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Studies on Treatment
of Nerve Retrograde Affection
with Naokang Capsule (Originally Li's Prescription No.5)
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Nerve retrograde affection is a group of diseases of central nervous system
with unknown causes. It selectively involves nerve cells of one or two functional
systems, makes them atrophy and die and causes corresponding clinical symptoms.
Its common forms are Alzheimer's disease (AD), Parkinson's disease (PD)
and amyotrophic lateral sclerosis (ALS). The above diseases involve hippocampal
cholinergic neurons of forebrain, striatal dopaminergic neurons of black
substance and spinobulbar motor neurons, respectively; although supplementary
transmitter or its precursor can activate function of residual neurons and
abate symptoms of the diseases, this therapy cannot prevent the course of
neuronal retrograde affection. The prominent effect of Naokang Capsule on
developing, mature, declining and damaged neurons has received more and
more attention in recent years. Naokang Capsule is a pure Chinese medicinal
preparation successfully developed in recent years. This paper describes
biological functions of the medicine from three aspects: in vitro culture
studies on nerve cells, whole-body animal experiments and animal model test
of nerve retrograde affection.
Effect on in vitro Cultured Nerve Cells
Naokang has strong action of selective nutrition on dopaminergic (DA) neurons.
It specifically increases the growth and survival of dopaminergic neurons
in primary mesencephalic nerve cell culture. About 70% of mesencephalic
neuron culture of rat embryo
Author's unit: Guangdong Gaoming Medical and Medicinal Institute of Encephalopathy,
Gaoming, Guangdong 528500
will spontaneously decline and fall (cell apoptosis), whereas treatment
with Naokang will markedly decrease this cell apoptosis, but the change
in total number of neurons' apoptosis is not significant. After addition
of 1 mg/ml of Naokang to the culture fluid, the number of apoptosis of
tyrosine hydroxylase (TH) positive neurons decreases by 2.9 times as compared
with the control group. In addition, Naokang may also enlarge the surface
area of dopaminergic neuron's cell body and increase the uptaking of DA
by neurons. Therefore, it can significantly raise the survival rate of
dopaminergic neurons in period of growth, promote their morphologic differentiation
and enhance neuronal functions.
Effect on Dopaminergic Nervous System of Whole-body Animals
Normal rats fed with 40 mg/kg of body weight of Naokang Capsule by intubation
feeding for 100 days show marked increase in density of TH neurons. There
exists special transport system in endings of striatal dopaminergic neurons,
Naokang in the endings is reversely transported to cell bodies of dense
area of black substance. The cell bodies of dopaminergic neurons of dense
area of black substance of rats in the study group are larger than those
in the control group, the extent of the increase is related to the dosage
of Naokang. The medicine enhances levodopa-induced mechanical movement
in the mice, indicating that it has the action of enhancing dopaminergic
nervous function. Growth hormone secreted by lobus anterior hypophyseos
increases in excitation of DA nerve in the passage of tuberculum cinereum-infundibulum,
it obviously promotes weight gain of immature rats, causes proliferation
of cells in the liver and thymus gland of young rats with deficiency of
the kidney and increases the synthesis of protein in the liver, thymus
gland and brain and of hemoglobin. The above findings indicate that the
medicine has extensive influence on dopaminergic neurons of central nervous
system, its growth hormone-like action is advantageous to the development
of the organism.
Protection on Experimental Animal Model of Nerve Retrograde Affection
At present, ideal model for nerve retrograde affection is lacking, 6-hydroxydopamine
(6-OHDA) or 1-methyl-4-phenyl-tetrahydropyridine (MPTP) injured dopaminergic
neurons or transverse medial forebrain bundle (MFB) is generally used
as PD model.
Nerve Protection on Experimental PD Model
Rotatory behaviour induced by apomorphine or benzedrine has been regarded
as an important index for interpreting degree of injury of striatal dopaminergic
nervous system, the deeper the injury, the more the number of rotation.
Infusion of 6-OHDA in MFB with weekly determination of apomorphine-induced
rotation frequency to the 8 th week leads to an increase in number of
rotation to 650, whereas the number of rotation of animals given Naokang
in the dosage of 20 mg/kg and 40mg/kg of body weight one week before is
only 320 and 120, a decrease by 50% and 80%, respectively, as compared
with the control group. Morphological studies show that rats with increased
number of rotation have extensive injury of striatal dopaminergic neurons
of black substance with almost complete disappearance of TH pigmentation
in black substance and that reappearance of TH neurons is observed in
models given medicine, indicating that Naokang promotes the reappearance
of dopaminergic phenotype in damaged cells in black substance.
Protection on Motor Nerve Injury Model In nerves on cross section at the
level of stylomastoid foramen, interruption of association is brought
about between facial neuro-motor branch and facial muscle of new-born
rats, the cell count of motor neurons rises by 60% at the section after
Naokang is given as compared with the control group, and the volume of
nucleus of damaged facial nerve is restored to nearly normal.
It is evident from the experiments mentioned above that there is a greater
potentiality for Naokang Capsule to treat nerve retrograde affection,
and it is also observed in clinical application that Naokang Capsule has
the effects of improving dyskinesia and dystropy and delaying development
of such diseases.
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