resumo
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.
palavras-chave
HMG-COA REDUCTASE; DENSITY-LIPOPROTEIN RECEPTOR; SUBTILISIN/KEXIN TYPE 9; FACTOR-LIKE REPEAT; POLYMERIC MICELLES; INHIBITION; BERBERINE; EXTRACTS; BINDING; PROTEIN
categoria
Plant Sciences
autores
Ongtanasup, T; Prommee, N; Jampa, O; Limcharoen, T; Wanmasae, S; Nissapatorn, V; Paul, AK; Pereira, MD; Wilairatana, P; Nasongkla, N; Eawsakul, K
nossos autores
Maria de Lourdes Gomes Pereira
Professor Associado com AgregaçãoProjectos
CICECO - Aveiro Institute of Materials (UIDB/50011/2020)
CICECO - Aveiro Institute of Materials (UIDP/50011/2020)
Associated Laboratory CICECO-Aveiro Institute of Materials (LA/P/0006/2020)
agradecimentos
This research is partially financially supported by Walailak University, Thailand (Grant no. WU-IRG-65-013) and partially supported by New Strategic Research (P2P) project, Walailak University, Thailand. Project CICECO-Aveiro Institute of Materials, UIDB/50011/2020, UIDP/50011/2020 & LA/P/0006/2020, financed by national funds through the FCT/MEC (PIDDAC).