Luận án tiến sĩ nghiên cứu thành phần hóa học và tác dụng dược lý của sâm việt nam chế biến

BỘ GIÁO DỤC VÀ ĐÀO TẠO ĐẠI HỌC Y DƯỢC THÀNH PHỐ HỒ CHÍ MINH LÊ THỊ HỒNG VÂN NGHIÊN CỨU THÀNH PHẦN HOÁ HỌC VÀ TÁC DỤNG DƯỢC LÝ CỦA SÂM VIỆT NAM CHẾ BIẾN LUẬN ÁN TIẾN SĨ DƯỢC HỌC Thành phố Hồ Chí Minh - Năm 2018 BỘ GIÁO DỤC VÀ ĐÀO TẠO ĐẠI HỌC Y DƯỢC THÀNH PHỐ HỒ CHÍ MINH LÊ THỊ HỒNG VÂN KHƯU NGHIÊN CỨU THÀNH PHẦN HOÁ HỌC VÀ TÁC DỤNG DƯỢC LÝ CỦA SÂM VIỆT NAM CHẾ BIẾN Chuyên ngành: Dược liệu - Dược học cổ truyền Mã số: 9720206 LUẬN ÁN TIẾN SĨ DƯỢC HỌC Người hướng dẫn khoa học: GS TS Nguyễn Minh Đức PGS TS Nguyễn Ngọc Khôi GS.TS NGUYỄN MINH ĐỨC GS.TS NGUYỄN NGỌC KHÔI Thành phố Hồ Chí Minh - Năm 2018 LỜI CAM ĐOAN Tơi xin cam đoan cơng trình nghiên cứu riêng tơi Các số liệu, kết trình bày luận án trung thực chưa cơng bố cơng trình khác Tác giả Lê Thị Hồng Vân MỤC LỤC Trang Trang phụ bìa Lời cam đoan DANH MỤC CÁC KÝ HIỆU, CHỮ VIẾT TẮT, BẢNG ĐỐI CHIẾU THUẬT NGỮ ANH VIỆT i DANH MỤC CÁC HỢP CHẤT PHÂN LẬP iv DANH MỤC HÌNH v DANH MỤC BIỂU ĐỒ vii DANH MỤC BẢNG .viii MỞ ĐẦU Chương TỔNG QUAN TÀI LIỆU 1.1 THỰC VẬT HỌC CÁC LOÀI THUỘC CHI PANAX 1.2 THÀNH PHẦN HĨA HỌC CỦA CÁC LỒI THUỘC CHI PANAX 1.3 THÀNH PHẦN HÓA HỌC VÀ TÁC DỤNG SINH HỌC TỪ CÁC DẠNG CHẾ BIẾN KHÁC NHAU CỦA CÁC LOÀI THUỘC CHI PANAX 13 1.4 PHÂN TÍCH SAPONIN TRONG CÁC LỒI THUỘC CHI PANAX 24 1.5 SÂM VIỆT NAM 30 Chương NGUYÊN VẬT LIỆU VÀ PHƯƠNG PHÁP NGHIÊN CỨU 42 2.1 NGUYÊN VẬT LIỆU 42 2.2 NƠI THỰC HIỆN ĐỀ TÀI 45 2.3 PHƯƠNG PHÁP NGHIÊN CỨU 45 Chương KẾT QUẢ 64 3.1 KIỂM NGHIỆM NGUYÊN LIỆU 64 3.2 PHÂN TÍCH THÀNH PHẦN SAPONIN TRONG CÁC BỘ PHẬN CỦA SÂM VN 64 3.3 THÀNH PHẦN SAPONIN CỦA SÂM VN CHẾ BIẾN 74 3.4 NGHIÊN CỨU SỰ THAY ĐỔI THÀNH PHẦN HĨA HỌC SAPONIN TRONG Q TRÌNH CHẾ BIẾN SÂM VN 107 3.5 SỰ THAY ĐỔI TÁC DỤNG SINH HỌC CỦA SÂM VN QUA QUÁ TRÌNH CHẾ BIẾN 113 Chương BÀN LUẬN 121 4.1 PHÂN TÍCH THÀNH PHẦN SAPONIN TRONG SÂM VN 121 4.2 THÀNH PHẦN SAPONIN CỦA SÂM VN CHẾ BIẾN 125 4.3 SỰ THAY ĐỔI TÁC DỤNG SINH HỌC DO QUÁ TRÌNH CHẾ BIẾN SÂM VN 133 KẾT LUẬN 137 KIẾN NGHỊ 139 DANH MỤC CÁC CƠNG TRÌNH NGHIÊN CỨU LIÊN QUAN 140 TÀI LIỆU THAM KHẢO i DANH MỤC CÁC KÝ HIỆU, CHỮ VIẾT TẮT, BẢNG ĐỐI CHIẾU THUẬT NGỮ ANH VIỆT Chữ viết tắt ACN Chữ nguyên Acetonitrile Nghĩa tiếng Việt Acetonitril ADP Adenosine Diphosphate Adenosin Diphosphat AF Arginine-Fructose Arginin-Fructose AFG Arginine-Fructose-Glucose Arginin-Fructose-Glucose ALT Alanine Aminotransferase APCI Atmospheric Pressure Chemical Ionization Ion hóa hóa học áp suất khí Ara α-L-arabinopyranosyl α-L-arabinopyranosyl AST Aspartate Aminotransferase Bcl-2 B-cell lymphoma COSY Correlation Spectroscopy Phổ tương quan COX Cyclooxygenase Cyclooxygenase CTPT Công thức phân tử DBMA 7,12-Dimethylbenz[a]anthracene DCF-DA 2′,7′-Dichlorodihydrofluorescein diacetate DHPPD Dihydro Protopanaxadiol Dihydro Protopanaxadiol DHPPT Dihydro Protopanaxatriol Dihydro Protopanaxatriol DPPH 1,1-diphenyl-2-picrylhydrazyl 1,1-diphenyl-2-picrylhydrazyl EA Ethyl acetate ELISA Enzyme-linked immunosorbent assay Xét nghiệm hấp thụ miễn dịch liên kết với enzym ELSD Evaporative light scattering detector Đầu dò tán xạ ánh sáng bay EP European Pharmacopeia Dược điển Châu Âu ESI Electrospray Ionization Ion hóa phun điện tử FBS Fetal bovine serum G- Ginsenoside Ginsenosid Glc β-D-glucospyranosyl β-D-glucospyranosyl HMBC Heteronuclear Multiple Bond Coherence Kết nối dị hạt nhân nhiều nối ii Chữ viết tắt HPLC Chữ nguyên High Performance Liquid Chromatography Nghĩa tiếng Việt Sắc ký lỏng hiệu cao HPMAE High Pressure Microwave Assisted Extraction Chiết xuất hỗ trợ vi sóng áp suất cao HR-ESI-MS High Resolution ElectroSpray Ionisation Mass Spectrometry Phổ khối phân giải cao ion hóa HSQC Heteronuclear Single Quantum Correlation Phổ tương quan dị hạt nhân IBα Nuclear Factor of Kappa Light Polypeptide Gene Enhancer in B-Cells Inhibitor alpha IC50 Inhibition Concentration 50% IL Interleukin iNOS Inducible NO Synthase Enzyme cảm ứng tổng hợp nitric oxit IRAK1 IL-1 Receptor Associated Kinase Kinase kết hợp với thụ thể IL-1 IT-TOF-MS Iontrap-Time of Flight-Mass Spectroscopy Khối phổ bẫy ion thời gian bay J Coupling constant Hằng số ghép KLTP Khối lượng phân tử KP Korean Pharmacopeia Dược điển Hàn Quốc LC/MS Liquid Chromatography-Mass Spectroscopy Sắc ký lỏng ghép khối phổ LPS Lipopolysaccharides Lipopolysaccharid MAE Microwave assisted extraction Chiết xuất hỗ trợ sóng siêu âm MDA Malondialdehyde Malondialdehyd MeOH Methanol MG Malonyl ginsenoside miRNA Micro RNA M-R2 Majonoside-R2 Majonosid-R2 NF-B Nuclear Factor Kappa Beta Yếu tố nhân kappa B NMR Nuclear Magnetic Resonance Cộng hưởng từ hạt nhân N-R1 Notoginsenoside R1 Notoginsenosid R1 Nồng độ ức chế 50% Malonyl ginsenosid iii Chữ viết tắt OA Chữ nguyên Oleanolic acid Nghĩa tiếng Việt Acid oleanolic OCT Ocotillol Ocotillol p53 Protein p53 PDA Photodiod array PG Prostaglandin PLE Pressurized liquid extraction Chiết lỏng áp suất cao PPD Protopanaxadiol Protopanaxadiol ppm Parts per million Phần triệu PPT Protopanaxatriol Protopanaxatriol Prep-HPLC Preparative High Performance Liquid Chromatography Sắc ký lỏng hiệu cao điều chế P-RT4 Pseudoginsenoside RT4 Pseudoginsenosid RT4 Q-TOF-MS Quadrupole-Time of flight-Mass Spectroscopy Khối phổ Tứ cực - Thời gian bay RID Refractive Index Detector Đầu dò số khúc xạ ROESY Rotating Frame Nuclear Overhauser Effect Spectroscopy Hiệu ứng hạt nhân Overhauser ROS Reactive Oxygen Species Gốc tự oxy hóa RP-18 Reversed Phase C-18 Pha đảo C-18 Rt Retention Time Thời gian lưu Sâm VN Sâm Việt Nam SKC Sắc ký cột SKĐ Sắc ký đồ SKLM Sắc ký lớp mỏng TAK1 Tumor Growth Factor-β-Activated Kinase Enzyme Kinase hoạt hóa yếu tố sinh trưởng β khối u TNF Tumor Necrosis Factor Yếu tổ hoại tử khối u TPA 12-O-Tetradecanoylphorbol-13-acetate USP United State Pharmacopeia Dược điển Mỹ UV Ultraviolet Tử ngoại Xyl β-D-xylopyranosyl β-D-xylospyranosyl Đầu dò dãy diod quang iv DANH MỤC CÁC HỢP CHẤT PHÂN LẬP STT Tên gọi 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 20(R) Ginsenosid Rg3 20(R) Ginsenosid Rh1 20(S) Ginsenosid Rg3 20(S) Ginsenosid Rh1 20(S) Protopanaxatriol oxid II (OCT) 3-O-β-D-Xylopyranosyl-(1→2)-β-Dglucopyranosyl(1→2)-β-D-glucopyranosyl20(S)-protopanaxadiol 20-O-β-Dxylopyranosyl (1→3)- β -D-xylopyranosyl (1→6)-β-D-glucopyranosid Daucosterol Ginsenosid Ra1 Ginsenosid Rb1 Ginsenosid Rb2 Ginsenosid Rd Ginsenosid Re Ginsenosid Rg1 Ginsenosid Rg3 Ginsenosid Rg5 Ginsenosid Rh1 Ginsenosid Rh4 Ginsenosid Rk1 Ginsenosid Rk3 Majonosid R1 Majonosid R2 Notoginsenosid D Notoginsenosid R1 Notoginsenosid R2 Notoginsenosid R4 Panaxynol Pseudo-ginsenosid RT4 Stigmasterol & sitosterol Vina-ginsenosid R11 Vina-ginsenosid R2 Ký hiệu Hợp chất đánh số 20(R) G-Rg3 1a 20(R) G-Rh1 3b 20(S) G-Rg3 1b 20(R) G-Rh1 3a OCT 26 22 G-Ra1 G-Rb1 G-Rb2 G-Rd G-Re G-Rg1 G-Rg3 G-Rg5 G-Rh1 G-Rh4 G-Rk1 G-Rk3 M-R1 M-R2 N-D N-R1 N-R2 N-R4 P-RT4 V-R11 V-R2 20 19 18 17 16 14 10 11 12 23 15 21 24 25 13 v DANH MỤC HÌNH Trang Hình 1.1 Cấu trúc gen trnK “Nguồn: Zhu, 2003” Hình 1.2 Cây phát sinh loài dựa kết hợp liệu gen trnK trình tự gen 18S rRNA Hình 1.3 Khung saponin phần đường phổ biến saponin thuộc chi Panax Hình 1.4 Sự hình thành ginsenosid trình chế biến (hấp) 15 Hình 1.5 Nhận diện truyền tín hiệu lipopolysacharid (LPS) đại thực bào 23 Hình 1.6 Phần mặt đất (a) phần mặt đất (b) Sâm VN 32 Hình 1.7 Các hợp chất polyacetylen phân lập từ phần mặt đất Sâm VN 34 Hình 1.8 Cấu trúc saponin phân lập từ Sâm VN 35 Hình 3.9 Bộ phận mặt đất Sâm VN 64 Hình 3.10 SKĐ SKLM phận khác Sâm VN 64 Hình 3.11 SKĐ ELSD (a) LC/MS (b) rễ Sâm VN 66 Hình 3.12 SKĐ HPLC/ELSD đại diện cho phận khác Sâm VN 68 Hình 3.13 Hình ảnh đại diện Sâm VN tươi (A), sấy khô (B) sau chế biến (C) 74 Hình 3.14 SKĐ đại diện HPLC/ELSD phân tích mẫu Sâm VN chưa chế biến (A) Sâm VN chế biến (B) 75 Hình 3.15 Sơ đồ quy trình chiết cao từ dược liệu Sâm VN chế biến 76 Hình 3.16 Sơ đồ phân lập thành phần từ cao EA 78 Hình 3.17 SKĐ HPLC/ELSD phân tích mẫu rễ (a) phân đoạn Bu1.25 (b) 80 Hình 3.18 Sơ đồ phân lập thành phần từ cao Bu1 80 Hình 3.19 Quy trình phân lập hợp chất từ cao chiết Bu2 82 Hình 3.20 Cấu trúc phần đường gắn vào vị trí C-20 hợp chất 22 (a) notoginsenosid Q (b) 101 Hình 3.21 Cấu trúc hợp chất 22 102 Hình 3.22 Cấu trúc notoginsenosid D (hợp chất 23) 105 Hình 3.23 SKĐ HPLC/ELSD đại diện Sâm VN chế biến 105 ℃ 109 Hình 3.24 SKĐ HPLC/ELSD đại diện Sâm VN chế biến 120 ℃ 110 140 DANH MỤC CÁC CƠNG TRÌNH NGHIÊN CỨU LIÊN QUAN TẠP CHÍ TRONG NƯỚC Isolation of Ginsenoside Isomers from Processed Vietnamese Ginseng by Preparative HPLC Journal of Medicinal Materials (2015) Ginsenoside-Rk1 and ginsenoside-Rg5 isolated from processed Vietnamese ginseng Journal of Medicinal Materials (2015) Phân lập thiết lập chất chuẩn majonosid–R2 từ sâm Việt Nam (Panax vietnamensis Ha et Grushv.), Tạp chí Dược học, Số 53, tập 8, tr 14-20, Tạp chí Dược học (2014) Ginsenoside-Rk3 and ginsenoside-Rh4 isolated from processed Vietnamese ginseng (Panax vietnamensis Ha et Grushv.) Journal of Medicinal Materials (2013) TẠP CHÍ QUỐC TẾ Ginseng Saponins in Different Parts of Panax vietnamensis Chemical & pharmaceutical bulletin 01/2015; 63(11):950-954 Anti-inflammatory effects of vina-ginsenoside R2 and majonoside R2 isolated from Panax vietnamensis and their metabolites in lipopolysaccharidestimulated macrophages International Immunopharmacology 09/2015; 28(1):700-706 Effects of steaming on saponin compositions and antiproliferative activity of Vietnamese ginseng Journal of ginseng research 07/2015; 39(3) Processed Vietnamese ginseng: Preliminary results in Chemistry and Biological activity, Journal of Ginseng Research, 2014, 38(2) TÀI LIỆU THAM KHẢO TIẾNG VIỆT Nguyễn Như Chính, Nguyễn Hữu Đồng, Đặng Ngọc Phái, Nguyễn Minh Đức, Nguyễn Minh Cang, Nguyễn Đức Hạnh, et al (2009), "Đánh giá chất lượng Sâm Việt nam di thực", Tạp chí Y học TP Hồ Chí Minh, 13 (1), tr 96-102 Nguyễn Thượng Dong, Trần Công Luận, Nguyễn Thị Thu Hương (2007), Sâm Việt Nam số thuốc thuộc họ Nhân sâm, Nxb Khoa học Kỹ thuật, Hà Nội, tr 69-70, 119-126, 141 Nguyễn Minh Đức, Nguyễn Viết Tựu, Võ Văn Chín (1998), "Khảo sát so sánh Sâm Việt nam từ nguồn thiên nhiên trồng trọt - Thông báo số 1", Tạp chí Dược liệu, (1), tr Nguyễn Minh Đức, Nguyễn Viết Tựu, Nguyễn Thị Hồng Hoa, Võ Duy Huấn, Yamasaki Kazuo, Kasai Ryoji (1999), "Khảo sát so sánh sánh Sâm Việt nam từ nguồn thiên nhiên trồng trọt - Thơng báo số 2: Cấu trúc hóa học saponin sâm trồng", Tạp chí Dược liệu, (1), tr Vũ Bình Dương, Đào Văn Đơn, Nguyễn Văn Long, Hồng Văn Lương, Trịnh Văn Lẩu (2008), "Nghiên cứu định lượng số ginsenosid sinh khối Sâm Ngọc Linh phương pháp HPLC", Tạp chí Dược học, 390 (48), tr 41-43 Phan Kế Long, Vũ Đình Duy, Phan Kế Lộc, Nguyễn Giang Sơn, Nguyễn Thị Phương Trang, Lê Thị Mai Linh, et al (2014), "Mối quan hệ di truyền mẫu sâm thu lai châu sở phân tích trình tự nucleotide vùng matk ITS – rDNA", Tạp Chí Công Nghệ Sinh Học, 12 (2), tr 327-337 Nguyễn Tập (2005), "Các loài thuộc chi Panax L Việt Nam", Tạp chí Dược liệu, 3, tr 71-76 Viện Dược liệu (2006), Cây thuốc động vật làm thuốc Việt Nam, Tập II, Nxb Khoa học Kỹ thuật, Hà Nội, tr 704-706 Bùi Thế Vinh, Trần Công Luận (2011), "Xây dựng phương pháp định lượng G-Rb1, G-Rg1 M-R2 Sâm Việt Nam kỹ thuật sắc ký lỏng hiệu cao ", Tạp chí Dược liệu, 16 (1+2), tr 44-50 TIẾNG ANH 10 Hasturk Hatice, Kantarci Alpdogan, Van Dyke Thomas (2012), "Oral inflammatory diseases and systemic inflammation: Role of the macrophage", Frontiers in Immunology, (118), 11 Joh E H., Lee I A., Jung I H., Kim D H (2011), "Ginsenoside Rb1 and its metabolite compound K inhibit IRAK-1 activation the key step of inflammation", Biochem Pharmacol, 82 (3), pp 278-286 12 Yang H., Lee D Y., Kang K B., Kim J Y., Kim S O., Yoo Y H., et al (2015), "Identification of ginsenoside markers from dry purified extract of Panax ginseng by a dereplication approach and UPLC-QTOF/MS analysis", J Pharm Biomed Anal, 109, pp 91-104 13 Zawawi K H., Kantarci A., Schulze-Spate U., Fujita T., Batista E L., Jr., Amar S., et al (2010), "Moesin-induced signaling in response to lipopolysaccharide in macrophages", Journal Periodontal Research, 45 (5), pp 589-601 14 Zhang Y G., Zhang H G., Zhang G Y., Fan J S., Li X H., Liu Y H., et al (2008), "Panax notoginseng saponins attenuate atherosclerosis in rats by regulating the blood lipid profile and an anti-inflammatory action", Clin Exp Pharmacol Physiol, 35 (10), pp 1238-1244 15 An I S., An S., Kwon K J., Kim Y J., Bae S (2013), "Ginsenoside Rh2 mediates changes in the microRNA expression profile of human non-small cell lung cancer A549 cells", Oncology Reports, 29 (2), pp 523-528 16 Bae Hye-Min, Kim Sung-Soo, Cho Chang-Won, Yang Deok-Chun, Ko Sung Kwon, Kim Kyung-Tack (2012), "Antioxidant activities of ginseng seeds treated by autoclaving", Journal of Ginseng Research, 36 (4), pp 411-417 17 Baek Nan In, Kim Dong Seon., Lee Youn Hyung, Park Jong Dae., Lee Chun Bae, Kim Shin Il (1996), "Ginsenoside Rh4, a genuine dammarane glycoside from Korean red ginseng", Planta Medica, 62 (1), pp 86-87 18 Besso Hiromichi, Kasai Ryoji, Saruwatari Yuhichiro, Fuwa Tohru, Tanaka Osamu (1982), "Ginsenoside Ra1 and Ginsenoside Ra2, new dammarane saponins of ginseng roots", Chemical & Pharmaceutical Bulletin, 30, pp 19 Chan H H., Hwang T L., Reddy M V., Li D T., Qian K., Bastow K F., et al (2011), "Bioactive constituents from the roots of Panax japonicus var major and development of a LC-MS/MS method for distinguishing between natural and artifactual compounds", Journal of Natural Product, 74 (4), pp 796-802 20 Chen R J., Chung T Y., Li F Y., Lin N H., Tzen J T (2009), "Effect of sugar positions in ginsenosides and their inhibitory potency on Na+/K+-ATPase activity", Acta Pharmacol Sin, 30 (1), pp 61-69 21 Cho In Hee (2015), "Volatile compounds of ginseng (Panax sp.): a review", Journal of the Korean Society for Applied Biological Chemistry, 58 (1), pp 67-75 22 Christensen L P (2009), "Ginsenosides chemistry, biosynthesis, analysis, and potential health effects", Advance in Food and Nutrition Research, 55, pp 1-99 23 Christensen L P., Jensen M., Kidmose U (2006), "Simultaneous determination of ginsenosides and polyacetylenes in American ginseng root (Panax quinquefolium L.) by high-performance liquid chromatography", Journal of Agricultural and Food Chemistry, 54 (24), pp 8995-9003 24 Chunghee Lee , Jun Wen (2004), "Phylogeny of Panax using chloroplast trnC–trnD intergenic region and the utility of trnC–trnD in interspecific studies of plants", Molecular Phylogenetics and Evolution, 31, pp 894-903 25 Corbit R M., Ferreira J F., Ebbs S D., Murphy L L (2005), "Simplified extraction of ginsenosides from American ginseng (Panax quinquefolius L.) for high-performance liquid chromatography-ultraviolet analysis", Journal of Agriculture and Food Chemistry, 53 (26), pp 9867-9873 26 Corthout J., Naessens T., Apers S., Vlietinck A J (1999), "Quantitative determination of ginsenosides from Panax ginseng roots and ginseng preparations by thin layer chromatography-densitometry", Journal of Pharmaceutical and Biomedical Analysis, 21 (1), pp 187-192 27 Court Williams E (2000), Ginseng The genus Panax, CRC Press pp 28 Gazdar Adi F., Girard Luc, Lockwood William W., Lam Wan L., Minna John D (2010), "Lung Cancer Cell Lines as Tools for Biomedical Discovery and Research", JNCI Journal of the National Cancer Institute, 102 (17), pp 1310-1321 29 Guan J., Lai C M., Li S P (2007), "A rapid method for the simultaneous determination of 11 saponins in Panax notoginseng using ultra performance liquid chromatography", Journal of Pharmaceutical and Biomedical Analysis, 44 (4), pp 996-1000 30 Ha Thi Dung, Grushvisky IV (1985), "A new species of the genus Panax L., Araliaceae in Vietnam: Panax vietnamensis Ha et Grushv ", Journal of Vietnam Botany, 70, pp 518-522 31 Jeong S M., Lee, J H., Kim, J H., Lee, B H.,Yoon,I S., Kim, D H (2004), "Stereospecificity of ginsenoside Rg3 action on ion channels", Molecules and Cells, 18, pp 383–389 32 Kanazawa Hideko, Nagata Yoshiko, Kurosaki Emi, Matsushima Yoshikazu, Takai Nobuharu (1993), "Comparison of columns of chemically modified porous glass and silica in reversed-phase high-performance liquid chromatography of ginsenosides", Journal of Chromatography A, 632 (1), pp 79-85 33 Kang S.Y., Kim J.M., KIM N.D.S.A., Kim W.Y., Park J.H., PARK M.K.S.A Processes for preparation of G-Rg3 and G-Rg5 ginsenosides Google Patents; 2004 pp 34 Kim Il-Woung, Cha Kyu-Min, Wee Jae Joon, Ye Michael B., Kim Si-Kwan (2013), "A new validated analytical method for the quality control of red ginseng products", Journal of Ginseng Research, 37 (4), pp 475-482 35 Kim Il-Woung, Sun Won Suk, Yun Bong-Sik, Kim Na-Ri, Min Dongsun, Kim SiKwan (2013), "Characterizing a full spectrum of physico-chemical properties of (20S)- and (20R)-ginsenoside Rg3 to be proposed as standard reference materials", Journal of Ginseng Research, 37 (1), pp 124-134 36 Kim K H., Choi I., Lee Y W., Cho C K., Yoo H S., Lee S B., et al (2014), "Target genes involved in antiproliferative effect of modified ginseng extracts in lung cancer A549 cells", Acta Biochimica et Biophysica Sinica, 46 (6), pp 441-449 37 Kim Mi Hyun, Lee Young Chul, Choi Sang Yoon, Cho Chang-Won, Rho Jeonghae, Lee Kwang-Won (2011), "The changes of ginsenoside patterns in red ginseng processed by organic acid impregnation pretreatment", Journal of Ginseng Research, 35 (4), pp 497-503 38 Kim S N., Ha Y W., Shin H., Son S H., Wu S J., Kim Y S (2007), "Simultaneous quantification of 14 ginsenosides in Panax ginseng C.A Meyer (Korean red ginseng) by HPLC-ELSD and its application to quality control", Journal of pharmaceutical and biomedical analysis, 45 (1), pp 164-170 39 Kim W Y., Kim J M., Han S B., Lee S K., Kim N D., Park M K., et al (2000), "Steaming of ginseng at high temperature enhances biological activity", Journal of Natural Product, 63 (12), pp 1702-1704 40 Kim Y J., Kwon H C., Ko H., Park J H., Kim H Y., Yoo J H., et al (2008), "Antitumor activity of the ginsenoside Rk1 in human hepatocellular carcinoma cells through inhibition of telomerase activity and induction of apoptosis", Biological & Pharmaceutical Bulletin, 31 (5), pp 826-830 41 Komatsu K, Zhu S , Fushimi H, Qui TK, Cai S, Kadota S (2001), "Phylogenetic analysis based on 18S rRNA gene and matK gene sequences of Panax vietnamensis and five related species.", Planta Medica, 67 (5), pp 461-465 42 Konoshima Takao, Takasaki Midori, Ichiishi Eiichiro, Murakami Teruo, Tokuda Harukuni, Nishino Hoyoku, et al (1999), "Cancer chemopreventive activity of majonoside-R2 from Vietnamese ginseng, Panax vietnamensis", Cancer Letters, 147 (1–2), pp 11-16 43 Lau A J., Seo B H., Woo S O., Koh H L (2004), "High-performance liquid chromatographic method with quantitative comparisons of whole chromatograms of raw and steamed Panax notoginseng", Journal of Chromatography A, 1057 (1-2), pp 141-149 44 Lau A J., Woo S O., Koh H L (2003), "Analysis of saponins in raw and steamed Panax notoginseng using high-performance liquid chromatography with diode array detection", Journal of Chromatography A, 1011 (1-2), pp 77-87 45 Le Thi Hong Van, Nguyen Ngoc Khoi, Nguyen Minh Duc (2011), "Isolation of ginsenoside-Rh1 in higher yield from process Vietnamese ginseng", Tạp chí dược liệu, 16 (3), pp 187 46 Le Thi Hong Van, Nguyen Thi Minh Thao, Nguyen Ngoc Khoi, Nguyen Duc Tuan, Nguyen Minh Duc (2012), "Simultaneous quantitative analysis of major saponins in vietnamese ginseng by HPLC", Tạp Chí Dược học, 17 (1), pp 42-47 47 Lee Hyejin, Kim Jinhee, Lee Seo Young, Park Jeong Hill, Hwang Gwi Seo (2012), "Processed Panax ginseng, sun ginseng, decreases oxidative damage induced by tert- butyl hydroperoxide via regulation of antioxidant enzyme and anti-apoptotic molecules in hepg2 cells", Journal of Ginseng Research, 36 (3), pp 248-255 48 Lee IK, Kang KA, Lim CM, Kim KC, Kim HS, Kim DH, et al (2011), "Compound K, a metabolite of ginseng saponin, induces mitochondria-dependent and caspasedependent apoptosis via the generation of reactive oxygen species in human colon cancer cells", International Journal of Molecular Science, 11, pp 4916 - 4931 49 Lee Jeong Hee, Lee Gwang Jin, Kwon Sung Won, Park Jeong Hill, editors Factor influencing the detection sensitivity of ginsenosides with evaporative light scattering detector The 11th International Symposium on Ginseng: Evidence-based Efficacy of Ginseng; 2014; Seoul, Korea pp P-157 50 Lee Sang Myung, Bae Bong-Seok, Park Hee-Weon, Ahn Nam-Geun, Cho Byung-Gu, Cho Yong-Lae, et al (2015), "Characterization of Korean Red Ginseng (Panax ginseng Meyer): History, preparation method, and chemical composition", Journal of Ginseng Research, 39 (4), pp 384-391 51 Lee Yoon-Mi, Yoon Haelim, Park Hyun-Min, Song Byeng Chun, Yeum Kyung-Jin (2016), "Implications of red Panax ginseng in oxidative stress associated chronic diseases", Journal of Ginseng Research, 52 Li B., Zhao, J.,Wang, C Z., Searle, J., He, T C., Yuan, C S., and Du, W (2011), "Ginsenoside Rh2 induces apoptosis and paraptosis-like cell death in colorectal cancer cells through activation of p53.", Cancer Letters, 301, pp 185–192 53 Li L., Zhang J L., Sheng Y X., Guo D A., Wang Q., Guo H Z (2005), "Simultaneous quantification of six major active saponins of Panax notoginseng by high-performance liquid chromatography-UV method", Journal of Pharmaceutical and Biomedical Analysis, 38 (1), pp 45-51 54 Li W., Fitzloff J F (2001), "Determination of 24(R)-pseudoginsenoside F(11) in North American ginseng using high performance liquid chromatography with evaporative light scattering detection", Journal of Pharmaceutical and Biomedical Analysis, 25 (2), pp 257-265 55 Liang Chun, Ding Yan, Nguyen Huu Tung, Kim Jeong-Ah, Boo Hye-Jin, Kang HeeKyoung, et al (2010), "Oleanane-type triterpenoids from Panax stipuleanatus and their anticancer activities", Bioorganic & Medicinal Chemistry Letters, 20 (23), pp 71107115 56 Lieber Michael, Todaro George, Smith Barry, Szakal Andras, Nelson-Rees Walter (1976), "A continuous tumor-cell line from a human lung carcinoma with properties of type II alveolar epithelial cells", Internaltional Journal of Cancer, 17 (1), pp 62-70 57 Liu S., Zhong J J (1998), "Phosphate effect on production of ginseng saponin and polysaccharide by cell suspension cultures of Panax ginseng and Panax quinquefolium", Process Biochemistry, 33 (1), pp 69-74 58 Lutomski Habil Jerzy, Nguyen Thoi Nham (1976), "Study on species of Panax growing in Vietnam I Comparative study on the saponins from Panax K5VN and Panax ginseng by TLC", Herbal Polonica, 1, pp 23-27 59 Lutomski Habil Jerzy, Tran Cong Luan (1992), "Polyacetylenes in the Araliaceae family Part IV - The antibacterrial and antifungal activities of two main polyacetylenes from Panax vietnamensis Ha et Grushv and Polyscias fruticosa (L.) Harms", Herba Polonica, XXXVIII (3), pp 137-140 60 Ma Wei Guang, Mizutani Masanori, Malterud Karl Egil, Lu Shao Long, Ducrey Bertrand, Tahara Satoshi (1999), "Saponins from the roots of Panax notoginseng", Phytochemistry, 52 (6), pp 1133-1139 61 Matsuura Hiromichi, Kasai Ryoji, Tanaka Osamu, Saruwatari Yuhichiro, Fuwa Tohru, Zhou Jun (1983), "Further Studies on Dammarane-Saponins of Sanchi-Ginseng", Chemical & Pharmaceutical Bulletin, 31 (7), pp 2281-2287 62 Mochizuki Mami, Yoo YungChoon, Matsuzawa Kaori, Sato Katsuaki, Saiki Ikuo, Tono-Oka Shuichi, et al (1995), "Inhibitory effect of tumor metastasis in mice by saponins, ginsenoside Rb2, 20(R)- and 20(S)-ginsenoside Rg3, of red ginseng.", Biological & Pharmaceutical Bulletin, 18, pp 1197–1202 63 Morita Toshinobu, Kasai Ryoji, Kohda Hiroshi, Tanaka Osamu, Zhou Jun, Yang Tsungren (1983), "Chemical and Morphological Study on Chinese Panax japonicus C A Meyer (Zhujie-Shen)", Chemical & Pharmaceutical Bulletin, 31 (9), pp 32053209 64 Morita Toshinobu, Tanaka Osamu, Kohda Hiroshi (1985), "Saponin composition of rhizomes of Panax japonicus collected in South Kyushu, Japan, and its significance in oriental traditional medicine", Chemical & Pharmaceutical Bulletin, 33 (9), pp 38523858 65 Nam Ki Yeul (2005), "The Comparative Understanding between Red Ginseng and White Ginsengs, Processed Ginsengs (Panax ginseng C A Meyer)", Journal of Ginseng Research, 29 (1), pp 1-18 66 Nguyen Huu Tung, Tran Hong Quang, Nguyen Thi Thanh Ngan, Chau Van Minh, Bui Kim Anh, Pham Quoc Long, et al (2011), "Oleanolic triterpene saponins from the roots of Panax bipinnatifidus", Chemical & Pharmaceutical Bulletin, 59 (11), pp 1417-1420 67 Nguyen Minh Duc Chemical study on the saponin composition of Vietnamese ginseng, Panax vietnamensis Ha et Grushv.: Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine; 1994 68 Nguyen Minh Duc, Kasai Ryoji, Ohtani Kazuhiro, Ito Aiko, Yamasaki Kazuo, Nguyen Thoi Nham, et al (1996), "New saponins from Vietnamese ginseng: highlights on biogenesis of dammarane triterpenoids.", Advances in Experimental Medicine and Biology, 404, pp 129-149 69 Nguyen Minh Duc, Kasai Ryoji, Yamasaki Kazuo, Nguyen Thoi Nham, Tanaka Osamu New dammarane saponins from Vietnamese ginseng In: Chong-Ren Yang, Osamu Tanaka, editors Studies in Plant Science 6: Elsevier; 1999 pp 77-82 70 Nguyen Minh Duc, Nguyen Minh Cang, Nguyen Duc Dieu Trang, editors Quantitative determination of major saponin contents of cultivated vietnamese ginseng – Panax vietnamensis Ha et Grushv.-Araliaceae- by HPLC Pharma Indochina; 2001; Ho Chi Minh city, Vietnam pp 247-251 71 Nguyen Minh Duc, Nguyen Thoi Nham, Kasai Ryoji, Ito Aiko, Yamasaki Kazuo, Tanaka Osamu (1994), "Saponins from Vietnamese ginseng, Panax vietnamensis Ha et Grushv collected in central Vietnam III.", Chemical & Pharmaceutical Bulletin, 42 (3), pp 634-640 72 Nguyen Minh Duc, Nguyen Thoi Nham, Kasai Ryoji, Ito Aiko, Yamasaki Kazuo, Tanaka Osamu (1993), "Saponins from Vietnamese ginseng, Panax vietnamensis Ha et Grushv Collected in central Vietnam I.", Chemical & Pharmaceutical Bulletin, 41 (11), pp 2010-2014 73 Nguyen Minh Duc, Nguyen Thoi Nham, Kasai Ryoji, Ito Aiko, Yamasaki Kazuo, Tanaka Osamu (1994), "Saponins from Vietnamese Ginseng, Panax vietnamensis Ha et Grushv Collected in central Vietnam II.", Chemical & Pharmaceutical Bulletin, 42 (1), pp 115-122 74 Nguyen Ngoc Khoi, Dao Xuan Son, Nguyen Minh Duc (2008), "Majonoside R2 Modulates Anxiety- and Depression-like Behaviours in Mice", Journal of Medicinal materials, 5, pp 240-244 75 Nguyen Ngoc Khoi, Le Thi Hong Van, Nguyen Minh Duc (2009), "The effect of steaming on saponin components and endurance swimming capacity of Vietnamese ginseng Panax vietnamesis Ha et Grushv.", Tạp chí Dược liệu, 14 (5), pp 288-293 76 Nguyen Thi Thu Huong, Matsumoto Kinzo, Kasai Ryoji, Yamasaki Kazuo, Watanabe Hiroshi (1998), "In vitro antioxidant activity of Vietnamese ginseng saponin and its components.", Biological & Pharmaceutical Bulletin, 21 (9), pp 978-981 77 Nguyen Thi Thu Huong, Matsumoto Kinzo, Yamasaki Kazuo, Nguyen Minh Duc, Nguyen Thoi Nham, Watanabe Hiroshi (1996), "Effects of Vietnamese ginseng on opioid agonist — and conditioned fear stress-induced antinociception", Phytomedicine, (1), pp 33-39 78 Nguyen Thi Thu Huong, Matsumoto Kinzo, Yamasaki Kazuo, Watanabe Hiroshi (1997), "Majonoside-R2 reverses social isolation stress-induced decrease in pentobarbital sleep in mice: Possible involvement of neuroactive steroids", Life Sciences, 61 (4), pp 395-402 79 Nguyen Thi Thu Huong, Yukihisa Murakami, Michihisa Tohda, Hiroshi Watanabe, Kinzo Matsumoto (2005), "Social isolation stress-induced oxidative damage in mouse brain and its modulation by majonoside-R2, a Vietnamese ginseng saponin", Chemical & Pharmaceutical Bulletin, 28 (8), pp 1389-1393 80 Nguyen Thoi Nham, Phan Van De, Tran Cong Luan, Nguyen Minh Duc, Shibata S, Tanaka Osamu, et al (1995), "Pharmacognostical and Chemical Studies on Vietnamese Ginseng, Panax vietnamensis Ha et Grushv (Araliaceae).", Journal of Japanese Botanical, 70, pp 1-10 81 Nguyen Tuan Dung, Villard Pierre Henri, Barlatier A., Elsisi A E., Jouve Elisabeth, Nguyen Minh Duc, et al (2000), "Panax vietnamensis protects mice against carbon tetrachloride-induced hepatotoxicity without any modification of CYP2E1 gene expression", Planta Medica, 66 (8), pp 714-719 82 Nong Van Duy, Le Ngoc Trieu, Nguyen Duy Chinh, Van Viet Tran (2016), "A new variety of Panax (Araliaceae) from Lam Vien Plateau, Vietnam and its molecular evidence", Phytotaxa, 277 (1), pp 47-58 83 Oh G S., Pae H O., Choi B M., Seo E A., Kim D H., Shin M K., et al (2004), "20(S)-Protopanaxatriol, one of ginsenoside metabolites, inhibits inducible nitric oxide synthase and cyclooxygenase-2 expressions through inactivation of nuclear factor-κB in RAW 264.7 macrophages stimulated with lipopolysaccharide", Cancer Letters, 205 (1), pp 23-29 84 Park Hee-Won, In Gyo, Han Sung-Tai, Lee Myoung-Woo, Kim So-Young, Kim Kyung-Tack, et al (2013), "Simultaneous determination of 30 ginsenosides in Panax ginseng preparations using ultra performance liquid chromatography", Journal of Ginseng Research, 37 (4), pp 457-467 85 Park I H., Kim N Y., Han S B., Kim J M., Kwon S W., Kim H J., et al (2002), "Three new dammarane glycosides from heat processed ginseng", Archive Pharmaceutical Research, 25 (4), pp 428-432 86 Park Il Ho, Kwon Sung Won, Lee Young Yae, Cho Sool Yeon, Park Man Ki, Park Jeong Hill (2002), "Cytotoxic dammarane glycosides from processed ginseng", Chemical & Pharmaceutical Bulletin, 50 (4), pp 538-540 87 Park J., Cho, J Y (2009), "Antiinflammatory effects of ginsenosides from Panax ginseng and their structural analogs.", African Journal of Biotechnology, 8, pp 3682– 3690 88 Park M.H Method for processing ginseng and the uses of extract of processed ginseng Google Patents; 2009 pp 89 Park M.H.E.T.P., inventor; Google Patents, assignee Method for processing ginseng and the uses of extract of processed ginseng2004 90 Park Man Ki, Park Jeong Hill, Han Sang Beom, Shin Young Geun, Park Il Ho (1996), "High-performance liquid chromatographic analysis of ginseng saponins using evaporative light scattering detection", Journal of Chromatography A, 736 (1–2), pp 77-81 91 Phan Ke Long, Le Thanh Son , Phan Ke Loc , Vu Dinh Duy, Pham Van The, editors Lai Chau ginseng Panax vietnamensis var fuscidiscus K.Komatsu, S.Zhu&S.Q.Cai.I Morphology, ecology, distribution and conservation status Proceeding of the 2nd VAST-KAST workshop on biodiversity and bio-active compounds; 2013; Vietnam pp 65-73 92 Popovich David G Kitts, David D (2002), "Structure–function relationship exists for ginsenosides in reducing cell proliferation and inducing apoptosis in the human leukemia (THP-1) cell line", Archives of Biochemistry and Biophysics, 406 (1), pp 18 93 Qi L W., Wang C Z., Yuan C S (2011), "Isolation and analysis of ginseng: advances and challenges", Natuaral Product Research, 28 (3), pp 467-495 94 Qian Z M., Lu J., Gao Q P., Li S P (2009), "Rapid method for simultaneous determination of flavonoid, saponins and polyacetylenes in folium ginseng and radix ginseng by pressurized liquid extraction and high-performance liquid chromatography coupled with diode array detection and mass spectrometry", Journal of Chromatography A, 1216 (18), pp 3825-3830 95 Qu Chenling, Bai Yuping, Jin Xiangqun, Wang Yutang, Zhang Kun, You Jingyan, et al (2009), "Study on ginsenosides in different parts and ages of Panax quinquefolius L", Food Chemistry, 115 (1), pp 340-346 96 Ríos J L., Recio M C., Mấđez S., Giner R M Natural Triterpenoids as AntiInflammatory Agents In: Atta ur Rahman, editor 22: Elsevier; 2000 pp 93-143 97 Rongwei Teng, Haizhou Li, Jiangtao Chen, Dezu Wang, Yineng He , Chongren Yang (2002), "Complete assignment of 1H and 13C NMR data for nine protopanaxatriol glycosides", Magnetic Resonance Chemical, 40, pp 483-488 98 Shin Byong-Kyu, Kwon Sung Won, Park Jeong Hill (2015), "Chemical diversity of ginseng saponins from Panax ginseng", Journal of Ginseng Research, 39 (4), pp 287298 99 Shin Y W., Bae, E A., Han, M J., Kim, D H (2006), "Metabolism of ginsenoside Rg5, a main constituent isolated from red ginseng, by human intestinal microflora and their antiallergic effect.", Journal of Microbiology and Biotechnology, 16, pp 1791– 1798 100.Shinkai Kiyoko , Akedo Hitoshi, Mukai Mutsuko, Imamura Fumio, Isoai Atsushi, Kobayashi Motomasa , et al (1996), "Inhibition of in vitro tumor cell invasion by ginsenoside Rg3", Journal of Cancer Research, 87, pp 357–362 101.Shu Youn Yuen, Ko Ming Yu, Chang Yuan Shiun (2003), "Microwave-assisted extraction of ginsenosides from ginseng root", Microchemical Journal, 74 (2), pp 131-139 102.Sohn Sang-Hyun, Kim Si-Kwan, Kim Young-Ock, Kim Hyung-Don, Shin Yu-Su, Yang Seung-Ok, et al (2013), "A comparison of antioxidant activity of Korean White and Red Ginsengs on H2O2-induced oxidative stress in HepG2 hepatoma cells", Journal of Ginseng Research, 37 (4), pp 442-450 103.Song G.Y., Lee J.H., Park Y.J., Myung C.S., Oh H.J., Shin H.J., et al., inventors; Google Patents, assignee A novel process for preparing black ginseng and the composition comprising the same patent WO2007133054A1 2007 104.Sultana Nasim, Afolayan A J (2007), "A novel daucosterol derivative and antibacterial activity of compounds from Arctotis arctotoides", Natural Product Research, 21 (10), pp 889-896 105.Sun Chengxin, Chen Yan, Li Xinzhi, Tai Guihua, Fan Yuying, Zhou Yifa (2014), "Anti-hyperglycemic and anti-oxidative activities of ginseng polysaccharides in STZinduced diabetic mice", Food & Function, (5), pp 845-848 106.Sun Yongxu (2011), "Structure and biological activities of the polysaccharides from the leaves, roots and fruits of Panax ginseng C.A Meyer: An overview", Carbohydrate Polymers, 85 (3), pp 490-499 107.Sung Kwon Ko, Kyung Hee Lee, Jun Kee Hong, Sung An Kang, Uy Dong Sohn, Byung Ok Im, et al (2005), "Change of Ginsenoside Composition in Ginseng Extract by Vinegar Process", Food Science and Biotechnology, 14 (4), pp 509-513 108.SW Kwon, SB Han, IH Park, JM Kim, MK Park, JH Park (2001), "Liquid chromatographic determination of less polar ginsenosides in processed ginseng", Journal of chromatography A, 921 (2), pp 335-339 109.Takahashi M., Yoshikura M (1964), "Studies on the components of Panax ginseng C A Meyer on the ethereal extract of ginseng radix alba (3) on the structure of a new acetylene derivative "panaxynol"", Yakugaku Zasshi, 84, pp 757-759 110.Taniyasu Shigenori, Tanaka Osamu, Yang Tsung Ren, Zhou Jun (1982), "Dammarane saponins of flower buds of Panax notoginseng (Sanchi-Ginseng)", Planta Medica, 44 (2), pp 124-125 111.Toh Ding-Fung, Patel Dhavalkumar Narendrabhai, Chan Eric Chun-Yong, Teo Alvin, Neo Soek-Ying, Koh Hwee-Ling (2011), "Anti-proliferative effects of raw and steamed extracts of Panax notoginseng and its ginsenoside constituents on human liver cancer cells", Chinese Medicine, 6, pp 4-4 112.Tran Le Quan, Adnyana I Ketut, Tezuka Yasuhiro, Nagaoka Takema, Tran Qui Kim, Kadota Shigetoshi (2001), "Triterpene saponins from Vietnamese ginseng (Panax vietnamensis) and their hepatocytoprotective activity", Journal of Natural Product, 64 (4), pp 456-461 113.Tran Le Quan, Adnyana I K., Tezuka Y., Harimaya Y., Saiki I., Kurashige Y., et al (2002), "Hepatoprotective effect of majonoside R2, the major saponin from Vietnamese ginseng (Panax vietnamensis)", Planta Medica, 68 (5), pp 402-406 114.Vanhaelen-Fastre R J., Faes M L., Vanhaelen M H (2000), "High-performance thinlayer chromatographic determination of six major ginsenosides in Panax ginseng", Journal of chromatography A, 868 (2), pp 269-276 115.Vo Duy Huan, Kazuhiro Ohtani, Ryoji Kasai, Nguyen Thoi Nham, Hoang Minh Chau, Nguyen Minh Duc, et al., editors New dammarane saponins from leaves of Panax vietnamensis Proceeding of the Third Indochina Conference on Pharmaceutical Sciences; 2003; Bangkok, Thailand pp pp OP65-OP75 116.Wan J B., Li P., Li S., Wang Y., Dong T T., Tsim K W (2006), "Simultaneous determination of 11 saponins in Panax notoginseng using HPLC-ELSD and pressurized liquid extraction", Journal of Separation Science, 29 (14), pp 2190-2196 117.Wan J B., Li S P., Chen J M., Wang Y T (2007), "Chemical characteristics of three medicinal plants of the Panax genus determined by HPLC-ELSD", Journal of Separation Science, 30 (6), pp 825-832 118.Wang A., Wang C Z., Wu J A., Osinski J., Yuan C S (2005), "Determination of major ginsenosides in Panax quinquefolius (American ginseng) using highperformance liquid chromatography", Phytochemical Analysis, 16 (4), pp 272-277 119.Wang C Z., Wu J A., McEntee E., Yuan C S (2006), "Saponins composition in American ginseng leaf and berry assayed by high-performance liquid chromatography", Journal of Agricultural and Food Chemistry, 54 (6), pp 2261-2266 120.Wang Chong-Zhi, Aung Han H., Ni Ming, Wu Ji-An, Tong Robin, Wicks Sheila, et al (2007), "Red American Ginseng: Ginsenoside Constituents and Antiproliferative Activities of Heat-Processed Panax quinquefolius Roots", Planta Medica, 73 (7), pp 669-674 121.Wang D Q., Fan J., Feng B S., Li S R., Wang X B., Yang C R., et al (1989), "Studies on saponins from the leaves of Panax japonicus var bipinnatifidus (Seem.)Wu et Feng", Yao Xue Xue Bao, 24 (8), pp 593-599 122.Wang J., Li S., Fan Y., Chen Y., Liu D., Cheng H., et al (2010), "Anti-fatigue activity of the water-soluble polysaccharides isolated from Panax ginseng C A Meyer", Journal of Ethnopharmacol, 130 (2), pp 421-423 123.Wang J R., Yamasaki Y., Tanaka T., Kouno I., Jiang Z H (2009), "Dammarane-type triterpene saponins from the flowers of Panax notoginseng", Molecules, 14 (6), pp 2087-2094 124.Wang J., Sun C., Zheng Y., Pan H., Zhou Y., Fan Y (2014), "The effective mechanism of the polysaccharides from Panax ginseng on chronic fatigue syndrome", Archives of Pharmacal Research, 37 (4), pp 530-538 125.Wang W., Rayburn E R., Hang J., Zhao Y., Wang H., Zhang R (2009), "Anti-lung cancer effects of novel ginsenoside 25-OCH(3)-PPD", Lung Cancer, 65 (3), pp 306311 126.Wang W., Rayburn, E R., Zhao, Y., Wang, H., Zhang, R (2009), "Novel ginsenosides 25-OHPPD and 25-OCH3-PPD as experimental therapy for pancreatic cancer: anticancer activity and mechanisms of action.", Cancer Letters, 278, pp 241–248 127.Wang W., Zhao, Y., Rayburn, E R., Hill, D L., Wang, H., Zhang, R (2007), "In vitro anti-cancer activity and structure-activity relationships of natural products isolated from fruits of Panax ginseng.", Cancer Chemotherapy and Pharmacology, 59, pp 589–601 128.Wang Yutang, You Jingyan, Yu Yong, Qu Chenling, Zhang Huarong, Ding Lan, et al (2008), "Analysis of ginsenosides in Panax ginseng in high pressure microwaveassisted extraction", Food Chemistry, 110 (1), pp 161-167 129.Wen Jun, Zimmer E A (1996), "Phylogeny and biogeography of Panax L (the ginseng genus, araliaceae): inferences from ITS sequences of nuclear ribosomal DNA", Molecular Phylogenetics and Evolution, (2), pp 167-177 130.Wong Alice S T., Che Chi-Ming, Leung Kar-Wah (2015), "Recent advances in ginseng as cancer therapeutics: a functional and mechanistic overview", Natural Product Reports, 32 (2), pp 256-272 131.Xia Pengguo, Li Jiazhou, Wang Ruilin, Zhang Yu, Guo Hongbo, Yan Xijun, et al (2015), "Comparative study on volatile oils of four Panax genus species in Southeast Asia by gas chromatography–mass spectrometry", Industrial Crops and Products, 74, pp 478-484 132.Xu T M., Cui, M H., Xin, Y., Gu, L P., Jiang, X., Su, M M., Wang, D D., Wang, W J (2008), "Inhibitory effect of ginsenoside Rg3 on ovarian cancer metastasis.", Chinese Medical Journal, 121, pp 1394–1397 133.Yang Di-Qing (1981), "The cyto-taxonomic studies on some species of Panax L.", Acta Phytotaxonomica Sinica, 19, pp 298-303 134.Yang Heejung, Kim Jeom Yong, Kim Sun Ok, Yoo Young Hyo, Sung Sang Hyun (2014), "Complete 1H-NMR and 13C-NMR spectral analysis of the pairs of 20(S) and 20(R) ginsenosides", Journal of Ginseng Research, 38 (3), pp 194-202 135.Yang Wen-zhi, Hu Ying, Wu Wang-Ying, Ye Min, Guo De An (2014), "Saponins in the genus Panax L (Araliaceae): a systematic review of their chemical diversity", Phytochemistry, 106, pp 7-24 136.Yang WZ, Ye M, Qiao X, Liu CF, Miao WJ, Bo T, et al (2012), "A strategy for efficient discovery of new natural compounds by integrating orthogonal column chromatography and liquid chromatography/mass spectrometry analysis: its application in Panax ginseng, Panax quinquefolium and Panax notoginseng to characterize 437 potential new ginsenosides", Analytica Chimica Acta, 739, pp 56 66 137.Yoshikawa M., Morikawa T., Kashima Y., Ninomiya K., Matsuda H (2003), "Structures of new dammarane-type Triterpene Saponins from the flower buds of Panax notoginseng and hepatoprotective effects of principal Ginseng Saponins", Journal of Natural Product, 66 (7), pp 922-927 138.Yoshikawa Masayuki, Morikawa T, Yashiro Kenichi, Murakami T., Matsuda Hisashi (2001), "Bioactive saponins and glycosides XIX Notoginseng (3): immunological adjuvant activity of notoginsenosides and related saponins: structures of notoginsenosides-L, -M, and -N from the roots of Panax notoginseng (Burk.) F H Chen", Chemical & Pharmaceutical Bulletin, 49 (11), pp 1452-1456 139.Yoshikawa Masayuki, Murakami Toshiyuki, Ueno Takahiro, Hirokawa Nobuko, Yashiro Kenichi, Murakami Nobutoshi, et al (1997), "Bioactive Saponins and Glycosides IX Notoginseng (2) : Structures of Five New Dammarane-Type Triterpene Oligoglycosides, Notoginsenosides-E, -G, -H, -I, and -J, and a Novel Acetylenic Fatty Acid Glycoside, Notoginsenic Acid β-Sophoroside, from the Dried Root of Panax notoginseng (Burk.) F H Chen", Chemical & Pharmaceutical Bulletin, 45 (6), pp 1056-1062 140.Yoshikawa Masayuki, Murakami Toshiyuki, Ueno Takahiro, Yashiro Kenichi, Hirokawa Nobuko, Murakami Nobutoshi, et al (1997), "Bioactive saponins and glycosides VIII Notoginseng (1): new dammarane-type triterpene oligoglycosides, notoginsenosides-A, -B, -C, and -D, from the dried root of Panax notoginseng (Burk.) F.H Chen", Chemical & Pharmaceutical Bulletin, 45 (6), pp 1039-1045 141.Zhang Y L., Zhang R., Xu H L., Yu X F., Qu S C., Sui D Y (2013), "20(S)protopanaxadiol triggers mitochondrial-mediated apoptosis in human lung adenocarcinoma A549 cells via inhibiting the PI3K/Akt signaling pathway", The American journal of Chinese Medicine, 41 (5), pp 1137-1152 142.Zhou D., Hu C., Su X., Yang H (2005), "Study on apoptosis of human lung adenocarcinoma cell line A549/DDP induced by ginsenoside Rh2 in vitro", Zhongguo Fei Ai Za Zhi, (4), pp 257-260 143.Zhou J., Huang, W.-G., Wu, M.-Z., Yang, C.-R., Feng, K.-M., and Wu, Z.-Y (1975), "Triterpenoids from Panax Linn and their relationship with taxonomy and geographical distribution.", Acta Phytotaxonomica Sinica, 13 (2), pp 29-45 144.Zhu J J., Wang Z M., Kuang Y H., Zhang Q W., Gao Q P., Ma N (2008), "A quantitative method using one marker for simultaneous assay of ginsenosides in Panax ginseng and P notoginseng", Yao Xue Xue Bao, 43 (12), pp 1211-1216 145.Zhu Shu , Zou Kun, Cai Shaoqing, Meselhy Ragab, Komatsu Katsuko (2004), "Simultaneous determination of triterpene saponins in ginseng drugs by highperformance liquid chromatography", Chemical & Pharmaceutical Bulletin, 52 (8), pp 995-998 146.Zhu Shu, Fushimi H, Cai ShaoQing, Chen HuBiao, Komatsu Katsuko (2003), "A new variety of the genus Panax from Southern Yunnan, China and its nucleotide sequences of 18S ribosomal RNA gene and matK gene", Journal of Japanese Botany, 78 (2), pp 86-94 147.Zhu Shu, Fushimi H, Cai ShaoQing, Komatsu Katsuko (2003), "Phylogenetic relationship in the genus Panax: inferred from chloroplast trnK gene and nuclear 18S rRNA gene sequences", Planta Medica, 69 (7), pp 647-653 148.Zou Kun, Zhu Shu, Meselhy Ragab Meselhy, Tohda Chihiro, Cai Shaoqing, Komatsu Katsuko (2002), "Dammarane-type Saponins from Panax japonicus and their neurite outgrowth activity in SK-N-SH cells", Journal of Natural Product, 65 (9), pp 12881292 149.Zou Kun, Zhu Shu, Tohda Chihiro, Cai Shaoqing, Komatsu Katsuko (2002), "Dammarane-type triterpene saponins from Panax japonicus", Journal of Natural Product, 65 (3), pp 346-351 150.http://www.theplantlist.org/tpl1.1/search?q=panax [cited 2016 07/12] 151.http://www.catalogueoflife.org/col/search/all/key/Panax/ 2016 [cited 2016 07/12] 152.http://www.hc-sc.gc.ca/dhp-mps/prodnatur/applications/licenprod/monograph/mono_panax_ginseng-eng.php 2016 153.http://apps.who.int/medicinedocs/en/d/Js2200e/19.html#Js2200e.19 2016 ... GIÁO DỤC VÀ ĐÀO TẠO ĐẠI HỌC Y DƯỢC THÀNH PHỐ HỒ CHÍ MINH LÊ THỊ HỒNG VÂN KHƯU NGHIÊN CỨU THÀNH PHẦN HOÁ HỌC VÀ TÁC DỤNG DƯỢC LÝ CỦA SÂM VIỆT NAM CHẾ BIẾN Chuyên ngành: Dược liệu - Dược học cổ truyền... Sâm VN chế biến cần thiết Với lý trên, đề tài ? ?Nghiên cứu thành phần hóa học tác dụng dược lý Sâm VN chế biến? ?? thực với mục tiêu sau: Phân tích, phân lập xác định thành phần hóa học saponin Sâm. .. định cấu trúc thành phần saponin Sâm VN chế biến khảo sát thay đổi thành phần hóa học saponin qua trình chế biến Sâm VN Khảo sát tác dụng sinh học Sâm VN chế biến thành phần saponin Sâm VN: + Khảo