Monthly Archives: May 2017

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Freezing Broccoli Sprouts Increases Sulforaphane Yield

Three-day old broccoli sprouts are concentrated sources of glucoraphanin, which is the precursor to sulforaphane.  Fresh broccoli sprouts contain 10 to 100 times more glucoraphanin by weight than mature broccoli plants. 1  Fresh broccoli sprouts can contain at least 73 mg of glucoraphanin (also called sulforaphane glucosinolate) per 1-oz serving.

A study from 2015 published in the journal RSC Advances by researchers from the College of Food Science and Technology, Nanjing Agricultural University, Nanjing, People’s Republic of China and the College of Food Science and Engineering, Qingdao Agricultural University, Qingdao, People’s Republic of China, investigated whether freezing broccoli sprouts would have an effect on glucoraphanin and ascorbic acid content, myrosinase activity, sulforaphane and sulforaphane nitrile formation.  2

The researchers froze broccoli sprouts at −20 °C (DF-20), −40 °C (DF-40) and −80 °C (DF-80) or stored at −20 °C (LN-20), −40 °C (LN-40) and −80 °C (LN-80) after being frozen in liquid nitrogen for 5 min or always frozen in liquid nitrogen (LN).

The results showed the following:

  • glucoraphanin content was not significantly affected by freezing
  • myrosinase activity was enhanced
  • sulforaphane yield  was increased by 1.54–2.11 fold
  • sulforaphane nitrile formation decreased
  • ascorbic acid content was decreased

By freezing fresh broccoli sprouts, sulforaphane can be increased by on average 1.825 times its original value when fresh and not frozen. 

Eating frozen broccoli sprouts may not be very appetizing.  Instead it is recommended to use the frozen broccoli sprouts in a smoothie.  Make sure you use the broccoli sprouts straight from the freezer and do not allow them to thaw.  

The Multiple Health Benefits of Tributyrin, a Triglyceride Form of Butyrate

Short-Chain Fatty Acids

A considerable amount of scientific interest has been focused on short chain fatty acids (SCFAs) for improving colonic and systemic health, and specifically reducing the risk of inflammatory diseases, diabetes, and cardiovascular disease.

Researchers have shown that SCFAs have distinct physiological effects:  1

  • they contribute to shaping the gut environment
  • they influence the physiology of the colon
  • they can be used as energy sources by host cells and the intestinal microbiota 
  • they also participate in different host-signaling mechanisms

Prebiotics, which consist of primarily dietary carbohydrates such as resistant starch and dietary fibers, are the substrates in the large intestine for fermentation that produce SCFAs.  The other source of SCFA, although in smaller amounts than dietary carbohydrates, are amino acids.  Three amino acids:

  • valine
  • leucine
  • isoleucine

obtained from protein breakdown can be converted into isobutyrate, isovalerate, and 2-methyl butyrate, known as branched-chain SCFAs (BSCFAs), which contribute very little (5%) to total SCFA production.  2

There are seven short-chain fatty acids that are produced by the large intestine through the fermentation of dietary fiber and resistant starch.  Of these seven short-chain fatty acids, three of them are the most important and common:

  • acetate
  • propionate
  • butyrate

These three represent about 90–95% of the SCFA present in the colon.  The rate and amount of SCFA production depends on the species and amounts of microflora present in the colon, the substrate source and gut transit time.

Butyrate is the major energy source for colonocytes. Propionate is largely taken up by the liver. Acetate enters the peripheral circulation to be metabolized by peripheral tissues and is the principal SCFA in the colon, and after absorption it has been shown to increase cholesterol synthesis.

Image result for Short-Chain Fatty Acids

Figure 1.  Fibers, specific oligosaccharides and resistant starch reach the colon intact, where they induce shifts in the composition and function of intestinal bacteria (shifts indicated by different colors). Intestinal bacteria use these compounds as substrates for the production of the short-chain fatty acids acetate, propionate and butyrate. These microbial metabolites are taken up by intestinal epithelial cells called enterocytes. Butyrate mainly feeds the enterocytes, whereas acetate and propionate reach the liver by the portal vein.  (Source:  You are what you eat,  Nature Biotechnology  32, 243–245 (2014) doi:10.1038/nbt.2845)

Butyrate (Butyric Acid)

The most important short-chain fatty acid is butyrate.

Butyrate is a primary energy source for colonic cells.  3 4   Butyrate also has demonstrated anti-inflammatory properties.  5  Butyrate may also have a role in preventing certain types of colitis. A diet low in resistant starch and fiber, which will result in a low production of SCFAs in the colon, may explain the high occurrence of colonic disorders seen in the Western civilization.  6

Studies have demonstrated that butyrate has anti-carcinogenic properties:

  • It inhibits the growth and proliferation of tumor cell lines in vitro.  7
  • It induces differentiation of tumor cells, producing a phenotype similar to that of the normal mature cell.  8
  • It induces apoptosis or programmed cell death of human colorectal cancer cells.  9 10
  • It inhibits angiogenesis by inactivating Sp1 transcription factor activity and down regulating VEGF gene expression. 11

Butyrate has been studied for its role in nourishing the colonic mucosa and in the prevention of cancer of the colon, by promoting cell differentiation, cell-cycle arrest and apoptosis of transformed colonocytes; inhibiting the enzyme histone deacetylase and decreasing the transformation of primary to secondary bile acids as a result of colonic acidification.

Therefore, a greater increase in SCFA production and potentially a greater delivery of SCFA, specifically butyrate, to the distal colon may result in a protective effect.   12

Butyrate is mainly taken up by the colon epithelial cells, only small amounts reach the portal vein and the systemic circulation.  The primary beneficial effects of butyrate occurs at the intestinal level, yet there are additional benefits at the extra intestinal level:

Intestinal effects

  • Is the preferred energy source for the colon epithelial cells
  • Decreases the pH of the colon (which decreases bile salt solubility, increases mineral absorption, decreases ammonia absorption, and inhibits growth of pathogens)
  • Stimulates proliferation of normal colon epithelial cells
  • Prevents proliferation and induces apoptosis of colorectal cancer cells
  • Affects gene expression of colon epithelial cells
  • Plays a protective role against colon cancer and colitis
  • Improves the gut barrier function by stimulation of the formation of mucin, antimicrobial peptides, and tight-junction proteins
  • Interacts with the immune system and regulates immune function
  • Has anti-inflammatory effects
  • Stimulates the absorption of water and sodium
  • Reduces oxidative stress in the colon
  • Assists in ion absorption
  • Assists in proper intestinal motility
  • Induces cell cycle arrest, differentiation, and apoptosis in colon cancer cells

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Figure 2.  The multiple effects of butyrate at the intestinal level.  (Source:  Potential beneficial effects of butyrate in intestinal and extra intestinal diseases)

Extra intestinal effects  13

  • Insulin sensitivity
  • Cholesterol synthesis
  • Energy expenditure
  • Ammonia scavenger
  • Stimulation of β-oxidation of very long chain fatty acids and peroxisome proliferation
  • CFTR function
  • Neurogenesis
  • HbF production

Tributyrin

The major problem with butyrate is achieving high concentrations in the blood. Butyrate is metabolized rapidly as soon as it enters the enteroocytes via its active transport system, and its plasma concentrations are far below those required to exert its antiproliferative/differentiating actions.  14 

An alternative and more advantageous form of butyric acid is the triglycerine form called Tributyrin, also known as glyceryl tributyrate. Tributyrin is a triglyceride containing 3 molecules of butyric acid which are bound by a glycerol molecule. 

Tributyrin is naturally present in butter in trace amounts.  However, it is not recommended to consume butter as a means to obtain therapeutic amounts of tributyrin.  There is no point to recommend consuming butter to someone if the intention is to increase butyric acid consumption.

As an alternative to consuming butter, tributyrin can now be consumed in the form of a supplement or a food additive and can provide considerable amounts of butyrate to the intestine in addition to the endogenous production of SCFAs (butyrate) from the fermentation of dietary fibers.

Tributyrin is known to overcome the pharmacokinetic drawbacks of butyrate.  Because it is rapidly absorbed and chemically stable in plasma, tributyrin diffuses through biological membranes and is metabolized by intracellular lipases, releasing therapeutically effective butyrate over time directly into the cell. 

Ball-and-stick model of the butyrin molecule

Figure 3.  Ball-and-stick model of the tributyrin molecule, the triglyceride of butyric acid.  Source:  By Jynto (talk) – Own workThis chemical image was created with Discovery Studio Visualizer., CC0, https://commons.wikimedia.org/w/index.php?curid=20234384

The technique of attaching butyrate to a glycerol molecule turns the new molecule (tributyrin) into a fat. The attachment of a glycerol molecule to 3 butyric acid molecules is through an ester bond which can only be broken by a specific enzyme called pancreatic lipase.  

Pancreatic lipase is secreted from the pancreas into the small intestine (duodenum) and not in the stomach.  Because of this, tributyrin stays intact in the stomach but once it reaches the small intestine (duodenum), the 3 butyric acid molecules are released by the pancreatic lipase enzyme. 

After the pancreatic lipase action, two free butyric acid molecules and one monobutyrin molecule are formed where they are used in the intestine and taken up by the enterocytes. After transportation through the portal vein they are metabolized in the liver. 

chem formula

Figure 4.  Ester bond of glycerol and 3 butyric acid molecules.  (Source: Bioremediation of Fats and Oils)

The tributyrin form of butyrate ensures high bioavailability of butyrate in all the sections of the small intestine.  Because tributyrin is a delayed release source of butyrate, it achieves more sustained plasma levels. 

According the the U.S. Federal Drug Administration (FDA), tributyrin is a food substance affirmed as Generally Recognized As Safe (GRAS).  15

Multiple Health Benefits of Tributyrin 

Specific studies on tributyrin have demonstrated multiple benefits in a number of disease conditions by releasing therapeutically effective butyrate over time directly into the cell.  The advantage with tributyrin is that it has all the health benefits of butyrate, as evidenced above, as well as its own specific targeted health benefits.

Some of the more important and specific health benefits of tributyrin include:

  • Anticarcinogenic potential
    • Colon cancer
    • Leukemia
    • Melanoma
    • Liver cancer (apoptosis)
  • Alzheimer’s disease and Dementia
  • Antibiotic-associated diarrhea (AAD)
  • Lipopolysaccharide (LPS)-induced liver injury
  • Inflammation

Anticarcinogenic potential

In vitro and in vivo studies have shown that tributyrin acts on multiple anticancer cellular and molecular targets without affecting non-cancerous cells. The mechanisms of action of tributyrin as a anticarcinogenic agent include:  16

  • the induction of apoptosis
  • cell differentiation
  • the modulation of epigenetic mechanisms

Due to the minimum toxicity profile of tributyrin, it is an excellent candidate for combination therapy with other agents for the control of cancer. 

Colon cancer

Tributyrin was shown to be more potent in inhibiting growth and inducing cell differentiation than natural butyrate on growth, differentiation and vitamin D receptor expression in Caco-2 cells, a human colon cancer cell line.  17

Tributyrin provides a useful therapeutic approach in chemoprevention and treatment of colorectal cancer.   

In another in vitro study, tributyrin showed potent antiproliferative, proapoptotic and differentiation-inducing effects in neoplastic cells.  18

Leukemia

In this study monobutyrin (MB) and tributyrin (TB) were studied in vitro for their effects on inducing differentiation of human myeloid leukemia HL60 cells and murine erythroleukemia cells. On a molar basis TB was about 4-fold more potent than either BA or MB for inducing differentiation of HL60 cells. BA, MB, or TB induced erythroid differentiation of murine erythroleukemia cells.  19

Melanoma

A study from February 2011 sought to investigate a possibility to develop tributyrin emulsion as a potent anti-cancer agent against melanoma. Tributyrin emulsion was more potent than butyrate in inhibiting the growth of B16-F10 melanoma cells. Accumulation of cells at sub G(0)/G(1) phase and the DNA fragmentation induced by tributyrin emulsion treatment revealed that tributyrin emulsion inhibited the growth of B16-F10 cells by inducing apoptosis. Treatment with tributyrin emulsion suppressed the colony formation of melanoma cells in a dose-dependent manner.  20

The data from this study suggests that tributyrin emulsion may be developed as a potent anti-cancer agent against melanoma.

Liver cancer

Researchers in this study from November 1999 investigated whether butyrate could induce apoptosis in transformed human liver (Hep G2) cells. Hep G2 cells treated with butyrate displayed acetylated histones, increased DNA fragmentation and morphological features consistent with apoptosis. 

They also investigated whether butyrate present in tributyrin, a triacylglycerol more compatible for inclusion into colloidal lipid structures than butyrate, could also induce apoptosis in Hep G2 cells.

Tributyrin induced DNA fragmentation and morphological features characteristic of apoptotic cells in Hep G2 cells.

These results are a significant advance towards delivering butyrate via colloidal lipid particles to cancerous sites in vivo. This study showed that butyrate and tributyrin are potent apoptotic agents. 21

Alzheimer’s disease and Dementia

Recent research at MIT has determined that, in rodent models of Alzheimer’s dementia, the negative impact of amyloid beta exposure on neuronal function and new memory formation results largely from increased neuronal expression of an enzyme known as HDAC2 (histone deacetylase 2).

A study from March 2004 showed that tributyrin may have the most practical potential to inhibit HDAC by blunting microglial activation. Tributyrin is anti-inflammatory in primary, brain-derived microglial cells.  A blunting of microglial cytokine production might in itself have a favorable impact on progression of Alzheimer’s.  22  23  

Antibiotic-associated diarrhea (AAD)

In a recent study from November 2014, researchers hypothesized that antibiotic-induced changes in gut microbiota reduce butyrate production, varying genes involved with gut barrier integrity and water and electrolyte absorption, lending to AAD, and that simultaneous supplementation with the probiotic Lactobacillus GG  and/or tributyrin would prevent these changes.

Optimizing intestinal health with Lactobacillus GG and/or tributyrin may offer a preventative therapy for AAD.  24  Lipopolysaccharide (LPS)-induced liver injury

In this study from April 2015, researchers elucidated the protective effect of oral administration of tributyrin against LPS-mediated lipid metabolism disorder in rats.  Tributyrin suppresses lipopolysaccharide (LPS)-induced liver injury through attenuating nuclear factor-κB activity with an increased hepatoportal butyrate level.  25

Inflammation

Another study from May 2015 was carried out to investigate the effects of tributyrin (TB) on the growth performance, pro-inflammatory cytokines, intestinal morphology, energy status, disaccharidase activity, and antioxidative capacity of broilers challenged with lipopolysaccharide (LPS).

Taken together, these results suggest that the TB supplementation was able to reduce the release of pro-inflammatory cytokines and improve the energy status and anti-oxidative capacity in the small intestine of LPS-challenged broilers.  26

ELiE Health Solutions

Tributyrin is now available for purchase by consumers and professionals directly from ELiE Health Solutions as a product called BUTYCAPS.

ELiE Health Solutions, based in Sevilla, Spain, was formed through a project based on the science of the microbiota and probiotics.

ELiE Health Solutions is named after Elie Metchnikoff, famed microbiologist and the recipient of the 1908 Nobel Price in Physiology. A century ago he proposed the benefit of acid lactic bacteria to the human host and their role in health and longevity.

David Manrique, a pharmacist with ELiE Health Solutions describes the challenges of finding a more bio-available form of butyric acid:

“The challenge was to find a chemical form of enteric release of butyric acid, and also to ensure microencapsulated as slowly and delayed release possible. It has been a great innovative effort, but we are very satisfied with the results.”  27 

ELiE Health Solutions was successful in developing a delayed release form of butyric acid (tributyrin) using microencapsulation technology in their product BUTYCAPS.  The microencapsulation technology of BUTYCAPS allows a slower and gradual release along the intestine. 

BUTYCAPS contains 900 mg of Tributyrin equivalent to 787 mg of butyric acid in each sachet. Each box contains 30 sachets.  BUTYCAPS are non-chewable granules.

170126_3dbutycaps

Figure 5.  BUTYCAPS product from ELiE Health Solutions

BUTYCAPS can be purchased directly from ELiE Health Solutions. 

Figure 6.  Formulation process of microencapsulated tributyrin. (Source:  ELiE Health Solutions)

Resources:

Purchase BUTYCAPS

Cover photo:  Enterocytes were butyrate is taken up in the intestine (Source)

Inhibiting the Fibrillogenesis of Alpha-synuclein and Amyloid-beta by Natural Substances

Synucleinopathies

A group of neurodegenerative disorders characterized by fibrillary aggregates of alpha-synuclein protein in the cytoplasm of selective populations of neurons and glia is called Synucleinopathies or alpha-Synucleinopathies. 

Synucleinopathies include:

  • Parkinson’s disease (PD)
  • Dementia with Lewy bodies (DLB)
  • Pure autonomic failure (PAF)
  • Multiple system atrophy (MSA)

These neurological disorders are characterized by a chronic and progressive decline in the following bodily functions:

  • autonomic
  • behavioral
  • cognitive
  • motor skills

Alpha-synuclein protein

Synucleinopathies are caused by the abnormal accumulation of aggregates of alpha-synuclein protein in:

  • glial cells
  • nerve fibers
  • neurons

Alpha-synuclein is a protein that is abundant in the human brain and is predominantly expressed in the:

  • cerebellum
  • hippocampus
  • neocortex
  • substantia nigra
  • thalamus

It is also found in smaller amounts in the heart, muscles, and other tissues. 

Figure 1.  This a rendering of the Alpha-synuclein protein, based the PDB file of 1XQ8 using Rasmol.  (Source:  Hantanplan)

In the brain, alpha-synuclein is found primarily at the end of the neurons in specialized structures called the presynaptic terminal. The presynaptic terminal is a specialized area within the axon of the presynaptic cell that contains neurotransmitters enclosed in small membrane-bound spheres called synaptic vesicles.  The release of neurotransmitters from the presynaptic terminal relays signals between neurons.  Dysfunctional presynaptic terminals due to aggregation of alpha-synuclein can compromise normal brain function.

Lewy bodies

When alpha-synuclein aggregates, it forms insoluble fibrils in pathological conditions characterized by Lewy bodies.  Alpha-synuclein is the primary structural component of Lewy body fibrils, even though Lewy bodies may also contain:

  • alpha B crystallin
  • neurofilament protein
  • tau protein
  • ubiquitin

Lewy neurites are abnormal neurites in diseased neurons, containing granular material and abnormal alpha-synuclein filaments similar to those found in Lewy bodies.

Figure 2.  Microscope photograph of a Lewy body  (Source:  By Dr. Andreas Becker upload here Penarc – Own work, CC BY-SA 3.0)

Inhibiting the Fibrillogenesis of alpha-synuclein and amyloid-beta by Natural Substances

Researchers have focused on finding ways to inhibit the fibrillogenesis of alpha-synuclein in order to halt the formation of pathological conditions characterized by Lewy bodies.

Beginning in 2008, then in 2010 and 2011, researchers have been able to identify two natural substances that not only inhibits the fibrillogenesis of alpha-synuclein, but also at the same time inhibits amyloid-beta fibrillogenesis, the major cause of vascular dementia and Alzheimer’s disease.

These two natural substances include:

  • (-)-epigallocatechin gallate  (EGCG)  
  • theaflavins  

(-)-epigallocatechin gallate (EGCG) is found in high content in the dried leaves of white tea (4245 mg per 100 g), green tea (7380 mg per 100 g) and, in smaller quantities, black tea.  Smaller trace amounts can be found in apple skin, plums, onions, hazelnuts, and pecans.

Theaflavins are formed from the condensation of flavan-3-ols in tea leaves during the enzymatic oxidation of black tea.

In 2008, researchers demonstrated the redirection of amyloid fibril formation through the action of a small molecule, resulting in off-pathway, highly stable oligomers.

The polyphenol (-)-epigallocatechin gallate efficiently inhibits the fibrillogenesis of both alpha-synuclein and amyloid-beta by directly binding to the natively unfolded polypeptides and preventing their conversion into toxic, on-pathway aggregation intermediates. Instead of beta-sheet-rich amyloid, the formation of unstructured, nontoxic alpha-synuclein and amyloid-beta oligomers of a new type is promoted, suggesting a generic effect on aggregation pathways in neurodegenerative diseases.  1

Researchers in 2010 reconfirmed the fact that the polyphenol (-)-epi-gallocatechine gallate (EGCG) inhibits alpha-synuclein and amyloid-beta fibrillogenesis.  2  They showed that EGCG has the ability to convert large, mature alpha-synuclein and amyloid-beta fibrils into smaller, amorphous protein aggregates that are nontoxic to mammalian cells.

Finally, in 2011, researchers showed that theaflavins (TF1, TF2a, TF2b, and TF3), the main polyphenolic components found in fermented black tea, are potent inhibitors of amyloid-beta and alpha-synuclein fibrillogenesis.  3  Theaflavins stimulate the assembly of amyloid-beta and alpha-synuclein into nontoxic, spherical aggregates that are incompetent in seeding amyloid formation and remodel amyloid-beta fibrils into nontoxic aggregates.

Their conclusion suggested that theaflavins might be used to remove toxic amyloid deposits.

These three studies confirm the fact that adding green tea, white tea and/or black tea to your diet in order to obtain both EGCG and theaflavins may be a promising therapy to prevent Synucleinopathies, Dementia and Alzheimer’s disease.   

Cover photo credit: SUNY Oneonta

Delaying the Chronological Aging of the Yeast Saccharomyces cerevisiae by Six Plant Extracts

Researchers from Concordia University in Montreal, Quebec, Canada, in collaboration with the Quebec-based biotech company Idunn Technologies, published a study in the Journal Oncotarget on 29 March 2016, describing their discovery of six plant extracts that increase yeast chronological lifespan to a significantly greater extent than any of the presently known longevity-extending chemical compounds.  1

For the study, the researchers examined many plant extracts that would increase the chronological lifespan of yeast.  They finally found and used 37 plant extracts for this study.  These plant extracts are listed in the Table 1 below:

Table 1: List of plant extracts that have was used in this study

Abbreviated nameBotanical namePlant part used
PE1Echinacea purpureaWhole plant
PE2Astragalus membranaceousRoot
PE3Rhodiola rosea L.Root
PE4Cimicifuga racemosaRoot and rhizome
PE5Valeriana officinalis L.Root
PE6Passiflora incarnate L.Whole plant
PE7Polygonum cuspidatumRoot and rhizome
PE8Ginkgo bilobaLeaf
PE9Zingiber officinale RoscoeRhizome
PE10Theobroma cacao L.Cacao nibs
PE11Camellia sinensis L. KuntzeLeaf
PE12Apium graveolens L.Seed
PE13Scutellaria baicalensisRoot
PE14Euterpe oleraceaFruit
PE15Withania somniferaRoot and leaf
PE16Phyllanthus emblicaFruit
PE17Camellia sinensisLeaf
PE18Pueraria lobataRoot
PE19Silybum marianumSeed
PE20Eleutherococcus senticosusRoot and stem
PE21Salix albaBark
PE22Glycine max L.Bean
PE24Calendula officinalisFlower
PE25Salvia miltiorrhizaRoot
PE27Panax quinquefoliumRoot
PE28Harpagophytum procumbensRoot
PE29Olea europaea L.Leaf
PE30Gentiana luteaRoot
PE31Piper nigrumFruit
PE32Aesculus hippocastanumSeed
PE33Mallus pumila Mill.Fruit
PE34Fragaria spp.Fruit
PE35Ribes nigrumLeaf
PE36Dioscorea oppositaRoot
PE37Cinnamomum verumBark

Table source:  Discovery of plant extracts that greatly delay yeast chronological aging and have different effects on longevity-defining cellular processes

The means by which these six plant extracts (PEs) delays the onset and decreases the rate of yeast chronological aging is by eliciting a hormetic stress response. The budding yeast Saccharomyces cerevisiae is a beneficial model organism for the discovery of genes, signaling pathways and chemical compounds that slow cellular and organismal aging in eukaryotes across phyla.  Yeast was chosen in this study because aging progresses similarly in both yeast and humans.

The six PEs that were identified include:  2

  • Black Cohosh (Cimicifuga racemosa) (PE4)
  • Valerian  (Valeriana officinalis L.)  (PE5)
  • Passion Flower  (Passiflora incarnata L.)  (PE6)
  • Ginko Biloba  (Ginko biloba)  (PE8)
  • Celery Seed  (Apium graveolens L.)  (PE12)
  • White Willow  (Salix alba)  (PE21)

 

The six identified PEs out of the thirty-seven PEs that were examined showed the highest percentage increase of lifespan, (also known as the chronological lifespan (CLS)), in the yeast,   The researchers determined both the mean (average) CLS and the maximum CLS of the six PEs.

Table 2 below list the six PEs and their mean and max. CLS:

Table 2: Percent increase of lifespan of S. cerevisiae by 6 PEs

Plant Extract (PE)Mean CLSMax CLS
PE4 (Black Cohosh)195%100%
PE5 (Valerian)185%87%
PE6 (Passion Flower)180%80%
PE8 (Ginko Biloba)145%104%
PE12 (Celery Seed)160%107%
PE21 (White Willow)475%369%
CLS - Chronological Lifespan

(Source:  Discovery of plant extracts that greatly delay yeast chronological aging and have different effects on longevity-defining cellular processes)

The researchers noted that PE21 appears to be the most potent longevity-extending pharmacological intervention presently known. It increases the mean and maximum CLS of yeast by 475% and 369%, respectively.  PE21 or White Willow bark represents a much greater effect than rapamycin and metformin, the two best drugs known for their anti-aging effects.

These findings by the researchers imply that these extracts slow aging in the following ways:  3

  • PE4 (Black Cohosh) decreases the efficiency with which the pro-aging TORC1 pathway inhibits the anti-aging SNF1 pathway;
  • PE5 (Valerian) mitigates two different branches of the pro-aging PKA pathway;
  • PE6 (Passion Flower) coordinates processes that are not assimilated into the network of presently known signaling pathways/protein kinases;
  • PE8 (Ginko biloba) diminishes the inhibitory action of PKA on SNF1;
  • PE12 (Celery Seed) intensifies the anti-aging protein kinase Rim15; and
  • PE21 (White Willow) inhibits a form of the pro-aging protein kinase Sch9 that is activated by the pro-aging PKH1/2 pathway.

The researchers showed that each of these six PEs decelerates yeast chronological aging and has different effects on several longevity-defining cellular processes, as illustrated in Figure 1.

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Figure 1.  A model for how PE4, PE5, PE6, PE8, PE12 and PE21 delay yeast chronological aging via the longevity-defining network of signaling pathways/protein kinases.  Activation arrows and inhibition bars denote pro-aging processes (displayed in blue color) or anti-aging processes (displayed in red color). Pro-aging or anti-aging signaling pathways and protein kinases are displayed in blue or red color, respectively.  (Source: Discovery of plant extracts that greatly delay yeast chronological aging and have different effects on longevity-defining cellular processes)

Each of the six PEs have different effects on cellular processes that define longevity in organisms across phyla. These effects include the following:

  • increased mitochondrial respiration and membrane potential;
  • augmented or reduced concentrations of reactive oxygen species;
  • decreased oxidative damage to cellular proteins, membrane lipids, and mitochondrial and nuclear genomes;
  • enhanced cell resistance to oxidative and thermal stresses; and
  • accelerated degradation of neutral lipids deposited in lipid droplets.

The researchers also revealed that certain combinations of the six PEs could markedly increase aging-delaying proficiencies of each other.

In conclusion, the study stated that the obvious challenge was to assess whether any of the six PEs can delay the onset and progression of chronic diseases associated with human aging.  Idunn Technologies is collaborating with four other universities for six research programs, to go beyond yeast, and work with an animal model of aging, as well as two cancer models.  4

This study and ongoing research reveals five features of the six PEs as potential interventions for decelerating chronic diseases of old age. These five features include:  5

  • the six PEs are caloric restriction (CR) mimetics that imitate the aging-delaying effects of the CR diet in yeast under non-CR conditions;
  • they are geroprotectors that slow yeast aging by eliciting a hormetic stress response;
  • they extend yeast longevity more efficiently than any lifespan-prolonging chemical compound yet described;
  • they delay aging through signaling pathways and protein kinases implicated in such age-related pathologies as type 2 diabetes, neurodegenerative diseases, cardiac hypertrophy, cardiovascular disease, sarcopenia and cancers; and
  • they extend longevity and delay the onset of age-related diseases in other eukaryotic model organisms.