J Food Bioact

Journal of Food Bioactives, ISSN 2637-8752 print, 2637-8779 online

Journal website www.isnff-jfb.com

Review

Volume 18, June 2022, pages 85-89

Hesperidin acts as a novel CaMKII-δ inhibitor to ameliorate cardiac ischemia/reperfusion injury

Figure 1. Independent effects of hesperidin in targeting I/R injury via CaMKII-δ9 and tumors via Aurora kinase.

**Table 1.** Flavanones of Gold Lotion (GL) formulated by an extract of multiple varieties of citrus peels (Lai et al., 2013)
Flavanones	Concentration (ppm, w/w)	Compound structure
Naringin	253.6
Hesperidin	104.7
Total measured flavonoid	358.3	–

Table 1. Flavanones of Gold Lotion (GL) formulated by an extract of multiple varieties of citrus peels (Lai et al., 2013)

Flavanones

Concentration (ppm, w/w)

Compound structure

Naringin

253.6

Hesperidin

104.7

Total measured flavonoid

358.3

–

**Table 2.** A summary of published clinical trials with regard to hesperidin
Cardiovascular targets	Experimental models or subjects	Mechanisms and effects	References
Cardiovascular diseases prevention	healthy volunteers	improved postprandial microvascular endothelial reactivity	Morand et al., 2011
Cardiovascular diseases prevention	nondiabetic subjects with increased cardiovascular risk compared with healthy, nonobese control subjects	Amelioration of endothelial function and reduction of inflammation	Buscemi et al., 2012
Cardiovascular disease risk	Men at moderate CVD risk	not acutely affecting cardiovascular risk biomarkers	Schär et al., 2015
Cardiovascular disease risk	healthy overweight individuals	hesperidin protects overweight and obese individuals with a relatively healthy endothelium	Salden et al., 2016
Insulin resistance	Hypertension (A randomized controlled trial)	Action on inflammation pathway identified by the transcriptomic profile	Pla-Pagà et al., 2021b
Metabolic syndrome	Subjects with metabolic syndrome on oral hesperidin therapy	Hesperetin has vasculoprotective actions with regard to improve endothelial dysfunction and reduce circulating markers of inflammation	Rizza et al., 2011
Prediabetes	Prediabete subjects	intervention on controlling cardiovascular risk in prediabetes	Yari et al., 2021
Hypertension	Mildly hypertensive individuals	Hesperidin decreases systemic and transcriptomic biomarkers	Valls et al., 2021
Hypertension	Targeted and Non-Targeted Metabolomic Approaches on the samples from pre- and stage-1 hypertension subjects	Changing several metabolites related with an anti-inflammatory and antioxidant actions; lowering blood pressure levels and uremic toxins	Pla-Pagà et al., 2021a
Thrombotic complications	Type 1 or type 2 diabetes patients	Improvement of the antioxidant and antithrombotic profile of enrolled patients	Bagnati et al., 2021
Anaerobic capacity	moderately trained athletes	Improvement of anaerobic capacity and peak power during high intensity exercise in moderately trained individuals	van Iersel et al., 2021
Hypercholesterolemia	Mild hypercholesterolemic men	Decrease in reactive oxygen species; Tendency towards reduction of endothelial dysfunction and modest increase in plasma apoA-I	Constans et al., 2015

Table 2. A summary of published clinical trials with regard to hesperidin

Cardiovascular targets

Experimental models or subjects

Mechanisms and effects

References

Cardiovascular diseases prevention

healthy volunteers

improved postprandial microvascular endothelial reactivity

Morand et al., 2011

Cardiovascular diseases prevention

nondiabetic subjects with increased cardiovascular risk compared with healthy, nonobese control subjects

Amelioration of endothelial function and reduction of inflammation

Buscemi et al., 2012

Cardiovascular disease risk

Men at moderate CVD risk

not acutely affecting cardiovascular risk biomarkers

Schär et al., 2015

Cardiovascular disease risk

healthy overweight individuals

hesperidin protects overweight and obese individuals with a relatively healthy endothelium

Salden et al., 2016

Insulin resistance

Hypertension (A randomized controlled trial)

Action on inflammation pathway identified by the transcriptomic profile

Pla-Pagà et al., 2021b

Metabolic syndrome

Subjects with metabolic syndrome on oral hesperidin therapy

Hesperetin has vasculoprotective actions with regard to improve endothelial dysfunction and reduce circulating markers of inflammation

Rizza et al., 2011

Prediabetes

Prediabete subjects

intervention on controlling cardiovascular risk in prediabetes

Yari et al., 2021

Hypertension

Mildly hypertensive individuals

Hesperidin decreases systemic and transcriptomic biomarkers

Valls et al., 2021

Hypertension

Targeted and Non-Targeted Metabolomic Approaches on the samples from pre- and stage-1 hypertension subjects

Changing several metabolites related with an anti-inflammatory and antioxidant actions; lowering blood pressure levels and uremic toxins

Pla-Pagà et al., 2021a

Thrombotic complications

Type 1 or type 2 diabetes patients

Improvement of the antioxidant and antithrombotic profile of enrolled patients

Bagnati et al., 2021

Anaerobic capacity

moderately trained athletes

Improvement of anaerobic capacity and peak power during high intensity exercise in moderately trained individuals

van Iersel et al., 2021

Hypercholesterolemia

Mild hypercholesterolemic men

Decrease in reactive oxygen species; Tendency towards reduction of endothelial dysfunction and modest increase in plasma apoA-I

Constans et al., 2015