Anticholesterolemic Activity of Three Vegetal Extracts (Artichoke, Caigua, and Fenugreek) and Their Unique Blend

Abstract

Hepatic-related diseases, in particular hyperlipidemia and hypercholesterolemia, are a thorn on the side of the national health institutes around the globe. Indeed, liver lipid and cholesterol dysregulation could lead to atherosclerotic plaque formation and cardiovascular diseases. Currently, statin administration and monacolin K consumption are the main therapies proposed to counter this alarming connection, but relevant side effects are known. To overcome this issue, safe nutraceutical formulations and/or vegetal extracts, endowed with anticholesterolemic activity, could be instrumental in hypercholesterolemia prevention and treatment. In the present work, 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 based on hepatic cell line HepG2. The impact on cholesterol of the three extracts, their blend, and RYR were investigated by determining hepatocyte total and free cholesterol and bile acids biosynthesis. According to our results, the anticholesterolemic activity of the vegetal extracts was confirmed, and a novel choleretic activity of caigua extract was evidenced. ACFB showed to be safer than RYR while showing a similar effect on total and free cholesterol and bile acids synthesis compared to it. The anticholesterolemic activity of the blend was obtained with lower vegetal extract concentrations compared with the single vegetal extract, potentially indicating an additive effect between the extracts. In conclusion, the vegetal extracts and their blend, ACFB, are safe and are endowed with anticholesterolemic activity, potentially providing complementary therapies to the statin-based ones for hyperlipidemia and hypercholesterolemia-related complications.

The Activity of Ten Natural Extracts Combined in a Unique Blend to Maintain Cholesterol Homeostasis—In Vitro Model

“…Furthermore, these cells maintain the ability to express the main enzymes that regulate the metabolism of hepatic, plasma, and biliary cholesterol and appear to be able to synthesize and secrete bile acids. These activities respond consistently to what is known about human cholesterol metabolism [ 24 ]. For this reason, this cellular model was applied in this study to verify the safety and efficacy of a new combination of various natural ingredients with RYR in order to create the basis for a new therapeutic strategy for humans.…”

“…In this context, this is the first study that investigates the anti-cholesterol activity of a new formulation, called Esterol10 ® , obtained by combining Salvia Extract 10 µM, Quercetin 10 µM, Vitamin D3 1 nM, Vitamin K2 1 µM, CoQ10 1 µM, Resveratrol 1 µM, 9 nM astaxanthin, 1 µM sodium selenite, 1 µM folic acid and 1 µM RYR in an in vitro study. Indeed, when mixed together, the three extracts proved to be more effective than RYR in promoting the lowering of cholesterol in hepatocytes, through a reduction in the synthesis of cholesterol and its conversion into bile acids through the choleresis process which is a complex biochemical process that leads to the production of bile, an iso-osmotic electrolyte solution that forms in the liver as a product of its secretory function [ 24 ]. Taken together, these results demonstrated that Esterol10 ® significantly improves hepatic metabolism by regulating the synthesis of cholesterol through the improvement of HMGCoA reductase and the reduction of its receptor expression.…”

“…The human epithelial hepatocellular carcinoma HepG2 cells were purchased from the American Type Culture Collection (ATCC, Manassas, VA, USA) and were grown in Dulbecco’s modified Eagle’s medium (DMEM, Merck Life Science, Milano, Italy), supplemented with 10% fetal bovine serum (FBS, Merck Life Science, Milano, Italy), 2 mM L-glutamine (Merck Life Science, Milano, Italy) and 1% penicillin-streptomycin (Merck Life Science, Milano, Italy) at 37 °C and 5% CO 2 [ 37 ]. The cells used in these experiments had a passage range of 90–95% [ 24 ]. After reaching 80–90% confluence, the cells were cultured in different ways based on different experimental protocols: 1 × 10 4 cells in 96 well plates to study cell viability by MTT test and LDL uptake; 1 × 10 6 cells were cultured in 6-well plates to measure the total cholesterol, and ALT quantification, HMGCoA reductase and related metabolic pathways using ELISA assay and Western blot analysis.…”

“…The stimulation time was 24 h [ 9 , 47 ], corresponding to the duration of anticholesterolemic activity experiments as described above. Atorvastatin (1.25 μM), a concentration comparable with that available in the literature, was applied as a positive control [ 24 ] because it is a well-known anticholesterolemic substance [ 24 ]. All reported data were obtained by comparing results with those obtained on untreated cells under physiological or high glucose medium.…”

“…The anticholesterolemic activity was determined by a Cholesterol Quantitation Kit (Merck Life Science, Milan, Italy) following the manufacturer’s instructions. The fractions of the total, free, and esterified cholesterol were analyzed [ 24 ]. Briefly, after stimulation, the medium was removed and the cells were extracted with 200 µL of chloroform:isopropanol:IGEPAL CA-630 (7:11:0.1).…”