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116 Flavonoids as Nutraceuticals
blockage. Induction of ornithine decarboxylase by TPA was decreased by
green tea as well as its catechin components in 2C5 cells (Steele et al.,
2000); and by topical apigenin application to mouse skin (Wei et al., 1990).
Prostate-specic antigen synthesis and secretion from prostate carcinoma
cells were decreased by silibinin treatment (Agarwal, 1999). Inhibition
of cyclooxygenase-2 activity has been linked to the prevention of colon
carcinogenesis.
In breast carcinoma cells, avopiridol (a synthetic avonoid) induced
cell cycle arrest and downregulated cyclin D I, which is an important protein
for both cell cycle progression and neoplastic transformation (Carlson et al.,
1999).
5.5.3 REGULATION OF CYTOKINE RELEASE AND CYTOKINE
RESPONSE
Cellular responses are maintained by essential mediators called Cytokines.
It was found that flavonoids tend to reduce the basal and induced secretion
level of cytokines. In the research conducted (Tabary et al., 1999). Genistein
dose-dependently decreased the production of IL-8 by human bronchial
gland cells. Genistein was also responsible for decreasing the secretion of
IL-2 and leukotriene B4 from lectin-stimulated human mononuclear cells
(Atluru et al., 1991). In a study directed, it was observed that lipopolysac
-
charide (LPS)-induced TNF-a release was decreased by quercetin in the
macrophage cell line RAW 264.7 (Wadsworth & Koop, 1999).
Hypoxia-induced transcription of the plasminogen activator inhibitor-I
gene was blocked by genistein avonoid in bovine aortic endothelial cells
(Uchiyama et al., 2000). Under the stimulated condition, it was proposed
that the inhibition of protein tyrosine kinases was done by genistein
-
inhibited cytokine secretion (Atluru et al., 1991; Uchiyama et al., 2000).
Cell growth and differentiation is regulated by transforming growth factor
B (TGFB). Quercetin was shown to increase TGFB activity in the cultured
medium of ovarian cancer cells (Scambia et al., 1994); genistein, on the
other hand, enhanced TGF expression only in normal human mammary
epithelial cells but not in breast tumor cells (Sathyamoorthy et al., 1998).
It was shown that genistein impacted the expression of TGFa, epidermal
growth factor (EGF), and EGF receptor (EGFR) in the rat mammary gland
in an age-dependent manner in a study assessing the effects of prepubertal
genistein administration (Brown et al., 1998). The natural immunological
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Regulation of Gene Expression by Flavonoids 117
response includes the creation of nitric oxide (NO). Flavonoids lowered
NO generation, which is consistent with their immunomodulatory prop
-
erties. Apigenin and kaempferol inhibited LPS-inducible nitric oxide
synthase (iNOS) in macrophages, according to the ndings (Liang et al.,
1999). Many cytokines' signaling is maintained via the signal transducer
and activator of the transcription (STAT) pathway. STAT proteins are phos
-
phorylated on tyrosine and then translocated to the nucleus once the cyto-
kine binds to its receptor. STAT proteins, by binding to specic sequences
in the promoter region of target genes, exert their gene regulatory functions
(Hill & Treisman, 1995). Many avonoids, especially genistein, inhibit
protein kinases. Therefore, avonoids could inhibit STAT activation and
thus modulate various cytokines actions.
5.6 EFFECTS ON DRUG DETOXIFICATION ENZYMES
Chemical carcinogenesis could be prevented by the enhancement of
drug detoxification activity. Thus, it is observed that the drugs for cancer
chemoprevention include medicinal chemicals or dietary components that
can increase the activity of phase II detoxification enzymes. Contrary to
this, modulators of phase I enzymes could possibly give mixed results.
When examined together, flavonoids were revealed to exhibit structural-
dependent effects on both phase I and phase II enzymes. Tea and its catechin
components were the potent inducers of NADPH: quinone reductase and
glutathione S-transferase, both of them being phase II enzymes, in human
Chang liver cells (Steele et al., 2000). However, 4′-bromoflavone which
is a synthetic flavonoid, induced phase I and phase II enzymes adjunctly
in rat hepatoma cell culture and in rat tissues, even though the impact was
remarkable for its induction of phase II enzymes (Song et al., 1999). The
activation of a xenobiotic response element (XRE) and an antioxidant
response element (ARE) in the quinone reductase gene mediated the
induction of quinone reductase by 4′-bromoflavone (Song et al., 1999).
Consistent with this observation, equol and genistein – the two isoflavones
that failed to enhance glutathione S-transferase in a mouse study also could
not activate XRE (Helsby et al., 1997). Genistein and equol also could not
affect the phase I enzyme activity (Helsby et al., 1997), but quercetin was
shown to inhibit cytochrome P-450 1Al gene expression in Hep G2 cells
(Kang et al., 1999).
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118 Flavonoids as Nutraceuticals
KEYWORDS
• epigenetics
• flavonoids
• gene expression
• regulation of gene
• transcription
• translation
REFERENCES
Atluru, S., & Atluru, D., (1991). Evidence that genistein, a protein-tyrosine kinase inhibitor,
inhibits CD28 monoclonal-antibody-stimulated human T cell proliferation. Transplantation,
51(2), 448–450.
Bird, A., (2007). Perceptions of epigenetics. Nature, 447(7143), 396–398.
Bibcode:2007Natur.447.396B.
Bos, J. L., (1989). Ras oncogenes in human cancer: A review. Cancer Res., 49(17), 4682–4689.
Brad, C., (1999). Down-regulation of cyclin D1 by transcriptional repression in MCF-7
human breast carcinoma cells induced by flavopiridol. Cancer Res., 59(18), 4634–4641.
Brown, E. T., & Fuller, G. M., (1998). Detection of a complex that associates with the Bbeta
fibrinogen G-455-A polymorphism. Blood, 92(9), 3286–3293.
Buslig, B., & Manthey, J., (2002). Flavonoids in Cell Function (pp. 191–200). Kluwer
Academic/Plenum Publishers.
Culver, K. W., & Labow, M. A., (2002). Genomics. In: Robinson, R., (ed.), Genetics.
Macmillan Science Library. Macmillan Reference USA.
Dees, C., et al., (1997). Dietary estrogens stimulate human breast cells to enter the cell cycle.
Environment Health Perspective, 105(3).
Dixon, R., & Pasinetti, G., (2010). Flavonoids and isoflavonoids: From plant biology to
agriculture and neuroscience. Plant Physiol., 154, 453–457.
Dupont, C., Armant, D. R., & Brenner, C. A., (2009). Epigenetics: Definition, mechanisms
and clinical perspective. Seminars in Reproductive Medicine, 27(5), 351–357.
Griesbach, R., (2005). Biochemistry and genetics of flower color. Plant Breed Rev., 25,
89–114.
Helsby, et al., (1997). The isoflavones equol and genistein do not induce xenobiotic-
metabolizing enzymes in mouse and in human cells. Xenobiotica, 27(6).
Hill, C. S., & Treisman, R., (1995). Differential activation of c-fos promoter elements by
serum, lysophosphatidic acid, G proteins and polypeptide growth factors. EMBO J., 14(20),
5037–5047.
Hunter, P., (2008). What Genes Remember. Prospect Magazine. Archived from the original
on 1 May 2008.
https://t.me/medicina_free
119 Regulation of Gene Expression by Flavonoids
Jorgensen, J. R., (1995). Co-suppression, flower color patterns, and metastable gene
expression states. Science, 268, 686–691.
Kang, et al., (1999). Quercetin inhibits benzo[a]pyrene-induced DNA adducts in human hep
G2 cells by altering cytochrome P-450 1A1 gene expression. Nutrition and Cancer, 35(2),
175–179.
Kawada, et al., (1998). Effect of antioxidants, resveratrol, quercetin, and N-acetylcysteine,
on the functions of cultured rat hepatic stellate cells and Kupffer cells. Hepatology, 27(1),
1265–1274.
Klug, W. S., & Cummings, M. R., (2012). Concepts of Genetics (10
th
edn.). San Francisco:
Pearson Education.
Kuiper, et al., (1998). Interaction of estrogenic chemicals and phytoestrogens with estrogen
receptor beta. Endocrinology, 139(10), 4252–4263.
Kumar, S., & Pandey, A. K., (2013). Chemistry and biological activities of flavonoids: An
overview. Scientific World Journal, 2013, 16275.
Kurzer, M. S., & Xu, X., (1997). Dietary phytoestrogens. Annu. Rev. Nutr., 17, 353–381.
Mathesius, U., (2018). Flavonoids function in plants and their interaction with other
organisms. Plants (Basel), 7(2), 30.
Miksicek, (1993). Commonly occurring plant flavonoids have estrogenic activity. Molecular
Pharmacology, 44(1), 37–43.
Nadine, M. B., et al., (1998). Prepubertal genistein treatment modulates TGF-α, EGF, and
EGF-receptor mRNAs and proteins in the rat mammary gland. Molecular and Cellular
Endocrinology, 144(1, 2), 149–165.
Olivier, T., et al., (1999). Genistein inhibits constitutive and inducible NFκB activation and
decreases IL-8 production by human cystic fibrosis bronchial gland cells. The American
Journal of Pathology, 155(2), 473–481.
Panche, A., Chandra, S., Diwan, A., et al., (2015). Alzheimer’s and current therapeutics: A
review. Asian J. Pharm. Clin. Res., 8, 14–19.
Patch, C., & Middleton, A., (2018). Genetic counseling in the era of genomic medicine.
British Medical Bulletin, 126(1), 27–36.
Ranelletti, F. O., et al., (2000). Quercetin inhibits p21-RAS expression in human colon cancer
cell lines and in primary colorectal tumors. Int. J. Cancer, 85(3), 438–445.
Rieger, R., Michaelis, A., & Green, M. M., (1968). A Glossary of Genetics and Cytogenetics:
Classical and Molecular. New York: Springer-Verlag.
Rutherford, A., (2015). Beware The Pseudo Gene Genies. The Guardian.
Samanta, A., Das, G., & Das, S., (2011). Roles of flavonoids in plants. Int. J. Pharm. Sci.
Tech., 6, 12–35.
Sathyamoorthy, N., Gilsdorf, J. S., & Wang, T. T., (1998). Differential effect of genistein on
transforming growth factor beta 1 expression in normal and malignant mammary epithelial
cells. Anticancer Research, 18(4A), 2449–2453.
Scambia, et al., (1994). Quercetin potentiates the effect of Adriamycin in a multidrug-
resistant MCF-7 human breast-cancer cell line: P-glycoprotein as a possible target. Cancer
Chemotherapy and Pharmacology, 34, 459–464.
Segaert, et al., (2000). Vitamin D receptor expression is linked to cell cycle control in normal
human keratinocytes. Biochemical and Biophysical Research Communications, 279(1),
89–94.
https://t.me/medicina_free
120 Flavonoids as Nutraceuticals
Servedio, M. R., Brandvain, Y., Dhole, S., Fitzpatrick, C. L., Goldberg, E. E., Stern, C. A.,
Van, C. J., & Yeh, D. J., (2014). Population Genetics – Latest Research and News. www.
nature.com. (accessed on 24 June 2023).
Song, et al., (1999). Cancer chemopreventive activity mediated by 4′-bromoflavone, a potent
inducer of phase II detoxification enzymes. Cancer Res., 59(3), 578–585.
Takahashi, A., & Ohnishi, T., (2004). The significance of the study about the biological effects
of solar ultraviolet radiation using the exposed facility on the international space station.
Biol. Sci. Space, 18, 255–260.
Tyagi, A., Agarwal, C., & Agarwal, R., (2002). Inhibition of retinoblastoma protein (Rb)
phosphorylation at serine sites and an increase in Rb-E2F complex formation by silibinin
in androgen-dependent human prostate carcinoma LNCaP cells: Role in prostate cancer
prevention. Mol. Cancer Ther., 1(7), 525–532.
Uchiyama, et al., (2000). Hypoxia induces transcription of the plasminogen activator
inhibitor-1 gene through genistein-sensitive tyrosine kinase pathways in vascular endothelial
cells. Arteriosclerosis, Thrombosis, and Vascular Biology, 20, 1155–1161.
Vernon, E. S., et al., (2000). Progress in cancer chemoprevention: Development of diet-
derived chemopreventive agents. The Journal of Nutrition, 130(2), 467S–471S.
Vernon, E. S., Gary, J. K., Douglas, B., Charles, W. B., Rajendra, M., Donya, B., Caroline,
C. S., Songyun, Z., & Sheela, S., (2000). Comparative chemopreventive mechanisms of
green tea, black tea, and selected polyphenol extracts measured by in vitro bioassays.
Carcinogenesis, 21(1), 63–67.
Wadsworth, T. L., & Koop, D. R., (1999). Effects of the wine polyphenolics quercetin and
resveratrol on pro-inflammatory cytokine expression in RAW 264.7 macrophages. Biochem.
Pharmacol., 57(8), 941–949.
Waters, K., (2013). Molecular genetics. In: Zalta, E. N., (ed.), The Stanford Encyclopedia of
Philosophy (Fall 2013 ed.). Metaphysics Research Lab, Stanford University. Alberts, Bruce
(2014–11–18). Molecular Biology of the Cell (6
th
edn.). New York, NY.
Wei et al., (1990). Inhibitory effect of apigenin, a plant flavonoid, on epidermal ornithine
decarboxylase and skin tumor promotion in mice. Birt. Cancer Res., 50(3), 499–502.
Yu-Chih, L., et al., (1999). Suppression of inducible cyclooxygenase and inducible nitric
oxide synthase by apigenin and related flavonoids in mouse macrophages. Carcinogenesis,
20(10), 1945–1952.
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Flavonoids as Nutraceuticals. Rajesh K. Kesharwani, Deepika Saini, Raj K. Keservani, and
Anil Kumar Sharma (Eds.)
© 2024 Apple Academic Press, Inc. Co-published with CRC Press (Taylor & Francis)
CHAPTER 6
FLAVONOIDS OF ASTERACEAE-
PROMISING ANTI-INFLAMMATORY
AGENTS
S. R. SUJA,
1
V. ASWATHY,
1
B. S. BIJUKUMAR,
2
and
R. PRAKASHKUMAR
1
1
Ethnomedicine and Ethnopharmacology Division, KSCSTE–Jawaharlal
Nehru Tropical Botanic Garden and Research Institute, Palode,
Thiruvananthapuram, Kerala, India
2
Post-Graduate, Department of Zoology and Research Center,
Mahatma Gandhi College, Thiruvananthapuram, Kerala, India
ABSTRACT
One of the most important plant families is the Asteraceae, and their medic-
inal effects are attributed to phytochemical compounds such as polyphenols,
synthetic resin acids, flavonoids, acetylenes, and triterpenes. Nowadays,
there is a growing interest in natural sources, which has sparked study
interest in the Asteraceae family. The majority of non-infectious diseases are
developed and worsened by prolonged and persistent chronic inflammation.
The prevailing therapies for many of those chronic diseases generally cause a
lot of deleterious side effects, warranting the requirement of safer, less toxic,
and less expensive treatment for patients. For hundreds of years, flavonoids
and their preparations were used to treat numerous human diseases. Recent
studies have additionally shown that flavonoids, particularly flavone deriva
-
tives, regulation of pro-inflammatory mediators such as cyclooxygenase,
shown unique therapeutic activity, inducible nitric oxide synthase (iNOS),
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122 Flavonoids as Nutraceuticals
and a number of other cytokines. Because of these diverse mechanisms of
action, flavonoids are thought to be affordable candidates for drug devel
-
opment. Understanding the involvement of inflammatory mediators in
several disease conditions and, additionally, the mechanism of action of
phytochemical compounds from natural sources can open the way for herbal
drug development against inflammatory diseases. The chapter explored the
role of flavonoids of plants of the Asteraceae family in combating several
inflammatory processes underlying chronic disease conditions.
6.1 INTRODUCTION
India is one of the largest biodiversity-rich countries with an immense
wealth of medicinal plants. With about 1,620 genera and 23,600 species
of plants with a worldwide distribution, the Asteraceae family (Sunflower
family) is one of the largest plant groups. The Asteraceae family includes
a variety of well-known species like chicory, sunflower, lettuce, coreopsis,
dahlias, wormwood, and other medicinal plants. The main characteristics of
the family are the presence of composite flower heads and one-seeded fruits.
The medicinal plants coming under the family are traditionally used against
many diseases. The plants are typically found within numerous ecosystems
of India because of their adaptations, like floral characteristics, fertilization,
seed spreading mechanisms, etc. A large number of Asteraceae family plants
have numerous medicinal applications. For more than thousands of years,
some of the medicinal plants coming under the Asteraceae family have been
cultivated for food and medical purposes. Asteraceae members are commonly
found in subtropical regions with arid and semi-arid conditions, but they are
enjoying a cosmopolitan distribution. The medicinal plants coming under
the Asteraceae family exhibited therapeutic effects such as antimicrobial,
anti-inflammatory, antioxidant, and hepatoprotective (Rolnik et al., 2021).
Traditional knowledge of medicine is referred to as knowledge of the
medicinal property of a particular plant species and its use against some
disease conditions. It has been in use for many years, and the knowledge has
been passed down the generations. It has been used since time immemorial
by the ancient traditional healers to improve human health. In the villages
and remote areas, traditional medicine has maintained its popularity, and it
is considered a primary healthcare practice at the community level (WHO).
Generally, the traditional knowledge is communicated and transferred orally,
and it is informal. Traditional medicine and other indigenous medicinal
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Flavonoids of Asteraceae-Promising Anti-Inflammatory Agents 123
practices are based on the use of potential medicinal plants for treating
various ailments. According to WHO, 3.5 billion people in developing and
under-developing countries use herbal medicaments for primary health care.
Traditional healers use different plant parts to make crude medicines and
are used for treating diseases such as wounds, inammation, fever, cough,
kidney problems, etc. Recently erosion of traditional knowledge among
the people was serious due to many factors such as the lack of interest of
the young generation in gaining knowledge, agricultural expansion, Orally
transferred knowledge without any documentation, species unavailability,
and modern education inuence, the unwillingness of the traditional healers
to disclose their secret knowledge to others. The indiscriminate use of root
plants for the preparation of traditional medicine could also be considered
as a threat.
Asteraceae plants have been used to cure various diseases from ancient
times. Studies showed that they exhibit analgesic, antimicrobial, antiviral,
antioxidant, anti-proliferative, anti-inammatory, and Vasodilatory activi-
ties. These plants are an inevitable part of traditional treatments such as
dermatological problems, wounds, and associated inammations, etc. The
pharmacological effects of Asteraceae plant species are due to the presence
of a wide range of phytochemical compounds, including alkaloids, avo
-
noids, polyphenolic compounds, phenolic acids, etc.
6.2 INFLAMMATION
Inflammation refers to the physiological response to different cellular,
vascular, and pathological injuries. When the body reacts to inflammation,
it starts to activate the inflammatory cells. The activation of inflammatory
cells such as neutrophils, basophils, and eosinophils, and mononuclear cells
like monocytes and macrophages leads to the release of many inflammatory
mediators. Inflammation is characterized by pain, redness on the inflamed
area, heat or burning sensation, and swelling. Inflammation results increase
in the blood flow to the injured area or infected tissue. It results in the redness
and warmth of the inflamed area. Some of the inflammatory mediators cause
fluid to leak into the tissues of the affected area. This fluid leakage results
in swelling.
Microorganisms or tissue damage can induce inammatory responses
in body tissues. It will activate the release of PAMPs (pathogen-associated
molecular patterns) and DAMPs (damage-associated molecular patterns).
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124 Flavonoids as Nutraceuticals
The antigen-specic and nonspecic immune cells, like dendritic cells
(DCs) and macrophages, can recognize these molecules through various
receptors found on their cell surface, like pattern recognition receptors
(PRRs). When get activated, these immune cells start to produce chemo
-
attractant molecules, which are controlled by the transcription factor NF-κB.
The transcription factor NF-κB is highly signicant in the regulation of the
expression of inammatory enzymes like COX and other pro-inammatory
cytokines, which makes it one of the most signicant transcription factors
(TFs) during the inammatory process and pain. Cytokines and chemokines
produced by these immune cells and formyl-peptide (fMLP) released by
dying cells activate vascular endothelial cells. This activation provides
a gradient of signals to guide neutrophils precisely to the inamed area
following a spatial, temporal, and hierarchic cascade of mediators (Catherine
et al., 1998).
Non-steroidal anti-inammatory drugs or NSAIDs are commonly used
for treating inammatory diseases and other health problems associated with
inammation. The common side effects of NSAIDs include renal problems,
stomach ulcers, vomiting, headache, nausea, blurred vision, dizziness, and
other allergic reactions. In this scenario, plant-based natural anti-inam
-
matory drugs have a signicant position in the treatment of inammatory
conditions. When compared to conventional medicines, plant-based drugs
and other herbal remedies have fewer side effects. Natural drugs can be
carefully selected as a novel therapeutic agent for managing inammatory
ailments. The phytochemical constituents present in medicinal plants have
many therapeutic properties, including anti-inammatory, wound healing,
anti-arthritic analgesics, etc. Among these bioactive phytochemicals' avo
-
noids have a signicant position. They occur in many foods like vegetables
and fruits, and medicinal plants, and they are the most active constituent,
having the ability to reduce and cure inammation.
6.3 FLAVONOIDS
Flavonoids are an important class of plant constituents like polyphenolic
compounds with great structural diversity found in plants and commonly
consumed in diets. These secondary metabolites are the most important
plant pigments which impart flower coloration and produce red/blue- or
yellow-colored petals to attract pollinator animals. Flavonoids are the major
plant pigments which are synthesized from phenylalanine. They display
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125 Flavonoids of Asteraceae-Promising Anti-Inflammatory Agents
bright colors known from flower petals; they can emit brilliant fluorescence
when get excited by UV and are present in green plant cells. The flavonoid
compounds are used in taxonomical classification, especially in chemotax
-
onomy. They have an important role in the regulation of plant growth by
inhibiting exocytosis of the auxin and indole acetic acid, and they influence
other biological activities of cells in various ways. Some of the flavonoid
compounds showed antimicrobial effects and inhibited viral enzymes like
reverse transcriptase and protease, and destroyed some pathogenic proto
-
zoans (Havsteen, 2002).
The other functions of avonoids in plants include plant development
regulation, pigmentation, protection from damage due to UV exposure,
roles in plant defense mechanisms, and signaling. Many avonoids act as
bioactive compounds that interact with nucleic acids or proteins and show
different kinds of pharmacological properties such as antimicrobial, insec
-
ticidal, antifungal, etc. They act as symbionts, allelochemicals, and antimi-
crobial and anti-herbivory factors in plants. Flavonoids are one of the major
dietary components in many fruits and vegetables. Because of their common
occurrence in the human diet, many avonoids present in medicinal plants
are used for controlling inammatory responses and tumor development.
Many studies have shown that avonoids exhibit biological and pharma-
cological activities, including antioxidant, cytotoxic, anticancer, antiviral,
antibacterial, anti-inammatory, anti-allergic, antithrombotic, cardio-
protective, hepatoprotective, neuroprotective, antimalarial, anti-leishmanial,
antitrypanosomal, and antimonial properties (Erica et al., 2017). Aglycones,
glycosides, and methylated derivatives are all examples of avonoids. The
basic structure of the avonoid compound is the aglycone six-member ring
condensed with the benzene ring and is either α-pyrone (avonols and ava-
nones) or its dihydroderivative (avonols and avanones).
Flavonoids constitute one of the most important classes of bioactive
compounds in higher medicinal plants. Flavonoids are divided into six
subclasses based on their chemical structure, such as avones, avanones,
isoavones, avanols, neoavonoids, avan-3-ols, chalcones, and antho-
cyanidins. Flavones are present in the leaves of many plants, owers, and
fruits. Luteolin and apigenin are the most studied avones.
Flavones can be found as glucosides in owers, plants, and fruits. The
hydroxyl group in the fth position of the A ring is found in the majority of
avones found in plants and fruits, While hydroxylation in other sites, most
notably in the seventh position of the A ring or the 3′ and 4′ positions of the
B ring, varies depending on taxonomic categorization (Panche et al., 2016).
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