CN-121987615-A - Application of SIRT1 activator dihydromyricetin in preparation of medicine for treating acute liver injury

CN121987615ACN 121987615 ACN121987615 ACN 121987615ACN-121987615-A

Abstract

The invention discloses an application of SIRT1 activator dihydromyricetin in preparing a medicament for treating acute liver injury. The invention demonstrates for the first time that dihydromyricetin is an effective liver protectant, and relieves acute liver injury by an unrecognized mechanism dependent on acetylation. DMY reduces ALI by reducing oxidative stress and inhibiting inflammatory responses. Mechanically, DMY restores expression of the deacetylase SIRT1 in liver macrophages, SIRT1 interacting directly with PRDX1 and deacetylating it at the lysine 35 site. This deacetylation event re-activates the antioxidant function of PRDX1, inhibits the production of pro-inflammatory cytokines, and inhibits M1 type macrophage polarization, thus remodelling the inflammatory microenvironment during ALI. The protective effect of DMY was reproduced by gene restoration of SIRT1, establishing the SIRT1-PRDX1 axis as the core mediator of its action.

Inventors

SHI MIN
WANG CHEN
YU HEGUO
HU HONG
CHEN MENGYAN
CHEN ZIKE
ZHAO JIAWEI
XU LING
WANG YUGANG

Assignees

上海市同仁医院

Dates

Publication Date: 20260508
Application Date: 20260211

Claims (6)

Application of SIRT1 activator dihydromyricetin in preparing medicine for treating acute liver injury is provided.
2. The use of claim 1, wherein the treatment of acute liver injury with dihydromyricetin is achieved by up-regulating the expression or activity of SIRT1 in liver macrophages.
3. The use of claim 2, wherein upregulation of SIRT1 promotes deacetylation of target protein PRDX 1.
4. The use according to claim 1, wherein the medicament further comprises pharmaceutically acceptable excipients.
5. The use according to claim 4, wherein the formulation of the medicament is an oral formulation.
6. The use according to claim 5, wherein the oral formulation is a tablet, capsule, pill or oral liquid.

Description

Application of SIRT1 activator dihydromyricetin in preparation of medicine for treating acute liver injury Technical Field The invention relates to the technical field of biological medicines, in particular to application of SIRT1 activator dihydromyricetin in preparation of a medicine for treating acute liver injury. Background Acute liver injury is a serious clinical pathological condition characterized by excessive inflammatory response and oxidative stress in the liver, and currently there is no highly effective therapeutic strategy. Dihydromyricetin is a natural flavonoid extracted from Ampelopsis grossedentata. Studies have shown that it exhibits antioxidant, anti-inflammatory and liver protective activities in a variety of liver disease models, suggesting its prospect as a potential therapeutic drug for liver injury. However, whether dihydromyricetin is capable of ameliorating acute liver injury, and in particular the precise molecular mechanism by which it acts, has not yet been fully elucidated. Recent studies have found that the pharmacological actions of many natural products are closely related to the post-translational modification of regulatory proteins. Among them, lysine acetylation, as a dynamic and reversible modification, plays a central role in regulating the activation, polarization and inflammatory response of immune cells (especially macrophages). Reprogramming Cheng Mianyi microenvironment by modulating the acetylation status of key proteins has become a potential new strategy for the treatment of inflammatory diseases including liver injury. The protein acetylation level is regulated by both acetyltransferase and deacetylase. Sirtuin family proteins are a class of nad+ dependent deacetylases, where SIRT1 is widely found in the nucleus and cytoplasm, and its deacetylase activity is critical for maintaining intracellular homeostasis, regulating inflammatory pathways. Although the role of SIRT1 in metabolic and aging related diseases has been widely studied, it is currently unclear whether and how it exerts anti-inflammatory effects through deacetylation of specific targets during acute liver injury. Therefore, whether the dihydromyricetin relieves the acute liver injury by regulating and controlling a SIRT1 mediated protein deacetylation pathway has important significance for revealing a novel action mechanism and developing a novel therapeutic target. Disclosure of Invention The invention aims at overcoming the defects in the prior art and provides application of SIRT1 activator dihydromyricetin in preparation of a medicament for treating acute liver injury. In order to achieve the above purpose, the technical scheme adopted by the invention is as follows: provides an application of SIRT1 activator dihydromyricetin in preparing a medicament for treating acute liver injury. Further, the treatment of acute liver injury with dihydromyricetin is achieved by up-regulating the expression or activity of SIRT1 in liver macrophages. Still further, upregulation of SIRT1 facilitates deacetylation of target protein PRDX 1. Further, the medicament also comprises pharmaceutically acceptable auxiliary materials. Further, the preparation of the medicament is an oral preparation. Further, the oral preparation is a tablet, a capsule, a pill or an oral liquid. Compared with the prior art, the invention has the following technical effects: The present invention demonstrates for the first time that Dihydromyricetin (DMY) is an effective liver protectant that alleviates Acute Liver Injury (ALI) by an unrecognized acetylation-dependent mechanism. DMY reduces ALI by reducing oxidative stress and inhibiting inflammatory responses. Mechanically, DMY restores expression of the deacetylase SIRT1 in liver macrophages, SIRT1 interacting directly with PRDX1 and deacetylating it at the lysine 35 (K35) site. This deacetylation event re-activates the antioxidant function of PRDX1, inhibits the production of pro-inflammatory cytokines, and inhibits M1 type macrophage polarization, thus remodelling the inflammatory microenvironment during ALI. The protective effect of DMY was reproduced by gene restoration of SIRT1, establishing the SIRT1-PRDX1 axis as the core mediator of its action. Taken together, these findings indicate that SIRT 1-mediated PRDX1 deacetylation is the core mechanism of DMY-induced liver protection and locates DMY as a promising therapeutic agent for ALI. Drawings FIG. 1 shows the improvement of DMY-induced hepatotoxicity and liver inflammation, where a is the experimental design, C57BL/6 mice were subjected to DgalN and LPS treatment to induce Acute Liver Injury (ALI) and compared under different doses of DMY pretreatment, liver samples were collected after 6 hours, b is the change of survival rate of mice over time (n=10 mice per group), C is DgalN/LPS-induced, serum ALT and AST levels of mice were subjected to different doses of DMY pretreatment (n=5 mice per group), d is representative H & E stai