J A H G Volume 11 | Number 2 Journal of the American Herbalists Guild 71

Reductionist’s Rant
Neurogenesis:
Nerve Growth or Regeneration
with Herbs and Food Plants
James Duke, PhD
Thanks to Kevin Spelman, PhD, and Alan Tillotson, PhD, for constructive criticisms and suggestions.

M
y reliable Dorland’s Illustrated base it on some challenging assumptions: In his distinguished career,
James Duke served the US
Medical Dictionary (25th edition,
Department of Agriculture
1974) defines “neurogenic” 1. A
 ll food plants contain thousands of different
for over 30 years. Before
first as “forming nervous biologically active phytochemicals familiar retiring, he developed
tissue, or stimulating nervous to our genes from when our ancestors his ethnobotanical and
energy”; but I define it as first ingested plants containing such phytochemical database
“stimulating nerve growth or regeneration.” phytochemicals possibly millions of years ago. online at www.ars-grin.gov/
duke. It is one of the most
Dorland’s didn’t define the word “neuritogenic”
frequently consulted areas
back in 1974, but I define it as “stimulating 2. W
 hen chemically out of balance (diseased),
of the USDA website. Duke
growth or regeneration of small nerves called our bodies try to achieve health by getting grows hundreds of plants on
axons or neurites.” Doctors have prescribed or in balance homeostatically, mostly his six-acre Green Farmacy
suggested many medicines and modalities for sequestering needed (phyto)chemicals Garden with his wife, Peggy.
Since retiring from the USDA,
progressive neuropathy (in Dorland’s defined as and voiding unneeded or contraindicated
Dr. Duke has served for
a “disturbance of the nerves”). In the 83 year-old (phyto)chemicals. It is my questionable
five years as Senior Science
me, it’s catastrophic, causing tingling feet and assumption, after compiling data for 30 Advisor to Nature’s Herbs and
creaking knees. In other words, I have arthritic years, that probably all edible plants contain with allherb.com. Since 2001,
and wobbly knees that creak as I climb the stairs. both some neurogenic and antineurogenic he has been a distinguished
Below the knee, my legs are numb and tingly. phytochemicals. Ingesting plants that contain herbal lecturer at Tai Sophia
Healing Institute (now
Your reductionistic ranter, senile senior greater quantities of needed chemicals
Maryland University of
Jim Duke, suffers serious neuropathy, possibly can help bring the body back to health.
Integrative Health). He has
caused by one or more of the following: most written over 30 books on
likely spinal stenosis and spondylosis; cryptic 3. M
 y public domain USDA database already has medicinal plants.
Lyme disease for nearly a decade; possibly identified many of the chemicals in many food
pesticides (many of my USDA colleagues seem plants that might help preserve, protect, or
to have suffered pesticide poisonings, but not even generate new nerves or neurites. Queried
many of them worked with Agent Orange as did intelligently, the database can identify the
I); alcohol (my liver tests have never fingered my most promising food “farmaceuticals” to help
generous consumption of alcohol); or diabetes the body heal itself. And that is why, in this
(my tests have never indicated diabetes). rant, I list some of the phytochemicals and
I seek a “food farmacy” approach that herbs that offer hope for neuropaths who are
might reduce neuropathic suffering, but it too old to go the surgical route (like me). If I do
may be more expansive than reductive. I an equally intense review of antineuritogenic
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Reductionist’s Rant J A H G Volume 11 | Number 2 Journal of the American Herbalists Guild

and antineurogenic phytochemicals, we acupuncture and meditation, can generate NGF

can better identify edible food farmacy which makes the neuritogenic phytochemicals
“prescriptions” for various neuropathies more active. Thus there is an apparent
and related diseases. Some studies refer to synergy between our NGF and neuritogenic
the herb itself or the extracts of the herb; in foods, supplements or phytochemicals.
my opinion, better studies refer to both.
Neurogenic Spices
Most of the PubMed research on this topic is Some spices contain neurogenic compounds:
done on tissue culture (PC12D cells), cultures angelica, anise, applemint, basil, bay, caraway,
derived from animal cells, most often rats, cayenne, celery, citrus, clary sage, clove,
and some tissue cultures called astrocytes or coriander, fenugreek, ginger, horseradish,
stellar cells. In these cultures, nerve growth lavender, marjoram, orange peel, onion, oregano,
factor (NGF) increases the proportions of nerve parsley, pennyroyal, rosemary, sage, spearmint,
cells called neurites (hence “neuritogenic” or summer savory, tarragon, thyme, turmeric, and
“generating nerves”) and increases the length of wasabi. It is easy to say that these spices contain
the nerves. The Japanese studied Verbena littoralis neurogenic compounds, but I am trying to
(Paraguayan beach verbena), and their extracts figure those which have more neurogenic than
barely changed the neurites in the absence of antineurogenic phytochemicals. Big Pharma is
Cannabis sativa plant. NGF at rather high dosages. But in the presence not going to do that; clinical herbalists can.
Image by Petr Brož (CC- of very low levels of NGF (2 nanograms per
BY-SA 3.0). Source: http:// milliliter), the regrowth of nerves was much more Cannabis sativa (Marijuana)
commons.wikimedia.org/wiki/
dramatic (Li, Matsunaga et al 1999; Li, Ishibashi We have plenty of marijuana, mostly illegal, but
File:Cannabis_sativa_plant_(4).
JPG
et al 2003). The human immune system, like soon to be legally grown, in the nation’s capital.
There will be political roadblocks to using this
medicinal plant; “grass” ain’t GRAS (generally
regarded as safe by the FDA). We dare not plant
it in our Green Farmacy Garden, even though it is
very promising in neuropathy. I suspect it is still
illegal in Maryland, but in my woodland rambles
near the Middle Patuxent River just north of
my garden, I have stumbled on three small
clandestine plots. Larger plots are often booby-
trapped, making wandering through the woods
dangerous. Some chronic users anecdotally
claim it can expand the mind. German scientists
advise that long-time Cannabis use may increase
innate NGF. On the downside, it may increase
risk of schizophrenia (Jockers-Scherübl 2003).
There are hundreds of PubMed citations
on cannabinoids and multiple sclerosis (MS),
a demyelinating disease of the central nervous
system (CNS). Current pharmaceutical
treatments are sometimes ineffective and may
have noteworthy side effects. Hence, some MS
patients may resort to Cannabis, anecdotally
believed to help some symptoms like bladder
dysfunction, pain, spasticity, and tremors.
Animal research shows cannabinoids to be
J A H G Volume 11 | Number 2 Journal of the American Herbalists Guild 73

Reductionist’s Rant
Neurogenic:
helpful with spasticity and tremor. Phase III Onjisaponins A, B, E, F and G, major
stimulating
clinical trials may rationalize cannabinoids
for MS (Croxton & Miller 2004).
saponins in Polygala, strongly
increased NGF level, much more
nerve growth or
Cannabidiol (CBD) is currently used for
MS spasticity and pain. (Karmaus, Wagner et al
than the ginsenosides Rb1 and Rg1
(Yabe et al 2003). Another study
regeneration
2012). A 1:1 mix of delta-9-tetrahydrocannabinol found that Asian goldthread (Coptis)
plus cannabidiol, oromucosally introduced, extracts neuritogenically enhanced
has been approved in some countries, reducing the activities of NGF in tissue culture. Neuritogenic:
traditional psychotropic Cannabis actions. No Weaker activity was demonstrated by
tolerance, abuse or addictive issues were found berberine and even less by coptisine stimulating
(Oreja-Guevara 2012). Germany approved a
Cannabis extract in 2011 to treat refractory
and palmatine, alkaloids present in
goldthread, but also in American growth or
spasticity in MS, but it is often used off-label
for anorexia, nausea, and neuropathic pain
barberries, goldenseal, goldthread
and yellowroots (Shigeta et al 2002).
regeneration
(Grotenhermen & Müller-Vahl 2012).
The endogenous cannabinoids, anandamide
Syracuse scientists studying the
important hepatoprotective Silybum
of small nerves
and 2-arachidonoyl glycerol, interact with the marianum (milk thistle) extract called axons or
G-protein coupled cannabinoid (CB) receptors found it also to be neuritogenic
CB(1) and CB(2). The CB system is emerging as and NGF-genic (Kittur 2002). neurites
a key regulator of neuronal cell fate, conferring
neuroprotection. Many poor neurological Legumes
conditions are associated with excitotoxicity, Wake Forest scientists found that estradiol was
oxidative stress, and neuroinflammation. Some nearly twice as active as soy phytoestrogens
CB molecules inhibit these events and slow or at stimulating NGF (Pan, Anthony et al
stop the neurodegeneration. Such may offer 1999). Notice that the authors specify soy
hope in Alzheimer’s disease, MS, and cerebral phytoestrogens, most of whose phytoestrogens
ischemia (Gowren, Noonan et al 2011). are shared by many other edible legumes
much more pleasing to my occidental palate. (I
Various Familiar and Obscure Herbs suspect that most soy-sponsored phytoestrogen
A Finnish study showed that two of 10 policemen studies will have “soy” specified in their title,
who volunteered to be sprayed with crowd- even though genistein is genistein is genistein.)
control pepper spray (Capsicum or its capsaicins) A Japanese study concluded that “genistein
had increased levels of NGF in their tears enhanced the NGF-induced neurite outgrowth”
(Vesaluoma et al 2000). In 1999 the Japanese in PC12 tissue culture cells (Nakajima, Niisato
added several neuritogenic species: the well et al 2011). A 2011 Italian study found that
known Equisetum giganteum (horsetail), Panax soy genistein injected in the paws of diabetic
ginseng (ginseng), and Ruta gravolens (rue), rats relieved painful peripheral neuropathy,
and the obscure Gymmopteris rufa, Picrorhiza and restored NGF in diabetic sciatic nerves
scrophulariiflora, Imperata cylindrica, and (Valsecchi et al 2011). Another study showed
Gochnatia polymorpha. Picrorhiza induced that daidzein and genistein found in most edible
the longest neurites, but horsetail was best at legumes (but in this case Pueraria thomsonii,
neurogenesis though the neurites were short kudzu) exhibited cytoprotective activity that
(Li, Matsunaga et al 1999). In 2003, Japanese might even help in Parkinson’s disease (Lin et
scientists studying the kampo medicine al 2010). As early as 1993, University of North
Ninjin-yoei-to found that it increased NGF Carolina researchers suggested that not only
secretion in cultured astrocytes. The compound genistein but other inhibitors of protein tyrosine
contained several species including roots of kinases increased the length of neurites in the
Polygala tenuifolia and Panax ginseng extracts. presence of NGF (Miller, Lee et al 1993).
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Reductionist’s Rant J A H G Volume 11 | Number 2 Journal of the American Herbalists Guild

Neuritogenic Aphrodisia? implicated as having a role in several neuronal

A California study showed that icariin from activities including cell–cell adhesion, neurite
Epimedium spp. (horny goat weed) was both outgrowth, synaptic plasticity, and learning
erectogenic and neuritogenic, at least in rats and memory” (personal communication
(Schindel et al 2010). Hmm, maybe a little Ginkgo on March 2, 2013; Spelman et al 2011).
biloba added to the horny goat weed might be
worth trying for erecto- and neuro-genesis, as Worms
ginkgo extracts also may promote peripheral I’ve eaten many wild critters, but I do not
nerve regeneration (Lin, Wang et al 2008). remember eating the traditional medicinal
The Amazonian aphrodisiac Ptychopetalum di long (earthworm) with potential for neural
olacoides (muira puama) also possesses some regeneration in China (Chang et al 2011). Di
neuritogenic phytochemicals (Tang et al 2008). long is part of the Traditional Chinese Medicine
Finally, some ginsenosides from Panax spp. (TCM) materia medica and has been long used
seem to be both neuritogenic and aphrodisiac in China to promote nerve function. The extract
(Rudakewich & Benishin 2001; Ma, Li et al 2010). seems to enhance sciatic nerve regeneration and
function recovery following injury, suggesting
Melatonin-Containing Food Plants the clinical potential of Lumbricus extract on the
N-acetylserotonin, a natural chemical treatment of peripheral nerve injury in humans
intermediate in the synthesis of melatonin, is (Wei, Yin et al 2009). TCM specialist Thomas
a potent neurogenic (Tosini, Ye et al 2012). The Garran tells me that there are four species listed:
following food plants are reported to contain Pheretina aspergillum, P. vulgaris, P. guillelmi, and
more than 100 picograms melatonin per gram: P. pectinifera. It is used in decoction at 5-10 g
oats (1,796), corn (1,366), rice (1,006), radish dosages or as a pill or powder at 1-2 g dosages. It
(657), angelica (623), ginger (584) tomato (506), is also applied externally. Studies show it is used
banana (466), chrysanthemum (417), barley also for a variety of inflammatory conditions from
(378), mustard greens (112), and cabbage (107). asthma to herpes zoster to urinary tract infections
These all contain melatonin and I assume that all (personal communication, Mar. 2, 2013). Several
melatonin-containing plants might also contain abstracts concern silkworm corpses which
the precursor N-acetylserotonin. Melatonin contain phospholipids and aromatic amines
injection has been shown to increase NGF content that stimulate production of NGF (Kwon et al
(Pongsa-Asawapaiboon et al 1998). A very recent 2003). I do not think I will ingest them either.
Turkish study with spinally damaged rats showed
that melatonin restored NGF levels to normal Antineuritogenic Compounds
after the spinal damage (Ersahin et al 2012). Fond of a nightly wine at happy hour, I was
My spine, on the other hand, has been slowly disappointed to be reminded that alcohol can
damaged over decades of abuse such as sitting too cause or aggravate alcoholic neuropathy (which
long at the computer, gardening, and even jogging has not yet been my diagnosis). In one study,
up into my 60s. Can melatonin help me at age 83? alcohol decreased NGF (Gottesfeld, Simpson et
al 1996). Some neuritogenic compounds occur in
Mushrooms plants whose extracts prove to be antineurogenic.
Several mushrooms exhibit neurogenic Extracts of Geranium thunbergii, Humulus lupulus,
activities. Pleurotus giganteus (oyster mushroom) Rosmarinus officinalis and Salvia officinalis
“contains bioactive compounds that mimic NGF inhibited NGF-induced neuritic outgrowth in
and are responsible for neurite stimulation” tissue culture (Takano, Inokuchi et al 2011).
(Phan, Wong et al 2012). My friend Dr. Kevin They might be avoided, but note that at least
Spelman, RH (AHG), notes that “CD56 two compounds in rosemary, carnosic acid and
(NCAM) is upregulated by an aqueous rosmarinic acid, are neurotrophic. Excitotoxins
extract of Ganoderma lucidum (reishi), and is and glutamates are also antineuritogenic. An
 J A H G Volume 11 | Number 2 Journal of the American Herbalists Guild 75

Table 1: Some Neurogenic Phytochemicals and Their Sources

Reviews
Phytochemical Plant Source PubMed ID
ASIATIC-ACID: Neurogenic 16105244 gotu kola
ASTRAGALOSIDE-IV: Neurogenic 19409437 astragalus
ASTRAGALOSIDES: NGF-Activator 19409437 astragalus
BAICALEIN: Neuritogenic 19327378 Baikal skullcap
BAICALEIN: Neuroprotective 19327378 Baikal skullcap
BERBERINE: Neuritogenic, NGF-Genic 12506995 goldthread, goldenseal, barberry, amur cork tree, prickly poppy
BISDEMETHOXYCURCUMIN: Neuritogenic 22145830 turmeric
BETA-BOSWELLIC-ACID: Neuritogenic 20217445 Boswellia serrata
CARNOSOL: NGF-Genic 14600414 rosemary, sage
COPTISINE: Neuritogenic, NGF-Genic 12506995 bloodroot, California poppy, celandine, fumitory, goldthread,
great scarlet poppy, opium poppy, plume poppy, prickly poppy
CURCUMIN: Neurogenic 16646663; 17617388; 18299980;
18362141; 19882093; 22145830 turmeric
DOPAMINE: Neurogenic 15128392; 16246330 banana peel, avocado, cacao
ELEUTHEROSIDE-B: Neuritogenic 18612196 eleuthero
ELEUTHEROSIDE-E: Neuritogenic 18612196 eleuthero
ESTRADIOL: NGF-Genic 10352122 pomegranate
(+)-EUDESMIN: Neuritigenic, NGF-Genic 17225460 magnolia
beta-EUDESMOL: Neurogenic 12023507 ginger, celery seed, hops, walnut, angelica, watermint
FALCARINONE: Neuritogenic 16219303 celery, caraway, dang gui, ivy, notoginseng, parsley
FERULIC-ACID: Neuritogenic 21809545 asafetida, chia, pineapple, apple, peanut, lemon, tarragon,
grapefruit, wheat, potato, garlic, corn, cabbage etc.
GARCINIA-XANTHONE-E: NGF-genic 14600386 garcinia
GARCINOL: `Neurogenic 21214247 garcinia
GENTISIDE-A: Neuritogeni 20189814 some gentian
GENTISIDE-B: Neuritogeni 20189814 some gentian
GENTISIDES C-K, esp.
GENTISIDE C: Neuritogenic 20813533 some gentian
GINKGOLIDE: possibly NGF-Genic 16716609 ginkgo
5-HYDROXY-3,6,7,8,3’,4’-
HEXAMETHOXYFLAVONE: Neuritogenic 22140566 citrus, esp. orange peel
ISORHAMNETIN: Neurogenic 22761636 tarragon, dill, ginkgo, grapefruit, yarrow
NEOVIBSANIN-A: Neuritogenic 20233658 Viburnum
NEOVIBSANIN-B: Neuritogenic 20233658 Viburnum
NEOVIBSANIN-L: Neuritogenic 20233658 Viburnum
(8Z)-NEOVIBSANIN-M (4) Neuritogenic 20233658 Viburnum
OLEANOLIC-ACID: Neuritogenic 12762811, 15235225 clove, thyme, sage, lavender, marjoram, basil, summer savory
PARTHENOLIDE: Neurogenic 19900365 feverfew, tansy
PEONY-GLYCOSIDES: NGF-Genic 20176057 peony
PROTOCATECHUIC-ACID: `Neurogenic 21946114 onion, coriander, oregano, wheat
QUERCETIN: NGF-Genic 19370542 ubiquitous
ROSMARINIC-ACID: Neurotrophic 20633629 heal-all, oregano, marjoram, spearmint, rosemary, bugle, clary
sage, applemint, european pennyroyal
SCHISANDRIN: Neurogenic 21302324; 18547723 schisandra
SCOPARONE: Neuritogenic 218547723 tarragon
SOMINONE: Neurogenic 16553605; 19594760 ashwagandha
WITHANOLIDE-A: Neurogenic 15711595; 18670181 ashwagandha
WITHANOSIDE-IV: Neurogenic 16553605; 19594760 ashwagandha
WITHANOSIDE-VI: Neurogenic 18670181 ashwagandha
WOGONIN: Neuritogenic 20888794 Baical skullcap
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Reductionist’s Rant J A H G Volume 11 | Number 2 Journal of the American Herbalists Guild

Argentinian study suggests that aggregated HDL REFERENCES

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Jockers-Scherübl MC, Matthies U, Danker-Hopfe H,

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J A H G Volume 11 | Number 2 Journal of the American Herbalists Guild 77

Reductionist’s Rant
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