Chrysanthemum flower, Shen Nong the Father of Chinese Medicine classified it as Superior Herb. More than 4,000 phytochemicals are known but only a few have been studied in details. Major phytochemicals are flavonoids, phenolic acids and anthocyanins. Anti-microbial, antioxidant, anti-inflammatory, immuno-modulatory, anticancer, anti-hyperglycemic and anti-hyptensive properties have been shown. Therapeutic effects have yet to be established.

1. FLOWER AS MEDICINE:
CHRYSANTHEMUM,
CHRYSANTHEMUM MORIFOLIUM
By
Kevin KF Ng, MD, PhD.
Former Associate Professor of Medicine
University of Miami. Miami, FL. USA
Email: kevinng68@gmail.com
A slide presentation for HealthCare Provider Seminar Sept. 2019

2. Outline of Lecture
▪ What is chrysanthemum?
▪ History, scientific classification
▪ Composition, Bioactive compounds
▪ Bioavailability, pharmacological actions
▪ Clinical studies
▪ Meta-analysis
▪ Summary

3. What is chrysanthemum?
▪ Chrysanthemums (/krɪˈsænθəməm/), sometimes called mums or chrysanths,
are flowering plants of the genus Chrysanthemum in the family Asteraceae.
▪ They are native to Asia and northeastern Europe.
▪ Most species originate from East Asia and the center of diversity is in China.
▪ Shen Nong, the father of Chinese Medicine, classified it as a superior herb.
▪ Countless horticultural varieties and cultivars exist.

4. Other names of chrysanthemum
▪ Anthemis grandiflorum
▪ Anthemis stipulacea
▪ Chrysanthemum indicum
▪ Chrysanthemum sinense
▪ Chrysanthemum stipulaceum
▪ Chrysanthemum morifolium
▪ Crisantemo
▪ Dendranthema grandiflorum
https://www.webmd.com/vitamins/ai/ingredientmono-904/chrysanthemum

5. Historical milestones of chyrsanthemum flower

6. Scientific classification of chrysanthemum

7. Anatomy of a chrysantemum flower
https://www.researchgate.net/figure/Typical-structure-of-a-chrysanthemum-
flower-showing-disc-and-ray-florets-Reprinted-with_fig1_280483116

8. Nutrient composition of raw chrysanthemum
https://ndb.nal.usda.gov/ndb/foods/
macronutrients g/100g minerals mg/100g vitamins mg/100g

9. More than 4,000 phytochemicals in Chrysanthemums:
only 150 are studied in some detail
▪ Major phytochemicals in chrysanthemum:
▪ Flavonoids
▪ Phenolic acids
▪ Anthocyanins
▪ Floral scent volatile compounds in essential oil
https://pdfs.semanticscholar.org/5b79/66a5e47b01153d351c57c8d7cf3d5ac6583f.pdf

10. Extraction of bioactive compounds from chrysanthemum flowers
https://www.ncbi.nlm.nih.gov/pubmed/23427540

11. 11 compounds have been identified in two different color
chrysanthemum flowers. (2019)
https://www.mdpi.com/1420-3049/24/2/329/htm

12. Six new compounds are discovered from the flowers of
Chrysanthemum morifolium (2018)
https://www.sciencedirect.com/science/article/pii/S0045206818308253#f0025

13. Bioactive compounds of purple and yellow chrysanthemum
https://pdfs.semanticscholar.org/5b79/66a5e47b01153d351c57c8d7cf3d5ac6583f.pdf

14. Compounds isolated from essential oil of Chrysanthemum plants
https://www.researchgate.net/figure/Compounds-isolated-from-essential-oil-of-Chrysanthemum-plants_tbl2_215802093

15. Summary of Phytochemicals in
chrysanthemum flowers
Photosynthesis

16. HPLC chromatograms of (a) the dark purple chrysanthemum cultivar
infusion and (b) the yellow chrysanthemum cultivar infusion
detected at 280 nm (2019)
purple chrysanthemum
yellow chrysanthemum
https://pdfs.semanticscholar.org/5b79/66a5e47b01153d351c57c8d7cf3d5ac6583f.pdf
Chlorogenic acid
Luteolin-7-O-β-glucoside
Apigenin-7-O-β-glucoside 2
3,5-Dicaffeoylquinic acid
ApigeninLuteolin
Apigenin-malonylglucoside
Luteolin-malonylglucoside
Luteolin-7-O-β-glucoside

17. Major classes of natural products (A) flavonoids, (B) anthocyanidins,
(C) phenolic acids, (D) alkaloids in plants (2014)
https://www.researchgate.net/publication/266681184

18. Basic structures of Flavonoid Subclasses
https://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/flavonoids

19. Classification of flavonoids
Six classes of flavonoids
1. Flavan-3-ols
2. Flavonols
3. Anthocyanins
4. Isoflavones
5. Flavanones
6. Flavones
https://pdfs.semanticscholar.org/635a/f47f33a89f5ef633fcf161d94658cc483c43.pdf?_ga=
2.258124106.1749932037.1564010839-321613291.1564010838

20. Structural modification of luteolin from Chrysanthemum flower
leads to increased tumor cell growth inhibitory activity (2016)
https://www.sciencedirect.com/science/article/pii/S0960894X16306540

21. Anatomy of the gastrointestinal tract

22. First by-pass effect through the liver
Liver
systemic circulation

23. Pharmacokinetic (PK) parameters of unconjugated luteolin after
oral and i.v. administration of luteolin at a dose 50 mg/kg in rats. (2008)
IV oral
https://journals.sagepub.com/doi/pdf/10.1177/1934578X0800301218

24. Absorption and Excretion of Luteolin and Apigenin in Rats after
Oral Administration (200 mg/kg)of Chrysanthemum morifolium Extract (2006)
https://www.ncbi.nlm.nih.gov/pubmed/17227053
systemic circulation

25. Oral Bioavailability of Luteolin and Apigenin in Chrysanthemum
Morifolium Extract Is Much Higher Than When They are Given As
Pure Individual Compounds in Rats (2008)
https://www.researchgate.net/publication/268145508_

26. Pharmacokinetic study of luteolin and apigenin after
oral administration of Chrysanthemum extract in rats (2012)
▪ Luteolin and apigenin are two main bioactive components in Flos Chrysanthemi
▪ chrysoeriol and diosmetin are two methylated metabolites of luteolin in vivo by
cathechol-O-methyltransferase (COMT).
https://www.sciencedirect.com/science/article/pii/S0367326X12002584

27. Pharmacological actions of major bioactive compounds in
chrysanthemum flowers

28. Number of articles on luteolin, apigenin and chlorogenic acid
in PubMed from 1946 to 2018
https://www.ncbi.nlm.nih.gov/pubmed/
Chlorogenic acid

29. Scientific studies of luteolin on cell lines, animals and human
Cells
• Antioxidant
• Antimicrobial
• Antiinflammatory
• Immunmodulatory
• Anticancer
• Antihyperglycemia
• Antihyperlipidemia
• Antihypertensive
• Antiestrogenic
Animal
• Antioxidant
• Antiinflammatory
• Immunmodulatory
• Anti-obesity
Human
• Limited number
• of studies
Adapted from https://www.mskcc.org/cancer-care/integrative-medicine/herbs/cinnamon

30. Scientific studies of Apigenin on cell lines, animals and human.

31. Total flavonoids of Flos Chrysanthemi protect arterial
endothelial cells against oxidative stress (2012)
https://www.sciencedirect.com/science/article/pii/S0378874111008063

32. The inhibitory effect of luteolin on Angiotensin II-induced
migration of vascular smooth muscles
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4606148/

33. Anti-inflammatory effects of luteolin: A review of in vitro, in
vivo, and in silico studies (2018)
https://www.ncbi.nlm.nih.gov/pubmed/29801717

34. Anti-inflammatory effects of chlorogenic acid in
lipopolysaccharide-stimulated RAW 264.7cells (2013)
https://link.springer.com/article/10.1007/s00011-013-
0674-4

35. Luteolin in the Management of Type 2 Diabetes Mellitus 2019
https://www.foodandnutritionjournal.org/volume7number2/luteolin-in-the-
management-of-type-2-diabetes-mellitus/

36. In vitro effect of L7G (Luteolin-7-glucoside) on
HMGCR (HMG-CoA reductase) enzyme activity:
Inhibition of cholesterol synthesis
https://www.hindawi.com/journals/ecam/2015/647832/fig7

37. Anti-degenerative effect of Apigenin, Luteolin and Quercetin on
human keratinocyte and chondrocyte cultures: SAR evaluation 2018
https://www.ncbi.nlm.nih.gov/pubmed/29108086

38. Chlorogenic acid alleviates obesity and modulates gut
microbiota in high‐fat‐fed mice (2019)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6392816/

39. Neuroprotective compound from flower of chrysanthemum
https://www.sciencedirect.com/science/article/pii/S0045206818308253#f0025

40. Luteolin from Flos Chrysanthemi and its derivatives:
New small molecule Bcl-2 (B-cell lymphoma 2) protein inhibitors. (2014)
▪ Over-expression of the Bcl-2 anti-apoptotic proteins is closely related to
tumorigenesis and associated with drug resistance.
▪ Here we report that luteolin, a main substance found in Flos Chrysanthemi, directly
binds to and shows inhibitory activity against the Bcl-2 protein.
▪ We studied the binding mode of luteolin and its derivatives with target proteins, their
structure-activity relationship, and their effect on the human leukemia cell line HL-
60.
▪ The results suggest that luteolin and its derivatives with a benzyl group introduced to
the B ring, are new small molecule Bcl-2 protein inhibitors, and their anti-tumor
activity is likely related to their effect on the Bcl-2 protein
https://www.semanticscholar.org/paper/Luteolin-from-
Flos-Chrysanthemi-and-its-New-small

41. Effect of flavonoid on c-reactive protein in mice (2006)
https://academic.oup.com/jn/article/136/9/2331/4664906
flavonoid

42. Synergism between flavonoids and anticancer drugs
https://www.semanticscholar.org/paper/Flavonoids-from-Artemisia-annua-L.-as-Antioxidants-
Ferreira-Luthria/addbbfa0b7fe58e7d069f9b1f7c2fae5765c86b7/figure/4
TRAIL=TNF Related APOTOSIS-INDUCING LIGAND
https://www.ncbi.nlm.nih.gov/pubmed/18980244

43. Current usage of chrysanthemum flowers
Traditional
Chinese
Medicine
Beverage
Cold-energizer:
Lung
Liver
Spleen
kidneys
Conventional
use
Beverage
Ornament
Research
Anti-
inflammation
Immuno-
modulation

44. Side effects and safety issues
▪ Side effects:
▪ No information available
▪ May cause photo sensitivity
▪ Special Precautions on Pregnancy and breast-feeding:
▪ No information available
▪ Plant allergies:
▪ May cause allergic reaction in persons sensitive to plants from Asteraceae family:
▪ Ragweed
▪ Marigold
▪ Daisies
▪ Others
▪ Interactions:
▪ No information available.

45. Comparison of serum IL-6 levels in normal and ASDs children (a).
Serum IL-6 levels in children with ASDs before and after treatment
with a luteolin-containing dietary formulation (b) 2015
https://www.nature.com/articles/tp2015142

46. Dietary flavonoid intake and the risk of stroke:
a dose-response meta-analysis of prospective cohort studies (2015)
https://bmjopen.bmj.com/content/6/6/e008680
favors flavonoid favors control

47. Consumption of the Dietary Flavonoids Quercetin, Luteolin and
Kaempferol and Overall Risk of Cancer:
A Review and Meta-Analysis of the Epidemiological Data (2013)
▪ Numerous epidemiological and preclinical studies suggest that flavonoids may play an
important role in the decreased risk of cancer associated with a diet rich in plant-
derived foods.
▪ In this article, we have reviewed the epidemiological studies assessing the relationship
between the consumption of three of the most common flavonoids, i.e. quercetin,
luteolin and kaempferol, and the risk of developing cancer.
▪ We have also performed a meta-analysis on the consumption of these three flavonoids
(alone and combined) and overall risk of cancer.
▪ The analysis of data from 18 case-control studies (8585 cases with cancer and 9975
control subjects) revealed that a high consumption of these three flavonoids (combined)
was associated with a statistically significant reduction of overall cancer risk (OR: 0.73;
95% CI: 0.63, 0.84; p0.05) and luteolin (OR: 0.90; 95% CI: 0.69, 1.18; p>0.05), which was
statistically significant for quercetin.
▪ A high intake of these three flavonoids (combined) was also associated with a
statistically significant reduction of lung cancer risk (OR: 0.67; 95% CI: 0.49, 0.91; p0.05).
These results suggest that consumption of foods rich in the flavonoids quercetin,
kaempferol and luteolin may reduce the risk of developing cancer.
https://www.webmedcentral.com/wmcpdf/Article_WMC004264.pdf

48. Brain Inflammation, Neuropsychiatric Disorders, and
Immunoendocrine Effects of Luteolin (2014)
▪ Recent publication reported that luteolin and quercetin have detrimental effects on
the hormonal ‘‘system’’ and in ‘‘models’’ of breast and endometrial cancer.
▪ These authors reported that luteolin has estrogenic activity and antagonizes
progesterone receptor activation. The results were obtained using transformed cell
lines.
▪ Other authors using different cell lines have reached opposite conclusions.
▪ 1 study reported that luteolin inhibits estrogen production, whereas another showed
that progesterone does not bind to the progesterone receptor.
▪ There are hundreds of publications showing that luteolin have potent anticancer
actions. Combining luteolin with quercetin, as well as with celcoxib, had more potent
anticancer effect than each one individually
https://pdfs.semanticscholar.org/8c00/2a8c647234d8140fe2bbbbccb56c77e2e622.pdf

49. Commercial chrysanthemum products
▪ Fresh chrysanthemum flower
▪ Dry chrysanthemum flower
▪ Chrysanthemum powder
▪ Chrysanthemum drink
▪ Chrysanthemum cake
▪ Chrysanthemum essential oil
▪ INSECTICIDE
▪ INSECT REPELLANT

50. Some delicious cuisine with chrysanthemum

51. Summary
▪ Chrysanthemums are flowering plants of the genus Chrysanthemum
in the family Asteraceae.
▪ Shen Nong, the father of Chinese Medicine, classified it as a
superior herb.
▪ More than 4,000 phytochemicals in Chrysanthemums are known
but only 150 are studied in detail.
▪ The major bioactive compounds flavonoids, phenolic acids and
antocyanins had been studied for their bioavailabilities and
pharmacological actions
▪ Antioxdant, anti-inflammatory, anti-cancer, anti-diabetic, anti-
hyperlipiemic, ant-obesity properties have been demonstrated.
▪ Scientific research is still ongoing to establish the therapeutic
values of the bioactive compounds.

52. ANY QUESTION?
Contact
Kevin KF Ng, MD, PhD
Email: kevinng68@gmail.com
52