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126 Flavonoids as Nutraceuticals
6.3.1 FLAVONOLS
Another important class of flavonoids is flavanols, generally found in
citrus fruits like lemons, oranges, and grapes. Flavanones are present in
all citrus fruits having the characteristic bitter taste of the peel and juice.
Fruits like lemons, oranges, and grapes are rich in flavanones, and major
phytoconstituents are naringenin, hesperitin, etc. Flavanol compounds like
quercetin, rutin, kaempferol, myricetin, fisetin, silymarin, and isorham
-
netin are present in foods such as saffron, apple, onions, kale, lettuce, etc.
Flavan-3-ols, also known as dihydroflavonols, include compounds such
as epicatechin, catechin, gallocatechin, epicatechin gallate, epigallocat-
echin, epigallocatechin gallate (EGCG) and procyanidin. The flavan-3-ol
compound is commonly present in black and green tea and fruits like
bananas, pears, etc.
6.3.2 ISOFLAVONOIDS
Isoflavonoids are a subclass of flavonoids with a small distribution in the
plant kingdom. They are dominantly present in leguminous plants such as
soya beans. During plant-microbe interactions and plant defense mecha-
nisms, they serve as a precursor for the synthesis of phytoalexins.
6.3.3 NEOFLAVONOIDS
The chemical structure of neoflavonoids includes a 4-phenylchromen back-
bone without hydroxyl group substitution at the second position. The first
neoflavone compound isolated from natural sources is calophyllolide, from
the seeds of Calophyllum inophyllum.
6.3.4 FLAVANOLS, FLAVAN-3-OLS, OR CATECHINS
Flavanols are a diversified and multi-substituted subgroup of flavanones
and 3-hydroxy derivatives. They are also called flavan-3-ols, as the third
position of the C ring is occupied by the hydroxyl group. There is no double
bond between the second and third positions. Fruits like apples, blueberries,
peaches, bananas, and pears are high in flavanols.
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Flavonoids of Asteraceae-Promising Anti-Inflammatory Agents 127
6.3.5 ANTHOCYANINS
Anthocyanins are pigments which impart various colors to flowers and fruits
of plants. The most common and abundant anthocyanins present in plants
include cyanidin, malvidin, delphinidin, peonidin, and pelargonidin. They
are the most studied anthocyanins (Choy et al., 2019). The outer layer of
fruits such as grapes, strawberries, raspberries, and cranberries are rich in
anthocyanin content.
6.3.6 CHALCONES
Chalcones are another major subclass of flavonoids, which are distinguished
by the absence of the basic flavonoid skeleton's 'ring C.' Open-chain flavo
-
noids are another name for them. The most common chalcones found in
plants are phloridzin, arbutin, phloretin, and chalconaringenin. Chalcones are
present in fruits like tomatoes, strawberries, pears, bearberries, and certain
wheat products. Nowadays, chalcones and their derivatives are getting
considerable attention because of their various biological and nutritional
benefits.
Recently avonoids are considered as important compounds in a number
of nutraceutical products (Keservani et al., 2010a, b), pharmaceutical,
medicinal, and cosmetic applications. They provide a wide spectrum
of health benets and disease prevention. This is due to their therapeutic
efcacies like anti-inammatory, anti-oxidative, anti-carcinogenic, and anti-
mutagenic properties and their capacity to control and inuence key cellular
enzyme functions. They are strong inhibitors of inammatory enzymes like
cyclo-oxygenase (COX), xanthine oxidase (XO), phosphoinositide 3-kinase,
and lipoxygenase. Flavonoids lowered the cardiovascular mortality rate and
prevented CHD. The mechanism by which avonoids work is still a mystery
(Pancheetal, 2016; Keservani & Sharma, 2014).
6.4 ANTI-INFLAMMATORY MECHANISM OF FLAVONOIDS
Many recent studies have shown that the daily intake of flavonoids will
help to reduce the risk of cardiovascular problems (Keservani et al., 2016).
The antithrombotic, anti-ischemic, and antioxidant properties of flavonoids
(Keservani et al., 2020) can give a protective effect against coronary heart
problems. Flavonoids work in three ways to minimize the risk of coronary
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128 Flavonoids as Nutraceuticals
heart disease. They can improve the coronary vasodilation, platelets in the
blood are less likely to clot, and low-density lipoproteins are less likely to
oxidize. The flavonoids found in citrus plants have significant anti-inflamma
-
tory properties. The compounds inhibited the synthesis and biological activi-
ties, including signal transduction pathways of different pro-inflammatory
mediators (Benavente et al., 2008).
Inammation is the complex biological response of the immune system
against some harmful stimuli, such as foreign particles, antigens, pathogens,
damaged cells, and other irritants. It is a protective mechanism of the body
to remove the injurious stimuli. The inammatory response also initiates
the healing process for the tissue. The inammatory response involves the
action of many enzymes, such as phosphodiesterase, phospholipase A2,
lipoxygenases, COX, protein tyrosine kinases, and protein kinase C. These
enzymes are vital in the activation of cells, such as endothelial cells, which
are involved in generating inammatory responses. Cyclooxygenase (COX)
is an enzyme that plays a crucial role as an inammatory mediator and is
involved in the release of arachidonic acid, a precursor for the biosynthesis
of eicosanoids like prostaglandins and prostacyclin. COX enzyme cata
-
lyzes the conversion reaction of arachidonic acid into prostaglandins and
thromboxanes; COX-2 is an inducible enzyme that is only expressed after
some inammatory stimuli, whereas COX-1 is responsible for the supply
of prostaglandins for preserving the integrity of the stomach mucosa and
provide appropriate vascular homeostasis (Walker et al., 2000). An inam
-
matory reaction begins with the generation and release of arachidonic acid.
Prostaglandins and nitric oxide (NO) biosynthesis play a role in the inam-
matory response, and isoforms of inducible nitric oxide synthase (iNOS) and
cyclooxygenase (COX-2) produce a signicant amount of these mediators
(Permender et al., 2009). The anti-inammatory effect of most avonoids,
notably avone derivatives, is mediated by modication of proinamma-
tory gene expression, such as cyclooxygenase-2, iNOS, and numerous key
cytokines.
6.5 MEDICINAL USES OF ASTERACEAE PLANTS
Plants of the Asteraceae family feature hairy, fragrant leaves and flat clusters
of flowers with a head inflorescence and terminal position; some are popular
garden plants with a variety of colorful flowers (asters, chrysanthemum,
cosmos, dahlia, marigolds, and zinnias). The majority of the Asteraceae
family members are medicinal plants which have therapeutic properties.
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129 Flavonoids of Asteraceae-Promising Anti-Inflammatory Agents
Achillea, Carthamus, Chromolaena, Emilia, and Pluchea are among them
(Achika et al., 2018).
Ethnopharmacological studies have been performed in different countries
from the ancient time. The Asteraceae family of medicinal plants is used to
treat wounds and cuts; they are highly efcient wound-healing agents. Infor
-
mation and evidence obtained from the traditional medicinal practices have
the potential to open new ways for the development of novel and highly ef
-
cient therapies based on the medicinal properties of these plants (Alexander
et al., 2018). Asteraceae family plants have a signicant role in traditional
medicinal practices. They are used to cure wounds, cuts, dermatological
problems, inammation, etc. The uses of medicinal plants from the Astera-
ceae family in dermatological diseases are listed in Table 6.1. Asteraceae is
a widely distributed family, and most of the plants coming under this family
share a similar chemical composition for the compounds: for example, a
natural polysaccharide with strong prebiotic properties is found in almost
all Asteraceae members. They are anti-inammatory, antioxidant, wound
healing, diuretic, and antimicrobial properties. Their potent pharmacological
effects and medicinal properties, avonoids, a s is attributed to the presence
of their wide range of phytochemical constituents, including phenolic acids,
polyphenols, acetylenes, and triterpenes.
All parts of the plant Tagetes erectus L. (Asteraceae) are of medicinal
value and used to treat many diseases, including pain, inammation, tumors,
and various gastrointestinal diseases. It also has therapeutic uses in traditional
medicine. Studies showed that the leaves of T. erectus showed antinocicep-
tive and anti-inammatory activities (Shinde et al., 2009).
Porophyllum ruderale (Jacq.) Cass. is a common weed widespread in
subtropical America and Conyza bonariensis (L.) Cronq. is a prolic agri-
cultural weed, and both of the species are used in folk medicine for treating
various ailments. Conyza bonariensis nds popular use in the treatment
of diarrhea and hemorrhoids. Species of this genus are used, among other
purposes, for treating diabetes, malaria, and gastrointestinal inammation
(Souza, 2003).
Eclipta alba is an herb coming under the Asteraceae family, commonly
known as Bringharaj according to the Ayurvedic system of medicine. It is
used as a liver tonic to rejuvenate and for good hair. Eclipta prostrata is
used for athlete foot eczema. It is also used for anti-venom treatment against
snake bites. It is used as a scalp tonic for hair care (Bruneton et al., 2007).
The leaf decoction of Eclipta is used by the Rakhain tribal healers of Chit-
tagong Division, Bangladesh for treating Malaria.
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130 Flavonoids as Nutraceuticals
Helianthus annuus Linn. belongs to the family Asteraceae, having many
folkloric uses and ethnomedicinal practices in India, Pakistan, and Southeastern
Nigeria. The plant is used against the conditions of inammation, pyrexia, worm
infestation, diabetes mellitus, and other stomach ailments (
Samuel et al., 2019).
Senecio serratuloides (Asteraceae) is a traditional herbal drug used against
skin wounds in South Africa. The plant contains compounds like hepatotoxic
alkaloids, which may cause the death of herbivorous animals. The plant is
traditionally used to cure wounds and cuts (Gould et al., 2015).
Aspilia africana is a plant that grows in Africa (Pers.) C. D. Adams is a less
toxic plant that has been used in African traditional medicine for generations
to treat wounds and other related conditions, including stopping bleeding
from severed arteries. They are commonly called wild sunower, one of the
highly valued wound healing plants throughout its distribution range and
beyond this unique wound healing plant, commonly known as “hemorrhage
plant” due to its signicant ability to stop serious bleeding. A. africana is
reported to be crucial in the treatment and management of many serious
diseases and disorders, including headaches, corneal opacities, rheumatic
arthritis, stomach problems, cough, gonorrhea, pains, and tuberculosis. The
leaf decoction is taken as a tonic by the women immediately after delivery.
A. africana plant is known to possess signicant antimicrobial, antimalarial,
and anti-inammatory properties (Richard et al., 2019).
Elaphantopus scaber Linn. (Asteraceae) is distributed in the moist and
deciduous forests of central Western Ghats region. The plant is popularly
known as Elephant foot in English. In the Indian system of medicine, the
medicinal attribution of the plant has been known for a long time. As per
the traditional claims, the roots of this plant are used as antipyretic, cardio-
tonic, and diuretic. The whole plant material is macerated and applied on
the surface of wounds to cure. The aqueous extract of the plant is applied
externally to cure eczema and ulcers (Singh et al., 2005).
Wedelia chinensis belonging to the family Asteraceae, is often infused
with hot water and is often used as herbal tea and also as an anti-inammatory
tonic or medicinal food (Lin, 2014). Tridax procumbens is commonly used
to treat anti-inammatory conditions and as an analgesic agent. The crude
decoction prepared from leaves of Tridax procumbens and Andrographis
paniculata (Acanthaceae) is used by some tribal healers for the cure of
malaria fever.
Artemisia absinthium, commonly known as wormwood, is a peren-
nial herb. Because of its strong odor, it is frequently used with biological
pesticides. The plant showed medicinal properties like diuretic, balsamic,
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Flavonoids of Asteraceae-Promising Anti-Inflammatory Agents 131
digestive, and depurative. It's also utilized as a supplement in the treatment
of leukemia. The aerial part of the plant shows snake anti-venom activity.
Acmella oleracea is a source plant of the compound spilanthol, which
belongs to N-acrylamides, exhibits a diuretic effect, and is used in oral
healthcare frequently used as a toothpaste additive. Achillea kellalensis
owers contain avonoids, and their topical application can hasten wound
healing. The extract of Achillea millefolium possesses estrogenic proper-
ties due to the presence of phytoestrogens like luteolin and apigenin. They
have a stronger binding afnity to estrogen receptors (ERs) than estradiol.
Calendula ocinalisis exhibited wound-healing effects and antibacterial
and antiviral properties (Rolnik et al., 2021).
Ageratum conyzoides (L.) (Asteraceae), herbal infusion of which is given
for gastrointestinal ailments such as diarrhea, dysentery, and intestinal colic
with atulence. This plant is used as a worm medicine in Cameroon. The
crushed fresh fruits of Xanthium strumarium L. are used by the coastal tribes
of Odisha state, India for the treatment of lariasis (unpublished observa
-
tions). The plant is used against chronic malaria by the tribes of Bannu
district, Pakistan.
6.6 ETHNOMEDICINALLY IMPORTANT PLANTS FROM
ASTERACEAE
TABLE 6.1 Application of Traditional Medicine
Sl. Botanical Name Local Name Applications in Traditional Medicine
No.
1.
Acanthospermum
Kadalmullu Juice of leaf and young stem is used
hispida DC.
against wounds and skin scratches with 2%
calcium carbonate solution.
2.
Agreratum conyzoides
Nayitulasi Leaf juice is used on skin scars and
L.
Leprosy.
3.
Artemisia absinthum
Vilayeti The whole plant paste is an antiseptic and
L.
used as a detergent agent for skin diseases.
4.
Artemisia pallenswall
Davan Leaf juice is applied against wounds and
cuts of skin.
5.
Calendula officinalis
Giragola An ointment prepared from the flowers of
Corolla is used on skin ailments. Leaf paste
is being used on external ulcers and on
open sores.
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132 Flavonoids as Nutraceuticals
TABLE 6.1 (Continued)
Sl.
No.
Botanical Name
Local Name Applications in Traditional Medicine
6.
Carthumus tinctorius
Kusabhe Leaf paste with a few drops of Pongamia
L.
seed oil is used on skin eruptions and
eczema.
7.
Chrysanthemum
Jamanthi Leaf juice is used for the burning sensation
coronarium L.
of skin diseases externally.
8.
Chrysanthemum
Jamanthi The paste prepared with flower sepals and
indicum L.
a few drops of lemon juice is applied on
scars on the facial cheeks externally to
remove pimples.
9.
Eclinops echinatus
Kantalu Root paste is most useful to heal skin
Roxb.
wounds within 3–5 days.
10.
Eclipta alba (L.)
Brungaraja Leaf paste is applied twice a day and
found to be most useful for eczema and
ringworms.
11.
Eclipta prostrata L.
Kesharaja The paste prepared from the whole plant
part is useful for skin cuts and wounds.
12.
Helianthus annus L.
Surya kanthi Young Leaves tender-made bandages on
wound swellings, and a leaf decoction is
used for washing wounds.
13.
Tridax procumbens L.
Chiravanaku Leaf juice and powder are applied on cuts
and injured parts of the skin.
14.
Vernonia cinerae (L.)
Poovamkurunthal The whole plant paste is used to cure
Less.
eczema and ringworms and is also used for
skin eruptions.
6.7 FLAVONOIDS IN ASTERACEAE
The medicinal plants coming under the family Asteraceae are widely used
in traditional medicine and Ayurveda due to the presence of secondary
metabolites such as alkaloids, flavonoids, phenolic compounds, terpenoids,
and coumarins. Phenolic compounds and flavonoids are widely distributed
in the plants of the Asteraceae family, and some of them have the ability
to inhibit parasites. Flavonoids are classified into several subgroups, like
flavone, flavonol, flavanone, dihydro-flavonol, flavan-3-ol, flavan-3,4-diol,
chalcone, aurone, and anthocyanidine. Some plant flavonoids exist in biofla-
vonoids and glycosidic forms.
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Flavonoids of Asteraceae-Promising Anti-Inflammatory Agents 133
6.8 COMMON FLAVONOIDS IN ASTERACEAE FAMILY
Kristó et al. (2002) analyzed the antioxidant avonoids by capillary
electrophoresis (CE) from the plants Solidago gigantean, Taraxacum oci
-
nale Wiggers and Webers (Asteraceae). Solidago gigantea was investigated
because it has diuretic, spasmolytic, and wound-healing effects. Taraxacum
ocinale was investigated because; it has good diuretic and choleretic
activity. The study identied quercetin-3-O-β-rutinoside (rutin), quercetin-
3-O-β-D-glucoside (iso-quercitrin), and the most prevalent component
in Solidago gigantea is chlorogenic acid and apigenin-7-O-β-glucoside,
luteolin-7-O-β-glucoside, and chlorogenic acid in Taraxacum ocinale and
discovered that quercetin-3-O-α-rhamnoside (quercitin) and quercetin-3-O
-
β-galactoside (hyperoside) were absentin Solidago gigantea and quercitin
from Morus nigra. Quercetin is a avonoid found in fruits, vegetables, and
medicinal plants. It has very potent and unique biological activities that help
to improve mental and physical performance and helps to reduce infection-
related health problems. These effects of the compound are responsible for
the potential health benets and disease resistance.
Quercetin and isoquercetin are known for their anti-inammatory activity.
The anti-inammatory property of quercetin and iso-quercetin investigated
were reported in an experimental murine allergic asthma model in mice.
Quercetin and isoquercitrin are particularly effective in eosinophilic inam-
mation suppressors, and they can be good against allergies, according to the
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134 Flavonoids as Nutraceuticals
ndings (Rogerio et al., 2007). Quercetin also inhibits NLRP3 inamma-
some formation by affecting TXNIP (Al-Saeedi et al., 2021). iNOS, cyclo-
oxygenase-2 (COX-2), and reactive C-protein (CRP) expression levels may
be regulated by kaempferol and quercetin. In a human hepatocyte-derived
cell line, they can also promote alterations in the nuclear factor kappa B
(NFB) pathway (Garca et al., 2007).
Sphaeranthus indicus is an aromatic, potent medicinal herb in the
Asteraceae family and has been studied for its potential health-promoting
properties, mainly for its anti-inammatory activity. In traditional medi
-
cine, this plant is used to treat glandular swelling, urethral discharge, and
jaundice in the neck. This plant is rich with a number of phytoconstituents
such as β-sitosterol, lupeol, β-daucosterol, 7-hydroxy sitosterol, erythrodiol
-
3-palmitate, quercetagetin, erythrodiol, gallic acid, syringic acid, quercetin,
quercetagetin-7-methyl ether, quercetagetin-7-O-glucoside and tagetone
(Shetty et al., 2015). Gallic acid, quercetin, and syringic acids are phenolic
compounds which are known for their signicant anti-inammatory activity.
The anti-inammatory potential of gallic acid was studied in zymosan
-
induced acute food pad swelling in mice. The analysis of the observation
made from the study showed that the o-dihydroxy group of gallic acid is
responsible for the inhibitory and anti-inammatory activity in vitro (Kroes
et al., 1992).
Tagetes erecta is an ornamental as well as a medicinal herb in the Astera-
ceae family used for digestive tract problems, including poor appetite, gas,
stomach pain, intestinal worms, and dysentery. It is also used for coughs,
colds, mumps, inammations, and sore eye. It has a rich quantity of avo-
noids, and its high therapeutic value is related to the high yield of avonoids
which is of effective medicinal value (Devika et al., 2014).
Sunower, Helianthus annuus is the most common member of the
Asteraceae family. It is grown all over the world for the seeds, which are used
to obtain sunower oil. Anti-inammatory, antipyretic/antifebrile/febrifuge,
and other therapeutic qualities are abundant in Helianthus annuus. Helian-
thus seeds and sprouts are high in avonoids and phenolic acids, which have
been found in sunower seeds and sprouts and have been linked to medicinal
activity. Sunower seeds and sprouts have avonoid levels of 25 and 45
mg/g quercetin, respectively. The anti-inammatory effect of sunower seed
oil and sprouts is due to the presence of the principal kind of avonoids.
Eclipta prostrata or (syn. E. Alba), (Asteraceae) is widely distributed
in tropical and subtropical regions and is used as an anti-inammatory,
wound healing drug. Many studies showed that the stem of E. prostrata was
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135 Flavonoids of Asteraceae-Promising Anti-Inflammatory Agents
effective against hyperlipidemia, hypercholesterolemia, hepatic disorders,
and spleen enlargement. The stems of this plant have been used to cure
anemia, asthma, and tuberculosis, while the leaves have been used to treat
skin problems like inammation and scalp infection. The quantitative and
qualitative analysis of ethanolic and aqueous extracts of E. prostrate identi-
ed the presence of avonoids and phenolics. The presence of avonoids in
E. prostrata was thought to be responsible for the anti-inammatory and free
radical scavenging properties (Wipawan et al., 2014). Tridax procumbens
is used by the local natives against body pain, rheumatic pains of joints,
and gastric problems. The plant is enriched with therapeutically important
avonoid compounds. The leaves of T. procumbens are highly medicinal
due to the presence of bioactive molecules. They possess a high amount
of avonoids, alkaloids, hydroxyl cinnamates, tannins, and phytosterols,
a moderate amount of lignans and benzoic acid derivatives, and very low
carotenoid contents. Around 39 known alkaloids, 23 known avonoids
were identied in the leaves. The avonoid content in the leaves is high
(6477.706 g/kg). Around 23 known avonoid compounds were detected in
the leaves, consisting of (–)-epicatechin (12.538%), kaempferol (17.593%),
(+)-catechin (7.968%), biochanin (8.202%), naringenin (6.254%), apigenin
(7.875%), daidzein (6.124%), butein (4.376%), quercetin (4.418%),
robinetin (3.895%), baicalein (3.047%), nobiletin (2.986%), (–)-epigallo-
catechin (2.806%), genistein (2.444%), (+)-gallocatechin (2.338%), ellagic
acid (1.818%), luteolin (1.707%), myricetin (1.406%), baicalin (0.735%),
isorhamnetin (0.498%), (–)-epigallocatechin-3-gallate (0.404%), silymarin
(0.359%) and (–)-epicatechin-3-gallate (0.207%). The rich avonoid content
is responsible for the signicant anti-inammatory potential of Tridax (Cath-
erine et al., 2008).
Chrysanthemum morifolium is an Asteraceae decorative and medicinal
herb used to treat hypertension, type 2 diabetes, fever, cold, headache, dizzi-
ness, and edema. It is commonly used against dermatological problems such
as skin irritations, infections, and inammations on skin. Studies on Chry-
santhemum varieties, such as C. morifolium and C. indicum, showed that the
plants contain 21 avones and avonols. The avonoids are responsible for
the ower color of Chrysanthemum and their medicinal activities, including
anti-inammatory activity.
Eupatorium species are a commonly used wound-healing medicinal
herb. It is widely used by the rural communities in India in wound-healing
treatments. The squeezed plant extract is directly applied to the wounds
and cuts for the instant stopping of blood and inammation related to
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