Herbal Extracts - Neurogenesis & Recovery of Cognition Impairments

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.

• NEUROGENESIS - is the formation of new neurons, specifically in the hippocampus area in the brain.The hippocampus is essential in providing the capacity for memory and learning. Dementia and Alzheimer's disease are associated with brain shrinkage which is correlated to the loss of neurons in the hippocampus. The formation of new neurons may reverse brain shrinkage.

                    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)
  

• BRAIN TISSUE REGENERATION. While in the same theme as neurogenesis, brain tissue regeneration refers to the enhancement and regeneration of critical neuron structures - axons and dendrites. Dendrites transmit signals from the synapse to the body of the neuron. Axons transmit signals away from the body of the neuron and are covered with a myelin sheath which increase speed of the impulse providing rapid impulse transmission. Aging degenerates the structural integrity of dendrites and axon/myelin complex.
  

                     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)

• RECOVERY OF COGNITIVE IMPAIRMENT - the  to reversal of certain functional impairments which may improve cognitive function. Many research animal models for cognitive impairment are characteristically similar to Alzheimer's disease (AD). Impairment usually involves cerebral vascular disease, synaptic dysfunction. and more.

          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)

• NEUROPROTECTION - AMYLOID & NON-AMYLOID (α-synuclein) TOXICITY | CHRONIC INFLAMMATION - The aging brain is under continual assault and must be protected to prevent cognitive decline and loss of neurons. Key areas of protection include the build-up of amyoid plaques which are toxic to neurons and synapses. Moreover, chronic inflammation in the brain accelerates destruction of the brain and is believed to be the facilitator of degenerative brain diseases.
• Centella asiatica (15)
  
• Epimedium (Icariin)(16,17)
• Apigenin and luteolin (18,19)
  
• Baicalin (20)
  
• Schisandra (21)
• Rosemary (Carnosic Acid)(22)

• REVERSES INSULIN RESISTANCE IN BRAIN NEURONS - Aging brains become increasingly incapable of using glucose as an energy source. Without this energy neurons age faster and die. Reversing the insulin resistance maintains healthy neurons. Brain insulin resistance is associated with Alzheimer's Disease.
• Further reduction in glucose availability is caused by methylglyoxal - a powerful intermediate in the formation of Advanced Glycation End Products (AGEs).
• Curcumin - Improves insulin sensitivity in neurons. (23)
• Sulforaphane - Reverses reduction of glucose uptake by neurons caused by methylglyoxal (a precusor of advanced glycation end products). Sulforaphane also normalizes brain-derived neurotrophic factor (BDNF) signaling, which is critical for maintaining brain function. BDNF pathways are disrupted in Alzheimer's Disease. (24)

YELLOW LONGEVITY

YELLOW NATURALLY

MEMORY ACTION

XGEVITY

LONGEVITY NATURALLY

REFERENCES:

NEUROGENESIS

(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

(19) Rezai-Zedeh K, et al. Apigenin and luteolin modulate microglial activation via inhibition of STAT1-induced CD40 expression. J Neuroinflammation. 2008 Sep

(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

Anti-Stress Effects - Schisandra & Rhodiola Rosea

Natural Support for Inflammatory Skin Diseases - Psoriasis and Eczema

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)

• PSORIASIS. An autoimmune disease, which is associated with activation of the TH1 and TH17 lymphocytes. The presence of TH1/TH17 occur is high amounts in autoimmune diseases. Inflammatory skin diseases are characterized by dry, itchy and red skin are caused by an abnormal inflammation response in the body.  Psoriasis is a common form of inflammatory skin disease and is symptomatic of an autoimmune disease and may further indicate the presence of other autoimmune conditions such as rheumatoid arthritis.
• ECZEMA. An allergic response of lymphocytes in the skin. In contrast with psoriasis, eczema is characterized by activation of TH2 lymphocytes. Also inflammatory cytokines IL-4, IL-6 and IL-13 are increased in eczema (atopic dermatitis).
  

• Inflammatory Factors. While there are a number of inflammatory cytokines involved in the inflammation of the skin, a particular key one is TNF-α (TNF-alpha). Studies show high levels of TNF-alpha in the inflamed skin. Not only is TNF-alpha derived from the immune cells, but also has a feedback mechanism which further strengthens the pathological response of the activated T-cells (especially increasing differentiation of TH17). (2)

INGREDIENT SUPPORT:

• Curcumin - Significantly inhibted T-cell secretion of pro-inflammatory factors, including TNF-alpha, by 30-60%. Furthermore, inhibited 50% T-cell proliferation.(3) Oral treatment with curcumin significantly reduced a key psoriasis inflammation factor IL-22. Keratinocyte (skin cell) proliferation in psoriasis is due to IL-22. (4,5) No side effects reported from curcumin (3). Also shown to suppress TH1 induce inflammation in skin cells.(6)
• Andrographolide Supports homeostasis of TH1 / TH2 /TH17 (11). Also effective against rheumatoid arthritis (an autommune disease by suppressing TH17)(8, 9)
• Schisandra Supports suppression of Th2 invoking an anti-allergic effect.(10) Further, schisandra effectively reduced inflammatory Th2 inflammatory cytokines IL-4 and IL-13 as well as TNF-alpha and IL-6 in research studies on inflammatory skin disease.(11). In particular IL-4 and IL-13 are the focus of new drug development for atopic dermatitis.(12)
  
• Anthocyanins with C3G (Blueberry, other dark berries) 
  Suppresses levels of TH2 cytokines and TH17.(13-15)

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)

CURCUMIN XTRA-MAX (BCM-95 Curcumin, Andrographolide, Schisandra)

BLUE NATURALLY (C3G and other anthocyanins)

REFERENCES:

(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.