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Family Compositae
Manzanilla
Chrysanthemum indicum
WINTER ASTER; GROUND APPLE
Nue ji cao

Scientific names  Common names 
Achillea bandana Buch.-Ham. [Invalid] Dolontas (Tag.) 
Acrotis elegans Thunb. Manzanilla (Sp., Fil.) 
Bidens bardanna Wall. [Invalid] Mansanilya-a-babasit (Ilk.) 
Bidens marginata DC. Roman camomile (Engl.)
Chrysanthemum indicum L. Garden camomile (Engl.) 
Chrysanthemum japonicum Thunb. Winter aster (Engl.)
Chrysanthemum koraiense Nakai Ground apple (Engl.) 
Chrysanthemum lushanense Kitam. Mother's daisy (Engl.)
Chrysanthemum nankingense Hand.-Mazz. Whig plant (Engl.)
Chrysanthemum procumbens Lour.  
Chrysanthemum purpureum Pers.  
Chrysanthemum tripartitum Sweet  
Collaea procumbens (Rich.) Spreng  
Dendranthema indicum (L.) Des Moul.  
Dendranthema nankingense (Hand.-Mazz.) P.S.Hsu  
Matricaria indica (L.) Desr.  
Pyrethrum indicum (L.) Cass.  
Tanacetum indicum (L.) Sch.Bip.  
Some compilations list C. indicum and C. sinense as synonyms. Quisumbing's compilation lists them separately. Mansanilla is a shared common name by the two species. C. sinense is similar to C. indicum, burt usually taller.
Chrysanthemum indicum L. is an accepted name The Plant List

Other vernacular names
CHINESE: Chua hua, Hsia yeh chua hua, Ku yi, Lu bian huang, Shan ju hua, Huang ju zi, Ju hua nao, Ye ju, Nui ji cao.
ITALIAN: Crisantemo comune.
TAMIL: Civanti.

Botany
Manzanilla is an erect or ascending, aromatic, somewhat hairy herb, 30 to 60 centimeters in height. Leaves are thin, pinnately lobed, ovate to oblong-ovate, and 4 to 6 centimeters long. Lobes 2 to 3 on each side, ovate or oblong-ovate, and sharply toothed. Upper surface of the leaves deep green while the under surface gray-green. Flowering heads are yellow, peduncled, corymbosely panicled, and 1.5 to 2.5 centimeters in diameter. Involucre bracts are oblong or elliptic, as large as the achenes. Receptacle is smooth or pitted, not paleaceous. Ray flowers are 1-seriate, female, ligule spreading, disc flowers numerous, perfect, limb 4- to 5-fid. Fruits are achenes, very small, cuneate-oblong, somewhat compressed and grooved.

Distribution
- Widely scattered in cultivation, esteemed for ornamental and medicinal purposes.
- Established in Benguet at 1,800 meters altitude.

- A native of China and Japan, now cultivated in most warm countries.

Constituents
- Leaves and flowers of C. japonicum yielded a volatile oil (kiku oil), 0.16%; glucoside; chrysanthemin, 7%; anthocyanin.
- The active ingredient is chrysanthemin.
- Essential oil contains chrysanthenone.
- A glucoside, chrysanthemin, an isomer of asterin, has been isolated from the flowers of the red variety.
-From the "Ruby King" variety, a glucoside has been isolated, monoglucoside of cyanidine, 7 per cent.
- Study of methanolic extract of flowers yielded flavone and flavone glycosides together with three new eudesmane-type sesquiterpenes, kikkanols A, B, and C. (see study below) (
27)
- Ethanol extract of flowers yielded seven compounds: acacetin, acacetin-7-O-(6"-O-acetyl) beta-D-glucopyranoside, linarin, apigenin-7-O-beta-D-glucopyranoside, chlorogenic acid, vanillic acid, and sucrose. (13)
- Flower oil yields 1,8-cineole, germacrene D, camphor, α-cadinol, camphene, pinocarvone, β-caryophyllene, 3-cyclohexen-1-ol, and γ-curcumene. (see study beloow) (22)

Properties
- Considered antifungal, antiviral, antiinflammatory, analgesic, antipyretic, bactericidal, febrifuge, vulnerary, depurative and tonic.
- Glycoside chrysanthemin considered antibacterial.
- Studies have shown antimicrobial, immunomodulatory, anti-inflammatory, anticancer, hepatoprotective, anti-diabetic, anti-dermatitis, antioxidant, acetylcholinesterase inhibitory properties.

Parts utilized
· Flowering heads.
· Entire plant also used.


Uses
Culinary / Edibility
· Seeds, flowers, leaves are edible.
Folkloric
· Preventive for cough, flu, epidemic meningitis.
· Entire plant or flower used for whooping cough.
· For gas pains -- warm oil, add and mix the flower heads, let stand for 30 mins and strain. Then apply the warm oily solution to abdomen.
· Used for eczema, poisonous snake bites, sprains and bruises. Also used for mammary carbuncles.
· Flowers used for hypertension.
· Emulsion of flowers used for infections of the cervix .
· Flowers are burned for use as Insect repellent.
· Tea used as a wash for sore eyes, open sores, and wounds.
· Infusion of flowering heads used as carminative.
· In Deccan, plant used in conjunction with black pepper for treatment of gonorrhea.
· Combined with bitter sweet as ointment, used for bruises, sprains, calluses.
· In China, used for migraines, hypertension, inflammation, respiratory problems. Also, flowering heads are made into tonic and sedative preparations. Infusions are used as collyrium in eye affections.
· In Malaya flowers are used for sore eyes and to promote longevity.
· The Hindus consider the plant heating and aperient; used for affections of the brain, calculus, as well as antidote to mental depression.
· In Indo-China leaves are used as depurant and prescribed for migraine. Also, flowers are used for sore eyes and inflammation of the abdomen.
· In Guam infusion of flowers are used as remedy for intermittent fevers; also, used by women as remedy for hysteria and monthly irregularities.



Studies
· Antimicrobial / Essential Oils:
Study yielded three essential oils with major constituents of 1,8-cineole, camphor, borneol and bornyl acetate. Results showed both essential oils from air-dried and processed flowers possessed significant antimicrobial effect. With higher camphor percentage, the oil of processed flowers greater bacteriostatic activity than air-dried ones. (1)
Antiinflammatory / Immunomodulatory:
Anti-inflammatory and immunomodulatory activities of the extracts from the inflorescence of Chrysanthemum indicum Linné: Study showed CI possesses antiinflammatory, humoral and cellular immunomodulatory and phagocytic activity probably from its flavonoid contents. (2)
Antiinflammatory: Study showed C indicum extract to be an effective anti-inflammatory agent in murine phorbol ester-induced dermatitis and suggests a potential for treatment of immune-related cutaneouse diseases.
Anti-Cancer:
Study of C indicum extract showed a significant apoptotic effect through a mitochondrial pathway and arrested cell cycle by regulation of cell cycle-related proteins in MHCC97H cells lines without effect on normal cells. The cancer-specific selectivity suggests the plant extract could be a potential new treatment for human cancer. (4)
Anti-Cancer / Hepatocellular Carcinoma: Study documents anti-metastatic effect through a decrease of MMP expression, simultaneous increase of TIMP expression. Results suggest CI is a potential novel medicinal plant for treatment of hepatocellular carcinoma or cancer invasion and metastasis. (6)
Anti-Cancer / Antiproliferative In Human Hepatocellular Cells: Study performed in rats with human cells showed CI extract inhibited proliferation of human hepatocellular cells in a time- and dose-dependent manner without cytotoxicity.
Flavonoids / Anti-Arthritis:
Study showed the total flavonoids of C indicum, extracted from the dried buds could induce synoviocytes apoptosis and suppress proliferation of synoviocytes in adjuvant-induced arthritis rats. (7)
Flowers / Chemical Composition:
Study of C. indicum flowers yielded 63 volatiles which included eucalyptol, a-pinene, a-neoclovene among others. Ten flavonoids were identified, including quercitrin, myricetin and luteolin-7-glucoside. It suggests C indicum flower is a good source of natural quercitrin and myricetin for the development of potential pharmaceuticals. (8)
Aldose Reductase Inhibitory Activity:
Study has shown inhibitory activity against rat lens aldose reductase and nitric oxide (NO) production in lipopolysaccharide-activated macrophages.
Anti-Inflammatory:
Study suggest the anti-inflammatory properties of CIE might results from the inhibition of inflammatory mediators, such as NO, PGE2, TNF-alpha and IL01beta, via suppression of MAPKs and NF-kappaB-dependent pathways. (9)
Flavanone Glycosides / Rat Lens Aldose Reductase Inhibition:
Study isolated two flavanone glycosides and a new phenylbutanoid glycoside from the flowers of Chrysanthemum indicum together with eight flavonoids. Both of the new flavanone glycosides showed inhibitory activity for rat lens aldose reductase. (10)
Aldose Reductase Inhibitors: Methanol extract of flowers yielded flavone and flavone glycosides, together twith three new eudesmane-type sesquiterpenes, kikkanols A, B, C. (12)
Hepatoprotective / Flowers:
Study evaluated the hepatoprotective effect of a hot water extract of CI flowers in in vitro and in vivo systems using normal human hepatocytes and hepatocellular carcinoma cells against CCl4-induced hepatotoxicity. Results showed HCIF inhibited bioactivation of CCl4-induced hepatotoxicity and downregulated CYP2E1 expression in vitro and in vivo.
(14)
Topical Application Attenuates Atopic Dermatitis:
Study evaluated the effect of topically applied C. indicum in mice with atopic dermatitis-like symptoms. CIL treatment dose-dependently reduced severity of clinical symptoms of dorsal skin, ear thickness, and number of mast cells and eosinophils. Improvement with CIL-high was similart to hydrocortisone but without skin atrophy and secondary infection. Study concludes CIL may be an alternative substance for management of atopic dermatitis.   (15)
Teratogenicity Study / Safety:
Under experimental conditions, C. indicum extract did not show any significant effects in SD pregnant rats, with no apparent teratogenicity and embryotoxicity. (16)
Apoptosis in Huan Hepatocellular Carcinoma:
CI extract exerted a significant apoptotic effect through a mitochondrial pathway and arrested the cell cycle by regulation of cell-cycle related proteins. A cancer-specific selectivity suggests a promising novel treatment for human cancer. (17)
Antioxidant / Prevention of Radical-Induced DNA Damage / Flowers:
Ethanol-based extract of flowers prevented free radical-induced DNA damage and did not show any cytotoxicity. Antioxidant activity was highly correlated with phenolic and flavonoid contents.
(18)
Silver Nanoparticles from C. indicum / Antibacterial:
The antimicrobial effect of synthesized AgNPs from C. indicum revealed a significant effect against K. pneumonia, E. coli, and P. aeruginosa, with no toxicity toward mouse embryo fibrobalst cells. (19)
Acetylcholinesterase Inhibitors / Flowers / Alzheimer's Disease:
Ethanol extract of flowers markedly decreased AChE activity. Study yielded acaiin and acacetin-7-O-ß-D-galactopyranoside as active compounds responsible for the AChE inhibition which present as potential therapeutic agents for Alzheimer's disease. (
20)
Safety and Mutagenicity Evaluation of Flower Oil:
Acute oral toxicity evaluation of flower oil showed no mortality or clinical signs of toxicity at 2,000 mg/kg body weight per day. Levels of 15.63-500 µg C. indicum flower oil/plate did not induce mutagenicity in S. typhimurium and E. coli. Results showed the flower oil produced no bone marrow micronucleus abnormalities, mutagenicity, or chromosomal aberrations, and can be considered a functional food or medicinal ingredient. (see constituents above)    (
22)
Anti-Tyrosinasec/ Skin Whitening:
Study evaluated the ability of C. indicum extracts to inhibit in vitro tyrosinase activity and skin care effects of cosmetic formulations containing 0.5% water extracts in human volunteers. Methanol and water extracts dose dependently inhibited mushroom tyrosinase activity. Methanol extract effect was similar to kojic acid, a known tyrosinase inhibitor. Water extract also reduced melanin levels. Luteolin and acacetin-7-O-rutinoside were the major flavonoid compounds in the weater extract. Results suggest the water extract has potential as a natural skin-whitening agent for functional cosmetic uses, due to its melanin-reducing efficacy. (
23)
Attenuation of Atopic Dermatitis:
Study evaluated the effect of topically applied C. indicum in mice with atopic dermatitis (AD)-like symptoms. CIL treatment dose-dependently reduced severity of cliical symptoms of dorsal skin, ear thickness, and number of mast cells and eosinophils, together with significantly reduced IgE, IgG1, IL-4, and IFN-γ levels and reduced mRNA levels of IFN-γ, IL-4, and IL-13 in dorsal skin lesion. Results suggest a potential alternative for the treatment of AD. (
24)
Linarin / Inhibition of Proliferation of A549 Cells / Lung Cancer / Flowers:
Study reported on the anti-proliferative and molecular mechanism of C. indicum on A549 human alveolar basal epithelial cells. Results showed linarin-mediated inhibition of cell prolifereation is associated withh suppression of Akt activation and induction of cyclin-dependent kinase inhibitory p27. Findings suggest a further evaluation and a potential for linarin for the treatment and prevention of lung cancer. (
25)
Enhancement of Osteoblast Function / Prevention of Osteoporosis:
Study evaluated the protective effects of Chrysanthemum indicum extract on response of osteoblasts to oxidative stress. Results showed CIE signficantly increase cell survival, ALP activity, and calcium deposition, and decreased the production of Reactive Oxygen Species (ROS) and Tumor Necrosis Factor-α (TNF-α) in osteoblasts. The enhancement of osteoblast function by CI extract may prevent osteoporosis and inflammatory bone disease. (
26)
Aldose Reductase Inhibitors / Flowers:
A methanolic extract from flowers of C. indicum was shown to have inhibitory adtivity against rat lens aldose reductase. Bioassay guided separation yielded flavone and flavone glycosides and three new eudesman-type sesquiterpenes. (see constituents above)
(27)

Availability
- Wild-crafted.
- Cultivated for ornamental use.

- Herbs, granules, extracts in the cybermarket. 
- Chrysanthemum tea from flowers.


Last Update Se[tember 2016

Photo © Godofredo Stuart / StuartXchange
OTHER IMAGE SOURCE: / Chrysanthemum Indicum / Photo id: 178443 / Credit: L. R. / alterVISTA  / Click on image to see source page

Additional Sources and Suggested Readings
(1)
Chemical composition and antimicrobial activity of the essential oils of Chrysanthemum indicum / Zhu Zhu Shunying1, Yang Yang, Yu Huaidong, Ying Yue, Zou Guolin
/Journal of Ethnopharmacology, Volume 96, Issues 1-2, 4 January 2005, Pages 151-158 / doi:10.1016/j.jep.2004.08.031
(2)
Anti-inflammatory and immunomodulatory activities of the extracts from the inflorescence of Chrysanthemum indicum Linné / J Ethnopharmacol. 2005 Oct 3;101(1-3):334-7.
(3)
Dendranthema indicum - (L.)Des Moul. / Chrysanthemum / Plants For A Future

(4)
Chrysanthemum indicum extract holds promise for treating human cancer
/ Zong-fang Li et al / World Journal of Gastroenterology 2009; 15(36); 4538-4546
(5)
Anti-inflammatory activity of Chrysanthemum indicum extract in acute and chronic cutaneous inflammation / Do Yeon Lee et al / Journal of Ethnopharmacology • Volume 123, Issue 1, 4 May 2009, Pages 149-154
/ doi:10.1016/j.jep.2009.02.009
(6)
Chrysanthemum indicum ethanolic extract inhibits invasion of hepatocellular carcinoma via regulation of MMP/TIMP balance as therapeutic target / Wang Z D et al / Oncol Rep. 2010 Feb;23(2):413-21
(7)
Effect of total flavonoids of Chrysanthemum indicum on the apoptosis of synoviocytes in joint of adjuvant arthritis rats / Chen XY et al / Am J Chin Med. 2008;36(4):695-704

(8)
Analysis of chemical composition of Chrysanthemum indicum flowers by GC/MS and HPLC
/ Liang-Yu Wu, Hong-Zhou Gao et al / Journal of Medicinal Plants Research Vol. 4(5), pp. 421-426, 4 March, 2010
(9)
Chrysanthemum indicum Linné extract inhibits the inflammatory response by suppressing NF-kappaB and MAPKs activation in lipopolysaccharide-induced RAW 264.7 macrophages / Cheon MS, Yoon T et al / J Ethnopharmacol. 2009 Apr 21;122(3):473-7. Epub 2009 Feb 3.
(10)
Medicinal Flowers. VI.1) Absolute Stereostructures of Two New Flavanone Glycosides and a Phenylbutanoid Glycoside from the Flowers of Chrysanthemum indicum L.: Their Inhibitory Activities for Rat Lens Aldose Reductase / Hisashi Matsuda, Toshio Morikawa et al / Chem. Pharm. Bull. 50(7) 972—975 (2002) Vol. 50, No. 7
(11)
Chrysanthemum indicum L. / Catalogue of Life, China
(12)
Medicinal Flowers. I. Aldose Reductase Inhibitors and Three New Eudesmane-Type Sesquiterpenes, Kikkanols A, B, and C, from the Flowers of Chrysanthemum indicum L. / YOSHIKAWA M, MORIKAWA T, MURAKAMI T, TOGUCHIDA I, HARIMA S, MATSUDA H / Chem Pharm Bull, VOL.47;NO.3;PAGE.340-345(1999)
(13)
Studies on chemical constituents from flowers of Chrysanthemum indicum. / Gao MH, Li H, Zhang L, Xiao SX. / Zhong Yao Cai. 2008 May;31(5):682-4.
(14)
Hepatoprotective effect of water extract from Chrysanthemum indicum L. flower / Sang Chul Jeong, Sang Min Kim, Yong Tae Jeong and Chi Hyun Song* / Chinese Medicine 2013, 8:7 doi:10.1186/1749-8546-8-7
(15)
Topical Application of Chrysanthemum indicum L. Attenuates the Development of Atopic Dermatitis-Like Skin Lesions by Suppressing Serum IgE Levels, IFN-γ, and IL-4 in Nc/Nga Mice / Sunmin Park, Jung Bok Lee, and Suna Kang / Evidence-Based Complementary and Alternative Medicine, Volume 2012 (2012) / http://dx.doi.org/10.1155/2012/821967
(16)
Study on teratogenicity of Chrysanthemum indicum extract in SD rats / WANG Feng-yan;CHEN Rui-yi; ZHOU Yi-lin; ZHANG Zi-hong; TAN Jian-bin; YANG Mei-ling; HU Shuai-er; LI Xin / Carcinogenesis, Teratogenesis & Mutagenesis, 2012, 24(5): 386-388./ DOI: 10.3969/j.issn.1004-616x.2012.05.017
(17)
Induction of apoptosis and cell cycle arrest in human HCC MHCC97H cells with Chrysanthemum indicum extract. / Li ZF1, Wang ZD, Ji YY, Zhang S, Huang C, Li J, Xia XM. / World J Gastroenterol. 2009 Sep 28;15(36):4538-46.
(18)
ANTIOXIDANT POTENTIAL AND OXIDATIVE DNA DAMAGE PREVENTIVE ACTIVITY OF CHRYSANTHEMUM INDICUM EXTRACTS / TRISHNA DEBNATH, HAI LAN JIN, MD ABUL HASNAT, YUNSUK KIM, NADIRA BINTE SAMAD, PYO-JAM PARK andBEONG OU LIM* / Journal of Food Biochemistry, Volume 37, Issue 4, pages 440–448, August 2013 / DOI: 10.1111/j.1745-4514.2011.00644.x
(19)
Rapid green synthesis of silver nanoparticles from Chrysanthemum indicum L and its antibacterial and cytotoxic effects: an in vitro study / Selvaraj Arokiyaraj, Mariadhas Valan Arasu, Savariar Vincent, Nyayirukannaian Udaya Prakash, Seong Ho Choi, Young-Kyoon Oh, Ki Choon Choi, and Kyoung Hoon Kim / Int J Nanomedicine. 2014; 9: 379–388. / doi: 10.2147/IJN.S53546
(20)
Isolation of Acetylcholinesterase Inhibitors from the Flowers of Chrysanthemum indicum Linne / Seung-Kyoung Jeung, Hyun Jae Yim, Hye Mi Kim, Se Gye Shin, Seoung Jun Han, Jung HY Park and Il-Jun Kang / The FASEB Journal. 2007;21:lb189 /
(21)
Chrysanthemum indicum / Synonyms / The Plant List
(22)
Safety Evaluation of Chrysanthemum indicum L. Flower Oil by Assessing Acute Oral Toxicity, Micronucleus Abnormalities, and Mutagenicity / Eun-Sun Hwang, and Gun-Hee Kim / Prev Nutr Food Sci. 2013 Jun; 18(2): 111–116. / doi: 10.3746/pnf.2013.18.2.111
(23)
Dermatologic evaluation of cosmetic formulations containing Chrysanthemum indicum extract
/ Keun Taek Choi PhD, Jun Ho Kim PhD, Hyung Taek Cho MS, Soon Sung Lim PhD, Sun Soon Kwak PhD, Young Jun Kim PhD / Journal of Cosmetic Dermatology / DOI: 10.1111/jocd.12211
(24)
Topical Application of Chrysanthemum indicum L. Attenuates the Development of Atopic Dermatitis-Like Skin Lesions by Suppressing Serum IgE Levels, IFN-γ, and IL-4 in Nc/Nga Mice / Sunmin Park, Jung Bok Lee, and Suna Kang / Evidence-Based Complementary and Alternative Medicine, Volume 2012 (2012) /
http://dx.doi.org/10.1155/2012/821967
(25)
Phytochemical Linarin Enriched in the Flower of Chrysanthemum indicum Inhibits Proliferation of A549 Human Alveolar Basal Epithelial Cells Through Suppression of the Akt-Dependent Signaling Pathway /
Seo Dong-Wan, Cho Young-Rak, Kim Wooki, and Eom Seok Hyun. / Journal of Medicinal Food. December 2013, 16(12): 1086-1094 doi:10.1089/jmf.2012.2674.
(26)
Effects of Chrysanthemum indicum L. Extract on the Function of Osteoblastic MC3T3-E1 Cells under Oxidative Stress Induced by Hydrogen PeroxideJee / Yun, Jee-Hye; Hwang, Eun-Sun; Kim, Gun-Hee / Korean Journal of Food Science and Technology, Volume 44, Issue 1, 2012, pp.82-88 / DOI : 10.9721/KJFST.2012.44.1.082
(27)
Medicinal Flowers. I. Aldose Reductase Inhibitors and Three New Eudesmane-Type Sesquiterpenes, Kikkanols A, B, and C, from the Flowers of Chrysanthemum indicum L. / Masayuki YOSHIKAWA, Toshio MORIKAWA, Toshiyuki MURAKAMI, Iwao TOGUCHIDA, Shoichi HARIMA, and Hisashi MATSUDA / Chem. Pharm. Bull. 47(3) 340—345 (1999) Vol. 47, No. 3

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