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

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.

Hesperidin and SARS-CoV-2: New Light on the Healthy Function of Citrus Fruits

“…Hesperidin has multiple antimicrobial, antioxidant, anti-tumor, antihypertensive and immunostimulant medicinal properties [14,57,[88][89][90][91][92][93][94][95][96][97]. Therefore, citrus fruits could have positive effects in the course of COVID-19 with additional mechanisms, besides the inhibition of virus replication and antioxidant activity.…”

“…Furthermore, this infection is known to affect elderly people with other cardiovascular and respiratory systems ailments. Consequently, any lifestyle-related intervention, including dietary interventions that increase hesperidin bioavailability [95] and help to maintain the health of the cardiovascular and respiratory systems, may make the person infected with SARS-CoV-2 less susceptible to its more severe complications. The risk of some chronic diseases like cerebrovascular disease and asthma is lower at higher dietary hesperetin intake [100], and a number of papers report beneficial effects in animal models of neurodegenerative disorders [96,101,102] and hyperthermia-induced febrile seizures [103].…”

8 Weeks of 2s-Hesperidin Supplementation Improves Power Output at Estimated Functional Threshold Power and Maximum Power in Amateur Cyclist

“…In particular, Amaretti et al [36] established that the species Bifidobacterium catenulatum and Bifidobacterium pseudocatenultum had the ability to hydrolyze hesperidin, because in their genome they have the gene encoding for the enzyme α-L-rhamnose (limiting enzyme), which contributes to the release of aglycone from certain routine-conjugated polyphenols, such as hesperidin. A recent study suggests that the contradictory finding regarding the intake of hesperidin in humans may be due, in part, to the interindividual variability in its bioavailability, which highly depends on the α-rhamnosidase activity and the composition of the gut microbiota [37]. On the other hand, hesperidin has shown to have a probiotic effect by promoting the growth of some beneficial bacterial species in the colon, the key role being the production of short-chain fatty acids (SCFA) (Bifidobacterium spp., Lactobacillus spp., or Akkermansia muciniphila) [37].…”

“…A recent study suggests that the contradictory finding regarding the intake of hesperidin in humans may be due, in part, to the interindividual variability in its bioavailability, which highly depends on the α-rhamnosidase activity and the composition of the gut microbiota [37]. On the other hand, hesperidin has shown to have a probiotic effect by promoting the growth of some beneficial bacterial species in the colon, the key role being the production of short-chain fatty acids (SCFA) (Bifidobacterium spp., Lactobacillus spp., or Akkermansia muciniphila) [37].…”

“…SCFA are absorbed with healthy effects on the permeability of the intestinal barrier and the distal organs and tissues. In addition, hesperidin has the ability to inhibit the growth of harmful bacteria, such as Escherichia coli, Pseudomonas aeruginosa, Prevotella spp., Porphyromonas gingivalis and Fusobacterium nucleatum, among others [37]. SCFA are key mediators of mitochondria energy metabolism and act as ligands for free fatty acid receptors 2 and 3 (FFAR2, FFAR3) that regulate glucose and fatty acid metabolism, sirtuin 1(SIRT1), which plays a role in mitochondrial biogenesis via PGC-1α deacetylation [38].…”