Diosgenin alleviates hypercholesterolemia via SRB1/CES-1/CYP7A1/FXR pathway in high-fat diet-fed rats

Yu, Lu; Lu, Haifei; Yang, Xiufen; Li, Ruoqi; Shi, Juanjuan; Yu, Yantong; Ma, Chaoqun; Sun, Fengcui; Zhang, Shizhao; Zhang, Fengxia

doi:10.1016/j.taap.2020.115388

Cited by 27 publications

(18 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Excess cholesterol caused several diseases including atherosclerosis ( Hall, 2016 ), infertility ( Mahdavi et al., 2021 ) and toxicity in different organs as the liver ( Yu et al., 2021 ), thyroid gland ( Rasekh et al., 2021 ) and kidney ( Kaur et al., 2021 ). Zălar et al.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Histological, ultrastructural and immunohistochemical studies on the ameliorative role of Cinnamon zeylanicum against high cholesterol diet-induced hypercholesterolemia in the kidney of adult male albino rats

Arisha

Saif

Kandil

2022

Heliyon

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

RETRACTED: Histological, ultrastructural and immunohistochemical studies on the ameliorative role of Cinnamon zeylanicum against high cholesterol diet-induced hypercholesterolemia in the kidney of adult male albino rats

Arisha

Saif

Kandil

2022

Heliyon

View full text Add to dashboard Cite

“…BAs, specifically hydrophobic BAs, act as ligands for FXR and utilize it in their negative feedback loop. 48 In an in vivo experiment, Yu et al 49 demonstrated that diosgenin (150 or 300 mg/kg/d) can reduce body weight and blood lipid levels of rats fed a HFD, and significantly improve liver steatosis and intestinal structure. Further, diosgenin can increase the expression of SRB1, CES-1, and CYP7A1 in rat liver and inhibit FXR-mediated signal transduction, as well as increasing SRB1 and CES-1 expression in rat intestine, inhibiting cholesterol absorption, and promoting RCT.…”

Section: The Pharmacological Mechanism Underlying the Use Of Diosgenin For Treatment Of Hyperlipidemiamentioning

confidence: 99%

Section: Regulation Of Cholesterol Transportmentioning

confidence: 99%

The Effects of Diosgenin on Hypolipidemia and Its Underlying Mechanism: A Review

Sun

Yang

et al. 2021

DMSO

Self Cite

View full text Add to dashboard Cite

Hyperlipidemia is a disorder of lipid metabolism, which is a major cause of coronary heart disease. Although there has been considerable progress in hyperlipidemia treatment, morbidity and risk associated with the condition continue to rise. The first-line treatment for hyperlipidemia, statins, has multiple side effects; therefore, development of safe and effective drugs from natural products to prevent and treat hyperlipidemia is necessary. Diosgenin is primarily derived from fenugreek ( Trigonella foenum graecum ) seeds, and is also abundant in medicinal herbs such as Dioscorea rhizome, Dioscorea septemloba , and Rhizoma polygonati , is a well-known steroidal sapogenin and the active ingredient in many drugs to treat cardiovascular conditions. There is abundant evidence that diosgenin has potential for application in correcting lipid metabolism disorders. In this review, we evaluated the latest evidence related to diosgenin and hyperlipidemia from clinical and animal studies. Additionally, we elaborate the pharmacological mechanism underlying the activity of diosgenin in treating hyperlipidemia in detail, including its role in inhibition of intestinal absorption of lipids, regulation of cholesterol transport, promotion of cholesterol conversion into bile acid and its excretion, inhibition of endogenous lipid biosynthesis, antioxidation and lipoprotein lipase activity, and regulation of transcription factors related to lipid metabolism. This review provides a deep exploration of the pharmacological mechanisms involved in diosgenin-hyperlipidemia interactions and suggests potential routes for the development of novel drug therapies for hyperlipidemia.

show abstract

“…Recent evidence has been proved that FXR is a bile acid sensor, which could control series of molecules involved in BA transport, such as Bsep, Mrps, and Ntcp. Furthermore, FXR activation increases the detoxification of bile acid by increasing Sult2a1 as well as indirectly inhibiting the synthesis of bile acid through Cyp7a1 or Cyp8b1 ( Xu et al, 2003 ; Pathak et al, 2017 ; Al-Aqil et al, 2018 ; Chambers et al, 2019 ; Yu et al, 2021 ). Similar to previous studies, we found that the ANIT significantly inhibited the FXR and its target genes, including Ntcp, Bsep, Cyp8b1, and Ugt1a1 ( Jahan and Chiang, 2005 ; Bertaggia et al, 2017 ; Petrov et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Arbutin Alleviates the Liver Injury of α-Naphthylisothiocyanate-induced Cholestasis Through Farnesoid X Receptor Activation

Liao

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Cholestasis is a kind of stressful syndrome along with liver toxicity, which has been demonstrated to be related to fibrosis, cirrhosis, even cholangiocellular or hepatocellular carcinomas. Cholestasis usually caused by the dysregulated metabolism of bile acids that possess high cellular toxicity and synthesized by cholesterol in the liver to undergo enterohepatic circulation. In cholestasis, the accumulation of bile acids in the liver causes biliary and hepatocyte injury, oxidative stress, and inflammation. The farnesoid X receptor (FXR) is regarded as a bile acid–activated receptor that regulates a network of genes involved in bile acid metabolism, providing a new therapeutic target to treat cholestatic diseases. Arbutin is a glycosylated hydroquinone isolated from medicinal plants in the genus Arctostaphylos, which has a variety of potentially pharmacological properties, such as anti-inflammatory, antihyperlipidemic, antiviral, antihyperglycemic, and antioxidant activity. However, the mechanistic contributions of arbutin to alleviate liver injury of cholestasis, especially its role on bile acid homeostasis via nuclear receptors, have not been fully elucidated. In this study, we demonstrate that arbutin has a protective effect on α-naphthylisothiocyanate–induced cholestasis via upregulation of the levels of FXR and downstream enzymes associated with bile acid homeostasis such as Bsep, Ntcp, and Sult2a1, as well as Ugt1a1. Furthermore, the regulation of these functional proteins related to bile acid homeostasis by arbutin could be alleviated by FXR silencing in L-02 cells. In conclusion, a protective effect could be supported by arbutin to alleviate ANIT-induced cholestatic liver toxicity, which was partly through the FXR pathway, suggesting arbutin may be a potential chemical molecule for the cholestatic disease.

show abstract

Diosgenin alleviates hypercholesterolemia via SRB1/CES-1/CYP7A1/FXR pathway in high-fat diet-fed rats

Cited by 27 publications

References 52 publications

RETRACTED: Histological, ultrastructural and immunohistochemical studies on the ameliorative role of Cinnamon zeylanicum against high cholesterol diet-induced hypercholesterolemia in the kidney of adult male albino rats

RETRACTED: Histological, ultrastructural and immunohistochemical studies on the ameliorative role of Cinnamon zeylanicum against high cholesterol diet-induced hypercholesterolemia in the kidney of adult male albino rats

The Effects of Diosgenin on Hypolipidemia and Its Underlying Mechanism: A Review

Arbutin Alleviates the Liver Injury of α-Naphthylisothiocyanate-induced Cholestasis Through Farnesoid X Receptor Activation

Contact Info

Product

Resources

About