Carnosic acid, an extract from the herb Rosemary, is a powerful activator of cellular endogenous antioxidants, through involvement in increasing Nrf2 transcription. Since carnosic acid crosses the blood-brain barrier, there is significant provisioning of protection of the brain and neural tissue.(1) In addition, the retina is primarily neural tissue, which benefits greatly from carnosic acid.
RETINA - MITIGATING AGING EYE DETERIORATION
CARTILAGE - BENEFICIAL EFFECTS FOR OSTEOARTHRITIS
(1) Rezaie T, et al. Protective effect of carnosic acid, a pro-electrophilic compound, in models of oxidative stress and light-induced retinal degeneration. Invest, Ophthalmol Vis Sci, 2012 Nov
(2) Contin MA, et al. Light pollution: the possible consequences of excessive illumination on retina. Eye (Lond). 2016 Feb
(3) Wong P, et al, Enhancing the efficacy of AREDS antioxidants in light-induced retinal degeneration. Mol Vis. 2017 Oct
(4) Kang K, et al. Carnosic acid slows photoreceptor degeneration in the Pde6b(rd10) mouse model of retinitis pigmentosa. Sci Rep. 2016 Mar
(5) Albalawi A, et al. Protective effect of carnosic acid against acrylamide-induced toxicity in RPE cells. Food Chem Toxicol. 2017 Oct
(6) Albalawi A, et al. Carnosic acid attenuates acrylamide-induced retinal toxicity in zebrafish embryos. Exp Eye Res. 2018 Oct;
(6) Ishitobi H, et al. Carnosic acid attenuates cartilage degeneration through induction of heme oxygenase-1 in human articular chondrocytes.
(7) Ravaili S, et al. Recently highlighted nutraceuticals for preventive management of osteoarthritis. World J Orthop. 2018 Nov
(8) Schwager J, et al. Carnosol and Related Substances Modulate Chemokine and Cytokine Production in Macrophages and Chondrocytes. Molecules. 2016 Apr
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
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