16-Dehydropregnenolone lowers serum cholesterol by up-regulation of CYP7A1 in hyperlipidemic male hamsters

Ramakrishna, Rachumallu; Kumar, Durgesh; Bhateria, Manisha; Gaikwad, Anil Nilkanth; Bhatta, Rabi Sankar

doi:10.1016/j.jsbmb.2017.02.013

Cited by 13 publications

(7 citation statements)

References 41 publications

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“…As reported, phosphorylated AMPK attenuates the proteolytic processing of SREBP-2, inhibiting HMGCR expression to reduce lipid accumulation in the liver [25]. So, some studies showed some bioactive component and some Chinese medicines could downregulate CYP7A1 expression to decrease cholesterol [26,27].…”

Section: Discussionmentioning

confidence: 91%

The Potential Mechanism of Wuwei Qingzhuo San against Hyperlipidemia Based on TCM Network Pharmacology and Validation Experiments in Hyperlipidemia Hamster

Wang

Song

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Wuwei Qingzuo San (WWQZS), as a renowned traditional Mongolian patent medicine approved by Chinese State Food and Drug Administration, is used to treat hyperlipidemia, indigestion, and other ailments related to disorder of production of essence and phlegm, a typical abnormal metabolism of blood in traditional Mongolian medicine. A combination of network pharmacology and validation experiments in hyperlipidemia hamster is used to understand the potential mechanism of WWQZS for hypolipidemic effects, further for an integrated concept of traditional theory, bioactive constituents, and molecular mechanism for TMM. Through network pharmacology, we obtained 212 components, 219 predicted targets, and 349 known hyperlipidemia-related targets form public database and used Metascape to carry out enrichment analysis of 43 potential and 45 candidate targets to imply numerous BP concerned with metabolism of lipid, regulation of kinases and MF related to lipid binding, phosphatase binding, and receptor ligand activity that are involved in anti-hyperlipidemia. In addition, KEGG pathways that explicated hypolipidemic effect were involved in pathways including metabolism associated with kinase function according to MAPK signaling pathway, AMPK signaling pathway, and PI3K-Akt signaling pathway. Meanwhile, in HFD-induced hamster model, WWQZS could significantly reduce TC and ALT and help decrease TG, LDL-C as well; liver pathological section implied that WWQZS could relieve liver damage and lipid accumulation. Western blot indicated that WWQZS may upregulate CYP7A1 and activate AMPK to suppress the expression of HMGCR in livers. In conclusion, our results suggest that WWQSZS plays important dual hypolipidemic and liver-protective role in livers in HFD-induced hamster model. Through this research, a new reference is also provided to other researches in the study of ethnopharmacology.

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Section: Discussionmentioning

confidence: 91%

The Potential Mechanism of Wuwei Qingzhuo San against Hyperlipidemia Based on TCM Network Pharmacology and Validation Experiments in Hyperlipidemia Hamster

Wang

Song

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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“…Its main function is to maintain the balance of the cholesterol metabolism and is easily affected by food, drugs, and other factors [42]. Ramakrishna et al found that 16-dehydropregnenolone (DHP) profoundly decreased the serum TC and TG levels and the hypolipidemic activity of DHP by upregulating the hepatic CYP7A1 pathway that promotes cholesterol-to-bile acid conversion and bile acid excretion [43].…”

Section: Discussionmentioning

confidence: 99%

Analysis of Serum Biochemical Indexes, Egg Quality, and Liver Transcriptome in Laying Hens Fed Diets Supplemented with Gynostemma pentaphyllum Powder

Zhang

et al. 2021

Genes

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Gynostemma pentaphyllum (GP), known as “southern ginseng”, can reduce the blood pressure and blood lipid levels. In this study, 300 layer chicks of one day old were divided randomly into three groups (control group (base diet), high addition group (base diet with 1% GP), and low addition group (base diet with 0.5% GP)). After 29 weeks, the growth performance, egg quality, and serum index were determined. Additionally, liver mRNA was identified using RNA-seq to investigate the molecular mechanisms. The results indicated that the serum total cholesterol and triglycerides decreased significantly in the GP addition group. The addition of GP increased the egg weight, Haugh unit and redness (a*) of the egg yolk color, and reduced the yolk cholesterol concentration. Moreover, 95 differentially expressed genes (DEGs) were screened between the control and GP addition group. GO and the KEGG analysis showed that the PPAR pathway was significantly enriched. Five fatty acid metabolism-related genes (FABP3, CYP7A1, ANKRD22, SCD1, and PCK1) were validated by qRT-PCR analysis, which confirmed the tendency of the expression. These DEGs in the PPAR pathway may be the key factors of GP affecting fatty acid metabolism. These results may provide a theoretical basis for further research and new insights into GP as a feed additive.

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“…Salvianolic acid B and tanshinone II-A could attenuate atherosclerotic lesions by reducing vascular oxidative stress or regulating lipid metabolism (Xu et al, 2011;Zhang et al, 2011;Yue et al, 2015). Moreover, for PPAR signaling pathway and nuclear receptors in lipid metabolism and toxicity pathway, PPARa plays a role in scavenging circulating or cellular lipids by forming heterodimers with retinoid X receptor and regulating the expressions of genes involved in lipid metabolism such as biosynthesis of bile acids, cholesterol efflux, and so on (Ogata et al, 2009;Filip-Ciubotaru et al, 2011;Ramakrishna et al, 2017). In SREBP control of lipid synthesis pathway, SREBPs could bind to the LDL receptor promoter to enhance the expression of LDLR on cell surface to promote the internalization of plasma LDL (Ochiai et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…CYP7A1, the rate-limiting enzyme in the classical bile acid biosynthetic pathway, catalyzing about 2/5 synthesized cholesterol transformed into bile acids, has a critical function in keeping homeostasis of cholesterol (Li et al, 2011;Cao et al, 2012). It is reported that PPARa and LXRa mediate feedforward induction of CYP7A1, contributing to the clearance of excess cholesterol by increasing the formation of bile acids (Beaven and Tontonoz, 2006;Singh et al, 2013;Ramakrishna et al, 2017). In this study, DHG-H treatment significantly increased the mRNA and protein expressions of PPARa, LXRa, and CYP7A1, and enhanced the fecal TC and TBA levels in hyperlipidemic hamsters.…”

Section: Discussionmentioning

confidence: 99%

“…SREBP-2 (SREBF-2) and its related gene LDLR involved in cholesterol uptake (Kartawijaya et al, 2016). The target PPARa and its related genes LXRa, CYP7A1, and ABCA1 played a regulatory role in the process in the transformation of cholesterol into bile acids and cholesterol efflux (Wang et al, 2001;Basso et al, 2003;Cao et al, 2012;Ramakrishna et al, 2017). Taken together, these results indicated that the lipid-lowering mechanism of DHG may be that the 6 active components (quercetin, (Beaven and Tontonoz, 2006) emodin, salvianolic acid B, etc.)…”

Section: C-t-p Networkmentioning

confidence: 96%

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Investigation of the Lipid-Lowering Mechanisms and Active Ingredients of Danhe Granule on Hyperlipidemia Based on Systems Pharmacology

Chen

Yan

et al. 2020

Front. Pharmacol.

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Objective: Investigate the active ingredients and underlying hypolipidemic mechanisms of Danhe granule (DHG). Methods: The lipid-lowering effect of DHG was evaluated in hyperlipidemic hamsters induced by a high-fat diet. The ingredients absorbed into the blood after oral administration of DHG in hamsters were identified by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). A systems pharmacology approach incorporating target prediction and network construction, gene ontology (GO) enrichment and pathway analysis was performed to predict the active compounds and map the compounds-targets-disease network. Real-time polymerase chain reaction (RT-PCR) and Western blot were utilized to analyze the mRNA and protein expression levels of predicted targets. Results: DHG remarkably lowered the levels of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and arteriosclerosis index (AI), at the same time, elevated the levels of serum high-density lipoprotein cholesterol (HDL-c) and HDL-c/TC ratio in hyperlipidemic hamsters. Sixteen ingredients absorbed into blood after oral administration of DHG were identified as the possible components interacted with targets. Moreover, 65 potential targets were predicted after targets intersection and compounds-targets-disease network mapping. Then, compounds-targets-pathways network mapping revealed that six active compounds (emodin, naringenin, etc.) compounds could interact with 10 targets such as sterol regulatory element binding protein (SREBP) 1c, SREBP-2 and peroxisome proliferation-activated receptor (PPAR) a, regulate three lipid metabolism-related pathways including SREBP control of lipid synthesis pathway, PPAR signaling pathway and nuclear receptors in lipid metabolism and toxicity pathway, and further affect lipid metabolic processes including fatty acid biosynthesis, low-density lipoprotein receptor (LDLR)-mediated cholesterol uptake, bile acid biosynthesis, and cholesterol efflux. Experimental results indicated that DHG significantly increased SREBP-2, LDLR, PPARa, liver X receptor alpha (LXRa),

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16-Dehydropregnenolone lowers serum cholesterol by up-regulation of CYP7A1 in hyperlipidemic male hamsters

Cited by 13 publications

References 41 publications

The Potential Mechanism of Wuwei Qingzhuo San against Hyperlipidemia Based on TCM Network Pharmacology and Validation Experiments in Hyperlipidemia Hamster

The Potential Mechanism of Wuwei Qingzhuo San against Hyperlipidemia Based on TCM Network Pharmacology and Validation Experiments in Hyperlipidemia Hamster

Analysis of Serum Biochemical Indexes, Egg Quality, and Liver Transcriptome in Laying Hens Fed Diets Supplemented with Gynostemma pentaphyllum Powder

Investigation of the Lipid-Lowering Mechanisms and Active Ingredients of Danhe Granule on Hyperlipidemia Based on Systems Pharmacology

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