Berberine inhibits dyslipidemia in C57BL/6 mice with lipopolysaccharide induced inflammation

Xiao, Hong-Bo; Sun, Zhi-Liang; Zhang, Hengbo; Zhang, Dasheng

doi:10.1016/s1734-1140(12)70883-6

Cited by 70 publications

(45 citation statements)

References 31 publications

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“…To determine whether the LDLR was similarly causal for LPS clearance effects, we used pharmacological inhibition of PCSK9 in Ldlr knockout (Ldlr −/− ) mice and compared them with genetic background control mice. Indeed, pretreatment with berberine (34, 35) for 72 hours inhibited hepatic PCSK9 mRNA expression by 65 ± 20% ( P < 0.05). In the background control mice, we confirmed that pharmacological inhibition of PCSK9 using berberine blunted the effect of LPS injection on the activity index ( P = 0.007) and body temperature ( P = 0.046) (table S1).…”

Section: Resultsmentioning

confidence: 97%

PCSK9 is a critical regulator of the innate immune response and septic shock outcome

et al. 2014

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A decrease in the activity of proprotein convertase subtilisin/kexin type 9 (PCSK9) increases the amount of lowdensity lipoprotein (LDL) receptors on liver cells and, therefore, LDL clearance. The clearance of lipids from pathogens is related to endogenous lipid clearance; thus, PCSK9 may also regulate removal of pathogen lipids such as lipopolysaccharide (LPS). Compared to controls, Pcsk9 knockout mice displayed decreases in inflammatory cytokine production and in other physiological responses to LPS. In human liver cells, PCSK9 inhibited LPS uptake, a necessary step in systemic clearance and detoxification. Pharmacological inhibition of PCSK9 improved survival and inflammation in murine polymicrobial peritonitis. Human PCSK9 loss-of-function genetic variants were associated with improved survival in septic shock patients and a decrease in inflammatory cytokine response both in septic shock patients and in healthy volunteers after LPS administration. The PCSK9 effect was abrogated in LDL receptor (LDLR) knockout mice and in humans who are homozygous for an LDLR variant that is resistant to PCSK9. Together, our results show that reduced PCSK9 function is associated with increased pathogen lipid clearance via the LDLR, a decreased inflammatory response, and improved septic shock outcome.

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Section: Resultsmentioning

confidence: 97%

PCSK9 is a critical regulator of the innate immune response and septic shock outcome

et al. 2014

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“…For instance, LPS-binding protein is an acute-phase protein that catalyzes the transfer of LPS into lipoproteins, and is predominantly associated with VLDL and LDL fractions in healthy humans [49]. LPS-induced inflammation in mice increased PCSK9 secretion [50] and this effect was inhibited by berberine, implicating HNF1α-mediated transcriptional regulation [51]. Hepatic LDLRs also function in a process termed reverse cholesterol transport (RCT), in which excess cholesterol from peripheral tissues is exported to preβ-HDL acceptors and transported through the plasma compartment back to the liver for eventual intestinal excretion [52,53].…”

Section: Potential Roles Of Pcsk9 In Reverse Cholesterol Transport Anmentioning

confidence: 99%

PCSK9 and LDLR degradation

Lagace

2014

Current Opinion in Lipidology

253

107

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Purpose of reviewProprotein convertase subtilisin/kexin type-9 (PCSK9) binds to LDL receptor (LDLR) and targets it for lysosomal degradation in cells. Decreased hepatic clearance of plasma LDL-cholesterol is the primary gauge of PCSK9 activity in humans; however, PCSK9's evolutionary role may extend to other lipoprotein classes and processes. This review highlights studies that are providing novel insights into physiological regulation of PCSK9 transcription and plasma PCSK9 activity.Recent findingsRecent studies indicate that circulating PCSK9 binds to apolipoprotein B100 on LDL particles, which in turn inhibits PCSK9's ability to bind to cell surface LDLRs. Negative feedback of secreted PCSK9 activity by LDL could serve to increase plasma excursion of triglyceride-rich lipoproteins and monitor lipoprotein remodeling. Recent findings have identified hepatocyte nuclear factor-1α as a key transcriptional regulator that cooperates with sterol regulatory element-binding protein-2 to control PCSK9 expression in hepatocytes in response to nutritional and hormonal inputs, as well as acute inflammation.SummaryPCSK9 is an established target for cholesterol-lowering therapies. Further study of PCSK9 regulatory mechanisms may identify additional control points for pharmacological inhibition of PCSK9-mediated LDLR degradation. PCSK9 function could reflect ancient roles in the fasting-feeding cycle and in linking lipoprotein metabolism with innate immunity.

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“…27,28 In fact herbs that contain berberine are used to prevent hypertriglyceridemia. 29 Xiao et al 30 investigated that the berberine regulates the proprotein convertase subtilisin/kexin type 9-low-density lipoprotein receptor (PCSK9-LDLR) pathway, and balance the lipid levels in the body. Among the main constituents in PHF, gallic acid and quercetin have also been demonstrated to exhibit beneficial effects in attenuating disturbances of lipid metabolism.…”

Section: Discussionmentioning

confidence: 99%

Effects of a standardized Ayurvedic formulation on diabetes control in newly diagnosed Type-2 diabetics; a randomized active controlled clinical study

Awasthi¹,

Nath²,

Usman³

et al. 2015

Complementary Therapies in Medicine

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Berberine inhibits dyslipidemia in C57BL/6 mice with lipopolysaccharide induced inflammation

Abstract: The present results suggest that berberine inhibits dyslipidemia in C57BL/6 mice with LPS induced inflammation through regulating PCSK9-LDLR pathway.

Cited by 70 publications

References 31 publications

PCSK9 is a critical regulator of the innate immune response and septic shock outcome

PCSK9 is a critical regulator of the innate immune response and septic shock outcome

PCSK9 and LDLR degradation

Effects of a standardized Ayurvedic formulation on diabetes control in newly diagnosed Type-2 diabetics; a randomized active controlled clinical study

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