The Cholesterol-Modulating Effect of the New Herbal Medicinal Recipe from Yellow Vine ( Coscinium fenestratum (Goetgh.)), Ginger ( Zingiber officinale Roscoe.), and Safflower ( Carthamus tinctorius L.) on Suppressing PCSK9 Expression to Upregulate LDLR Expression in HepG2 Cells.

PCSK9 is a promising target for developing novel cholesterol-lowering drugs. We developed a recipe that combined molecular docking, GC-MS/MS, and real-time PCR to identify potential PCSK9 inhibitors for herb ratio determination. Three herbs, Carthamus tinctorius , Coscinium fenestratum , and Zingiber officinale, were used in this study. This work aimed to evaluate cholesterol-lowering through a PCSK9 inhibitory mechanism of these three herbs for defining a suitable ratio. Chemical constituents were identified using GC-MS/MS. The PCSK9 inhibitory potential of the compounds was determined using molecular docking, real-time PCR, and Oil red O staining. It has been shown that most of the active compounds of C. fenestratum and Z. officinale inhibit PCSK9 when extracted with water, and C. fenestratum has been shown to yield tetraacetyl-d-xylonic nitrile (27.92%) and inositol, 1-deoxy-(24.89%). These compounds could inhibit PCSK9 through the binding of 6 and 5 hydrogen bonds, respectively, while the active compound in Z. officinale is 2-Formyl-9-[.beta.-d-ribofuranosyl] hypoxanthine (4.37%) inhibits PCSK9 by forming 8 hydrogen bonds. These results suggest that a recipe comprising three parts C. fenestratum , two parts Z. officinale , and one part C. tinctorius is a suitable herbal ratio for reducing lipid levels in the bloodstream through a PCSK9 inhibitory mechanism.