Monthly Archives: June 2017

image_pdfimage_print

Beta-hydroxybutyrate Extends Lifespan and Protects Against Certain Neurological Diseases

Ketone bodies

Ketone bodies are produced by the liver from fatty acids under the following conditions:

  • low food intake (fasting)
  • low carbohydrate diets (ketogenic diet)
  • starvation
  • prolonged intense exercise

There are three water soluble ketone bodies:

  • acetone
  • acetoacetate
  • beta-hydroxybutyric acid

Image result for ketone bodies

Figure 1.  Ketone bodies  (Source)

Ketone bodies are converted to acetyl-CoA in the mitochondria which is then oxidized in the citric acid cycle to produce energy in the form of ATP.

Beta-hydroxybutyrate  (Beta-Hydroxybutyric acid)

Beta-Hydroxybutyric acid is synthesized in the liver from acetoacetate.  Beta-Hydroxybutyric acid is able to cross the blood-brain-barrier into the central nervous system.

Image result for Beta-Hydroxybutyric acid

Figure 1.  Beta-hydroxybutyric acid molecule

It has been determined that beta-hydroxybutyric acid has clinical relevance in a number of health related matters:

  • found to act as a histone deacetylase (HDAC) inhibitor.  1 
  • found to increase brain-derived neurotrophic factor (BNDF) levels  2
  • found to increase TrkB signaling in the hippocampus  3 

Beta-Hydroxybutyric acid extends lifespan in C. elegans

A study published in the Journal Aging in August 2014 demonstrated that beta-hydroxybutyric acid (BHB) supplementation extended mean lifespan of the worm C. elegans by approximately 20%.  4

Image result for c. elegans

Figure 3.  Caenorhabditis elegans nimatode (roundworm); C. elegans has been a model organism for research into ageing

What the researchers of this study discovered was that supplementing with BHB had the same effect as caloric restriction.  Caloric restriction has been known to activate longevity genes such as:

  • DAF-16/FOXO
  • SKN-1/Nrf
  • SIR-2.1
  • AMPK

The finding of the researchers in this study was that BHB supplementation also activated these longevity gene pathways.  5

In addition to activating these longevity gene pathways, the researchers found that BHB supplementation also had the following effects:

  • increased worm thermotolerance
  • partially prevented glucose toxicity
  • delayed Alzheimer’s amyloid-beta toxicity
  • decreased Parkinson’s alpha-synuclein aggregation

Alzheimer’s disease

The researchers administered the toxic protein amyloid-beta to the nimatode worms and found that they stopped moving only hours after being given the protein.  However, when the nimatodes were supplemented with BHB, the time to stop moving took longer.

Parkinson’s disease

Alpha-synuclein accumulates in the brains of people suffering from Parkinson’s disease.  Researchers in this study found that BHB supplementation inhibited the accumulation of alpha-synuclein in NL5901 nematodes.

The researchers concluded that:

“Beta-HB (BHB) treatment extended lifespan and protected against metabolic, proteotoxic and thermal stress in Caenorhabditis elegans.  Our data support the hypothesis that beta-HB is a dietary restriction mimetic and that beta-HB treatment will likely be useful in the treatment of many human aging-associated disorders.”  

Resources:

Beta-hydroxybutyric acid is synthesized in the liver under the conditions of low food intake and/or the consumption of a low carbohydrate diet (ketogenic diet). 

However, it is possible to supplement with Beta-hydroxybutyric acid (BHB) which is known as exogenous BHB Ketone salt.  Exogenous BHB is beta-hydroxybutyric acid attached to a mineral salt, such as, sodium, potassium, calcium, or magnesium, in order that the body can adequately metabolize the beta-hydroxybutyric acid.

Perfect Keto

Nutricost 4-in-1 Exogenous Ketone Supplement

KetoSports KetoCaNa

Traditional Chinese Medicines Approach to Preventing and Treating Dementia and Alzheimer’s Disease with Medicinal Herbs

Dementia refers to a clinical syndrome seen mostly in the elderly and characterized by the impairment of memory and cognition.   The early stages of dementia is called mild cognitive impairment where around 70% progress to dementia at some point.

Dementia is an umbrella term that can manifest into four common types:

  • Alzheimer’s disease (50% to 80% of cases)
  • Vascular dementia (20% to 30% of cases)
  • Lewy body dementia (10% to 25% of cases)
  • Frontotemporal (10% to 15% of cases)

Image result for forms of dementia

Figure 1.  Types of Dementia

Alzheimer’s disease is a progressive neurodegenerative disease and has become the third greatest threat to the elderly, inferior only to cardiovascular disease and cancer.

Pathological hallmarks of Alzheimer’s disease include:

  • increased formation and aggregation of amyloid-beta peptide (Aβ) derived from amyloid precursor protein (APP)
  • formation of intracellular neurofibrillary tangles (NFT)
  • lesions of cholinergic neurons
  • synaptic alterations in cerebral cortex, hippocampus, and other brain regions essential for cognitive function
  • loss of neurons and synapses in the cerebral cortex and certain subcortical regions in the brain

Image result for alzheimer's disease

Figure 2.  Alzheimer’s disease – Healthy Brain and Alzheimer’s disease brain  (Source)

After many years of study, researchers have now accepted that dementia and Alzheimer’s disease are caused by a combination of multiple factors, such as:

  • dysfunctional apoptosis
  • oxidative stress
  • nitrosative stress
  • excitotoxicity
  • disturbance of energy metabolism homeostasis
  • mitochondrial dysfunction
  • inflammatory responses

Research has shown that there is a great deal of evidence indicating that the onset of Alzheimer’s disease is probably the consequences of complex interactions among genetic, environmental, and lifestyle factors.  1  

For over 2,000 years Traditional Chinese Medicine (TCM) has been part of the Chinese health care system.  TCM includes various forms of herbal medicine and hundreds of pharmacological herbal compounds have been identified in TCM for the treatment of many diseases, including:

  • diabetes
  • microbial infections
  • allergies
  • inflammation
  • cardiovascular disease
  • cancer

Many in vitro and in vivo studies have been completed that identify traditionally used medicinal plants and herbs from TCM for neurodegenerative diseases. 

In particular, a number of natural active ingredients from medicinal herbs for the treatment of dementia and Alzheimer’s disease has attracted substantial attention.

These medicinal plants and herbs have both direct and indirect effects on the prevention and treatment of dementia and Alzheimer’s disease.  Some of these mechanisms include, among others:

  • acetylcholinesterase activity
  • antioxidative activity
  • modulation of Amyloid-beta-producing secretase activities
  • amyloid-beta-degradation
  • heavy metal chelating
  • induction of neurotrophic factors
  • cell death mechanisms

Table 1 lists those Chinese herbs that have been used to treat and prevent dementia and Alzheimer’s disease.  Although not an exhaustive and complete list of herbs, these 18 Chinese herbs are the most recognized and studied herbs for the prevention and treatment of dementia and Alzheimer’s disease:

Table 1: Chinese Herbs Used for the Treatment and Prevention of Dementia and Alzheimer's Disease

Latin Botanical NameCommon NameChinese NamePinyin Name
Apium graveolens; Petroselinum crispumApigeninNoneNone
Camellia sinensisGreen tea茶花Cháhuā
Centella asiaticaGotu kola积雪草Ji Xue Cao
Galanthus woronowii.Galanthamine加兰他敏None
Ginkgo bilobaGinko biloba银杏叶Yin Xing Ye
Glycyrrhiza uralensis Fisch Liquiritin; Chinese liquorice甘草Gan Cao; gancao; kan-tsao
Huperzia serrata (Qian Ceng Ta) Huperzine A蛇足石杉she zu shi shan
Polygala tenuifoliaNone遠志Yuan Zhi
Paeonia suffruticosaPoeny牡丹皮Mu dan pi; Cortex Moutan
Panix ginsengGinseng人参Korean ginseng
Panax notoginsengSanchi ginsengtiánqī (田七), sānqī (三七)Tienchi ginseng
Radix puerariae (Pueraria lobata [Willd.] Ohwi) Kudzu; Puerarin葛根Gé gēn
Rhizoma anemarrhenae (Zhimu)Anemarrhena asphodeloides知母Zhi Mu
Rhodiola rosea L.Rhodiola紅景天Hong jing tian
Salvia miltiorrhiza Bunge.Red Sage; Chinese sage丹參Danshen
Salvia officinalisSage鼠尾草None
Scutellaria baicalensisChinese Skullcap; Baical Skullcap黄芩Huáng cen
Uncaria rhynchophylla Cat’s Claw釣鉤藤Gou Teng
Sources: A, B, C, D

Table 2 list those Chinese herbs that have been used to treat and prevent dementia and Alzheimer’s disease along with their medicinal effects and references:

Table 2: Chinese Herbs Used for the Treatment and Prevention of Dementia and Alzheimer's Disease (Medicinal Effects & References)

Latin Botanical NameCommon NameMedicinal EffectsReference
Apium graveolens; Petroselinum crispumApigenin
Apigenin is a potent chelating agent that could decrease the metal ions participating in radical reactions and therefore reduce the creation of free radicalsRef.
Apigenin was reported to protect human neuroblastoma cells SH-SY5Y against apoptosis induced by oxidative stress in vitroRef.
Apigenin was found to improve the memory and learning disorders of aging mice induced by D-galactoseRef.
Camellia sinensisGreen tea
Antioxidant properties of polyphenols, the active components enriched in green tea, may contribute to reducing the risk of dementiaRef.
The in vitro anti-beta-secretase and dual anticholinesterase activities of green tea was reported recently, indicating that tea contains active agents, which may function synergistically, to retard progression of the diseases, assuming that these agents, yet to be identified, reach the brainRef.
Long-term administration of green tea catechins provides effective prophylactic benefits against Abeta-induced cognitive impairment by increasing antioxidative defenses. Haque, A. M., et al. Green tea catechins prevent cognitive deficits caused by Abeta(1-40) in ratsRef.
A higher consumption of green tea is associated with a lower prevalence of cognitive impairment in humansRef.
Co-treated green tea extract (10-50 mug/ml) dose-dependently attenuated Abeta(25-35) (50 muM)-induced cell death, intracellular ROS levels, and 8-oxodG formation, in addition to p53, Bax, and caspase-3 expression, but upregulated Bcl-2. Furthermore, green tea extract prevented the Abeta(25-35)-induced activations of the NF-kappaB and ERK and p38 MAP kinase pathways. Green tea extract may usefully prevent or retard the development and progression of Alzheimer’s diseaseRef.
EGCG inhibited the fibrillization of Abeta in vitro with a half maximal inhibitory concentration of 7.5 mg/L. These studies suggest that EGCG may be a beneficial agent in the prevention of development or progression of ADRef.
Centella asiaticaGotu kola
Used medicinally as anxiolytic agent and as cerebral tonicRef.
Effective in preventing the cognitive deficits, as well as the oxidative stress, caused by intracerebroventricular injection of streptozotocin in ratsRef.
Neuroblastoma cells expressing Aβ identified the ERK/RSK signaling pathway to be involved in a possible molecular mechanism for memory enhancing property of Gotu Kola extractRef.
Selectively decrease hippocampal Aβ levels in AD mouse model expressing the Swedish’ APP and the M146L presenilin 1 mutationsRef.
Galanthus woronowii.Galantamine
Galantamine acts as a selective, reversible, and competitive inhibitor of AchERef.
Galantamine may potentiate memory deficitsRef.
Galantamine has the ability to selectively stimulate or/and modulate neuronal nicotinic acetylcholine receptor, which could facilitate an increase in the synthesis of neurotrophic factors and protect neuronal cells against hazardous effects of oxidative stress and injuryRef.
The combination of galantamine and nicotine works synergistically in inhibiting microglia activationRef.
A clinical trial has confirmed the efficacy and safety of galantamine in the treatment of ADRef.
At six months, patients in the higher dose galantamine group had significantly better scores on the disability assessment for dementia scale than patients in the placebo group (mean treatment effect 3.4 points,). Apolipoprotein E genotype had no effect on the efficacy of galantamine. 80% (525) of patients completed the study. Galantamine is effective and well tolerated in Alzheimer's diseaseRef.
Ginko bilobaGinko biloba
Leaf extract of G biloba (EGb), labeled EGb761, possesses the capacity to treat a variety of neurological disorders, including AD and age-related dementiaRef.
The antioxidant activity of EGb761 may play a substantial role in neuroprotection by decreasing bax/bcl-2 ratiosRef.
EGb761 shows reversal of ischemia-induced reductions of cycloxygenase III mRNA in hippocampal CA1 neurons, inhibition of nitric oxide synthesis, scavenging of free radicals, and attenuation of lipid peroxidationRef.
The effects of oxidative stress were reduced in lymphocytes and brain cells derived of EGb 761-treated AD-transgenic and non-transgenic miceRef.
EGb 761 also affects the production of neurotoxic beta-amyloid peptides (Aβ), for example, by up-regulating α-secretase activity both in cells and animalsRef.
Treatment with EGb761 could partially prevent the indices of oxidative damage in brain from old animalsRef.
One randomized, double-blind, placebo-controlled, and multicenter clinical trial indicated that EGB was safe and capable of stabilizing and improving the cognitive performance and the social functioning of AD patients for 6 months to 1 yearRef.
Pharmacological studies demonstrated that EGb can reverse yohimbine-induced spatial working memory deficit in ratsRef.
EGb761 can improve learning performance in cerebral ischemic miceRef.
EGb761 reduces infarct volume and cell apoptosis in cortex of ischemic miceRef.
EGb761 can reverse memory deficit and decline in choline actyltransferase activities in the hippocampus of rats infused intracerebroventricularly with Aβ1–40Ref.
EGb761 can protect against apoptosis induced by hydroxyl radicalsRef.
EGb761 can protect against cell death induced by beta-amyloidRef.
EGb761 can protect against nitric oxide-induced toxicityRef.
Ginkgolide B were reported to attenuate glutamate-induced neuronal damageRef.
EGb761 can attenuate lipid peroxidationRef.
EGb has potent antioxidant activity and may play a role in the neuroprotective process by attenuating the ischemia/reperfusion-induced oxidative protein modification and lipoperoxidationRef.
Double-blinded randomized controlled clinical trial has demonstrated the efficacy of EGb 761, the standardized preparation of EGb, in treatment for mild to moderate Alzheimer’s diseaseRef.
A 24-week, multicenter, double-blind, placebo-controlled, randomized trial confirmed that EGb 761 improves cognitive function in a clinically relevant manner in patients suffering from dementiaRef.
A randomized placebo-controlled double-blind study showed that EGb 761 (160 mg/d) had a comparable efficacy with donepezil (5 mg/d) in treating mild to moderate AD, and also suggested the efficacy and tolerability of the Ginkgo biloba special extract (Flavogin) in the dementia of the Alzheimer type with special respect to moderately severe stagesRef.
EGb 761 has been suggested to prevent neurodegenerative pathologiesRef.
Glycyrrhiza uralensis Fisch Chinese liquorice
Liquiritin has protective effects on cultured rat hippocampal neuronsRef.
Liquirtin is capable of enhancing the effects of nerve growth factor in extending neuraxonsRef.
Liquirtin can inhibit the activity of acetylcholinesterase and promote the differentiation of neuronal stem cells into cholinergic neuronsRef.
Huperzia serrataHuperzine A
Huperzine A is considered the most potent acetylcholinesterase (AchE) inhibitorRef.
Hup A is also found to be an effective cognition enhancerRef.
Hup A exerts multiple neuroprotective effects, in which the mechanisms may involve the activation of both muscarinic and nicotinic acetylcholine receptors; enhancement of the production of neurotrophic factors; as well as blocking of overstimulated NMDA receptorsRef.
Hup A is effective in improving cognitive impairments in multi-infarct dementia, brain trauma, schizophrenia, and benign senescent forgetfulnessRef.
Hup A neuroprotective effects may be the result of the upregulation of c-jun gene and downregulation of bcl-2 geneRef.
Hup A upregulats nerve growth factor secretion and its downstream signaling; the inhibition of oxidative stress; and the improvement in energy metabolismRef.
Hup A can modulate the processing of amyloid precursor protein (APP) by the regulation of protein kinase CRef.
Hup A can significantly improve the memory of elderly people and AD patients without any notable side effectsRef.
All the advantageous effects of Hup A may be attributed to its potent, reversible, and selective inhibition of AchERef.
Phase IV clinical trials conducted in China have demonstrated that HupA can significantly improve memory of elderly people and patients with AD and VD without any notable side effectsRef.
In the cortex, hippocampus, and striatum of mammalian brain, HupA exerts preferential inhibition against G4 (10S) AChE, which is the physiologically relevant form at cholinergic synapses and is the major form for metabolizing AChRef.
Hup A has been demonstrated by recent studies in our laboratory to protect against H2O2- and β-amyloid (Aβ)-induced cell lesion, decrease the level of lipid peroxidation, increase antioxidant enzyme activities in rat PC12 and NG108–15 cell lines and primary cultured cortical neuronsRef.
Hup A has been demonstrated to protect against serum deprivation-induced toxicityRef.
Hup A has been demonstrated to protect against oxygen-glucose deprivation-induced toxicityRef.
Hup A has been demonstrated to protect against ischemia-induced toxicityRef.
Hup A regulates apoptosis-related genesRef.
Hup A upregulates NGF secretion and its down-stream signalingRef.
Hup A can modulate the processing of amyloid precursor protein (APP) in both rats infused intracerebroventricularly with Aβ1–40 and HEK293sw cell line, via regulating protein kinase C (PKC)Ref.
Polygala tenuifoliaYuan Zhi
An effective compound from the dried root of P tenuifolia, tenuifolin, could inhibit AchE activity or could enhance cholinergic neurotransmissionRef.
Tenuifolin could penetrate the blood–brain barrier and improve cognitive impairment through elevation of the cholinergic system by blocking acetylcholine hydrolysisRef.
A decrease in the secretion of A β 1–40 and A β 1–42 by tenuifolin was reportedRef.
Tenuifolin was found to decrease A β secretion from transfected cells, probably due to inhibition of the beta-site APP cleaving enzymeRef.
A β 25–35-induced cell damage was completely inhibited by Polygala tenuifolia extractRef.
Polygala tenuifolia is classically mentioned as an anti-dementia drug in Chinese and Japanese traditional medicineRef.
It has been shown that Polygala tenuifolia can improve hippocampus-dependent learning and memory, possibly through improvement of synaptic transmission, activation of the MAP kinase cascade, and enhancement BDNF levelsRef.
Polygala tenuifolia up-regulated the expression of BDNF and TrkB mRNA to promote the recovery of the neurons from chronic stress-induced damagesRef.
The methanol fraction of an ethanolic extract from Polygala tenuifolia showed antagonistic action on neurotoxicity induced by glutamate and serum deficiency in PC12 cellsRef.
Paeonia suffruticosaPoeny
Penta-O-galloyl-beta-d-glucopyranose (PGG), a major component of the traditional herb Paenoia suffruticosa, inhibits Aβ fibril formation and destabilizes preformed Aβ fibrils in a concentration dependent matterRef.
Improved long-term memory impairment in an AD mouse model and inhibited Aβ accumulation in brains of treated miceRef.
PGG could protect neuronal cells from oxidative stress by induction of HO-1 gene expressionRef.
Panax ginsengGinseng
Ginsenosides Rb1 and Rg3 exerted significant neuroprotective effects on cultured cortical cells against glutamate-induced neurodegenerationRef.
Protopanaxadiol-type saponins were reported to enhance axonal and dendritic formation activityRef.
Saponins can improve learning and memory in animals impaired with scopolamineRef.
Saponins can improve transient global ischemiaRef.
Saponins can protect brain function and postpone brain aging by decreasing free radicals damage and increasing activities of GSH-Px and SODRef.
The ability of ginsenoside to enhance TrkB expression might also be involved in its protective effectRef.
Panax notoginsengSanchi ginseng
Protective actions against cerebral ischemia, beneficial effects on the cardiovascular system, and haemostatic, antioxidant, hypolipidemic, hepatoprotective, renoprotective, and estrogen-like activities have been describedRef.
Ginsenoside Rg1, a major active component of sanchi ginseng (P. notoginseng), was shown to inhibit β-secretase activity in vitro, to protect PC12 cells against Aβ25–35Ref.
Ginsenoside Rg1 can exert neuroprotective effectsRef.
Ginsenoside Rg3 significantly reduced the levels of Aβ1–40 and Aβ1–42 in SK–N–SH cells transfected with Swedish mutant beta-APPRef.
Radix puerariae (Pueraria lobata [Willd.] Ohwi) Kudzu; Puerarin
Puerarin can protect from learning and memory impairment induced by D-galactoseRef.
Puerarin can protect from β-amyloid peptideRef.
Puerarin can protect from ischemic brain injuryRef.
Puerarin decreases the lipid peroxidase levels and increases superoxide dismutase levels in brain tissuesRef.
Rhizoma anemarrhenae (Zhimu)Zhi Mu
Pharmacological studies demonstrated that Rhizoma anemarrhenae can protect from learning and memory impairment induced by D-galactoseRef.
Rhizoma anemarrhenae can protect from learning and memory impairment induced by β-amyloid peptideRef.
Rhizoma anemarrhenae can enhance memory of normal aged animalsRef.
Rhizoma anemarrhenae is due to its activity of improving the synthetic speed of acetylcholine (ACh) and density of M-type ACh receptorsRef.
Rhizoma anemarrhenae is due to its activity of scavenging free radicalsRef.
Rhizoma anemarrhenae is due to its activity of upregulating brain-derived neurotrophic factor (BDNF)Ref.
Rhodiola rosea L.Rhodiola
Rhodosin can protect from learning and memory impairment induced by D-galactoseRef.
Rhodosin can protect from β-amyloid peptideRef.
Rhodosin can protect from hypoxiaRef.
Rhodosin can protect from cerebral ischemia-reperfusionRef.
Rhodosin can enhance memory of normal-aged ratsRef.
Rhodosin can increase ACh content and reduce cholinesterase activity in the brainRef.
Rhodosin reduces the content of lipid peroxide, and inhibits degeneration of mitochondria in cerebrum cells and hippocampal pyramidal cellsRef.
Salvia miltiorrhiza Bunge.Red sage; danshen
Tanshinone can improve cholinergic functions in central nervous systemRef.
Tanshinone can inhibit inflammatory reaction by inhibiting the expression of pro-inflammatory cytokinesRef.
Tanshinone can inducible nitrogen oxidase (iNOS)Ref.
Salvianolic acid protects from ischemic brain injuryRef.
Tanshinone modulates AChE and NOS protein concentrations in the hippocampus of cranial A β 1–42 injected ratsRef.
Neuroprotective effects of tanshinone was demonstrated in cortical neuronsRef.
Pretreatment of the cells with Tanshinone prior to A β 25–35 exposure suppressed A β -induced cellular events, such as loss in viability, apoptosis, decrease in superoxide dismutase, and glutathione peroxidase activity, increased ROS and decreased mitochondrial membrane potentialRef.
Salvia officinalisSage
Ursolic acid, a pentacyclic triterpenoid carboxylic acid, which can effectively reduce the level of lipid peroxidation and efficiently reverse d-galactose-induced learning and memory impairmentRef.
Extracts of S officinalis are effective in treating mild to moderate ADRef.
Ursolic acid also efficaciously inhibits AchE activity in vitroRef.
Rosmarinic acid, a phenolic derivative of caffeic acid, is also found in water extracts of S officinalis, which exhibits a dose-dependent stalling of the A β fibril formation from A β 1–40 and A β 1–42 as well as A β fibril aggregation, and it can also destabilize the integrity of A β fibrilsRef.
Sage protects PC12 cells from A β 1–42 induced neurotoxicity, which include reactive oxygen species formation, lipid peroxidation, DNA fragmentation, caspase-3 activation, and tau protein hyperphosphorylationRef.
At 4 months, S. officinalis extract produced a significant better outcome on cognitive functions than placeboRef.
Scutellaria baicalensisChinese skullcap
Prevention from myocardial damage induced by ischemia-reperfusion, and improved cerebral ischemiaRef.
Capable of protecting hippocampal neurons against damage induced by injection of Aβ25–35 in hippocampus in ratRef.
Decreases the accumulation of lipid peroxide and proliferation of glial cells induced by Aβ25–35Ref.
Alleviated memory and learning injury and protected morphological change of hippocampal neurons in AD rats induced by Aβ25–35 injectionRef.
Uncaria rhynchophylla Cat's Claw
Our results suggest that Uncaria rhynchophylla has remarkably inhibitory effects on the regulation of Abeta fibrils, and we conclude that this medicinal herb could have the potency to be a novel therapeutic agent to prevent and/or cure AD.Ref.
The active mechanisms were related to blocking of calcium channels, opening of potassium channels, and regulating of nerve transmitters transport and metabolismRef.
Suppression of c-Jun N-terminal kinase (JNK) phosphorylationRef.
U. rhynchophylla significantly inhibited NMDA receptor-activated ion currents in acutely dissociated hippocampal CA1 neurons in cultured brain slicesRef.
In view to AD, U. rhynchophylla intensively inhibited A β aggregation and significantly destabilized preformed A β 1–40 and A β 1–42 fibrilsRef.

 

F2-Isoprostanes: A Major Aging Marker of Lipid Peroxidation and Risk Marker for Developing Coronary Heart Disease

Arachidonic acid

Arachidonic acid (AA) is a polyunsaturated omega-6 fatty acid (20:4(ω-6)) and is converted from linoleic acid, which is an essential fatty acid, known as omega-6 fatty acid.

In the body, arachidonic acid is present in the phospholipids of cell membranes and mostly abundant in the:

  • brain
  • muscles (accounting for roughly 10-20% of the phospholipid fatty acid content on average)
  • liver

Only animals and not plants can convert linoleic acid to arachidonic acid.  Arachidonic acid can also be obtained endogenously from the diet by consuming primarily animal foods, such as:

  • meat
  • poultry
  • eggs

Physiologically, the body requires a certain level of AA.  However, when that level is outside the accepted reference range, this can progress into a pro-inflammatory environment.  AA is actually considered to produce various pro-inflammatory eicosanoids. 

Image result for Arachidonic acid

Figure 1.  Arachidonic Acid cascade  (Source)

One measure of cellular inflammation is the AA:EPA Ratio.  The AA: EPA ratio provides a more specific indicator of the balance between omega-6 and omega-3 fatty acids in circulation. When this ratio is higher, there is preferred incorporation of AA into cell membranes over EPA, leading to a pro-inflammatory environment.

While both of these fatty acids are essential to human health, the optimal ratio of AA:EPA is around 1.7.  1 

Isoprostanes

Isoprostanes are prostaglandin-like compounds formed in the body from the free radical-catalyzed peroxidation of arachidonic acid.  Isoprostanes acts as inflammatory mediators and possess potent biological activity.  They are accurate markers of lipid peroxidation of oxidative stress.  2

Image result for lipid peroxidation

Figure 2.  Harmful Effects of Lipid Peroxidation  (Source)

Lipid peroxidation occurs in the cell membrane when free radicals oxidize or degrades the lipids contain the the cell membranes.  This ultimately results in cell damage.  Polyunsaturated fatty acids (mostly AA) are particularly vulnerable to lipid peroxidation due to the numerous double bonds in their structure.

F2-Isoprostanes

F2-Isoprostanes are produced by the reaction of free radicals with arachidonic acid.

Image result for F2-Isoprostanes

Figure 3.  Metabolism of F2-Isoprostanes  (Source)

The damage done by F2-Isoprostanes can be widespread, since they can generally cause:

  • blood vessels to constrict
  • blood pressure to raise
  • promotion of blood clots
  • promotion of the clumping of platelets

Numerous studies carried out over the past decade have shown that these compounds are extremely accurate measures of lipid peroxidation and have illuminated the role of oxidant injury in a number of human diseases including atherosclerosis, Alzheimer’s disease and pulmonary disorders.  3

Measuring and Testing for F2-isoprostanes

The F2-isoprostanes test is considered the gold standard for oxidative stress and is measured in a urine specimen. 

Elevated F2-isoprostanes levels are at a more than 30-fold risk for developing coronary heart disease compared with those with normally low levels.  4

According to the Cleveland HeartLab, Inc., your F2-isoprostanes risk is low when your level is less than 0.86 ng/mg; at or above that level places you at high risk.  5

 

Cleveland HeartLab, Inc.

Reference Range for F2-isoprostanes

Age                                                                ng/mg creatinine

All Ages                                                                  <0.86

 

 

Informational References:

Cleveland HeartLab, Inc. offers the F2-isoprostanes Test through the Know Your Risk Program®

Cleveland HeartLab, Inc. F2-isoprostanes Handout

Video:  Marc Penn – Trials and Tribulations of Assessing CVD Risk in 2013 (Cleveland HeartLab)

 

Puerarin, a Potent Bioactive Ingredient from Kudzu, Shows Promise as a Neuroprotective Agent

Kudzu, also called Japanese arrowroot, is a group of plants in the genus Pueraria, in the pea family Fabaceae.  It is native to Asia and the Pacific Islands.  The name is derived from the Japanese name for the plants, kuzu (クズ or 葛?).  It tends to be a very invasive plant and grows as a vine.

Image result for Kudzu root

Figure 1.  Kudzu root  (Source)

 

Figure 2.  Flowers of Pueraria montana var. lobata  (Source)

The Chinese derived the traditional medicine called Gegen (Ge Gen) from Pueraria lobata (Willd.) Ohwi, a specieis of Pueraria.

Image result for puerarin

Figure 3.  Puerarin molecule  (Source)

One of the major bioactive ingredients of Kudzu is puerarin and is its is most abundant secondary metabolite.  Since its isolation in the 1950’s, puerarin has been extensively investigated for its pharmacological properties.  It has been widely used in the treatment of:

  • cardiovascular and cerebrovascular diseases
  • diabetes and diabetic complications
  • osteonecrosis
  • Parkinson’s disease
  • Alzheimer’s disease
  • endometriosis
  • cancer

The beneficial effects of puerarin on the various medicinal purposes may be due to its wide spectrum of pharmacological properties such as:

  • vasodilation
  • cardioprotection
  • neuroprotection
  • antioxidant
  • anticancer
  • antiinflammation
  • alleviating pain
  • promoting bone formation
  • inhibiting alcohol intake
  • attenuating insulin resistance

Recent studies have revealed that puerarin can be neuroprotective in the following areas:

  • learning and memory impairment induced by D-galactose  1
  • protected neurons against apoptosis in the cortex and hippocampus of Alzheimer’s diseased rats caused by Aβ25–35 through downregulating Aβ1–40 and Bax expression in brain tissues, therefore alleviating the spatial learning and memory impairment of diseased animals.  2 
  • ischemic brain injury.  Puerarin could improve the learning-memory ability after global cerebral ischemia and reperfusion in rats. The protective mechanism might be related to the effect of inhibiting or delaying the cell apoptosis through up-regulating the expression of Bcl-2 after ischemia and reperfusion.  3 

The anti-Alzheimer’s disease effects of puerarin were also suggested to be related to its abilities in decreasing the lipid peroxidase levels and increasing superoxide dismutase levels in brain tissues, enhancing cerebral blood flow, and improving brain microcirculation   4  

Sulforaphane Improves Glucose Control

A recently published study on 14 June 2017 in the journal Science Translational Medicine entitled, “Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes”, found that sulforaphane-containing broccoli sprout extract was well tolerated and improved fasting glucose in human patients with obesity and dysregulated type 2 diabetes.  1 

The authors of the study analyzed the pattern of gene expression associated with type 2 diabetes and compared it to the gene signatures for thousands of drug candidates to find compounds that could counteract the effects of diabetes. By interrogating a library of 3800 drug signatures, the leading candidate from this analysis was sulforaphane, a natural compound found in broccoli,broccoli sprouts, brussel sprouts and other vegetables.

Image result for Sulforaphane

Figure 1.  Sulforaphane molecule

The authors showed that sulforaphane inhibits glucose production in cultured cells by activating nuclear translocation of nuclear factor erythroid 2–related factor 2 (NRF2) and improves glucose tolerance in rodents on high-fat or high-fructose diets.  It also decreased expression of key enzymes in gluconeogenesis.

Moreover, sulforaphane reversed the disease signature in the livers from diabetic animals and attenuated exaggerated glucose production and glucose intolerance by a magnitude similar to that of the drug metformin.

Finally, sulforaphane, provided as concentrated broccoli sprout extract, reduced fasting blood glucose and glycated hemoglobin (HbA1c) in obese patients with dysregulated type 2 diabetes.

  

Summary of Benefits of Sulforaphane in Type 2 Diabetes

  • Inhibits glucose production by activating NRF2
  • Improves glucose tolerance
  • Decreased expression of key enzymes in gluconeogenesis
  • Reduced fasting blood glucose
  • Reduced glycated hemoglobin (HbA1c)

Related article:  Broccoli Sprouts and the Health Benefits of Sulforphane

Support and Enhancement of Phase II Detoxification Pathways Using Foods, Food-Derived Components and Nutrients

Phase II Detoxification Pathways

There are 6 Phase II detoxification pathways in the body.  Each conjugation pathway serves a specific purpose of detoxifying certain toxins and requires specific nutrients to function.  These 6 detoxification pathways include:

  • Glutathione conjugation
  • Methylation
  • Sulfation
  • Acylation/Glycation
  • Acetylation
  • Glucuronidation

These 6 conjugation pathways are found primarily in the liver and in various other locations within the body:

Locations of Phase 2 Conjugation
Pathways

Conjugation System Location in Body
Acylation/Glycation conjugation liver, kidney
Glutathione conjugation liver, kidney
Glucuronidation liver, kidney, intestine, lung, skin, prostate,
brain
Acetylation liver, lung, spleen, gastric mucosa, RBCs,
lymphocytes
Sulfation liver, kidney, intestine
Methylation liver, kidney, lung,
CNS

Source:  Liston HL, Markowitz JS, DeVane CL, (October 2001). “Drug glucuronidation in clinical psychopharmacology”. J Clin Psychopharmacol 21 (5): 500–15.doi:10.1097/00004714-200110000-00008. PMID 11593076

Phase II Conjugation Enzymes

After a toxin (xenobiotic) has gone through the process of becoming hydrophilic (water-soluble) through reactions overseen by Phase I enzymes, its intermediate molecules are then conjugated with endogenous hydrophilic enzymes.  These endogenous enzymes include:  1

  • glucuronic acid (glucuronyl transferases)
  • sulfate (sulfotransferases)
  • glutathione (glutathione transferases)
  • amino acids (amino acid transferases)
  • acetyl group (N-acetyl transferases)
  • methyl group (N- and O-methyltransferases)

These enzymatic reactions result in an increase in the hydrophilicity of the metabolite leading to enhanced excretion in the bile and/or urine.

The modulation of phase II enzymes by food-based bioactive compounds can support and enhance the Phase II process, especially when there are issues with:

  • genetic polymorphisms that inhibnit Phase II
  • high toxic burden due to chronic exposure to environmental pollutants
  • overactive Phase I activity
  • hormonal imbalance

Each of the 6 Phase II pathways are supported and enhanced by various foods, food-derived components and nutrients.

Amino Acid Conjugation:  Acylation/Glycation

In acylation/glycation, toxins are attached to amino acids, especially glycine. A low protein diet can inhibit acylation/gylcation.  Acylation/glycation detoxifies compounds like benzoate, aspirin and toluene (a widely used industrial solvent).

AminoAcidConjugation

Glucuronidation

Glucuronic acid is a metabolite of glucose that can be attached to toxins. This pathway is used as a back-up for sulfation or acylation/glycination. It is used to eliminate chemical and bacterial toxins, excess steroidal hormones (like estrogen), toxins from fungal infections and a variety of chemical toxins such as nitrosamines, aromatic amines, alcohols and phenols.

Glucuronidation

Glutathione Conjugation

Attaching toxins to glutathione helps to detoxify and eliminate poisons in the liver, lungs, intestines and kidneys. Glutathione helps the body get rid of a wide variety of chemical compounds including aromatic disulphides, paththalene and anthracene.

GlutathioneNutrients

Glutathione

Methylation

Methylation attaches toxins to the amino acid methionine. This process occurs in every cell of the body and helps the body get rid of excess hormones and neurotransmitters, including steroidal hormones like estrogen, adrenaline, dopamine, melatonin, histamine and serotonin. It also helps eliminate homecysteine, a compound associated with increased risk of heart disease. A variety of chemicals (amines, phenols, etc.) are also eliminated through methylation.

Methylation

Sulfation

Sulfation eliminates toxins by attaching them to sulphate. This is the principle pathway for eliminating excess neurotransmitters, several drugs (including acetaminophen, some food additives and toxins from intestinal bacteria. It also removes many forms of environmental toxins. Reduced sulfation may be involved in Parkinson’s disease, Alzheimer’s disease and other nervous system disorders and in environmental illness.

Sulfation

Acetylation

Acetylation involves attaching acetyl co-A to toxins for elimination. People who are chemically sensitive are usually slow acetylators. Slow acetylation enhances the toxicity of drugs because it prolongs their life span in the body. Acetylation is used to eliminate excess histamine, serotonin, sulfa drugs, PABA and chemicals like sulphur amides and hydranzines.

Acetylation

Download Phase II Infographics in PDF format:  

Right click on title and Save As PDF or

Left click on Title which opens into new window then right click in body of document and Save As PDF

Glutathione conjugation (page 1)

Glutathione conjugation  (page 2)

Methylation

Sulfation

Acylation/Glycation

Acetylation

Glucuronidation

Maximizing The Sulforaphane Content of Broccoli and Broccoli Sprouts

Glucosinolates

Glucosinolates are natural components of many pungent plants that occur as secondary metabolites of most of the Brassicales family, or the cruciferous vegetables.   When these vegetables are chewed, a pungent taste arises due to the breakdown products of glucosinolates.

Each vegetable, sprout and seed usually contains more than one glucosinolate.  However, certain vegetables, sprouts and seeds may contain a predominant amount of one glucosinolate.  An example is the following:

  • Broccoli and broccoli sprouts contain large amounts of glucoraphanin
  • Mustard seeds and Brussel sprouts contain a large amount of Sinigrin
  • Garden cress and cabbage contain a large amount of glucotropaeolin
  • Watercress contains a large amount of gluconasturtiin

The total number of documented glucosinolates from nature can be estimated to around 132, as of 2011.  1  For purposes of this article, we will focus on the 4 most important glucosinolates and the ones that have been the subject of the majority of medical research.  These 4 glucosinolates include:

  • Gluconasturtiin
  • Glucoraphanin
  • Glucotropaeolin
  • Sinigrin

Gluconasturtiin, also known as phenethylglucosinolate, is a widely distributed glucosinolate in cruciferous vegetables.  The name is derived from it occurrence in watercress which has the botanical name Nasturtium officinale.

Glucoraphanin is a glucosinolate distributed in broccoli, Brussel sprouts, cabbage and cauliflower.  It is also found in large amounts in young sprouts of cruciferous vegetables, like broccoli sprouts.

Glucotropaeolin is a phytochemical from Tropaeolum majus, which is commonly known as garden nasturtium, Indian cress or monks cress.  It is also found in cabbage.

Sinigrin is widely distributed in the plants of the Brassicaceae such as Brussel sprouts, broccoli, horseradish and black mustard seeds.

Myrosinase

Each of the vegetables, sprouts and seeds contain the enzyme myrosinase, which is activated when the vegetable, sprout or seeds is damaged (chopped or chewed) in the presence of water.  The glucosinolate converts to an isothiocyanate (or thiocyanate) through the enzymatic activity of myrosinase.  These isothiocyanates are the defensive substances of the plant.

Thus glucosinolates are the precursors to isothiocyanates through the breakdown of the enzyme myrosinase.  Myrosinase activity on the glucosinolate also continues in the gastrointestinal tract through intestinal bacteria which allows for some further formation and absorption of isothiocyanates. 2

Image result for glucosinolates myrosinase pathway

Figure 1:  Glucosinolates Hydrolysis by Myrosinase  (Source:  Linus Pauling Institute – Isothiocyanates)

Sulforaphane

Sulforaphane is obtained from cruciferous vegetables such as broccoli, broccoli sprouts, Brussels sprouts, and cabbages. It is produced when the enzyme myrosinase transforms glucoraphanin into sulforaphane upon damage to the plant (such as from chewing), which allows the two compounds to mix and react.

When the enzyme myrosinase acts on glucoraphanin, an unstable intermediate is produced.  This unstable intermediate is then acted on by a protein called epithiospecifier protein (ESP) to produce sulforaphane or sulforaphane nitrile.

If epithiospecifier protein (ESP) is abundant in the plant and is active, it will convert this unstable intermediate to a sulforaphane nitrile.  This sulforaphane nitrile has no anti-cancer activity.  3 

If epithiospecifier protein (ESP) is not abundant and is low-active, then it will convert this unstable intermediate into sulforaphane.  Sulforaphane has anti-cancer activity.  4

Image result for sulforaphane nitrile

Figure 2.  ESP converts into sulforaphane and sulforaphane nitrile  (Source

Decreasing Epithiospecifier Protein Activity

A research paper entitled “Heating decreases epithiospecifier protein activity and increases sulforaphane formation in broccoli”, published in Phytochemistry in 2004, examined the effects of heating broccoli florets and sprouts on sulforaphane and sulforaphane nitrile formation, to determine if broccoli contains ESP activity, then to correlate heat-dependent changes in ESP activity, sulforaphane content and bioactivity, as measured by induction of the phase II detoxification enzyme quinone reductase (QR) in cell culture.  5

Researchers experimented with cooking broccoli at different temperatures and at different times periods.  They then measured the point at which the epithiospecifier protein is destroyed. 

What they learned was that they only had to heat the broccoli for a short time in order to destroy the epithiospecifier protein thus yielding more sulforaphane and little to no sulforaphane nitrile.

Specifically, to maximize the sulforaphane in broccoli, they found that heating it for 10 minutes at 140 degrees Fahrenheit (60 degrees Celsius).  This can translate to steaming broccoli lightly for about 3 to 4 minutes.

When they heated the broccoli for 10 minutes at 158 degrees Fahrenheit (70 degrees Celsius) it not only destroyed the epithiospecifier protein but also the sulforaphane content. 

Broccoli sprouts

Broccoli sprouts are germinated from broccoli seeds for about 3 days minimum and 5 days maximum. 

Image result for broccoli sprouts

Figure 3.  Broccoli sprouts

Broccoli sprouts that are 3 days old have very concentrated sources of glucoraphanin.  It is estimated that broccoli sprouts have 10 to 100 times more glucoraphanin by weight than mature broccoli plants.  6

Three-day-old broccoli sprouts have been shown to be highly effective in reducing the incidence, multiplicity, and rate of development of mammary tumors in dimethylbenz(a)anthracene-treated rats.  7  Small quantities of crucifer sprouts may protect against the risk of cancer as effectively as much larger quantities of mature vegetables of the same variety.

The activity of the epithiospecifier protein (ESP) in broccoli sprouts fluctuates based on the number of days the sprouts have grown.  8

ESP activity increases up to day 2 after germination before decreasing again to seed activity levels at day 5.

Thus, the optimal amount of days to grow broccoli sprouts is probably 5 days since the amount of glucoraphanin in broccoli seeds remains more or less constant as those seeds germinate and grow into mature plants.  9

When the researchers heated broccoli sprouts for 10 minutes at 158 degrees Fahrenheit (70 degrees Celsius) in water, it minimized the epithiospecifier protein and maximized the sulforaphane content.

Heating broccoli sprouts in water under these exact specifications will increase the sulforaphane content for maximum anti-cancer benefit.

Compare the technique of heating broccoli sprouts in water with the study from China where they increased the sulforaphane yield by freezing the broccoli sprouts:

An example of heating broccoli sprouts in water using the specifications of the researchers can be viewed in the experiment conducted by Dr. Rhonda Patrick:

Natural Rapalogs that Inhibit the mTOR Pathway

In 1975 scientists discovered the mycelial bacterium Streptomyces hygroscopicus on Rapa Nui, the native name of Easter Island.  From this bacterium they created the molecule named Rapamycin, a pharmaceutical drug which requires a doctor’s prescription.  Also known as Sirolimus, it is an immunosuppressant drug used in orthodox medicine to prevent rejection following organ transplantation.

In addition to its use as an immunosuppressant drug, Rapamycin inhibits the mTOR signalling pathway and studies show it can significantly extend lifespan in mammals, even when taken in later life, with increases in life expectancy for males and females of between 9% and 14% respectively.


 

mTOR Pathway  

“mTOR” or the mechanistic target of rapamycin (mTOR), (formerly mammalian target of rapamycin before it was recognized to be highly conserved among eukaryotes) refers to an enzyme from the serine/threonine protein kinase family encoded by the mTOR gene. It is found in humans as well as worms, mice, flies and yeasts. It regulates the growth, proliferation, motility and survival of cells.

Successfully inhibiting mTOR signalling pathways has been shown to produce increased lifespan in worms, flies, yeasts and even mice if accompanied by calorie restriction and the consumption of adequate protein.

 

Image result for mtor pathway

Figure 1.  mTOR Pathway  (Source)

Since Rapamycin is poorly water soluble, which effects its bioavailability, several analogs of Rapamycin have been developed and are termed rapalogs.  Some of these rapalogs have improved pharmacokinetics and include:

  • temsirolimus
  • everolimus
  • ridaforolimus
  • 32-deoxo-rapamycin
  • zotarolimus

The use of these pharamaceutical rapalogs have been generally disappointing in human trials.  One possible explanation for the disappointing results to date is that in human cancer, rapalogs predominately inhibit mTORC1, leading to increased PI3K and AKT signaling by preventing negative feedback through S6K and GRB10.  1 

Recent studies have demonstrated that a number of natural products (or nutraceuticals) isolated from plants (e.g. fruits, vegetables, spices, nuts, legumes, herbs, etc.) also inhibit the mTOR pathway, and exhibit potent anticancer activities. These particular natural products are considered “natural rapalogs”.

The Table below lists the identified natural substances that are considered natural rapalogs or mTOR inhibitors:

Natural Rapalogs (mTOR Inhibitors)

CategorySubstanceReference
Alkaloids
Caffeine1
Amino Acids
NAC2
Herbs
Astragalus3
β-elemene (from the traditional Chinese medicinal herb Rhizoma zedoariae)4
Butein (in the stems of Rhus verniciflua)5
Capsaicin (in chili peppers)6
Celastrol (in the traditional Chinese medicine named “Thunder of God Vine”)7
Cryptotanshinone (Salvia miltiorrhiza Bunge) (Danshen)8
Rhodiola rosea9
Indoles
Indole-3-carbinol and 3,3′-diindolylmethane)10
Mushrooms
Reishi11
Peptides
Carnosine12
Polyphenols
Apigenin13
Curcumin14
Epigallocatechin gallate (EGCG, in green tea)15
Fisetin16
Isoflavones (genistein and deguelin)17
Quercetin18
Resveratrol19
Vitamins
R-Lipoic Acid20
Tocotrienol (Vitamin E)21

Increasing the Klotho Protein Extends Lifespan and Healthspan

According to Greek mythology, Clotho (Greek: Κλωθώ) is part of the Three Fates or Moirai who spin (Clotho), draw out (Lachesis) and cut (Atropos) the thread of Life.

Clotho was responsible for spinning the thread of human life. She also determined when a person was born and when they died.

Clotho represented the thread of human life and her decisions represented the fate of all people in society.

Similar to Clotho from Greek mythology, Klotho is an enzyme that in humans is encoded by the KL gene.  It was discovered in 1997 by scientists and involves the suppression of several ageing phenotypes.  It was appropriately named after Clotho from Greek mythology due to its relations to the thread of life.

Discovered in 1997, Klotho is considered a longevity gene which is expressed in various organs and cells, such as renal tubular cells and the brain choroid.  

Klotho fluctuates with age, where in a persons first decade (0 to 10), serum levels are low, then from ages 20 to 40 years, it increases and reaches its peak, and finally after 40 years old it gradually decreases.  1 

Image result for klotho

Figure 1.  Klotho Functions

Klotho has many physiological functions, including:  2  3

  • Regulating calcium and phosphorus levels
  • Delaying senescence
  • Improving cognition function and improves intelligence 
  • Reducing oxidative stress
  • Protecting vascular endothelial cells
  • Reduces coronary artery disease
  • Suppress’ insulin resistance

A study from 2005 showed that over-expression of Klotho in mice extends their average life span between 19% and 31% compared to normal mice.  4 

Klotho protein functions as a circulating hormone that binds to a cell-surface receptor and represses intracellular signals of insulin and insulin-like growth factor 1 (IGF1), an evolutionarily conserved mechanism for extending life span. Alleviation of aging-like phenotypes in Klotho-deficient mice was observed by perturbing insulin and IGF1 signaling, suggesting that Klotho-mediated inhibition of insulin and IGF1 signaling contributes to its anti-aging properties.

Image result for klotho

Figure 2.  Life Extension Factor Klotho Enhances Cognition  (Source)

A single-nucleotide polymorphism (SNP) in the Klotho gene, known as rs9536314, is associated with longevity and increased cognition.  5 

The “GT” allele in the rs9536314 SNP is associated with an increase in the Klotho protein which results in life extension and enhanced cognitive function. 

It is estimated that 80% of the population has the “TT” allele and less than 20% have the “GT” allele, with the rest of the population having the “GG” allele. 

Having the “GT” allele of rs9536314 has been associated with: 

  • Increased longevity
  • Improved cardiovascular function
  • Improved kidney health
  • Larger brain volume
  • Improved cognitive function

Regardless of what variation of the rs9636314 SNP of the Klotho gene one may have, certain natural substances can increase and enhance Klotho expression.  These natural substances are listed in the Table below:

KLOTHO Activators

CategorySubstanceReference
Fungi
CordycepsRef.
Red Yeast RiceRef.
Herbs
Clotholine® (from the seeds of Centaurea cyanus)Ref.
Gentian rootRef.
Probiotics
Lactobacillus acidophilusRef.
Bifidobacterium bifidumRef.
Vitamins
Vitamin DRef.
 

Summer Savory: Potential Prevention and Treatment of a Number of Serious Health Conditions

Summer savory (Satureja hortensis) belongs to the Lamiaceae family which contains about 200 species of herbs and shrubs which are grown mostly in the Mediterranean region, Europe, West Asia, North Africa, the Canary Islands, and South America.

Summer savory has lilac tubular flowers which bloom in the northern hemisphere from July to September. It grows to around 30 to 60 cm (0.98 to 1.97 ft) in height and has very slender, bronze-green leaves. 

Summer Savory is used as a spice in many European countries.  It has a spicy aroma and pungent, peppery flavor.  It is one of the ingredients in the popular spice blend called Herbes de Provence.

Compounds in Summer Savory

Summer savory contains the following compounds:  1

  • rosmarinic acid (α-O-caffeoyl-3,4-dihydroxy-phenyl lactic) (the major compound in the ethanolic extracts of summer savory)  2 
  • carvacrol (30 to 45%)
  • thymol
  • α-terpinene
  • γ-terpinene
  • β-caryophyllene
  • β-bisabolene
  • p-cymene (max. 30%)
  • α-pinene (8%)
  • dipentene
  • borneol
  • 1-linalool
  • terpineol
  • l-carvone 

Medicinal Properties of Summer Savory

There have been a number of published studies on the medicinal benefits of the Satureja species in general and Satureja hortensis (Summer Savory) in particular.

Following is a list of the various conditions that are effected by the use of Satureja hortensis:

Antispasmodic

The protective properties of Satureja hortensis on the rat lymphocytes DNA lesions were tested.  Both the ethanolic extract and the essential oil of the plant reversed the oxidative damage to rat lymphocytes induced by hydrogen peroxide.  3

Antinociceptive

Antinoiceptive is the action or process of blocking the detection of a painful or injurious stimulus by sensory neurons.  Results suggest that S. hortensis L. has antinociceptive and anti-inflammatory effects and probably mechanism(s) other than involvement of opioid and adenosine receptors mediate(s) the antinociception.  4

Anti-inflammatory

Studies have shown that polyphenolic compounds and essential oil of Satureja species have potent anti-inflammatory effects. The studies support the traditional usage of S. hortensis as a remedy for reducing inflammation and relieving pain.  5 

Antioxidant Activity

The leaves of summer savory are rich in phenolic compounds, particularly rosmarinic acid and flavonoids, which account for the high antioxidant capacity of the leaves.  6 

Anticoagulant

S. hortensis appears to have blood anticoagulant activity. Carvacrol and other monoterpene hydrocarbons, flavonoids like apigenin, and phenolic acids like labiatic acid could contribute to the anti-platelet property of S. hortensis.   7 

Alzheimer’s disease

The essential oil and the methanol extract of Satureja thymbra were evaluated for cholinesterase inhibitory effects against acetylcholinesterase and butyrylcholinesterase which are the chief enzymes of Alzheimer’s disease.  The experimental findings indicated that the compounds, except p-cymene, were active in both activity tests. Moreover, the extract exhibited a good lipid peroxidation inhibitory activity.  8

Anti-bacterial and Anti-fungal

The essential oil of S. hortensis contains significant amounts of two phenolic ketones: Carvacrol and thymol. Carvacrol and thymol have been generally reported to have a strong inhibitory effect on the growth of wide range of microorganisms including fungi and bacteria.  9  10  11

Thymol, p-cymene, γ-terpinene and carvacrol were the main components of S. hortensis oil while thymol, γ-terpinene, and o-cymene were the major components of T. copticum oil. Two essential oils exhibited strong antimicrobial activity but the antimicrobial activity of T. copticum oil was higher than that of S. hortensis oil.  12

The essential oil and methanol extract of Satureja hortensis were tested for antifungal activity against Aspergillus flavus in vitro on Petri plates and liquid culture, and under storage conditions. The oil showed strong antifungal activity based on the inhibition zone and minimal inhibitory concentration values against the pathogen on Petri plates assays. The results in this study showed that the essential oil of S. hortensis had strong antifungal activity against pathogen fungi tested. So, the essential oil of S. hortensis could be used for management of this pathogen as a potential source of sustainable eco-friendly botanical fungicides.  13

arNOX inhibitor

Aging-Related Cell Surface NADH Oxidase (arNOX) generates the potent free radical superoxide.  The aging-related ECTO-NOX protein (arNOX) provides a mechanism to transmit cell surface oxidative changes to surrounding cells and circulating lipoproteins potentially important to atherogenesis.   S. hortensis actively inhibits arNOX.  14

Cancer

The effect of carvacrol on a human non-small cell lung cancer (NSCLC) cell line known as A549 shows that carvacrol has an inhibitory effect on the cancer cells, but does not have a significant effect on normal lung cells (HFL1).  15 


Resources:

Summer Savory (dried spice)


    Print This Post Print This Post