Mineral elements found in the flowers were K 37.55 mg/g, P 4.8 mg/g, Ca 9.73 mg/g, Mg 3.01 mg/g, Na 0.77 mg/g, Fe 1426.63 μg/g, Mn 109.22 μg/g, Zn 58.2 μg/g, Cu 19.95 μg/g, and Mo 0.37 μg/g (Cui and Guo 2012).

Chrysanthemum indicum flowers were found to contain a sesquiterpene lactone, arteglasin-A (Hausen et al. 1975; Hausen and Schulz 1976). A sesquiterpene lactone of guaianolide-type, yejuhua lactone, was isolated from the flowers and later confirmed to be handelin (Chen and Xu 1987). The flowers contained chrysanthemaxanthine, chrysanthemin (asterin, kuromamin) luteolin glucoside, n-hexacosane, n-tetracosane, stachydrine, adenine and vitamin A (Le and Nguyen 1999). Three new eudesmane-type sesquiterpenes called kikkanols A, B, and C; flavones, luteolin and eupatilin; three flavone glycosides luteolin 7-O-β-d-glucopyranoside, luteolin 7-O-β-d-glucopyranosiduronic acid, and acacetin 7-O-(60-α-l-rhamnopyranosyl)-β-d-glucopyranoside; two polyacetylenes cis-spiroketalnenolether polyyne and trans-spiroketalenolether polyyne; three sesquiterpenes clovanediol, caryolane 1,9β-diol, and oplopanone; and chlorogenic acid were isolated from the flowers (Yoshikawa et al. 1999). Five germacrane-type sesquiterpenes kikkanols D, D monoacetate, E, F, and F monoacetate and chrysanthemol (trans-eudesmane type sesquiterpene) were isolated from the flowers (Yoshikawa et al. 2000). Two flavanone glycosides, (2S)-eriodictyol 7-O-β-d-glucopyranosiduronic acid and (2R)-eriodictyol 7-O-β-d-glucopyranosiduronic acid, and a phenylbutanoid glycoside, (2S, 3S)-1-phenyl-2,3-butanediol 3-O-β-d-glucopyranoside and flavonoids: apigenin 7-O-β-d-glucopyranoside (apigetrin); diosmetin 7-O-β-d-glucopyranoside; quercetin 3,7-di-O-β-d-glucopyranoside; eriodictyol; (2S, 3S)-1-phenyl-2,3-butanediol, luteolin, luteolin 7-O-β-d-glucopyranoside; luteolin 7-O-β-d-glucopyranosiduronic acid; acacetin 7-O-(60-α-l-rhamnopyranosyl)-β-d-glucopyranoside; and eupatilin were isolated from the flowers (Matsuda et al. 2002). From the methanol flower extract were isolated: two polyacetylenes (cis-spiroketalenolether polyyne and trans-spiroketalenolether polyyne), eleven sesquiterpenes (kikkanol A, kikkanol B, kikkanol C, kikkanol D, kikkanol D monoacetate, kikkanol E, kikkanol F, kikkanol F monoacetate, clovanediol, caryolane 1,9β-diol, oplopanone), ten aromatic flavonoids ((2S)-eriodictyol 7-O-β-d-glucopyranosiduronic acid, (2R)-eriodictyol 7-O-β-d-glucopyranosiduronic acid, eupatilin, luteolin, luteolin 7-O-β-d-glucopyranosid, luteolin 7-O-β-d-glucopyranosiduronic acid, apigenin 7-O-β-d-glucopyranoside, diosmetin 7-O-β-d-glucopyranoside, acatin-7-O-(6″-α-l-rhamnopyranosyl)-β-d-glucopyranoside, quercetin 3,7-di-O-β-d-glucopyranoside), and two other aromatics (a phenylbutanoid glycoside (2S,3S)-1-phenyl-2,3-butanediol 3-O-β-d-glucopyranoside and chlorogenic acid) (Morikawa 2007).

Seven compounds were isolated 80 % ethanol flower extract: acacetin, acacetin-7-O-(6″-O-acetyl) β-d-glucopyranoside, linarin, apigenin-7-O-β-d-glucopyranoside, chlorogenic acid, vanillic acid and sucrose (Gao et al. 2008). Tang et al. (2009) isolated seven compounds from the 80 % ethanol flower extract luteolin, luteolin-7-O-β-d-glucopyranoside, luteolin-7-O-(6″-O-acetyl)-β-d-glucopyranoside, diosmetin, diosmetin-7-O-β-d-glucopyranoside, eupatilin and apigenin. Lu et al. (2009) isolated seven compounds from the flowers: acacetin, apigenin, acacetin-7-O-β-d-glucopyranoside, apigenin-7-O-β-d-glucopyranoside, luteolin, β-sitosterol and daucosterol. Thirteen compounds were isolated from the flowers, and identified as acacetin-7-O-β-d-glucopyranoside (1), luteolin (2), luteolin-7-O-β-d-glucopyranoside (3), acaciin (4), acacetin 7-O-(6″-O-α-l-rhamnopyranosyl)-β-sophoroside (5), 3-O-caffeoylquinic acid (6), syringaresinol O-β-d-glucopyranoside (7), 5,7-dihydroxychromone (8), uracil (9), p-hydroxybenzoic acid (10), 4-O-β-d-glucopyranosyloxybenzoic acid (11), boscialin (12) and blumenol A (13) (Feng et al. 2010). Four new polyacetylenes, namely, chrysindins A–D, together with 6 known polyacetylenes, were isolated from the flowers (Liu et al. 2011).

Twelve compounds were isolated and identified as acacetin; tricin; 2′,4′-dihydroxychalcone; 5-hydroxy-4′,7-dimethoxyflavon; 7-hydroxyflavonone; isorhamnetin (6),5,6,7-trihydroxy- 3′,4′, 5′-trimethoxyflanon; quercetin; (3β, 5α, 6β, 7β, 14β)-eudesmen-3,5,6,11-tetrol; syringaresinol; liriodendrin and genkwanin from the flowers (Wang et al. 2010a). Three germacrane-type sesquiterpene stereoisomers 1β,3α,5β-trihydroxyl-7-isopropenyl-germacren-4(15),10(14)-diene; 1β,3β,5α-trihydroxyl-7-isopropenyl-germacren-4(15),10(14)-diene; 1β,3β,5β-trihydroxyl-7-isopropenyl-germacren-4(15),10(14)-diene were isolated from the flowers (Wang et al. 2012). One new disesquiterpenoid and two new sesquiterpenoids were isolated from the dried flowers (Zhou et al. 2012).

The yield of C. indicum flower oil was 2.0 % (w/w), and 63 volatile flavour components comprising 89.28 % of the total aroma composition were characterized (Chang and Kim 2008). The essential oil contained 35 hydrocarbons (48.75 %), 12 alcohols (19.92 %), 6 ketones (15.31 %), 3 esters (4.61 %), 5 aldehydes (0.43 %), 1 oxide (0.22 %) and 1 miscellaneous component (0.04 %). α-Pinene (14.63 %), 1,8-cineol (10.71 %) and chrysanthenone (10.01 %) were the predominant volatile components. Chang and Kim (2009) reported the yield of flower oils from Korean and Chinese gamguk were 2.0 and 0.5 % (v/w), respectively. Sixty-three volatile compounds of Korean gamguk representing 89.28 % of the total peak area were tentatively identified, including 35 hydrocarbons, 12 alcohols, 6 ketones, 3 esters, 5 aldehydes, 1 oxide, and 1 miscellaneous component. Thirty-six volatile components of Chinese gamguk constituted 58.15 % of the total volatile composition, consisting of 19 hydrocarbons, 7 alcohols, 2 ketones, 2 esters, 4 aldehydes, 1 oxide, and 1 miscellaneous component. The predominant components of Korean oil were α-pinene, 1,8-cineol, and chrysanthenone. Whereas camphor, α-curcumene, and β-sesquiphellandrene were the main aroma compounds of Chinese gamguk. Thirty-six, 63, and 55 volatiles constituents were detected in the essential oil from fresh and shade-dried and freeze-dried flowers (Choi and Kim 2011). Ketones were predominant in the volatiles of gamguk flowers: fresh, 43.8 %; shade dried, 30.3 %; and freeze dried, 36.1 %. Camphor was the most abundant volatile component; borneol was also significant. The content of camphor was higher in fresh sample than those of dried samples, while borneol concentration was significantly increased in the dried samples. Five major components of the flower essential oil are α-pinene, 1,8-cineol, chrysanthenone, germacrene-D, and α-curcumene (Kim and Lee 2009). Germacrene-D decreased by the increase of nitrogen application. However, cumambrin A contents in the flower parts were affected negatively by the increase of nitrogen application, but total yields of cumambrin A in flower parts significantly increased.

Chang et al. (2010) found 63 volatile flavour components which comprised 89.28 % of the total aroma composition of the flower oil. The predominantly abundant volatile chemical components were α-pinene (14.63 %), 1,8-cineol (10.71 %), and chrysanthenone (10.01 %). The other components included germacrene D (5.25 %), β-bisabolene (3.95 %), (−)-sinularene (3.95 %), bornyl acetate (3.64 %), β-elemene (3.18 %), borneol (3.02 %), zingiberene (2.70 %), camphor (2.64 %), terpinene-4-ol (2.41 %), filifolone (2.24 %), γ-terpinolene (2.04 %), (E)-β-farnesene (1.87 %), α-curcumene (1.80 %), isopinocarveol (1.55 %), sabinene (1.24 %), β-sesquiphellandrene (1.19 %), pinocarvone (1.19 %), myrcene (1.17 %) and (E)-chrysanthenol (1.17 %).

Wu et al. (2010a) detected 63 volatiles in the flower essential oil, and the major volatiles included 2,6,6-trimethyl-bicyclo[3.1.1]hept-2-en-4-ol (21.67 %); 2-(2,4-hexadiynylidene)-1,6-dioxaspiro[4.4]non-3-ene (21.41 %); germacrene D (6.15 %); α-neoclovene (5.10 %); eucalyptol (4.94 %); α-pinene (3.64 %); and 1,4-bis(1-methylethyl)-benzene (3.03 %). Other minor constituents included β-sesquiphellandrene (2.90 %), longipinane (2.89 %), 7, 11-dimethyl-3-methylene-1,6,10-dodecatriene (2.17 %), β-myrcene (1.78 %), caryophyllene (1.77 %), 2,6-dimethyl-6-(4-methyl-3-pentenyl)-bicyclo[3.1.1]hept-2-ene (1.71 %), 1,2,3,6-tetramethyl-bicyclo[2.2.2]octa-2,5-diene (1.64 %), 4-(1,5-dimethylhex-4-enyl)cyclohex-2-enone (1.56 %), caryophyllene oxide (1.25 %), isocyclocitral (1.23 %), cadina-1,6,8-triene (0.99 %), α,α-4-trimethyl-3-cyclohexene-1-methanol (0.84 %), 4-methylene-1-(1-methylethyl)-icyclo[3.1.0]hexane (0.74 %), 3,4-dihydro-1-naphthaleneboronic acid diethyl ester (0.71 %), borneol (0.70 %), (Z)-3,7-dimethyl-2,6-octadien-1-ol acetate (0.66 %), trans-3-methyl-6-(1-methylethyl)-2-cyclohexen-1-ol (0.64 %), isobornyl acetate (0.63 %), 1,3,3-trimethylcyclohex-1-ene-4-carboxaldehyde (0.60 %), butylated hydroxytoluene (0.59 %), 4-methyl-1-(1-methylethyl)- 3-cyclohexen-1-ol (0.57 %), (E)-3(10)-caren-2-ol (0.57 %), 2-isopropyl-5-methyl-9-methylene-bicyclo[4.4.0]dec-1-ene (0.53 %), cis-1-methyl-4-(1-methylethyl)-2-cyclohexen-1-ol (0.48 %), iridomyrmecin (0.37 %), benzoic acid, 2-(dimethylamino)-methyl ester (0.37 %), 6,6-dimethyl-2-methylene-icyclo[2.2.1]heptan-3-one (0.35 %), 2-methyl butanoic acid phenylmethyl ester (0.34 %), α-caryophyllene (0.31 %), 5-ethylcyclopent-1-enecarboxaldehyde (0.31 %), camphene (0.30 %), 1,2,5,5-tetramethyl-1,3-cyclopentadiene (0.29 %), 3,7,11-trimethyl-2,6,10-dodecatrien-1-ol (0.29 %), benzyl acetoacetate (0.28 %), 3,7,11-trimethyl-1,3,6,10-dodecatetraene (0.21 %), 6,6-dimethyl-bicyclo[3.1.1]hept-2-ene-2-methanol (0.21 %), 4-dcetyl-3-carene (0.21 %), β-phellandrene (0.19 %), 1-methyl-8-(1-methylethyl)- tricyclo[4.4.0.02,7]dec-3-ene-3-methanol (0.18 %), copaene (0.17 %), 1,5,5-trimethyl-6-methylene-cyclohexene (0.16 %), 3,4-dihydro-2,2-dimethyl-2H-1-benzopyran (0.15 %), (S)-2-methyl-5-(1-methylethenyl)-2-cyclohexen-1-one (0.14 %), 4-methylene-2,8,8-trimethyl-2-vinyl-bicyclo[5.2.0]nonane (0.12 %), 2-n-butyl furan (0.10 %), phytol (0.10 %), 4,6,6-trimethyl- bicyclo[3.1.1]hept-3-en-2-ol (0.09 %), 1,2-diethyl-3,4-dimethyl-benzene (0.09 %), isoaromadendrene epoxide (0.08 %), 2,3-dihydro-2,2,4,6-tetramethyl-benzofuran (0.08 %), alloaromadendrene oxide-(I) (0.08 %), 4,6-dimethyl-2-pyrimidone (0.08 %), 2-methoxy-4-methyl-4-phenyl-2,5-cyclohexadien-1-one (0.07 %), tetracosane (0.07 %), hexatriacontane (0.06 %), and 3,7-dimethyl-1,3,6-octatriene (0.06 %). Further, ten flavonoids (mg/g) were identified, namely, quercitrin 51.88 mg, myricetin 37.81 mg, luteolin-7-glucoside 17.24 mg, quercetin-3-galactoside 12.55 mg, quercetin-3-glucoside 9.88 mg, luteolin 7.29 mg, kaempferol 0.22 mg, vitexin 0.17 mg, rutin 0.16 mg, apigenin 0.09 mg and total flavonoids 137.29 mg (Wu et al. 2010a).

The major constituents of the essential oils from three samples fresh, air-dried and processed flowers of Chrysanthemum indicum were 1,8-cineole, camphor, borneol and bornyl acetate (Zhu et al. 2005). The oils also contained α-terpineol, cis-sabinol, thujone, terpinen-4-ol, ρ-cymene and linalool. Fresh, air-dried and processed flowers of Chrysanthemum indicum shared similar qualitative composition of essential oils; the difference was quantitative. The fresh flower oil had a high percentage of 1.8-cineole (30.41 %) and camphor (23.52 %), although air-dried flower oil had a high content of camphor. Chrysanthemum indicum essential oil also had chrysanthenone, limonene, β-caryophyllene oxide and α-pinene and β-pinene. The essential oils of dried gamguk flowers were composed of hydrocarbons (shade dried (SD) 20.1, freeze dried (FD) 21.9 %), alcohols (SD 39.7, FD 33.9 %), esters (SD 7.7, FD 7.1 %), ketones (SD 30.3, FD 36.1 %), aldehydes (SD 0.1, FD 0.4 %), oxides (SD 0.7, FD 0.1 %), acids (SD 1, FD 0.4 %), and miscellaneous ones (SD 0.4, FD 0.1 %) (Choi and Kim 2011). The oxygenated compounds were important contributors to aromatic flower flavour. Camphor (SD 28.8, FD 35.2 %) and borneol (SD 28.3, FD 24.3 %) were the most abundant volatile component of shade- and freeze-dried samples, respectively. The newly identified compounds in shade-dried sample in comparison with a fresh sample were (3E)-2,5,5-trimethylhepta-1,3,6-triene, isogeraniol, p-cymen-8-ol, myrtenol, cis-piperitol, trans-3(10)-caren-2-ol, 1-methyl-4-(1-methylethyl)-benzene, trans-piperitol, verbenene, 4-ethenyl-1,2-dimethyl-benzene, bicyclogermacrene, α-farnesene, α-muurolene, dicyclohexyl-propanedinitrile, 2,3,6-trimethyl-1,4,6-heptatriene, nerolidol, spathulenol, caryophyllene oxide, 5-ethenyl-2-methyl-pyridine, citral, β-bisabolene, trans-α-bisabolene, α-gurjunene, β-eudesmol, E-3-phenyl-2-propenyl 3-methylbutanoate, valerenic acid, vulgarone B, aromadendrene epoxide, hexadecanoic acid, p-mentha-1(7)2-dien-8-ol, (Z,Z)-9,12-octadecadienoic acid, tricosane and pentacosane. Shade-dried gamguk flower had the greatest total number of volatile flavour compounds. α-Copaene, isobornyl-3-methylbutanoate and heptacosane were the compounds identified in only the freeze-dried sample.

Sixty-three volatile compounds of Korean gamguk representing 89.28 % of the total composition were identified, including 35 hydrocarbons, 12 alcohols, 6 ketones, 3 esters, 5 aldehydes, 1 oxide and 1 miscellaneous component (Chang and Kim 2009). Thirty-six volatile components of Chinese gamguk that constituted 58.15 % of the total volatile composition were characterized, consisting of 19 hydrocarbons, 7 alcohols, 2 ketones, 2 esters, 4 aldehydes, 1 oxide and 1 miscellaneous component. The predominant components of Korean oil were α-pinene, 1,8-cineol and chrysanthenone, whereas camphor, α-curcumene and β-sesquiphellandrene were the main aroma compounds of Chinese gamguk.

A total of 169 compounds representing 88.79–99.53 % of the oils were identified in the flower-head essential oil of 8 Chinese C. indicum populations (Zhang et al. 2010a). The predominant components were 1,8-cineole (0.62–7.34 %), (+)-(1R,4R)-camphor (0.17–27.56 %), caryophyllene oxide (0.54–5.8 %), β-phellandrene (0.72–1.87 %), (−)-(1S,2R,4S)-borneol acetate (0.33–8.46 %), 2-methyl-6-(p-tolyl)hept-2-ene (0.3–8.6 %), 4,6,6-trimethylbicyclo[3.1.1]hept-3-en-2-yl acetate (0.17–26.48 %), and hexadecanoic acid (0.72–15.97 %).

Mineral elements found in the leaves were K 31.52 mg/g, P 4.28 mg/g, Ca 14.14 mg/g, Mg 2.70 mg/g, Na 0.82 mg/g, Fe 1519.46 μg/g, Mn 186.7 μg/g, Zn 78.04 μg/g, Cu 30.26 μg/g and Mo 0.56 μg/g (Cui and Guo 2012).

Mineral elements found in the stems were K 17.74 mg/g, P 1.45 mg/g, Ca 5.52 mg/g, Mg 1.35 mg/g, Na 0.75 mg/g, Fe 433.36 μg/g, Mn 65.84 μg/g, Zn 76.6 μg/g, Cu 16.34 μg/g and Mo 0.21 μg/g (Cui and Guo 2012).

A flavones glucoside, isolated from C. indicum, identified as acacetin-7-rhamnosidoglucoside was found to be identical with buddleoglucoside (Cheng et al. 1962). The sesquiterpenoid valerone was found in C. indicum (Uchio et al. 1981). Indicumenone, a bisabolane ketodiol, was isolated from C. indicum (Mladenova et al. 1987). Sesquiterpenoids, chrysetunone, chrysetunone monacetate and tunefulin were isolated from aerial parts of C. indicum var. tuneful (Mladenova et al. 1988). A sesquiterpene compound, named chrysanthetriol, was isolated from the more polar fraction of the plant (Yu et al. 1992). (3β, 5α, 6β, 7β, 14β)-Eudesmen-3, 5, 6, 11-tetrol methanol solvate, systematic name: (3S,5S,6R,7R,10S)-7-(2-hydroxy-2-propyl)-10-methyl-4-methyleneperhydronaphthalene-3,5,6-triol methanol solvate, C₁₅H₂₆O₄ · CH₄O, a new sesquiterpenoid was isolated from C. indicum (Wang et al. 2006). Twelve compounds were obtained from C. indicum fraction with cardiovascular activity and identified as (2S)-eriodictyol-7-O-β-d-glucuronide (1), (2S)-eriodictyol-7-O-β-d-glucoside (2), (2S)-esperetin-7-O-β-d-glucuronide (3), luteolin-7-O-β–d-glucoside (4), luteolin-7-O-β-d-glucuronide (5), diosmetin-7-O-β-d-glucuronide (6), quercetin-7-O-β-d-glucoside (7), (2S)-eriodict-dicaffeoylquinate (8), 3,5-dicaffeoylquinic acid(9), 3,5-cis-dicaffeoylquinic acid (10), 1,5-dicaffeoylquinic acid (11) and 1,3-dicaffeoylquinic acid (12) (Sun et al. 2012). The following compounds were isolated from the methylene chloride fraction of C. indicum crude ethanol extract: sudachitin, hesperetin, chrysoeriol and acacetin (Kim et al. 2013).

Seventy-three compounds accounting for 96.65 % of the extracted essential oil of the aerial parts were identified (Jung 2009). The oil comprised 14.88 % monoterpene hydrocarbons (MH), 52.14 % oxygenated monoterpenes (OM), 22.9 % sesquiterpene hydrocarbons (SH), 5.97 % oxygenated sesquiterpenes (OS) and 0.75 % others (O). The main compounds in the oil were α-pinene (4.4 %, MH), 1,8-cineole (10.4 %, OM), α-thujone (6.05 % OM), camphor (10.12 %, OM), bornyl acetate (6.1 % OM), borneol (3.6 % OM), terpinen-4-ol (3.4 % OM), cis-chrysanthenol (3.4 % OM), β-caryophyllene (5.1 %,SH), germacrene D (10.6 %, SH) and α-cadinol (3.0 %, OS). The minor components included monoterpene hydrocarbons (tricyclene, α-thujene, camphene, β-pinene, sabinene, myrcene, α-terpinene, limonene, α-phellandrene, cis-β-ocimene, γ-terpinene, trans-β-ocimene, p-cymene, terpinolene), oxygenated monoterpenes (α-terpinolene, cis-3-hexen-1-ol, β-thujone, trans-sabinene hydrate, chrysanthenone, linalool, pinocarvone, cis-chrysanthenyl acetate, umbellulone, trans-chrysanthenyl acetate, trans-piperitol, α-terpineol, piperitone, carvone, myrtenol, trans-carveol, p-cymen-8-ol, cis-carveol), sesquiterpene hydrocarbons (α-copaene, α-gurjunene, berkheyaradulen, β-elemene, α-humulene, trans-β-farnesene, α-muurolene, γ-cadinene, α-zingiberene, β-selinene, cis, trans-α-farnesene, δ-cadinene, β-sesquiphellandrene, ar-curcumene), oxygenated sesquiterpenes (caryophyllene oxide, trans-nerolidol, globulol, guaiol, spathulenol, eugenol, α-cedrol, torreyol, T-muurolol, cis-trans-farnesol), and others (1,2,4 trimethylbenzene, n-hexanol, 1-octen-3-ol, tricosane, tetracosane). Steam distilled oil from the flowers, leaves and total aerial parts contained borneol, chrysanthenone and bornyl acetate as the major components (Stoianova-Ivanova et al. 1983).

A water-soluble neutral polysaccharide (CIP-C) was obtained from Chrysanthemum indicum (Jin et al. 2012). CIP-C was found to be a neutral branched heteropolysaccharide, mainly composed of D-Man, D-Glc and D-Gal, with a small quantity of D-Fuc, L-Ara and D-Xyl. The backbone of CIP-C was linked by β(or α)-d-1,4-Man, β-d-1,6-Glc and β-d-1,4-Gal. In addition,T-Araf,1,5-Araf and T-Gal,1,4-Gal,1,3,6-Gal,1,3,4,6-Gal may be linked as an arabinan branch and an AGI arabinogalactan branch.

Mineral elements found in the roots were K 15.84 mg/g, P 1.25 mg/g, Ca 10.10 mg/g, Mg 2.54 mg/g, Na 3.16 mg/g, Fe 3219.90 μg/g, Mn 144.33 μg/g, Zn 227.50 μg/g, Cu 64.60 μg/g and Mo 0.22 μg/g (Cui and Guo 2012).

The water extract of gamguk teas did not differ significantly in yield compared to methanol extracts and showed stronger antioxidant activity (Eom et al. 2008). Catechin contents in gamguk teas were 8–18 % of the extracts. Gamguk teas exhibited faster release of antioxidants, and the antioxidant activity was positively correlated with the thermal treatments. Gukhwacha was the best tea for rapid release (30 seconds) of antioxidants with the 50 °C treatment, whereas antioxidants in other teas were relatively slower.

Chrysanthemum indicum extract inhibited proliferation of human hepatocellular carcinoma (HCC) MHCC97H cells in a time- and dose-dependent manner without cytotoxicity in rat hepatocytes and human endothelial cells (Li et al. 2009). The extract CIE exerted a significant apoptotic effect through a mitochondrial pathway and arrested the cell cycle by regulation of cell cycle-related proteins in MHCC97H cells without an effect on normal cells. Yuan et al. (2009) found that C. indicum extract was effective in attenuating the mitogenic effect of isoproterenol on both HepG2 and MHCC97H human hepatocellular carcinoma cells. The inhibitory effect of the extract was mediated by inhibiting the isoproterenol -induced activation of MAPK/ERK1/2 via beta2-AR in tumour cells. In further studies, they found that C. indicum ethanol extract reduced MHCC97H cell metastatic capability, in part at least, through decrease of the MMP-2 and MMP-expression with a simultaneous increase of the TIMP-1 and TIMP-2 expression thus restoring their balance in the cancer cells (Wang et al. 2010b). Five Chinese herbs (Curcuma wenyujin, Chrysanthemum indicum, Salvia chinensis, Ligusticum chuanxiong and Cassia tora) were found to sensitize resistant cancer cells at a nontoxic concentration (10 μg/ml) and markedly increased doxorubicin accumulation in multidrug-resistant human breast cancer MCF-7/ADR cells (Yang et al. 2011b). Fractions from CH₂Cl₂ extracts were more effective than fractions from ethyl acetate extracts. Fractions from Curcuma wenyujin and C. indicum exhibited significant effects in sensitization of these resistant MCF-7/ADR cancer cells at nontoxic concentration to doxorubicin and docetaxel (Yang et al. 2011a). All the fractions could enhance the apoptosis induced by doxorubicin in MCF-7/ADR cells and restore the effect of docetaxel on the induction of G2/M arrest in A549/Taxol cells. The fractions also had to induce S-phase arrest.

The methylene chloride fraction of C. indicum crude ethanol extract exhibited strong cytotoxic activity as compared with the other fractions and clearly suppressed constitutive STAT3 activation against both human prostate cancer DU145 and U266 cells, but not human breast cancer MDA-MB-231 cells (Kim et al. 2013). It was found that the fraction could induce apoptosis through inhibition of the JAK1/2 and STAT3 signaling pathways. Furthermore, the major components of the fraction were bioactive compounds such as sudachitin, hesperetin, chrysoeriol and acacetin. Sudachitin, chrysoeriol and acacetin also exerted significantly cytotoxicity, clearly suppressed constitutive STAT3 activation, and induced apoptosis, although hesperetin did not show any significant effect in DU145 cells.