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罗沙维醇通过靶向肝脏细胞死亡改善 NASH 大鼠模型的肝脏炎症和纤维化。

Rosavin Ameliorates Hepatic Inflammation and Fibrosis in the NASH Rat Model via Targeting Hepatic Cell Death.

机构信息

Department of Gastroenterology, Hepatology & Infectious Disease, Faculty of Medicine, Benha University, Benha 13518, Egypt.

Clinical Pharmacology Department, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt.

出版信息

Int J Mol Sci. 2022 Sep 5;23(17):10148. doi: 10.3390/ijms231710148.

Abstract

BACKGROUND

Non-alcoholic fatty liver disease (NAFLD) represents the most common form of chronic liver disease that urgently needs effective therapy. Rosavin, a major constituent of the Rhodiola Rosea plant of the family Crassulaceae, is believed to exhibit multiple pharmacological effects on diverse diseases. However, its effect on non-alcoholic steatohepatitis (NASH), the progressive form of NAFLD, and the underlying mechanisms are not fully illustrated.

AIM

Investigate the pharmacological activity and potential mechanism of rosavin treatment on NASH management via targeting hepatic cell death-related () mRNAs and their upstream noncoding RNA regulators ( and ) in NASH rats.

RESULTS

High sucrose high fat (HSHF) diet-induced NASH rats were treated with different concentrations of rosavin (10, 20, and 30 mg/kg/day) for the last four weeks of dietary manipulation. The data revealed that rosavin had the ability to modulate the expression of the hepatic cell death-related RNA panel through the upregulation of both () mRNAs and their epigenetic regulators ( and ). Moreover, rosavin ameliorated the deterioration in both liver functions and lipid profile, and thereby improved the hepatic inflammation, fibrosis, and apoptosis, as evidenced by the decreased protein levels of IL6, TNF-α, and caspase-3 in liver sections of treated animals compared to the untreated NASH rats.

CONCLUSION

Rosavin has demonstrated a potential ability to attenuate disease progression and inhibit hepatic cell death in the NASH animal model. The produced effect was correlated with upregulation of the hepatic cell death-related (, , , and ) mRNAs-(-() RNA panel.

摘要

背景

非酒精性脂肪性肝病(NAFLD)是最常见的慢性肝病形式,迫切需要有效的治疗方法。罗萨文是景天科植物红景天的主要成分之一,据信对多种疾病具有多种药理作用。然而,它对非酒精性脂肪性肝炎(NASH),即 NAFLD 的进行性形式,以及潜在机制尚未完全阐明。

目的

通过针对 NASH 大鼠中与肝细胞死亡相关的 mRNAs(和)及其上游非编码 RNA 调节剂(和),研究罗萨文治疗 NASH 的药理活性和潜在机制。

结果

用高蔗糖高脂肪(HSHF)饮食诱导 NASH 大鼠,在饮食干预的最后四周用不同浓度的罗萨文(10、20 和 30 mg/kg/天)进行治疗。数据表明,罗萨文能够通过上调()mRNA 及其表观遗传调节剂(和)来调节与肝细胞死亡相关的 RNA 谱的表达。此外,罗萨文改善了肝功能和脂质谱的恶化,并通过降低肝组织中 IL6、TNF-α 和 caspase-3 的蛋白水平改善了肝炎症、纤维化和细胞凋亡,与未治疗的 NASH 大鼠相比,治疗动物的肝组织中。

结论

罗萨文已显示出在 NASH 动物模型中减轻疾病进展和抑制肝细胞死亡的潜在能力。所产生的效果与上调与肝细胞死亡相关的(、、、和)mRNA-(-()RNA 谱相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5e0/9456245/6640ed9be451/ijms-23-10148-g001.jpg

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