| Ginger is a fresh rhizoma of Zingiberaceae,Zingiber officinale Rosc.and is a perennial herb.Ginger is widely distributed and cultivated in the world and is a rhizomatous spice indispensable in people's daily life.Hosta plantaginea(Lam.)Aschers is one of herbs commonly used for Mongolian medicine.In this study,the active ingredients of these two medicinal plants were extracted by using CO2 percritical fluid extraction and traditional extraction system,were then isolated by using the MCI gel,macroporous resin,normal or reverse phase silica gel,Sephadex LH-20 and HPLC,and were finally identified by using several spectroscopic techniques(1H-NMR,13C-NMR,HSQC,HMBC,COSY,NOESY,HRTOF-ESI-MS,X-ray and IR,etc.).The antitumor activities of these compounds were screened and evaluated.We isolated 28 compounds(9 compounds were from ginger and 19 compounds were from hosta)and the chemical structures of 16 compounds were identified.In this study,we found that the chemical structures of 4 compounds from the hosta are novel and another 3 compounds were isolated for the first time in the hosta.9 compounds were isolated from ginger and the chemical structures of the 5 compounds were identified.These 5 compounds are gingerol compounds.The identified compounds are: ZR-1[5-hydroxy-1-(4-hydroxy-3-methoxy)-3-octanone,ZR-3:(4-hydroxy-3-methoxy)-3-decanone],ZR-4 [5-hydroxy-1-(4-hydroxy-)-3-dodecanone],ZR-8 [5-hydroxy-1-(4-hydroxy-3-methoxy)-3-tetradione] and ZR-5 [5-hydroxy-1-(4,5-dihydroxy-3-methoxy)-3-decanone],respectively.19 compounds were isolated from the Hosta plantaginea(Lam.)Aschers,and 11 identified compounds include phenylpropanoids,steroids and glycosides.They are HP-1 [(2-methyl)heptyl phthalate],HP-2 [3-(4-hydroxy-3-methoxyphenyl)acrylic acid methyl ester],HP-3 [(2-methylphenyl)(4-hydroxy-3-methoxyphenyl)-1,4-diene-3-pentanone],HP-4 [4-hydroxy-3-methoxybenzene],HP-6 [(25R)-2?,3?,17?,24?-tetrahydroxy-5?-spirostanane],HP-7 [25R-2?,3?,24?-Trihydroxy-5?-spirost-9(11)-en-12-one],HP-8 [25R)-2?,3?-Dihydroxy-5?-spirost-9(11)-en-12-one],HP-10 [16,22-oxido-26-hydroxycholest-4-en-3-one],HP-15 [(2S)-1-O-linenoyl-3-O-?-D-galactopyranosylglycerol],HP-16 [(2S)-1-O-(10,13)-octadecenoyl-3-O-?-D-galactopyranosyl glycerol],and HP-17 [1-O-?-Dglucopyranosyl-(2S,3R,4E,8Z)-2-[(2-hydroxytetradecanoyl)amido]-4,8-octadecadienyl-1,3-diol],respectively.The antitumor activities of 16 identified compounds were studied,and the molecular mechanism of these compounds-mediated anticancer activities was evaluated.Our results indicated that most of the compounds exhibited the inhibitory effects on cell proliferation in various cancer cell lines.All compounds isolated from ginger exhibited inhibitory effects on cell proliferation in human breast cancer cells,lung cancer cells,hepatocarcinoma cells,and esophageal cancer cells.Among them,ZR-4 and ZR-8 exhibited more potent activities,and particularly ZR-8 exhibited strongest in inhibiting cell proliferation.The IC50 are(25.08 ± 1.39)?mol/L and(35.29 ± 2.70)?mol/L in breast cancer MDA-MB-231 and MCF-7 cells treated with ZR-4 for 72 hours.Flow cytometry showed that treating cells with ZR-4 and ZR-8 caused G1 phase arrest in breast cancer cells.The percentage of G1 phase cells treated with ZR-8 in MDA-MB-231 and MCF-7 cells are(66.79 ± 2.97)% and(66.59 ± 2.49)% compared with that in control cells(47.39 ± 1.97)% and(49.17 ± 3.52)%(P <0.01).Western blot analysis showed that treatment of MDA-MB-231 and MCF-7 cells with ZR-4 and ZR-8 resulted in decreases in levels of CyclinD1 and CDK4.Treating cells with these compounds also resulted in decreases in levels of phospho-ERK and increases in levels of phospho-p38.The inhibitory effects of compounds separated from hosta on cell proliferation were also evaluated.Our results showed that compound HP-8 exhibited obvious inhibitory effects on cell proliferation in human breast cancer MDA-MB-231 cells.HP-6 and HP-8 exhibited the inhibitory effects on cell proliferation in human breast cancer MCF-7 cells,and particularly HP-6 exhibited most potent activity.HP-6 and HP-10 exhibited inhibitory effects on cell proliferation in human hepatocarcinoma SMMC-7721 cells.These results indicated that different compounds from hosta exhibited diverse inhibitory effects in different types of cancer cell lines,suggesting that these compounds selectively exhibited inhibitory activities in cancer cells.Our studies on bioactive constituents of ginger and Hosta will provide an important scientific basis and valuable lead compounds for the development of novel antitumor drugs.Therefore,the in-depth study on bioactive constituents of these natural products is of great theoretical significance and practical value for the development and utilization of traditional chinese medicine resources and improving the health level of our people. |
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