acid. The highest levels of ellagic acid are found in blackberries, cranberries, pecans, pomegranates, raspberries, strawberries, walnuts, wolfberries, and grapes. 24
Epigallocatechin GallateEpigallocatechin gallate (EGCG), also known as epigallocatechin-3-gallate, is the ester of epigallocatechin and gallic acid, and is a type of catechin. EGCG, the most abundant catechin in tea.25
Gallic AcidGallic acid is a trihydroxybenzoic acid, a type of phenolic acid, a type of organic acid, also known as 3,4,5-trihydroxybenzoic acid, found in gallnuts, sumac, witch hazel, tea leaves, oak bark, and other plants.26
GenisteinGenistein is a phytoestrogen and belongs to the category of isoflavones. Genistein is found in a number of plants including lupin, fava beans, soybeans, kudzu, and psoralea being the primary food source27
QuercetinQuercetin is a flavonol found in many fruits, vegetables, leaves and grains. 28
Quercetin DihydrateQuercetin Dihydrate is the dihydrate preparation of Quercetin, a ubiquitous natural flavonoid with antiproliferative properties. 29
Quercetin-3-O-Glucoside (Isoquercetin)Isoquercetin is a chemical compound. It can be isolated from mangoes and from Rheum nobile, the Noble rhubarb or Sikkim rhubarb, a giant herbaceous plant native to the Himalayas. Quercetin glycosides are also present in tea.30
Polydatin (Piceid)Piceid is a stilbenoid glucoside and is a major resveratrol derivative in grape juices. It can be found in the bark of Picea sitchensis. It can also be isolated from Polygonum cuspidatum, the Japanese knotweed (syn. Fallopia japonica). Resveratrol can be produced from piceid fermented by Aspergillus oryzae. 31
ResveratrolResveratrol (3,5,4′-trihydroxy-trans-stilbene) is a stilbenoid, a type of natural phenol, and a phytoalexin produced naturally by several plants in response to injury or when the plant is under attack by pathogens such as bacteria or fungi. Food sources of resveratrol include the skin of grapes, blueberries, raspberries, and mulberries and peanuts. 32
Rosmarinic AcidRosmarinic Acid is an organic acid found in Basil, Marjoram, Oregano, Perilla, Rosemary, Sage, Self-Heal (6.1% of the dry weight of Self-Heal) and Spearmint.33
Ursolic AcidUrsolic acid (sometimes referred to as urson, prunol, malol, or 3-beta-3-hydroxy-urs-12-ene-28-oic-acid), is a pentacyclic triterpenoid identified in the epicuticular waxes of apples as early as 1920 and widely found in the peels of fruits, as well as in herbs and spices like rosemary and thyme.34
Vitamins
Alpha Lipoic AcidLipoic acid (LA), also known as α-lipoic acid and alpha lipoic acid (ALA) and thioctic acid is an organosulfur compound derived from octanoic acid. ALA is made in animals normally, and is essential for aerobic metabolism.35
Ascorbic AcidAscorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form ("vitamer") of vitamin C.36
NicotinamideNicotinamide, (/ˌnɪkəˈtɪnəmaɪd/) also known as niacinamide and nicotinic amide, is the amide of nicotinic acid (vitamin B3 / niacin). Nicotinamide is a water-soluble vitamin and is part of the vitamin B group. Nicotinic acid, also known as niacin, is converted to nicotinamide in vivo, and, though the two are identical in their vitamin functions, nicotinamide does not have the same pharmacological and toxic effects of niacin37
Nicotinamide RibosideNicotinamide riboside (NR) is a pyridine-nucleoside form of vitamin B3 that functions as a precursor to nicotinamide adenine dinucleotide or NAD+.38
Vitamin B3Niacin (also known as vitamin B3 or nicotinic acid) is an organic compound.39
Vitamin B5Pantothenic acid, also called pantothenate or vitamin B5 (a B vitamin), is a water-soluble vitamin.40
Vitamin D3Cholecalciferol (vitamin D3) is one of the five forms of vitamin D. It is a secosteroid, that is, a steroid molecule with one ring open. 41


Informational Resources:

Geroprotectors.org

The JenAge Ageing Factor Database AgeFactDB


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Endogenous Glycation and its Effect on Human Health

Endogenous glycation is the chemical result of the bonding of a sugar molecule with a protein or lipid molecule that produces nonfunctioning and deformed molecules known as advanced glycation end products (AGE’s).

AGE’s that stem from a glycation reaction, produces cells that are stiffer and less pliable and more subject to damage and premature aging. When glycated proteins fuse together, this is known as cross-linking. The skin, eyes and heart are particular organs subject to cross-linking.

Exogenous glycation occurs when AGE’s are formed by heating proteins and lipids with sugar. Certain forms of cooking can accelerate the exogenous glycation process, such as grilling and frying.

AGEs have a range of pathological effects, such as:

  • Increased vascular permeability.
  • Oxidizing LDL.
  • Binding cells—including macrophage, endothelial, and mesangial—to induce the secretion of a variety of cytokines – promoting chronic inflammation.
  • Inhibition of vascular dilation by interfering with nitric oxide.
  • Enhanced oxidative stress – free radicals.

Once an AGE is produced through the endogenous glycation process, it is irreversible. It is therefore important to seek ways to prevent glycation, both endogenously and exogenously.

Compounds that are thought to inhibit AGE formation, at least in vitro, include:

Vitamins

  • Vitamin C [1]
  • Vitamin E [2]
  • Nicotinic Acid [3]
  • Benfotiamine [4]
  • Pyridoxamine [5]
  • Alpha-lipoic acid [6]
  • Pyridoral-5-phosphate (P-5-P) [7]

Amino Acids

  • Taurine [8]
  • Carnosine [9]
  • Beta-Alanine
  • Acety-L-Carnitine [10]
  • Ethylene-Diamine-Tetra-Acetate (EDTA) [11]

Minerals

  • Chromium [12]
  • Zinc [13]

Polyphenols

  • Diosmin [14]
  • Oligomeric Proanthocyanidins [15]
  • Quercetin [16]
  • Rutin [17]

Nootropics

  • Centrophenoxine [18]
  • Dimethylaminoethanol (DMAE) [19]

Herbs

  • Rosemary [20]
  • Astagalus [21]

Pharmaceuticals (Prescription required by licensed physician):

  • Acarbose [22]
  • Metformin [23]
  • Aminoguanidine [24]

Compounds that are thought to break some existing AGE crosslinks include:

  • Alagebrium (and related compounds ALT-462; ALT-486; ALT-946) [25]
  • N-phenacyl thiazolium bromide

References:

[1] Krone, C. A., et al. Ascorbic acid, glycation, glycohemoglobin and aging. Med Hypotheses. 62(2):275-279, 2004.

[2] Alderson, N. L., et al. Effect of antioxidants and ACE inhibition on chemical modification of proteins and progression of nephropathy in the streptozotocin diabetic rat. Diabetologia. 47(8):1385-1395, 2004.

[3] Rahbar, S., et al. Niacin (3-Pyridinecarboxylic Acid) is a potent inhibitor of advanced glycation endproducts (AGE’s). Diabetes. 48(5):SA375, 1999.

[4] Stirban, A., et al. Benfotiamine prevents macro- and microvascular endothelial dysfunction and oxidative stress following a meal rich in advanced glycation end products in individuals with type 2 diabetes. Diabetes Care. 29:2064-2071, 2006.

[5] Jain, S. K., et al. Pyridoxine and pyridoxamine inhibits superoxide radicals and prevents lipid peroxidation, protein glycosylation, and (Na+ + K+)-ATPase activity reduction in high glucose-treated human erythrocytes. Free Radic Biol Med. 30(3):232-237, 2001.

[6] Jain, S. K., et al. Lipoic acid decreases lipid peroxidation and protein glycosylation and increases (Na(+) + K(+))- and Ca(++)-ATPase activities in high glucose-treated human erythrocytes. Free Radic Biol Med. 29:1122-1128, 2000.

[7] Higuchi, O., et al. Aminophospholipid glycation and its inhibitor screening system: A new role of pyridoxal 5′-phosphate and pyridoxal as lipid glycation inhibitor. Journal of Lipid Research. 2006.

[8] Nandhini, A. T., et al. Stimulation of glucose utilization and inhibition of protein glycation and AGE products by taurine. Acta Physiol Scand. 181(3):297-303, 2004.

[9] Brownson, C., et al. Carnosine reacts with a glycated protein. Free Radic Biol Med. 28(10):1564-1570, 2000.

[10] Swamy-mruthinti, S., et al. Acetyl-L-carnitine decreases glycation of lens proteins: in vitro studies. Exp Eye Res. 69(1):109-115, 1999.

[11] Jorksten, J. Pathways to the decisive extension of the human specific lifespan. J American Geriatrics Society. 25:396-399, 1977.

[12] Evans, G. W. Conference of the American Aging Association. San Franciscio, California, USA. October 1992.

[13] Tupe, R., et al. Interaction of zinc, ascorbic acid, and folic acid in glycation with albumin as protein model. Biol Trace Elem Res. 2010.

[14] Manuel, Y., et al. The effect of flavonoid treatment on the glycation antioxidant status in Type-1 diabetic patients. Diabetes Nutr Metab. 12(4):256-263, 1999.

[15] Urios, P., et al. Flavonoids inhibit the formation of the cross-linking AGE pentosidine in collagen incubated with glucose, according to their structure. European Journal of Clinical Nutrition. 2007.

[16] Urios, P., et al. Flavonoids inhibit the formation of the cross-linking AGE pentosidine in collagen incubated with glucose, according to their structure. European Journal of Clinical Nutrition. 2007.

[17] Cervantes-Laurean, D., et al. Inhibition of advanced glycation end product formation on collagen by rutin and its metabolites. Journal of Nutritional Biochemistry. 2005.

[18] Nagy, I., et al. On the role of cross-linking of cellular proteins in aging. Mech Aging Dev. 14(1-2):245-251, 1980.

[19] Nagy, I., et al. On the role of cross-linking of cellular proteins in aging. Mech Aging Dev. 14(1-2):245-251, 1980.

[20] Dearlove, R. P., et al. Inhibition of protein glycation by extracts of culinary herbs and spices. Journal of Medicinal Food. 11(2):275-281, 2008.

[21] Motomura, K., et al. Astragalosides isolated from the root of Astragalus Radix inhibit the formation of advanced glycation end products. J Agric Food Chem. 2009.

[22] Cohen, M. P., et al. Alpha-glucosidase inhibition prevents increased collagen fluorescence in experimental diabetes. Gen Pharmacol. 22(4):607-610, 1991.

[23] Beisswenger, P., et al. Metformin inhibition of glycation processes. Diabetes Metab. 29(4 Part 2):95-103, 2003.

[24] Corman, B., et al. Aminoguanidine prevents age-related arterial stiffening and cardiac hypertrophy. Proceedings of the National Academy of Sciences of the United States of America. 95(3):1301-1306, 1998.

[25] Asif, M., et al. An advanced glycation endproduct cross-link breaker can reverse age-related increases in myocardial stiffness. Proc Natl Acad Sci USA. 97(6):2809-2813, 2000.


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Berberine exerts a hypoglycemic effect

Berberine is a type of Isoquinoline Alkaloid.

It is found in such plants as Berberis [e.g. Berberis aquifolium (Oregon grape), Berberis vulgaris (barberry), Berberis aristata (tree turmeric)], Hydrastis canadensis (goldenseal), Xanthorhiza simplicissima (yellowroot), Phellodendron amurense (Amur cork tree), Coptis chinensis (Chinese goldthread), Tinospora cordifolia, Argemone mexicana (prickly poppy), and Eschscholzia californica (Californian poppy).

Berberine exerts a hypoglycemic effect, but the mechanism remains unknown. In a study at the Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China, the effect of berberine on glucose uptake was characterized in 3T3-L1 adipocytes. It was revealed that berberine stimulated glucose uptake in 3T3-L1 adipocytes in a dose- and time-dependent manner with the maximal effect at 12 hours. Glucose uptake was increased by berberine in 3T3-L1 preadipocytes as well. Berberine-stimulated glucose uptake was additive to that of insulin in 3T3-L1 adipocytes, even at the maximal effective concentrations of both components.

Unlike insulin, the effect of berberine on glucose uptake was insensitive to wortmannin, an inhibitor of phosphatidylinositol 3-kinase, and SB203580, an inhibitor of p38 mitogen-activated protein kinase. Berberine activated extracellular signal-regulated kinase (ERK) 1/2, but PD98059, an ERK kinase inhibitor, only decreased berberine-stimulated glucose uptake by 32%. Berberine did not induce Ser473 phosphorylation of Akt nor enhance insulin-induced phosphorylation of Akt.

Meanwhile, the expression and cellular localization of glucose transporter 4 (GLUT4) were not altered by berberine. Berberine did not increase GLUT1 gene expression. However, genistein, a tyrosine kinase inhibitor, completely blocked berberine-stimulated glucose uptake in 3T3-L1 adipocytes and preadipocytes, suggesting that berberine may induce glucose transport via increasing GLUT1 activity.

In addition, berberine increased adenosine monophosphate-activated protein kinase and acetyl-coenzyme A carboxylase phosphorylation. These findings suggest that berberine increases glucose uptake through a mechanism distinct from insulin, and activated adenosine monophosphate-activated protein kinase seems to be involved in the metabolic effect of berberine. [1]


References:

[1] Zhou, L., et al. Berberine stimulates glucose transport through a mechanism distinct from insulin. Metabolism. 56(3):405-412, 2007.

Zhang Y, Li X, Zou D et al. (July 2008). “Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine”. The Journal of Clinical Endocrinology and Metabolism 93 (7): 2559–65.

Yin J, Xing H, Ye J (May 2008). “Efficacy of berberine in patients with type 2 diabetes mellitus”. Metabolism: Clinical and Experimental 57 (5): 712–7.

Wu LY, Ma ZM, Fan XL et al. (November 2009). “The anti-necrosis role of hypoxic preconditioning after acute anoxia is mediated by aldose reductase and sorbitol pathway in PC12 cells”. Cell Stress & Chaperones 15 (4): 387–94.

Yin J, Gao Z, Liu D, Liu Z, Ye J (January 2008). “Berberine improves glucose metabolism through induction of glycolysis”. American Journal of Physiology. Endocrinology and Metabolism 294 (1): E148–56.

Kong WJ, Zhang H, Song DQ et al. (January 2009). “Berberine reduces insulin resistance through protein kinase C-dependent up-regulation of insulin receptor expression”. Metabolism 58 (1): 109–19. 


Informational References:

Clinical Applications for Berberine

The Berberine Story Gets Better and Better (Life Enhancement July 2013)

Take This Dye for Diabetes From the ancient Silk Road to the modern nutritional pharmacopeia (By Will Block, Life Enhancement November 2010)


Resources:

Dr. Whittaker – Berberine (500mg)


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The Many Medicinal Benefits of Celastrus Paniculatus also known as “The Elixir of Life”

Celastrus Paniculatus is also known as:

  • Jyothismati Oil (Sanskrit: jyotishmati ज्योतीष्मती)
  • Celastrus Oil
  • Intellect Tree
  • Malkanguni Oil  (Hindi: Mal-kangani माल-कांगनी)
  • Deng You Teng  (Chinese: 灯油藤)
  • “The Elixir of Life”

due largely to its natural medicinal properties.  It has been an important and hot topic in the medical and botanical research fields for many decades.

Celastrus paniculatus is a member of the Celastraceae family and is a large, woody climber (called a climbing shrub), with a yellow, corky bark. 1 

It grows throughout India, and has been reported to grow as tall as 2,000m. The plants exhibit varying degrees of therapeutic values, some of which are its use in the treatment of:  2

  • cognitive dysfunction
  • epilepsy
  • insomnia
  • rheumatism
  • gout
  • dyspepsia

wps_clip_image-3534

Figure 1:  Celastrus paniculatus leaves, oil and seeds

The classes of molecules most predominant in this plant appear to be:

  • sequesterpene alkaloids
  • polyalcohols.  3

Overall, the phytochemical evaluation reveals the presence of:

  • carbohydrates
  • fixed oil
  • glycosides
  • cumarines
  • tannins
  • flavonoids
  • saponins
  • steroids
  • triterpenoids

which have been claimed to be responsible for its therapeutic uses.  13

The trace elements found in Celastrus paniculatus and known to be essential for humans and unquestionably associated with deficiency symptoms include:

  • chromium
  • copper
  • iodine
  • iron
  • manganese
  • molybdenum
  • selenium
  • zinc

wps_clip_image-2663

Figure 2:  a) Stem: Reddish brown stem covered with small elongated white lenticels b) Leaves: Alternately arranged c) Ovate leaf d) Capsules: Orange colored with 3-6 seeds inside e) Dehisced capsule without seeds f) Seeds: Single capsule showing seeds enclosed by an orange-red aril

In the Indian traditional system of medicine, called Ayruvedic medicine, Celastrus paniculatus extract has been used to improve intellect, memory and for the treatment of various mental disorders.  4 

The seeds of Celastrus paniculatus appear to be protective against cell death from glutamate at a very low concentrations, but the maximal protection observed is not too high. This may be, but is not confirmed, related to its antioxidant properties.

The plant’s usage has been extensively researched with promising results to treat neurodegenerative diseases such as Alzheimer’s.   Mice receiving Celastrus paniculatus showed significant memory enhancement as compared to the scopolamine group.

It has been demonstrated that Celastrus paniculatus seed oil has memory enhancing effects and hence can be developed as a potential drug in the treatment of dementia.  5

The seeds could be used to treat other mental disorders such as stress. The plant exhibits antioxidant properties which have several applications in medicinal biology, especially with respect to immunity and homeostasis. Stress alters the body’s homeostasis and is produced by several factors.

Celastrus paniculatus plant is considered to be rich in antioxidant content and so the seed oil extract’s efficacy was tested against immobilization stress in albino mice. The antioxidant enzyme levels of the animals regained and markedly increased in the acute and chronic immobilized groups, respectively. The results suggested that the extract of Celastrus paniculatus seed was highly efficacious in reducing the stress induced by least mobility for hours.  6 

In another study, the extract of Celastrus paniculatus seed was highly efficacious in reducing the stress induced by least mobility for hours which decreased the levels of reactive oxygen species (ROS) and increases level of thiobarbituric acid reactive substances (TBARS). Another neurological study has shown that the extracts increase ribonucleoproteins and Nissl substance -histologically and histochemically could be an indicator of hyperactivity of the brain cells which might correlate with the increased mental activity.  7

Effects of aqueous extracts of Celastrus paniculatus seeds were shown to have antioxidant properties in rats by neuroprotection against H2O2-induced neurotoxicity.  8

Apart from neurological properties, the alcoholic extracts of Celastrus paniculatus seeds (AlcE) possess significant antinociceptive and anti-inflammatory activity in-vivo.  9 

Histological studies show less cholesterol deposits in the aorta of animals fed with seed extract of Celastrus paniculatus compared to the induced hypercholesterolemic animals not given a Celastrus paniculatus supplement. It helps in reducing the activites of HMG-CoA reductase, glucose 6-phosphate dehydrogenase and malate dehydrogenase which are associated with cholesterol synthesis.  10

Figure 3:  Celastrus paniculatus flower buds and seeds

Ethnobotanical studies claim the significant use of its root as an antidote in snake bites and the use of its bark in bone fractures, bronchitis, abortion, gastric complaints and swollen veins. The leaves are used for sedative and wound healing activity in many regions. Modern research work evaluates the seed oil activity in favour of its ethnomedical claims.

The bark is abortifacient, depurative and a brain tonic.

The leaves are emmenagogue and the leaf sap is a good antidote for opium poisoning.

The seeds are acrid, bitter, thermogenic, emollient, stimulant, intellect promoting, digestive, laxative, emetic, expectorant, appetizer, aphrodisiac, cardiotonic, anti-inflammatory, diuretic, diaphoretic, febrifuge and tonic, abdominal disorders, leprosy, skin diseases, paralysis, asthma, leucoderma, cardiac debility, inflammation, nephropathy, amenorrhoea, dysmenorrhoea.  12

Other therapeutic properties of Celastrus paniculatus include the following in the Table below:  11

Therapeutic Properties of Celastrus Paniculatus

Therapeutic UseActivity
Learning and memorySelectively reverses the impairment in spatial memory produced by acute central muscarinic receptor blockade
AntioxidantDose-dependent free radical scavenging capacity and a protective effect on DNA cleavage
HypolipidaemicReduces serum cholesterol and LDL cholesterol levels; increaded fecal cholesterol excretion
Anti-arthriticActing on secondary lesions
Wound healingLupeol presence causes wound contraction
AntimicrobialInhibition by triterpenoid glycosides present in saponin extracts

Celastrus paniculatus can be taken by consuming the seeds or oil.  The oil can be consumed directly or encapsulated.


Statements made in this article have not been evaluated by the U.S. Food and Drug Administration. Any products referred to on this website are not intended to diagnose, treat, cure, or prevent any disease.

 


Resources:

Cognitol – Om-Chi Herbs

Intellect Tree Seed (Celastrus Paniculatus) Oil

Intellect Tree Seed

Pure Malkangani oil 30ml (Celastrus Paniculatus) (From India)

 


This article was written by BioFoundations contributing writer Nishant Nirale.

Nishant Nirale is a Biotechnology Professional who is presently pursuing his second Masters degree in Biotechnology Management from the University of California, Irvine to develop business acumen into the bioscience business. Nishant has completed his Masters and Bachelors of Science in Biotechnology from the University of Mumbai, India and has experience working in a variety of functional roles in healthcare/biotech sector. He believes that there is an underlying need to utilize the thrilling advents of science to its best potential. This aspires him to bridge the gap between the scientific fields of life-science/healthcare with management using the unique formula of “Science + Management” from a commercialization standpoint. Nishant is a health and fitness enthusiast and likes to study and educate people towards adapting a healthy lifestyle.

Nishant Nirale, MSc Biotechnology

Email: nnirale@uci.edu


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Chlorophyllin: Antimutagenic agent against Environmental Toxins

The exposure to environmental toxins is experienced on a daily basis by everyone.  Some have greater exposure than others, but it is clear that all people are under the exposure of environmental toxins.  This exposure occurs from a barrage of compounds through:

  • industrial and manufacturing facilities
  • agricultural runoff
  • pesticides and herbicides laced in foods
  • emissions from trucks, cars, and planes

This exposure was confirmed by the Centers for Disease Control and Prevention (CDC) in a published report entitled The Fourth National Report on Human Exposure to Environmental Chemicals, 2009, (the Fourth Report, 2009).   This CDC report examined the burden of 212 industrial chemicals in the bodies of U.S. citizens.  1 

Environmental toxins are known to create mutations in the p53 tumor suppressor gene which then leads to pathways involved in cancer development. 

“Turning on” the p53 Tumor Suppressor Gene also inhibits the genetic mutations that “turn off” the p53 Tumor Suppressor Gene.   2 

Chlorophyllin can accomplish the “turning on” of the p53 tumor suppressor gene and thus protect against mutations of the gene by exhibiting powerful anticarcinogenic effects in regards to a variety of environmental toxins.  3  4

Chlorophyllin forms complexes with the environmental toxins and limits their ability to bind to the normal cell and thus disables the potent carcinogen.

Certain common environmental toxins are disabled by chlorophyllin:


Resources:

Life Extension – Chlorophyllin


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Prunella vulgaris (Heal-all): The Antioxidant Herb Consumed by American Indians

Prunella vulgaris is an herbaceous plant in the genus Prunella and is often known by the name self-heal or heal-all. 

Heal-all is a perennial herb found throughout Europe, Asia and North America.  It has also been used for centuries in traditional Chinese medicine and is known as Xia Ku Cao.

prunella_vulgaris2

Since Heal-all is edible, there are a wide variety of uses of the plant, including:

  • Young leaves and stems can be eaten raw in salads, soups and stews
  • The plant in whole can be boiled and eaten as a leafy vegetable
  • Aerial parts of the plant are powdered and brewed in a cold infusion to make a beverage

The American Indians have been known to consume Heal-All for many centuries.  The Cherokee tribe cooked and ate the young leaves. The Nlaka’pamux tribe from Washington and British Columbia drank a cold infusion of the whole plant.

The plant has a wide range of chemical constituents, including:  1  2  3 

  • beta-sitosterol
  • betulinic acid
  • cyanidin
  • D-camphor
  • delphinidin
  • D-fenchone
  • hyperoside
  • lauric acid
  • linoleic acid
  • lupeol
  • manganese
  • myristic acid
  • oleanolic acid
  • rosmarinic acid
  • rutin
  • tannins
  • ursolic acid
  • vitamin A
  • vitamin C
  • vitamin K

Heal-all has very potent antioxidant activities.  The antioxidative activity was due partly in relation to the rosmarinic acid content.  In fact, Heal-all has 6.1% rosmarinic acid based on dry weight.  4  Heal-all probably has more rosmarinic acid than any other plant by dry weight. 

Heal-all also has been studied for its ability to inhibit the growth and metastasis of Melanoma cells.  5  The oral administrations of Heal-all reduced the lung metastasis and tumor cell growth by B16-F10 or B16-F1 melanoma cells. These results suggested that the anti-metastatic effect of Heal-all is mediated through the suppression of MMP-9 expression by the inhibition of NF-kappaB via ERK1/2 signaling pathway as well as MMP-9 activity.

In 2009, a study was conducted that exhibited significant antiestrogenic properties, both in vitro and in vivo, in Heal-all. This activity is likely due to the ability of Heal-all-activated AHR to interfere with estrogen. This herb may be useful as an adjunct for the treatment of estrogen-dependent processes like endometriosis and breast and uterine cancers. Full characterization of this herb will likely provide new insights into the crosstalk between AHR and ESR1, with potential for therapeutic applications in women.   6 


Informational Reference:

Prunella vulgaris L. : A Literature Review on its Therapeutic Potentials, Rafia Rasool and Bashir A. Ganai


Resources:

BioFoundations.net – Xia Ku Cao

Heal All(Prunella Vulgaris/Woundwort) 8oz/BP

Stakich All Heal (Prunella Vulgaris) 4 oz Liquid Extract


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Phytochemicals as Chemopreventive Agents

According to a remarkable article published in the September 2008 issue of Pharmaceutical Research (25(9): 2097–2116) (Published online 2008 Jul 15. doi: 10.1007/s11095-008-9661-9), entitled Cancer is a Preventable Disease that Requires Major Lifestyle Changes, the authors identified a number of phytochemicals that have been researched for their ability to act as chemopreventive agents.  A chemopreventive agent is a drug or compound to inhibit, delay, or reverse carcinogenesis.

Phytochemicals are chemical compounds that occur naturally in plants. Scientists have identified over 4,000 phytochemicals.  Various phytochemicals have been identified in fruits, vegetables, spices, and grains that exhibit chemopreventive potential. The consumption of these various phytochemicals in the diet has been researched in numerous studies to show that they can protect against cancer.  1 2 3 4

The consumption of these phytochemicals in the diet are considered safe and target multiple cell-signaling pathways.  5

The Table below lists some of the more common and researched phytochemicals as chemopreventive agents.  The phytochemical is listed with the foods, herbs and spices that contain the phytochemical.  There is then a link to any nutraceutical (if any) that contains the phytochemical.  The last column list a reference to a study on the chemopreventive potential of the phytochemical.  With many of the phytochemicals listed, there are numerous references that can be cited.  In this Table we are listing only one or two references as a starting point for further research.

PhytoChemicals as Chemopreventive Agents

#PhytochemicalFoods/Herbs/SpicesNutraceuticalReferences
1(-)-epicatechin gallate Green tea, buckwheat, grapesN NR
2(-)-epicatechinCocoa, prune juice, broad bean pod, Açaí oil, peaches, green tea, vinegar and barley grainNR
31’-actoxychavicol acetateAlpinia galanga (Languas galanga) Thai galangal Thai gingerNoneR
418-β-glycyrrhetinic acidLiquoriceNoneR
5Acetyl-11-keto-β-boswellic acid Indian frankincense, SalaiNR R
6AllicinGarlicNR
7Alpha-lipoic acidSpinach, Kidney, Liver Broccoli, Heart, Tissue, TomatoesNR
8Alpha-tocoperolWheat germ oil, Sunflower oil, Almond oil, Sunflower seed, Almond, Hazelnut, Walnut oil, Peanut oil, Olive oil NR
9AnetholeFennel, anise , liquorice (Fabaceae), camphor, magnolia blossoms, and star aniseNoneR R
10ApigeninChamomile tea, grapefruits, onions, oranges, parsley, celery, yarrow, tarragon, cilantro, foxglove, coneflower, licorice, flax, passion flower, horehound, spearmint, basil, and oregano, and Gingko BilobaNR
11Ascorbic acid Kiwi fruits, Citrus Fruits, Noncitrus fruits, Fruiting vegetables (usually peppers and sweet peppers), Potatoes, Leafy green vegetables, Cruciferous vegetablesNR
12BaicalinScutellaria baicalensis (Baikal skullcap), Scutellaria lateriflora (blue skullcap), Scutellaria galericulata (marsh skullcap)N
Baikal skullcap only
R
13Benzyl isothiocyanateCruciferous vegetables, green immature papayaNR
14BerberineGoldenseal, Oregon grape, Chinese Goldenthread, Tinospora cordifolia NR
15Beta-caroteneVietnamese gac (Momordica cochinchinensis Spreng.), palm oil, yellow and orange fruits, such as cantaloupe, mangoes, pumpkin and papayas, and orange root vegetables such as carrots and yams; spinach, kale, sweet potato leaves, and sweet gourd leaves, apricot, sweet potatoes, broccoli, turnip greens, winter squash and collard greensNR
16Beta-cryptoxanthinePetals and flowers of plants in the genus Physalis, orange rind, papaya, egg yolk, butter, apples, red peppers and bovine blood serum REFERENCENR
17Beta-lapachoneLapacho tree (Tabebuia avellanedae) Pau D’arcoNR
18Betulinic acidwhite birch (Betula pubescens), ber tree (Ziziphus mauritiana), selfheal (Prunella vulgaris), Triphyophyllum peltatum and Ancistrocladus heyneanus, Diospyros leucomelas, Tetracera boiviniana, (Syzygium formosanum), flowering quince (Pseudocydonia sinensis, rosemary, Chaga mushroom (Inonotus obliquus) and Pulsatilla chinensisN NR
19ButeinToxicodendron vernicifluum (formerly Rhus verniciflua), also known by the common name Chinese lacquer treeNR
20Caffeic acid phenethyl esterBee propolisNR
21CapsaicinCayenne, chilli peppersNR
22CarnosolRosemary and Mountain desert sage (Salvia pachyphylla)NR
23CelastrolRoot extracts of Tripterygium wilfordii (Thunder god vine) and Celastrus regeliiNR
24CurcuminTurmeric (Curcuma longa or JiangHuang), Common Ginger (Zingiber officinale) and shampoo ginger (Zingiber zerumbet)NR
25Dibenzoylmethane A structural analogue of curcumin (a bioactive phytochemical present in a widely used spice turmeric)NoneR
26DiosgeninTubers of Dioscorea wild yam, such as the Kokoro; fenugreek (Trigonella foenum graecum)NR
27EmodinRhubarb, buckthorn and Japanese knotweed (Fallopia japonica syn. Polygonum cuspidatum), aloe vera leavesNR
28Epigallocatechin gallate White tea (4245 mg per 100 g), green tea (7380 mg per 100 g) and, in smaller quantities, black tea; apple skin, plums, onions, hazelnuts, pecans and carob powder (at 109 mg per 100 g)NR
29Eugenol Clove oil, nutmeg, cinnamon, basil, bay leaf, wormwoodNR
30EvodiamineExtracted from the Tetradium genus of plants; Euodia, Evodia, or Bee bee treeNR
31Gamma-tocotrienol Rice bran oil and palm oil, wheat germ, barley, saw palmetto, anattoNR
32GarcinolRind of the fruit of Garcinia indica; popularly known as Kokum or MangosteenNR R
33GenisteinLupin, fava beans, soybeans, kudzu, and psoralea being the primary food source, also in the medicinal plants, Flemingia vestita and F. macrophylla, and coffee, Sophora japonicaNR
34GingerolGingerNR
35GlabridinRoot extract of licorice (Glycyrrhiza glabra).NR
36Glycyrrhetinic acidLiquoriceNR
37GlycyrrhizinGlycyrrhiza glabra (liquorice) rootNR
38GuggulsteroneResin of the guggul plant, Commiphora mukulNR
39Indiruibin-3’-monoximeActive ingredient of Danggui Longhui Wan, a mixture of plants that is used in traditional Chinese medicine; Indigo Plant (Isatis Root, Isatis Leaf)NoneR
40Indole 3-carbinol High levels in cruciferous vegetables such as broccoli, cabbage, cauliflower, brussels sprouts, collard greens and kaleNR
41KahweolBeans of Coffea Arabica; an antioxidant diterpene that remains in unfiltered coffee beverages, such as Turkish and Scandinavian coffee NoneR
42LinaloolCinnamomum tamala, Cannabis sativa, Ocimum basilicum, Solidago chilensis MeyenArtemisia vulgaris (mugwort), Humulus lupulus
NR
43LupeolMango, Acacia visco and Abronia villosa; dandelion coffeeNR
44LuteinHigh quantities in green leafy vegetables such as spinach, kale and yellow carrots, dandelion, NR
45Lycopene Tomatoes, red carrots, watermelons, gac, and papayas, asparagus, parsley, autumn olive, pink guava, papaya, seabuckthorn, wolfberry (goji, a berry relative of tomato), and rosehipNR
46MangiferinMangoes,in Iris unguicularis, Anemarrhena asphodeloides rhizomes, and in Bombax CeidaNoneR
47MangostinMangosteen tree (Garcinia mangostana)NoneR
48Myricetin Oranges, Sea Buckthorn, Chia seeds (Salvia hispanica), Carob extract (Ceratonia siliqua), Pistachio extract (Pistacia lentiscus), Grape Seed Extract, Cruciferous vegetables such as broccoli, cabbage, chinese cabbage, but not cauliflower, Peppers (capsicum family) including red chili, green chili, bell pepper,garlic, walnuts, onionsNR
49OleandrinOleander (Nerium oleander L.)NoneR R
50Oleanolic acid Olive oil, Phytolacca americana (American pokeweed), and Syzygium spp, Siberian Ginseng (leaves), Olive Leaf, European Mistletoe (leaves), Basil, garlicN NR
51Phenethyl isothiocyanate (PEITC)Cruciferous vegetablesNR
52Phytic acid (inositol hexakisphosphate (IP6))Grains, seeds and beans. Rich sources of phytic acid are wheat bran and flaxseed (3 % phytic acid)
NR
53Piceatannol Roots of Norway spruces (Picea abies), seeds of the palm Aiphanes horrida and in Gnetum cleistostachyum; Piceatannol is a metabolite of resveratrol found in red wine, grapes, passion fruit, white tea, and Japanese knotweed, blackberriesNoneR
54PiperineBlack pepper and long pepper, West African pepperN N NR R
55PlumbaginPlumbago, Drosera and Nepenthes, black walnut drupe (Juglans nigra)NoneR
56QuercetinApple, tea, onion, nuts, berries, cauliflower and cabbageN NR R
57Quinic acidCinchona bark, coffee beansNR
58RsveratrolSkin of grapes, blueberries, raspberries, and mulberries; Japanese knotweed; muscadine grapes; peanuts, especially sprouted peanuts; N NR
59SanguinarineBloodroot (Sanguinaria canadensis), Mexican prickly poppy Argemone mexicana, Chelidonium majus and Macleaya cordataNoneR
60SesaminSesame Seed Oil and Sesame Seeds (Sesamum indicum)NR
61Silymarin Milk thistle seedsNR
62SulforaphaneCruciferous vegetables such as Brussels sprouts, cabbage, cauliflower, bok choy, kale, collards, Chinese broccoli, broccoli raab, kohlrabi, mustard, turnip, radish, arugula, and watercress; highest levels in 3 day old broccoli sproutsNR
63TanshinonesSalvia miltiorrhiza (simplified Chinese: 丹参; traditional Chinese: 丹參; pinyin: dānshēn), also known as red sage, Chinese sage, tan shen, or danshenNR
64Tanshinones IIASalvia miltiorrhiza (simplified Chinese: 丹参; traditional Chinese: 丹參; pinyin: dānshēn), also known as red sage, Chinese sage, tan shen, or danshenNR
65Theaflavin-3,3’-digallate Black teaNR
66ThymoquinoneNigella sativa (Black cumin seed); kolanji seedsN N NR R
67Ursolic acidApples, basil, bilberries, cranberries, elder flower, peppermint, rosemary, lavender, oregano, thyme, sage, holy basil, hawthorn, and prunesNR R
68WogoninScutellaria baicalensis (Baikal skullcap); active ingredients of Sho-Saiko-To, a Japanese herbal supplementNR
69Yakuchinone AIsolated from Alpinia oxyphylla Miquel; Yi Zhi Ren; Sharp-Leaf Galangal(Seed)N NR
70Yakuchinone BIsolated from Alpinia oxyphylla Miquel; Yi Zhi Ren; Sharp-Leaf Galangal(Seed)N NR
71ZerumboneZingiber zerumbet also known as bitter ginger; locally known to the Malay as “Lempoyang” NoneR


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Summary of Substances for Neurotrophic Factors and Neurogenesis

Neurotrophins (also called Neurotrophic Factors) are a family of proteins that induce the survival, development, and function of neurons. Neurotrophic factors are secreted by target tissue and act by preventing the associated neuron from initiating programmed cell death – thus allowing the neurons to survive.

They are chemicals that assist in the stimulation and control of neurogenesis.

Neurotrophins consists of six structurally related neurotrophic factors:

  • Nerve growth factor (NGF)
  • Brain-derived neurotrophic factor (BDNF)
  • Glial Cell Line-Derived Neurotrophic factor (GDNF)
  • Ciliary neurotrophic factor (CNTF)
  • Neurotrophin-3 (NT-3)
  • Neurotrophin-4 (NT-4)

The Table (Downloadable PDF) is a summary and consolidation of the substances that can be consumed for both neurogenesis and all three main neurotrophic factors:

  • Nerve growth factor (NGF)
  • Brain-derived neurotrophic factor (BDNF)
  • Glial Cell Line-Derived Neurotrophic factor (GDNF)

Download PDF: Summary of Substances for Neurotrophic Factors and Neurogenesis

The Table is an excerpt from the E-Book:  Enhancing the Growth of New Brain Cells

Note: PDF files require a viewer such as the free Adobe Reader


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