Application of Baicalein in the Preparation of Drugs for Preventing and Treating Neonatal Hypoxic-Ischemic Encephalopathy

Abstract

The present invention provides the use of baicalein in the preparation of a drug for preventing and treating neonatal hypoxic-ischemic encephalopathy, belonging to the technical field of neonatal pharmaceutical preparations. The present invention discloses the use of baicalein in the preparation of a drug for preventing and treating neonatal hypoxic-ischemic encephalopathy. Baicalein can effectively cross the neonatal blood-brain barrier, reduce the ferroptotic neonatal brain tissue damage caused by ischemia and hypoxia, and thus play a role in preventing and treating neonatal hypoxic-ischemic encephalopathy. The present invention expands the application scope of baicalein in the drugs for preventing and treating neonatal hypoxic-ischemic encephalopathy.

Description

Technical Field

[0001] The present invention belongs to the technical field of neonatal pharmaceutical preparations, and relates to the application of baicalein in the preparation of drugs for preventing and treating neonatal hypoxic-ischemic encephalopathy. Background Art

[0002] Newborns refer to infants from birth to 28 days old. According to the gestational age at birth, newborns can be divided into premature infants (gestational age at birth < 37 weeks), full-term infants (gestational age at birth 37 - 41 weeks), and post-term infants (gestational age at birth ≥ 42 weeks). There is no exact definition for neonatal medication. Currently, it is generally considered that a drug with a research basis in neonatal pharmacokinetics and drug toxicology, and proven to be safe and effective through clinical applications in adults and children, and can be applied to newborns is neonatal medication. Newborns have physiological characteristics closely related to drug absorption and excretion, such as high gastric juice pH, delicate skin and mucous membranes, large body fluid volume, and immature liver and kidney functions. These physiological characteristics determine the great differences between neonatal medication and that of infants and adults. Due to reasons such as immature development, few suitable drugs, and lack of medication research information, the incidence of adverse drug reactions in newborns is relatively high.

[0003] Neonatal hypoxic-ischemic encephalopathy (HIE) refers to hypoxic-ischemic brain injury caused by perinatal asphyxia, which can lead to cerebral edema and abnormal neurodevelopment, and is an important cause of permanent neurological defects and even death in newborns. HIE is a common disease in newborns. Currently, about 750,000 infants suffer from moderate or severe HIE every year, resulting in about 400,000 infants having neurodevelopmental disorders. Among the affected children, 15% - 20% die in the neonatal period, and 20% - 30% of the survivors may have varying degrees of neurological damage, such as cerebral palsy (10% - 20%), hearing or vision problems (about 40%). HIE seriously affects the life and health of newborns.

[0004] Currently, the treatment methods for neonatal hypoxic-ischemic encephalopathy (HIE) are therapeutic hypothermia (TH) and corresponding supportive treatment. TH is the standard therapy for HIE, which involves cooling the neonatal brain to slow down the spread of cell damage and reduce brain injury. Although TH can reduce the mortality rate and the incidence of neurological dysfunction in moderate to severe neonatal HIE, the treatment time window of TH is extremely short, and the greatest benefit can only be achieved within 6 hours. Moreover, TH can induce potential complications such as sinus bradycardia and hypoglycemia, and there is still a 45-55% probability of death or progression to moderate to severe HIE. Importantly, surviving children still face sequelae such as developmental delay, mental retardation, and spastic paralysis. With the in-depth study of neonatal HIE, drugs targeting the pathogenesis of neonatal HIE and improving nerve injury have been successively discovered. Magnesium has been used in the adjuvant treatment of HIE due to its neuroprotective effect in the preterm population. Although drugs such as dexmedetomidine, N-acetylcysteine, xenon, 4-octyl itaconate, menadione-4, myricetin, tanshinone IIA, resveratrol, echinacoside, naringenin, and topiramate have certain effects in the treatment of HIE animal models, more clinical data are still needed to prove their efficacy in HIE. Drugs such as erythropoietin (EPO), melatonin, and cannabidiol have entered clinical trials. However, in animal models mimicking HIE, EPO can significantly reduce neuron apoptosis induced by hypoxic ischemic brain damage (HIBD) and improve HIBD. However, in a clinical trial, the combination of EPO and hypothermia treatment did not reduce the mortality rate and the risk of neurodevelopmental disorders in patients with moderate to severe HIE. On the contrary, the combination of EPO and hypothermia treatment led to a higher incidence of long-term sequelae of HIE. Melatonin is mainly used in the early stage of ischemic injury, but its practicality is limited due to the lack of drug-grade products. It can be seen that some drugs that significantly improve brain damage in animal models and in vitro experiments may not be applicable in clinical practice. Therefore, it is still of great significance to find treatment methods and drugs to improve neonatal HIE and reduce the mortality rate and long-term adverse prognosis of neonatal HIE.

[0005] Baicalein, also known as baicalin aglycone and baicalin flavin, is one of the flavonoid compounds with the highest content in Scutellaria baicalensis. The chemical structure of baicalein is shown as follows:

[0006] 。

[0007] Baicalein is the flavonoid structure part of baicalin. The molecular structure of baicalin is shown as follows:

[0008] 。

[0009] The topological molecular polar surface area of baicalein is 0.05×10 −6  cm•s −1 , which is much smaller than that of its similar molecule baicalin. The smaller the topological molecular polar surface area, the higher the blood-brain barrier permeability. Therefore, it is predicted that baicalein has a higher blood-brain barrier permeability than baicalin, which is conducive to maintaining a certain blood drug concentration in the brain tissue.

[0010] In recent years, a large number of studies have shown that baicalein can improve nerve injury by anti-apoptosis, anti-inflammation, anti-oxidation, and anti-excitotoxicity, playing a protective role in damaged nerves. For example, baicalein can improve the cognitive impairment of Alzheimer's disease rats caused by chronic cerebral hypoperfusion and the behavioral abnormalities of MPTP-induced Parkinson's mice. Baicalein alleviates cerebral injury induced by intracerebral hemorrhage by inhibiting reactive oxygen species (ROS) and NLRP3 inflammasome. In vitro studies have shown that baicalein has significant antioxidant stress injury and neuroprotective effects. Baicalein inhibits hydrogen peroxide-induced lipid peroxidation and ROS generation in a dose-dependent manner, thereby increasing the cell survival rate. Baicalein can inhibit rotenone-induced apoptosis, inhibit the accumulation of reactive oxidative substances and mitochondrial membrane potential dissipation, suggesting that baicalein may act as a mitochondria-targeted antioxidant and play a neuroprotective role against rotenone-induced neurotoxicity. Baicalein prevents 6-hydroxydopamine (6-OHDA)-induced mitochondrial dysfunction in SH-SY5Y cells by reducing ROS production and upregulating the expression of DJ-1 (also known as PARK7) protein. Baicalein can inhibit Aβ / AMPA / NMDA-induced neuronal depolarization. Baicalein treatment alleviates long-term nerve injury after ischemia and hypoxia by inhibiting neuronal death and enhancing neurite outgrowth through the GAP43-dependent pathway. Baicalein improves traumatic brain injury by inhibiting the oxidation of phosphatidylethanolamine. In addition, compared with the ferroptosis inhibitor ferrostatin-1 (Fer-1), baicalein has significant anti-ferroptosis activity. As a natural ferroptosis inhibitor, baicalein can inhibit the degradation of GPX4 protein induced by Erastin, thereby protecting cells from membrane lipid peroxidation and the occurrence of ferroptosis, while neuronal ferroptosis is one of the important pathophysiological mechanisms of neonatal hypoxic-ischemic encephalopathy (HIE) brain injury. As a selective inhibitor of 12 / 15-lipoxygenase (12 / 15-LOX), baicalein can also inhibit ferroptosis in acute lymphoblastic leukemia cells induced by RSL3.

[0011] All kinds of signs indicate that the multiple key roles of baicalein in neuroprotection provide a new potential therapeutic agent for the treatment of neonatal hypoxic-ischemic encephalopathy (HIE). However, compared with adults, the nervous system of neonates is not yet fully developed, and the brain injury mechanism of HIE is complex. There are technical bottlenecks in transferring adult medications to neonates, and the existing technology has not provided any records on the transfer of baicalein used in adults to medications for neonatal HIE. Summary of the Invention

[0012] In view of this, aiming at the problem that there is a lack of clear basis for the drug effect of baicalein in the preparation of medications for neonatal hypoxic-ischemic encephalopathy in the existing technology, the purpose of the present invention is to provide an application of baicalein in the preparation of medications for preventing and treating neonatal hypoxic-ischemic encephalopathy.

[0013] On the one hand, to achieve the above-mentioned invention purpose, the present invention provides an application of baicalein in the preparation of a medication for preventing and treating neonatal hypoxic-ischemic encephalopathy.

[0014] Preferably, the composition of the medication further includes pharmaceutically acceptable excipients.

[0015] Among them, the pharmaceutically acceptable excipients include diluents, buffers, flavoring agents, binders, surfactants, thickeners, lubricants, preservatives, antioxidants, etc.

[0016] Preferably, the active ingredient of the medication includes baicalein.

[0017] More preferably, the active ingredient of the medication is baicalein.

[0018] Preferably, the dosage form of the medication is a solution.

[0019] The solution includes, but is not limited to, injectable solutions and oral solutions.

[0020] More preferably, the dosage form of the medication is an injectable solution.

[0021] Preferably, the prevention and treatment of neonatal hypoxic-ischemic encephalopathy is manifested as a reduction in neurological deficit signs and / or a reduction in the infarct area of brain tissue.

[0022] Preferably, the neonatal hypoxic-ischemic encephalopathy includes at least one of the following:

[0023] Neuronal death in the CA1 region of the neonatal hippocampus;

[0024] Mitochondrial damage in neonatal brain tissue.

[0025] More preferably, the neonatal hypoxic-ischemic encephalopathy includes the following two:

[0026] Neuronal death in the CA1 region of the neonatal hippocampus;

[0027] Mitochondrial damage in neonatal brain tissue.

[0028] Preferably, the neonatal hypoxic-ischemic encephalopathy includes at least one of the following:

[0029] Increased concentration of malondialdehyde in neonatal hippocampal tissue;

[0030] Increased concentration of ferrous ions in neonatal hippocampal tissue;

[0031] Decreased concentration of reduced glutathione in neonatal hippocampal tissue;

[0032] Increased ratio of oxidized glutathione to reduced glutathione in neonatal hippocampal tissue.

[0033] More preferably, the neonatal hypoxic-ischemic encephalopathy includes all of the following items:

[0034] Increased concentration of malondialdehyde in neonatal hippocampal tissue;

[0035] Increased concentration of ferrous ions in neonatal hippocampal tissue;

[0036] Decreased concentration of reduced glutathione in neonatal hippocampal tissue;

[0037] Increased ratio of oxidized glutathione to reduced glutathione in neonatal hippocampal tissue.

[0038] Compared with the prior art, the present invention has the following beneficial effects:

[0039] (1) The present invention uses P7 rats to establish an HIE model according to the Rice-Vannucci method to study the mechanism of action of baicalein in neonatal HIE, explore the protective effect of baicalein in brain damage caused by HIE, and provide new ideas for the treatment of neonatal HIE brain damage with baicalein.

[0040] (2) It can be known from the experiments of the present invention that baicalein can effectively reduce ferroptosis of brain tissue caused by ischemia and hypoxia by targeting the ferroptosis pathway, and significantly improve the symptoms of brain damage caused by ischemia and hypoxia in young experimental animals.

[0041] (3) In the application provided by the present invention, baicalein can effectively prepare a drug for preventing and treating neonatal hypoxic-ischemic encephalopathy. Description of the Drawings

[0042] Figure 1 It is a flow chart for the construction of a neonatal HIE animal model.

[0043] Figure 2It is the result graph of baicalein reducing the Zea Longa score and decreasing the infarct area of brain tissue in HIBD rats. Among them, A is the line graph of Zea Longa scores of animals in each group. ns indicates no significant difference compared with the model group, indicating a significant difference compared with the model group and P < 0.001, indicating a significant difference compared with the model group and P < 0.0001; B is the brain anatomical photo of animals in each group after treatment; C is the bar graph of cerebral infarct volume of animals in each group. ns indicates no significant difference, indicating a significant difference and P < 0.001, indicating a significant difference and P < 0.0001.

[0044] Figure 3 It is the stained slice graph of neurons in the hippocampal CA1 region of HIBD rats at different magnifications after treatment with baicalein; among them, A is the H&E stained slice graph of the hippocampal CA1 region of animals in each group, and B is the Nissl stained slice graph of the hippocampal CA1 region of animals in each group.

[0045] Figure 4 It is the bar graph of the concentration levels of MDA (malondialdehyde), Fe 2+ and GSH (reduced glutathione) in the hippocampal tissue of HIBD rats after treatment with baicalein; among them, A is the bar graph of MDA concentration level, B is the bar graph of GSH concentration level, and C is the bar graph of Fe 2+ concentration level; ns indicates no significant difference, indicating a significant difference and P < 0.05, indicating a significant difference and P < 0.01, indicating a significant difference and P < 0.001, indicating a significant difference and P < 0.0001.

[0046] Figure 5 It is the result graph of baicalein improving the mitochondrial damage induced by the model group and reducing the level of lipid peroxidation product 4-HNE; among them, A is the biological transmission microscope graph of brain tissue slices in each group and the enlarged graph of the region of interest. The square indicates the region of interest, and the arrow indicates the region of mitochondrial damage; B is the confocal fluorescence staining graph of MAP2, 4-HNE, and DAPI in brain tissue cells in each group; C is the bar graph of the relative fluorescence staining intensity of 4-HNE, representing a significant difference and P < 0.05, Indicates significant differences and P <0.01.

[0047] Figure 6 It is the result graph of baicalein reducing the GSSG level induced by the model group and increasing the GSH level and targeting the ferroptosis pathway to improve cell damage. Among them, A is the bar graph of GSSG concentration, Indicates significant differences and P <0.05, Indicates significant differences and P <0.01; B is the bar graph of GSH concentration, Indicates significant differences and P <0.01, Indicates significant differences and P <0.001; C is the immunoblotting result graph of proteins related to the ferroptosis pathway. The baicalein concentration in the model + baicalein group is 10 μM, and the Fer-1 concentration in the model + Fer-1 group is 10 μM.

[0048] Figure 7 It is the immunoblotting result graph of ALOX15 and 4-HNE proteins expressed in the hippocampal tissue of rats by baicalein. Among them, the baicalein dose in the model + baicalein group is 60 mg / kg, and the Fer-1 dose in the model + Fer-1 group is 5 mg / kg. Detailed implementation methods

[0049] The following non-limiting examples can enable those of ordinary skill in the art to understand the present invention more comprehensively, but do not limit the present invention in any way. The following content is only an exemplary illustration of the scope claimed by the present invention. Those skilled in the art can make various changes and modifications to the present invention based on the disclosed content, and it should also fall within the scope claimed by the present invention.

[0050] The present invention will be further described below by way of specific examples. All chemical reagents used in the examples of the present invention are obtained through conventional commercial channels unless otherwise specified. Unless otherwise specified, the contents described below are mass contents. Unless otherwise specified, it is understood to be carried out at room temperature.

[0051] In the following examples, the methods for obtaining experimental animals are as follows.

[0052] 8-week-old SPF-grade SD female and male rats were purchased from Guangzhou Jinwei Biotechnology Co., Ltd. The SD rats were housed in a male-female cohabitation manner in an SPF barrier environment, ensuring sufficient food and water. The pups on the first day of pregnancy of the pregnant rats are called P0 rats, the pups on the second day of pregnancy are called P1 rats, and so on. The pups on the eighth day of pregnancy of the pregnant rats are called P7 rats.

[0053] The low-pressure oxygen environment control system used in the following examples was purchased from Yuyan Instrument Company.

[0054] In the following examples, the manufacturers and catalog numbers of the reagents used are summarized in Table 1.

[0055] Table 1

[0056]

[0057] In the following examples, the statistical analysis method was as follows: Graphpad Prism 8.0 was used for statistics, the data was expressed as mean ± standard error (mean ± SEM), and the One-Way ANOVA method was used to analyze the data. P <0.05 was considered a significant difference.

[0058] Example

[0059] The model construction, treatment, and characterization processes of this example are as Figure 1 shown.

[0060] 1. Construct an HIE model and treat it with baicalein.

[0061] P7 rats were used and randomly grouped, with 3 - 6 rats in each group according to different experiments. They were then labeled as the normal control group, sham operation group, model group, model + baicalein group, model + Fer-1 group, and model + solvent group:

[0062] Normal control group: P7 rats, without any treatment.

[0063] Sham operation group: When the rats were anesthetized, a 2-mm incision was made 1 mm to the left of the midline of the neck, the left common carotid artery was isolated, and then the incision was sutured and the postoperative rats were returned to their mother rats.

[0064] Model group: When the rats were anesthetized, a 2-mm incision was made 1 mm to the left of the midline of the neck, the left common carotid artery was isolated, and the left common carotid artery was ligated with 5-0 suture and the incision was sutured. The postoperative rats were returned to their mother rats to recover for 1 h, and then placed in an oxygen concentration control system (8% O2) for hypoxia for 2 h. Pay attention to keeping warm during the operation and hypoxia.

[0065] Model + Baicalein group: When the rats were under anesthesia, a 2-mm incision was made 1 mm to the left of the midline of the neck, the left common carotid artery was isolated, ligated with 5-0 suture, and the incision was sutured. The rats after surgery were returned to their mother rats for 1 h of recovery, and then placed in an oxygen concentration control system (8% O2) for 2 h of hypoxia. Then, baicalein (60 mg of baicalein per kilogram of rat body weight) was injected intraperitoneally.

[0066] Model + Fer-1 group: When the rats were under anesthesia, a 2-mm incision was made 1 mm to the left of the midline of the neck, the left common carotid artery was isolated, ligated with 5-0 suture, and the incision was sutured. The rats after surgery were returned to their mother rats for 1 h of recovery, and then placed in an oxygen concentration control system (8% O2) for 2 h of hypoxia. Then, the ferroptosis inhibitor ferrostatin-1 (Fer-1) (5 mg of Fer-1 per kilogram of rat body weight) was injected intraperitoneally.

[0067] Model + Solvent group: When the rats were under anesthesia, a 2-mm incision was made 1 mm to the left of the midline of the neck, the left common carotid artery was isolated, ligated with 5-0 suture, and the incision was sutured. The rats after surgery were returned to their mother rats for 1 h of recovery, and then placed in an oxygen concentration control system (8% O2) for 2 h of hypoxia. Then, the solvent (5% dimethyl sulfoxide + 45% PEG300 + 50% ultrapure water) was injected intraperitoneally.

[0068] 2. Behavioral scores were performed on the rats after hypoxia and 24 hours after treatment with baicalein.

[0069] Twenty-four hours after drug administration after the establishment of the rat model, behavioral scores were performed by two experimental personnel who were not in this research group and were unaware of the experimental grouping. The scoring criteria are as follows:

[0070] 0 point: The rats had no symptoms of nervous system damage.

[0071] 1 point: The rats could not fully extend their right forelimbs.

[0072] 2 points: The rats rotated to the right when walking and showed a "tail chasing" phenomenon.

[0073] 3 points: The rats were unsteady when standing and toppled to the right.

[0074] 4 points: The rats could not walk spontaneously and showed consciousness disorders.

[0075] 3. The rats in each group were sacrificed, dissected, and their brain tissues were taken.

[0076] The obtained brain tissues were subjected to TTC staining, photographs were taken, and the infarct area was calculated. Then the brain tissues were sectioned, and the sections were stained with H&E and Nissl. Further, the brain tissues were taken for Fe 2+ level determination, GSSG and GSH level determination, lipid peroxidation product 4-HNE level determination, and Western blotting.

[0077] 4. Results.

[0078] 4.1 Baicalein reduces the Zea Longa score and the infarct area of brain tissues in HIBD rats.

[0079] The experimental results are as Figure 2 shown. As can be seen from Figure 2 A in, compared with the blank control group, the Zea Longa score of the model group was significantly increased, that is, the modeling effectively increased the Zea Longa score; the Zea Longa score of the model + baicalein group and the model + Fer-1 group could be significantly reduced at 24 h, that is, baicalein and the ferroptosis inhibitor Fer-1 have similar functions in reducing the Zea Longa score.

[0080] TTC staining can make the infarcted brain tissues show white, and the proportion of the infarcted area in the whole brain can be calculated by calculating the area of the white area, so as to evaluate the degree of brain injury in the brain region. As can be seen from Figure 2 B and C in, compared with the blank control group, the white infarct area in the model group increased significantly; compared with the model group, the model + baicalein group and the model + Fer-1 group could significantly reduce the brain infarct area in HIBD rats, indicating that baicalein can improve the brain injury caused by HIE.

[0081] 4.2 Baicalein reduces the death of neurons in the CA1 region of the hippocampus in HIBD rats.

[0082] The survival of neurons in the CA1 region of the hippocampus was detected by H&E staining and Nissl staining, and the results are as Figure 3 shown. Specifically, the H&E results showed that the nerve cells in the CA1 region of the hippocampus in the model group were sparse, arranged disorderly, showed vacuolization, and the interstitial edema was loose. The model + baicalein group and the model + Fer-1 group could significantly improve this situation. The Nissl staining results showed that the number of neurons in the CA1 region of the hippocampus in the model group decreased, and the number of Nissl bodies in the cells decreased. The neuronal damage was reduced in the model + baicalein group and the model + Fer-1 group, manifested as an increase in the number of neurons in the CA1 region of the hippocampus and an increase in the number of Nissl bodies in the cells.

[0083] 4.3 Baicalein reduces the levels of malondialdehyde (MDA) and Fe 2+ in the hippocampal tissues of HIBD rats and upregulates the level of reduced glutathione (GSH).

[0084] The experimental results are as follows Figure 4 shown. Compared with the blank control group, the level of MDA in the model group was significantly increased, and the level of GSH was significantly decreased. The results suggest that the level of oxidative stress in the hippocampus of HIBD rats is increased. Fe 2+ is an early signal of ferroptosis. The increase of Fe 2+ can increase the sensitivity of tissues to ferroptosis, making cells and tissues more prone to ferroptosis. The experimental results show that compared with the blank control group, the level of Fe 2+ in the model group was increased, suggesting that the sensitivity of ferroptosis in the hippocampal tissue of HIBD rats was increased. In the model + baicalein group and the model + Fer-1 group, the level of MDA in the hippocampal tissue of HIBD rats was decreased, the level of GSH was increased, and the level of Fe 2+ was decreased. It is suggested that baicalein treatment can reduce the level of oxidative stress in the hippocampal tissue of HIBD rats and reduce the sensitivity of hippocampal tissue to ferroptosis under hypoxic-ischemic conditions.

[0085] 4.4 Baicalein improves model-induced mitochondrial damage and the level of lipid peroxidation product 4-HNE.

[0086] The experimental results are as follows Figure 5 shown. Transmission electron microscopy results showed that: in the model group, mitochondrial swelling, cristae rupture and disappearance, typical ferroptosis-like changes occurred in cells. In the model + baicalein group and the model + Fer-1 group, the mitochondrial morphology was improved: the degree of mitochondrial swelling was decreased, and the integrity of mitochondrial cristae was increased. Immunofluorescence results showed that: in the model group, cells lost their normal morphology, the cells transformed into oval and round shapes, the cell volume became smaller, and the level of lipid peroxidation product 4-HNE was significantly increased. In the model + baicalein group and the model + Fer-1 group, the cell morphology in the model group returned to normal, and the level of lipid peroxidation product 4-HNE was significantly decreased.

[0087] 4.5 Baicalein reduces the level of oxidized glutathione (GSSG), increases the level of GSH, and targets the ferroptosis pathway to improve cell damage.

[0088] The experimental results are as follows Figure 6 shown. The level of GSSG in the cells of the model group was significantly increased, and the level of GSH was significantly decreased. In the model + baicalein group and the model + Fer-1 group, the level of GSSG was significantly decreased, the level of GSH was significantly increased, and the antioxidant capacity of the cells was increased. Western blot results showed that the protein expressions of GPX4, ACSL1 and Claudin-5 in the cells of the model group were decreased, and the protein expression of 4-HNE was increased. In the model + baicalein group and the model + Fer-1 group, the protein expressions of GPX4, ACSL1 and Claudin-5 were all up-regulated, and the protein expression of 4-HNE was down-regulated.

[0089] 4.6 Baicalein targets the ferroptosis pathway to improve HIBD in rats.

[0090] The experimental results are as Figure 7 shown. Western blot was used to detect the expression levels of ALOX15 and 4-HNE proteins in the hippocampal tissues of rats. The results showed that compared with the blank control group, the protein expressions of ALOX15 and 4-HNE were up-regulated in the model group. In the model + baicalein group and the model + Fer-1 group, the protein expressions of ALOX15 and 4-HNE were down-regulated.

[0091] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than limiting the protection scope of the present invention. Any simple modification or equivalent replacement of the technical solution of the present invention by those of ordinary skill in the art shall not depart from the essence and scope of the technical solution of the present invention.

Claims

1. Use of baicalein as the sole active ingredient in the preparation of a drug for preventing and treating neonatal hypoxic-ischemic encephalopathy, characterized in that, The dosage form of the drug is an injection solution; The neonatal hypoxic-ischemic encephalopathy includes at least one of the following: Increased concentration of malondialdehyde in the neonatal hippocampal tissue; Increased concentration of ferrous ions in the neonatal hippocampal tissue; Decreased concentration of reduced glutathione in the neonatal hippocampal tissue; Increased ratio of oxidized glutathione to reduced glutathione in the neonatal hippocampal tissue.

2. The application according to claim 1, wherein The components of the drug also include pharmaceutically acceptable excipients.

3. The application according to claim 1, characterized in that, The prevention and treatment of neonatal hypoxic-ischemic encephalopathy is manifested as a decrease in neurological deficit signs and / or a reduction in the infarct area of brain tissue.

4. The application according to claim 1, characterized in that The neonatal hypoxic-ischemic encephalopathy includes at least one of the following: Neuronal death in the CA1 region of the neonatal hippocampus; Mitochondrial damage in the neonatal brain tissue.

5. The application according to claim 4, wherein The neonatal hypoxic-ischemic encephalopathy includes the following two items: Neuronal death in the CA1 region of the neonatal hippocampus; Mitochondrial damage in the neonatal brain tissue.

6. The application according to claim 1, wherein The neonatal hypoxic-ischemic encephalopathy includes all of the following items: Increased concentration of malondialdehyde in the neonatal hippocampal tissue; Increased concentration of ferrous ions in the neonatal hippocampal tissue; Decreased concentration of reduced glutathione in the neonatal hippocampal tissue; Increased ratio of oxidized glutathione to reduced glutathione in the neonatal hippocampal tissue.

Images