Coptis chinensis composition and medical application thereof

Abstract

The invention relates to application of a coptis chinensis composition in preparation of a medicine for treating traumatic brain injury (TBI). The coptis chinensis composition is prepared from the following raw materials in parts by weight: 1-5 parts of scutellaria baicalensis, 1-5 parts of coptis chinensis, 1-5 parts of golden cypress and 1-5 parts of gardenia. The rhizoma coptidis composition has the beneficial effect that the rhizoma coptidis composition for treating traumatic brain injury (TBI) is provided.

Description

Technical Field

[0001] The present invention belongs to the field of traumatic brain injury treatment, and particularly relates to a coptis root composition and its medical use. Background Art

[0002] Traumatic brain injury (TBI) is an external injury to the brain that can cause temporary or permanent brain dysfunction and is associated with high morbidity and disability. TBI is often followed by persistent neuroinflammation, a thorny clinical problem. Summary of the Invention

[0003] The present invention provides an application of a coptis chinensis composition in preparing a medicine for treating traumatic brain injury (TBI). The raw materials for preparing the coptis chinensis composition are 1 to 5 parts by weight of coptis chinensis, 1 to 5 parts by weight of scutellaria baicalensis, 1 to 5 parts by weight of phellodendron amurense, and 1 to 5 parts by weight of gardenia jasminoides.

[0004] In a further application, the traumatic brain injury is neuroinflammation after traumatic brain injury or traumatic brain injury accompanied by neuroinflammation.

[0005] In a further application, the treatment of traumatic brain injury includes regulating neuronal death, reducing oxidative stress, alleviating inflammatory response, protecting synaptic structure, regulating neurotransmitter system and restoring cell signaling.

[0006] In a further application, the weight ratio of the raw materials is: 3 parts by weight of Coptis chinensis, 2 parts by weight of Scutellaria baicalensis, 2 parts by weight of Phellodendron chinense and 3 parts by weight of Gardenia jasminoides; or, the weight ratio of the raw materials is: 5 parts by weight of Coptis chinensis, 2 parts by weight of Scutellaria baicalensis, 2 parts by weight of Phellodendron chinense and 3 parts by weight of Gardenia jasminoides; or, the weight ratio of the raw materials is: 5 parts by weight of Coptis chinensis, 1 part by weight of Scutellaria baicalensis, 1 part by weight of Phellodendron chinense and 1 part by weight of Gardenia jasminoides.

[0007] The present invention also provides an application of a coptis chinensis composition in a medicine for regulating microglial polarization through the TLR4 / histone H3 / α7nAChR pathway. The raw materials for preparing the coptis chinensis composition are 1 to 5 parts by weight of coptis chinensis, 1 to 5 parts by weight of scutellaria baicalensis, 1 to 5 parts by weight of phellodendron amurense, and 1 to 5 parts by weight of gardenia jasminoides.

[0008] The present invention also provides an application of a coptis chinensis composition in a medicine for exerting neuroprotective and repairing effects in the neuroinflammation process of a TBI animal model. The raw materials for preparing the coptis chinensis composition are 1 to 5 parts by weight of coptis chinensis, 1 to 5 parts by weight of scutellaria baicalensis, 1 to 5 parts by weight of phellodendron amurense, and 1 to 5 parts by weight of gardenia jasminoides.

[0009] The present invention also provides a coptis root composition. The raw materials for preparing the coptis root composition are 5 parts by weight of coptis root, 1-2 parts by weight of scutellaria baicalensis, 1-2 parts by weight of phellodendron amurense and 1-3 parts by weight of gardenia jasminoides.

[0010] The present invention also provides a preparation made from the Rhizoma Coptidis composition, which includes solid preparations and liquid preparations. The solid preparations include tablets, capsules, decoctions, oral liquids, soft capsules or granules. Preferably, the preparation is a decoction.

[0011] The beneficial effect of the present invention is that it provides a coptis root composition for treating traumatic brain injury (TBI). BRIEF DESCRIPTION OF THE DRAWINGS

[0012] Figure 1 .Schematic diagram of the mechanism of Huanglian Jiedu Decoction in treating neuroinflammation.

[0013] Figure 2 Huanglian Jiedu Decoction-TBI target Venn diagram. Note: The blue circle on the left represents the drug target, the green circle on the right represents the disease target, and the intersection of the two circles represents the common target of the drug and the disease.

[0014] Figure 3 Huanglian Jiedu Decoction-TBIPPI network intersection diagram. Note: Each polygonal node represents a corresponding protein. The darker, larger nodes on the inner edge represent key interacting proteins. The lines connecting each node represent interactions between proteins.

[0015] Figure 4 GO enrichment analysis of targets of Huanglian Jiedu Decoction in the treatment of TBI. Note: The top 10 nodes are shown, with the size representing the number of related targets. Orange represents biological process (BP), green represents cellular component (CC), and dark blue represents molecular function (MF).

[0016] Figure 5 Observation of the extent of brain tissue damage in mice in the sham-operated and TBI groups. a, b. Sham-operated group; c, d. TBI group.

[0017] Figure 6 CIRP protein expression levels in brain tissues of mice in the sham-operated and TBI groups. a, b. Western blot analysis shows CIRP expression levels. Compared with the sham-operated group: ***P < 0.001.

[0018] Figure 7Expression levels of CIRP, S100B, TNF-α, and IL-1β in the serum of mice in the sham-operated and TBI groups. a. Serum CIRP level in mice; b. Serum S100B level in mice; c. Serum TNF-α level in mice; d. Serum IL-1β level in mice. Compared with the sham-operated group: **P < 0.01, ***P < 0.001

[0019] Figure 8 Serum CIRP, S100B, TNF-α, and IL-1β expression levels in healthy volunteers and TBI patients. a. Human serum CIRP level; b. Human serum S100B level; c. Human serum TNF-α level; d. Human serum IL-1β level. Compared with the healthy volunteers: ***P < 0.001

[0020] Figure 9 Correlation between serum CIRP and S100B, TNF-α, and IL-1β expression levels. a. Mouse serum CIRP and S100B levels; b. Mouse serum CIRP and TNF-α levels; c. Mouse serum CIRP and IL-1β levels; d. Human serum CIRP and S100B levels; e. Human serum CIRP and TNF-α levels; f. Human serum CIRP and IL-1β levels

[0021] Figure 10 The expression levels of CIRP protein in the brain tissues of mice in the TBI group, HDD-3223 group, HDD-5223 group, and HDD-5111 group.

[0022] Figure 11 The expression levels of CIRP, S100B, TNF-α, and IL-1β in the TBI group, HDD-3223 group, HDD-5223 group, and HDD-5111 group. DETAILED DESCRIPTION

[0023] Traumatic brain injury (TBI) is an external injury to the brain that can cause temporary or permanent brain dysfunction and is associated with high morbidity and disability. TBI is often followed by persistent neuroinflammation, a thorny clinical problem.

[0024] Microglial polarization is key to the pathological mechanism of neuroinflammation after TBI. Modulating microglial polarization is a potential strategy for treating neuroinflammation, but known drugs are not effective in regulating microglial polarization.

[0025] In order to solve the above technical problems, some embodiments of the present invention relate to the use of a Coptis chinensis composition in the preparation of a drug for treating traumatic brain injury (TBI). The raw materials for preparing the Coptis chinensis composition are 1 to 5 parts by weight of Coptis chinensis, 1 to 5 parts by weight of Scutellaria baicalensis, 1 to 5 parts by weight of Phellodendron amurense, and 1 to 5 parts by weight of Gardenia jasminoides.

[0026] Currently, Traditional Chinese Medicine (TCM) lacks a comprehensive understanding of the etiology, pathogenesis, and treatment principles for TBI. With the increasing incidence of TBI and its increasing impact on the health of the Chinese people, there is an urgent need to improve research on the etiology, pathogenesis, syndrome differentiation and treatment, and prognosis and rehabilitation of the disease, and to establish a consensus and standard in TCM. The treatment principles and methods of the present invention are as follows:

[0027] Traditional Chinese Medicine (TCM) believes that the development of cerebral neuroinflammation is closely related to multiple factors, among which exogenous wind, cold, and dampness, internal emotional damage, and an unhealthy diet are the most common causes. TCM's understanding of these factors provides an important theoretical foundation for clinical treatment. Through syndrome differentiation and treatment, it can effectively alleviate the symptoms of cerebral neuroinflammation and improve the patient's overall health. TCM's understanding of the pathogenesis of cerebral neuroinflammation is multifaceted, involving multiple factors such as imbalances in qi and blood, imbalances in yin and yang, and dysfunction of internal organs. First, yin and yang imbalance is a key pathological factor in the development of cerebral neuroinflammation. This imbalance often manifests as yin deficiency or yang hyperactivity, leading to an imbalance in the body's internal environment. Yin deficiency can lead to insufficient body fluids, leading to dryness and inflammation; while yang hyperactivity can lead to the internal generation of heat, further exacerbating brain nerve damage and inflammation. According to the theories in the Su Wen (Suwen), the balance of yin and yang is crucial for maintaining good health. Only with a balanced yin and yang can normal brain function be maintained. Second, imbalances in qi and blood are closely linked to the development of cerebral neuroinflammation. Qi and blood are the essential physical foundations for maintaining normal bodily function. The Difficult Classic states, "Blood nourishes the brain," highlighting its crucial role in nourishing and maintaining brain health. Insufficient Qi and blood not only leads to insufficient oxygen supply to the brain but also impairs the repair and regeneration of brain nerve cells, further exacerbating the inflammatory response. Third, organ dysfunction is closely linked to the development of brain neuroinflammation. This dysfunction can lead to biochemical abnormalities in Qi and blood, further impacting brain health. From a Traditional Chinese Medicine (TCM) perspective, TBI patients often have normal constitutions, but the sudden onset of illness, leading to an imbalance in yin and yang, often presents with a syndrome of excess heat, characterized by predominant pathogenic Qi without deficient righteous Qi, or yang without deficient yin. Therefore, treatment can be targeted with heat-clearing and detoxifying methods that reduce the excess.

[0028] In some further embodiments, the traumatic brain injury is neuroinflammation after traumatic brain injury or traumatic brain injury accompanied by neuroinflammation.

[0029] In some further embodiments, the weight ratio of the raw materials is: 3 parts by weight of Coptidis Rhizoma, 2 parts by weight of Scutellaria Baicalensis, 2 parts by weight of Phellodendron Amurense and 3 parts by weight of Gardenia Fructus; or, the weight ratio of the raw materials is: 5 parts by weight of Coptidis Rhizoma, 2 parts by weight of Scutellaria Baicalensis, 2 parts by weight of Phellodendron Amurense and 3 parts by weight of Gardenia Fructus; or, the weight ratio of the raw materials is: 5 parts by weight of Coptidis Rhizoma, 1 part by weight of Scutellaria Baicalensis, 1 part by weight of Phellodendron Amurense and 1 part by weight of Gardenia Fructus.

[0030] The present invention found that Toll-like receptor 4 / histone H3 / α7 nicotinic acetylcholine receptor can be used as a new way to regulate microglial polarization. Figure 1 As shown, the present invention also provides a use of a Coptis chinensis composition (the figure shows Coptis chinensis Decoction, including an improved Coptis chinensis Decoction) in a drug for regulating microglial polarization through the TLR4 / histone H3 / α7nAChR pathway. The raw materials for preparing the Coptis chinensis composition are 1-5 parts by weight of Coptis chinensis, 1-5 parts by weight of Scutellaria baicalensis, 1-5 parts by weight of Phellodendron amurense, and 1-5 parts by weight of Gardenia jasminoides. In further embodiments, Coptis chinensis Decoction may regulate microglial polarization through the TLR4 / histone H3 / α7nAChR pathway, thereby exerting neuroprotective and repairing effects on neuroinflammation in TBI animal models, providing a basis for the treatment of post-TBI neuroinflammation with traditional Chinese medicine.

[0031] The present invention also provides a coptis chinensis composition, characterized in that the raw materials for preparing the coptis chinensis composition are 5 parts by weight of coptis chinensis, 1-2 parts by weight of scutellaria baicalensis, 1-2 parts by weight of phellodendron amurense and 1-3 parts by weight of gardenia jasminoides.

[0032] The present invention also provides a preparation made from the coptis root composition, which includes solid preparations and liquid preparations. The solid preparations include tablets, capsules, decoctions, oral liquids, soft capsules or granules.

[0033] Huanglian Jiedu Decoction (a Cui-style prescription cited in Wai Tai Mi Yao) is a representative prescription for clearing heat and detoxifying. Its four traditional Chinese medicine ingredients are coptis chinensis, scutellaria baicalensis, phellodendron amurense, and gardenia jasminoides. Whether the existing Huanglian Jiedu Decoction can be used to treat neuroinflammation after TBI has not been reported. In some further embodiments, the formulation is an improved Huanglian Jiedu Decoction, wherein the weight of coptis chinensis in the improved Huanglian Jiedu Decoction is approximately 1-3 times that of the original Huanglian Jiedu Decoction.

[0034] Explanation of terms:

[0035] Traumatic brain injury (TBI) is an injury caused by violence to the head, including soft tissue injury of the head, skull fracture, cerebral blood vessels, brain tissue and nerve damage.

[0036] HistoneH3 is a histone protein and a core component of the nucleosome. Its primary function is to package and compact DNA into chromatin, thereby limiting its access to other organelles within the cell. Histones play a central role in transcriptional regulation, DNA repair, DNA replication, and chromosome stability.

[0037] The α7nAChR (α7 nicotinic acetylcholine receptor) is an important neurotransmitter receptor, a type of nicotinic acetylcholine receptor (nAChR). It plays a key role in the body's cholinergic anti-inflammatory pathway, participates in the neural regulation of the immune system, and plays a role in various physiological and pathological processes.

[0038] Lipopolysaccharide (LPS).

[0039] BV2 is a microglial cell line derived from mice.

[0040] Source of medicinal materials: Scutellaria baicalensis, Coptis chinensis, Phellodendron amurense, and Gardenia jasminoides all comply with the provisions of the 2020 edition of the "Chinese Pharmacopoeia".

[0041] Example 1 Huanglian Jiedu Decoction (HDD-3223)

[0042] Prescription quantity: 9kg Coptis chinensis, 6kg Scutellaria baicalensis, 6kg Phellodendron amurense, 9kg Gardenia jasminoides

[0043] Preparation method: Weigh an appropriate amount of medicinal materials, soak them in water 10 times the total amount of the medicinal materials for 30 minutes, heat to boil, then simmer for 60 minutes, filter out the residue; add 8 times the amount of water, boil, then simmer for 30 minutes, combine the two filtrates, heat and concentrate to a solution containing 1g / ml of the traditional Chinese medicine Huanglian Jiedu Decoction, and store at 4°C for later use to obtain the decoction.

[0044] Example 2 Improved Huanglian Jiedu Decoction (HDD-5223)

[0045] Prescription quantity: 10kg Coptis chinensis, 4kg Scutellaria baicalensis, 4kg Phellodendron amurense, 6kg Gardenia jasminoides

[0046] Preparation method: Weigh an appropriate amount of medicinal materials, soak them in water 10 times the total amount of the medicinal materials for 30 minutes, heat to boil, then simmer for 60 minutes, filter out the residue; add 8 times the amount of water, boil, then simmer for 30 minutes, combine the two filtrates, heat and concentrate to a solution containing 1g / ml of the improved Huanglian Jiedu Decoction, and store at 4°C for later use to obtain the decoction.

[0047] Example 3 Improved Huanglian Jiedu Decoction (HDD-5111)

[0048] Prescription quantity: 10kg Coptis chinensis, 2kg Scutellaria baicalensis, 2kg Phellodendron amurense, 2kg Gardenia jasminoides

[0049] Preparation method: Weigh an appropriate amount of medicinal materials, soak them in water 8 times the total amount of the medicinal materials for 30 minutes, heat to boil, then simmer for 60 minutes, filter out the residue; add another 8 times the amount of water, boil, then simmer for 30 minutes, combine the two filtrates, heat and concentrate to a solution containing 1g / ml of the improved Huanglian Jiedu Decoction, and store at 4°C for later use to obtain the decoction.

[0050] Experimental Example 1 Network Pharmacology Study on Huanglian Jiedu Decoction in the Treatment of Traumatic Brain Injury (TBI)

[0051] The present invention studies the network pharmacology of Huanglian Jiedu Decoction. The results show that the number of targets of all target Chinese medicines in Huanglian Jiedu Decoction is 761, and the number of TBI targets is 1087, of which 132 are Huanglian Jiedu Decoction-TBI disease intersection targets (see Figure 2 ), the PPI network shows that its key targets include TLR4, IL-6, TNF, IL-1B, IL-10, etc. (see Figure 3 ), suggesting that these protein targets are the main molecules in Huanglian Jiedu Decoction acting on TBI. Subsequently, GO function and KEGG pathway enrichment analysis were performed on the Huanglian Jiedu Decoction-TBI intersection targets (see Figure 4 ) and found that the therapeutic effects of Huanglian Jiedu Decoction on TBI may mainly have the following mechanisms: 1) Alleviating neurological damage after TBI by regulating neuronal death. The "neuron death regulation" mentioned in the figure indicates that the drug may protect brain tissue from further damage by inhibiting neuronal apoptosis or necrosis; 2) Regulating ROS metabolism. Excessive production of reactive oxygen species (ROS) after TBI can lead to oxidative stress and further damage brain cells. The "regulation of reactive oxygen species metabolic processes" mentioned in the figure indicates that by regulating ROS metabolism, oxidative stress is reduced, thereby protecting neurons. 3) Regulation of protein kinase and phosphatase activity. After TBI, an imbalance in the activity of protein kinases and phosphatases may affect cell signaling. The "protein tyrosine kinase activity" and "protein phosphatase binding" mentioned in the figure indicate that Huanglian Jiedu Decoction may restore normal cell signaling by regulating the activity of these enzymes.

[0052] In summary, Huanglian Jiedu Decoction plays a role in the treatment of TBI through multiple mechanisms, including regulating neuronal death, reducing oxidative stress, alleviating inflammatory responses, protecting synaptic structure, regulating neurotransmitter systems, and restoring cell signaling. These actions collectively promote neuroprotection and functional recovery after brain injury.

[0053] Expression of extracellular cold-inducible RNA-binding protein (eCIRP) in serum and brain of patients with traumatic brain injury (TBI) and animal models of TBI

[0054] This experiment has been published in the Journal of Trauma and Acute Care Surgery 2024, Vol. 26, No. 11, “Changes in Cold-Inducible RNA-Binding Protein after Traumatic Brain Injury and Its Clinical Significance”.

[0055] Materials and Methods

[0056] 1 Experimental animals

[0057] Male wild-type C57BL / 6J mice, specific pathogen-free (SPF) level, 8 weeks old, 12, weighing 24-26 g, purchased from the Institute of Experimental Animal Science of Peking Union Medical College. All animal experiments were approved by the guidelines of the General Hospital of People's Liberation Army Ethics Committee (No. SYXK2019-0021).

[0058] 2 Patient general information TBI patient inclusion criteria: (1) Age 20-70 years old; (2) Diagnosed as moderate to severe TBI (GCS=3-12 points); (3) Injury to admission time ≤12 h. Exclusion criteria: (1) Died within 24 h after admission; (2) There are other parts of the trauma (such as open fracture, spinal cord injury, etc.) in addition to TBI; (3) Combined with cerebrospinal fluid leakage or open brain injury, chronic intracranial hematoma; (4) History of malignant tumors, nervous system diseases, coronary heart disease, hyperlipidemia.

[0059] Healthy volunteer inclusion criteria: (1) Age 20-70 years old; (2) Healthy, no history of malignant tumors, nervous system diseases, coronary heart disease, hyperlipidemia and other trauma.

[0060] This study prospectively selected 8 patients with moderate to severe TBI admitted to the Department of Neurosurgery of the General Hospital of People's Liberation Army from December 2022 to January 2024, 6 males and 2 females; age 30-66 years old, average 49.1 years old; 3 cases of road traffic injury, 3 cases of falling from a high place, 2 cases of violent injury; GCS score 3-8 points in 4 cases, 9-12 points in 4 cases. 10 healthy volunteers, 7 males and 3 females; age 26-64 years old, average 45.3 years old. The patient or his family signed the informed consent form. This study has been approved by the Medical Ethics Committee of the General Hospital of People's Liberation Army (S2021-539-01).

[0061] 3 Methods

[0062] 3.1 Establishment of a Moderate to Severe TBI Model in Mice Twelve mice were randomly divided into a sham operation group and a TBI group, with 6 mice in each group. All mice were fasted for 24 hours and deprived of water for 12 hours before surgery and anesthetized intraperitoneally with 5% chloral hydrate (10 mL / kg). The mouse head was fixed to a stereotaxic fixture. An incision was made along the midline of the head, the periosteum was separated, and the skull was exposed. The drill hole position was determined using the stereotaxic instrument. A circular bone window with a diameter of 3 mm was drilled at the location to expose the brain tissue. A custom catheter was adhered and fixed around the bone window using dental zinc phosphate cement and filled with sterile saline. Hydraulic percussion was used for percussion. After checking the hydraulic percussion instrument for leaks, the percussion hose was connected to the custom catheter, and the percussion pendulum angle was adjusted to 9.8° to 10.8°. After releasing the pendulum, a peak pressure of 1.1 to 1.3 atmospheres was generated. A Tektronix digital oscilloscope (TDS460A, Tektronix Inc., USA) was connected to monitor the duration and peak pressure of the fluid pulse. The sham-operated group underwent the same surgical procedures as the model group, except that the pendulum angle was set to 0°, resulting in a peak pressure of 0 atmospheres. After the impact, the mice were placed in a supine position, and their righting time was measured as an indicator of injury severity. After righting, the mice were re-anesthetized, the catheters were removed, and the scalp was sutured. According to the criteria of previous studies, a moderate to severe TBI model was successfully established when the righting time was >5 minutes.

[0063] 3.2 Western Blot Detection of β-actin and CIRP Expression. Cortical tissue from the injured mouse brain was lysed with radioimmunoprecipitation buffer (RIPA). After low-temperature high-speed centrifugation, the supernatant was aliquoted and stored at −80°C. Protein concentration was determined using a bicinchoninic acid (BCA) protein kit and denatured. 30 μg of sample protein was electrophoresed onto a nitrocellulose membrane using a wet transfer method and blocked with rapid blocking buffer for 1 h. Diluted primary antibodies (β-actin and CIRP, 1:1000, Abcam, USA) were then added and incubated overnight at 4°C. The next day, the membranes were washed three times with Tris-HCl buffered saline and incubated with a diluted horseradish peroxidase-conjugated secondary antibody (1:5000) at room temperature for 1 h. The membranes were washed again three times with Tris-HCl buffered saline, developed with a developer, and imaged with a chemiluminescent gel imaging system. Image-ProPlus 6.0 software was used to quantify the grayscale values ​​of the bands, and the relative expression of proteins was expressed as the grayscale value of the target protein CIRP / the grayscale value of the internal reference β-actin.

[0064] 3.3 ELISA method to detect the secretion of related index factors in serum

[0065] Peripheral venous blood (2–5 mL) was collected from TBI patients and healthy volunteers and transferred to coagulant tubes. The samples were gently inverted for thorough mixing, incubated at room temperature for 30–60 minutes, and the supernatant was collected after low-temperature high-speed centrifugation. Aliquots were stored in a −80°C freezer. Orbital blood (0.2–0.4 mL) was collected from mice in the TBI and sham-operated groups and transferred to coagulant tubes. The samples were gently inverted for thorough mixing, incubated at room temperature for 30–60 minutes, and the supernatant was collected after low-temperature high-speed centrifugation. Aliquots were stored in a −80°C freezer. Serum secretion of CIRP, S100B, TNF-α, and IL-1β was measured using ELISA kits (Ecosine Biotech) according to the manufacturer's instructions.

[0066] 3.4 HE staining to assess brain pathological changes and lesion volume in mice. Brain tissue from mice in the sham-operated and TBI groups was fixed overnight in 4% paraformaldehyde, embedded in paraffin, and sections (4 μm) were prepared. The sections were dewaxed in xylene and washed with ethanol. Sections were stained with HE to assess lesion volume. The area of ​​the lesion hemisphere was measured using ImageJ. The percentage of volume loss was calculated by comparing the damaged area with the uninjured hemisphere as previously reported.

[0067] 4 Statistical analysis

[0068] GraphPad Prism 9 software was used for statistical analysis. Results were expressed as x ± s. The Shapiro-Wilk test was used to determine normality of distribution. The Student t test was used to analyze significant differences between groups. The Spearman correlation test was used to analyze correlations between nonnormally distributed data. P < 0.05 was considered statistically significant.

[0069] result

[0070] 1 Observation of brain tissue pathology and morphology of mice in each group No mice in the sham operation group and TBI group died. HE staining results showed that compared with the sham operation group, the TBI group had obvious lesions in the cerebral cortex 24 hours later, and the volume loss of the mouse brain hemisphere accounted for (3.1 ± 0.5)%. The above results showed that the TBI model was successfully established. Figure 5 .

[0071] 2 Expression of CIRP in mouse cortex

[0072] Western blot results showed that the relative expression of CIRP protein in the brain injury site of mice in the TBI group was higher than that in the sham group 24 hours after TBI (t=12.050, P<0.001). The above results indicate that compared with the sham group, the expression of CIRP in the brain injury site was upregulated 24 hours after moderate or severe TBI. Figure 6 .

[0073] 3. Expression of related indicator factors in mouse serum

[0074] ELISA results showed that compared with the sham operation group, the levels of CIRP (t = 7.067, P < 0.001), S100B (t = 6.748, P < 0.001), TNF-α (t = 5.010, P < 0.001), and IL-1β (t = 4.898, P < 0.01) in the serum of mice in the TBI group were all increased. These results indicate that compared with the sham operation group, the expression levels of CIRP, S100B, TNF-α, and IL-1β in the peripheral blood of mice were synchronously increased 24 hours after moderate or severe TBI. Figure 7 .

[0075] 4. Expression of related indicator factors in human serum

[0076] ELISA test results showed that compared with healthy volunteers, the levels of CIRP (t = 7.457, P < 0.001), S100B (t = 5.811, P < 0.001), TNF-α (t = 4.496, P < 0.001), and IL-1β (t = 6.523, P < 0.001) in the serum of TBI patients were all increased. The above results show that compared with the healthy volunteer group, the expression levels of CIRP, S100B, TNF-α, and IL-1β in the peripheral blood of patients with moderate or severe TBI increased synchronously 24 hours after treatment. Figure 8 .

[0077] Correlation analysis between 5CIRP and serum markers such as S100B, TNF-α, and IL-1β

[0078] Correlation analysis revealed that the r values ​​for CIRP in mouse serum and the levels of S100B, TNF-α, and IL-1β were 0.923, 0.958, and 0.984, respectively (P < 0.05); and the r values ​​for CIRP in human serum and the levels of S100B, TNF-α, and IL-1β were 0.740, 0.664, and 0.662, respectively (P < 0.05). This indicates that CIRP in serum is positively correlated with the levels of S100B, TNF-α, and IL-1β. These results suggest that CIRP may serve as a biomarker for TBI. Figure 9 .

[0079] Experimental Example 3 Effect of Huanglian Jiedu Decoction on Extracellular Cold-Inducible RNA Binding Protein (eCIRP) in Mice

[0080] The modeling, detection, and analysis methods not specifically described in this experimental example are referred to Experimental Example 3 and will not be repeated here.

[0081] Experimental groups and dosing regimen:

[0082] Forty-two SPF C57BL / 6J mice weighing 28 g ± 2 g were enrolled and maintained at a temperature of 21-25°C with a daily temperature range of ±1°C and a humidity of 50-70%. They were randomly divided into seven groups according to the administration method: sham operation group, TBI group, low-dose Huanglian Jiedu Decoction group (HDD-3223-L group), medium-dose Huanglian Jiedu Decoction group (HDD-3223 group), high-dose Huanglian Jiedu Decoction group (HDD-3223-H group), improved medium-dose Huanglian Jiedu Decoction group (HDD-5223 group), and improved medium-dose Huanglian Jiedu Decoction group (HDD-5111 group), with 6 mice in each group. The medium-dose group of Huanglian Jiedu Decoction was a clinically equivalent dose, with a liquid dosage of 4 g / kg. The low-dose group received half the dosage of the medium-dose group, and the high-dose group received twice the dosage of the medium-dose group. The liquid dosage of the improved medium-dose group of Huanglian Jiedu Decoction (HDD-5223 group) and the improved medium-dose group of Huanglian Jiedu Decoction (HDD-5111 group) was also 4 g / kg. Each group received the drug twice daily for 3, 7, and 14 days, after which brain tissue samples were collected and serum tests were performed.

[0083] result

[0084] 1 Pathological morphological observation of brain tissues of mice in each group No mice in the sham operation group and the TBI group died. The results of HE staining showed that the TBI model was successfully established.

[0085] 2 Expression of CIRP in mouse cortex

[0086] Western blot analysis revealed that compared with the TBI group (600 pg / ml) (t=8.150, P<0.001), the relative expression of CIRP protein in the injured brain of mice in the HDD-3223 group (510 pg / ml) (t=7.110, P<0.001), HDD-5223 group (430 pg / ml) (t=7.123, P<0.001), and HDD-5111 group (280 pg / ml) (t=6.068, P<0.001) 24 hours after TBI, the upregulation of CIRP expression in the injured brain of mice in the HDD-3223, HDD-5223, and HDD-5111 groups 24 hours after moderate or severe TBI was suppressed. The strongest inhibitory effect was observed in the HDD-5111 group (Fig. Figure 10 In addition, compared with the HDD-3223 group, there was no significant difference in the relative expression of CIRP protein in the brain injury site of mice in the HDD-3223-L and HDD-3223-H groups 24 hours after injection.

[0087] 2 Expression of related indicator factors in mouse serum

[0088] The results of ELISA showed that compared with the TBI group, the serum levels of CIRP (t=7.156, P<0.001; t=7.009, P<0.001; t=7.427, P<0.001), S100B (t=5.147, P<0.001; t=5.990, P<0.001) and , P < 0.001; t = 5.137, P < 0.001), TNF-α (t = 4.767, P < 0.001; t = 4.771, P < 0.001; t = 5.063, P < 0.001), and IL-1β (t = 6.931, P < 0.01; t = 6.991, P < 0.01; t = 6.108, P < 0.01) levels were all decreased. The above results show that compared with the TBI group, the synchronous increase in the expression levels of CIRP, S100B, TNF-α, and IL-1β in the peripheral blood of mice in the HDD-3223, HDD-5223, and HDD-5111 groups 24 hours after moderate or severe TBI was suppressed (see Table 1, Figure 11 In addition, compared with the HDD-3223 group, there was no significant difference in the relative expression of CIRP in the serum of mice in the HDD-3223-L and HDD-3223-H groups.

[0089] Table 1 Expression of related index factors in mouse serum

[0090] Indicator\Group TBI group HDD-3223 group HDD-5223 group HDD-5111 group CIRP 515pg / ml 415pg / ml 350pg / ml 215pg / ml S100B 135pg / ml 100pg / ml 85pg / ml 60pg / ml TNF-α 45pg / ml 38pg / ml 32pg / ml 28pg / ml IL-1β 115pg / ml 90pg / ml 80pg / ml 75pg / ml

[0091] The above-described embodiments are merely descriptions of preferred implementations of the present invention and are not intended to limit the scope of the present invention. Without departing from the design spirit of the present invention, various modifications and improvements made to the technical solutions of the present invention by ordinary technicians in this field should fall within the scope of protection determined by the claims of the present invention.

Claims

1. A use of a coptis root composition in preparing a medicament for treating traumatic brain injury (TBI), wherein the raw materials for preparing the coptis root composition are 1 to 5 parts by weight of coptis root, 1 to 5 parts by weight of scutellaria baicalensis, 1 to 5 parts by weight of phellodendron amurense, and 1 to 5 parts by weight of gardenia jasminoides.

2. The use according to claim 1, characterized in that: The traumatic brain injury is neuroinflammation after traumatic brain injury or traumatic brain injury accompanied by neuroinflammation.

3. The use according to claim 1, characterized in that: The treatment of traumatic brain injury includes regulating neuronal death, reducing oxidative stress, alleviating inflammatory response, protecting synaptic structure, regulating neurotransmitter system and restoring cell signaling.

4. The use according to any one of claims 1 to 3, characterized in that: The weight ratio of the raw materials is: 3 parts by weight of coptis chinensis, 2 parts by weight of scutellaria baicalensis, 2 parts by weight of phellodendron chinense and 3 parts by weight of gardenia jasminoides; or, the weight ratio of the raw materials is: 5 parts by weight of coptis chinensis, 2 parts by weight of scutellaria baicalensis, 2 parts by weight of phellodendron chinense and 3 parts by weight of gardenia jasminoides; or, the weight ratio of the raw materials is: 5 parts by weight of coptis chinensis, 1 part by weight of scutellaria baicalensis, 1 part by weight of phellodendron chinense and 1 part by weight of gardenia jasminoides.

5. A use of a coptis root composition in a drug for regulating microglial polarization through the TLR4 / histoneH3 / α7nAChR pathway, wherein the raw materials for preparing the coptis root composition are 1 to 5 parts by weight of coptis root, 1 to 5 parts by weight of scutellaria baicalensis, 1 to 5 parts by weight of phellodendron amurense, and 1 to 5 parts by weight of gardenia jasminoides.

6. A use of a coptis chinensis composition in a drug for protecting and repairing nerves during neuroinflammation in a TBI animal model, wherein the raw materials for preparing the coptis chinensis composition are 1 to 5 parts by weight of coptis chinensis, 1 to 5 parts by weight of scutellaria baicalensis, 1 to 5 parts by weight of phellodendron amurense, and 1 to 5 parts by weight of gardenia jasminoides.

7. A Coptidis rhizome composition, characterized in that: The raw materials for preparing the coptis root composition are 5 parts by weight of coptis root, 1-2 parts by weight of scutellaria baicalensis, 1-2 parts by weight of phellodendron amurense and 1-3 parts by weight of gardenia jasminoides.

8. A preparation made from the Coptidis rhizome composition according to claim 7, characterized in that: The preparation includes solid preparations and liquid preparations. The solid preparation includes tablets, capsules, decoctions, oral liquids, soft capsules or granules. Preferably, the preparation is a decoction.

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