While we live in an age where people are living longer, an important limiting factor on longevity is the ability of the heart to maintain function. Known causes of death for the oldest people on record (over 110 years old) were recorded as heart failure. Heart failure is due to the gradual loss of cardiomyocytes (heart muscle cells) and the increase in scarring of the heart muscle. The process may take place due to low grade inflammation of the muscle, which progresses with age, or injury (such as a heart attack) which may cause a more sudden loss of heart function. Inflammation in the cardiovascular system is common with the aging process, being the result of hypertension, high blood glucose, trigylcerides, or oxidized VDL cholesterol.
Cardiac Aging Characteristics:
Key Conditions of the Aging Heart
Natural support for Cardio Anti-aging
*Andrographolide is also included
(1) Steenman M, et al. Cardiac aging and heart disease in humans. Biophys Rev. 2017 Apr;
(2) Zhu ZY, et al. Apigenin ameliorates hypertension-induced cardiac hypertrophy and down-regulates cardiac hypoxia inducible factor-lα in rats. Food Funct. 2016 Apr;7
(3) Liu HJ, et al. Apigenin alleviates STZ-induced diabetic cardiomyopathy. Mol Cell Biochem. 2017 Apr
(4) Hu W, et al. Luteolin improves cardiac dysfunction in heart failure rats by regulating sarcoplasmic reticulum Ca2+-ATPase 2a. Sci Rep. 2017 Jan
(5) Oberoi L, et al. The aqueous extract, not organic extracts, of Terminalia arjuna bark exerts cardiotonic effect on adult ventricular myocytes. Phytomedicine. 2011 Feb 15
(6) Parveen A, et al. Terminalia arjuna enhances baroreflex sensitivity and myocardial function in isoproterenol-induced chronic heart failure rats. J Cardiovasc Pharmacol Ther. 2012 Jun
(7) Kaliq F, et al, Improvement in myocardial function by Terminalia arjuna in streptozotocin-induced diabetic rats: possible mechanisms. J Cardiovasc Pharmacol Ther. 2013 Sept.
(8) Kumar S, et al. Proteomic analysis of the protective effects of aqueous bark extract of Terminalia arjuna (Roxb.) on isoproterenol-induced cardiac hypertrophy in rats. J Ethnopharmacol. 2017 Feb 23
(9) Kocak C, et al, Molecular and biochemical evidence on the protective effects of embelin and carnosic acid in isoproterenol-induced acute myocardial injury in rats. Life Sci. 2016 Feb 15
(10) Chung RWS, et al. Lutein exerts anti-inflammatory effects in patients with coronary artery disease. Atherosclerosis. 2017 May 6;
(11) Girandola RN, et al. Effect of E-OJ-01 on Cardiac Conditioning in Young Exercising Adults: A Randomized Controlled Trial. Am J Ther. 2017 May
(12) Qian ZQ, et al. Icariin prevents hypertension-induced cardiomyocyte apoptosis through the mitochondrial apoptotic pathway. Biomed Pharmacother. 2017 Apr.
(13) Gu J, et al. Metallothionein Is Downstream of Nrf2 and Partially Mediates Sulforaphane Prevention of Diabetic Cardiomyopathy. Diabetes. 2017 Feb;
(14) Lin CM, et al. Suppressive effect of epigallocatechin-3-O-gallate on endoglin molecular regulation in myocardial fibrosis in vitro and in vivo. J Cell Mol Med. 2016 Nov;
(15) Tan WS, et al. Is there a future for andrographolide to be an anti-inflammatory drug? Deciphering its major mechanisms of action. Biochem Pharmacol. 2017 Apr 2
(16) Lv FH, et al. Effects of curcumin on the apoptosis of cardiomyocytes and the expression of NF-κB, PPAR-γ and Bcl-2 in rats with myocardial infarction injury. Exp Ther Med. 2016 Dec
(17) Khaliq F, et al. Improvement in myocardial function by Terminalia arjuna in streptozotocin-induced diabetic rats: possible mechanisms. J Cardiovasc Pharmacol Ther, 2013 Sep
(18) Hashemzaei M, et al. Regulation of autophagy by some natural products as a potential therapeutic strategy for cardiovascular disorders. Eur J Pharmacol. 2017 May
(19) Hu J, et al. Luteolin alleviates post-infarction cardiac dysfunction by up-regulating autophagy through Mst1 inhibition. J Cell Mol Med, 2016 Jan
(20) Meghwani H, et al. Beneficial effects of aqueous extract of stem bark of Terminalia arjuna (Roxb.), An ayurvedic drug in experimental pulmonary hypertension. J Ethnopharmocol. 2017 Feb 2
(21) Woo AY, et al. Andrographolide up-regulates cellular-reduced glutathione level and protects cardiomyocytes against hypoxia/reoxygenation injury. J Pharmacol Exp Ther. 2008 Apr
(22) Zhang J, et al. Andrographolide Attenuates LPS-Induced Cardiac Malfunctions Through Inhibition of IκB Phosphorylation and Apoptosis in Mice. Cell Physiol Biochem. 2015
(23) Fernandes RO, et al. Sulforaphane effects on postinfarction cardiac remodeling in rats: modulation of redox-sensitive prosurvival and proapoptotic proteins. J Nutr Biochem. 2016 Aug
Aging of the brain involves the loss of neurons (hippocapmus shrinkage), loss of synapse integrity between neurons, build-up of toxic amyloid proteins, neuron tangles, defects in blood flow and chronic inflammation. Under normal age progression, these events do not happen over night and may take years before impairments in cognition become noticed.
Ultimate anti-aging strategies for the brain and memory should target the progressive decline of the brain and promote reversal and recovery of some cognition impairments.
Emerging research in the study of herbal ingredients show their tremendous potential use in mitigating the decline in brain function with age.
Herbs and Extracts
- Andrographolide - As an extract from Andrographis Paniculata. Lab research has shown stimulation of neurogenesis in the hippocampus by andorgrapholide. Specifically " increased cell proliferation and the density of immature neurons in the dentate gyrus." (1) The dentate gyrus is an area of the hippocampus involved in memory formation.
- Centella asiatica - Acts as a potent memory enhancer, via increasing hippocampus neurogenesis and support for brain tissue regeneration. (2)
- Baicalin (3)
- Panax Ginseng (4)
- Curcumin (5)
- Epimedium (Icariin) (6)
- Apigenin (7)
Herbs and Extracts
- Centella asiatica - Improves structural integrity of axons / myelination and proliferation of dendritic branching and length. Such improvements have been shown to enhance learning and improve memory. (8) Centella asiatica also has been shown to improve learning and memory in normal lab mice.
- Luteolin - Baicalin - promote neuronal survival and neuron differentiation through the outgrowth of neurites (axons and dendrites) from the neuron.(9.10)
- Rosemary (Carnosic Acid) - Strongly promotes neurite outgrowth as a function of powerful Nrf2 activity. Suppressed Nrf2 activation suppresses neuron differentiation.(11)
Herbs and Extracts
- Andrographolide - Impairment of synaptic function between neurons plays a significant role in the loss of cognitive function. This is seen in the progression of AD. In research animals with AD-like cognitive disease, the treatment of andrographolide over a 3 month span imporved synaptic function and protected important synaptic proteins.
- Furthermore, andrographolide has been shown to reduce inflammation in the brain and levels of pathological tau protein and beta amyloid in animal models.(12)
- Andrographolide reduces inflammation and dysfunction of the cerebral endothelial cells, which may affect vascular flow to the brain.(13)
- Centella asiactica - in senescence-accelerated lab mice, which had accelerated aging of the brain, administration of centella asiatica significantly improved synaptic plasticity and reduced beta amyloid build-up. Such treated mice showed significant benefits in memory and learning. (14)
(1) Varela-Nallar L, et al. Andrographolide Stimulates Neurogenesis in the Adult Hippocampus. Neural Plast, 2015.
(2) Sirichoat A, et al. Effects of Asiatic Acid on Spatial Working Memory and Cell Proliferation in the Adult Rat Hippocampus. Nutrients. 2015 Oct 5
(3) Zhang K, et al. Baicalin promotes hippocampal neurogenesis via SGK1- and FKBP5-mediated glucocorticoid receptor phosphorylation in a neuroendocrine mouse model of anxiety/depression. Sci Rep. 2016 Aug 9
(4) Jiang B, et al. Antidepressant-like effects of ginsenoside Rg1 are due to activation of the BDNF signalling pathway and neurogenesis in the hippocampus. Br J Pharmacol. 2012 Jul;
(5) Pluta R, et al. Neurogenesis and neuroprotection in postischemic brain neurodegeneration with Alzheimer phenotype: is there a role for curcumin? Folia Neuropathol. 2015
(6) Li F, et al. Icariin decreases both APP and Aβ levels and increases neurogenesis in the brain of Tg2576 mice. Neuroscience. 2015 Sep 24
(7) Taupin P. Apigenin and related compounds stimulate adult neurogenesis. Mars, Inc., the Salk Institute for Biological Studies: WO2008147483. Expert Opin Ther Pat. 2009 Apr
BRAIN TISSUE REGENERATION
(8) Yogeswarin L, et al. Recent Updates in Neuroprotective and Neuroregenerative Potential of Centella asiatica. Malays J Med Sci 2016 Jan.
(9) Chen PY, et al. Up-Regulation of miR-34a Expression in Response to the Luteolin-Induced Neurite Outgrowth of PC12 Cells. J Agric Food Chem. 2015 Apr
(10) Li M, et al. Neuronal differentiation of C17.2 neural stem cells induced by a natural flavonoid, baicalin. Chembiochem. 2011 Feb 11;
(11) Kosaka K, et al. Role of Nrf2 and p62/ZIP in the neurite outgrowth by carnosic acid in PC12h cells. J Biochem. 2010 Jan;
RECOVERING COGNITIVE DYSFUNCTION
(12) Rivera DS, et al. Andrographolide recovers cognitive impairment in a natural model of Alzheimer's disease (Octodon degus). Neurobiol Aging. 2016 Jul 5
(13) Chang CC, et al. Andrographolide, a Novel NF-κB Inhibitor, Inhibits Vascular Smooth Muscle Cell Proliferation and Cerebral Endothelial Cell Inflammation. Acta Cardiol Sin. 2014 Jul;
(14) Xing L, et al. Beneficial effects of asiaticoside on cognitive deficits in senescence-accelerated mice. Fitoterapia. 2013 Jun.
NEUROPROTECTION - AMYLOID TOXICITY AND INFLAMMATION
(15) Gray NE, et al. Centella asiatica Attenuates Amyloid-β-Induced Oxidative Stress and Mitochondrial Dysfunction. J Alzheimers Dis. 2015
(16) Zhang L, et al. Icariin reduces α-synuclein over-expression by promoting α-synuclein degradation. Age (Dondr.) 2015 Aug
(17) Chen YJ, et al. Neuroprotective Effects of Icariin on Brain Metabolism, Mitochondrial Functions, and Cognition in Triple-Transgenic Alzheimer's Disease Mice. CNS Neurosci Ther, 2016 Jan
(18) Dirscherl K, et al. Luteolin triggers global changes in the microglial transcriptome leading to a unique anti-inflammatory and neuroprotective phenotype. J Neuroinflammation 2010 Jan
(20) Chen C, et al. Baicalin attenuates alzheimer-like pathological changes and memory deficits induced by amyloid β1-42 protein. Metab Brain Dis. 2015 Apr
(21) Song F, et al. Schizandrin A Inhibits Microglia-Mediated Neuroninflammation through Inhibiting TRAF6-NF-κB and Jak2-Stat3 Signaling Pathways. PLoS One. 2016 Feb 26;
(22) Habtemariam S. The Therapeutic Potential of Rosemary (Rosmarinus officinalis) Diterpenes for Alzheimer's Disease. Evid Based Complement Alternat Med, 2016
REVERSES BRAIN INSULIN RESISTANCE IN BRAIN NEURONS
(23) Feng HL, et al. Curcumin ameliorates insulin signalling pathway in brain of Alzheimer's disease transgenic mice. Int J Immunopathol. 2016 Jul 27
(24) Angeloni C, et al. Neuroprotective effect of sulforaphane against methylglyoxal cytotoxicity. Chem Res Toxicol, 2015 Jun 15
INFLAMMATION OF THE SKIN Common forms of inflammatory skin diseases include psoriasis and eczema. Primary common features of these diseases include chronic inflammation, including break down of the skin barrier, dryness and redness and itchiness. Hyper proliferation of skin cells, adding a thickness to the affected areas, is also common, and caused by inflammatory factors.
Psoriasis and eczema are both immune initiated diseases involving lymphocytes (T-Cells: TH1. TH2 and TH17), which cause the secretion of pro-inflammatory factors (called cytokines). The T-cells migrate into the skin where they chronically secret inflammatory factors which inflame the skin. Among the methods to reduce skin inflammation is to decrease the proliferation of T-cells in the skin and to prevent the secretion of pro-inflammatory cytokines. While both psoriasis and eczema are immune T-cell based diseases, the causative basis of the immune response are not the same, and therefore the effects and targets are different.(1)
NOTE: In contrast to natural ingredients, standard immunosuppressive drugs (which reduce the immune response, and are marketed for psoriasis) may have side effects, including kidney fibrosis.(16)
(1) Coimbra S, et al. A specific molecular signature for psoriasis and eczema. Annals of Translational Medicine. 2015 Apr.
(2) Ke F, et al. Soluble Tumor Necrosis Factor Receptor 1 Released by Skin-Derived Mesenchymal Stem Cells Is Critical for Inhibiting Th17 Cell Differentiation. Stem Cells Transl Med. 2016 Jan 27
(3) Kang D, et al. Curcumin shows excellent therapeutic effect on psoriasis in mouse model. Biochimie. 2016 January 27.
(4) Zhao Y, et al. Curcumin inhibits proliferation of interleukin-22-treated HaCaT cells. Int J Clin Exp Med. 2015 Jun
(5) Antiga E, et al. Oral Curcumin (Meriva) Is Effective as an Adjuvant Treatment and Is Able to Reduce IL-22 Serum Levels in Patients with Psoriasis Vulgaris. Biomed Res Int. 2015.
(6) Sun J, et al. Curcumin relieves TPA-induced Th1 inflammation in K14-VEGF transgenic mice. Int. Immunopharmacol. 2015 Apr.
(7) Zhang C, et al. Preventive effects of andrographolide on the development of diabetes in autoimmune diabetic NOD mice by inducing immune tolerance. Int. Immunopharmacol. 2013 Aug.
(8) Liu W, et al. Andrographolide sulfonate ameliorates experimental colitis in mice by inhibiting Th1/Th17 response. Int Immunopharmacol. 2014 Jun
(9) Ku CM, et al. Anti-inflammatory effects of 27 selected terpenoid compounds tested through modulating Th1/Th2 cytokine secretion profiles using murine primary splenocytes. Food Chem. 2013 Nov 15
(10) Lee KP. et al. Anti-allergic effect of α-cubebenoate isolated from Schisandra chinensis using in vivo and in vitro experiments. J Ethnopharmacol. 2015 Sep
(11) Lee HJ, et al. Effects of Schisandra chinensis Turcz. fruit on contact dermatitis induced by dinitrofluorobenzene in mice. Mol Med Rep. 2015 Aug
(12) Lauffer F, et al. Target-oriented therapy: Emerging drugs for atopic dermatitis. Expert Opin Emerg. Drugs. 2016 Jan 25.
(13) Pyo MY, et al. Cyanidin-3-glucoside suppresses Th2 cytokines and GATA-3 transcription factor in EL-4 T cells. Biosci Biotechnol Biochem 2014
(14) Kim MJ, et al. Mixture of Polyphenols and Anthocyanins from Vaccinium uliginosum L. Alleviates DNCB-Induced Atopic Dermatitis in NC/Nga Mice. Evid. Based Complement Alternat. Med. 2012.
(15) Min HK, et al. Anthocyanin Extracted from Black Soybean Seed Coats Prevents Autoimmune Arthritis by Suppressing the Development of Th17 Cells and Synthesis of Proinflammatory Cytokines by Such Cells, via Inhibition of NF-κB. PLoS One. 2015 Nov 6
(16) Kedzierska K, et al. The effect of immunosuppressive therapy on renal cell apoptosis in native rat kidneys. Histol Histopathol. 2015 Jan.
All aging starts at the cellular level including degeneration of the brain. Science has now identified dysfunction of the neuron mitochondria as the early central initiator in brain degeneration. When the neuronal mitochondria become dysfunctional, there is an inadequate supply of energy to the neuron, and subsequently the neuron dies. Early stages of neurodegenerative diseases have mitochondrial dysfunction common in their pathogenesis including Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Huntington’s Disease (HD) and amyotrophic lateral sclerosis (ALS). Indeed, the failure of cellular bioenergetics has been linked to neuron death and dementia.(1,2)
Research suggests that modulation and inhibition of mitochondrial dysfunction may increase neuron survival and provide a basis for extended brain longevity. As a cytoprotective agent, activation of transcription factor nuclear factor erythroid-2-related factor 2 (Nrf2) protects the functioning of the mitochondria and is viewed as a target for possible prevention and treatment of neurodegenerative diseases associated with aging. Sulforaphane (and precursor Glucoraphanin) is one of the most powerful natural nrf2 activators, and may play a role in the intervention of age-related brain degeneration. (2) In addition, the natural extract andrographolide, carnosic acid and carnosol have been identified as a very strong nrf2 activators. (3, 4)
Both Contain the following nrf2 activators:
(1) Grimm A, et al. Mitochondrial dysfunction: the missing link between aging and sporadic Alzheimer's disease. Biogerontology. 2015 Oct 14.
(2) Denzer I, et al. Modulation of mitochondrial dysfunction in neurodegenerative diseases via activation of nuclear factor erythroid-2-related factor 2 by food-derived compounds.
Pharmacol Res. 2015 Nov 25.
(3) Wu KC, et al. Screening of natural compounds as activators of the keap1-nrf2 pathway.
Planta Med. 2014
(4) de Oliveira MR. The Dietary Components Carnosic Acid and Carnosol as Neuroprotective Agents: a Mechanistic View. Mol Neurobiol. 2015 Nov 9