Đang tải... (xem toàn văn)
Nghiên cứu thành phần hóa học và hoạt tính sinh học của củ rễ cây Mạch môn (Ophiopogon japonicus (L.f.) KerGawl.)Nghiên cứu thành phần hóa học và hoạt tính sinh học của củ rễ cây Mạch môn (Ophiopogon japonicus (L.f.) KerGawl.)Nghiên cứu thành phần hóa học và hoạt tính sinh học của củ rễ cây Mạch môn (Ophiopogon japonicus (L.f.) KerGawl.)Nghiên cứu thành phần hóa học và hoạt tính sinh học của củ rễ cây Mạch môn (Ophiopogon japonicus (L.f.) KerGawl.)Nghiên cứu thành phần hóa học và hoạt tính sinh học của củ rễ cây Mạch môn (Ophiopogon japonicus (L.f.) KerGawl.)Nghiên cứu thành phần hóa học và hoạt tính sinh học của củ rễ cây Mạch môn (Ophiopogon japonicus (L.f.) KerGawl.)Nghiên cứu thành phần hóa học và hoạt tính sinh học của củ rễ cây Mạch môn (Ophiopogon japonicus (L.f.) KerGawl.)Nghiên cứu thành phần hóa học và hoạt tính sinh học của củ rễ cây Mạch môn (Ophiopogon japonicus (L.f.) KerGawl.)
i B GIÁO D O VI N HÀN LÂM KHOA H C VÀ CÔNG NGH VI T NAM H C VI N KHOA H C VÀ CÔNG NGH Nguy NGHIÊN C U THÀNH PH N HỐ H C VÀ HO T TÍNH SINH H C C A R C CÂY M CH MÔN (OPHIOPOGON JAPONICUS (L.f.) KER-GAWL.) LU N ÁN TI N S HÓA H C Hà N i 2018 ii B GIÁO D O VI N HÀN LÂM KHOA H C VÀ CÔNG NGH VI T NAM H C VI N KHOA H C VÀ CÔNG NGH Nguy NGHIÊN C U THÀNH PH N HOÁ H C VÀ HO T TÍNH SINH H C C A R C CÂY M CH MÔN (OPHIOPOGON JAPONICUS (L.f.) KER-GAWL.) Chuyên ngành: Hóa h Mã s : 62.44.01.14 LU N ÁN TI N S HÓA H C NG D N KHOA H C: PGS TS Nguy n Ti TS Nguy Hà N i 2018 t i L uc Nguy n Ti is ng d n c a PGS TS t TS Nguy Các s li u k t qu lu n án hoàn tồn trung th c cơng b b t k cơng trình khác Hà N Tác gi lu n án Nguy ii L IC Lu c hoàn thành t i Vi n Hoá sinh bi n, Vi n Hàn lâm Khoa h c Công ngh Vi t Nam V i lòng bi c, tơi xin bày t lòng bi t TS Nguy ch b o t o m i PGS TS Nguy n Ti n i th u ki ng d n, h t lòng tơi th i gian làm lu n án Tôi xin trân tr ng c b c a Vi o Vi n Hóa sinh bi n t p th cán om u ki n thu n l i cho tơi su t q trình h c t p nghiên c u th c hi n lu n án Tôi xin chân thành c - Vi n Hóa Sinh bi Ho t ch t sinh h c bi t TS Nguy n ThS Ph m Thanh Bình c ng s c li u bi n o, TS Nguy n H u ki , có nh ng l i khun b ích nh ng góp ý quý báu vi c th c hi n hồn thi n lu n án Tơi xin bày t lòng bi b n bè nh c nh t t i tồn th quan tâm, khích l ng viên tơi su t q trình h c t p nghiên c u Xin trân tr ng c Tác gi Nguy iii M CL C Trang ph bìa L i L ic ii M cl c iii Danh m c ch vi t t t vi Danh m c b ng ix Danh m c hình x M U NG QUAN 1.1 Gi i thi u v chi Ophiopogon 1.2 Gi i thi u v M ch môn 1.2.1 Vài nét v th c v t h c 1.2.2 Cơng d ng tính v 1.2.2.1 T i Vi t Nam 1.2.2.2 Trên th gi i 1.2.3 Các nghiên c u v thành ph n hóa h c ho t tính sinh h c c a M ch mơn 1.2.3.1 Thành ph n hóa h c 1.2.3.2 Ho t tính sinh h c 18 U 2.1 2.2 2.3 2.4 26 26 ng nghiên c u 26 u nh c u trúc hóa h c h p ch t t tính sinh h c 27 29 iv 2.4.1 c t bào 2.4.2 s n sinh NO 29 31 C NGHI M VÀ 34 34 3.1 Chi t phân l p h p ch t 3.2 H ng s v t lý d ki n ph c a h p ch TH O LU N 4.1 nh c u trúc h p ch t phân l c nh c u trúc nhóm ch t benzofuran p 39 45 45 47 4.1.1.1 H p ch t OJ-1 47 4.1.1.2 H p ch t OJ-2 53 4.1.1.3 H p ch t OJ-3 58 4.1.1.4 H p ch t OJ-4 62 4.1.1.5 H p ch t OJ-5 68 4.1.2 nh c u trúc nhóm ch t homoisoflavonoid 72 4.1.2.1 H p ch t OJ-6 72 4.1.2.2 H p ch t OJ-7 77 4.1.2.3 H p ch t OJ-8 82 4.1.2.4 H p ch t OJ-9 87 4.1.3 nh c u trúc nhóm ch t flavonoid 92 4.1.3.1 H p ch t OJ-10 92 4.1.3.2 H p ch t OJ-11 97 4.1.4 nh c u trúc nhóm ch t eudesmane sesquiterpenoid 97 4.1.4.1 H p ch t OJ-12 99 4.1.4.2 H p ch t OJ-13 104 4.1.4.3 H p ch t OJ-14 107 v 4.1.5 nh c u trúc h p ch t khác 110 4.1.5.1 H p ch t OJ-15 4.2 4.2.1 Ho t tính sinh h c c a h p ch t phân l c t bào 4.2.2 Ho t tính c ch s n sinh NO K T LU N VÀ KI N NGH 110 c 116 116 119 121 123 124 vi DANH M C CH Human A549 lung adenocarcinoma epithelial cell line BEL-7402 Human hepatoma cell line CC Column Chromatography 13 Carbon-13 C NMR CH2Cl2 Nuclear DMEM Magnetic Resonance Spectroscopy cacbon 13 dichloromethan Diclometan Distortionless DEPT VI T T T Enhancement by Polarisation Transfer Medium DMEM DMSO Dimethylsulfoside Dimethylsulfoside EC100 Effective concentration 100% EC50 Effective concentration 50% ED50 Effective dose 50% Epidermal EGFR ESI-MS 1 H- H COSY Hela mô Electronspray Ionization Mas ù Spectrum Magnetic Resonance Spectroscopy 1 Factor T Receptor Proton H NMR Growth H-1H Chemical Correlation Spectroscopy Hela human cervix cell line proton Shift vii Hep-3B Hep-G2 Human hepatoma cell line Human hepatocellular carcinoma cell line Heteronuclear HMBC HSQC Bond Connectivity High HR-TOF-MS Multiple Resolution Time of-Flight Mass Spectrometer Heteronuclear Single Quantum Coherence IC50 Inhibitory concentration 50% IR Infrared Spectroscopy IUPAC KB International Union of Human epidemoid carcinoma cell line Lipopolysaccharide LU Lung carcinoma cell lines MeOH Methanol Mp MTT Lipopolysacaride Human breast adenocarcinoma cell line Minimal MIC Pure and Applied Chemistry LPS MCF-7 gian bay ú inhibitory concentration Melting Point [3-(4,5-dimethylthiazol-2- [3-(4,5-dimetylthiazol-2-yl)2,5- yl)2,5-diphenyltetrazolium diphenyltetrazoli bromua] viii bromide] NSCLC Non-small cell lung cancer U i t bào không nh SK-MEL-2 Human melanoma cell line TKI Tyrosine kinase inhibitor yrosine kinase TLC Thin layer chromatography ng TMS Tetrametyl Silan s Tetrametyl Silan 120 OJ-2 50 = 29,1 µ ( c bi m ) 2,3- t h p ch t có tác d ng kháng viêm c ch ng minh th hi n r ng h p ch t có khung 2,3nh th nghi m in vivo dihydrobenzofuran-2-one có kh Các h p ch t có khung 5-chloro-6-cyclohexyl-2,3-dihydrobenzofuran-2-one có ý c ch m nh i ch t tham kh o diclofenac t t c thí nghi m [100] tomentosa c phân l p t h t Prunus p ch c th nghi c k t qu dòng t bào BV-2 [101] T k t qu nghiên c c ch m nh s s n sinh NO r ng, nhóm ch t dihydrobenzofuran t r c M ch môn m t ngu n kháng viêm t t nhiên r t ti c nghiên c u sâu công nghi p s n xu tìm ngu n kháng viêm m i c ph m Hai h p ch t thu c nhóm homoisoflavonoid homoisopogon A (OJ-6) homoisopogon B (OJ-7 22,5 19,3 M n hi n tác d ng c ch s n sinh NO v i giá tr IC50 ng Các h p ch th nghi m l n nh t 30 M u không th hi n tác d ng 121 K T LU N VÀ KI N NGH V nghiên c u thành ph n hóa h c T r c M ch môn (O japonicus), 15 h p ch t ã g m 09 h p ch t m i, 02 h p ch t l h p ch c phân l p bao c phân l p t thiên nhiên 04 t Các h p ch t thu c nhóm ch t benzofuran (05 ch t), homoisoflavonoid (04 ch t), flavonoid (02 ch t), eudesmane sesquiterpenoid (03 ch t) steroidal glycoside (01 ch t) C u trúc hóa h c c a nh : Nhóm ch t benzofuran: (2R)-(4-methoxybenzyl)-5,7-dimethyl-6-hydroxyl2,3-dihydrobenzofuran (OJ-1, ch t m i), 2-(2-hydroxyl-4-methoxy-benzyl)-5methyl-6-methoxyl-2,3-dihydrobenzofuran (OJ-2, ch t m i), 2-(4-hydroxy- benzyl)-5,6-dihydroxylbenzofuran (OJ-3, ch t m i), 2-(4-methoxy-benzyl)-6,7dimethoxyl-2,3-dihydrobenzofuran (OJ-4, ch t m i l u phân l p t thiên nhiên) 2-(4-methoxy-benzyl)-6,7-methylenedioxy-2,3-dihydrobenzofuran (OJ-5, ch t m i l u phân l p t thiên nhiên) Nhóm ch t homoisoflavonoid: homoisopogon A (OJ-6, ch t m i), homoisopogon B (OJ-7, ch t m i), homoisopogon C (OJ-8, ch t m i) homoisopogon D (OJ-9, ch t m i) Nhóm ch t flavonoid: 8-C-methyl-3',5,5',7-tetrahydroxy- -dimethoxy flavone (OJ-10, ch t m i) myricetin 3,4'-dimethyl ether (3',5,5',7-tetrahydroxy3,4'-dimethoxyflavone) (OJ-11) Nhóm ch t eudesmane sesquiterpenoid: ,4 ,6 -trihydroxy-5,10-bis-epieudesmane-6-O- -D-glucopyranoside (OJ-12), ,6 -dihydroxy-5,10-bis-epi- eudesm -4(15)-ene-6-O- -D-glucopyranoside (OJ-13) ,6 -dihydroxy-5,10-bisepi-eudesm-3-ene-6-O- -D-glucopyranoside (OJ-14) Nhóm ch t steroidal glycoside: (25R)-ruscogenin 1-O-(4-O-sulfo)- -Dfucopyranoside (OJ-15, ch t m i) Các h p ch t có khung 2-benzylbenzofuran r t hi m g 2-benzyl-2,3-dihydrobenzofuran h n xu t c phân l p t thiên nhiên Lu n 122 c c u trúc hoá h c c a 05 h p ch t thu c nhóm ch t Cùng v i h p ch t m i thu c nhóm ch t nh ng m i n i b t c a lu m li u hoá h c h p ch t thiên nhiên V nghiên c u ho t tính sinh h c c t bào in vitro c a h p ch t phân l p o sát ho c dòng t i kháng thu c (A549), bi u mô (KB) c t ph i (LU-1), ung (SK-Mel-2) K t qu cho th y h p ch t homoisopogon A (OJ-6) có ho t tính r t m nh dòng t bào th nghi m (LU-1, KB SK-Mel-2) v i giá tr IC50 t 0,51 n 0,66 µM, so sánh v i ch i ch ng ellipticine H p ch t (2R)-(4-methoxybenzyl)-5,7-dimethyl-6-hydroxyl-2,3dihydro benzofuran (OJ-1) có tác d ng m nh v i giá tr IC50 t 8,86 i v i dòng t i kháng thu c (A549), homoisopogon A (OJ-6) th hi n tác d ng m nh so v th hi n tác d ng gây ch t t n n 14,0 µM i ch camptothecin H p ch t A549 gây ch t th nghi m 25 50 M t tính kháng viêm d a ng c ch s s n sinh NO c a 15 h p ch t nhóm OJ-1 µ 50 OJ-2 29,1 µM H = 11,4 50 = homoisoflavonoid homoisopogon A (OJ-6) homoisopogon B (OJ-7 hi n tác d ng c ch s n sinh NO v i giá tr IC50 22,5 19,3 M u v M ch môn (O japonicus), Ki n ngh h p ch t phân l p th hi n ho r t nhi u ti c viêm ct t tính kháng viêm c bi t h p ch t homoisopogon A (OJ-6) c ho t tính sinh h c theo tác d ng gây ch t t c nghiên 123 DANH M C CƠNG TRÌNH CƠNG B C A TÁC GI N LU N ÁN Nguyen Dinh Chung, Nguyen Phuong Thao, Ha Manh Tuan, Nguyen Van Thanh, Nguyen Hai Dang, Nguyen Tien Dat New steroidal glycoside and flavonoid constituents from Ophiopogon japonicus Nat Prod Commun., 2017, 12(6), 905 906 Nguyen Hai Dang, Nguyen Dinh Chung, Ha Manh Tuan, Nguyen Tuan Hiep, Nguyen Tien Dat Cytotoxic homoisoflavonoids from Ophiopogon japonicus tubers Chem Pharm Bull., 2017, 65(2), 204 207 Nguyen Hai Dang, Nguyen Dinh Chung, Ha Manh Tuan, Nguyen Van Thanh, Nguyen Tuan Hiep, Dongho Lee, and Nguyen Tien Dat 2-Benzyl-benzofurans from the tubers of Ophiopogon japonicus Chem Cent J., 2017, 11:15 Nguyen Dinh Chung, Nguyen Tien Dat, Le Thi Van Anh, Jeong-Hyung Lee, Nguyen Hai Dang Homoisopogon A from Ophiopogon japonicus induced apoptosis in A549-a non small cell lung cancer cell line 2017, 15(1), 35 39 Nguyen Dinh Chung, Nguyen Hai Dang, Nguyen Van Thanh, Nguyen Tien Dat Eudesmane sesquiterpene glucosides from Ophiopogon japonicus , 2015, 53(4C), 56 62 chí 124 [1] Editorial board of flora of China Flora of China Science Publishing House, Beijing 1978, Vol 24, p 252 [2] Masaoud, M.; Ripperger, H.; Porzel, A.; Adam, G Flavonoids of dragon's blood from Dracaena cinnabari Phytochemistry 1995, 38, 745 749 Cây thu [3] ng v t làm thu c Nhà xu t b n Khoa h c K thu t 2004, T p 2, 216 220 [4] Chi, V.V T n thu c Vi t Nam Nhà xu t b n Y h c, Hà N i 2012, 1, 1023 [5] Hung, T.M.; Thu, C.V.; Dat, N.T.; Ryoo, S.W.; Lee, J.H.; Kim, J.C.; Na, M.; Jung, H.J.; Bae, K.; Min, B.S Homoisoflavonoid derivatives from the roots of Ophiopogon japonicus and their in vitro anti-inflammation activity Bioorg Med Chem Lett., 2010, 20, 2412 2416 [6] Anh, N.T.H.; Sung, T.V.; Porzel, A.; Franke, K.; A, L.; Wessjohann Homoisoflavonoids from Ophiopogon japonicus Ker-Gawler Phytochemistry 2003, 62, 1153 1158 , N.T Th c v t chí Vi t Nam Nhà xu t b n Khoa h c K thu t 2007, T p [7] 8, 16 192 [8] L h ng thu c v thu c Vi t Nam Nhà xu t b n Y h c 2006, pp 428 429 [9] Feng, Z.Y.; Jin, Q.; Ni, Z.D.; Yang, Y.B Homoisoflavonoids from Ophiopogon japonicus and its oxygen free radicals (OFRS) scavenging effects Chinese J Nat Med., 2008, 6(3), 201 204 [10] Chi, V.V Dictionary of common plants Science and Technology: Hanoi 1999, Vol 1, p 709 [11] State administration of traditional chinese medicine of PRC Chinese materia medica Shanghai Science and Technology Publishers, Shanghai, China 1999 125 [12] Liang, H.; Xing, Y.; Chen, J.; Zhang, D.; Guo, S.; Wang, C Antimicrobial activities of endophytic fungi isolated from Ophiopogon japonicus (Liliaceae) BMC Complement Altern Med., 2012, 238, 1472 1477 [13] Xia, C.H.; Sun, J.G.; Wang, G.J.; Shang, L.L.; Zhang, X.X.; Zhang, R.; Wang, X.J.; Hao, H.P.; Xie, L Differential effect of shenmai injection, a herbal preparation, on the cytochrome P450 3a-mediated -hydroxylation and 4-hydroxylation of midazolam Chem Biol Interact., 2009, 180(3), 440 448 [14] Yao, H.T.; Chang, Y.W.; Chen, C.T.; Chiang, M.T.; Chang, L.; Yeh, T.K Shengmai san reduces hepatic lipids and lipid peroxidation in rats fed on a high-cholesterol diet J Ethnopharmacol., 2008, 116(1), 49 57 [15] Izawa, M.D Colored illustrations of medicinal plants (material medica) of Japan Seibundo-shinkosha Publishing Co Tokyo, Japan 1967, 272 273 [16] Iqbal, Z.; Hiradate, S.; Araya, H.; Fujii, Y Plant growth inhibitory activity of Ophiopogon japonicus Ker-Gawler and role of phenolic acids and their analogues: A comparative study Plant Grow Reg., 2004, 43(3), 245 250 [17] Tada, A.; Kobayashi, M.; Shoji, J Studies on the constituents of Ophiopogonis tuber III On the structure of ophiopogonin D Chem Pharm Bull., 1973, 21, 308 311 [18] Tada, A.; Shoji, J Studies on the constituents of Ophiopogonis tuber II On the structure of ophiopogonin B Chem Pharm Bull., 1972, 20(8), 1729 1734 [19] Watanabe, Y.; Sanada, S.; Tada, A.; Shoji, J Studies on the constituents of ophiopogonis tuber IV On the structures of ophiopogonin and Chem Pharm Bull., 1977, 25(11), 3049 3055 [20] Asano, T.; Murayama, T.; Hirai, Y.; Shoji, J Comparative studies on the constituents of ophiopogonis tuber and its congeners VIII Studies on the glycosides of the subterranean part of Ophiopogon japonicus Ker-Gawler cv nanus Chem Pharm., Bull., 1993, 41(3), 566 570 126 [21] Liu, N.; Wen, X.B.; Liu, J.H.; Liang, M.; Zeng, H.J.; Lin, Y Determination of ruscogenin in crude chinese medicines and biological samples by immunoassay Anal Bioanal Chem., 2006, 386(6), 1727 1733 [22] Duan, C.L.; Ma, X.F.; Jiang, Y.; Liu, J.X.; Tu, P.F Spirostanol saponins from the fibrous roots of Ophiopogon japonicus (Thunb.) Ker-Gawl Helv Chim Acta 2010, 93(2), 227 232 [23] Duan, C.L.; Ma, X.F.; Jiang, Y.; Liu, J.X.; Tu, P.F Two new furostanol glycosides from the fibrous root of Ophiopogon japonicus (Thunb.) KerGawl J Asian Nat Prod Res., 2010, 12(9), 745 751 [24] Zhang, T.; Kang, L.P.; Yu, H.S.; Liu, Y.X.; Zhao, Y.; Xiong, C.Q.; Zhang, J.; Zou, P.; Song, X.B.; Liu, C., et al Steroidal saponins from the tuber of Ophiopogon japonicus Steroids 2012, 77(12), 1298 1305 [25] Li, N.; Zhang, L.; Zeng, K.W.; Zhou, Y.; Zhang, J.Y.; Che, Y.Y.; Tu, P.F Cytotoxic steroidal saponins from Ophiopogon japonicus Steroids 2013, 78(1), [26] Zhou, Y.F.; Qi, J.; Zhu, D.N.; Yu, B Two new steroidal glycosides from Ophiopogon japonicus Chinese Chem Lett., 2000, 11, 901 904 [27] Xu, T.-H.; Xu, Y.-J.; Xie, S.-X.; Zhao, H.-F.; Han, D.; Li, Y.; Niu, J.-Z.; Xu, D.-M A novel steroidal glycoside, ophiofurospiside A from Ophiopogon japonicus (Thunb.) Ker-Gawl J Asian Nat Prod Res., 2008, 10(5-6), 415 418 [28] Liu, Y.X Study on steroidal saponins from Ophiopogon japonicus Master thesis of Nanhua University 2013 [29] Ye, Y.; Qu, Y.; Tang, R.; Cao, S.; Yang, W.; Xiang, L.; Qi, J Three new neuritogenic steroidal saponins from Ophiopogon japonicus (Thunb.) KerGawl Steroids 2013, 78(12-13), 1171 1176 [30] Liu, Y.; Meng, L.-Z.; Xie, S.-X.; Xu, T.-H.; Sun, L.-k.; Liu, T.-H.; Xu, Y.-J.; Xu, D.-M Studies on chemical constituents of Ophiopogon japonicus J Asian Nat Prod Res., 2014, 16(10), 982 990 127 [31] Li, N.; Zhang, J.Y.; Zeng, K.W.; Zhang, L.; Che, Y.Y.; Tu, P.F Antiinflammatory homoisoflavonoids from the tuberous roots of Ophiopogon japonicus Fitoterapia 2012, 83(6), 1042 1045 [32] Zhu, Y.; Yan, K.; Tu, G Two homoisoflavones from Ophiopogon japonicus Phytochemistry 1987, 26(10), 2873 2874 [33] Duan, C.L.; Kang, Z.Y.; Lin, C.R.; Jiang, Y.; Liu, J.X.; Tu, P.F Two new homoisoflavonoids from the fibrous roots of Ophiopogon japonicus (Thunb.) Ker-Gawl J Asian Nat Prod Res., 2009, 11(10), 876 879 [34] Zhou, Y.-F.; Qi, J.; Zhu, D.-N.; Yu, B.-Y Homoisoflavonoids from Ophiopogon japonicus and its oxygen free radicals (OFRS) scavenging effects Chinese J Nat Med., 2008, 6, 201 204 [35] Lan, S.; Yia, F.; Shuang, L.; ChenJie, W.; Zheng, X.W Chemical constituents from the fibrous root of Ophiopogon japonicus, and their effect on tube formation in human myocardial microvascular endothelial cells Fitoterapia 2013, 85, 57 63 [36] Wang, Y.Y.; Xu, J.Z.; Qu, H.B Determination of three steroidal saponins from Ophiopogon japonicus (Liliaceae) via high-performance liquid chromatography with mass spectrometry Nat Prod Res., 2013, 27(1), 72 75 [37] Tada, A.; Kasai, R.; Saitoh, T.; Shoji, J Studies on the constituents of ophiopogonis tuber V Isolation of a novel class of homoisoflavonoids and determination of their structures Chem Pharm Bull., 1980, 28, 1477 1484 [38] Kaneda, N.; Nakanishi, H.; Kuraishi, T.; Katori, T Studies on the components of Ophiopogon roots (China).I J Pharm Soc Japan 1983, 103, 1133 1139 [39] Asano, T.; Murayama, T.; Hirai, Y.; Shoji, J Comparative studies on the constituents of ophiopogonis tuber and its congeners VII Studies on the homoisoflavonoids of the subterranean part of Ophiopogon japonicus KerGawler cv Chem Pharm Bull., 1993, 41, 391 393 128 [40] Chang, J.M.; Shen, C.C.; Huang, Y.L.; Chien, M.Y.; Ou, J.C.; Shieh, B.J.; Chen, C.C Five new homoisoflavonoids from the tuber of Ophiopogon japonicus J Nat Prod., 2002, 65(11), 1731 1733 [41] Li, N.; Zhang, J.Y.; Zeng, K.W.; Zhang, L.; Che, Y.Y.; Tu, P.F Antiinflammatory homoisoflavonoids from the tuberous roots of Ophiopogon japonicus Fitoterapia 2012, 83(6), 1042 1045 [42] Zhou, C.; Zou, X.L.; Mo, J.X.; Wang, X.Y.; Yang, B.; He, Q.J.; Gan, L.S Homoisoflavonoids from Ophiopogon japonicus Helv Chim Acta 2013, 96, 1397 1405 [43] Cheng, Z.-H.; Wu, T.; Bligh, S.W.A.; Bashall, A.; Yu, B.-Y Cis-eudesmane sesquiterpene glycosides from Liriope muscari and Ophiopogon japonicus J Nat Prod., 2004, 67(10), 1761 1763 [44] Xiong, S.l.; Li, A.; Huang, N.; Lu, F.; Hou, D Antioxidant and immunoregulatory activity of different polysaccharide fractions from tuber of Ophiopogon japonicus Carbohydr Polym., 2011, 86(3), 1273 1280 [45] Chen, X.; Jin, J.; Tang, J.; Wang, Z.; Wang, J.; Jin, L.; Lu, J Extraction, purification, characterization and hypoglycemic activity of a polysaccharide isolated from the root of Ophiopogon japonicus Carbohydr Polym., 2011, 83(2), 749 754 [46] Wang, L.Y.; Wang, Y.; Xu, D.S.; Ruan, K.F.; Feng, Y.; Wa, S MDG-1, a polysaccharide from Ophiopogon japonicus exerts hypoglycemic effects through the PI3K/AKT pathway in a diabetic kkay mouse model J Ethnopharmacol., 2012, 143(1), 347 354 [47] She, G.; Shi, J Structural features of two neutral polysaccharides MD-1, MD-2 from Ophiopogon japonocus Zhong Yao Cai 2003, 26, 100 101 [48] Cheng, Z.H.; Wu, T.; Li, L.Z.; Liu, N.; Yu, B.Y.; Xu, L.S Studies on the liposoluble components from tuber of Ophiopogon japonicus Zhongguo Yao Xue Za Zhi 2005, 5, 337 341 [49] Cheng, Z.H.; Wu, T.; Yu, B.Y Chemical constituents in the tubers of Ophiopogon japonicus Nat Prod Res Devel., 2005, 17, 129 [50] Dai, H.; Mei, W Ophiopojaponin D, a new phenylpropanoid glycoside from Ophiopogon japonicus Ker-Gawl Arch Pharm Res., 2005, 28(11), 1236 1238 [51] Shen, H.L.; Xiang, N.J.; Xu, Y.; Gao, Q.; Miao, M.M.; Li, J.M Analysis of fatsoluble components of Ophiopogon japonicus by GC-MS Chinese J Spec Lab., 2008, 4, 669 672 [52] Nakanishi, H.; Kameda, N Studies on the component of ophiopogon tuber (China) II J Pharm Soc Japan 1987, 107, 780 784 [53] Kato, H.; Sakuma, S.; Tada, A.; Kawanishi, S.; Shoji, J Studies on the constituents of ophiopogonis tuber I Isolation of steroidal glycosides from tuber of Ophiopogon japonicus Ker-Gawler var genuinus Maxim J Pharm Soc Japan 1968, 88, 710 714 [54] Chen, X.; Tang, J.; Xie, W.; Wang, J.; Jin, J.; Ren, J.; Jin, L.; Lua, J Protective effect of the polysaccharide from Ophiopogon japonicus on streptozotocin-induced diabetic rats Carbohydr Polym., 2013, 94(1), 378 385 [55] Zhou, Y.F.; Qi, J.; Zhu, D.N.; Yu, B Two new steroidal glycosides from Ophiopogon japonicus Chinese Chem Lett., 2008, 1086 1088 [56] Song, J.; Kou, J.; Huang, Y.; Yu, B Ruscogenin mainly inhibits nuclear factorlategut microbiota in high-fat diet-induced obese C57BL/6 mice Int J Biol Macromol Urnal Pharm Sci., 2010, 113, 409 413 [57] Tian, Y.; Kou, J.; Li, L.; Yu, B Antifrom radix liriope muscari and its major active fraction and component Chinese J Nat Med., 2011, 9(3), 222 226 [58] Lina, Y.; Zhua, D.; Qia, J.; Qin, M.; Yu, B Characterization of homoisoflavonoids in different cultivation regions of Ophiopogon japonicus and related antioxidant activity J Pharm Bio Ana., 2010, 52(5), 757 762 [59] Wang, X.M.; Sun, R.G.; Zhang, J.; Chen, Y.Y.; Liu, N.N Structure and antioxidant activity of polysaccharide POJ-U1A extracted by ultrasound from Ophiopogon japonicus Fitoterapia 2012, 83, 1576 1584 130 [60] Huang, Q.; Gao, B.; Wang, L.; Zhang, H.Y.; Li, X.J.; Shi, J.; Wang, Z.; Zhang, J.K.; Yang, L.; Luo, Z.J., et al Ophiopogonin D: A new herbal agent against osteoporosis Bone 2015, 74, 18 28 [61] Sun, K.; Cao, S.; Pei, L.; Matsuura, A.; Xiang, L.; Qi, J.H A steroidal saponin from Ophiopogon japonicus extends the lifespan of yeast via the pathway involved in SOD and UTH1 Int J Mol Sci., 2013, 14(3), 4461 4475 [62] Xiong, S.; Li, A.; Huang, N.; Lu, F.; Hou, D Antioxidant and immunoregulatory activity of different polysaccharide fractions from tuber of Ophiopogon japonicus Carbohydr Polym., 2011, 86(3), 1273 1280 [63] Chen, M.; Du, Y.; Qui, M.; Wang, M.; Chen, K.; Huang, Z.; Jiang, M.; Xiong, F.; Chen, J.; Zhou, J., et al Ophiopogonin B-induced autophagy in non-small cell lung cancer cells via inhibition of the PI3K/AKT signaling pathway Oncol Rep., 2013, 29, 430 436 [64] Chen, M.; Yang, Z.W.; Zhu, J.T.; Xiao, Z.Y.; Xiao, R Antiarrhythmic effects and electrophysiological properties of ophiopogon total saponins Zhong Guo Yao Li Xue Bao 1990, 11, 161 165 65 Tao, J.; Wang, H.; Chen, J.; Xu, H.; Li, S Effects of saponin monomer 13 of dwarf lilyturf tuber on L-type calcium currents in adult rat ventricular myocytes American J Chinese Med., 2005, 33, 797 806 [66] Zhang, Y.-Y.; Meng, C.; Zhang, X.-M.; Yuan, C.-H.; Wen, M.-D.; Chen, Z.; Dong, D.-C.; Gao, Y.-H.; Liu, C.; Zhang, Z Ophiopogonin D attenuates doxorubicininduced autophagic cell death by relieving mitochondrial damage in vitro and in vivo J Pharmacol Exp Ther., 2015, 352, 166 174 [67] Guan, T.; Liu, Q.; Qian, Y.; Yang, H.; Kong, J.; Kou, J.; Yu, B Ruscogenin reduces cerebral ischemic injury via NF-kappab-mediated inflammatory pathway in the mouse model of experimental stroke European J Pharmacol., 2013, 714(1-3), 303 311 131 [68] Duan, C.; Wang, Y.; Ma, X.; Jiang, Y.; Liu, J.; Tu, P A new furostanol glycoside with fatty acid synthase inhibitory activity from Ophiopogon japonicus Chem Nat Comp., 2012, 48, 613 615 [69] Tian, Y.; Ma, S.; Lin, B.; Kou, J.; Yu, B Ruscogenin glycoside (LM-3) isolated from liriope muscari improves liver injury by dysfunctioning liverinfiltrating lymphocytes J Pharm Pharmacol., 2000, 53(5), 681 688 [70] Fan, Y.; Ma, X.; Zhang, J.; Ma, L.; Gao, Y.; Zhang, W.; Song, X.; Hou, W.; Guo, C.; Tong, D Ophiopogon polysaccharide liposome can enhance the non-specific and specific immune response in chickens Carbohydr Polym., 2015, 119, 219 227 [71] Linwei, D.; Peibo, L.; San, L.C.B.; Wa, C.Y.; Dingzhou, X.; Kwok-Pui, F.; Weiwei, S Mechanistic studies on the antidiabetic activity of a polysaccharide-rich extract of radix ophiopogonis Phytother Res., 2012, 26(1), 101 105 [72] Wang, H Preventive effects of ophiopogon-polysaccharide on apiponectin in gestational diabetes mellitus rat Asian Pac J Trop Med., 2013, 6(4), 296 299 [73] Li, P.-B.; Lin, W.-L.; Wang, Y.-G.; Peng, W.; Cai, X.-Y.; Su, W.-W Antidiabetic activities of oligosaccharides of Ophiopogonis japonicus in experimental type diabetic rats Int J Biol Macromol., 2012, 51(5), 749 755 [74] Wang, Y.; Zhu, Y.; Ruan, K.; Wei, H.; Feng, Y MDG-1, a polysaccharide from Ophiopogon japonicus, prevents high fat diet-induced obesity and increases energy expenditure in mice Carbohydr Polym., 2014, 114, 183 189 [75] Zhu, Y.; Cong, W.; Shen, L.; Wei, H.; Wang, Y.; Wang, L.; Ruan, K.; Wua, F.; Feng, Y Fecal metabonomic study of a polysaccharide, MDG-1 from Ophiopogon japonicus on diabetic mice based on gas chromatography/timeof-flight mass spectrometry (GC TOF/MS) Mol bioSys., 2014, 10, 304 312 132 [76] Tian, Q.; Wang, W.; Miao, C.; Peng, H.; Liu, B.; Leng, F.; Dai, L.; Chen, F.; Bao, J Purification, characterization and molecular cloning of a novel mannosebinding lectin from rhizomes of Ophiopogon japonicus with antiviral and antifungal activities Plant Sci., 2008, 175, 877 884 [77] Tian, Q.; Wang, W.; Miao, C.; Peng, H.; Liu, B.; Leng, F.; Dai, L.; Chen, F.; Bao, J mannosebinding lectin from rhizomes of Ophiopogon japonicus with antiviral and antifungal activities Plant Sci., 2008, 175, 877 884 [78] Zhang, M.; Liu, X.; Song, J.; Hu, Y.; Wang, X.; Li, B Effects of radix ophiopogonis is decoction on embryo-fetal development in rats China J Chinese Mat Med., 2010, 35, 2334 2337 [79] Ye, G.; Ye, M.; Guo, D.; Huang, C Determination of homoisoflavonoids in Ophiopogon japonicus by RP-HPLC Chromatographia 2005, 61, 121 125 [80] Ye, M.; Guo, D.; Ye, G.; Huang, C Analysis of homoisoflavonoids in Ophiopogon japonicus by HPLC-DAD-ESI-MSN1 J American Soc Mass Spec., 2005, 16, 234 243 [81] Mosmann, T Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays J Immunol Methods 1983, 65, 55 63 [82] Skehan, P.; Storeng, R.; Scudiero, D.; Monks, A.; McMahon, J.; Vistica, D.; Warren, J.T.; Bokesch, H.; Kenney, S.; Boyd, M.R New colorimetric cytotoxicity assay for anticancer-drug screening J Nat Cancer Ins.,1990, 82, 1107 1112 [83] Nathan, C Nitric oxide as a secretory product of mammalian cells FASEB journal: official publication Fed American Soci Exp Biol., 1992, 6, 3051 3064 [84] Dirsch, V.M.; Stuppner, H.; Vollmar, A.M The griess assay: Suitable for a bio-guided fractionation of anti-inflammatory plant extracts? Planta Med., 1998, 65(4), 423 426 133 [85] Hatziieremia, S.; Gray, A.I.; Ferro, V.A.; Paul, A.; Plevin, R The effects of cardamonin on lipopolysaccharide-induced inflammatory protein production and map kinase and nfkappab signalling pathways in monocytes/macrophages British J Pharmacol., 2006, 149, 188 198 [86] Ortega, N.; Urban, S.; Beiring, B.; Glorius, F Ruthenium nhc catalyzed highly asymmetric hydrogenation of benzofurans Angewandte Chem Int Edition 2012, 51, 1710 1713 [87] Qi, P.; Jiang, J.; Qi, H.; Jin, Y.; Shen, Q.; Wu, Y.; Song, H.; Zhang, W Synthesis and antiproliferative activity of new polyoxo 2-benzyl-2,3dihydrobenzofurans and their related compounds Lett Drug Design Dis., 2013, 10(9), 886 894 [88] Kwon, J.; Hiep, N.T.; Kim, D.W.; Hong, S.; Guo, Y.; Hwang, B.Y.; Lee, H.J.; Mar, W.; Lee, D Chemical constituents isolated from the root bark of Cudrania tricuspidata and their potential neuroprotective effects J Nat Prod., 2016, 79(8), 1938 1951 [89] Franke, K.; Porzel, A.; Masaoud, M.; Adam, G.; Schmidt, J Furanocoumarins from dorstenia gigas Phytochemistry 2001, 56, 611 621 [90] Zhang, W.; Song, H.; Wu, Y.; Shen, Q.; Jin, Y.; Qi, H.; Jiang, J.; Qi, P Synthesis and antiproliferative activity of new polyoxo 2-benzyl-2,3dihydrobenzofurans and their related compounds Lette Drug Design Dis., 2013, 10(6), 886 894 [91] Guo, H.; Zhao, H.; Kanno, Y.; Li, W.; Mu, Y.; Kuang, X.; Inouye, Y.; Koike, K.; Jiang, H.; Bai, H A dihydrochalcone and several homoisoflavonoids from Polygonatum odoratum are activators of adenosine monophosphateactivated protein kinase Bioorg Med Chem Lett., 2013, 23(11), 3137 3139 [92] Namikoshi, M.; Saitoh, T Homoisoflavonoids and related ompounds Iv.1) absolute configurations of homoisoflavonoids from Caesalpinia sappan L Chem Pharm Bull 1987, 35(9), 3597 3602 134 [93] Awale, S.; Miyamoto, T.; Linn, T.Z.; Li, F.; Win, N.N.; Tezuka, Y.; Esumi, H.; Kadota, S Cytotoxic constituents of Soymida febrifuga from Myanmar J Nat Prod., 72(9), 1631 1636 [94] Coxon, D.T.; O'Neill, T.M.; Mansfield, J.W.; Porter, A.E.A Identification of three hydroxyflavan phytoalexins from Daffodil bulbs Phytochemistry 1980, 19(5), 889 891 [95] Morimoto, S.; Nonaka, G.I.; Nishioka, I.; Ezakiand, N.; Takizawa, N Seven new methyl derivatives of flavan-3ols and a 1,3-diarylpropan-2-ol from Cinnamomum cassia, C Obtusifolium and Lindera umbellata var membranacea Chem Pharm Bull., 1985, 33, 2281 2286 [96] Fang, N.; Leidigand, M.; Mabray, T.J Highly oxygenated flavonoid aglycones from Gutierrezia grandis Phytochemistry 1985, 24(11), 2693 2698 [97] Hua, Y.; Zhou, J.; Chen, C.X A new eudesmane sesquiterpene glycoside from Parepigynum funingense Chinese Chem Lett., 2007, 18, 73 75 [98] Cheng, Z.H.; Wu, T.; Guo, Y.L.; Yu, B.Y.; Xu, L.S Two new steroidal glycosides from liriope muscari Chinese Chem Lett., 2006, 17, 31 34 [99] Yang, Z.G.; Matsuzaki, K.; Takamatsu, S.; Kitanaka, S Inhibitory effects of constituents from Morus alba var multicaulison differentiation of 3T3-L1 cells and nitric oxide production in RAW264.7 cells Molecules 2011, 16(17), 6010-6022 [100].Closse, A.; Haefliger, W.; Hausser, D.; U.Gubler, H.; Dewald, B.; Baggiolini, M 2,3-Dihydrobenzofuran-2-ones: A new class of highly potent antiinflammatory agents J Med Chem., 1981, 24(12), 1465 1471 [101] Liu, Q.-B.; Huang, X.-X.; Bai, M.; Chang, X.-B.; Yan, X.-J.; Zhu, T.; Zhao, W.; Peng, Y.; Song, S.-J Antioxidant and anti-inflammatory active dihydrobenzofuran neolignans from the seeds of Prunus tomentosa J Agri Food Chem., 2014, 62(31), 7796 7803 ... LÂM KHOA H C VÀ CÔNG NGH VI T NAM H C VI N KHOA H C VÀ CÔNG NGH Nguy NGHIÊN C U THÀNH PH N HỐ H C VÀ HO T TÍNH SINH H C C A R C CÂY M CH MÔN (OPHIOPOGON JAPONICUS (L.f.) KER-GAWL.)... M ch môn 1.2.1 Vài nét v th c v t h c 1.2.2 Cơng d ng tính v 1.2.2.1 T i Vi t Nam 1.2.2.2 Trên th gi i 1.2.3 Các nghiên c u v thành ph n hóa h c ho t tính sinh h c c a M ch môn 1.2.3.1 Thành. .. làm lu n án Tôi xin trân tr ng c b c a Vi o Vi n Hóa sinh bi n t p th cán om u ki n thu n l i cho tơi su t q trình h c t p nghiên c u th c hi n lu n án Tôi xin chân thành c - Vi n Hóa Sinh bi