Role of the Phytochemicals from the Cocoa Shell on the Prevention of Metabolic Syndrome by an Integrated Network Pharmacology Analysis

Miguel Rebollo-Hernanz,Maria A Martin-Cabrejas,Silvia M Arribas,Silvia Cañas,Cheyenne Braojos

doi:10.3390/ecb2021-10256

Miguel Rebollo-Hernanz, Maria A Martin-Cabrejas + Show 3 more

Open Access

https://doi.org/10.3390/ecb2021-10256

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Abstract

The metabolic syndrome is a cluster of conditions that occur together, increasing the risk of chronic diseases such as obesity, type II diabetes, or cardiovascular disease. Nutritional interventions improving inflammation, bioenergetics, and oxidative stress are proposed as effective tools in preventing metabolic syndrome. The cocoa shell is a by-product generated in large amounts during cocoa production. This by-product contains alkaloids and phenolic compounds as main compounds and has been investigated as an anti-obesity and anti-diabetic agent. Here, we used network pharmacology to explore the potential mechanism of the phytochemicals from the cocoa shell. We searched the cocoa shell’s phytochemical composition; then, oral bioavailability and drug-likeness were screened. We predicted the targets for the phytochemicals found in this by-product and used different databases to search for compound–protein and compound–gene interactions, and then protein–protein interaction networks were constructed. Moreover, pathway enrichment analysis was performed, and biological processes and signaling pathways were identified and illustrated through bioinformatics analyses. Theobromine, caffeine, procyanidin B2, (−)-epicatechin, (+)-catechin, and protocatechuic acid were identified in the cocoa shell as main components. Those phytochemicals were associated with inflammation (TNF-α, NF-κB, JNK)-, oxidative stress (CAT, SOD)-, obesity (adiponectin, leptin, FASN, PPAR-α)-, and diabetes (insulin, AKT)-related pathways. Results demonstrated that cocoa shell phytochemicals could modulate multiple biological processes and signaling pathways in a multimechanistic manner. Hence, cocoa shell consumption could support the nutritional prevention of metabolic syndrome. Future in vivo and clinical investigations will be needed to validate this potential nutraceutical and healthy ingredient’s effects and mechanisms.

Highlights

Metabolic syndrome is a group of clinical conditions and disorders, including obesity, insulin resistance, glucose intolerance, hypertension, and dyslipidemia, increasing the risk of cardiovascular disease [1]
Phenolic compounds and alkaloids are of particular interest among these bioactive compounds, which have been related to the prevention of diseases such as diabetes, obesity, or cancer, and exert neuroprotective, anti-inflammatory, and anti-hypertensive effects [3,4]
The main phytochemicals found in cocoa shells (Figure 1A) were methylxanthines (theobromine (TH) and caffeine (CAF)) and phenolic compounds (protocatechuic acid (PCA), procyanidin B2 (PB2), (−)-epicatechin (EPI), and (+)-catechin (CAT)) [14]

Summary

Introduction

Metabolic syndrome is a group of clinical conditions and disorders, including obesity, insulin resistance, glucose intolerance, hypertension, and dyslipidemia, increasing the risk of cardiovascular disease [1]. Research has focused on exploring and using bioactive compounds with beneficial properties to handle chronic metabolic diseases [3]. Phenolic compounds and alkaloids are of particular interest among these bioactive compounds, which have been related to the prevention of diseases such as diabetes, obesity, or cancer, and exert neuroprotective, anti-inflammatory, and anti-hypertensive effects [3,4]. The cocoa shell is a by-product obtained from the cocoa industry during the processing of cocoa beans. This by-product is removed from the outer portions of beans after the roasting process [5].

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