Hesperidin is a flavonoid glycoside found primarily in citrus fruits. It is known for its antioxidant, anti-inflammatory, and vasoprotective properties. Hesperidin interacts with various biological mechanisms, offering health benefits for cardiovascular health, the immune system, and beyond.

• Antioxidant Action. Hesperidin combats oxidative stress by neutralizing free radicals and protecting cells from oxidative damage (1). This helps to reduce the risk of chronic diseases related to oxidation.
• Anti-inflammatory Effect. It modulates the body's inflammatory response (2) by inhibiting the production of inflammatory mediators and the activation of inflammatory pathways, thus helping to reduce systemic inflammation.
• Vasoprotective Properties. It improves vascular health by strengthening endothelial function, reducing capillary permeability, and enhancing blood circulation. This is particularly beneficial for preventing venous disorders like varicose veins.
• Effects on Metabolism. Hesperidin can positively influence lipid and glucose metabolism, contributing to the prevention and treatment of diabetes and obesity (3).
• Immune System Support. It has been shown to enhance the immune response, improving resistance to infections and potentially reducing the risk of some autoimmune diseases (4).

Industrial Production Process

Sources. Rich in citrus fruits such as oranges, lemons, mandarins, and grapefruits, hesperidin is easily obtained through the diet. It is also available as a supplement, often in combination with other bioflavonoids.

• Extraction - Hesperidin is initially extracted from citrus sources, such as orange and lemon peels, through extraction processes that may involve the use of solvents like ethanol or water.
• Purification - After extraction, crude Hesperidin is purified to remove impurities and enhance its quality. This can include techniques such as crystallization, filtration, and chromatography.
• Synthesis/Modification - In some cases, Hesperidin may be chemically modified to improve its solubility and bioavailability. This can involve converting it into derivatives like Hesperidin methyl chalcone.
• Quality Control - The purified Hesperidin undergoes rigorous quality control checks to ensure its purity, potency, and compliance with specifications. This includes tests to identify the presence of heavy metals, residual solvents, and other contaminants.

Form and Color

Hesperidin is commonly found as a yellow or orange crystalline powder, used in capsules, tablets, or as part of powder blends.

Safety.

Generally considered safe when taken in appropriate doses, but it's always advisable to consult a healthcare professional before starting any supplementation, especially if you have pre-existing medical conditions.

Molecular Formula  C₂₈H₃₄O₁₅ 

Molecular Weight  610.6 g/mol

CAS  520-26-3

UNII    E750O06Y6O

EC Number 208-288-1

Synonyms

• hesperidine
• Cirantin
• Hesperidoside
• Hesper bitabs

References_____________________________________________________________________

(1) Buzdağlı Y, Eyipınar CD, Kacı FN, Tekin A. Effects of hesperidin on anti-inflammatory and antioxidant response in healthy people: a meta-analysis and meta-regression. Int J Environ Health Res. 2023 Dec;33(12):1390-1405. doi: 10.1080/09603123.2022.2093841. 

Abstract. Hesperidin is a prominent flavanone found in citrus fruits that has a broad range of biological effects, including anti-inflammatory and antioxidant capabilities. The study's objective was to evaluate the effects of hesperidin supplementation on anti-inflammatory and antioxidant parameters such as MDA, TAC, GSH, SOD, and CAT; CRP, TNF-α, IL-6, and IL-4 levels respectively, by analyzing human intervention trials. Google Scholar, PubMed, grey literature databases, and the ClinicalTrials website were scanned to identify eligible studies. For the meta-analysis, eighteen studies were chosen. Hesperidin supplementation had significant lowering effect on not only CRP, IL-6, and IL-4 levels but also MDA level (Meta-regression analysis revealed a non-significant direct relationship between hesperidin dosage and chance in CRP, IL-6, and MDA levels. As a result, it can be said that hesperidin supplementation contributes to the inflammatory and antioxidant response, but this contribution is independent of dosage.

(2) Choi SS, Lee SH, Lee KA. A Comparative Study of Hesperetin, Hesperidin and Hesperidin Glucoside: Antioxidant, Anti-Inflammatory, and Antibacterial Activities In Vitro. Antioxidants (Basel). 2022 Aug 20;11(8):1618. doi: 10.3390/antiox11081618. PMID: 36009336; PMCID: PMC9405481.

Abstract. The antioxidant, anti-inflammatory and antibacterial activities of hesperetin, hesperidin and hesperidin glucoside with different solubility were compared in vitro. Hesperetin was prepared by enzymatic hydrolysis from hesperidin, and hesperidin glucoside composed of hesperidin mono-glucoside was prepared from hesperidin through enzymatic transglycosylation. Solubility of the compounds was different: the partition coefficient (log P) was 2.85 ± 0.02 for hesperetin, 2.01 ± 0.02 for hesperidin, and -3.04 ± 0.03 for hesperidin glucoside. Hesperetin showed a higher effect than hesperidin and hesperidin glucoside on radical scavenging activity in antioxidant assays, while hesperidin and hesperidin glucoside showed similar activity. Cytotoxicity was low in the order of hesperidin glucoside, hesperidin, and hesperetin in murine macrophage RAW264.7 cells. Treatment of the cells with each compound reduced the levels of inflammatory mediators, nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). Hesperetin was most effective at relatively low concentrations, however, hesperidin glucoside was also effective at higher concentration. Hesperetin showed higher antibacterial activity than hesperidin in both Gram-positive and -negative bacteria, and hesperidin glucoside showed similarly higher activity with hesperetin depending on the bacterial strain. In conclusion, hesperetin in the form of aglycone showed more potent biological activity than hesperidin and hesperidin glucoside. However, hesperidin glucoside, the highly soluble form, has been shown to increase the activity compared to poorly soluble hesperidin.

(3) Xiong H, Wang J, Ran Q, Lou G, Peng C, Gan Q, Hu J, Sun J, Yao R, Huang Q. Hesperidin: A Therapeutic Agent For Obesity. Drug Des Devel Ther. 2019 Nov 12;13:3855-3866. doi: 10.2147/DDDT.S227499. 

Abstract. Obesity is a chronic metabolic disease caused by multiple factors and is considered to be a risk factor for type 2 diabetes, cardiovascular disease, hypertension, stroke and various cancers. Hesperidin, a flavanone glycoside, is a natural phenolic compound with a wide range of biological effects. Mounting evidence has demonstrated that hesperidin possesses inhibitory effect against obesity diseases. Our review discusses mechanisms of hesperidin in the treatment of obesity. Hesperidin regulates lipid metabolism and glucose metabolism by mediating AMPK and PPAR signaling pathways, directly regulates antioxidant index and anti-apoptosis, and indirectly mediates NF-κB signaling pathway to regulate inflammation to play a role in the treatment of obesity. In addition, hesperidin-enriched dietary supplements can significantly improve symptoms such as postprandial hyperglycemia and hyperlipidemia. Further clinical trials are also required for confirming lipid-lowering efficacy of this natural flavonoid and evaluating its safety profile.

(4) Camps-Bossacoma M, Franch À, Pérez-Cano FJ, Castell M. Influence of Hesperidin on the Systemic and Intestinal Rat Immune Response. Nutrients. 2017 Jun 6;9(6):580. doi: 10.3390/nu9060580. PMID: 28587283; PMCID: PMC5490559.

Abstract. Polyphenols, widely found in edible plants, influence the immune system. Nevertheless, the immunomodulatory properties of hesperidin, the predominant flavanone in oranges, have not been deeply studied. To establish the effect of hesperidin on in vivo immune response, two different conditions of immune system stimulations in Lewis rats were applied. In the first experimental design, rats were intraperitoneally immunized with ovalbumin (OVA) plus Bordetella pertussis toxin and alum as the adjuvants, and orally given 100 or 200 mg/kg hesperidin. In the second experimental design, rats were orally sensitized with OVA together with cholera toxin and fed a diet containing 0.5% hesperidin. In the first approach, hesperidin administration changed mesenteric lymph node lymphocyte (MLNL) composition, increasing the TCRαβ+ cell percentage and decreasing that of B lymphocytes. Furthermore, hesperidin enhanced the interferon (IFN)-γ production in stimulated MLNL. In the second approach, hesperidin intake modified the lymphocyte composition in the intestinal epithelium (TCRγδ+ cells) and the lamina propria (TCRγδ+, CD45RA+, natural killer, natural killer T, TCRαβ+CD4+, and TCRαβ+CD8+ cells). Nevertheless, hesperidin did not modify the level of serum anti-OVA antibodies in either study. In conclusion, hesperidin does possess immunoregulatory properties in the intestinal immune response, but this effect is not able to influence the synthesis of specific antibodies.