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基于代谢和炎症标志物评估 durva swaras(Cynodon dactylon L. Pers.)给药对 APAP 诱导的小鼠肝损伤模型的药理作用。

Pharmacological benefits of durva swaras (Cynodon dactylon L. Pers.) administration in APAP-induced liver injury model of mice - Assessment by metabolic and inflammatory markers.

机构信息

Division of Drug and Food Safety, ICMR-National Institute of Nutrition, Tarnaka, Jamai-Osmania, Hyderabad, Telangana, India.

Senior Scientist, Department of Innovation and R&D, Sarvotham Care Limited, Secunderabad, Telangana, India.

出版信息

Indian J Pharmacol. 2024 Jul 1;56(4):260-267. doi: 10.4103/ijp.ijp_133_24. Epub 2024 Sep 10.

Abstract

OBJECTIVE

Liver derangement underlies the development of metabolic syndrome in perimenopause. Previously, we have observed that durva swaras (DS) improved metabolic-associated fatty liver disease (MAFLD) and abnormal liver enzymes (aspartate aminotransferase and alanine aminotransferase) along with other complications of menopause in ovariectomized rats. We aimed to decipher the hepatoprotective mechanisms of DS in acetaminophen (APAP)-induced liver injury model, which is analogous to the pathophysiology of MAFLD.

MATERIALS AND METHODS

Male Swiss albino mice were distributed into three groups at random. Group I (Control) was administered with vehicle (distilled water) for 7 days. Group II (APAP) received vehicle for the first 6 days and APAP (350 mg/kg - single dose) on the 7th day. Group III (APAP + D) received test compound DS (quality complied) at a dose of 133 mg/kg for 6 days and APAP (350 mg/kg - single dose) on the 7th day. Subsequently, blood and liver tissues were subjected to biochemical, ultrastructural, and gene expression analysis.

RESULTS

DS pretreatment protected the liver from APAP-induced disruption of sinusoids and necrosis. DS prevented the elevation of liver enzymes - AST and ALT induced by APAP. Importantly, DS inhibited the APAP-elicited increase in messenger ribonucleic acid levels of hepatic nuclear factor-kappa beta (NF-κB) and pro-inflammatory cytokines, namely interleukin-1 beta, interleukin 6, and tumor necrosis factor-alpha. Moreover, DS activated gene expression of nuclear factor erythroid 2-related factor 2 and liver-X-receptor-alpha (LXR-α) to combat the liver damage.

CONCLUSION

DS hinders APAP-induced liver damage by activating LXR-α and inhibiting the NF-κB-associated pro-inflammatory cytokine gene expression. These observations confirm the protective role of DS in metabolic dysfunction-associated liver conditions.

摘要

目的

绝经前期,肝功能紊乱是代谢综合征发展的基础。此前,我们观察到 durva swaras(DS)可改善去卵巢大鼠的代谢相关脂肪性肝病(MAFLD)和异常肝酶(天冬氨酸氨基转移酶和丙氨酸氨基转移酶)以及其他更年期并发症。我们旨在破译 DS 在对乙酰氨基酚(APAP)诱导的肝损伤模型中的肝保护机制,该模型类似于 MAFLD 的病理生理学。

材料和方法

雄性瑞士白化病小鼠随机分为三组。第 I 组(对照组)给予载体(蒸馏水)7 天。第 II 组(APAP)在第 1 天至第 6 天给予载体,第 7 天给予 APAP(350mg/kg - 单次剂量)。第 III 组(APAP+D)给予试验化合物 DS(质量符合),剂量为 133mg/kg,连续 6 天,第 7 天给予 APAP(350mg/kg - 单次剂量)。随后对血液和肝脏组织进行生化、超微结构和基因表达分析。

结果

DS 预处理可保护肝脏免受 APAP 诱导的窦状隙破坏和坏死。DS 可防止 APAP 引起的肝酶 - 天冬氨酸氨基转移酶和丙氨酸氨基转移酶升高。重要的是,DS 抑制了 APAP 诱导的肝核因子-kappa beta(NF-κB)和促炎细胞因子,即白细胞介素-1β、白细胞介素 6 和肿瘤坏死因子-α mRNA 水平的升高。此外,DS 激活核因子红细胞 2 相关因子 2 和肝 X 受体-α(LXR-α)的基因表达,以对抗肝损伤。

结论

DS 通过激活 LXR-α和抑制 NF-κB 相关促炎细胞因子基因表达,阻止 APAP 诱导的肝损伤。这些观察结果证实了 DS 在代谢功能障碍相关肝脏疾病中的保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f84/11483052/a8dc1f03da06/IJPharm-56-260-g001.jpg

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