CN-121971414-A - Application of magnolol and pharmaceutically acceptable salt thereof in inhibiting chronic inflammation of bone marrow-derived foam macrophages after spinal cord injury

Abstract

The invention discloses application of magnolol and pharmaceutically acceptable salt thereof in inhibiting chronic inflammation of bone marrow-derived foam macrophages after spinal cord injury. The invention provides application of magnolol in preparing medicines for promoting macrophage lipid excretion, medicines for promoting spinal cord injury repair, medicines for inhibiting secondary inflammation mediated by lipid accumulation after spinal cord injury or neuroprotection medicines, and further provides medicines for promoting macrophage lipid excretion or reagents and medicines for inhibiting spinal cord inflammation, wherein the medicines comprise magnolol. According to the invention, magnolol is disclosed for the first time, through regulating and controlling immune cell lipid efflux-inflammatory factor axis, spinal nerve regeneration is obviously promoted, nerve function is improved, inflammatory reaction after lipid overload is relieved, spinal tissues are protected, and an innovative strategy is provided for spinal cord injury treatment. Magnolol provides a brand new direction for SCI treatment by improving lipid overload and immune double-channel synergistic intervention on secondary neurodegenerative diseases after spinal cord injury.

Inventors

• Qian Zhanchang
• ZHANG CHAOQIANG
• ZHU TIANYU
• XIA MINGJIE
• CUI ZHIMING

Assignees

• 南通市第一人民医院

Dates

Publication Date

20260505

Application Date

20260320

Claims (10)

1. 1. Use of magnolol or a pharmaceutically acceptable salt thereof in any one of the following: preparing a medicament for promoting lipid excretion of macrophages; Preparing a medicament for promoting spinal cord injury repair; preparing a medicament for inhibiting secondary inflammation mediated by lipid accumulation after spinal cord injury; Preparing neuroprotective medicine.
2. 2. The use according to claim 1, wherein the macrophages are bone marrow derived foam macrophages.
3. 3. The use according to claim 2, wherein the foam macrophages are foam macrophages in spinal cord tissue following spinal cord injury.
4. 4. The use of claim 1, wherein the site of occurrence of lipid accumulation-mediated secondary inflammation is spinal cord tissue.
5. 5. The use of claim 1, wherein the spinal cord injury repair comprises at least one of spinal cord nerve regeneration, promotion of nerve and motor function recovery.
6. 6. The use according to claim 1, wherein the spinal cord injury comprises spinal cord injury-related neurological dysfunction and/or spinal cord injury-related peripheral nerve injury and nerve conduction disorder.
7. 7. A spinal cord injury repair drug comprising magnolol or a pharmaceutically acceptable salt thereof.
8. 8. A medicament or agent for promoting lipid efflux from macrophages comprising magnolol or a pharmaceutically acceptable salt thereof.
9. 9. A spinal cord inflammation-inhibiting drug comprising magnolol or a pharmaceutically acceptable salt thereof.
10. 10. The medicament or agent of any one of claims 7-9, wherein magnolol or a pharmaceutically acceptable salt thereof is contained at a concentration of at least 300 μg/mL.

Description

Application of magnolol and pharmaceutically acceptable salt thereof in inhibiting chronic inflammation of bone marrow-derived foam macrophages after spinal cord injury Technical Field The invention relates to a spinal cord injury repair drug, in particular to application of magnolol and pharmaceutically acceptable salt thereof in inhibiting chronic inflammation of bone marrow-derived foam macrophages after spinal cord injury. Background Spinal cord injury (Spinal cord injury, SCI) is a traumatic disorder of the central nervous system that can lead to severe tissue damage and neurological dysfunction. Pathophysiological processes of spinal cord injury include primary and secondary injury involving a variety of pathological mechanisms such as oxidative stress, inflammation, autophagy, iron death, and mitochondrial dysfunction. The primary injury mainly refers to neuron axon fracture, spinal cord hemorrhage and blood-spinal cord barrier destruction caused by external force, and the secondary injury mainly comprises persistent inflammatory reaction, and is accompanied with changes such as apoptosis, glial scar formation, mitochondrial dysfunction and the like, so that the nerve function is further deteriorated. Studies have shown that a large number of bone marrow-derived macrophages enter the injury site from the periphery after spinal cord injury, and these bone marrow-derived macrophages engulf excessive lipid-rich myelin fragments, resulting in lipid accumulation, eventually forming foam cells, which continuously release inflammatory factors at the injury site, produce chronic inflammatory responses, exacerbate nerve tissue injury and dysfunction. At present, the clinical treatment is mainly performed by operation decompression, glucocorticoid impact and rehabilitation training, but the clinical treatment still has a plurality of limitations: (1) The traditional glucocorticoid is difficult to specifically inhibit inflammatory factors related to microglial oxidative stress, and is easy to induce infection after long-term use; (2) Drug delivery disorders many macromolecular drugs are difficult to deliver effectively under the scar barrier. The magnolia bark extract has thousands of years of application history in traditional Chinese medicine, and is still widely used as an herbal preparation to date, and has the effects of sedation, antioxidation, anti-inflammatory, antibiosis, antispasmodics and the like. Magnolol (Mag) is a main component of magnolia bark extract which has medicinal value, has good nervous system penetrability and biological safety, and has the following structural formula: The molecule exhibits significant protective effects in multiple models of neurodegenerative diseases. The action mechanism of magnolol comprises: Neuroprotection by Mag inhibiting prefrontal cortex oxidative stress and depression-like behavior by reducing IL-1 beta, IL-6 and TNF-alpha levels, while reducing microglial activation, HPA axis hyperactivity and lipid peroxidation, and increasing enzymatic activity; Mag inhibits the production of Nitric Oxide (NO) and the expression of phosphorylated IκBα (P-IκBα), phosphorylated P65 (P-P65), interleukin-1β (IL-1β) and TNF- α (TNF- α). Down-regulating phosphorylated JNK (p-JNK) and phosphorylated p38 (p-p 38); Antioxidant activity, effective in reducing oxidative stress, inhibiting cell proliferation and preventing AA-induced G2/M phase retardation. However, studies of magnolol in promoting lipid excretion from macrophages have not been reported. Disclosure of Invention The invention aims to provide application of magnolol or pharmaceutically acceptable salt thereof in preparing medicines for promoting macrophage lipid excretion, medicines for promoting spinal cord injury repair, medicines for inhibiting secondary inflammation mediated by lipid accumulation after spinal cord injury or neuroprotection medicines, and solve the problems of how to promote macrophage lipid excretion, promote spinal cord injury repair, inhibit secondary inflammation mediated by lipid accumulation after spinal cord injury and protect nerve tissues. A second object of the present invention is to provide a spinal cord injury repair drug comprising magnolol or a pharmaceutically acceptable salt thereof. A third object of the present invention is to provide a medicament or agent for promoting lipid efflux from macrophages comprising magnolol or a pharmaceutically acceptable salt thereof. The fourth object of the present invention is to provide a spinal cord inflammation-inhibiting drug comprising magnolol or a pharmaceutically acceptable salt thereof. The invention firstly discloses application of magnolol or pharmaceutically acceptable salt thereof in any one of the following steps: preparing a medicament for promoting lipid excretion of macrophages; Preparing a medicament for promoting spinal cord injury repair; preparing a medicament for inhibiting secondary inflammation mediated by lipid accumulati