Recapsoma®: A Novel Mixture Based on Bergamot, Ipomoea Batatas, Policosanol Extracts and Liposomal Berberine for the Treatment of Hypercholesterolemia

Abstract

Cardiovascular disease (CVD) is considered one of the major causes of mortality worldwide. Epidemiological studies have shown that regular consumption of phenols is inversely associated with cardiovascular disease, and the use of nutraceuticals and functional foods can provide protective, preventive, and possibly curative effects in CVD. A novel mixture of different natural substances named Recapsoma^® (bergamot, liposomal berberine, Ipomoea batatas, oleuropein, polycosanols, and vitamin E) has been produced, and its anti-dyslipidaemic efficacy has been tested, specifically studying the in vitro effects on the mechanisms of action underlying cholesterol synthesis, triglycerides, and LDL-cholesterol oxidation. The work has demonstrated the ability of this herbal extract mixture to inhibit the action of PCSK, ACAT, PAP, and HMGR and to increase the LDL receptor (LDLR), underlying the synergistic effect of the mixture over the single components. Such results suggest that the Recapsoma^® mixture could be used as a tool for controlling hypercholesterolemia, and an alternative to statins, especially for those patients with metabolic syndrome.

Keywords: LDLR expression; Recapsoma®; bergamot extract; cholesterol pathway; hypercholesterolemic activity; ipomea batatas extract; liposomal berberine; oleuropein; policosanol extract; vitamin E.

Figure 1

PCSK9 expression-related mRNA levels assessed by qRT-PCR using PCR primers specific primers after treatment of HepG2 cells with barberin (40 µM) and Recapsoma^® (barberin equivalent content 40 µM). The results shown are representative of three separate experiments averaged ± SD.

Figure 2

LDLR levels after treatment of HepG2 cells with berberine (40 µM) or Recapsoma^® (berberine equivalent content 40 µM). Values are presented as mean of three separate experiments ± S.E. (Error bars). *, p < 0.05; **, p < 0.01 vs. to DMSO used as control.

Figure 3

Fluorescence microscopy after incubation of cells with NBD-cholesterol. HepG2 cells (a) and HepG2 cells stably transfected with ACAT (b) were incubated with NBD-cholesterol. The bar in (a) = 10 μm.

Figure 4

Inhibition of human ACAT activity in HepG2 cells after treatment with a 100 µM solution of bergamot and with a solution of Recapsoma^® at an equivalent concentration of bergamot, prepared using berberine extract or berberine in liposomal form, compared to the control consisting of enriched culture medium alone. Values are presented as mean ± S.E. (Error bars). *, p < 0.05; **, p < 0.01; ***, p < 0.001.

Figure 5

Quantification of human PAP activity in HepG2 cells after treatment with a 100 μM solution of bergamot extract and with a solution of Recapsoma^® at an equivalent concentration of bergamot, prepared using berberine extract or berberine in liposomal form, compared to the control. The values are presented as mean ± S.E. (Error bars). *, p < 0.05; **, p < 0.01; ***, p < 0.001.

Figure 6

Inhibition of human HMGR activity in human hepatocytes by a 100 µM solution of Recapsoma^®, policosanols, and the mixture consisting of policosanols–oleuropein–Ipomea batata at an equivalent concentration of the individual components, compared to the control consisting of culture medium alone. Values are presented as mean ± S.E. (Error bars). *, p < 0.05; **, p < 0.01.

Figure 7

Inhibition of human HMG-CoA reductase activity in hepatocytes by a 100 µM solution of atorvastatin and Recapsoma^® dosed 1, 2, and 3 times in 24 h, compared to the control consisting of the culture medium alone. Values are presented as mean ± S.E. (Error bars). *, p < 0.05; **, p < 0.01; ***, p < 0.001.

Figure 8

Direct comparison of cellular ROS formation, quantified through DCFH-DA, in human hepatocytes after treatment with 5 μM of vitamin E, 100 µM bergamot extract, and with Recapsoma^® at an equivalent concentration of vitamin E and bergamot equivalent. The DMSO value was set to 100% and antimycin A was used as a positive control. Values are presented as mean ± S.E. (Bars of error). *, p < 0.05; **, p < 0.01; ***, p < 0.001.