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Review
. 2024 Aug 15:351:122823.
doi: 10.1016/j.lfs.2024.122823. Epub 2024 Jun 10.

Role of CETP, PCSK-9, and CYP7-alpha in cholesterol metabolism: Potential targets for natural products in managing hypercholesterolemia

Rita Ngozi Aguchem  1 , Innocent Uzochukwu Okagu  1 , Ekezie Matthew Okorigwe  2 , Jude Obiorah Uzoechina  3 , Stephen Chukwubuikem Nnemolisa  1 , Timothy Prince Chidike Ezeorba  4
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Free article
Review

Role of CETP, PCSK-9, and CYP7-alpha in cholesterol metabolism: Potential targets for natural products in managing hypercholesterolemia

Rita Ngozi Aguchem et al. Life Sci. .
Free article

Abstract

Cardiovascular diseases (CVDs) are a leading cause of mortality worldwide, primarily affecting the heart and blood vessels, with atherosclerosis being a major contributing factor to their onset. Epidemiological and clinical studies have linked high levels of low-density lipoprotein (LDL) emanating from distorted cholesterol homeostasis as its major predisposing factor. Cholesterol homeostasis, which involves maintaining the balance in body cholesterol level, is mediated by several proteins or receptors, transcription factors, and even genes, regulating cholesterol influx (through dietary intake or de novo synthesis) and efflux (by their conversion to bile acids). Previous knowledge about CVDs management has evolved around modulating these receptors' activities through synthetic small molecules/antibodies, with limited interest in natural products. The central roles of the cholesteryl ester transfer protein (CETP), proprotein convertase subtilisin/kexin type 9 (PCSK9), and cytochrome P450 family 7 subfamily A member 1 (CYP7A1), among other proteins or receptors, have fostered growing scientific interests in understanding more on their regulatory activities and potential as drug targets. We present up-to-date knowledge on the contributions of CETP, PCSK9, and CYP7A1 toward CVDs, highlighting the clinical successes and failures of small molecules/antibodies to modulate their activities. In recommendation for a new direction to improve cardiovascular health, we have presented recent findings on natural products (including functional food, plant extracts, phytochemicals, bioactive peptides, and therapeutic carbohydrates) that also modulate the activities of CETP, PCSK-9, and CYP7A1, and emphasized the need for more research efforts redirected toward unraveling more on natural products potentials even at clinical trial level for CVD management.

Keywords: Blood, inflammation; Cardiovascular; Peptide; Phytochemicals; Polysaccharides.

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Conflict of interest statement

Declaration of competing interest The authors declare no competing interests.

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