Rosmarinic acid exerts an antagonistic effect on nonalcoholic fatty liver disease by regulating the YAP1/TAZ‐PPARγ/PGC‐1α signaling pathway

Abstract

Rosmarinic acid (RA) is a water‐soluble phenolic compound extracted from Boraginaceae and Lamiaceae. This study was designed to investigate the role and mechanism of action of RA in improving nonalcoholic fatty liver disease (NAFLD). Male SD rats maintained on a high fat diet and L02 cells stimulated with oleic acid were treated with RA. Our results showed that RA significantly reduced total cholesterol, triglycerides, low‐density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, and malondialdehyde levels and increased high‐density lipoprotein cholesterol, superoxide dismutase and adenosine triphosphate levels both in vivo and in vitro. Hematoxylin and eosin staining and oil red O staining showed that RA had a good lipid‐lowering effect and substantial protective effects on liver injury. Transmission electron microscopy and JC‐1 fluorescence results showed that RA could improve mitochondrial damage in hepatocytes. Additionally, flow cytometry results indicated that RA inhibited ROS generation and apoptosis in L02 cells. The impaired hepatocytes were restored by using RA in NAFLD models characterized by down‐regulating YAP1 and TAZ, meanwhile up‐regulating PPARγ and PGC‐1α. When YAP1 was over‐expressed, RA reduced the expression of YAP1; however, the action of RA was significantly blocked by silencing YAP1. The experimental results indicated that RA markedly alleviated NAFLD by repairing mitochondrial damage and regulating the YAP1/TAZ‐PPARγ/PGC‐1α signaling pathway.

Lemon Balm and Corn Silk Extracts Mitigate High-Fat Diet-Induced Obesity in Mice

“…In particular, intraperitoneal injection of allantoin can alleviate HFD-induced obesity and hyperlipidemia, and those effects are abolished by efaroxan pretreatment [ 36 , 42 ], which provides evidence that the activation of the imidazoline I 1 -receptor is associated with allantoin-mediated maintenance of lipid homeostasis. Although rosmarinic acid (10–200 mg/kg) and allantoin (5 mg/kg) have been reported to possess beneficial effects in mice fed an HFD [ 36 , 43 , 44 , 45 ], the effective concentrations of rosmarinic acid and allantoin administered directly into animals in the aforementioned references appears too high to be reached in vivo by administration of 200 mg/kg M-LB/CS in the present study. In addition, HPLC chromatogram after eluting LBE and CSE indicated that there were many peaks beyond rosmarinic acid and allantoin, and several phytochemicals contained in two herbs (e.g., ursolic acid, oleanolic acid, caffeic acid, luteolin, rutin, maysin, and α-terpineol) also have potential to alleviate obesity [ 46 , 47 , 48 , 49 , 50 , 51 , 52 ].…”

Rosmarinic Acid Exhibits a Lipid-Lowering Effect by Modulating the Expression of Reverse Cholesterol Transporters and Lipid Metabolism in High-Fat Diet-Fed Mice

“…AMPK activation inhibits lipid accumulation and de novo lipid synthesis by inactivating acetyl-CoA carboxylase (ACC) and stimulates fatty acid oxidation by upregulating CPT1 [20,62]. A previous report showed that rosmarinic acid prevented NAFLD by maintaining mitochondrial integrity [63]. Vasileva et al [64] claimed that rosmarinic acid inhibited adipogenic genes and proteins in human adipocytes.…”

Biomedical features and therapeutic potential of rosmarinic acid

“…In several reports, RA has acted as hepatoprotective agent through modulation of inflammatory cascades and oxidative imbalances (Luo et al 2021 ; Touiss et al 2021 ). RA has attenuated chromium-induced hepatorenal oxidative damage and the formation of preneoplastic lesions in rats through upregulation of the Nrf2 signaling pathway and antioxidant actions (Khalaf et al 2020 ).…”