Studies on Treatment of Nerve Retrograde Affection
with Naokang Capsule (Originally Li's Prescription No.5)

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.