Use of d-borneol in the preparation of a drug for preventing and / or treating preeclampsia

Abstract

The application belongs to the field of biological medicine, and provides application of d-borneol in preparation of a drug for preventing and / or treating preeclampsia. A preeclampsia animal model is induced and established by subcutaneous injection of a solution of nitroso-L-arginine methyl ester (125 mg / kg), and d-borneol (15 mg / kg) is given to the animal by gavage from the 9th day of pregnancy every day until the end of pregnancy. Compared with the single treatment effect of the existing clinical commonly used antihypertensive drug labetalol, antispasmodic and anticonvulsant drug magnesium sulfate and the like, the d-borneol of the application not only can relieve hypertension and proteinuria of the preeclampsia model mouse, but also can improve pathological changes such as reduced placental weight, abnormal placental structure and function, intrauterine growth restriction of the fetus, and imbalance of pro-angiogenic factors and anti-angiogenic factors. Meanwhile, the d-borneol can also alleviate the preeclampsia related maternal kidney injury, and shows a more comprehensive intervention effect than the existing symptomatic treatment drug, thereby providing a new treatment drug for preventing or treating preeclampsia.

Description

Technical Field

[0001] This invention belongs to the field of biomedicine, specifically relating to the application of dextrorotatory borneol in the preparation of drugs for the prevention and / or treatment of preeclampsia. Background Technology

[0002] Preeclampsia (PE) is a pregnancy-specific condition, typically manifesting as new-onset hypertension after 20 weeks of gestation, accompanied by proteinuria and / or maternal organ dysfunction. Severe cases can lead to headaches, visual disturbances, seizures, liver and kidney damage, pulmonary edema, and multiple organ failure, even endangering the lives of both mother and baby. PE is a significant pregnancy complication threatening maternal and infant health, with a global incidence of approximately 2%–8%. PE not only increases the risk of maternal and perinatal mortality but is also closely associated with an increased risk of long-term maternal cardiovascular disease, stroke, diabetes, and chronic kidney disease. Furthermore, offspring born to mothers with PE have a significantly increased risk of premature birth, intrauterine growth restriction, neurodevelopmental abnormalities, and cardiovascular and metabolic diseases in adulthood. Therefore, effective prevention and treatment of preeclampsia are crucial for reducing adverse maternal and infant outcomes and improving long-term maternal health.

[0003] The pathogenesis of placental vasculopathy (PE) is complex and not yet fully understood. It is generally believed to be related to multiple factors, including abnormal uteroplacental vascular remodeling, insufficient placental perfusion, endothelial dysfunction, excessive activation of the inflammatory immune response, oxidative stress, and genetic susceptibility. Among these, the "two-stage model" is currently the most widely accepted hypothesis for the pathogenesis of PE. During normal pregnancy, trophoblastic cells invade the maternal decidua and uterine spiral arteries, remodeling the spiral arteries from high-resistance, low-volume vessels to low-resistance, high-volume vessels, thus ensuring adequate blood, oxygen, and nutrient supply to the placenta and fetus. When PE occurs, insufficient trophoblastic cell invasion and impaired spiral artery remodeling can lead to insufficient placental perfusion and ischemia-hypoxia, resulting in abnormal placental structure and function, and ultimately adverse pregnancy outcomes such as intrauterine growth restriction. Placental ischemia, hypoxia, and dysfunction can further promote the release of various placental-derived bioactive substances into the maternal circulation, including anti-angiogenic factors, inflammatory factors, and oxidative stress-related mediators. This can induce systemic vascular endothelial dysfunction, leading to increased vasoconstriction, impaired vasodilation, and increased peripheral resistance, ultimately manifesting as clinical symptoms such as hypertension. Furthermore, placental ischemia (PE) often affects the kidneys, causing glomerular endothelial damage, podocyte damage, and disruption of the glomerular filtration barrier, resulting in proteinuria and abnormal renal function. Recent studies have shown that an imbalance between pro-angiogenic and anti-angiogenic factors plays a crucial role in the development and progression of PE. Decreased placental growth factor (PlGF) and elevated soluble fms-like tyrosine kinase-1 (sFlt-1) are important molecular characteristics of PE. According to the 2021 ISSHP guidelines, an elevated sFlt-1 / PlGF ratio or decreased PlGF levels in the maternal circulation have been incorporated into the diagnostic and risk assessment system for PE. Angiogenesis imbalance can disrupt maternal endothelial homeostasis, while endothelial dysfunction can further aggravate placental insufficiency and abnormal angiogenesis. The two interact and jointly promote the occurrence and development of PE.

[0004] Currently, clinical intervention strategies for preeclampsia mainly include preventative and symptomatic treatment. Preventative treatment primarily involves oral low-dose aspirin to reduce the risk of PE in high-risk pregnant women. Symptomatic treatment mainly includes using antihypertensive drugs such as labetalol and nifedipine to control blood pressure, and intravenous magnesium sulfate to prevent or alleviate eclamptic seizures and related convulsive symptoms. However, existing treatments still have certain limitations. For example, aspirin may cause gastrointestinal adverse reactions such as nausea, vomiting, and upper abdominal pain; antihypertensive drugs such as labetalol may also cause discomfort such as headache, nausea, and arrhythmia, thus affecting the pregnant woman's pregnancy status and medication adherence. Furthermore, when drug treatment cannot effectively control the progression of the disease, early termination of pregnancy remains an important means to prevent further deterioration and ensure the safety of both mother and baby. However, iatrogenic preterm birth may increase the risk of infection in pregnant women and lead to fetal growth restriction, increased perinatal mortality, and an increased risk of neonatal asphyxia. Therefore, developing novel functional active substances with proven efficacy, good safety profiles, and applicability during pregnancy remains a crucial issue to be addressed in the prevention and treatment of preeclampsia. Considering the high disease burden of PE across various regions, especially in areas with relatively limited medical resources, developing a drug or drug with a simple administration method, good safety profile, and the ability to simultaneously improve multiple pathological changes such as maternal hypertension, proteinuria, placental dysfunction, fetal growth restriction, and kidney damage has significant clinical application value and practical implications.

[0005] Dextrorotatory borneol (BO) is a bicyclic monoterpene alcohol compound with the chemical formula C0. 10 H 18Borneol, with a molecular weight of 154.25 g / mol, can be derived from natural plant extracts or obtained through chemical synthesis. It possesses strong lipid solubility and biomembrane permeability, making it a common natural active ingredient in traditional and modern drug delivery research. Previous studies have shown that borneol exhibits various pharmacological activities, including anti-inflammatory, antioxidant, analgesic, microcirculation-improving, and biobarrier-regulating activities. Furthermore, borneol has demonstrated effects such as improving blood flow, resisting reactive oxygen species damage, inhibiting inflammatory responses, and protecting tissue function in studies related to ischemic injury. For example, relevant literature indicates that borneol can improve blood-brain barrier and tight junction damage caused by cerebral ischemia by activating the HIF-1α / VEGF signaling pathway. Borneol can inhibit the production of pro-inflammatory factors IL-1β, IL-6, and TNF-α, exerting anti-inflammatory effects, and can alleviate oxidative stress and exert neuroprotective effects by reducing MDA levels and increasing SOD and GSH-px activities. In addition, studies have found that borneol can relax blood vessels and has a hypotensive effect in rats with renovascular hypertension. The core pathological process of preeclampsia (PE) involves multiple aspects, including placental ischemia and hypoxia, oxidative stress, inflammatory response, angiogenic factor imbalance, endothelial dysfunction, and glomerular filtration barrier damage. Borneol's multi-target regulatory characteristics, such as anti-inflammatory, antioxidant, barrier function improvement, and antihypertensive effects, correspond to the multifactorial and multi-stage pathological mechanisms of PE. Therefore, exploring the pharmacological use of dextrorotatory borneol in the prevention and / or treatment of preeclampsia, especially its comprehensive improvement effects on PE-related hypertension, proteinuria, placental structural and functional abnormalities, intrauterine growth restriction, angiogenic factor imbalance, and maternal kidney damage, has high research value and application prospects. Currently, there is a lack of systematic research on the use of dextrorotatory borneol in the preparation of drugs for the prevention and / or treatment of preeclampsia and its related complications. Therefore, it is necessary to develop a drug application scheme for the prevention and treatment of preeclampsia using dextrorotatory borneol as the active ingredient. Summary of the Invention

[0006] To overcome the shortcomings of existing technologies, this invention provides the application of dextrorotatory borneol in the preparation of drugs for the prevention and / or treatment of preeclampsia. Compared with antihypertensive drugs such as labetalol and antispasmodic drugs such as magnesium sulfate, which have only single therapeutic effects, oral dextrorotatory borneol can not only significantly alleviate hypertension and proteinuria caused by preeclampsia, repair placental function, promote intrauterine fetal growth and development, and correct the imbalance of pro-angiogenic and anti-angiogenic factors, but also reduce preeclampsia-induced kidney damage in pregnant women, demonstrating a more comprehensive therapeutic effect and providing a new efficacy factor for the prevention or treatment of preeclampsia.

[0007] To achieve the above objectives, the present invention adopts the following technical solution: The first aspect of this invention provides the use of dextrorotatory borneol in the preparation of a medicament for treating preeclampsia.

[0008] Furthermore, the application of the dextrorotatory borneol in the preparation of a drug for reducing hypertension caused by preeclampsia, the drug being used to reduce hypertension caused by preeclampsia.

[0009] Furthermore, the use of the dextrorotatory borneol in the preparation of a drug for reducing proteinuria in preeclampsia, the drug being used to reduce proteinuria levels caused by preeclampsia.

[0010] Furthermore, the application of the dextrorotatory borneol in the preparation of a drug for improving placental dysfunction caused by preeclampsia, wherein the drug is used to repair placental dysfunction caused by preeclampsia.

[0011] Furthermore, the drug is used to improve placental weight reduction in preeclampsia.

[0012] Furthermore, the drug is used to improve placental structural abnormalities and functional disorders in preeclampsia.

[0013] Furthermore, the application of the dextrorotatory borneol in the preparation of a drug for improving intrauterine growth restriction in fetuses with preeclampsia, the drug being used to improve intrauterine growth restriction in fetuses caused by preeclampsia.

[0014] Furthermore, the drug is used to restore the imbalance between angiogenic factors and anti-angiogenic factors.

[0015] Furthermore, the angiogenic factors include vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), and the anti-angiogenic factors include soluble fms-like tyrosine kinase-1 (sFlt-1).

[0016] Furthermore, the use of the dextrorotatory borneol in the preparation of a drug for reducing preeclampsia-induced kidney injury, the drug being used to reduce preeclampsia-induced kidney injury.

[0017] Furthermore, the drug contains an effective amount of dextrorotatory borneol or a pharmaceutically acceptable salt thereof as the main active ingredient.

[0018] Furthermore, the drug also includes pharmaceutically acceptable carriers or excipients.

[0019] Furthermore, the dosage form of the drug is tablets, capsules, oral liquids, granules, powders, pills, powders, suspensions, or injections.

[0020] Furthermore, the drug is administered orally or by injection.

[0021] Furthermore, the dosage of the drug is: 15 mg / kg of dextrorotatory borneol orally daily.

[0022] The present invention has the following beneficial effects: This invention establishes an animal model of preeclampsia by subcutaneous injection of nitroso-L-arginine methyl ester solution (125 mg / kg), and administers dextrorotatory borneol (15 mg / kg) daily by gavage from the 9th day of pregnancy until the end of pregnancy. Compared with existing clinically used antihypertensive drugs such as labetalol and anticonvulsant and anticonvulsant drugs such as magnesium sulfate, which mainly target single symptoms, the dextrorotatory borneol described in this invention can comprehensively improve multiple pathological aspects related to preeclampsia. Experimental results show that dextrorotatory borneol can not only alleviate hypertension and proteinuria in preeclampsia model mice, but also improve pathological changes such as reduced placental weight, abnormal placental structure and function, intrauterine growth restriction of fetus, and imbalance of pro-angiogenic and anti-angiogenic factors. At the same time, dextrorotatory borneol can also reduce preeclampsia-related maternal kidney damage, showing a more comprehensive intervention effect than existing symptomatic treatments. Therefore, this invention provides a drug use scheme for the prevention and / or treatment of preeclampsia that combines antihypertensive, placental function improvement, fetal development promotion, and maternal kidney protection, providing a new drug option for the prevention or treatment of preeclampsia. Attached Figure Description

[0023] Figure 1 For the comparison of blood pressure in mice of each group in Example 1 (n=6), 'a' represents the comparison of systolic blood pressure between the NP group and the PE group on the corresponding date; 'aaa' indicates P<0.001; 'b' represents the comparison of systolic blood pressure between the PE group and the BO group on the corresponding date; 'bbb' indicates P<0.001; 'c' represents the comparison of systolic blood pressure between the NP group and the BO group on the corresponding date; 'ccc' indicates P<0.001. Figure 2 This is a comparison of urinary protein levels in mice in different groups in Example 2 (n=6).

[0024] Figure 3 This is a comparison of placental weight in each group of mice in Example 3 (n=6).

[0025] Figure 4 This is a comparison of placental regions in each group of mice in Example 4 (n=3).

[0026] Figure 5 This is a comparison of the fetal weights of mice in each group in Example 5 (n=6).

[0027] Figure 6 This is a comparison of the levels of pro-angiogenic factors and anti-angiogenic factors in the serum of mice in each group in Example 6 (n=6).

[0028] Figure 7 This is a comparison of kidney injury indicators in each group of mice in Example 7 (n=6).

[0029] It should be noted that in the attached figure, * indicates statistically significant difference, * indicates P<0.05, ** indicates P<0.01, and *** indicates P<0.001; T represents the standard deviation (SD) of the six independent experiments (n=6). Detailed Implementation

[0030] To make the above-mentioned objects, features, and advantages of the present invention more apparent and understandable, specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings, but this should not be construed as limiting the scope of the present invention. Unless otherwise specified, the reagents, methods, and equipment used in the present invention are conventional reagents, methods, and equipment in this technical field.

[0031] Unless otherwise specified, all reagents and materials used in the following examples are commercially available.

[0032] I. Preparation of experimental reagents, materials and animals.

[0033] Drug ingredients: Dextrorotatory borneol is a naturally derived bicyclic monoterpene alcohol compound with the chemical formula C0. 10 H 18 O, with a molecular weight of 154.25 g / mol, is commonly found in the volatile oils of various aromatic plants and has a good foundation for medicinal development.

[0034] Drug uses: Oral administration of dextrorotatory borneol can significantly alleviate hypertension and proteinuria caused by preeclampsia, repair placental pathological tissue structure and functional changes, restore fetal intrauterine growth and development, correct the imbalance between vascular and anti-angiogenic factors, and improve preeclampsia-induced kidney damage, proving that dextrorotatory borneol has a good therapeutic effect on preeclampsia.

[0035] Experimental basis: 1. Laboratory animals Male and female C57BL / 6 mice (8–10 weeks old, weighing 18–20 g) were purchased from SPF (Beijing) Biotechnology Co., Ltd. (Beijing, China). Mice were housed under standard light and dark cycles (12 h:12 h) with free access to food and water. One week after acclimatization, healthy male mice were mated with female mice at a 1:2 ratio overnight. Female mice with sperm plugs were considered pregnant, and this day was defined as the gestation day (GD0). All animal studies were conducted in accordance with protocols and guidelines approved by the Animal Ethics Committee of the Laboratory Animal Center of Southern Medical University.

[0036] 2. Experimental reagents The experimental reagents are shown in Table 1 below. Table 1

[0037] 3. Drug preparation 3.1 N-nitro-L-arginine methyl ester (L-NAME) solution: Weigh 125 mg of L-NAME powder and dilute to 10 mL with physiological saline.

[0038] 3.2 Dextrorotatory Borneol Solution: Weigh 3 mg of dextrorotatory borneol, add 1.94 mL of physiological saline, then add 0.06 mL of Tween 80, vortex and sonicate for 10 minutes to obtain a 1.5 mg / mL dextrorotatory borneol solution.

[0039] 4. Establishment and evaluation of the preeclampsia model 4.1 Establishment of the preeclampsia model Starting from GD9, pregnant mice were subcutaneously injected daily with 125 mg / kg of nitroso-L-arginine methyl ester (L-NAME) solution for 9 days.

[0040] 4.2 Evaluation of the preeclampsia model 4.2.1 Blood Pressure The blood pressure of mice in the preeclampsia model group was significantly higher than that of mice in the normal pregnancy group, which indicates that the model was successfully established.

[0041] 4.2.2 Proteinuria The proteinuria level in the preeclampsia model group was significantly higher than that in the normal pregnancy group, indicating that the model was successfully established.

[0042] 5. Real-time quantitative PCR 5.1 Reverse transcription of RNA Prepare a total reaction volume of 20 μL according to the instructions of the reverse transcription kit. Add the required amount of RNA and 4 μL of HiScript II Q RT SuperMix for qPCR reagent to each 200 μL PCR tube, and then add ddH2O to a final volume of 20 μL. Place the PCR tubes in a PCR amplification instrument and perform the following operations: 50℃, 15 min; 85℃, 5 s; 4℃, ∞. After the reaction, centrifuge, label the time, and store the obtained cDNA at -80℃ for later use.

[0043] 5.2 Real-time quantitative PCR (RT-qPCR) All reverse transcription products were subjected to real-time quantitative PCR, and the reaction system is shown in Table 2. The primer sequences for the relevant genes are shown in Table 3. A two-step PCR amplification system was used, and the method settings are shown in Table 4.

[0044] Table 2 PCR Reaction System

[0045] Table 3 Primer sequences

[0046] Table 4 RT-qPCR reaction procedure

[0047] Data processing: Using Gapdh as an internal reference gene, the relative expression level of the target gene was calculated using the 2-ΔΔCt method.

[0048] II. Implementation Examples Example 1: Dextrorotatory borneol can significantly reduce hypertension in preeclampsia mice. Hypertension is an important clinical manifestation of preeclampsia. To investigate the effect of dextrorotatory borneol on blood pressure in preeclampsia mice, pregnant mice were randomly divided into a normal pregnancy group (NP, n=6), a preeclampsia model group (PE, n=6), and a dextrorotatory borneol intervention group (BO, n=6). Mice in the dextrorotatory borneol intervention group were administered dextrorotatory borneol daily by gavage starting from day 9 of gestation (GD9) at a dose of 15 mg / kg. Mice in the normal pregnancy group and the preeclampsia model group were administered an equal volume of 3% Tween 80 solution daily by gavage. All groups were administered the medication once daily for 9 consecutive days.

[0049] The results are as follows Figure 1 As shown, after GD9, the blood pressure of mice in the preeclampsia model group was significantly higher than that in the normal pregnancy group; compared with the preeclampsia model group, the blood pressure of mice in the dextrorotatory borneol intervention group was significantly lower. These results indicate that dextrorotatory borneol can significantly improve hypertension in preeclampsia model mice. (a represents the comparison of systolic blood pressure between the NP group and the PE group on the corresponding date; aaa indicates P<0.001; b represents the comparison of systolic blood pressure between the PE group and the BO group on the corresponding date; bbb indicates P<0.001; c represents the comparison of systolic blood pressure between the NP group and the BO group on the corresponding date; ccc indicates P<0.001.) Example 2: Dextrorotatory borneol can significantly reduce proteinuria levels in preeclampsia model mice. Having confirmed that dextrorotatory borneol can lower blood pressure in preeclampsia model mice, this embodiment further investigates its intervention effect on proteinuria. Proteinuria is one of the important clinical features of preeclampsia and a key indicator reflecting preeclampsia-related kidney damage. Therefore, this embodiment measures the proteinuria levels of mice in each group to evaluate the ameliorative effect of dextrorotatory borneol on proteinuria in preeclampsia model mice.

[0050] See results Figure 2The proteinuria level in the preeclampsia model mice was significantly higher than that in the normal pregnancy group. After intervention with dextrorotatory borneol, the proteinuria level in the preeclampsia model mice was significantly reduced, indicating that dextrorotatory borneol can significantly reduce the urinary protein level in the preeclampsia model mice.

[0051] Example 3: Dextrorotatory borneol significantly increased placental weight in preeclampsia model mice. The placenta is a vital organ for maintaining pregnancy and supporting fetal growth and development. Its developmental status is closely related to fetal nutrient supply, gas exchange, and pregnancy outcomes. Reduced placental weight is one of the important manifestations of placental developmental restriction and placental dysfunction in preeclampsia. To further evaluate the ameliorative effect of dextrorotatory borneol on preeclampsia-related placental damage, this example measured changes in placental weight in mice of different groups.

[0052] The results of placental weight changes in each group of mice are as follows: Figure 3 Compared with the normal pregnancy group, the placental weight of mice in the preeclampsia model group was significantly reduced, indicating that the preeclampsia model mice had obvious placental developmental restriction; compared with the preeclampsia model group, the placental weight of mice in the dextrorotatory borneol intervention group was significantly increased. These results indicate that dextrorotatory borneol can effectively improve the pathological manifestations of reduced placental weight in preeclampsia model mice, suggesting that it has a protective effect against preeclampsia-related placental developmental disorders.

[0053] Example 4: Dextrorotatory borneol can improve placental structural abnormalities and functional disorders in preeclampsia model mice. The mouse placenta is mainly composed of the decidual region, the junctional region, and the labyrinthine region. The labyrinthine region is the main functional area for maternal-fetal material exchange, responsible for the exchange of oxygen, nutrients, and metabolic products, playing a crucial role in maintaining normal fetal growth and development. The junctional region, mainly composed of trophoblast cells such as spongy trophoblast cells, glycogen cells, and trophoblast giant cells, is an important endocrine regulatory region of the placenta, secreting various hormones, growth factors, and cytokines, participating in maintaining the pregnancy process and placental homeostasis.

[0054] The results are as follows Figure 4 As shown in the figure, compared with the normal pregnancy group, the area ratio of the placental labyrinth to the connective tissue in the preeclampsia model group mice was significantly increased, suggesting that the preeclampsia model mice had placental tissue structural disorders and placental functional impairment. After intervention with dextrorotatory borneol, the area ratio of the placental labyrinth to the connective tissue in the preeclampsia model group mice was significantly reduced. The results indicate that dextrorotatory borneol can alleviate the pathological damage of placental tissue in preeclampsia model mice and improve placental structural abnormalities and related functional impairments.

[0055] Example 5: Dextrorotatory borneol can improve intrauterine growth restriction in preeclampsia model mice. Intrauterine growth restriction is a common adverse pregnancy outcome in preeclampsia, usually closely related to placental developmental abnormalities, insufficient placental perfusion, and maternal-fetal material exchange disorders. To further evaluate the intervention effect of dextrorotatory borneol on fetal developmental abnormalities in preeclampsia, this example measured the changes in fetal weight in each group of mice.

[0056] The results are as follows Figure 5 As shown, compared with the normal pregnancy group, the fetal weight of mice in the preeclampsia model group was significantly reduced, indicating that the model mice experienced intrauterine growth restriction; compared with the preeclampsia model group, the fetal weight of mice in the dextrorotatory borneol intervention group was significantly increased. These results indicate that dextrorotatory borneol can effectively improve the reduced fetal weight in preeclampsia model mice, suggesting that it has a protective effect against intrauterine growth restriction in preeclampsia fetuses.

[0057] Example 6: Dextrorotatory borneol can improve the imbalance of pro-angiogenic and anti-angiogenic factors in preeclampsia model mice. An imbalance between pro-angiogenic and anti-angiogenic factors is one of the important pathological features in the development of preeclampsia. In preeclampsia, placental-derived anti-angiogenic factors are abnormally elevated, interfering with normal angiogenesis and endothelial function, and are closely related to impaired uterine spiral artery remodeling, insufficient placental perfusion, and maternal clinical symptoms. To further evaluate the regulatory effect of dextrorotatory borneol on the angiogenic imbalance in preeclampsia, this study measured the serum levels of soluble fms-like tyrosine kinase-1 (sFlt-1), vascular endothelial growth factor (VEGF), and placental growth factor (PlGF) in mice of each group, and calculated the sFlt-1 / PlGF ratio as a further indicator of PE.

[0058] The results are as follows Figure 6 As shown, compared with the normal pregnancy group, the serum levels of anti-angiogenic factor sFlt-1 in preeclampsia model mice were significantly increased, while the levels of pro-angiogenic factors VEGF and PlGF were significantly decreased, and the sFlt-1 / PlGF ratio was significantly increased, indicating a significant imbalance between pro-angiogenic and anti-angiogenic factors in the preeclampsia model mice. After intervention with dextrorotatory borneol, the sFlt-1 level in the preeclampsia model mice decreased, while the levels of VEGF and PlGF increased, and the sFlt-1 / PlGF ratio decreased. These results indicate that dextrorotatory borneol can improve the imbalance between pro-angiogenic and anti-angiogenic factors in preeclampsia model mice, suggesting that it may improve placental dysfunction and maternal vascular endothelial damage in preeclampsia by regulating angiogenesis-related factors.

[0059] Example 7: Dextrorotatory borneol can improve renal function damage in preeclampsia model mice. Kidney injury is a significant pathological manifestation of preeclampsia, often presenting as proteinuria, abnormal glomerular filtration function, and podocyte damage. Serum creatinine (Scr) and blood urea nitrogen (BUN) are commonly used indicators for evaluating kidney function impairment; elevated levels suggest impaired renal excretion. Nephrin and podocin are important components of the podocyte slit diaphragm structure, playing a crucial role in maintaining the integrity of the glomerular filtration barrier; decreased expression of these proteins typically indicates impaired podocyte structure and function. To further evaluate the ameliorative effect of dextrorotatory borneol on preeclampsia-related kidney injury, this study measured serum Scr and BUN levels in mice across different groups and detected the mRNA expression levels of Nephrin and podocin in kidney tissue.

[0060] The results are as follows Figure 7 As shown, compared with the normal pregnancy group, the preeclampsia model mice had elevated serum Scr and BUN levels, and significantly reduced mRNA expression levels of nephrin and podocin in kidney tissue, suggesting renal dysfunction and podocyte-related filtration barrier damage in the preeclampsia model mice. After intervention with dextrorotatory borneol, serum Scr and BUN levels decreased, while nephrin and podocin mRNA expression in kidney tissue increased in the preeclampsia model mice. These results indicate that dextrorotatory borneol can improve renal dysfunction in preeclampsia model mice and has a protective effect against podocyte filtration barrier damage.

[0061] Through the above embodiments, this invention further demonstrates that dextrorotatory borneol can comprehensively improve multiple pathological aspects related to preeclampsia. Experimental results show that dextrorotatory borneol can not only alleviate hypertension and proteinuria in preeclampsia model mice, but also improve pathological changes such as decreased placental weight, abnormal placental structure and function, intrauterine growth restriction of fetus, and imbalance between pro-angiogenic and anti-angiogenic factors. Simultaneously, dextrorotatory borneol can also reduce maternal kidney damage associated with preeclampsia, exhibiting a more comprehensive intervention effect than existing symptomatic treatments, proving that dextrorotatory borneol has a good therapeutic effect on preeclampsia.

[0062] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the invention patent. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these all fall within the protection scope of the present invention. Therefore, the protection scope of this invention patent should be determined by the appended claims.

Claims

1. The use of dextrorotatory borneol in the preparation of drugs for the prevention and / or treatment of preeclampsia.

2. The application according to claim 1, characterized in that, The application of dextrorotatory borneol in the preparation of drugs to reduce preeclampsia and hypertension.

3. The application according to claim 1, characterized in that, The application of dextrorotatory borneol in the preparation of drugs to reduce proteinuria in preeclampsia.

4. The application according to claim 1, characterized in that, The application of dextrorotatory borneol in the preparation of drugs to improve placental dysfunction in preeclampsia.

5. The application according to claim 1, characterized in that, The application of dextrorotatory borneol in the preparation of drugs to improve intrauterine growth restriction in preeclamptic fetuses.

6. The application according to claim 1, characterized in that, The application of dextrorotatory borneol in the preparation of drugs to alleviate kidney damage in preeclampsia.

7. The application according to any one of claims 1-6, characterized in that, The drug contains an effective amount of dextrorotatory borneol or its pharmaceutically acceptable salt as the main active ingredient.

8. The application according to claim 7, characterized in that, The drug also includes pharmaceutically acceptable carriers or excipients.

9. The application according to claim 7, characterized in that, The dosage form of the drug is tablets, capsules, oral liquids, granules, powders, pills, powders, suspensions, or injections; the method of administration of the drug is oral or injection.

10. A pharmaceutical composition for the prevention / treatment of preeclampsia, comprising dextrorotatory borneol and a pharmaceutically acceptable carrier.

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