Monthly Archives: February 2016

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Geroprotectors: Agents for Prolonging the Lifespan of Animals

A geroprotector is one of the five different types of senotherapeutic strategies that aims to affect the root cause of aging and age-related diseases, and thus prolong the life span of animals.  Geroprotectors utilize agents and strategies which prevent or reverse the senescent state by preventing triggers of cellular senescence, including:

  • DNA damage
  • Oxidative stress
  • Proteotoxic stress
  • Telomere shortening

Senotherapeutics refers to therapeutic agents and strategies that specifically target cellular senescence and include any of the following therapies:

  • Gene therapy
  • Geroprotectors
  • Immune clearance of senescent cells
  • SASP inhibitors
  • Senolytics

An excellent and resourceful database of current geroprotectors is Geroprotectors.org.

According to the geroprotectors website, the purpose of the database is described:

“The Geroprotectors.org database comprises more than 250 life-extension experiments in 11 wild-type model organisms (including M. musculus and C. elegans, among others). We gathered data about more than 200 chemicals promoting longevity, including compounds approved for human use. This database integrates information about lifespan-increasing experiments and related compounds, suppression of aging mechanisms, activation of longevity mechanisms and age-related diseases obtained from research papers and databases.

Geroprotectors.org is intended as a tool for accelerating the process of identifying geroprotectors from a variety of existing substances through pharmacological modeling and biostatistical analysis to reveal new substances with geroprotective effects.”

They further define a geroprotector as follows:

“A “geroprotector” is any intervention that aims to increase longevity, or that reduces, delays or impedes the onset of age-related pathologies by hampering aging-related processes, repairing damage or modulating stress resistance.”

Examples of various geroprotectors from the database include:

  • Baicalein  1
  • Berberine  2
  • Carnosine  3
  • Glutathione  4

Informational References:

Geroprotectors.org


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Spermidine Promotes Longevity through the Induction of Autophagy

Spermidine is a polyamine compound that has various metabolic functions within organisms.   It was originally isolated from semen and is found in ribosomes and living tissues.  

Spermidine is synthesized from putrescine, using an aminopropylic group from decarboxylated S-adenosyl-L-methionine (SAM). The reaction is catalyzed by spermidine synthase.

Spermidine has recently emerged as exhibiting anti-aging properties. Its supplementation increases lifespan and resistance to stress, and decreases the occurrence of age-related pathology and loss of locomotor ability. 

The Table below lists the Spermidine content in certain foods:  1

Spermidine Content in Certain Foods

FoodSpermidine mg/kg
Chickpea~29
Broccoli (cooked)~25
Cauliflower (cooked)~25
Cheddar, 1yr old199.5
chicken liver48.7
Green peas46.6
Mango30
Mushroom88.6
Rice bran50
Soybean,dried (German)128
Soybean,dried (Japanese)207

The mechanism of spermidine at the molecular level appears to multi-faceted, including:  2

  • autophagy
  • inflammation reduction
  • lipid metabolism
  • regulation of cell growth
  • proliferation and death

Research indicates that the main pathway used by Spermidine to effectuate its benefits is the MAPK pathway.  2   The MAPK/ERK pathway (also known as the Ras-Raf-MEK-ERK pathway) is a chain of proteins in the cell that communicates a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell.  The signal starts when a signaling molecule binds to the receptor on the cell surface and ends when the DNA in the nucleus expresses a protein and produces some change in the cell, such as cell division.

Researchers conducted a study wherein they administered spermidine and found that it markedly extended the lifespan of yeast, flies and worms, and human immune cells. In addition, Spermidine administration potently inhibited oxidative stress in ageing mice.

In ageing yeast, Spermidine treatment triggered epigenetic deacetylation of histone H3 through inhibition of histone acetyltransferases (HAT), suppressing oxidative stress and necrosis. Conversely, depletion of endogenous polyamines led to hyperacetylation, generation of reactive oxygen species, early necrotic death and decreased lifespan. The altered acetylation status of the chromatin led to significant upregulation of various autophagy-related transcripts, triggering autophagy in yeast, flies, worms and human cells.

The researchers found that enhanced autophagy is crucial for polyamine-induced suppression of necrosis and enhanced longevity.   3  

Ingestion of Spermidine is either accomplished by consuming foods containing Spermidine (See Table above) or through the conversion of Putrescine to Spermidine.  Putrescine is a precursor for the endogenous production of Spermidine. 

S-Adenosylmethionine (SAMe) is an essential cofactor for the conversion of Putrescine to Spermidine. 

Currently, there are no Spermidine supplements for consumer purchase.


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GABA: Enhancing this Important Neurotransmitter

Gamma-Aminobutyric acid (γ-Aminobutyric acid) or GABA, is the chief inhibitory neurotransmitter in the mammalian central nervous system. It plays the principal role in reducing neuronal excitability throughout the nervous system.

The features of the GABA system are characterized in the following Table:

GABA System

SystemGABA
SystemGABAergic
TypeInhibitory
Lobe of the BrainTemporal lobes
BrainwaveTheta
Brain MeasurementBalance (Calm)
Balanced CharacteristicsCalmness
Stability
Even mood
Make good decisions
Deficiency CharacteristicsHeadaches
Palpitations
Seizures
Anxiety
DietComplex carbohydrates: Brown rice; broccoli; lentils; almonds; bananas; whole grain oats; oranges; spinach; walnuts; whole grain wheat..
SupplementsInositol powder; thiamine; tryptophan; passionflower; melatonin; magnesium; glutamine; niacinamide; pyridoxine; valerian root.

GABA Synthesis

GABA is synthesized from glutamate using the enzyme L-glutamic acid decarboxylase and pyridoxal phosphate (which is the active form of vitamin B6) as a cofactor.

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Figure 1:  GABA Biosynthesis Pathway

The enzymes and cofactors that product GABA are listed in the Table below: 

GABA - Enzymes and CoFactors

Amino Acid/NeuroTEnzymeCofactor(s)
GlutamineGlutaminaseH2O
GlutamateGlutamate decarboxylasePyridoxal 5’-phosphate (P5P) (active form of Vitamin B6)

It is vitally important to not be deficient in Vitamin B6 as it is critical in producing GABA.

GABA Receptor Complex

The GABA receptors are a class of receptors that respond to the neurotransmitter gamma-aminobutyric acid (GABA), the chief inhibitory neurotransmitter in the vertebrate central nervous system.

There are two classes of GABA receptors:

  • GABAa receptors
  • GABAb receptors

GABAa Receptors

The GABAa receptor (GABAaR) is an ionotropic receptor and ligand-gated ion channel. Its endogenous ligand is γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system.

Upon activation, the GABAa receptor selectively conducts Cl− through its pore, resulting in hyperpolarization of the neuron. This causes an inhibitory effect on neurotransmission by diminishing the chance of a successful action potential occurring.

GABAa Receptors

CategoryNatural SubstancesReference
Amino Acids
GABA Not well absorbed - Phenibut
Taurine1
Theanine2
Herbs
Ashwagandha3
MagnoliaHonokiol 4
Valerian5
Hormones
DHEA6
Pregnenolone7
Minerals
Magnesium8
Polyphenols
Amentoflavone [ http://en.wikipedia.org/wiki/Amentoflavone ]9
Quercetin10

GABAb receptors

GABAb receptors (GABAbR) are metabotropic trans-membrane receptors for gamma-aminobutyric acid (GABA) that are linked via G-proteins to potassium channels.

GABAb receptors are found in the central as well as in the autonomic division of the peripheral nervous system.

GABAb Receptors

CategoryNatural SubstanceReference
Amino Acids
GABA Does not cross BBB effectively
Phenibutβ-Phenyl-γ-aminobutyric acid 1

GABA Enhancement and Precursors

The Table below lists the substances that enhance GABA and can be considered precursors of GABA:

Substance that Enhance and are Precursors to GABA

CategoryNatural SubstanceReference
Amino Acids
Glutamine1
Taurine2
Theanine3
GABANot very bioavailable
Herbs
Ginko Biloba4
St. John’s Wort5
Valerian6
Passionflower7
Gastrodinincreases levels of the inhibitory neurotransmitter GABA by as much as 34% 8
Hormones
Melatonin9
Nootropics
Phenibut10
Pyroglutatmate11
Vitamins
Alpha-GPC12
Inositol13
Vitamin B3 (niacinamide) 14
Vitamin B615


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Steaming is the Most Health-Promoting Form of Cooking Cruciferous Vegetables

An interesting study was published in August 2009 in the Journal Zhejiang University Science B entitled Effects of different cooking methods on health-promoting compounds of broccoli in which the researchers determined that of the five cooking methods, including:

  • steaming
  • microwaving
  • boiling
  • stir-frying
  • stir-frying followed by boiling (stir-frying/boiling)

steaming retained the highest levels of chlorophyll, vitamin C, soluble proteins and soluble sugars.  1 

In addition, steaming demonstrated less modifications to total aliphatic and indole glucosinolates which led to the lowest loss of total glucosinolates.  Whereas, stir-frying and stir-frying/boiling presented the highest loss of glucosinolates.

The researchers concluded that stir-frying and stir-frying/boiling cause great losses of chlorophyll, soluble protein, soluble sugar, vitamin C, and glucosinolates, but the steaming method appears the best in retention of the nutrients in cooking broccoli.

The researchers determined the main aliphatic glucosinolates in the tested broccoli were:

  • glucoraphanin
  • glucoiberin

The main indole glucosinolates were:

  • glucobrassicin
  • neoglucobrassicin

The chlorophyll content in boiled, stir-fried/boiled, stir-fried, and microwaved broccoli was reduced by 27%, 23%, 18%, and 16%, respectively (P<0.05), while it was almost unchanged in steamed broccoli.  3

An external file that holds a picture, illustration, etc. Object name is JZUSB10-0580-fig01.jpg

Figure 1:  Each value is mean±SD of three replicate samples. Values not sharing a common letter are significantly different at P<0.05. Cooking methods: 1. Raw; 2. Boiled; 3. Streamed; 4. Microwaved; 5. Stir-fried; 6. Stir-fried/boiled  (Source:  Effects of different cooking methods on health-promoting compounds of broccoli)


 

The highest contents of total soluble proteins and soluble sugars (2.6 m/g FW and 3.5 mg/g FW, respectively) in broccoli were obtained after steaming. The lowest retention of total soluble proteins was observed in broccoli after boiling and stir-frying/boiling, while the lowest retention of total soluble sugars was found in broccoli after stir-frying/boiling and stir-frying.  4

An external file that holds a picture, illustration, etc. Object name is JZUSB10-0580-fig02.jpg

Figure 2:  Each value is mean±SD of three replicate samples. Values not sharing a common letter are significantly different at P<0.05. Cooking methods: 1. Raw; 2. Boiled; 3. Streamed; 4. Microwaved; 5. Stir-fried; 6. Stir-fried/boiled  (Source:  Effects of different cooking methods on health-promoting compounds of broccoli)


 

The greatest loss of vitamin C was observed in broccoli after stir-frying/boiling and boiling (38% and 33%, respectively) treatments, followed by microwaving and stir-frying (16% and 24%, respectively) treatments. In contrast, steaming did not cause any significant loss of vitamin C, compared with the raw sample.  5

An external file that holds a picture, illustration, etc. Object name is JZUSB10-0580-fig03.jpg

Figure 3:  Each value is mean±SD of three replicate samples. Values not sharing a common letter are significantly different at P<0.05. Cooking methods: 1. Raw; 2. Boiled; 3. Streamed; 4. Microwaved; 5. Stir-fried; 6. Stir-fried/boiled  (Source:  Effects of different cooking methods on health-promoting compounds of broccoli)


 

The contents of total aliphatic and indole glucosinolates in broccoli after different cooking treatments are presented in Fig.​Fig.4.4. Total aliphatic glucosinolates were significantly decreased by 55%, 54%, 60%, and 41%, respectively in stir-fried, stir-fried/boiled, microwaved, and boiled broccoli (P<0.05). However, the contents of total aliphatic glucosinolates remained almost unchanged in steamed broccoli.  6

An external file that holds a picture, illustration, etc. Object name is JZUSB10-0580-fig04.jpg

Figure 4:  Each value is mean±SD of three replicate samples. Values not sharing a common letter are significantly different at P<0.05. DW: dry weight. Cooking methods: 1. Raw; 2. Boiled; 3. Streamed; 4. Microwaved; 5. Stir-fried; 6. Stir-fried/boiled  (Source:  Effects of different cooking methods on health-promoting compounds of broccoli)


 

The main glucosinolate found in broccoli is glucoraphanin.  When raw or steamed broccoli is consumed consumed, the enzyme myrosinase transforms glucoraphanin into raphanin and into sulforaphane, which exhibits anti-cancer and antimicrobial properties in experimental models.   2

Other important glucosinolates include:

  • Glucotropaeolin is the precursor to benzyl isothiocyanate
    • Glucotropaeolin is a phytochemical from Tropaeolum majus, which is commonly known as garden nasturtium, Indian cress or monks cress.
  • Gluconasturtiin is the precursor to phenethyl isothiocyanate
    • Gluconasturtiin is named from its occurrence in watercress (Nasturtium officinale) and horseradish (Armoracia rusticana)
  • Sinigrin is the precursor to allyl isothiocyanate
    • Sinigrin is found in some plants of the Brassicaceae family such as Brussels sprouts, broccoli, and the seeds of black mustard (Brassica nigra)

 


Resources:

Sur La Table® Bamboo Steamers

Bella 7-Liter Multi-Tier Food Steamer

 


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Phase III Detoxification: Transporters of Phase 2 Products from the Cell

After the completion of Phase II conjugation, unwanted compounds are now hydrophilic and ready for excretion from the cell. However, these compounds still remain in the cell and must be transported out of the cell in order for them to be eliminated from the body. This is obviously a vital function in the detoxification process and is accomplished by none other than the efflux transporters or efflux pumps -the same efflux pumps involved in the antiporter mechanism. It is this process, of transporting Phase II conjugates out of the cell, which is now being referred to as Phase III.

Phases-of-Detoxification

Phase III transporters, for example, P-glycoprotein (P-gp), are expressed in many tissues such as the liver, intestine, kidney, and brain.  Phase III transporters are present in many tissues, including the liver, intestines, kidneys, and brain, where they can provide a barrier against xenobiotic entry, or a mechanism for actively moving xenobiotics and endobiotics in and out of cells. Since water-soluble compounds require specific transporters to move in and out of cells, phase III transporters are necessary to excrete the newly formed phase II products out of the cell.

In the liver, phase III transporters move glutathione, sulfate, and glucuronide conjugates out of cells into the bile for elimination. In the kidney and intestine, phase III transporters can remove xenobiotics from the blood for excretion from the body.  Phase III transporters act to remove phase II products to the extracellular medium, where they may be further metabolised or excreted.

antiporter activity (p-glycoprotein or multi-drug resistance) has been defined as the Phase III detoxification system.  The antiporter is an energy-dependent efflux pump, which pumps xenobiotics out of a cell, thereby decreasing the intracellular concentration of xenobiotics.

The antiporter is an energy dependent efflux pump (transport protein), contained within the enterocytes, whose function is to export unwanted compounds immediately back into the intestines. Once the exported unwanted compound arrives back into the intestine one of several things can take place:

  • It can be eliminated in the stool
  • It can re-enter the enterocyte only to be exported back out into the intestine and start the cycle over again
  • It can re-enter the enterocyte and pass into the blood stream and travel to the liver
  • It can re-enter the enterocyte and be acted on by the Phase I CYP3A4 enzymes thereby starting the biotransformation process before it is passed into the blood stream to travel to the liver

This makes antiporter activity an important factor in the first pass metabolism of pharmaceuticals and other xenobiotics. First pass effect is the biotransformation of unwanted compounds by intestinal enzymes and the liver before the compound reaches systemic circulation.

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Figure 1 Phase III Transporters:  The Antiporter

Efflux transporters / pumps serve a dual function with the Phase III terminology used to refer to both functions of:

  • Phase III metabolism – transporters act by eliminating both endogenous and exogenous Phase II conjugated metabolites from hepatocytes and other tissues
  • Antiporter action – transporters acting as nature’s gatekeeper for cellular entry by eliminating unwanted compounds pre-biotransformation

More than 350 unique human transporters have been identified. The best known and most studied transporter is the P-glycoprotein.  Efflux transporters can also be induced –increasing the transporters activity, and can be inhibited – causing substrate levels to become higher.

Table 1:  Activators and Inhibitors of Phase 3 Detoxification

Activators and Inhibitors of Phase 3

 

 

Activator/Inhibitor

Substance

Activators

 

 

Apple Polyphenols

 

Sulforaphane from Cruciferous vegetables

 

Licorice

Inhibitors

 

 

Curcumin

 

Resveratrol

 

Milk Thistle (Silymarin)

Several transport proteins (cMOAT, OAT, MRP1, MRP2, GS-X) of the phase 3 detoxification system can be enhanced by the following substances:

  • sufficient water ingestion
  • green foods
    • Spirulina
    • Chlorella
    • Barley grass
    • Wheatgrass

Prevention of absorption through trapping of potential toxins (such as surface adhesion to another molecule in the gut, like activated charcoal or kaolin clay) is an effective means of mitigating exposure; this mechanism has the requirement of some dietary adsorbent to be taken while the toxin is in transit in the GI tract. Uptake of potential toxins and their detoxification by beneficial colonic microflora could have a similar effect.

Bile Flow and Excretion

The liver’s third detoxification process involves the synthesis and secretion of bile. Each day the liver manufactures bile, which serves as a carrier in which many toxic substances are effectively eliminated from the body. Sent to the intestines, the bile and its toxic load is absorbed by fiber and excreted from the body.  However, a diet low in fiber means these toxins are not bound effectively and may be reabsorbed.

The liver’s second detoxification process involves the synthesis and secretion of bile for the elimination of modified toxins. Each day the liver manufactures approximately 1 quart of bile, which serves as a carrier in which many toxic substances are dumped into the intestines. In the intestines, the bile and its toxic load are absorbed by fiber and excreted. However, a diet low in fiber results in inadequate binding and reabsorption of the toxins. This problem is magnified when bacteria in the intestine modify these toxins to more damaging forms.

When the excretion of bile is inhibited (i.e. cholestasis), toxins stay in the liver longer. Cholestasis has several causes, including obstruction of the bile ducts and impairment of bile flow within the liver. The most common cause of obstruction of the bile ducts is the presence of gallstones. Perhaps the most common cause of cholestasis and impaired liver function is alcohol ingestion. In some especially sensitive individuals, as little as 1 ounce of alcohol can produce damage to the liver, which results in fat being deposited within the liver. All active alcoholics demonstrate fatty infiltration of the liver.

It is important to get the toxins out the the liver as fast as possible.  This can be down by increasing the flow of bile.  The role of fiber is very important in this instance since once the bile (with the toxins) is secreted into the intestines, there must be adequate fiber for the bile to bind to for elimination from the body.

Impairment of bile flow is going to reduce the bodies ability to eliminate toxins.  This is typically caused by a congested liver, inflammation and scarring of the bile duct and/or gall stones.

The compounds that help improve bile flow include:

Table 2:  Foods, Spices and Vitamins/Amino Acids that Improve Bile Flow

Improved Bile Flow

 

 

Category

Substance

Food

 

 

Garlic

 

Onions

 

Beet root

 

Lecithin

 

Resveratrol

 

Artichoke

 

Yarrow

 

Dandelion root

Spices

 

 

Ginger

 

Cumin

 

Curry

 

Fennel

 

Ajowan (carom seed)

 

Milk Thistle (Silymarin)

 

Tumeric

Vitamins and Amino Acids

 

 

Taurine

 

Vitamin C

 


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Natural Substances that Enhance the Health of the Spinal Cord

The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the medulla oblongata in the brainstem. The brain and spinal cord together make up the central nervous system (CNS).

The spinal cord begins at the occipital bone and extends down to the space between the first and second lumbar vertebrae; it does not extend the entire length of the vertebral column. It is around 45 cm (18 in) in men and around 43 cm (17 in) long in women. Also, the spinal cord has a varying width, ranging from 13 mm (1⁄2 in) thick in the cervical and lumbar regions to 6.4 mm (1⁄4 in) thick in the thoracic area. The enclosing bony vertebral column protects the relatively shorter spinal cord.

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Figure 1  Spinal Cord

The spinal cord functions primarily in the transmission of neural signals between the brain and the rest of the body but also contains neural circuits that can independently control numerous reflexes and central pattern generators.

The spinal cord has three major functions: as a conduit for motor information, which travels down the spinal cord, as a conduit for sensory information in the reverse direction, and finally as a center for coordinating certain reflexes.  1

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Figure 2  Gross anatomy of the spinal cord

The human spinal cord is divided into 31 different segments. At every segment, right and left pairs of spinal nerves (mixed; sensory and motor) form. Six to eight motor nerve rootlets branch out of right and left ventro lateral sulci in a very orderly manner. Nerve rootlets combine to form nerve roots. Likewise, sensory nerve rootlets form off right and left dorsal lateral sulci and form sensory nerve roots. The ventral (motor) and dorsal (sensory) roots combine to form spinal nerves (mixed; motor and sensory), one on each side of the spinal cord.

The Table below list the natural substance that can enhance the health of the spinal cord, especially post spinal cord injury:

Natural Substances that Enhance the Health of the Spinal Cord

CategorySubstanceReference
Amino Acids
Acetyl-L-Carnitine (ALCAR)1
Glycine2
N-Acetyl-Cysyteine (NAC)3
Taurine4
Herbs
Ginko Biloba5
St. John’s Wort6
Skullcap (Scutellaria baicalensis)7
Hormones
Pregnenolone8
Progesterone9
Lipids
DHA10
Omega 3 Fatty Acids11
Minerals
Magnesium12
Selenium13
Nootropics
CDP-Choline14
Polyphenols
Curcumin15
Quercetin16
Vitamins
Folic Acid17
Vitamin B12 (Methylcobalamin)18
Vitamin C19
Vitamin E20
Vitamin D21


Informational Reference:

BioFoundations – Natural Substances that Enhance the Health of the Spinal Cord (PDF)

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


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Nimbolide from Neem (Azadirachta indica) Inhibits Pancreatic Cancer Growth and Metastasis

Neem, also known as Nimtree or Indian Lilac is known by its botanical name, Azadirachta indica, and is a tree in the mahogany family Meliaceae.  It is one of two species in the genus Azadirachta, and is native to India and the Indian subcontinent including Nepal, Pakistan, Bangladesh and Sri Lanka.

Neem-Tree

Neem tree

Neem (नीम) is a Hindi noun derived from Sanskrit Nimba (निंब).

Neem leaves and Neem leaf products have been traditionally used in Ayurvedic medicine for centuries.  Ayurevedic practitioners have used Neem leaves and the oil for a number of conditions and believe it to be:  1

  • antihelmenthic
  • antifungal
  • antidiabetic
  • antibacterial
  • antiviral

Researchers have identified more than 135 compounds from different parts of Neem, primarily from the leaves and seeds.  A short list of the chemical constituents of Neem are as follows:  2

  • isoprenoids
  • protomeliacins
  • limonoids
  • azadirone
  • secomeliacins
  • nimbin
  • salanin
  • azadirachtin
  • isomeldenin
  • nimbin
  • nimbinene
  • 6-desacetyllnimbinene
  • nimbandiol, immobile
  • nimocinol
  • quercetin
  • beta-sitosterol
  • zafaral [24,25,26,27-tetranorapotirucalla-(apoeupha)-6alpha-methoxy-7alpha-acetoxy-1,14-dien-3,16-dione-21-al]
  • meliacinanhydride [24,25,26,27-tetranorapotirucalla-(apoeupha)-6alpha-hydroxy,11alpha-methoxy-7alpha,12alpha-diacetoxy,1,14,20(22)-trien-3-one]

One very important tetranortriterpenoid limonoid isolated from the leaves and flowers of Neem is Nimbolide.  3  This limonoid has been shown to possess numerous biological activities such as:

  • antifeedant  4
  • antimalarial  5 
  • antimicrobial  6 
  • anticancer   7  8  9  10  11 

Nimbolide exhibits antiproliferative activity in a wide variety of tumor cells, including:

  • neuroblastoma
  • osteosarcoma
  • choriocarcinoma  12 
  • cervical cancer  13 
  • leukemia
  • melanoma  14
  • colorectal cancer  15 

Chemoprevention is a strategy by using medicines to treat a precancerous condition or to keep cancer from starting and to reverse or retard the multistep process of carcinogenesis.

Nimbolide is such a potenetial natural medicine used for chemoprevention since it exhibits multiple pharmacological effects by inhibiting tumorigenesis and metastasis without any toxicity and unwanted side effects.

Nimbolide exhibits anticancer activity through selective modulation of multiple cell signaling pathways linked to:  16

  • inflammation
  • survival
  • growth
  • invasion
  • angiogenesis
  • metastasis

A study published 25 January 2016 in Nature.com Scientifc Reports entitled “Nimbolide inhibits pancreatic cancer growth and metastasis through ROS-mediated apoptosis and inhibition of epithelial-to-mesenchymal transition”, assessed the anticancer properties of nimbolide against pancreatic cancer.

The researchers stated:

“Our data reveal that nimbolide induces excessive generation of reactive oxygen species (ROS), thereby regulating both apoptosis and autophagy in pancreatic cancer cells. Experiments with the autophagy inhibitors 3-methyladenine and chloroquine diphosphate salt and the apoptosis inhibitor z-VAD-fmk demonstrated that nimbolide-mediated ROS generation inhibited proliferation (through reduced PI3K/AKT/mTOR and ERK signaling) and metastasis (through decreased EMT, invasion, migration and colony forming abilities) via mitochondrial-mediated apoptotic cell death but not via autophagy. In vivo experiments also demonstrated that nimbolide was effective in inhibiting pancreatic cancer growth and metastasis. Overall, our data suggest that nimbolide can serve as a potential chemo–therapeutic agent for pancreatic cancer.”  17

An area of further research is the complex interplay between apoptosis and autophagy resulting from the nimbolide-induced boost in ROS.  In this study, the anti-cancer effect of nimbolide seems to be via apoptosis, and not via autophagy, which other studies suggest may actually increase cancer cell survival.


Resources:

Organic India – Neem

TheraNeem Organix Neem Leaf

Himalaya Herbal Healthcare Neem


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Piperlongumine from Long Pepper Selectively Kills Cancer Cells

Long pepper and sometimes called Indian Long Pepper is known by its botanical name Piper longum.  It is a flowering vine in the family Piperaceae, and its fruit is dried and used as a spice or seasoning.  Distinguished from its close relative, Piper nigrum, Long Pepper is a hotter variety.

800px-Piper_longum_plant

Piper longrum plant. Source: By I,, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=2228700

Long Pepper contains two main alkaloids:

  • Piperine
  • Piperlonguminine       
PL

Piperlongumine molecule

Piperlongumine has been recently been shown in 2011 that it may have anti-cancer properties by selectively killing some types of cancer cells and ignoring normal cells.  1

The study was published online on 13th July 2011 in Nature, and researchers at the Broad Institute and Massachusetts General Hospital (MGH) discovered that Piperlongumine blocks the response to oxidative stress selectively in cancer cells but spares normal cells.

The researchers tested Piperlongumine against cancer cells and normal cells engineered to develop cancer. The researchers injected mice with human bladder, breast, lung, or melanoma cancer cells.  They then administered Piperlongumine to the mice and discovered that it inhibited tumor growth in the cancerous mice but showed no toxicity in normal mice.

A second test was conducted with mice that developed breast cancer spontaneously.  The results showed that , Piperlongumine blocked both tumor growth and metastasis.

What the researchers realized is that Piperlongumine increases reactive oxygen species (ROS) and apoptotic cell death in both cancer cells but no effect on normal cells.  Essentially Piperlongumine induces apoptosis selectively in cancerous cells.

The researchers stated that:

“The novelty of this compound was that it was able to recognize cancer cells from normal cells.”  2


Informational Reference:

U.S. Patent US20090312373 A1 – Methods for the treatment of cancer using piperlongumine and piperlongumine analogs


Resources:

Long Pepper – Spice Jungle

Organic India, Trikatu


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Vitamin E Needed for Getting DHA into the Brain

Findings in an article published in The Journal of Lipid Research (First Published on April 8, 2015, doi: 10.1194/jlr.M058941) indicates that vitamin E deficiency may cause neurological damage by interrupting a supply line of specific nutrients and robbing the brain of the “building blocks” it needs to maintain neuronal health.

A story appeared on the Oregon State University website entitled Mechanism outlined by which inadequate vitamin E can cause brain damage (04/13/2015) that outlines and describes the findings in The Journal of Lipid Research article.

Read:  Mechanism outlined by which inadequate vitamin E can cause brain damage (04/13/2015) (Oregon State University)

Foods that are highest in Vitamin E (tocopherols and tocotrienols) are:

  • Almonds, raw or dry roasted
  • Avocado and avocado oil
  • Blueberries
  • Collard greens, cooked
  • Egg yoke
  • Milk
  • Mustard greens, cooked
  • Olives and olive oil
  • Papaya
  • Raw sunflower seeds and sunflower oil
  • Spinach, cooked
  • Swiss chard, cooked
  • Turnip greens, cooked
  • Wheat germ and wheat germ oil

VitaminEChart


References:

Novel function of vitamin E in regulation of zebrafish (Danio rerio) brain lysophospholipids discovered using lipidomics, Jaewoo Choi, Scott W. Leonard, Katherine Kasper, Melissa McDougall, Jan F. Stevens, Robert L. Tanguay and Maret G. Traber


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Eggshell Membrane for the Treatment of Joint and Connective Tissue Pain

Eggshell membrane is a dietary supplement made from chicken eggs. It is used for :

  • Osteoarthritis
  • Stiffness and pain of the joints

The membrane is the clear film lining the eggshell, visible when one peels a boiled egg. Eggshell membrane is composed of: [1]

  • Collagen
  • Glycosaminoglycans
    • Chondroitin sulfate
    • Dermatan sulfate
  • Sulfated glycoproteins
    • Glucosamine
  • Hyaluronic acid
  • Sialic acid
  • Desmosine
  • Isodesmosine
  • Ovotransferrin
  • Lysyl oxidase
  • Lysozyme
  • β-N-acetylglucosaminidase

Natural Eggshell Membrane (NEM®) is a possible new effective and safe therapeutic option for the treatment of pain and inflexibility associated with joint and connective tissue (JCT) disorders. Supplementation with NEM®, 500 mg taken once daily, significantly reduced pain, both rapidly (seven days) and continuously (30 days).

It also showed clinically meaningful results from a brief responder analysis, demonstrating that significant proportions of treated patients may be helped considerably from NEM® supplementation. [2]

The Clinical Trial Registration numbers for these trials are: NCT00750230 and NCT00750854.


References:

[1] Eggshell membrane: a possible new natural therapeutic for joint and connective tissue disorders. Results from two open-label human clinical studies.

[2] Eggshell membrane: A possible new natural therapeutic for joint and connective tissue disorders. Results from two open-label human clinical studies

NEM Brand Eggshell Membrane Effective in the Treatment of Pain Associated with Knee and Hip Osteoarthritis: Results from a Six Center, Open Label German Clinical Study


Resources:

100% Natural Eggshell Membrane – Swansons


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