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The effect of extract of ginkgo biloba added to haloperidol on superoxide dismutase in inpatients with chronic schizophrenia.

The purpose of the study was to evaluate the effect of the classic antipsychotic haloperidol plus extract of ginkgo biloba (EGb) on treatment-resistant chronic schizophrenia and on blood superoxide dismutase (SOD) levels. Eighty-two patients with chronic refractory schizophrenia were studied. Forty-three patients were treated with haloperidol plus extract of ginkgo biloba (group 1), and 39 received haloperidol plus placebo (group 2). SOD levels of these patients were measured before and after treatment and were compared with SOD levels of 30 healthy volunteers. Therapeutic efficiency was equated with a change in clinical rating scores assessed by standardized measurement tools that included the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms (SANS) over this period. Patients in group 1 improved significantly as demonstrated by scores from these two assessment instruments; those in group 2 improved significantly only as shown by scores on SANS. SOD levels before treatment in all patients were significantly higher than those in healthy controls; after treatment, the SOD level decreased significantly in group 1 but not in group 2. These results suggest that EGb may enhance the efficiency of the classic antipsychotic haloperidol in patients with schizophrenia, especially on their positive symptoms, and that EGb may work through an antioxidant effect that is involved in the therapeutic mechanism in patients with chronic refractory schizophrenia.

Adult↗

Ginkgo biloba extract: from molecular mechanisms to the treatment of Alzhelmer's disease.

Ginkgo biloba is registered for the treatment of several diseases and disorders in Europe. In the United States, it is marketed as a dietary supplement; the French and the German agencies consider it to be effective for the treatment of several diseases, and the immense amount of clinical studies concerning Ginkgo biloba makes it worth revising the existing literature about this notable plant. A brief history of the common use of this drug will be followed by a short botanic characterization. The biochemical composition of the original drug, the leaf itself, will be described in detail together with a brief discussion of commercial extracts and the problem of studying Ginkgo biloba clinically to verify the safety and efficacy of its extracts in the treatment of disorders like Alzheimer's diseases. Aspects of molecular mechanisms modifying the efficacy of this drug will be outlined. Several agents like antioxidants, anti-inflammatory drugs, cholinergic agents, estrogens, or neurotrophic factors are in use for the treatment of this neurodegenerative disease, but none can prove fully convincing benefit. In this field, Ginkgo biloba appears as a useful and sensible supplementary medication to treat Alzheimer's disease, as it seems to be a synthesis of all the different profiles of action of the various, commonly used drugs but with less side effects.

Alzheimer Disease↗

Feeding of Ginkgo biloba extract (GBE) enhances gene expression of hepatic cytochrome P-450 and attenuates the hypotensive effect of nicardipine in rats.

Ginkgo biloba extract (GBE) has been used clinically for improving peripheral vascular diseases in France and Germany and is ingested widely as a herbal medicine in some countries. However, accurate information about its safety as an herbal medicine has not been sufficiently established. To address this issue, we examined the effect of GBE on hepatic drug metabolizing enzymes and their influence on hypotensive drug in rats. Male rats were fed either a control diet or diet containing GBE (0.5% w/w) for 4 weeks. The feeding of a GBE diet did not change the serum transaminase activity, but increased the liver weight and the phospholipid concentration in the liver. In addition, the GBE diet markedly increased the content of cytochrome P-450 (CYP), and the activity of glutathione S-transferase in the liver. Furthermore, the GBE diet markedly induced levels of CYP2B1/2, CYP3A1 and CYP3A2 mRNA in the liver. The levels of CYP1A1, CYP1A2, CYP2E1, CYP2C11 and CYP4A1 were unchanged. The feeding of GBE for 4 weeks significantly reduced the hypotensive effect of nicardipine that was reported to be metabolized by CYP3A2 in rats. These findings suggest that GBE reduces the therapeutic potency of the Ca2+ channel blocker, nicardipine, via enhancement of cytochrome P-450 expression.

Animals↗

The effect of Ginkgo biloba extract (EGb 761) on hepatic sinusoidal endothelial cells and hepatic microcirculation in CCl4 rats.

It has been shown that Ginkgo biloba Extract (EGb 761) increases peripheral and cerebral blood flow and microcirculation and improves myocardial ischemia reperfusion injury. This study was designed to investigate the effect of EGb 761 on hepatic endothelial cells and hepatic microcirculation. Sixty male Wister rats were divided into normal, carbon tetrachloride (CCl4) and EGb groups, and were given normal saline, CCl4 and CCl4 plus EGb 761, respectively, for 10 weeks. Samples were taken from the medial lobe of the rat livers ten weeks later. Hepatic sinusoidal endothelial cells and other parameters of hepatic microcirculation were observed under transmission electron microscopy (TEM). The amount of malondialdehyde (MDA), endothelin (ET-1), platelet-activating factor (PAF) and nitric oxide (NO) in liver tissue was determined by spectrophotometry and radioimmunoassay, respectively. Compared with the CCl4 group, aggregation of blood cell or micro thrombosis in hepatic sinusoids, deposition of collagen in hepatic sinusoids and space of Disse, injury of endothelial cells and capillization of hepatic sinusoid was significantly reduced in the EGb group. The amount of MDA, ET-1 and PAF was markedly reduced in the EGb group than in the CCl4 group, while no significant difference in the amount of NO was observed between the two groups. The results demonstrate that EGb 761 has protective effect on hepatic endothelial cells and hepatic microcirculation in rats with chronic liver injury induced by CCl4. The mechanisms may involve its inhibition on ET-1, PAF and lipid peroxidation.

Animals↗

Study of the long-term action of a Ginkgo biloba extract on vigilance and mental performance as determined by means of quantitative pharmaco-EEG and psychometric measurements.

The action of a Ginkgo biloba extract (rökan, Tanakan, G.B.E.) in promoting blood flow has been demonstrated in several animal and human pharmacological studies. The aim of this present study was to estimate the action of the substance on the central nervous system in order to be able to assess its potential use as a therapeutic agent in geriatric patients with cerebral insufficiency. Quantitative pharmaco-EEG is the method of choice for studying the vigilance-promoting effects of a drug. It is incomparable for confirming the findings of behavioural and psychometric studies. 60 volunteers of either sex participated in the double-blind trial. They were aged 57-77 years and showed mental deterioration corresponding to their age. They were randomly divided into three experimental groups: 20 subjects received 3 X 40 mg/day G.B.E., 20 received 5 mg nicergoline and 20 received a placebo of similar appearance. The subjects underwent an extensive series of examinations before and 4, 8 and 12 weeks after the start of medication. Analysis of the EEG results for the whole group revealed no significant advantage of G.B.E. over the two reference substances with regard to vigilance. However, a subclassification of the subjects showed that the vigilance of those persons with a more unfavourable initial situation measured in the resting EEG could be clearly improved by chronic G.B.E. medication. This increase in vigilance was reflected at the behavioural level by an improvement of reaction times in the G.B.E. group by comparison with the reference substances.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Short-term oral ingestion of Ginkgo biloba extract (EGb 761) reduces malondialdehyde levels in washed platelets of type 2 diabetic subjects.

We have recently reported that ingestion of Ginkgo biloba extract (EGb 761) (a) significantly reduced collagen-induced platelet aggregation and thromboxane B2 (TXB2) production in both non-diabetic individuals as well as those with type 2 diabetes mellitus (T2DM), (b) significantly reduced platelet malondialdehyde (MDA), an index of lipid peroxidation, in non-diabetic subjects. In the present study we report that ingestion of EGb 761 (120 mg daily for 3 months), significantly decreased platelet MDA-thiobarbituric acid reacting substances (TBARS) (41 +/- 9 pmol/10(7) platelets versus 30 +/- 11 pmol/10(7) platelets) (p < 0.005) in T2DM subjects with normal cholesterol levels (total cholesterol, 164 +/- 22 mg/dl; age, 54 +/- 9 years; BMI, 35.0 +/- 8.8 kg/m2, n = 12). In T2DM subjects with high cholesterol (total cholesterol, 218 +/- 15 mg/dl; age, 52 +/- 5 years; BMI, 36.2 +/- 6.6 kg/m2, n = 7), EGb 761 ingestion reduced the platelet TBARS from 29 +/- 9 to 22 +/- 9 pmol/10(7) platelets (p < 0.04). Because ingestion of EGb 761 did not alter platelet counts it is concluded that EGb 761, probably due to the flavonoid fraction, reduced the TBARS by inhibiting cyclooxygenase (COX)-1-mediated arachidonic acid oxygenation or by reducing the arachidonic acid pool. This is likely to lead to a reduction of platelet hyperactivity, a significant contributor to the development of cardiovascular disease in T2DM patients. Because of other reported beneficial properties of EGb 761, such as stimulation of pancreatic beta-cell function in T2DM subjects with pancreatic exhaustion, it appears that T2DM subjects might benefit from ingesting EGb 761 as a dietary supplement.

Administration, Oral↗

Involvement of monoamine oxidase inhibition in neuroprotective and neurorestorative effects of Ginkgo biloba extract against MPTP-induced nigrostriatal dopaminergic toxicity in C57 mice.

The present study investigated the neuroprotective and neurorestorative effects of Ginkgo biloba extract (EGb 761) and its two components ginkgolides A (BN52020) and B (BN52021) in mice. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30 mg/kg/d i.p. for six days) significantly reduced striatal dopamine (DA) levels in C57 mice measured by high performance liquid chromatography with electrochemical detection (HPLC-EC). When C57 mice were pretreated with EGb 761 (20, 50, 100 mg/kg/d i.p.) for 7 days and then treated with the same extract 30 min before MPTP injection for 6 days, the neurotoxic effect of MPTP was antagonized in a dose-dependent fashion. Similar treatment with ginkgolides A and B (5, 10, 50 mg/kg/d i.p.) showed no protective effect. When C57 mice were treated with EGb 761 (50 mg/kg/d i.p.) after MPTP-lesion, the recovery of striatal dopamine (DA) levels was accelerated. However, similar treatment with ginkgolides A or B (10 mg/kg/d i.p.) did not show any effect. EGb 761, but not ginkgolides A and B, nonselectively inhibited mouse brain MAO activity in vitro (IC50 = 36.45 +/- 1.56 microg/ml) tested by an improved fluorimetric assay. The results demonstrate that EGb 761 administered before or after MPTP treatment effectively protects against MPTP-induced nigrostriatal dopaminergic neurotoxicity and that the inhibitory effect of EGb 761 on brain MAO may be involved in its neuroprotective effect.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Effect of ginkgo biloba extract on livers in aged rats.

AIM: To investigate the protective effect of ginkgo biloba extract (GBE) on livers of aged rats and the associated mechanisms. METHODS: Two-mo- and 20-mo-old rats were treated with GBE/saline for 3 mo. Liver tissue samples from 5-mo-old rats treated with saline (group Y) and 23-mo-old rats treated with GBE (group E) or saline (group N) were used for histopathological examinations (hematoxylin-eosin and Masson staining, Lipofuscin staining-Schmorl staining) and determination of expression of tissue inhibitor-1 of metalloproteinase (TIMP-1) and the level of malondialdehyde (MDA), glutathione peroxidase (GPx) and superoxide dismutase (SOD). Blood samples were collected for determination of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and albumin. RESULTS: Microscopic studies with Masson staining revealed mild liver fibrosis in aged rats (group N), while the livers of aged rats receiving GBE (group E) showed amelioration in fibrosis (2.2+/-0.1 vs 2.8+/-0.1, P<0.01) and deposition of lipofuscin (33.7+/-5.3 vs 62.8+/-5.7, P<0.01). The expression of TIMP-1 and the level of liver MDA (1.0+/-0.1 vs 1.2+/-0.2, P<0.05) also decreased but the activity of GPx (97.1+/-15.3 vs 61.8+/-14.5, P<0.01) increased in group E. Compared with group Y, the level of liver MDA (0.8+/-0.1 vs 1.2+/-0.2, P<0.01), lipofuscin (32.4+/-6.0 vs 62.8+/-5.7, P<0.01) and TIMP-1 expression were increased, while the activity of GPx (103.2+/-17.6 vs 61.8+/-14.5, P<0.01) and SOD (16.7+/-4.4 vs 11.8+/-3.9, P<0.05) was decreased in group N. There was no difference in liver function among these three groups. CONCLUSION: GBE has protective effects on aging liver. The possible mechanisms might be its antioxidant activity and inhibition of TIMP-1 expression.

Aging↗

[Effect of Ginkgo biloba extract (EGb 761) on rats in an experimental model of acute encephalopathy after total body irradiation].

PURPOSE: To define the therapeutic effect of Ginkgo biloba extract (EGb 761) in an experimental model of acute encephalopathy following total body irradiation in rats. MATERIAL AND METHODS: Ninety four-month-old rats received 4.5 Gy total body irradiation (TBI) at day 1 while 15 rats received sham irradiation. A behavioural study based on a conditioning test of negative reinforcement, the one-way avoidance test, was performed test, was performed after irradiation. Orally treatment was started one day (study A) or twenty two days (study B) after irradiation and repeated daily for twelve days. In the irradiated group, three subgroups were defined according to the treatment received: EGb 761 (50 mg/kg), EGb 761 (100 mg/kg), water. RESULTS: This work comprised two consecutive studies. In study A (45 rats) the one-way avoidance test was administered daily from day 7 to day 14. In study B (45 rats) the behavioural test was performed from day 28 to day 35. Study A (three groups of 15 rats): following TBI, irradiated rats treated with water demonstrated a significant delay in a learning the one-way avoidance test in comparison with sham-irradiated rats (P < 0.0002) or irradiated rats treated with EGb 761 (50 mg/kg; P < 0.0017) or EGb 761 (100 mg/kg; P < 0.0002). The irradiated rats, treated with EGb 761 (50 or 100 mg/kg) did not differ from the sham-irradiated controls. Study B (three groups of 15 rats): the irradiated rats, treated with water or EGb 761 (50 or 100 mg/kg) did not differ from the sham-irradiated controls. CONCLUSION: This study indicates that a relatively low dose of total body irradiation induces a substantial acute learning dysfunction in the rat, which persists fourteen days after TBI. This effect is prevented by the administration of EGb 761 (50 or 100 mg/kg) started twenty-four hours after irradiation.

Animals↗

Effects of repeated treatments with an extract of Ginkgo biloba (EGb 761) on cerebral glucose utilization in the rat: an autoradiographic study.

1. The autoradiographic method based on 2-deoxy-D[1-14C]glucose ([14C]DG) was used to determine glucose utilization in 49 discrete structures of rat brain under control conditions and after the animals had received repeated treatment with an extract of Ginkgo biloba (EGb 761). 2. Oral administration of EGb 761 (50 or 150 mg/kg/day) to adult male rats for 15 days did not modify body weight, mean arterial blood pressure, the concentrations of glucose or hemoglobin in blood, blood gases or arterial pH. 3. EGb 761 treatments produced only slight-to-moderate changes in glucose utilization in the various brain structures; i.e. decreases to an extent not exceeding 18.4% at the 50 mg/kg dose or 11.7% at the 150 mg/kg dose. 4. Glucose utilization was significantly decreased only in the frontoparietal somatosensory cortex, nucleus accumbens, cerebellar cortex and pons and only with the 50 mg/kg dose of EGb 761. 5. Although the four brain structures affected by EGb 761 treatment do not, in themselves, constitute a specific functional system of the CNS, these effects appear useful in explaining mechanisms underlying the clinical use of EGb 761 in treating problems associated with deficient somatosensory processing (e.g. impairment of "vigilance") and vestibular mechanisms (e.g. vertiginous syndromes).

Administration, Oral↗

Effects of ginkgo biloba extract on impairment of learning induced by cerebral ischemia in mice.

The effect of Ginkgo biloba extract (GbE) on cerebral ischemia induced by 10-min bilateral occlusion of the carotid arteries in mice was studied. Severe impairment of memory was apparent when the passive avoidance test was carried out 48 hr after bilaterally induced ischemia. When GbE at doses of 50 and 100 mg/kg was given p.o. 1 hr before the 10-min occlusion, there was a significant improvement in memory. The i.p. injection of ifenprodil (30 mg/kg) also showed improvement on learning tasks. The p.o. administration of flavonoid, a fraction isolated from GbE, showed high step-through latency on scopolamine-induced amnesia. All these findings indicate that GbE is beneficial for clinical use in amnesia accompanied with cerebral vascular disease.

Amnesia↗

Demonstration of the "anti-stress" activity of an extract of Ginkgo biloba (EGb 761) using a discrimination learning task.

1. Young (4-month-old) and old (20-month-old) rats, maintained under water restriction, were trained to discriminate to obtain a small amount of drinking water as a reward. Each animal had to learn to press a lever corresponding to a light that was randomly distributed on the left or right. 2. Introduction of an auditory perturbation ("stress") during the discriminative phase of learning modified the capacity and rate of acquisition in both young and old animals, changes that were correlated with increases in plasma concentrations of epinephrine, norepinephrine and corticosterone. 3. Stress-induced detrimental changes in both discrimination learning and plasma hormones were suppressed by 20 days of oral treatment with an extract of Ginkgo biloba leaves (EGb 761; 50 or 100 mg/kg/day) in both young and old rats, effects that became statistically significant by the third day of learning (time of maximal acquisition rate). 4. EGb 761 treatment was less effective in increasing the percentage of efficient lever presses in old than in young rats, but more effective in decreasing the number of inefficient lever presses and reaction time in the older animals. 5. These results indicate that EGb 761 can facilitate behavioral adaptation despite adverse environmental influences, a property that supports its clinical use in treating cognitive impairment, especially in elderly patients.

Age Factors↗

Preventive effect of Ginkgo biloba extract on apoptosis in rat cerebellar neuronal cells induced by hydroxyl radicals.

The ability of oxidative stress to induce apoptosis, and the effect of Ginkgo biloba extract (EGb761) on this induction were studied in primary cultured rat cerebellar neuronal cells. Cells were exposed to hydroxyl radicals by treating them with 20-50 microM hydrogen peroxide (H2O2) and 100 microM ferrous sulfate. Hydroxyl radical treatment fragmented the DNA in a manner typical of apoptosis cells, producing a ladder pattern of 200 base pair increments on 1% agarose gel electrophoresis. Pretreatment of cells with 100 micrograms/ml EGb reduced hydroxyl radical induced cells apoptosis (determined by flow cytometry) and DNA fragmentation. The results indicate that hydroxyl radicals induce apoptosis in rat cerebellar neuronal cells and this induction can be prevented by EGb.

Animals↗

In vitro antioxidant effect of Ginkgo biloba extract (EGb 761) on lipoperoxidation induced by hydrogen peroxide in erythrocytes of Behçet's patients.

Excessive superoxide radical production and an impaired antioxidant mechanism in both the neutrophils and plasma of patients with Behçet's disease (BD) have been reported. To provide clinical support for the earlier data, erythrocyte membrane integrity was investigated by measuring malondialdehyde (MDA, a marker of lipid peroxidation) levels in the erythrocytes of BD patients. In addition, the antioxidant effect of Ginkgo biloba extract (EGb 761) at 25 and 250 microg/ml concentrations on lipoperoxidation induced by hydrogen peroxide (H2O2) in erythrocyte obtained from BD patients was examined in in vitro conditions. When compared to healthy controls, basal erythrocyte MDA levels were found to be higher in BD patients. In the in vitro study, there was also a significant increase in H2O2-induced MDA production in the medium containing no EGb 761 in the patient group, whereas significant decreases in MDA levels were observed in the mediums containing EGb 761 both in the patient and control groups. The decrease in MDA production was found to be related to EGb 761 concentration. These data indicate that an oxidative damage is present in erythrocytes obtained from Behçet's patients, and EGb 761, which may strengthen the antioxidant defense system, may contribute to the treatment of BD.

Adolescent↗

[Protective effect of ginkgo biloba extract on cerebral ischemia/reperfusion injury in rats].

OBJECTIVE: To study the effect of Ginkgo biloba extract (GbE) on dynamic equilibrium of free radicals and amino-acids in cortex of rats with cerebral ischemia/reperfusion (I/R) injury and its influence and characteristics to intracellular free calcium concentration ([Ca2+]i) in primary cultured hippocampal neuron of rats. METHODS: Amino-acids were quantified by high performance liquid chromatographic (HPLC) analysis. Concentration of MDA and GSH-Px were determined by thiobarbituric acid (TBA) technique. SOD was assayed through xanthine method, and microfluoremetric technique was used to assay the change of [Ca2+]i and its characteristics. RESULTS: Compared with the non-treated groups, at all time points (3 hrs after ischemia, 1 and 2 hrs after I/R separately), in the GbE treated groups, the levels of Glu, Asp and MDA were lower and SOD and GSH-Px were higher (P < 0.01 or P < 0.05), the GABA and Gly levels were lower in groups treated with middle (10 mg/kg) or high dosage (15 mg/kg) of GbE (P < 0.05). Compared with the group treated with small dosage GbE (5 mg/kg), Glu, Asp and MDA were lower and GABA, Gly, SOD and GSH-Px were higher in the groups treated with middle or high dosage of GbE (P < 0.05), while the difference in the latter two groups was insignificant. Level of [Ca2+]i in cultured neurons treated with 1 x 10(-5) mol/L glutamate combined 25 micrograms/ml GbE for 20s was lower with lower peak value and longer time for reaching the peak than that in neurons treated with 1 x 10(-5) mol/L glutamate alone. Besides, the time of decline phase was also shorter in the former, so the flatform stage was prolonged. The response was recovered by re-applying of glutamate after [Ca2+]i back to base line. CONCLUSION: GbE can protect damaged neurons through keeping the balance of inhibitory/excitatory amino-acids, enhancing free radicals scavengers system, and inhibiting the effect of glutamate to [Ca2+]i.

Amino Acids↗

[The effect of Ginkgo biloba extract in patients with intermittent claudication].

Eighteen patients with stable intermittent claudication were randomized in a double blind cross-over study comparing the effects of the Ginkgo biloba extract GB-8 at a dose of 120 mg o.d. with placebo. All patients were treated for three months with the active extract and three months with placebo. The effects of treatment on arterial insufficiency were quantified by measurements of systemic and peripheral systolic blood pressures, and pain-free and maximal walking distances on a tread-mill. Questionnaires based on visual analogue scales were used to quantify the severity of leg pain, impairment of concentration, and inability to remember. Short-term memory was objectively assessed. We did not find any significant changes in either peripheral blood pressures, walking distances or the severity of leg pain. Systemic blood pressure was reduced both by placebo and GB-8. The impairment of concentration and the inability to remember were both reduced, when comparing results during active treatment to placebo. Short-term memory did not change significantly. In conclusion, our study has shown that treatment with the Ginkgo biloba extract GB-8 improves some cognitive functions in elderly patients with moderate arterial insufficiency, whereas the extract did not change signs and symptoms of vascular disease in the patients.

Aged↗

Ginkgo biloba extract protects brain neurons against oxidative stress induced by hydrogen peroxide.

Effect of Ginkgo biloba extract was examined on dissociated rat cerebellar neurons suffering from oxidative stress induced by hydrogen peroxide using a flow cytometer and ethidium bromide. Hydrogen peroxide at a concentration of 3 mM increased the number of neurons stained with ethidium (presumably dead neurons) in a time-dependent manner. Pretreatment of neurons with G. biloba extract (10 micrograms/ml) greatly delayed a time-dependent increase in number of dead neurons during exposure to hydrogen peroxide. It was true, but less effective, in the case of treatment with G. biloba extract immediately or 60 min after start of oxidative stress. Results implicate G. biloba extract as a potential agent in protecting the neurons suffering from oxidative stress induced by hydrogen peroxide.

Animals↗

[Effect of extract of ginkgo bilboa leaf on early diabetic nephropathy].

OBJECTIVE: To study the effect of extract of Ginkgo bilboa leaf (EGB) on renal lesions of early diabetic nephropathy (DN). METHODS: Sixty-eight patients with early DN were randomly divided into two groups, the control group (34 patients) and the treated group (34 patients). Patients in both groups received conventional therapy, while additional 9.6 mg EGB was orally taken by patients in the treated group, three times per day. The therapeutic course for both groups was three months. Indexes such as urinary microalbumin (mALB), alpha1-microglobulin (alpha1-MG), immunoglobulin (IgG), transferrin (TF), retinal binding protein (RBP) and N-acety-beta-D-glucosaminidase (NAG) before and after treatment between the two groups were compared respectively. RESULTS: Compared with before treatment, mALB, alpha1-MG, IgG, TF, RBP and NAG obviously decreased with significant difference in the treated group after treatment (P < 0.05). However, no significant decrease in the above-mentioned indexes in the control group (P > 0.05). CONCLUSION: EGB has the protective action on early DN.

Adult↗