Effect of Hesperidin on Cardiovascular Disease Risk Factors: The Role of Intestinal Microbiota on Hesperidin Bioavailability

Anna Mas-Capdevila, Joan Teichenne, Cristina Domenech-Coca, Antoni Caimari, Josep M Del Bas, Xavier Escoté, Anna Crescenti, Anna Mas-Capdevila, Joan Teichenne, Cristina Domenech-Coca, Antoni Caimari, Josep M Del Bas, Xavier Escoté, Anna Crescenti

Abstract

Recently, hesperidin, a flavonone mainly present in citrus fruits, has emerged as a new potential therapeutic agent able to modulate several cardiovascular diseases (CVDs) risk factors. Animal and in vitro studies demonstrate beneficial effects of hesperidin and its derived compounds on CVD risk factors. Thus, hesperidin has shown glucose-lowering and anti-inflammatory properties in diabetic models, dyslipidemia-, atherosclerosis-, and obesity-preventing effects in CVDs and obese models, and antihypertensive and antioxidant effects in hypertensive models. However, there is still controversy about whether hesperidin could contribute to ameliorate glucose homeostasis, lipid profile, adiposity, and blood pressure in humans, as evidenced by several clinical trials reporting no effects of treatments with this flavanone or with orange juice on these cardiovascular parameters. In this review, we focus on hesperidin's beneficial effects on CVD risk factors, paying special attention to the high interindividual variability in response to hesperidin-based acute and chronic interventions, which can be partly attributed to differences in gut microbiota. Based on the current evidence, we suggest that some of hesperidin's contradictory effects in human trials are partly due to the interindividual hesperidin variability in its bioavailability, which in turn is highly dependent on the α-rhamnosidase activity and gut microbiota composition.

Keywords: bioavailability; cardiovascular diseases; dysbiosis; gut microbiota; hesperetin; hesperidin.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of hesperidin metabolization in the colon. Enzymatic deglycosylation of hesperidin to yield hesperetin: via hesperetin-7-O-glucoside by two specific monoglycosidases, α-rhamnosidase and β-glucosidase, and via one-step deglycosylation through α-rhamnosyl-β-glucosidase (αRβGl).
Figure 2
Figure 2
Summary of the most representative effects of hesperidin consumption and its derivatives on cardiovascular risk factors, including glucose homeostasis, blood pressure and endothelial function, and lipid profile and adiposity. SBP: systolic blood pressure; DBP: diastolic blood pressure; NO: nitric oxide; FFA: free fatty acids; TG: triglycerides; Chol: cholesterol.
Figure 3
Figure 3
Illustrative diagram of hesperidin absorption in the colon. The flavones present in oranges reach the colon almost unchanged in their structure. In the lumen of the colon, hesperidin is converted to its active form by the α-rhamnosidase activity of the microbiota (Bifidobacterium pseudocatenulatum), releasing the rutinose moiety and hesperetin for further absorption by the colonocytes. In the colon, hesperidin promotes the growth of some beneficial bacteria species, with a key role in the SCFA production (Bifidobacterium spp., Lactobacillus spp., or Akkermansia muciniphila). SCFAs are absorbed with healthy effects in the permeability of the gut barrier and in distal organs and tissues. Moreover, hesperidin has other beneficial effects by inhibiting the proliferation of detrimental bacteria, such as Escherichia coli, Pseudomonas aeruginosa, Prevotella spp., Porphyromonas gingivalis, and Fusobacterium nucleatum, among others. SCFAs: short chain fatty acids.

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