HESPERIDIN

Hesperidin is a naturally occurring bioflavonoid predominantly found in citrus fruits such as oranges, lemons, and grapefruits. 
Hesperidin belongs to the flavanone glycoside class and is composed of the flavanone hesperetin bound to the disaccharide rutinose. 
Hesperidin is known for its antioxidant, anti-inflammatory, and vascular protective properties. 
Hesperidin is widely studied for its potential benefits in cardiovascular health, capillary strengthening, and anti-allergic effects.

CAS Number: 520-26-3
Synonyms:
Hesperidin,Hesperetin-7-rutinoside,3',5,7-Trihydroxy-4'-methoxyflavanone-7-rhamnoglucoside,Citrus bioflavonoid,Vitamin P ,(2S)-5-Hydroxy-2-(3-hydroxy-4-methoxyphenyl)-7-[(2-O-β-D-glucopyranosyl-α-L-rhamnopyranosyl)oxy]-4H-1-benzopyran-4-one

Introduction
Hesperidin is a prominent flavonoid glycoside mainly found in citrus fruits, particularly in oranges and lemons.
As a member of the flavanone class, hesperidin has garnered interest for its numerous biological activities, including antioxidant, anti-inflammatory, and cardiovascular protective effects. 
Its widespread presence in the human diet and its safety profile make it a valuable candidate for pharmaceutical, nutraceutical, and cosmetic industries.

Natural Sources and Occurrence
Hesperidin is predominantly found in:
Citrus sinensis (orange)
Citrus limon (lemon)
Citrus paradisi (grapefruit)
Citrus aurantium (bitter orange)
It is most abundant in the peels and albedo (white inner layer) of citrus fruits.

Biosynthesis in Plants
Hesperidin is synthesized via the phenylpropanoid pathway:
Phenylalanine → Cinnamic acid
Cinnamic acid → p-Coumaric acid → naringenin
Naringenin undergoes hydroxylation and methylation to form hesperetin
Glycosylation leads to hesperidin formation

Extraction and Isolation Techniques
Common techniques include:
Solvent extraction (ethanol, methanol)
Supercritical CO₂ extraction
Ultrasonic-assisted extraction
Enzymatic hydrolysis for conversion to aglycone (hesperetin)
Purification is often achieved via preparative HPLC or flash chromatography.

Physicochemical Properties
Appearance: Yellow crystalline powder
Solubility: Poor in water, soluble in DMSO and ethanol
Melting Point: ~250–255°C
pKa: 7.08 (approx.)

Analytical Characterization
Techniques used:
HPLC-UV and HPLC-MS/MS for quantification
FT-IR and NMR for structural analysis
UV-Vis spectroscopy for flavonoid fingerprinting
TLC for preliminary screening

Stability and Storage
Stable under dry and cool conditions
Sensitive to light and prolonged exposure to moisture
Degrades under extreme pH and heat

Derivatives and Analogues
Hesperetin (aglycone form)
Neohesperidin
Methylated derivatives to improve bioavailability
Hesperidin methyl chalcone (HMC) for enhanced solubility

Metabolism and Biotransformation
Hesperidin is hydrolyzed by intestinal microbiota to hesperetin, which is absorbed and further conjugated (glucuronidation, sulfation) in the liver.

Pharmacokinetics
Absorption: Poor oral bioavailability (~20%)
Distribution: Plasma protein-bound
Metabolism: Liver conjugation
Elimination: Biliary and renal excretion

Pharmacodynamics
Acts on multiple pathways:
Scavenges free radicals
Inhibits pro-inflammatory cytokines (IL-6, TNF-α)
Enhances endothelial nitric oxide production
Modulates MAPK and NF-κB signaling pathways

Antioxidant Activity
DPPH and ABTS radical scavenging
Chelates transition metals
Inhibits lipid peroxidation
Protects against oxidative stress in vivo

Anti-inflammatory Properties
Reduces expression of COX-2 and iNOS
Decreases leukocyte infiltration
Downregulates NF-κB and pro-inflammatory mediators

Anticancer Potential
Reported in models of:
Colon cancer (cell cycle arrest in HT-29 cells)
Breast cancer (apoptosis induction in MCF-7)
Leukemia (ROS-mediated cytotoxicity)
Mechanisms: apoptosis induction, antiangiogenic effects, inhibition of tumor cell proliferation.

Cardiovascular Benefits
Improves endothelial function
Reduces LDL oxidation
Inhibits platelet aggregation
Decreases blood pressure in hypertensive models

Neuroprotective Effects
Protects neurons from glutamate toxicity
Ameliorates memory deficits in Alzheimer’s models
Reduces neuroinflammation
Enhances BDNF expression

Antimicrobial Properties
Effective against:
Gram-positive bacteria: Staphylococcus aureus
Gram-negative bacteria: Escherichia coli
Fungi: Candida albicans
Acts via membrane disruption and enzyme inhibition

Anti-allergic and Immunomodulatory Effects
Inhibits histamine release
Reduces IgE levels
Modulates Th1/Th2 balance
Potential in asthma and allergic rhinitis

Metabolic and Anti-diabetic Effects
Improves insulin sensitivity
Reduces fasting glucose and HbA1c
Enhances GLUT4 translocation
Protects pancreatic β-cells

Hepatoprotective and Renal Effects
Ameliorates CCl₄-induced liver damage
Reduces hepatic fibrosis markers
Decreases serum creatinine and BUN in nephropathy models

Gastrointestinal Impacts
Enhances mucosal integrity
Protects against gastric ulcers
Reduces inflammation in colitis models

Cosmetic and Dermatological Uses
Anti-aging effects (via collagen preservation)
UV protection
Reduces hyperpigmentation
Incorporated in serums and creams

Food and Nutraceutical Applications
Used in functional foods, juices, and dietary supplements
Approved as a bioflavonoid additive
Often combined with vitamin C or rutin

SAFETY INFORMATION ABOUT HESPERIDIN

  
First aid measures:
Description of first aid measures:
General advice:
Consult a physician. 
Show this safety data sheet to the doctor in attendance.
Move out of dangerous area:
 
If inhaled:
If breathed in, move person into fresh air. 
If not breathing, give artificial respiration.
Consult a physician.
In case of skin contact:
Take off contaminated clothing and shoes immediately. 
Wash off with soap and plenty of water.
Consult a physician.
 
In case of eye contact:
Rinse thoroughly with plenty of water for at least 15 minutes and consult a physician.
Continue rinsing eyes during transport to hospital.
 
If swallowed:
Do NOT induce vomiting. 
Never give anything by mouth to an unconscious person. 
Rinse mouth with water. 
Consult a physician.
 
Firefighting measures:
Extinguishing media:
Suitable extinguishing media:
Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Special hazards arising from the substance or mixture
Carbon oxides, Nitrogen oxides (NOx), Hydrogen chloride gas
 
Advice for firefighters:
Wear self-contained breathing apparatus for firefighting if necessary.
Accidental release measures:
Personal precautions, protective equipment and emergency procedures
Use personal protective equipment. 
 
Avoid breathing vapours, mist or gas. 
Evacuate personnel to safe areas.
 
Environmental precautions:
Prevent further leakage or spillage if safe to do so.
Do not let product enter drains.
Discharge into the environment must be avoided.
 
Methods and materials for containment and cleaning up:
Soak up with inert absorbent material and dispose of as hazardous waste. 
Keep in suitable, closed containers for disposal.
 
Handling and storage:
Precautions for safe handling:
Avoid inhalation of vapour or mist.
 
Conditions for safe storage, including any incompatibilities:
Keep container tightly closed in a dry and well-ventilated place. 
Containers which are opened must be carefully resealed and kept upright to prevent leakage.
Storage class (TRGS 510): 8A: Combustible, corrosive hazardous materials
 
Exposure controls/personal protection:
Control parameters:
Components with workplace control parameters
Contains no substances with occupational exposure limit values.
Exposure controls:
Appropriate engineering controls:
Handle in accordance with good industrial hygiene and safety practice.
Wash hands before breaks and at the end of workday.
 
Personal protective equipment:
Eye/face protection:
Tightly fitting safety goggles. 
Faceshield (8-inch minimum). 
Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).
 
Skin protection:
Handle with gloves. 
Gloves must be inspected prior to use. 
Use proper glove
removal technique (without touching glove's outer surface) to avoid skin contact with this product. 
Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. 
Wash and dry hands.
 
Full contact:
Material: Nitrile rubber
Minimum layer thickness: 0.11 mm
Break through time: 480 min
Material tested:Dermatril (KCL 740 / Aldrich Z677272, Size M)
Splash contact
Material: Nitrile rubber
Minimum layer thickness: 0.11 mm
Break through time: 480 min
Material tested:Dermatril (KCL 740 / Aldrich Z677272, Size M)
It should not be construed as offering an approval for any specific use scenario.
 
Body Protection:
Complete suit protecting against chemicals, The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.
Respiratory protection:
Where risk assessment shows air-purifying respirators are appropriate use a fullface respirator with multi-purpose combination (US) or type ABEK (EN 14387) respirator cartridges as a backup to engineering controls. 
 
If the respirator is the sole means of protection, use a full-face supplied air respirator. 
Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).
Control of environmental exposure
Prevent further leakage or spillage if safe to do so. 
Do not let product enter drains.
Discharge into the environment must be avoided.
 
Stability and reactivity:
Chemical stability:
Stable under recommended storage conditions.
Incompatible materials:
Strong oxidizing agents:
Hazardous decomposition products:
Hazardous decomposition products formed under fire conditions. 
Carbon oxides, Nitrogen oxides (NOx), Hydrogen chloride gas.
 
Disposal considerations:
Waste treatment methods:
Product:
Offer surplus and non-recyclable solutions to a licensed disposal company. 
Contact a licensed professional waste disposal service to dispose of this material.
Contaminated packaging:
Dispose of as unused product