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

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

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

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

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

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

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

The six PEs that were identified include:  2

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

 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The Proposed Nine Hallmarks of Aging

Scientist and researchers have attempted to identify and categorize the cellular and molecular hallmarks of aging in a published paper in the research journal Cell on 6th June 2013.  1 

In this paper, researchers proposed nine candidate hallmarks that are generally considered to contribute to the aging process and together determine the aging phenotype.

These nine hallmarks include:

  • altered intercellular communication
  • cellular senescence
  • deregulated nutrient-sensing
  • epigenetic alterations
  • genomic instability
  • loss of proteostasis
  • mitochondrial dysfunction
  • stem cell exhaustion
  • telomere attrition

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The 9 Hallmarks of Aging  (Source: The Hallmarks of Aging)

Researchers set three criteria for each ‘hallmark’:  2

  • it should manifest during normal aging;
  • its experimental aggravation should accelerate aging; and
  • its experimental amelioration should retard the normal aging process and, hence, increase healthy lifespan.

The challenge that the researchers encountered was to show the interconnectedness between the candidate hallmarks and their relative contribution to aging.  The ultimate goal of the research was to “identifying pharmaceutical targets to improve human health during aging with minimal side-effects.”  3

A clear and easy to understand article on the nine Hallmarks of Aging was published by Geroscience.com on 23rd February 2017.  This article, written by Alexandra Bause, PhD, examines each of the nine hallmarks in plain English and provides a better understanding beyond the original publication in the journal Cell.   

Despite the fact that these hallmarks can be complex and complicated and the understanding of them are still limited, there is hope that new medical strategies will emerge that will ameliorate the the normal aging process.

Geroscience.com is the premier site for news, discussion, and scientific insight related to the basic biology of aging and the development of new medicines with the ability to cure or prevent the diseases of aging.

Geroscience.com is committed to bringing its readers the most interesting developments in the science of aging and will: 4

  • Feature a wide range of multimedia content including interviews with experts, looks behind the scenes of everyday lab life, and the latest trends from longevity conferences
  • Capture the perspectives of leading researchers, entrepreneurs, and other experts to act as a platform to share ideas about aging and longevity
  • Cover the emerging biotechnology business of geroscience, including investment coverage, clinical trial data, and insight into the regulatory world
  • Aid collaboration between cross-functional scientific communities, connecting researchers, investors, and industry heads from around the globe

  

Read the article at Geroscience.com:

The hallmarks of aging, in plain English, by Alexandra Bause, PhD at Geroscience.com

 

Free E-Book: The Health and Medicinal Benefits of Ashitaba

Ashitaba, which is the common name used in Japan, is botanically known as Angelica keiskei or Angelica Keiskei Koidzumi. The English translation of the Japanese word “Ashitaba” (アシタバ or 明日葉) is “Tomorrow’s Leaf”. Ashita means ‘tomorrow and ba means ‘leaf.’ The name stems from the plant’s ability to quickly regenerate new leaves after taking cuttings. This give an indication of its potential for longevity of life.

asitab_5

Ashitaba plant

There are two separate substances (products) that are derived from the Ashitaba plant.

The first is the hot-air dried powder of Ashitaba from the leaves and stems. The color of this powder is bright green. The leaves of the Ashitaba plant contain approximately 0.25% to 0.35% chalcones.

The second is the powder made from the unique yellow sap which is collected from the Ashitaba’s stem. It is commonly called Ashitaba Chalcone Powder which consists up to 8% chalcones. The color of Ashitaba Chalcone Powder is bright yellow and is a fat-soluble substance.

Although the green Ashitaba powder from the leaves and stems provide nutritional and health benefits, it is the Ashitaba Chalcone Powder (bright yellow powder from the sap of the stem) that is the Chalconoids are natural phenols related to chalcone. They form the central core for a variety of important biological compounds.

997422_orig

Chalcone sap from Ashitaba stem

Chalcones are the active factors in Angelica Keiskei Koidzumi. At least 20 chalcones have been identified in Angelica Keiskei.

Ashitaba contains a thick, sticky yellow sap, which is not found in other celery plants, and are unique to this strain of angelica. This yellowish element in Ashitaba contain the chalconoids.

 

Download the Free E-Book (PDF): The Health and Medicinal Benefits of Ashitaba

Left-click to download into new window, then right-click (in new window) to save as PDF file.

Ginkgo biloba Increases Global Cerebral Blood Flow

One of the leading factors of cognitive impairment leading to dementia and eventually Alzheimer’s disease is a condition where there is insufficient blood flow to the brain or an inadequate supply of blood to the brain. 

The condition of reduced blood flow to the brain is called cerebral ischemia or hypoperfusion of the brain.

Hypoperfusion of the brain can severely diminish neurological function and is often the first indication of changes that impact the brain and which precedes structural deterioration of the brain.  1

Researchers published a study in March 2011 that sought to determine if changes in cerebral blood flow could be detected by dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSC-MRI) in elderly human subjects taking an Extract of Ginkgo biloba (EGb).   2

Image result for ginkgo biloba

Ginko biloba leaves

The test subjects were nine healthy men with a mean age of 61±10 years.  They took 60 mg EGb twice daily for 4 weeks.

Cerebral blood flow (CBF) values were computed before and after EGb, and analyzed at three different levels of spatial resolution, using voxel-based statistical parametric mapping (SPM), and regions of interest in different lobes, and all regions combined.

Test results showed a small CBF increase in the left parietal–occipital region. CBF in individual lobar regions did not show any significant change post-EGb, but all regions combined showed a significant increase of non-normalized CBF after EGb (15% in white and 13% in gray matter, respectively, P≤0.0001).

Researchers concluded that a mild increase in CBF is found in the left parietal–occipital WM after EGb, as well as a small but statistically significant increase in global CBF.

Cover Photo credit: Radu Jianu, Brown University

In Search of Geroprotectors: The Final Four Have Been Identified

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  (compounds capable of identifying and eliminating senescent cells)

Senescent cells enter a stage in which they no longer properly divide and function and become dysfunctional, which utlimately leads to organ failure.  Senescent cells also generate pro-inflammatory compounds which potentially damage healthy tissues.

Senolytics and geroprotectors eliminate aging and senescent cells from the tissues which then makes room for newer more active cells.

Life Extension® has partnered with Insilico Medicine to identify nutrient cocktails that function as geroprotectors by employing artificial intelligence biomedical algorithms.  These strategic uses of high-speed computer programs accelerates the research into potential geroprotectors. 

In a study published on April 23, 2016 in the Journal Aging, the authors, including Life Extension® and Insilico Medicine, among others, used GeroScope to develop a list of geroprotectors. 1

GeroScope is a computational tool that can aid prediction of novel geroprotectors from existing human gene expression data. GeroScope maps expression differences between samples from young and old subjects to aging-related signaling pathways, then profiles pathway activation strength (PAS) for each condition.

Known substances are then screened and ranked for those most likely to target differential pathways and mimic the young signalome. 

The study identified and shortlisted ten substances, all of which have lifespan-extending effects in animal models.  These ten substances include:

  • 7-Cyclopentyl-5-(4-phenoxy)phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine
  • Epigallocatechin gallate (EGCG)
  • Fasudil (HA-1077)
  • HA-1004
  • Myricetin
  • N-acetyl-L-cysteine (NAC)
  • Nordihydroguaiaretic acid (NDGA)
  • PD-98059
  • Staurosporine
  • Ursolic acid
Drug Code Model Organism Lifespan (LS) Parameter % Increase Ref.
Nordihydroguaiaretic acid A D. melanogaster Median LS 23 [47]
Mus Musculus Median LS 12 [48]
Myricetin B C. elegans Mean LS 32.9 [48,49]
HA-1004 C D. melanogaster Mean LS 18 [50]
7-Cyclopentyl-5-(4-phenoxy)phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine D C. elegans Mean LS 11 [51]
Staurosporine E D. Melanogaster Mean LS 34.8 [50]
Ursolic acid F C. elegans Mean LS 39 [52]
N-acetyl-L-cysteine G Mice Max LS 40 [53]
Fasudil (HA-1077) H D. melanogaster Mean LS 14.5 [50]
PD-98059 I D. melanogaster Mean LS 27 [50]
Epigallocatechin gallate J C. elegans Mean LS 10.1 [54]
Rattus norvegicus Median LS 13.5 [55]

Table 3. Previously reported lifespan effects of test substances in animal models (compiled from geroprotectors.org [15].)  Source:  In search for geroprotectors: in silico screening and in vitro validation of signalome-level mimetics of young healthy state

The researchers narrowed down the list of ten substances to the final four compounds, which include:

  • Gamma tocotrienol (Vitamin E)
  • Epigallocatechin gallate (EGCG) (found in Green tea)
  • N-acetyl-L-cysteine (NAC)
  • Myricetin

These final four compounds combat numerous aging factors throughout the body by working together by influencing key anti-aging pathways. 

The researchers concluded that these four compounds reduced cellular aging and protect against the development of senescent cells by modulating a group of signaling pathways.

For a breakdown of the various pathways modulated by the final four compounds, read and review the April 2017 article from Life Extension®.

Life Extension® has combined these final four compounds into a new supplement product called GEROPROTECT™ Ageless Cell™.  Supplementing with this product may reduce the body’s burden of senescent cells.  

The Potent Compounds of Salvia militorrhiza (Danshen)

Salvia miltiorrhiza, also known as red sage, Chinese sage, tan shen, or danshen, is a perennial plant in the genus SalviaSalvia miltiorrhiza is native to China and Japan where it grows at 90 to 1,200 m (300 to 3,940 ft) elevation, preferring grassy places in forests, hillsides, and along stream banks. The specific epithet miltiorrhiza means “red ochre root” as can be seen in the photo below:

DanshenRoot

Salvia militorrhiza BUNGE (Danshen) roots

Scientist have identified over 80 compounds in Danshen, both water soluble and fat soluble:  1  2  3

  • 50 water soluble compounds
    • Salvianolic acid B
    • Danshensu (Salvianolic acid A)
    • Protocatechuic aldehyde
  • 30 fat soluble compounds
    • Tanshinones
      • Tanshinone I
      • Tanshinone IIA 
      • Cryptotanshinone

The two compounds that show the most pharmalogical significance is the Salvianolic acids, Salvianolic acid A (danshensu) and the tanshinones, Tanshinone I and Tashinone IIA.

Salvianolic acid B is a potent antioxidant and has been investigated for its ability to protect against cerebrovascular disorders.  4  5

The Tanshinones (Dihydrotanshinone, tanshinone I, and tanshinone IIA) are currently being investigated for their anti-cancer effects.  6  7

The Table below lists the active compounds that have been studied for their therapeutic benefits in human health with references to various scientific studies for each compound:

Active Compounds in Salvia miltorrhiza Bunge

Compounds in Salvia miltorrhiza Bunge Clinical ApplicationsFunctions and UsesReferences
Cryptotanshinone1. Coronary heart disease and sugar diabetes; 2. Anti-infections; 3. To treat hepatitis and lepra disease.Cryptotanshinone is a major tanshinone isolated from Salvia miltiorrhiza that uses in many different fields. It has a good effection cardiovascular disease resisting fungus, also been effective to inhibit bacterium and diminish inflammation.1 2 3
Danshensu sodium1. Anti-bacterial 2. Anti-atherosclerotic 3. Enhancing immune1. Prevention for cardiac muscle, inhibit platelet aggregation; 2. Prevention for nerve cell and hepatic fibrosis; 3. Anti-bacterial, anti-inflammatory, anti-atherosclerotic and anticoagulation. Hypolipidemic effect and enhancing immune1 2 3
Danshensu/Salvianic Acid A1. Coronary heart disease 2. Anti-platelet aggregation 3. Protection for heartDanshensu is mainly used as raw material for clearing heat, anti-inflammation, detumescence and increasing coronary flow.1 2 3
Dihydroanshinone1. Antibacterium 2. Antifungal activity 3. Anti-thromboticSome inhibitory effects on Staphylococcus aureus, human-type Mycobacterium tuberculosis, Mycobacterium, leather bacteria etc. Inhibit platelet aggregation, anti-oxidants and expansion of coronary activity. Applied in medicine, healthcare food, food additive1 2 3 4 5 6
Magnesium Lithospermate B1. Anti-oxidative junction 2. Protection for heart 3. Protection for brain 4. Prevention for hepatic fibrosis 5. Anti-aging and anti-tumorPromoting blood circulation and removing blood stasis, Stimulate the menstrual flow and activate the collaterals. It is used for apoplexy and the angina caused by coronary artery disease. Anti-fibrosis of liver. Mainly applied in Medicine, healthcare food, food additive.1 2 3 4 5 6 7 8
Protocatechuic aldehyde1. Anti-inflammation 2. anti-prostaglandin 3. anti-lipid peroxidationIt has a strong effect on antithrombotic, improving the blood circulation and anti-oxidant. Applied in medicine, healthcare food, food additive.1 2 3 4
Salvianolic Acid B1. Anti-oxidative junction 2. Protection for heart 3. Protection for brain 4. Prevention for hepatic fibrosis 5. Anti-aging and anti-tumorPromoting blood circulation and removing blood stasis, Stimulate the menstrual flow and activate the collaterals. It is used to cure apoplexy and the angina caused by coronary artery disease. Anti-fibrosis of liver. Mainly applied in Medicine, healthcare food, food additive.1 2 3 4 5 6 7 8
Sodium tanshinoneⅡA sulfonate1. To ease postpartum pain 2.To remove goreSodium tanshinoneⅡA sulfonate is used to remove blood stasis and relieve pain, promote the flow of blood and stimulate menstrual discharge, expand blood vessels. It has a good effect on abnormal menstruation.1 2 3 4 5 6
Tanshinone I1. To depress pains in bodies 2. Promote the secretion of estrogen 3. Against angina pectoris1.It has a strong inhibition on human strains of Mycobacterium and is for the treatment of acne, and angina pectoris; 2. It is effective on the treatment of hepatitis and lepra disease. Applied in medicine, healthcare food, food additive.1 2 3 4 5 6 7 8
Tanshinone IIA1. To expend vessel 2. Depress blood pressure 3. Anti-thrombotic 4 AntioxidantUsed in medicine, healthcare food, food additive.1 2 3 4 5 6 7 8
Source of Columns 1, 2 and 3 is Xi 'an Honson Biotechnology Co., Ltd.
References provided by BioFoundations.org

 


Hibiscus sabdariffa (Roselle) Shows Promise as an Antihypertension Agent

Hibiscus sabdariffa, commonly known as Roselle is a member of the species of Hibiscus.  It is an annual or perennial that is native to West Africa.  The leaves and stems of Roselle are commonly used throughout the world as a tea.

The leaves of Roselle has been used medicinally for centuries and contain a large variety of polyphenols.  The major identified compounds include:  1

  • anthocyanins
  • caffeoylshikimic acid
  • chlorogenic acid
  • chrysanthenin
  • cryptochlorogenic acid
  • daphniphylline
  • delphinidin
  • gossypetin
  • hibiscetine
  • hibiscin
  • kaempferol
  • neochlorogenic acid
  • protocatechuic acid
  • quercetin
  • sabdaretine

Image result for hibiscus sabdariffa

Figure 1.  Dried Hibiscus sabdariffa (used in tea)

Extracts of the calyces of Roselle have demonstrated hypocholesterolemic and antihypertensive properties. The potential mechanisms for Roselle’s antihypertensive effects may be the antioxidant effects of the anthocyanins inhibition of LDL-C oxidation, which impedes atherosclerosis, an important cardiovascular risk factor.   2 

There are five important researched studies that have found consumption of Roselle had antihypertensive effects and were able to lower systolic and diastolic blood pressure:

Study 1

A study from February 2010 examined the antihypertensive effects of Hibiscus sabdariffa tisane (hibiscus tea) consumption in humans. A randomized, double-blind, placebo-controlled clinical trial was conducted in 65 pre- and mildly hypertensive adults, age 30–70 y, not taking blood pressure (BP)-lowering medications, with either 3 240-mL servings/d of brewed hibiscus tea or placebo beverage for 6 wk. A standardized method was used to measure BP at baseline and weekly intervals. At 6 wk, hibiscus tea lowered systolic BP (SBP) compared with placebo (−7.2 ± 11.4 vs. −1.3 ± 10.0 mm Hg; P = 0.030). Diastolic BP was also lower, although this change did not differ from placebo (−3.1 ± 7.0 vs. −0.5 ± 7.5 mm Hg; P = 0.160). The change in mean arterial pressure was of borderline significance compared with placebo (−4.5 ± 7.7 vs. −0.8 ± 7.4 mm Hg; P = 0.054). Participants with higher SBP at baseline showed a greater response to hibiscus treatment (r = −0.421 for SBP change; P = 0.010).  3

These results suggest daily consumption of hibiscus tea, in an amount readily incorporated into the diet, lowers BP in pre- and mildly hypertensive adults and may prove an effective component of the dietary changes recommended for people with these conditions. 

Study 2

Previous studies have demonstrated that Hibiscus sabdariffa extracts reduce blood pressure in humans, this study from 2010 demonstrated that this effect is due to angiotensin converting enzyme (ACE) inhibitor activity.  The aim of the current study was to isolate and characterizer the constituents responsible of the ACE activity of the aqueous extract of H. sabdariffa.  Bioassay-guided fractionation of the aqueous extract of dried calyces of H. sabdariffa using preparative reversed-phase HPLC, and the in vitro ACE Inhibition assay, as biological monitor model, were used for the isolation.  The isolated compounds were characterized by spectroscopic methods.  The anthocyanins delphinidin-3-O-sambubioside (1) and cyanidin-3-O-sambubioside (2) were isolated by bioassay-guided purification.  These compounds showed IC(50) values (84.5 and 68.4mug/mL, respectively), which are similar to those obtained by related flavonoid glycosides.  4   Researchers in this study did not find that Roselle was not as strong an ACE inhibitor as pharmaceutical reference drugs.

Study 3

In this study from 2004, researchers compared the antihypertensive effectiveness and tolerability of a standardized extract from Hibiscus sabdariffa with captopril, a controlled and randomized clinical trial was done. Patients from 30 to 80 years old with diagnosed hypertension and without antihypertensive treatment for at least 1 month before were included. The experimental procedure consisted of the administration of an infusion prepared with 10 g of dry calyx from H. sabdariffa on 0.51 water (9.6 mg anthocyanins content), daily before breakfast, or captopril 25 mg twice a day, for 4 weeks. The outcome variables were tolerability, therapeutic effectiveness (diastolic reduction > or = 10 mm Hg) and, in the experimental group, urinary electrolytes modification.

The results showed that H. sabdariffa was able to decrease the systolic blood pressure (BP) from 139.05 to 123.73mm Hg (ANOVA p < 0.03) and the diastolic BP from 90.81 to 79.52mm Hg (ANOVA p < 0.06). At the end of the study, there were no significant differences between the BP detected in both treatment groups (ANOVA p > 0.25).  5

Study 4

This study from 2009 compared the antihypertensive effectiveness of sour tea (ST; Hibiscus sabdariffa) with black tea (BT) infusion in diabetic patients.

Sixty diabetic patients with mild hypertension, without taking antihypertensive or antihyperlipidaemic medicines, were recruited in the study. The patients were randomly allocated to the ST and BT groups and instructed to drink ST and BT infusions two times a day for 1 month. Their blood pressure (BP) was measured on days 0, 15 and 30 of the study. The mean of systolic BP (SBP) in the ST group decreased from 134.4+/-11.8 mm Hg at the beginning of the study to 112.7+/-5.7 mm Hg after 1 month (P-value <0.001), whereas this measure changed from 118.6+/-14.9 to 127.3+/-8.7 mm Hg (P-value=0.002) in the BT group during the same period. The intervention had no statistically significant effect on the mean of diastolic BP (DBP) in either the ST or BT group. The mean pulse pressure (PP) of the patients in the ST group decreased from 52.2+/-12.2 to 34.5+/-9.3 mm Hg (P-value <0.001) during the study, whereas in the BT group, it increased from 41.9+/-11.7 to 47.3+/-9.6 mm Hg (P-value=0.01). In conclusion, consuming ST infusion had positive effects on BP in type II diabetic patients with mild hypertension.  6

Study 5

This study from 2012 investigated the effect of the water extract of the dried calyx of HS and Hibiscus anthocyanins (HAs) on left ventricular myocardial capillary length and surface area in spontaneously hypertensive rats (SHRs). Twelve-week-old male SHRs were divided into eight groups (six rats in each group). Three groups were given three doses; 10%, 15% and 20% of the water extract of HS in lieu of drinking water for 10 consecutive weeks (HS10, HS15 and HS20) with one group kept as control (C). Another three groups were given three doses of the HAs orally at doses of 50, 100 and 200 mg/kg for five consecutive days with one group kept as a control (C). Systolic (SBP) and diastolic (DBP) blood pressures, as well as heart rate (HR), were measured weekly. After the experimental protocols, the left ventricles (LV) of all rats were obtained. Capillary surface area density and length density were determined by unbiased sterological methods on 3 μm LV tissue samples from perfusion-fixed hearts. HS ingestion significantly reduced SBP, DBP and LV mass in a dose-dependent fashion but did not affect the HR. HS significantly increased surface area and length density of myocardial capillaries by 59%, 65% and 86%, and length density by 57%, 77% and 57%, respectively. Myocyte nuclear volume was significantly decreased in HS-treated rats. There was a decrease (although insignificant) in SBP and DBP with HA ingestion compared with controls. These changes suggest that the observed beneficial effect of HS on high BP in SHRs could be mediated through a reduction in the diffusion distance between capillaries and myocytes, as well as new vessel formation.  7

A published paper from January 2010 concluded that there is insufficient clinical evidence that Roselle can control and lower blood pressure.

The Cochrane Database of Systematic Reviews published an meta-analysis in which they searched for evidence from clinical studies to evaluate the effectiveness of red tea compared with placebo or no treatment in hypertensive patients. They found that there is a lack of evidence from randomised control trials to demonstrate a benefit of Roselle tea in reducing blood pressure. They concluded that rigorous studies need to be done in order to answer this question.  8  

Lactobacillus reuteri NCIMB 30242 is a Heart Healthy Probiotic

Lactobacillus reuteri is a Gram-positive bacterium that is naturally found in the microbiome and is considered one of the most ubiquitous members of the naturally occurring gut bacteria.

Lactobacillus reuteri NCIMB 30242 or LRC™ is a unique superstrain of Lactobacillus reuteri that was initially developed by Micropharma Limited based in Canada.  In 2014, the U.S. company UAS Laboratories acquired the rights of this superstrain probiotic from Micropharma Limited.

Lactobacillus reuteri NCIMB 30242 is the first clinically proven heart health probiotic.  1

Clinical trials have been conducted with Lactobacillus reuteri NCIMB 30242 and the results were very promising for cardiovascular health.  The health benefits of Lactobacillus reuteri NCIMB 30242 include:

  • Supports healthy cholesterol already within normal range by reducing total cholesterol and LDL cholesterol
  • Supports healthy LDL particle size by supporting healthy apoB-100 (a marker for LDL particle number)
  • Promotes a healthy inflammatory response by supporting healthy C-reactive protein
  • Maintains healthy fibrinogen levels, helping to prevent blood clot formation
  • Supports and increases vitamin D levels (25-hydroxyvitamin D)
How L. Reuteri Helps The Body

Figure 1.  How L. Reuteri Helps the Body  (Source:  Life Extension Foundation: Unique Probiotic Targets Cardiovascular Disease)

Supports Healthy Total and LDL Cholesterol

In clinical trials, Lactobacillus reuteri NCIMB 30242 demonstrated an ability to support healthy cholesterol in adults already within the normal range.  2

It supports healthy total cholesterol and LDL-cholesterol levels in two ways:

  • By supporting the natural elimination of cholesterol, and
  • By helping to maintain the normal amount of cholesterol the body produces

Lactobacillus reuteri NCIMB 30242 produces an enzyme called bile salt hydrolase.  This enzyme breaks apart bile acids which are natural detergents made by the liver from cholesterol.  3  4

Supports Healthy LDL Particle Size

The size of LDL particles is governed by and influenced by a lipoprotein called apoB-100.  The particle size of LDL is critical to maintaining heart health.

Lactobacillus reuteri NCIMB 30242 has been shown to support healthy apoB-100 levels, which in turn may help to maintain healthy LDL particle size.  5

In one study of adults with elevated cholesterol, apoB-100 fell by 8% after consuming Lactobacillus reuteri NCIMB 30242.  6

Supports Healthy C-reactive protein (CRP) Levels

C-reactive protein (CRP) is a sensitive marker of inflammation that is used by medicine as a predictor of overall cardiovascular health. Lactobacillus reuteri NCIMB 30242 has been shown to support healthy CRP levels.  7

Maintains Healthy Fibrinogen Levels

Lactobacillus reuteri NCIMB 30242 has been shown to support healthy fibrinogen levels.  8

Increases Mean Circulating 25-hydroxyvitamin D

Oral supplementation with probiotic Lactobacillus reuteri NCIMB 30242 increases mean circulating 25-hydroxyvitamin D.  Lactobacillus reuteri NCIMB 30242 increased serum 25-hydroxyvitamin D by 14.9 nmol/L, or 25.5%, over the intervention period, which was a significant mean change relative to placebo of 17.1 nmol/L, or 22.4%, respectively (P = .003).  9  

Informational References:

UAS Labs  

Natural Anticoagulant Regimen from Dr. Phillip Lee Miller

Dr. Philip Lee Miller, MD is the Founder, Medical Director and CEO of California Age Management Institute.  He has been in medical practice for over 43 years.

He graduated from UC Berkeley in 1968 (Centennial ) with a degree in Biochemistry.  In 1972 he graduated from the School of Medicine at UC San Diego with an MD degree.  This was the school’s first (charter) graduating class.  There was further training in Neurology at UC Davis.  He was ABEM Board Certified in Emergency and is currently a Diplomat of the ABAAM Board.

Dr. Miller has become a recognized leader in anti aging and integrative medicine.

Dr. Miller has written a very interesting four-part series on a natural anticoagulant regimen on his antiaging blog.

The four articles include:

Coagulation Stroke Heart Attack Part 1

Coagulation Heart Attack and Stroke – Part 2

AntiPlatelet AntiCoagulant Drugs

Anticoagulant Natural Alternative

Dr. Miller’s has identified five powerful natural anticoagulants.  They include the following:

  • Nattokinase — 100 mg (2000 FU) twice daily
  • Ginkgo biloba — 120 mg daily
  • High-dose fish oils — 1 tablespoon (10 grams) daily
  • Vitamin E — 400-800 units of mixed tocopherols daily
  • Adequate hydration — many glasses of pure water daily  

Centella asiatica (Gotu Kola): Considered a “Miracle Elixir of Life” by Traditional Chinese Medicine*

Introduction of Centella asiatica

Centella asiatica is a small perennial plant of the family Mackinlayaceae or subfamily Mackinlayoideae of family Apiaceae, and is native to wetlands in Asia.  It is commonly known as Gotu Kola.

centella-asiatica-plant

Centella asiatica plant

Centella asiatica (CA) has been used extensively in Asia and is considered a very important medicinal herb in that region of the world.  In India, it is commonly known as mandukparni or Indian pennywort or jalbrahmi, and is used as a medicine in the Ayurvedic medicine.  It has been listed in the ancient Indian medical text, ‘Sushruta Samhita’ for thousands of years. 

In China it is known as gotu kola or Jī Xuě Cǎo.  The Chinese name is 积雪草, which is translated as “accumulation of snow herb”.   Gotu kola is has been used extensively in traditional Chinese medicine and has been reported as one of the “miracle elixirs of life” for over 2000 years.  1

Active constituents of Centella asisatica

The main active constituents of CA are saponins or triterpenoids.

Triterpenoids

Plants with Triterpenoids

(Source:  Targeting Inflammatory Pathways by Triterpenoids for Prevention and Treatment of Cancer, Toxins 2010, 2(10), 2428-2466; doi:10.3390/toxins2102428)

The triterpenoids include:

  • asiaticosides,
  • madecassoside
  • madasiatic

Other components isolated from CA include:

  • asiaticoside
  • asiatic acid
  • brahmic acid
  • brahmoside
  • brahminoside
  • centelloside
  • centellose
  • chercetin
  • isothankuniside
  • kempferol
  • madecassoside
  • thankuniside
  • vallerine

Mechanisms of Actions Based on Preclinical Studies

The triterpenoids listed above, being the primary constituents of Centella asiatica, are considered responsible for its wide therapeutic actions.  2

Following is a list of some of the known therapeutic actions of Centella asiatica, based on preclinical studies:  3

Antidepressant properties

The results of a study from 2008  showed that the high dose of the plant extract enhanced working memory and increased N100 component amplitude of event-related potential.  Improvements of self-rated mood were also found following the Centella asiatica treatment.  The present findings suggest the potential of Centella asiatica to attenuate the age-related decline in cognitive function and mood disorder in the healthy elderly.  4

Antiepileptic properties

CA increases the cerebral levels of GABA, and can be used as an anxiolytic and anticonvulsant.The extract (200 mg/kg body weight) completely inhibited pentylenetetrazol-induced convulsions. In pentylenetetrazol-kindled seizures and strychnine-induced convulsions, the extract showed protection at a dose of 100 mg/kg body weight. The doses of the extract selected for remaining studies were based on pilot studies, animal model used, and so forth. These findings suggested its potential anticonvulsant as well as antioxidant, and CNS depressant actions.  5 

Antinociceptive and antiinflammatory properties

The aqueous Centella asiatica extract (CAE) revealed significant antinociceptive activity with both the models similar to aspirin but less potent than morphine and significant antiinflammatory activity comparable to mefenamic acid. These results suggested that the aqueous CA extracts possesses antinociceptive and antiinflammatory activities which justified the traditional use of this plant in the treatment of inflammatory conditions or rheumatism.   6 

Cardiovascular properties

Gotu kola inhibited shear-induced platelet activation (blood clotting).  7

Asiatic acid, a pentacyclic triterpene from Centella asiatica, is neuroprotective in a mouse model of focal cerebral ischemia.  Asiatic acid significantly reduced the infarct volume by 60% at day 1 and by 26% at day 7 postischemia and improved neurological outcome at 24 hr postischemia.  These studies also showed that the neuroprotective properties of asiatic acid might be mediated in part through decreased blood-brain barrier permeability and reduction in mitochondrial injury.  The present study suggests that asiatic acid may be useful in the treatment of cerebral ischemia.   8

Gastric ulcer

Oral administration of CE (0.05 g/kg, 0.25 g/kg and 0.50 g/kg) before ethanol administration significantly inhibited gastric lesions formation (58% to 82% reduction) and decreased mucosal myeloperoxidase (MPO) activity in a dose dependent manner.  These results suggested that Gotu kola prevented ethanol induced gastric mucosal lesions by strengthening the mucosal barrier and reducing the damaging effects of free radicals.   9

Neurological properties

CA is known to re-vitalize the brain and nervous system, increase attention span and concentration and combat aging.  10 

Derivatives of asiatic acid derivatives were shown to exert significant neuroprotective effects from the oxidative damage caused by exposure to excess glutamate.  11 

Asiaticoside derivatives protect against beta-amyloid neurotoxicity.  They showed a strong inhibition of beta-amyloid- and free radical-induced cell death and can be candidates for the treatment of Alzheimer›s disease that protects neurons from beta-amyloid toxicity.  12 

Supplementation of CAE reduced LPO and PCC and significantly increased (p < 0.01) TA and antioxidant enzyme levels (p < 0.01) in corpus striatum and hippocampus.  These results show that administration of C. asiatica was effective in protecting the brain against neurodegenerative disorders such as Parkinsonism.  13

Male Sprague-Dawley rats given Centella ethanolic extract in their drinking water (300-330 mg kg-1 daily) demonstrated more rapid functional recovery and increased axonal regeneration (larger calibre axons and greater numbers of myelinated axons) compared with controls, indicating that the axons grew at a faster rate.  Components in Centella ethanolic extract may be useful for accelerating repair of damaged neurons.   14

CA fresh leaf extract has a neuronal dendritic growth stimulating property; hence, the extract can be used for enhancing neuronal dendrites in stress and neurodegenerative and memory disorders.  15

Radioprotective

Centella asiatica extract significantly reduced radiation-induced damage to DNA.  Centella asiatica rendered radioprotection to DNA and membranes against radiation exposure, both in vitro and in vivo.  The authors have earlier reported that administration of the extract can prevent a radiation-induced decline in antioxidant enzyme levels.  This suggests that radioprotection by Centella asiatica extract could be mediated by mechanisms that act in a synergistic manner, especially involving antioxidant activity.  16

Sedative and anxiolytic properties

CA has been used as a stimulatory-nervine tonic, rejuvenant, sedative, tranquilizer and intelligence promoting property.  17 

Venous insufficiency

CA has been used to strengthen weakened veins in the case of venous insufficiency.  18 

Centella asiatica’s active constituents include pentacyclic triterpene derivatives.  Studies have been conducted in particular to investigate the madecassosides and asiaticosides.  In contrast to other medicinal plants, Centella asiatica has been subjected to quite extensive experimental and clinical investigations.  Studies done in accordance with standardized scientific criteria have shown it to have a positive effect in the treatment of venous insufficiency.  19

Wound healing

Wound healing is what CA has been traditionally been used for by Asian practitioners.  20 

Asiaticoside, a constituent in CA, has been reported to possess wound healing activity by increasing collagen formation and angiogenesis.  21   


Resources:

Gotu Kola (supplement)

Gotu Kola Extract (powder)


*

These statements have not been evaluated by the Food and Drug Administration (F.D.A). This product is not intended to diagnose, treat, cure or prevent any disease. Individual results obtained from taking these products may vary and are not guaranteed.  Please consult your doctor before starting any exercise or nutritional supplement program or before using these or any product during pregnancy or if you have a serious medical condition.


 

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