Pharmaceutical composition of artesunate and Xuebijing and application thereof

Abstract

The invention discloses a pharmaceutical composition of artesunate combined with Xuebijing and application of the pharmaceutical composition, and relates to the technical field of pharmacy, effective components of the pharmaceutical composition comprise artesunate and Xuebijing injection, and application of the artesunate and Xuebijing injection in preparation of drugs for treating cerebral malaria. According to the application disclosed by the invention, the artesunate combined with Xuebijing has a remarkable treatment effect on experimental cerebral malaria mice, and the expression of NO is improved by activating a VEGF / Akt / eNOS signal channel, so that liver, spleen and brain tissues are protected, the immune function is recovered, and the survival rate is further improved. The research provides a new drug combination strategy for clinical treatment of cerebral malaria, and lays a theoretical foundation for deep understanding of the action mechanism of cerebral malaria.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, and more specifically, to a pharmaceutical composition of artesunate combined with Xuebijing and its application. Background Technology

[0002] Cerebral malaria (CM) is the most serious malaria complication caused by Plasmodium falciparum infection. Its high mortality rate and the resulting neurological sequelae pose a significant challenge to clinical treatment. Currently, artesunate, as a first-line antimalarial drug, can effectively eliminate Plasmodium parasites, but its intervention on pathological processes such as microcirculatory disturbances caused by the adhesion of infected red blood cells in cerebral microvessels, blood-brain barrier damage, and secondary neuroinflammation is limited, resulting in unsatisfactory clinical treatment outcomes.

[0003] In recent years, traditional Chinese medicine (TCM) has demonstrated unique advantages in improving microcirculation disorders and regulating inflammatory responses. Among these, Xuebijing injection, a representative compound preparation for promoting blood circulation, removing blood stasis, clearing heat, and detoxifying, can exert a significant protective effect in microcirculation-related diseases such as sepsis and acute respiratory distress syndrome by regulating the inflammatory factor network and vascular endothelial function through multiple targets. Currently, the therapeutic efficacy and mechanism of artesunate combined with Xuebijing injection in the treatment of cerebral malaria remain unclear.

[0004] In view of this, the present invention is proposed. Summary of the Invention

[0005] The present invention aims to provide a pharmaceutical composition of artesunate combined with Xuebijing and its application. By using artesunate and Xuebijing in combination, this pharmaceutical composition can effectively improve the general condition of experimental cerebral malaria mice, enhance their autonomous behavior, protect liver, spleen, and brain tissue, and restore their immune function. This pharmaceutical composition effectively protects the blood-brain barrier and reduces brain tissue damage by activating the VEGF / Akt / eNOS signaling pathway and increasing NO expression. This innovative combination therapy not only enhances the antimalarial efficacy but also provides a new approach to improving the neurological sequelae caused by cerebral malaria.

[0006] This invention is implemented as follows: The present invention provides a pharmaceutical composition for treating cerebral malaria, wherein the active ingredients of the pharmaceutical composition include artesunate and Xuebijing injection.

[0007] In some preferred embodiments, the pharmaceutical composition further includes a pharmaceutically acceptable carrier.

[0008] This application also provides the use of artesunate and sertin in the preparation of a drug for treating cerebral malaria.

[0009] In some preferred embodiments, the drug is used to protect liver, spleen, and brain tissue.

[0010] In some preferred embodiments, the drug is used to reduce inflammation of the nervous system.

[0011] In some preferred embodiments, the drug is used to enhance immune function.

[0012] In some preferred embodiments, the drug is used to enhance the expression level of VEGF protein.

[0013] In some preferred embodiments, the drug is used to enhance Akt protein expression levels.

[0014] In some preferred embodiments, the drug is used to enhance the expression level of eNOs protein.

[0015] In some preferred embodiments, the drug is used to increase NO expression.

[0016] The present invention has the following beneficial effects: This invention innovatively combines artesunate and Xuebijing injection for the treatment of cerebral malaria. This combined medication effectively improves the general health of ECM mice, significantly enhances their autonomous behavior, and protects vital organs such as the liver, spleen, and brain, thereby helping to restore the mice's immune function and ultimately achieving the therapeutic goal of improving survival rate. Furthermore, the mechanism of action of this combined medication lies in activating the VEGF / Akt / eNOS signaling pathway. Activation of this pathway further increases NO expression levels, thereby exerting multiple biological effects such as anti-inflammatory effects, tissue and organ protection, and vasodilation. This discovery not only reveals the potential mechanism of the combined use of artesunate and Xuebijing injection but also provides a theoretical basis and experimental support for its clinical application. This combined medication strategy opens up new avenues for the treatment of endotoxemia and related diseases, possessing significant scientific value and clinical significance. Attached Figure Description

[0017] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings used in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of the present invention and should not be regarded as a limitation on the scope. For those skilled in the art, other related drawings can be obtained based on these drawings without creative effort.

[0018] Figure 1 This is a schematic diagram showing the general characteristics of mice in each group in the embodiments of this application; a: infection rate; b: body weight; c: body temperature; d: survival rate; Figure 2 This is a schematic diagram of the coma behavior scale scores for each group of mice in the embodiments of this application; Figure 3 This is a schematic diagram illustrating the changes in open field behavior of mice in each group before drug administration intervention in the embodiments of this application; Figure 4 This is a schematic diagram illustrating the changes in open field behavior of mice in each group after drug intervention in the embodiments of this application; Figure 5 This is a comparison chart of various blood biochemical indicators of mice in each group in the embodiments of this application; a: urea; b: uric acid; c: lactate dehydrogenase; d: serum total protein; e: aspartate aminotransferase; f: alanine aminotransferase; g: alkaline phosphatase; h: serum albumin; Figure 6 These are visual images of the liver and spleen and organ tissue index images of mice in each group in the embodiments of this application; a: Visual comparison of liver and spleen tissue in each group of mice; b: Liver tissue index image of each group of mice; c: Spleen tissue index image of each group of mice. Figure 7 These are pathological images of important organs and tissues of mice in each group in the embodiments of this application; Figure 8 These are images showing the appearance of the brain tissue of mice in each group in the embodiments of this application; Figure 9 Here are the proportions of T and B cells in each group of mice in the embodiments of this application; a: flow cytometry gating logic diagram for B cell analysis; b: flow cytometry gating logic diagram for T cell analysis; c: CD4 + T, CD8 + T cell analysis flow cytometry gate logic diagram; d: B cell proportion plot; e: T cell proportion plot; f: CD4 + T cell percentage map; g: CD8 + T cell percentage map; h: CD4 + T / CD8 + T-scale diagram; Figure 10 The expression of GFAP protein in brain tissue of mice in each group was detected by immunofluorescence assay in the embodiments of this application. Figure 11 The expression of NeuN protein in brain tissue of mice in each group was detected by immunofluorescence assay in the embodiments of this application. Figure 12 The expression of CD31 protein in brain tissue of mice in each group was detected by immunofluorescence assay in the embodiments of this application. Figure 13 The expression of ICAM-1 protein in brain tissue of mice in each group was detected by immunofluorescence assay in the embodiments of this application. Figure 14The following figures illustrate the expression levels of angiopoietin protein and inflammatory factors in the serum of mice in each group of examples of this application: a: IFN-γ level in mouse serum; b: TNF-α level in mouse serum; c: IL-10 level in mouse serum; d: Ang-1 level in mouse serum; e: Ang-2 level in mouse serum. Figure 15 The following figures illustrate the expression of CD31-related factors in the brain tissue of mice in each group of embodiments of this application: a: Western Blot bands; b: Occludin protein content in mouse brain tissue; c: ZO-1 protein content in mouse brain tissue; d: VE-Cadherin protein content in mouse brain tissue. Figure 16 The following figures illustrate the expression of angiopoietin protein in mice in each group of embodiments of this application: a: Western Blot band image; b: Ang-1 protein content in mouse brain tissue; c: Ang-2 protein content in mouse brain tissue; Figure 17 The following figures illustrate the expression of adhesion factors in the brain tissue of mice in each group of embodiments of this application: a: Western Blot band image; b: ICAM-1 protein content in mouse brain tissue; c: VCAM-1 protein content in mouse brain tissue; Figure 18 The following figures illustrate the expression of VEGF / Akt / eNOS pathway-related proteins in mice in each group of mice in this application: a: Western Blot bands; b: VEGF protein content in mouse brain tissue; c: PI3K protein content in mouse brain tissue; d: P-Akt / Akt protein content in mouse brain tissue; e: P-eNOS / eNOS protein content in mouse brain tissue. Figure 19 The following figures illustrate the expression of genes related to leukocyte adhesion molecules in the brain tissues of mice in each group of embodiments of this application: a: melting curve of LFA-1; b: amplification curve of LFA-1; c: relative expression level of LFA-1 gene in mouse brain tissue; d: schematic diagram of HE staining. Figure 20 This is a schematic diagram of NO levels in the brain tissue of mice in each group in the embodiments of this application. Detailed Implementation

[0019] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall apply. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased commercially.

[0020] In a first aspect, this application provides a pharmaceutical composition for treating cerebral malaria, wherein the active ingredients of the pharmaceutical composition include artesunate and cyclophosphamide injection; the pharmaceutical composition also includes a pharmaceutically acceptable carrier.

[0021] This invention innovatively discovers that artesunate combined with Xingnaojing injection has multiple clinical advantages in the treatment of malaria, especially severe cerebral malaria. First, artesunate, as one of the most effective antimalarial drugs currently available, can rapidly kill malaria parasites in the blood and effectively control protozoemia. However, its intervention on the pathological processes caused by cerebral malaria, such as microvascular obstruction, blood-brain barrier damage, and neuroinflammation, is limited. Second, Xuebijing injection, as a classic traditional Chinese medicine compound preparation for promoting blood circulation and removing blood stasis, has multiple pharmacological effects, including improving microcirculation, anti-inflammation, anti-oxidation, and protecting vascular endothelium. It can specifically alleviate microvascular adhesion, inflammatory cascade reactions, and neurological damage caused by cerebral malaria. Therefore, the combined use of the two can directly eliminate pathogens through artesunate and improve cerebral microcirculatory disorders and reduce neuroinflammation with the help of Xuebijing, forming a dual intervention strategy of "pathogen treatment - pathological repair." Furthermore, the research of this invention confirms that this combined drug treatment can activate the VEGF / Akt / eNOS signaling pathway, effectively protecting the integrity of the blood-brain barrier. This combined approach can also reduce the dosage requirements of single-drug therapy, potentially reducing the risk of drug resistance, and providing a more optimized integrated traditional Chinese and Western medicine treatment plan for the clinical treatment of cerebral malaria and its neurological sequelae.

[0022] Secondly, this application also proposes the use of artesunate and sertin in the preparation of a drug for treating cerebral malaria.

[0023] In some embodiments, the drug can be used to protect liver, spleen and brain tissue, reduce inflammation of the nervous system, enhance immune function, increase VEGF protein expression levels, increase Akt protein expression levels, increase eNOs protein expression levels and increase NO expression.

[0024] The features and performance of the present invention will be further described in detail below with reference to embodiments.

[0025] Example 1: Study on the pharmacodynamic effects of artesunate combined with Xuebijing injection on ECM mice.

[0026] One hundred C57BL / 6 mice were randomly divided into 20 control mice (based on body weight) and the remaining mice were intraperitoneally inoculated with 5 × 10⁻⁶ mg / L. 6ECM mouse model was established by infecting red blood cells with the ANKA strain of Plasmodium berghei. When the infection rate reached approximately 5% and symptoms such as hair wrinkling, arched back, and gait changes appeared, mice were randomly divided into four groups based on the infection rate: Infected group, XBJ group (containing Xuebijing injection), AST group (containing Artesunate), and AST+XBJ group (containing Artesunate combined with Xuebijing injection), with 20 mice in each group. The day of inoculation was designated D0. From D4 to D8, the mice were administered the following intraperitoneal injections once daily: XBJ group (Xuebijing injection, 8 mL·kg⁻¹), AST group (Artesunate injection, 20 mg·kg⁻¹, double the first dose), AST+XBJ group (Xuebijing injection, 8 mL·kg⁻¹ + Artesunate injection, 20 mg·kg⁻¹, double the first dose). The Control and Infected groups received an intraperitoneal injection of the same volume of 0.9% NaCl solution as the AST+XBJ group, once daily. Ten mice per group were used for general monitoring and tissue sampling. Body temperature and weight were measured daily from Day 1 to Day 9. Peripheral blood infection rates were calculated daily from Day 4 to Day 9 using blood smears. The Coma Behavior Scale was used to assess mice before (Day 4), Day 6, and after (Day 8) drug administration. An open field test was performed once each on Day 4 and Day 8 to evaluate voluntary behavior. At the end of the experiment on Day 9, three mice were randomly selected for Evans blue staining, and the spleens of three mice were randomly selected for flow cytometry examination. The remaining mice were anesthetized with ether, euthanized by blood collection from the orbital venous plexus, and serum was collected. Liver, spleen, and brain tissues were weighed and the liver and spleen indices were calculated. Serum was used for liver and kidney function tests, and liver, spleen, and brain tissues were used for HE staining for pathological observation. An additional 10 mice in each group were also observed daily from Day 1 for 21 consecutive days.

[0027] Evaluation indicators: (1) Effects on the general condition of mice: The results are as follows Figure 1As shown, compared with the Control group, the infection rate of mice in the Infected group was 31.00%±7.66% at D9. The body weight and body temperature of the mice decreased significantly. Mice died on day 9 after infection, and all died successively from day 11 to day 13. The median survival time was 12.0 days, and the survival rate on day 21 was 0. After drug administration, compared with the Infected group, the infection rates of mice in the AST and AST+XBJ groups were 1.99%±1.25% and 0.67%±0.51% at D9, respectively. The body weight of mice in the XBJ, AST, and AST+XBJ groups increased significantly, and the body temperature of mice in the AST and AST+XBJ groups increased significantly. The median survival time of mice in the AST group was 17.0 days, and the survival rate on day 21 was 0. The median survival time of mice in the AST+XBJ group was 17.0 days, and the survival rate on day 21 was 20%. The above results indicate that the damage caused by Plasmodium to mice is becoming increasingly severe, leading to decreased body temperature and pale skin due to weakened physiological activity. After treatment with artesunate or artesunate combined with Xuebijing, the decline in body weight of the mice was significantly alleviated, and their body temperature gradually returned to the normal range.

[0028] (2) Effects on the autonomous behavior of mice: The results are as follows Figures 2 to 4 As shown, compared with the Control group, the RMCBS score of mice in the Infected group decreased significantly at D8. The mice exhibited ataxia, with almost complete loss of exploration ability, muscle tone, and reflexes, arched backs, and wrinkled fur. The open field test showed that the mice's total distance, maximum speed, total activity time, central distance, central activity time, and number of line crossings were all significantly reduced. After drug administration, compared with the Infected group, the RMCBS scores of mice in the AST group and AST+XBJ group increased significantly at D8. Among them, the AST+XBJ group showed the best recovery, with the mice's exploration ability, muscle tone, and reflex behavior basically returning to normal. The open field test showed that the mice in the AST+XBJ group had significantly increased total distance, maximum speed, total activity time, central distance, central activity time, and number of line crossings.

[0029] (3) Effects on liver and kidney function in mice: Results are as follows Figure 5 As shown, compared with the Control group, the Infected group mice had significantly higher serum urea (UREA), uric acid (UA), and lactate dehydrogenase (LDH) levels, and significantly lower serum total protein (TP), alkaline phosphatase (ALP), and serum albumin (ALB) levels. After drug administration, compared with the Infected group, the AST+XBJ group mice had significantly lower serum UREA, UA, and LDH levels, and significantly higher TP, ALP, and ALB levels. This indicates that cerebral malaria infection leads to significant liver and kidney dysfunction in mice, and the combined treatment effectively improved the infection-induced liver and kidney dysfunction.

[0030] (4) Effects on organ indices in mice: Results are as follows Figure 6 As shown, compared with the Control group, the liver and spleen indices of mice in the Infected group were significantly increased. Grossly, the liver and spleen were enlarged, dark purple in color, and firmer in texture. After administration, compared with the Infected group, the liver and spleen indices of mice in the AST group and AST+XBJ group were significantly decreased. Grossly, the liver and spleen were slightly enlarged and dark red in color. The combined administration of drugs was more effective in improving liver indices than artesunate alone.

[0031] (5) Effects on the pathological characteristics of mouse liver, brain, and spleen tissues: HE staining results are as follows Figure 7 As shown, compared with the Control group, mice in the Infected group showed pRBCs and mononuclear cell infiltration in the brain microvessels, as well as malarial pigment accumulation and scattered hemorrhages. In the liver, hepatic sinusoids were dilated and congested, with a large number of lymphocytes migrating and accumulating in the portal areas and central veins, along with a large amount of Plasmodium and malarial pigment deposition. In the spleen, the white pulp area was enlarged, the boundary between the red and white pulp was unclear, and local immune cell infiltration and a large amount of malarial pigment deposition were observed. After drug administration, compared with the Infected group, mice in the AST+XBJ group showed a significant decrease in pRBCs and mononuclear cells in the brain blood vessels, no endothelial cell swelling, slight dilation of the hepatic sinusoids in the liver, normal arrangement of hepatic cords, and a small amount of Plasmodium and malarial pigment deposition in the liver. In the spleen, the boundary between the red and white pulp was clear, with no obvious malarial pigment deposition or lymphocyte infiltration.

[0032] (6) Effect on blood-brain barrier permeability in mice: Evans blue staining results are as follows Figure 8 As shown, compared with the Control group, the brain tissue of mice in the Infected group showed varying degrees of blue staining, and the Evans blue exudate concentration was significantly increased. After administration, compared with the Infected group, the brain tissue of mice in the AST group and AST+XBJ group was close to that of normal mice, and the Evans blue exudate concentration was further reduced. Among them, the Evans blue exudate concentration was lower in the combined drug group.

[0033] (7) Effect on the ratio of T and B cells in mice: Flow cytometry results are as follows Figure 9 As shown, the proportion of T cells in the mouse spleen was significantly decreased, but CD4 cells were present. + / CD8 + The proportion of T cells in the spleen of mice in the AST group and AST+XBJ group increased significantly after drug administration compared with the Infected group; CD4 + / CD8 + The proportion decreased, and the proportion of T cells increased more significantly in the combination therapy group.

[0034] Example 2: Effects of artesunate combined with Xuebijing on the VEGF / Akt / eNOS signaling pathway.

[0035] Mouse serum and brain tissue collected in Example 1 were used to detect the levels of tumor necrosis factor α (TNF-α), interferon γ (IFN-γ), interleukin-10 (IL-10), angiopoietin-1 (Ang-1), and Ang-2 in mouse serum using ELISA; Western spectroscopy was used to detect the levels of tumor necrosis factor α (TNF-α), interferon γ (IFN-γ), interleukin-10 (IL-10), angiopoietin-1 (Ang-1), and Ang-2 in mouse serum. The levels of tight junction protein (Occludin), atresia band 1 (ZO-1), vascular endothelial cadherin (VE-Cadherin), Ang-1, Ang-2, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), vascular endothelial growth factor (VEGF), phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt), P-Akt, endothelial nitric oxide synthase (eNOS), and P-eNOS proteins in mouse brain tissue were detected by blotting. The levels of ICAM-1, platelet-endothelial cell adhesion protein (CD31), glial fibrillary acidic protein (GFAP), and neuronal nuclear antigen (NeuN) proteins in mouse brain tissue were detected by immunofluorescence. The mRNA expression level of leukocyte adhesion molecule (LFA-1) in mouse brain tissue was detected by qPCR. The level of nitric oxide (NO) in mouse brain tissue was detected by a total nitric oxide assay kit.

[0036] Immunofluorescence (IF) detection results are as follows Figures 10-13 As shown, compared with the Control group, the expression of ICAM-1 and GFAP proteins in the brain tissue of infected mice was significantly increased, while the expression of NeuN and CD31 proteins was significantly decreased. After drug administration, compared with the Infected group, the expression of ICAM-1 and GFAP proteins in the brain tissue of mice in the AST+XBJ group was significantly decreased, while the expression of NeuN and CD31 proteins was significantly increased. These results indicate that infection may induce neuronal damage and blood-brain barrier dysfunction, and promote pRBC adhesion in brain tissue. AST+XBJ has a protective effect against infection-induced ECM mouse brain tissue damage, and can alleviate neuronal damage, improve blood-brain barrier function, and inhibit pRBC adhesion by regulating the expression of related proteins.

[0037] ELISA kit test results are as follows: Figure 14As shown, compared with the Control group, the expression levels of Ang-1 in the serum of mice in the Infected group were significantly decreased, while the expression levels of Ang-2, TNF-α, IFN-γ, and IL-10 were significantly increased. After drug administration, compared with the Infected group, the serum Ang-1 level in mice in the AST+XBJ group was significantly increased, and the recovery level was close to that in the Control group, while the levels of Ang-2, TNF-α, IFN-γ, and IL-10 were significantly decreased. These results indicate that infection may induce vascular homeostasis imbalance and exacerbate inflammatory response, while combined drug administration can effectively regulate the balance of angiopoietin proteins, inhibit excessive inflammatory response, thereby restoring vascular homeostasis and reducing inflammatory damage in the infection model.

[0038] Western blotting results are as follows: Figures 15-18 As shown, compared with the Control group, the expression of Occludin, ZO-1, VE-Cadherin, Ang-1, and P-Akt / Akt proteins in the brain tissue of infected mice was significantly decreased, while the expression of ICAM-1 and VCAM-1 proteins was significantly increased. The expression levels of VEGF, PI3K, and P-eNOS / eNOS proteins showed no significant change. After drug administration, compared with the Infected group, the expression of Occludin, ZO-1, VE-Cadherin, Ang-1, VEGF, PI3K, P-eNOS / eNOS, and P-Akt / Akt proteins in the brain tissue of AST+XBJ mice was significantly increased, while the expression levels of ICAM-1 and VCAM-1 proteins were significantly decreased. These results indicate that infection may disrupt the integrity of the blood-brain barrier and promote the inflammatory response. Combined drug administration can effectively restore the integrity of the blood-brain barrier, inhibit the inflammatory response, and activate the VEGF / Akt / eNOS signaling pathway, thereby improving infection-induced brain tissue damage.

[0039] qPCR results and HE staining results are as follows Figure 19 As shown, compared with the Control group, the expression level of LFA-1 mRNA in the brain tissue of infected mice was significantly increased, and HE staining of mouse brain tissue revealed increased leukocyte infiltration in brain microvessels. After drug administration, compared with the Infected group, the expression of LFA-1 mRNA in the brain tissue of AST+XBJ mice was significantly decreased, and no large number of leukocytes were observed adhering to the brain tissue in HE staining. These results indicate that infection leads to the upregulation of the leukocyte adhesion molecule LFA-1, which in turn promotes leukocyte infiltration into brain tissue and exacerbates the inflammatory response. The combined drug administration can effectively inhibit the expression of the LFA-1 gene, reduce leukocyte infiltration into brain tissue, and thus alleviate the inflammatory response.

[0040] NO test results are as follows Figure 20As shown, compared with the Control group, the NO level in the brain tissue of infected mice was reduced; after drug administration, compared with the Infected group, the NO level in the brain tissue of AST+XBJ mice was significantly increased. These results indicate that infection may inhibit NO production, thereby affecting functions such as vasodilation and inflammation regulation, while combined drug administration can effectively restore NO production, promote vasodilation, and improve the inflammatory response.

[0041] In summary, artesunate combined with Xuebijing injection significantly improved the general condition of ECM mice, including increasing body weight and body temperature, enhancing autonomous behavior, and effectively protecting the liver, spleen, and brain tissue from infection-induced damage. Furthermore, this combination therapy restored the immune function of mice, particularly the proportion of T cells, thereby improving survival rates. Further mechanistic studies suggest that the therapeutic effect of artesunate combined with Xuebijing injection may be related to its activation of the VEGF / Akt / eNOS signaling pathway. Activation of this pathway helps increase nitric oxide (NO) expression, thereby promoting vasodilation and inflammation regulation. Therefore, artesunate combined with Xuebijing injection not only has significant potential value in clinical applications but also provides a novel treatment strategy for cerebral malaria.

[0042] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A pharmaceutical composition for treating cerebral malaria, characterized in that, The effective components of the pharmaceutical composition include artesunate and Xuesaitong injection.

2. A pharmaceutical composition for treating cerebral malaria according to claim 1, wherein The pharmaceutical composition further includes a pharmaceutically acceptable carrier.

3. Application of artesunate and Xuesaitong in preparation of a drug for treating cerebral malaria.

4. The use of artesunate and xuesaitong in combination according to claim 3 for the preparation of a medicament for the treatment of cerebral malaria, characterized in that, Application of the drug in protecting liver, spleen and brain tissues.

5. The use of artesunate and xuesaitong in combination according to claim 3 for the preparation of a medicament for the treatment of cerebral malaria, characterized in that, Application of the drug in reducing inflammation of the nervous system.

6. The use of artesunate and xuesaitong in combination according to claim 3 for the preparation of a medicament for the treatment of cerebral malaria, characterized in that, Application of the drug in improving immune function.

7. The use of artesunate and xuesaitong in combination according to claim 3 for the preparation of a medicament for the treatment of cerebral malaria, characterized in that, Application of the drug in improving the expression level of VEGF protein.

8. The use of artesunate and xuesaitong in combination according to claim 3 for the preparation of a medicament for the treatment of cerebral malaria, characterized in that, Application of the drug in improving the expression level of Akt protein.

9. The use of artesunate and xuesaitong in combination according to claim 3 for the preparation of a medicament for the treatment of cerebral malaria, characterized in that, Application of the drug in improving the expression level of eNOs protein.

10. The use of artesunate and xuesaitong in combination according to claim 3 for the preparation of a medicament for the treatment of cerebral malaria, characterized in that, Application of the drug in improving the expression of NO.

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