Linderae Radix Attenuates Hyperlipidemia by Regulating Reverse Cholesterol Transport through the miR-33-PPARα/LXRα...

Area of Science:

• Biochemistry
• Molecular Biology
• Pharmacology

Background:

• MicroRNA-33 (miR-33) down-regulates key proteins involved in reverse cholesterol transport (RCT).
• Linderae Radix (WY) exhibits anti-hyperlipidemic effects by modulating RCT.
• The precise role of miR-33 in WY's regulation of RCT remains to be elucidated.

Purpose of the Study:

• To investigate whether WY's regulation of RCT is mediated by miR-33.
• To explore the underlying molecular mechanisms of WY in managing hyperlipidemia.

Main Methods:

• In vivo studies using hyperlipidemic (HLP) mice with miR-33 over-expression models.
• In vitro experiments on ox-LDL-induced RAW 264.7 macrophages with manipulated miR-33 levels.
• Assessment of serum lipid profiles, liver lipid accumulation, and RCT-related protein expression (ABCA1, ABCG1, PPARα, LXRα, FXR, SR-BI) via RT-qPCR, Western blotting, and multiplex immunofluorescence.

Main Results:

• WY significantly reduced total cholesterol (TC), triglycerides (TG), and LDL-C levels in HLP mice.
• WY treatment increased RCT-related proteins (ABCA1, ABCG1, PPARα, LXRα, FXR) in vivo and in vitro.
• WY alleviated lipid deposition in macrophages and enhanced RCT protein expression in cells with both over-expressed and low miR-33 levels.

Conclusions:

• WY attenuates hyperlipidemia by regulating RCT through the miR-33-PPARα/LXRα axis.
• Activation of PPARα/LXRα via miR-33 inhibition by WY offers a distinct mechanism compared to statins or fibrates.
• This approach holds potential for statin-intolerant patients or as an adjunct therapy.