1. Phytopharmaceutical Update
James D. Key, M.D. & David Ponsonby, M.Ed.
AANOS
Montreal, 2009
Valley Orthopedics, Texas
Ginkgo + Ginseng
INTRODUCTION
Blueberries
In the context of already existing dementia, botanical medicines, such as Ginkgo biloba and Panax ginseng, especially when combined, may prove to be some of the most effective treatment options available.
Ginkgo biloba, 240 mg/day, if taken alone or
Ginkgo biloba 120 mg/day with 200 mg/day of Panax ginseng (Wesnes)
Several herbs have gained recognition in the marketplace for being beneficial to people battling against neurological disorders, the most frequent being Alzheimer’s and Parkinson’s, for example. The most publicized have been Ginkgo Biloba and Curcumin as well as Mucuna Pruriens for PD.
We have previously focused on curcumin and discussed Ginkgo (mostly within the context of anticoagulant complications).
This is an update, selectively looking at plants with recently established efficacy for improved neurological function and safety.
Enhanced striatal dopamine recovery appeared in animals treated with diet enriched in antioxidants and anti-inflammatory phytochemicals… (i.e. blueberry or spirulina) (Strömberg)
Blueberry extract flavonoids may:
Prevent oxidative stress-associated impairment of striatal motor function during aging & restore lost motor function in aged rats. (McGuire)
Inhibit inflammatory activation of microglia (Lee et al. 2003),
Alter the temporal activation and duration of microglia and astrocytes (Wu and Yu 2000).
Suppress injury-induced TNF alpha production. (McGuire)
Calcium buffering ability (Shukitt-Hale)
SYNONYMS
Phytopharmaceutical
Botanical Medicine
Ethnopharmacology
“Folk Medicine”
“Green Pharmacy” (Duke)
Herbal Medicine
“Nature’s Bounty”
Traditional Medicine
Ginkgo
Panax Ginseng
India – What else?
Huperzine A or Club Moss
Top Twenty Neuro-Herbs
“Chemicals from rosemary (rosmarinic acid) and ginger (vanillin and zingerone), are also high in Indian diets and have similar structure and should be tested.“ (Frautschy )
Huperzine A (HupA), a novel alkaloid isolated from the Chinese herb Huperzia serrata, is a potent, highly specific and reversible inhibitor of acetylcholinesterase (AChE).
Compared with tacrine, donepezil, and rivastigmine, HupA has better penetration through the blood-brain barrier, higher oral bioavailability, and longer duration of AChE inhibitory action. (Wang)
Bacopa (Brahmi)
Blueberries
Club Moss (Huperzine A)
Curcumin
Ginkgo Biloba
Ginseng
Gotu Kola
Green Tea
Velvet Bean (Mucuna Pruriens)
Withania (Ashwagandha)
Baicalein (Skullcap)
Ginger
Kava Kava
Lemon Balm (Melissa)
Rhodiola
Rosemary
Sage
Spinach
St. John’s Wort
Valerian
Top Ten Neuro-Herbs
Bacopa (Brahmi) Ayurveda
Blueberries
Club Moss (Huperzine A) TCM
Curcumin Ayurveda
Ginkgo Biloba TCM*
Ginseng TCM
Gotu Kola Ayurveda
Green Tea TCM
Velvet Bean (Mucuna Pruriens) Ayurveda
Withania (Ashwagandha) Ayurveda
Mechanisms of action relevant to Alzheimer's Disease:
Acetyl cholinesterase (AChE) inhibition
Huperzine A is a potent, selective and reversible inhibitor of acetyl cholinesterase (AChE) that breaks down or degrades acetylcholine (ACh).
NMDA receptor antagonism
Huperzine A blocks excessive N-methyl-D-aspartate (NMDA) receptor activity, which may protect against glutamate mediated excito-toxicity and nerve cell death.
Anti-oxidant activity
Huperzine A demonstrated significant reductions in blood markers of oxidative stress.
Anti-amyloid activity
Huperzine A is protective against β-amyloid induced nerve cell death.
CONCLUSIONS
Ayurveda protocol
Even if you are not considering the addition of herbal medicine to your own practice, almost every other patient may be consuming one or more of these herbs. Physicians must gain some knowledge of this burgeoning field in order to stay abreast of the direction many patients are taking.
This is essential where there may be duplication of prescription drugs and/or adverse reactions.
We have chosen to select some of the better known herbs, many of which are already familiar from the supermarket or spice rack.
In the near future there is every expectation that we will have to discuss perhaps sixty more herbs as China completes research projects examining its rich Traditional heritage.
Ayurveda treatment
Preceded by cleansing (Panchakarma)
Mixture taken in cow’s milk:
Mucuna pruriens
Hyoscyamus reticulates seeds
Withania somnifera roots and
Sida cordifolia roots
Nagashayana N, Sankarankutty P, Nampoothiri MR et al., Association of L-DOPA with recovery following Ayurveda medication in Parkinson’s disease. J Neurol Sci Jun 15; 176(2):124-7.
Gotu Kola
Centella asiatica extract can:
impact the amyloid cascade (Dhanasekaran)
significantly increase the dendritic length (intersections) & branching points along the length of both apical and basal dendrites. (Gadahad)
decreased blood-brain barrier permeability & reduction in mitochondrial injury. (Krishnamurthy)
enhances phosphorylation of cyclic AMP response element binding protein in neuroblastoma cells expressing amyloid beta peptide. (Xu)
Ayurveda - medhya rasayanas -1
Epigallocatechin gallate (green tea)
In Ayurveda, selected plants have long been classified as ‘medhya rasayanas’, from the Sanskrit words ‘medhya’, meaning intellect or cognition, and ‘rasayana’, meaning ‘rejuvenation’.
Kumar V: Potential medicinal plants for CNS disorders: an overview. Phytother Res Dec; 20(12):
The polyphenol epigallocatechin gallate efficiently inhibits the fibrillogenesis of both alpha-synuclein and amyloid-beta by directly binding to the natively unfolded polypeptides and preventing their conversion into toxic, on-pathway aggregation intermediates.
Ehrnhoefer, DE et al., EGCG redirects amyloidogenic polypeptides into unstructured, off-pathway oligomers. Nature Structural & Molecular Biology 2008, 15:
Ayurveda - medhya rasayanas - 2
The popular Medhya Rasayanas are:
Ashwagandha (Withania somnifera Dunal),
Brahmi (Bacopa monnieri Linn),
Mandukaparni (Centella asiatica Linn) and
Sankhapuspi (Convolvulus pluricaulis Chois).
Singh RH, Narsimhamurthy K, Singh G: Neuronutrient impact of Ayurvedic Rasayana therapy in brain aging. Biogerontology, 2008 Dec; 9(6):
Daehan Tea Plantation
Ashwagandha
Treatment with withanolide A (1 microM) (from Ashwagandha root) induced :
Regeneration of neurites
i.e. regeneration of axons
i.e. regeneration of dendrites
Reconstruction of synapses in the neurons
i.e. reconstruction of pre- and postsynapses in the neurons
WL-A is therefore an important candidate for neurodegenerative diseases, reconstructing neuronal networks.
Kuboyama T et al., Neuritic regeneration and synaptic reconstruction induced by withanolide A. Br J Pharmacol Apr; 144(7):
India – Update?
Significant cognitive gains when the administration of Bacopa monniera extract is continued over a 12 week period.
Stough C, Lloyd J, Clarke J, et al., The chronic effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human subjects. Psychopharmacology 2001; 156:
RESOURCES
According to PharmacoInformatics, these had the best patient education:
Natural Medicine Database
The Natural Pharmacist
AltMed on MICROMEDEX
REFERENCES
A full list of references is available from the authors by contacting:
James D Key:
Ashwagandha /
Withania
Ashwagandha Root
Bacopa monniera (Brahmi)