Phytopharmaceuticals: Occurrence, isolation and characteristic features (chemical nature, uses in pharmacy, medicinal and health benefits) of Quercetin

1. Quercetin
v Dey
m (Pharmacognosy) 1st Sem
y Institute of Pharmaceutical Sciences
niversity

2. Contents
 Introduction
 Sources
 Extraction & Isolation
 Chemistry & its properties
 Medicinal benefits & Uses

3. Introduction
 Quercetin, a member of the flavonoids family, is one of the most
prominent dietary antioxidants.
 It is ubiquitously present in foods including vegetables, fruit, tea and
wine as well as countless food supplements and is claimed to exert
beneficial health effects.
 This includes protection against various diseases such as osteoporosis,
certain forms of cancer, pulmonary and cardiovascular diseases but
also against aging.
 Especially the ability of quercetin to scavenge highly reactive species
such as peroxynitrite and the hydroxyl radical is suggested to be
involved in these possible beneficial health effects

4. Introduction
 Quercetin is one of a group of over 4000 naturally available plant
phenolics whose isolation and biological identification were first
described by Szent-Gyorgyi in 1936.
 Quercetin is a flavonol subclass of flavonoid.
 It has a bitter flavour and is used as an ingredient in dietary
supplements, beverages, and foods.
 The name quercetin comes from the Latin word “Quercetum” which
means Oak Forest
 Quercetin is said to be one of the most widely used bioflavonoids for
the treatment of metabolic and inflammatory disorders.
 Recommended dose of Quercetin for oral human intake – 500 mg

5. Sources
 It is one of the most
abundant dietary flavonoids
found in fruits (mainly
citrus), green leafy
vegetables as well as many
seeds, buckwheat, nuts,
flowers, barks, broccoli, olive
oil, apples, onions, green
tea, red grapes, red wine,
dark cherries, and berries
such as blueberries and
cranberries.

6. Sources
 The highest concentrations of flavonols were found in vegetables such
as onions and broccoli, fruits such as apples, cherries, and berries,
and drinks such as tea & red wine.
 Quercetin is also found in medicinal botanicals, including Ginkgo biloba
(Family- Ginkgoaceae), Hypericum perforatum (Family- Hypericaceae)
(St. John's Wort), and Sambacus canadesis (Family- Adoxaceae).
 In red onions, higher concentrations of quercetin occur in the
outermost rings and in the part closest to the root.
 One study found that organically grown tomatoes had 79% more
quercetin than chemically grown ones with the help of fertilizer.

7. Extraction & Isolation
Shade dry flowers of Tridax
procumbens L.(Coat buttons or
Tridax Daisy) and grind to obtain
a coarse powder
●Using Soxhlet apparatus
extract 100 gm of the coarse
powder using 750 ml. each of
petroleum ether, chloroform
and methanol respectively.
●Extract each solvent for a
period of 24 hours
●Concentrate the
methanolic extract to
obtain a semisolid
consistency (13 gm).
Extract 2gm of this fraction with
50 ml of petroleum ether
(fraction І), 50 ml of diethyl
ether (fraction ІІ) and 50 ml of
ethyl acetate (fraction ІІІ) with
the help of a separating funnel.
Repeat each extraction for
three times to ensure
complete extraction in
each case.

8. Extraction & Isolation
Do this for the entire
methanolic extract.
Fraction І and ІІ may be
rejected because of the
presence of fatty acids and
free flavonoids
respectively.
Further process Fraction III
as it contains Quercetin in
its glycoside form.
Concentrate fraction ІІІ and
hydrolyze using 7% H2SO4
(10 ml/ gm extract) for 5
hrs.
Filter the hydrolyzed
fraction and extracte with
ethyl acetate (1:1/ thrice)
by using a separating
funnel.
Then concentrate it to get
the crude Quercetin which
may be later crystallize
with 10% ethanol to get
pure Quercetin.
Quercetin may be
subjected to various
spectral and
chromatographic
techniques for
identification

9. Chemistry
 IUPAC Name - 2-(3,4-Dihydroxyphenyl)-
5,7-dihydroxy-4H-1-benzopyran-4-one
 Chemical formula - C15H10O7
 Quercetin is an aglycone, lacking an
attached sugar.
 Quercetin has an OH group attached at
positions 3, 5, 7, 3’ , and 4’ .
Quercetin

10. Chemistry
 Common forms of quercetin –
 It is a naturally occurring polar auxin
transport inhibitor .
 A quercetin glycoside is formed by
attaching a glycosyl group (a sugar
such as glucose, rhamnose, or rutinose)
as a replacement for one of the OH
groups (commonly at position 3).

11. Chemistry
 The attached glycosyl group can change the solubility, absorption,
and in vivo effects.
 As a general rule of thumb, the presence of a glycosyl group
(quercetin glycoside) results in increased water solubility compared to
quercetin aglycone.
 Generally, the term quercetin should be used to describe the aglycone
only; however, the name is occasionally used to refer to
quercetin‐type molecules, including its glycosides in research and the
supplement industry

12. Chemistry
 Quercetin is the aglycone form of a number of other flavonoid
glycosides, such as rutin (also known as quercetin-3-O-rutinoside) and
quercitrin.
 Quercetin forms the glycosides quercitrin and rutin together with
rhamnose and rutinose, respectively.
 Likewise guaijaverin is the 3-O-arabinoside, hyperoside is the 3-O-
galactoside, isoquercitin is the 3-O-glucoside and spiraeoside is the 4′-
O-glucoside.
 Miquelianin is the quercetin 3-O-β-D-glucuronopyranoside.
 Isoquercetin is the 3-O-glucoside of quercetin

13. Physical & Chemical Properties
 Physical appearance - brilliant citron yellow needle crystal
(Converts to anhydrous form at 203-207°F )
 Solubility –
○ entirely insoluble in cold water
○ poorly soluble in hot water
○ quite soluble in alcohol and lipids
 Molecular Weight – 302.3 Dalton
 Melting point - 316º C
 Boiling point – Sublimes
 UV max: 259, 364 nm

14. Benefits & Uses

15. Antioxidant action
 The formation of reactive oxygen
species (ROS) has been reported to
contribute to the diabetes,
atherosclerosis, hypertension, ischemic
heart disease and heart failure.
 Quercetin acts as an antioxidant by
preventing oxidative stress, the major
cause for generation of ROS.
 The antioxidant property of Quercetin
principally neutralizes the free radicals
by donating hydrogen atoms to it.

16. Neurological effects
 Quercetin has been proved to be neuroprotective as well as neurotoxic.
 Quercetin shows neuroprotective action in rat brain when used in
combination with fish oil, where it shows beneficial effects against
neurodegenerative diseases (e.g. Alzheimer’s disease).
 In another instance quercetin treatment affects the working of the
nervous system by depleting the intracellular glutathione contents.
 On the other hand, whether the prolonged usage of antioxidant
supplements can be considered safe for human health is still a big
question.

17. Antiviral activity
 Quercetin is effective against viruses such as herpes simplex type I,
parainfluenza type 3, respiratory syncytial, pseudorabies, sindbis and
cardio virus42.
 The antiviral activity of quercetin is due to its ability to bind to viral coat
protein and polymerases and also to damage DNA.
 The mutagenic, carcinogenic, and anti carcinogenic activity of quercetin
is due to its ability to impose or prevent damage to DNA.
 If quercetin is stabilized with ascorbate, it enhances its antiviral activity.

18. Anti-Cancer agent
 Quercetin and other flavonoids, derived from fruits and vegetables are
important compounds as it is considered to positively help in
preventing cancer.
 Various studies is done to evaluate the anti-carcinogenic effect of
quercetin on cell cultures, where it is found that it slows the growth of
cancer cells and it also helped to foster apoptosis.
 The induction of apoptosis in cancer cells is an vital step in the
development of novel anticancer drug.
 Some animal studies conducted have shown that quercetin helps in
the protecting form certain type of cancers, especially colon cancer.

19. P-glycoprotein inhibitor
 P-glycoprotein (Pgp) causes the efflux of chemotherapeutic drugs
from cells and is believed to be an important mechanism in multidrug
resistance (MDR) in human cancer.
 Flavonoid such as quercetin increases the sensitivity of the multidrug-
resistant human cervical carcinoma KB-V1 cells (high Pgp
expression) to vinblastine and paclitaxel dose-dependently, and also
decreases the relative resistance of these anti-cancer-drugs in KB-V1
cells.
 It also causes an increase in intracellular accumulation, and reduces
the efflux of vinblastine in KB-V1 cells
 Thus , quercetin reduces Pgp expression and function resulting in the
inhibition of Pgp activity.

20. Cardiovascular properties
 Quercetin is under investigation for its possible utilization as a safe
alternative to the antioxidant and anti-inflammatory drugs used for
conditions like cardiovascular disease.
 The studies have shown that, both in preclinical and clinical study,
quercetin positively reduces several of the risk factors related with
heart disease, including blood pressure and cytokine-induced C-
reactive protein (CRP) expression.
 It is also a potent vasodilatory agent.

21. Anti-inflammatory actions
 Quercetin has been widely known for its anti-inflammatory activity.
 During a in vivo study , when the rats are treated with quercetin
mixed with polysorbate 80, it resulted in the inhibition of edema in the
paw of the rats.
 The applications of quercetin glycoside through the skin surface is
ineffective against inflammation due to low absorption value.
 The quercetin pentamethyl ether formulation is highly absorbed
through the skin route in rat, and it was found to be effective against
inflammation, thereby proving it to be a potent anti-inflammatory
agent.

22. Asthma
 Asthma is a chronic lung-disease that swells and narrows the airways,
thereby causing difficulty in breathing.
 Quercetin is found to ease the symptoms of asthma. It is found to induce
reduction in the inflammatory immune cells number and activation, cuts off
the histamine level and also eases the airway smooth muscle.
 Even at the minimum concentration, quercetin is effective against asthma, in
comparison to the standard asthma maintenance medications and steroid
inhalers that reduces the resistance to air flow.
 Quercetin is also reported to reduce pathologies of asthma, such as
eosinophil and neutrophil enrollment, bronchial epithelial cell activation,
mucus and collagen production and airway hyperactivity.

23. References
1. Alam, F., Badruddeen, Kharya, A. K., Juber, A., & Khan, M. I. (2020). Naringin: Sources,
Chemistry, Toxicity, Pharmacokinetics, Pharmacological Evidences, Molecular Docking
and Cell line Study. Research Journal of Pharmacy and Technology, 13(5).
https://doi.org/10.5958/0974-360X.2020.00447.3
2. David, A. V. A., Arulmoli, R., & Parasuraman, S. (2016). Overviews of Biological Importance
of Quercetin: A Bioactive Flavonoid. Pharmacognosy Reviews, 10(20), 84.
https://doi.org/10.4103/0973-7847.194044
3. Frutos, M. J., Rincón-Frutos, L., & Valero-Cases, E. (2019). Rutin. Nonvitamin and Nonmineral
Nutritional Supplements, 111–117. https://doi.org/10.1016/B978-0-12-812491-8.00015-1
4. Garg, A., Garg, S., Zaneveld, L. J. D., & Singla, A. K. (2001). Chemistry and pharmacology of
the citrus bioflavonoid hesperidin. Phytotherapy Research, 15(8).
https://doi.org/10.1002/ptr.1074
5. Panche, A. N., Diwan, A. D., & Chandra, S. R. (2016). Flavonoids: An overview. In Journal of
Nutritional Science (Vol. 5). Cambridge University Press. https://doi.org/10.1017/jns.2016.41

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