CN-122005545-A - Application of dehydrocostuslactone and medicine for treating steatohepatitis

Abstract

The application of dehydrocostuslactone and a medicine for treating steatohepatitis relate to the technical field of biological medicine, and solve the problems that the application of dehydrocostuslactone in the prior art is limited in scene and the application of dehydrocostuslactone in complex pathological environment of steatohepatitis related to metabolic dysfunction is technically blank. Dehydrocostuslactone can reduce lipid accumulation, inflammation and fibrosis in liver cells, reduce body weight, liver weight, serum triglyceride content, serum total cholesterol content and insulin resistance level of animals with steatohepatitis, reduce serum glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, tumor necrosis factor alpha, interleukin 1 beta, malondialdehyde, ferrous ion content and improve serum glutathione content, regulate lipid metabolism and mitochondrial energy metabolism pathway, and reprogram energy metabolism phenotype of steatohepatitis liver cells, and can be used for preparing medicine for treating steatohepatitis, iron death inhibitor, glutamic-oxaloacetic transaminase and/or glutamic-pyruvic transaminase inhibitor.

Inventors

• Yin Xunzhe
• YE ZHIKAI
• WANG JIN

Assignees

• 国科温州研究院(温州生物材料与工程研究所)

Dates

Publication Date

20260512

Application Date

20260413

Claims (4)

1. 1. The application of dehydrocostuslactone is characterized in that the dehydrocostuslactone is applied to preparing a medicine for treating steatohepatitis, and the structural formula of the dehydrocostuslactone is shown as formula I: A formula I; The fatty hepatitis is fatty hepatitis related to metabolic dysfunction caused by high-fat high-cholesterol high-fructose diet.
2. 2. The use of dehydrocostuslactone according to claim 1, characterized in that the medicament for treating steatohepatitis is an iron death inhibitor or a glutamate oxaloacetate and/or glutamate pyruvate transaminase inhibitor.
3. 3. The medicament for treating steatohepatitis according to claim 1, which is prepared from dehydrocostuslactone and comprises dehydrocostuslactone and pharmaceutically acceptable auxiliary materials.
4. 4. The drug for treating steatohepatitis according to claim 3, wherein the pharmaceutical dosage form of the drug for treating steatohepatitis comprises any one of injection, tablet, powder, suspension, capsule, pill or syrup.

Description

Application of dehydrocostuslactone and medicine for treating steatohepatitis Technical Field The invention relates to the technical field of biological medicines, in particular to application of dehydrocostuslactone and a medicine for treating steatohepatitis. Background Inflammatory subtype of metabolic dysfunction-related fatty liver disease (Metabolic dysfunction-associated steatotic LIVER DISEASE, MASLD) -metabolic dysfunction-related steatohepatitis (Metabolic dysfunction-associated steatohepatitis, MASH), clinically manifested as liver steatosis, lesions and inflammation in non-alcoholism people, often accompanied by different degrees of liver fibrosis, and some patients may progress to cirrhosis. Along with the continuous prevalence of metabolic diseases such as obesity and type 2 diabetes mellitus, MASLD has become the most prominent chronic progressive liver disease worldwide, and is particularly prominent in China. MASLD is different from malignant liver diseases such as liver cancer which take abnormal cell proliferation as a core, and the nature of the malignant liver diseases belongs to chronic inflammatory liver injury driven by metabolic disorder, and the malignant liver disease is mainly caused by lipid deposition, insulin resistance and oxidative stress unbalance. In terms of therapeutic concept, liver cancer focuses on tumor cell clearance and proliferation inhibition, while MASH emphasizes metabolic remodeling, inflammatory control and reversible regulation of cell damage, and needs to delay disease progression and promote liver function recovery by intervening lipid metabolic homeostasis, oxidative stress pathways and programmed cell death processes. MASH is in bidirectional promotion relation with diseases such as metabolic syndrome and can accelerate complications such as atherosclerosis, chronic kidney disease, liver function decompensation, hepatocellular carcinoma and the like, and MASH becomes an increasingly serious public health challenge facing China currently or in the future. Iron death is an iron-dependent cell death mode and is characterized in that iron overload in cells causes abnormal accumulation of active oxygen and cascade amplification of lipid peroxidation, and simultaneously, glutathione depletion and loss of GPX4 activity are accompanied, so that cell membrane rupture and death are finally caused. Studies have shown that iron death plays a key role in the development and progression of MASH, and MASH patients are often accompanied by imbalance in liver iron homeostasis and elevated oxidative stress, thereby exacerbating insulin resistance and metabolic disorders. Given the central role of the liver in iron homeostasis and lipid metabolism, targeted inhibition of iron death is considered a potential therapeutic strategy for MASH. However, currently, intervention approaches to the iron death pathway are still limited, and development of therapeutic strategies with both safety and effectiveness is highly desirable to meet clinical demands for MASH that have not yet been met. Dehydrocostuslactone (Dehydrocostus lactone, dehy) is a natural sesquiterpene lactone compound extracted from traditional Chinese medicine radix aucklandiae. Studies have demonstrated that this compound has a wide range of biological activities, including antiulcer, anti-inflammatory, anti-tumor, antioxidant, immunomodulating, and smooth muscle relaxing and spasmolytic effects. In terms of chemical structure, the compound has good stability and can maintain the active conformation and function under different physiological environments. At the same time, its moderately liposoluble character helps to penetrate the cell membrane barrier, thereby more effectively delivering to the intracellular action target, exerting the desired biological activity. The prior researches focus on the iron-promoting death effect of dehydrocostuslactone in the treatment of tumors (such as liver cancer), and are mainly based on a single application path of inducing tumor cell damage by regulating and controlling oxidative stress pathways. However, the above research has not systematically revealed the mechanism of action of dehydrocostuslactone in non-neoplastic chronic liver disease, and in particular lacks clear knowledge of the direction of iron death regulation in the coexistence of inflammation and metabolic disorders, which makes the biological effect of the compound exhibit obvious disease situation dependence, thereby limiting its application potential in the field of metabolism-related liver injury. In addition, the application research of the existing dehydrocostuslactone in non-tumor chronic liver diseases is still mainly limited to an in-vitro adipose-modified cell model, only the local improvement effect of the dehydrocostuslactone on lipid accumulation and oxidative stress is shown, and a whole disease model capable of reflecting complex pathological environments of inflammatory reaction, metabolic state