Scientific writing: vegetal extracts as a replacement for statins to reduce cholesterol

Federico Benetti – Executive Director at ECSIN LAB, a Mérieux NutriSciences Company – has been involved in the publication of a scientific paper entitled “Anticholesterolemic activity of three vegetal extracts (Artichoke, Caigua, and Fenugreek) and their unique blend” on Frontiers in Pharmacology (2021).

In vitro studies to pave the way toward new therapies

The liver is considered one of the most active organs in the human body, dealing with the regulation of many critical processes, such as bile secretion, metabolic detoxification, etc., and it is the mastermind behind nutrient metabolism and waste metabolites excretion. The liver also regulates lipid homeostasis, of which cholesterol is definitely one of the most important. So, the liver is the principal site for cholesterol homeostasis, mainly via biosynthesis, uptake through low-density lipoprotein receptors, lipoprotein release in the blood, storage by esterification and degradation, and conversion into bile acids. Liver failure in regulating cholesterol homeostasis, leading to hypercholesterolemia, is known to be a key point in cardiovascular disease development, such as coronary artery diseases (CAD), linked with the progressive accumulation of cholesterol at the atherosclerotic plaque level.

Currently, statins (as atorvastatin, fluvastatin, etc.) are the most widely prescribed drugs to lower plasma and hepatic cholesterol levels and, in response to the increased hypercholesterolemia population incidence, their use has grown exponentially. Despite their undeniable efficacy, some concerns were raised regarding statin- and monacolin-based therapy safety. Therefore, anticholesterolemic therapies based on novel and safer vegetal extracts and their blends may become a very interesting option to assist or replace statins.

While in vivo studies remain the more reliable approach to investigate the effect of novel substances on liver metabolism, for a preliminary screening of vegetal extracts and formulation efficacy and safety, in vitro approach is preferred, which allows point assessment of the target mechanisms responsible for cholesterol control.

The aim of the study

The anticholesterolemic efficacy of three vegetal extracts used in traditional medicine – artichoke, caigua, and fenugreek -, their unique blend (ACFB), and the monacolin K-containing red yeast extract (RYR), was investigated with an in vitro approach (hepatic cell line HepG2) in order to evaluate their impact on cholesterol through the investigation of hepatocyte total and free cholesterol, and bile acids biosynthesis.

The main points analysed:

• Species identification by DNA barcoding. DNA barcoding approach is a molecular-based identification system based on the analysis of the variability within a standard region of the genome.
• UHPLC-ESI-HRMS untarget analysis of ACFB. The UHPLC-ESI-HRMS analysis was carried out in order to verify the content of active substances within the blended extract (ACFB).
• Cytotoxicity evaluation of the three vegetal extracts, ACFB, and red yeast rice. Before exploring the potential anticholesterolemic activity of the three vegetal extracts, ACFB, atorvastatin, and RYR, their impact on HepG2 cell viability was evaluated by dose–response toxicological analysis.
• Effect of vegetal extracts, ACFB, and red yeast rice on bile acid biosynthesis – in vitro hepatic model. One of the main mechanisms by which the liver regulates the overall cholesterol level is via choleresis.
• Impact of vegetal extracts, ACFB, and red yeast rice on hepatic cholesterol biosynthesis – in vitro hepatic model. The liver is the principal site for cholesterol homeostasis maintenance via a plethora of mechanisms, such as biosynthesis, uptake through low-density lipoprotein receptors (LDLr), lipoprotein release in the blood, storage by esterification, and degradation and conversion into bile acids.

Results

This is the first study to investigate anticholesterolemic activity of a novel formulation, and the results suggest that combining active ingredients in a unique blend could enhance their curative effects, potentially providing complementary therapies to the statin-based ones for hyperlipidemia and hypercholesterolemia-related complications.

Although the results from in vitro experiments cannot be directly extrapolated to antilipidemic and anticholesterolemic clinical effects, such studies could assist in screening novel vegetal extracts and blends for their safety and anticholesterolemic efficacy, while starting to elucidate the mechanism through which cholesterol is lowered.

Although the results from in vitro experiments cannot be directly extrapolated to antilipidemic and anticholesterolemic clinical effects, of course such studies will assist in screening novel vegetal extracts and blends for their safety and anticholesterolemic efficacy, while starting to elucidate the mechanism through which cholesterol is lowered.