KR20090087626A - The pharmaceutical agents for the improvements and prevention of the symptoms in the neurodegenerative diseases from the extracts of gynostemma pentaphyllum - Google Patents

Abstract

A pharmaceutical composition for treating and preventing neurodegenerative diseases, which containing Gynostemma pentaphyllum extracts is provided to increase the viability of dopamine nerve cell and induce dopamine synthesis. A pharmaceutical composition for treating and preventing Parkinson's disease and depression caused by Alzheimer disease(AD) or Parkinson's disease comprises a Gynostemma pentaphyllum extract. The Gynostemma pentaphyllum extract is obtained by extracting dried Gynostemma pentaphyllum with 60% ethanol and compressing at low temperature. The pharmaceutical composition is used in a form of filler, extender, binder, moisturizer, disintegrant, and diluents or excipient of surfactant.

Description

The pharmaceutical agents for the improvements and prevention of the symptoms in the neurodegenerative diseases from the extracts of Gynostemma pentaphyllum}

The present invention relates to a pharmaceutical composition for the treatment and prevention of depressive diseases caused by Parkinson's disease, Alzheimer's (AD) or Parkinson's disease, which is a neurodegenerative disease containing Gynostemma pentaphyllum extract as an active ingredient.

As people's lifespan increases and aging society progresses, neurodegenerative diseases increase. In neurodegenerative diseases, a beta-amyloid (Aβ) plaque (senile plaque) (Aβ-plaque) accumulates in the brain tissue, and neurofibrillary tangles (NFTs) appear in the brain cells, thereby degenerating throughout the brain tissue. Atrophy occurs and various symptoms occur. Whether Aβ plaques and NFTs kill brain cells or whether degeneration of brain cells promotes the development of Aβ plaques and NFTs is clearly identified. Among neurodegenerative diseases, depressions caused by Parkinson's disease, Alzheimer's (AD) or Parkinson's disease are important examples.

Parkinson's disease is a degenerative change in dopaminergic neurons of the substantia nigra (pars compacta) in the basal ganglia, which causes dopamine, a neurotransmitter of the corpus striatum. It is caused by a deficiency of the disease, and when more than 70-80% of the striatum is lost, it is characterized by movement disorders such as tremer, bradykinesia, and rigidity (Fearney et al., 1991).

Dopamine deficiency is known to be due to a decrease in the activity of dopamine biosynthetic enzyme tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) caused by neuronal death.

Alzheimer's disease (AD) is a complex neurodegenerative disease caused by a number of factors characterized by a gradual decline in memory, behavior, language, and spatiotemporal capacity, leading to death.

AD is about twice as many females as males, and is reported to be due to a decrease in postmenopausal estrogen. Although the exact number of patients in Korea is not reported, it is estimated that 50-70% of the aged population is AD patients considering the average life expectancy of 75-80 years.

The main symptom is cognitive function and memory loss caused by brain cell death, which can lead to death. Onset between 40 and 65 years of age is classified as early-onset or familial AD, and over 65 years as late-onset or sporadic AD. The family type has many genetic factors. Some people develop neurodegenerative diseases due to aging and have a slow progression. Senile dementia is a progressive condition. AD is progressive and causes symptoms to progress faster than senile dementia.

Biosynthetic pathways of the neurotransmitter catecholamines (dopamine, norepinephrine, and epinephrine) are biosynthesized from tyrosine to L-DOPA, followed by dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline). Tyrosine hydroxylase (TH), aromatic L-amino acid dicarboxylase (AADC), dopamine beta-hydroxylase (DBH), phenylethanolamine N-methyltransferase, PNMT) enzyme is involved. In addition, monoamine oxidase (MAO) and catechol O-methyltransferase (COMT) are involved in the metabolism of dopamine, and the main metabolite of dopamine is 3,4-dihydroxyacetic acid. (3,4-dihydroxyphenylacetic acid, DOPAC) and homovanillic acid (HVA) are known.

As for the pathogenesis of Parkinson's disease, there are various factors including genetic factors, oxidative stress (Jenner et al., 1996), genetic susceptibility (Bandmann et al., 1998), and cell necrosis (Ziv et al., 1998). The causes of internal and external development are being discussed, but the exact mechanism is not yet known (Calne and Langston, 1983).

Black dopamine neurons in Parkinson's disease are known to continue to lose in proportion to the duration of the disease (Fearney et al., 1991), and to date there is no known way to prevent this persistent neuronal loss. not. Dopamine neurons are lost and dopamine deficiency of the striatum leads to clinical symptoms, and thus studies on neuroprotective actions that prevent or delay the loss of neurons, and the development of therapeutics that induce activation of dopamine nervous system and increased efficacy. Research is actively underway (Yamada et al., 1990, German et al., 1992, Iacopion et al., 1992).

Drug therapy, surgery, and exercise therapy are used for the treatment of neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease (AD) or Parkinson's disease, and the most widely used drug is L-DOPA therapy (Fahn). et al., 2006.). L-DOPA therapy has a good effect on improving symptoms of Parkinson's disease (such as dyskinesia), but L-DOPA passes through the blood-brain barrier (BBB) to convert dopamine from the brain into the dopamine. As dopamine does not cross the blood-brain barrier, L-DOPA therapy has no effect on preventing denaturation of dopamine neurons in the black matter and cannot be used as a therapeutic.

In addition, long-term administration of L-DOPA eventually results in an unresponsive response to L-DOPA treatment and symptoms worsening (Rascol et al., 2000) (Wagner et al., 1996) (Colosimo et al., 2006). This is because long-term L-DOPA administration causes oxidative stress to cause cytotoxicity (dopamine neuronal apoptosis). Medication guidance and monitoring of symptoms should be made.

During L-DOPA therapy, aromatic L-amino acid dicarboxylase (AADC, dopamine in L-DOPA, such as carbidopa and benzrazide) is used to prevent the conversion of L-DOPA to dopamine. Combination therapy with biosynthetic catalytic enzyme) inhibitors is being conducted.

Therefore, therapies / therapies for depressive diseases caused by Parkinson's disease, Alzheimer's (AD) or Parkinson's disease, neurodegenerative diseases such as development of new therapeutics that can replace L-DOPA therapy, side effects of L-DOPA therapy, and improvement of neuronal cell death Needs to be developed and research on this is being actively conducted.

Meanwhile, the present invention is widely used for the development of new therapies associated with neurodegenerative diseases such as Parkinson's disease, Alzheimer's (AD) or Parkinson's disease, and the method is a stereotaxic method of an animal model such as Parkinson's disease (Paxinos). and Watson, 1982). The method injects 6-hydroxydopamine (6-hydroxydopamine, 6-OHDA), a neurotoxicity-inducing substance, into rat black matter / stratum, enters dopamine neurons and activates the active oxygen in the cells. species, ROS) (Cohen, 1984) and inhibiting the function of the electron transport chain of mitochondria are known to cause neuronal death and cause cell death (Ichitani et al., 1991, Cadet et al., 1991, Sauer et al., 1994, Lee et al., 1996).

6-OHDA causes dopamine neurological lesions at the site of injection and persists for about 12 weeks after the injection of 6-OHDA, and is a depressive disorder caused by Parkinson's disease, Alzheimer's disease (AD) or Parkinson's disease. It is very similar to biochemical changes, and it is an incomplete damage model that is frequently used for research on the mechanism of dopamine neuronal cell death and treatment. In addition, the dopamine neurons are denatured in only one region, and thus, rotational movement occurs when apomorphine and other drugs are administered (Bloem et al., 1990).

Therefore, after 6-OHDA injection, apomorphine was administered to determine the degree of neuronal cell death in the dopamine nervous system in autorotography analysis of increased rotational motion and dopamine receptors (D1, D2). As a result, neurodegenerative diseases such as Parkinson's disease, Alzheimer's (AD) or Parkinson's disease can be identified as the development of lesions (Prezedborski et al., 1995).

The present inventors studied the physiological activity of the development of neurodegenerative Parkinson's disease using Gynostemma pentaphyllum extract, and reduced the side effects of L-DOPA therapy to replace L-DOPA therapy. The present invention has been completed by discovering the development of therapies / therapies for depressive diseases caused by degenerative Parkinson's disease, Alzheimer's (AD) or Parkinson's disease.

The present invention provides a pharmaceutical composition for treating and preventing depressive diseases caused by Parkinson's disease, Alzheimer's disease (AD) or Parkinson's disease, which are new neurodegenerative diseases that can replace L-DOPA therapy by reducing the side effects of L-DOPA therapy. will be.

In order to achieve the above object, the present invention provides a pharmaceutical composition for the treatment and prevention of depressive diseases caused by Parkinson's disease, Alzheimer's (AD) or Parkinson's disease, which is a neurodegenerative disease using a vine tea (Gynostemma pentaphyllum) extract.

Gineostemma pentaphyllum is a plant belonging to the family Cucurbitaceae, also called doldol, and it is a perennial vine plant that grows in wild mountains of Ulleungdo, Jeju Island, etc. It contains a large amount of phonics diol-based saponin components such as Rb1 and Rb2, which are known to be distributed only in Gulf, and these saponins have the same dmaran skeleton as ginseng. Folk remedies have been used as sweeteners for diabetics, and are known to be effective in stress-induced diseases, bronchial system, gastrointestinal diseases, duodenal ulcers, and diuretic anti-inflammatory activity. In addition, the Republic of Korea Patent Publication No. 584039 is a composition for the treatment of atopic dermatitis by the extract of vine tea, diet, antidiabetic, antidepressant / anti-anxiety, anti-fatigue, immune enhancement / anticancer action, antioxidant activity, etc. However, the biologically active function for neurodegenerative diseases is not known.

According to the present invention, the leaves obtained by drying the vine tea (Gynostemma pentaphyllum) and then extracting from hot water with 60% ethanol and concentrated under reduced pressure at low temperature are referred to as 'vine tea extract'.

The present invention is to prepare a model of depression disease caused by Parkinson's disease, Alzheimer's disease (AD) or Parkinson's disease, which is a neurodegenerative disease caused by administration of 6-OHDA to mature rat striatum, according to pretreatment (oral administration) of vine tea extract. Examination of 6-OHDA-induced dopamine neuronal cell death, changes in TH immune response, a high-affinity immunochemical marker of dopamine neurons, and changes in the contents of dopamine, norephnephrine, DOPAC and HVA in striatum The ethanol extract of Gynostemma pentaphyllum revealed the physiological function as a treatment and prevention of depressive diseases caused by neurodegenerative Parkinson's disease, Alzheimer's disease (AD) or Parkinson's disease.

Neurodegenerative disease-inducing animals such as Parkinson's disease show a tendency / rotational movement in the opposite direction of the 6-OHDA administered striatum / black matter (lesion site) when apomorphine, an agonist of the dopamine receptor, is administered. . This is because apodopamine acts on dopamine receptor subtypes D1 and D2 receptors to enhance the motility of the leg opposite the lesion, and presynaptic neurons have already been destroyed, resulting in postsynaptic supersensitivity. Induction of apodopamine-induced rotational exercise has been used as an indicator of Parkinson's-like dyskinesia / Parkinson's incidence (Przedborski et al ., 1995).

The present invention has been shown to inhibit TH immune neurons by the neurotoxic effect of 6-OHDA by administering the vine tea extract to Parkinson's disease-induced animals, which is the oral administration of the vine tea extract to defend against the toxic effects of 6-OHDA It shows the action.

In addition, the present invention was administered to the Parkinson's disease-induced animals by measuring the change in the content of dopamine, norepinephrine, DOPAC and HVA, etc. As a result of the vine tea extract inhibits 6-OHDA induced neuronal cell death dopamine nerve It was confirmed that dopamine biosynthesis was induced by increasing cell survival.

Therefore, the present invention can be usefully used for the treatment and prevention of depressive diseases caused by Parkinson's disease, Alzheimer's disease (AD) or Parkinson's disease, which are neurodegenerative diseases using Gynostemma pentaphyllum extract.

The present invention can be administered in a variety of oral and parenteral formulations during actual clinical administration, with the most preferred route of administration being oral. In addition, when formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are generally used.

In addition, the dose or dosage of the extract of the vine tea according to the present invention varies depending on the weight, age, sex, health condition, diet, time of administration, administration method, excretion rate and severity of the patient, the adult standard It is preferable to take the dosage of 1 mg / kg to 500 mg / kg in one to several times.

Therefore, the present invention shows the protective action of toxic effects due to oxidative stress such as 6-OHDA or L-DOPA / dopamine by administering a pharmaceutical composition containing the extract of vine tea as an active ingredient Parkinson's disease, Alzheimer's disease It can be usefully used for the treatment and prevention of depressive diseases caused by (AD) or Parkinson's disease.

Hereinafter, the present invention will be described in detail by Examples and Experimental Examples. However, the following Examples and Experimental Examples are merely illustrative of the present invention, and the content of the present invention is not limited by the following Examples and Experimental Examples.

<Example 1> Preparation of Honeysuckle Tea Extract

A vine tea (Gynostemma pentaphyllum, herb, leaf) sample (20 kg) was dried and finely chopped, extracted three times in hot water with 60% ethanol (200 L), and concentrated under reduced pressure at a low temperature to obtain 2.7 kg.

Experimental Example 1 Determination of Tyrosine Hydroxylase Activity by Administration of Honeysuckle Tea Extract

1. Manufacturing and confirming Parkinson's disease animal model

Parkinson's disease model was prepared by administering 6-OHDA to the brain.

Anesthetized experimental animals (male, rat / rat, 250-300 g Sprague-Dawley system) (anesthetic: Zoletil 50 use, 100 mg / kg, im; vibac, Carros, France), stereotaxic apparatus After immobilization of the animal using the KOPF instrument, USA, 6-OHDA (Sigma, 8 μg / 2 μl, 1 μl / min) was administered to the black dense area of one site (see Paxions and Watson atlas). ; -5.3 mm in front of bregma, +1.9 mm in the middle line, -7.5 mm in the dura mater).

Two weeks later, apomorphine (0.5 mg / kg, subcutaneous injection) was used to evaluate rotational movement in order to select animals showing hemi-parkinsonism after the above method. Among the 6-OHDA-administered groups, animals that exhibited more than 300 rotations per hour in the opposite direction of apomorphine administration were selected to evaluate the formation of an appropriate Parkinson's disease model. The experimental groups were classified as follows.

1) Group A (Shame): 4 weeks breeding (6-OHDA untreated group) after injection / treatment with saline (2 μl in 0.2% ascorbate saline, 1 dose).

2) Group B (Lesioned): Breeding 4 weeks after injection / treatment with 6-OHDA (8 μg / 2 μl in 0.2% ascorbate saline, single dose).

3) Group C (low dose vine tea extract treatment group): 6 OHDA (8 μg / 2 μl in 0.2% ascorbate saline) injection / treatment of vine tea extract (10 mg / kg / mL, once daily) Breed with weekly oral administration.

Group D (high dose vine tea extract treatment group): 6 OHDA (8 μg / 2 μl in 0.2% ascorbate saline) injection / treatment of vine tea extract (30 mg / kg / mL, once daily) Breed with weekly oral administration.

2. Immunostaining and Measurement of Dopamine Neurons: Tyrosine Hydroxylase ( TH ) Activity

The number of animals in the experimental group was 20 animals, and each group of 10 animals was used for the simultaneous analysis of dopamine neuron immunostaining and neurotransmitters in the brain striatum.

Four weeks after 6-OHDA injection, an experimental animal evaluated to form Parkinson's disease was anesthetized with Zoletil 50 (100 mg / kg, im), followed by perfusion fixation through the left ventricle (4% paraform). Aldehyde / 0.05 M phosphate buffer solution) The brains were harvested and fixed in 4% paraformaldehyde solution for 24 hours (Muzamil et al ., 2006).

Frozen brain tissues were prepared and cryopreserved in cold form (thickness 35 μm; Cryostat, Leica, Nuolch, Germany) according to the method using 30% sucrose / PBS solution / isobutane (2-methyl butane).

Immunohistochemical staining was performed by free-floating method. The flake tissue was reacted with 1% hydrogen peroxide for 15 minutes, then washed with 2% normal horse serum for 30 minutes, and diluted with a monoclonal TH antibody (Calbiochem. USA) to detect TH enzyme activity. (0.05% BSA, 1.5% goat serum / 0.3% Triton X-100 solution, 1: 1000 dilution) for 24 hours. The biotinylated anti-mouse IgG (1: 200) reagent of the secondary antibody (Vector Laboratories. Inc., USA) and the reaction of Avidin-biotin peroxidase (Vectastain-Elite ABC kit, Vector Laboratories) for 2 hours at room temperature were washed for 2 hours. It was. In the final 0.003% hydrogen peroxidease and 0.05% 3,3'-diaminobenzidine solution, the color was developed for 4 minutes at room temperature, dehydrated, and then transparentized with xylane and encapsulated with polymount. As a control group for the staining process, all staining processes except the primary antibody (anti-TH) were treated in the same manner, and the nonspecific reaction was measured.

The distribution and staining of TH-immunostained cells in dense areas of the black matter were determined by counting the number of THCs immunostained with TH in the black matter, based on the degree of paxinos and others. Was performed by counting (Square eyepiece micrometer, ZEISS; magnification × 200 ×) (Ref). Student's t-test was used to determine the survival rate (number of lesion site / normal cell catchment) of TH immune cells in each experimental group.

TH immunohistochemical staining was performed on the midbrain tissues of the Parkinson's disease rat animal model, which showed a significant number of rotations by apomorphine induction. In Figure 1 A is a saline administration group, B is a 6-OHDA administration group, C is a 6-OHDA administration + vine tea extract (10mg / kg) administration group and D is a 6-OHDA administration + vine tea extract (30mg / kg) administration group (Scale bar = 100 μm).

In the saline injected animals (control), TH immune neurons were not reduced compared to normal sites, and TH immunostained cells in the medulla were polygonal or ovoid in cell body (FIGS. 1A and 1B). The lesion black matter was significantly decreased in the number of TH immunostained cells compared with the control group, and TH immunostaining was also markedly reduced in the lesion striatum (FIG. 1B).

TH immunonerve cells of sbustantia nigra compacta and substantia nigra reticulata had TH immunostained nerve fibers tangled like a net when viewed in normal areas (FIG. 1A), but in the 6-OHDA-administered site Stainability was markedly reduced (FIG. 1B), which was due to neuronal cell death (neurotoxic action) by oxidative stress of 6-OHDA (Cohen, 1984).

The decrease in TH immune neurons due to the neurotoxic action of 6-OHDA showed a significant dose-dependent inhibition by 6-OHDA administration after the vine tea extract administration (once daily, oral) according to the present invention. This suggests that oral administration of vine tea extract has a protective effect against toxic effects of 6-OHDA (FIGS. 1C and D).

In addition, the histological examination of the experimental results of the present experimental example and the survival rate of TH-containing neurons (number of lesion-site TH immune neurons / number of normal site TH immune neurons) at -5.2 mm from the bregma were calculated. Measured as shown in FIG.

As can be seen in Figure 2, the survival rate of TH immune neurons was 92% in the saline group administered saline, 38% in the group administered 6-OHDA (4 weeks of administration), 10 mg / kg after 6-OHDA administration In the group of oral administration of vine tea extract (once a day), the cell survival rate was 63% in the group of oral administration of 30 mg / kg vine tea extract (once a day) after 6-OHDA administration.

Therefore, it can be seen that the vine tea extract according to the present invention is useful for the treatment and prevention of depressive diseases caused by neurodegenerative diseases Parkinson's disease, Alzheimer's (AD) or Parkinson's disease.

< Experimental Example  2> Dopamine, noradrenaline, DOPAC  And HVA  Content measurement

Brain tissue samples of the classified animals were homogenized using 0.1 M perchloric acid (1 mL), centrifuged (10,000xg, 4 ° C, 30 minutes), and the supernatant was filtered (0.45 μm, Syringe filter) Dopamine, noradrenaline, DOPAC, HAV analysis samples (internal standard, isoproterenol), and the content of dopamine, noradrenaline, DOPAC, HAV in the brain tissue is shown in Figure 3 by using the HPLC method.

HPLC conditions: Waters 1525 pump, Waters 2996 photodiode array detector; ODS column, 15x0.45 cm; Mobile phase, MeOH: 35 mM sodium acetate buffer (10 mM citric acid-0.13 mM Na ₄ EDTA-0.58 mM SOS, pH 3.4) (10:90, v / v); Flow rate, 1 mL / min.

As can be seen in Figure 3, the dopamine, noradrenaline, DOPAC and HVA content of the striatum was reduced by 6-OHDA damage and the content was increased by oral administration of vine tea extract.

Dopamine content was decreased by 81% in the 6-OHDA-administered group (4 weeks of administration) compared to the control group (shame). And dopamine content decreased with striatum (Sctelo et. al ., 1973) (Perese et al ., 1989). The 10 mg / kg vine tea extract group (C group) and the 30 mg / kg vine tea extract group (D group), which were combined administration of vine tea extract after 6-OHDA administration, were 70.6% and 70.8, respectively, compared to the 6-OHDA alone group. There was a significant inhibitory effect on the DA content reduction effect of%, and no difference was observed in the concentration of vine tea extract. This indicates that vine tea extract increases dopamine neuron survival by inhibiting 6-OHDA induced neuronal cell death, thereby inducing dopamine biosynthesis.

The change of DOPAC content was decreased by 47.7% in the 6-OHDA group compared to the control (shame), and 39.3% in the 10 mg / kg vine tea extract group, 39.3% and 30 mg / kg vine tea extract group after 6-OHDA administration. In group D, the content was increased to 43.1% compared to the group treated with 6-OHDA only.

The change of norepinephrine content in the 6-OHDA-only group was decreased by 32.5% compared to the control group (shame), and after the 6-OHDA administration of the vine tea extract 10 mg / kg group C, 30 mg / In the D group, the kg administration group, 26.4% and 31.3% vine tea extracts were increased compared to the B group, respectively, but there was no significant difference between the two groups.

There was a similar trend in HVA content with 49.1% decrease in group B who received 6-OHDA only compared to the control group (shame), and dose-dependent difference was not found in the group that received oral vine tea extract after 6-ODHA. Compared to the 6-OHDA-only group, 44.3% of the vine-tea extract 10 mg / kg group treated with C and 45% of the 30 mg / kg-administered group, respectively.

Therefore, the vine tea extract according to the present invention prevents toxic effects (cell death) caused by 6-OHDA and shows a protective action against cell death, thereby treating depression disease caused by Parkinson's disease, Alzheimer's disease (AD) or Parkinson's disease, which are neurodegenerative diseases. And useful for prevention.

< Experimental Example  3> toxicity test

X 500 mg / kg and 1,000 mg / kg of the vine tea extract prepared in Example 1 was dissolved in phosphate-buffered saline (PBS) and orally administered once daily, 14 days using an oral administration device (Zonde). The control group was administered with PBS used to dissolve the test substance. The test animals used five or more females and females in each group, and 10 control groups, 12 500 mg / kg administration groups, and 12 1,000 mg / kg administration groups were used.

The day of dosing was observed from 1 hour to 6 hours after dosing, and the general symptoms, symptoms of poisoning, and death for all animals were observed once a day from the day after dosing to 14 days for the entire experimental period. Normal weight gain was observed in all dose groups, including the control group, and no dead animals were observed during the entire study period. In clinical observations, no toxicity was observed in the control group, 500 mg / kg group, or 1,000 mg / kg group, due to the administration of vine tea extract, and the minimum lethal dose was 1,000 mg / kg or more. It is feed.

1 shows immunohistochemical staining for tyrosine hydroxylase (TH) activity in substantia nigra, where A is a saline-administered group, B is a 6-OHDA group, and C is a 6-OHDA group. Administration + vine tea extract (10mg / kg) administration group and D is 6-OHDA administration + vine tea extract (30mg / kg) administration group (Scale bar = 100 ㎛).

2 is a diagram showing the survival rate of tyrosine hydroxylase (TH) active cells in substantia nigra, where A is a saline administration group, B is a 6-OHDA administration group, and C is a 6-OHDA administration + vine. Tea extract (10 mg / kg) administration group and D is 6-OHDA administration + vine tea extract (30 mg / kg) administration group.

Figure 3a shows the dopamine content in the striatum of each administration group measured using HPLC method, A is a saline administration group, B is a 6-OHDA administration group, C is a 6-OHDA administration + vine tea extract (10mg / kg) administration group and D represents the 6-OHDA administration + vine tea extract (30mg / kg) administration group,

Figure 3b shows the content of 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum of each administration group measured using the HPLC method, A is a physiological saline group, B is a 6-OHDA group, C 6-OHDA administration + vine tea extract (10mg / kg) administration group and D represents 6-OHDA administration + vine tea extract (30mg / kg) administration group,

Figure 3c shows the content of norepinephrine (NE) in the striatum of each administration group measured using HPLC method, A is a saline administration group, B is 6-OHDA administration group, C is 6-OHDA administration + vine Tea extract (10mg / kg) administration group and D represents 6-OHDA administration + vine tea extract (30mg / kg) administration group,

Figure 3d shows the content of homovanic acid (HVA) in the striatum of each administration group measured using HPLC method, A is a saline administration group, B is a 6-OHDA administration group, C is a 6-OHDA administration + The vine tea extract (10 mg / kg) administration group and D shows a 6-OHDA administration + vine tea extract (30 mg / kg) administration group.

Claims (1)

A pharmaceutical composition for the treatment and prevention of depression caused by Parkinson's disease, Alzheimer's (AD) or Parkinson's disease, which contains Gynostemma pentaphyllum extract as an active ingredient.

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