LUẬN án TS NGHIÊN cứu hóa học và THĂM dò HOẠT TÍNH SINH học của LOÀI THÔNG lá dẹt (PINUS KREMPFII LECOMTE) và NGŨ GIA bì HƯƠNG (ACANTHOPANAX TRIFOLIATUS l MERR )

www.DaiHocThuDauMot.edu.vn B GIO DC V O TO VIN KHOA HC V CễNG NGH VIT NAM VIN HO HC Lấ TH HNG NHUNG NGHIấN CU HểA HC V THM Dề HOT TNH SINH HC CA LOI THễNG L DT (PINUS KREMPFII LECOMTE) V NG GIA Bè HNG (ACANTHOPANAX TRIFOLIATUS L MERR.) LUN N TIN S HểA HC H Ni Nm 2014 www.DaiHocThuDauMot.edu.vn LI CAM OAN Tụi xin cam oan õy l cụng trỡnh nghiờn cu ca riờng tụi Cỏc s liu, kt qu nờu lun ỏn l trung thc v cha tng cú cụng b cỏc cụng trỡnh nghiờn cu trc õy Tỏc gi lun ỏn Lờ Th Hng Nhung www.DaiHocThuDauMot.edu.vn LI CM N Lun ỏn ny c hon thnh ti Phũng Tng hp hu c, Vin Húa hc, Vin Hn lõm Khoa hc v Cụng ngh Vit Nam Trong quỏ trỡnh nghiờn cu, tụi ó nhn c nhiu s giỳp chõn tỡnh ca cỏc thy cụ, cỏc nh khoa hc cng nh ng nghip, bn bố v ngi thõn Vi lũng bit n chõn thnh v sõu sc nht, tụi xin gi n PGS TS Trnh Th Thy v TS Nguyn Thanh Tõm nhng ngi thy ó to mi iu kin thun li, tn tỡnh hng dn v cú nhiu gúp ý quý bỏu thi gian thc hin lun ỏn Tụi xin chõn thnh cm n GS TSKH Trn Vn Sung ó to iu kin tt nht tụi c hc tp, nghiờn cu ti Phũng Tng hp hu c v cng l ngi ó ng h tụi thc hin lun ỏn ny Tụi cng xin cm n n cỏc cỏn b nghiờn cu phũng Tng hp hu c Vin Húa hc ó giỳp tụi rt nhiu quỏ trỡnh thc nghim v hon thnh bn lun ỏn Tụi xin gi li cm n n cỏc thy cụ, cỏc nh khoa hc Vin Húa hc ó ging dy, hng dn tụi hon thnh cỏc hc phn v cỏc chuyờn chng trỡnh o to Tụi trõn trng cm n Ban lónh o Trng i hc Cụng nghip H Ni cựng Ban lónh o Vin Húa hc ó to mi iu kin thun li cho tụi thi gian hc Cui cựng, tụi xin by t lũng cm n sõu sc n ton th gia ỡnh, ng nghip v bn bố ó ng h v ng viờn tụi hon thnh tt lun ỏn Tụi xin trõn trng cm n! H ni, ngy thỏng nm 2014 Tỏc gi lun ỏn www.DaiHocThuDauMot.edu.vn MC LC DANH MC CC S .. v DANH MC CC HèNH . vi DANH MC CC BNG iix DANH MC CC Kí HIU, CC CH VIT TTix M U.. CHNG TNG QUAN 1.1 Tng quan v hai loi nghiờn cu 1.1.1 Loi Thụng lỏ dt (Pinus krempfii Lecomte) 1.1.1.1 c im thc vt loi Thụng lỏ dt 1.1.1.2 Tỡnh hỡnh nghiờn cu loi Thụng lỏ dt 1.1.1.3 Tỡnh hỡnh nghiờn cu húa hc v hot tớnh sinh hc ca chi Pinus 1.1.2 Loi Ng gia bỡ hng (Acanthopanax trifoliatus L.Merr.) 1.1.2.1 c im thc vt loi Ng gia bỡ hng 1.1.2.2 ng dng y hc dõn gian ca loi Ng gia bỡ hng 1.1.2.3 Tỡnh hỡnh nghiờn cu ca loi Ng gia bỡ hng 1.2 Cỏc hp cht flavonoid 14 1.2.1 Cu trỳc húa hc 14 1.2.2 Hot tớnh sinh hc 16 1.3 Cỏc hp cht triterpene khung lupane 19 1.3.1 Cu trỳc húa hc 19 1.3.2 Hot tớnh sinh hc 19 1.4 Chuyn húa húa hc hp cht triterpene khung lupane v hot tớnh sinh hc ca chỳng 22 1.4.1 Chuyn húa nhúm OH 22 1.4.1.1 Chuyn húa thnh ester 22 1.4.1.2 Chuyn hoỏ thnh ketone, acid, oxime, amine 24 1.4.1.3 Chuyn húa thnh carbamate 26 1.4.2 Chuyn hoỏ nhúm isopropenyl 27 www.DaiHocThuDauMot.edu.vn 1.4.2.1 Kh hoỏ ni ụi 20(29) 27 1.4.2.2 Oxy hoỏ ni ụi 20(29) 28 1.4.2.3 Chuyn hoỏ v trớ allyl ca ni ụi 28 1.4.3 Chuyn húa nhúm 28-COOH 29 1.4.3.1 Chuyn húa thnh ester 29 1.4.3.2 Chuyn húa thnh amide 30 CHNG NGUYấN LIU, HểA CHT V PHNG PHP NGHIấN CU 32 2.1 Nguyờn liu, húa cht v thit b 32 2.1.1 Nguyờn liu 32 2.1.2 Húa cht 32 2.1.3 Thit b 32 2.2 Phng phỏp nghiờn cu 33 2.2.1.Phng phỏp chit tỏch 33 2.2.1.1 Phng phỏp chit tỏch cỏc cht t loi Thụng lỏ dt 33 2.2.1.2 Phng phỏp chit tỏch cỏc cht t loi Ng gia bỡ hng 34 2.2.2.Phng phỏp xỏc nh cu trỳc 34 2.2.3.Phng phỏp ỏnh giỏ hot tớnh sinh hc 35 2.2.3.1 Hot tớnh khỏng chng Bacillus subtilis 35 2.2.3.2 Hot tớnh gõy c t bo 35 2.2.3.3 Hot tớnh chng oxi húa 37 CHNG THC NGHIM 39 3.1 Loi Thụng lỏ dt (Pinus krempfii Lecomte) 38 3.1.1 Cn chit n-hexane 40 3.1.2 Cn chit ethyl acetate (EtOAc) 40 3.1.2.1 Phõn lp cht 40 3.1.2.2 D liu ph ca cỏc hp cht phõn lp c 42 3.1.3 Cn chit n-buthanol (n-BuOH) 43 3.2 Loi Ng gia bỡ hng (Acanthopanax trifoliatus (L.) Merr.) 45 3.2.1 Phõn lp cỏc hp cht t loi Ng gia bỡ hng 45 www.DaiHocThuDauMot.edu.vn 3.2.1.1 Quỏ trỡnh phõn lp 45 3.2.1.2 D liu ph ca cỏc hp cht phõn lp c 48 3.2.2 Tng hp cỏc dn xut ca hai cht AT1, AT2 48 3.2.2.1 Tng hp cỏc dn xut ca cht AT1 48 3.2.2.2 Tng hp cỏc dn xut ca cht AT2 57 CHNG KT QU V THO LUN 64 4.1 Kt qu t loi Thụng lỏ dt (Pinus krempfii Lecomte) 64 4.1.1 Thnh phn húa hc ca cn n-hexane 64 4.1.2 Cỏc cht phõn lp c t cn EtOAc 65 4.1.2.1 Tectochrysin (PK1) 65 4.1.2.2 Pinostrobin (PK2) 68 4.1.2.3 Pinobanksin (PK3) 71 4.1.2.4 Galangin (PK4) 75 4.1.2.5 Strobopinin (PK5) 78 4.1.2.6 Crytostrobin (PK6) 82 4.1.3 Cht phõn lp c t cn chit n-BuOH 85 4.2 Kt qu t loi Ng gia bỡ hng (Acanthopanax trifoliatus L Merr.) 92 4.2.1 Cỏc hp cht c phõn lp v xỏc nh t loi Ng gia bỡ hng 92 4.2.1.1 24-nor-11-hydroxy-3-oxo-lup-20(29)-ene-28-oic acid (AT1) 92 4.2.1.2 24-nor-3,11 dihydroxy-lup-20(29)-ene-28-oic acid (AT2) 95 4.2.1.3 11,23-dihydroxy-3-oxo-lup-20(29)-ene-28-oic acid (AT3) 98 4.2.2 Cỏc dn xut chuyn húa húa hc ca hp cht AT1, AT2 105 4.2.2.1 Cỏc dn xut ca AT1 106 4.2.2.2 Cỏc dn xut ca AT2 112 4.3 Hot tớnh sinh hc ca cỏc hp cht phõn lp v chuyn húa húa hc.117 4.3.1 Hot tớnh gõy c t bo 117 4.3.2 Hot tớnh khỏng chng Bacillus subtilis 119 4.3.3 Hot tớnh chng oxi húa 120 BNG TNG HP CC HP CHT PHN LP V CHUYN HểA HO HC T HAI LOI NGHIấN CU. 122 www.DaiHocThuDauMot.edu.vn KT LUN V KIN NGH 128 CC CễNG TRèNH LIấN QUAN N LUN N 130 NHNG ểNG GểP MI CA LUN N BNG TING ANH 132 TI LIU THAM KHO 133 PH LC www.DaiHocThuDauMot.edu.vn DANH MC CC S Trang S 1.1 Ester hoỏ acid betulinic v trớ 3-OH to cỏc hp cht 22 56.156.8 S 1.2 Ester hoỏ betulinic acid v trớ 3-OH to hp cht 57 23 S 1.3 Chuyn húa nhúm 3-OH, 28-OH ca betulin 23 S 1.4 Chuyn húa nhúm 28-OH ca betulin to dn xut 64, 65 24 S 1.5 Chuyn hoỏ nhúm 3-OH ca betulinic acid thnh ketone, 25 oxime, amine S 1.6 Tng hp acid betulinic t betulin 25 S 1.7 Tng hp cỏc dn xut carbamate ca betulinic acid 26 S 1.8 Chuyn húa cỏc dn xut carbamate ca betulin 27 S 1.9 Kh hoỏ ni ụi 20(29) ca betulinic acid 27 S 1.10 Oxi húa ni ụi 20(29) ca betulinic acid 28 S 1.11 Chuyn húa v trớ allyl ca ni ụi to hp cht 85- 87 29 S 1.12 Tng hp mt s dn xut este ca 23-hydroxy betulinic acid 30 S 1.13 Tng hp dn xut A43-D ca betulinic acid 31 S 3.1 Quy trỡnh chit r Thụng lỏ dt 39 S 3.2 Phõn lp cỏc cht t cn chit EtOAc ca r Thụng lỏ dt 41 S 3.3 Phõn lp cht PK7 t cn chit n-BuOH ca r Thụng lỏ dt 44 S 3.4 Quy trỡnh chit mu Ng gia bỡ hng 45 S 3.5 Phõn lp cỏc hp cht t cn chit dichlorometan ca loi 47 Ng gia bỡ hng S 4.1 Tng hp cỏc dn xut ca cht AT1 106 S 4.2 Tng hp cỏc dn xut ca cht AT2 112 www.DaiHocThuDauMot.edu.vn DANH MC CC HèNH Trang Hỡnh 1.1 nh cõy v tiờu bn ca loi Thụng lỏ dt Hỡnh 1.2 Hỡnh nh v loi Ng gia bỡ hng Hỡnh 1.3 Vũng benzopyrano ca hp cht flavonoid 14 Hỡnh 4.1 Ph ESI-MS (positive) ca cht PK1 67 Hỡnh 4.2 Ph 1H-NMR ca cht PK1 (500 MHz, DMSO-d6) 67 Hỡnh 4.3 Ph 13C-NMR v DEPT ca cht PK1 (125 MHz, DMSO-d6) 68 Hỡnh 4.4 Ph 1H-NMR ca cht PK2 (500 MHz, CD3OD) 70 Hỡnh 4.5 Ph 1H-NMR (gión) ca cht PK2 (500 MHz, CD3OD) 70 Hỡnh 4.6 Ph 13C-NMR v DEPT ca cht PK2 (125 MHz, CD3OD) 71 Hỡnh 4.7 Ph FT-IR ca cht PK3 73 Hỡnh 4.8 Ph ESI-MS (positive ion) ca cht PK3 73 Hỡnh 4.9 Ph 1H-NMR ca cht PK3 (500 MHz, CD3OD) 74 Hỡnh 4.10 Ph 1H-NMR (gión) ca cht PK3 (500 MHz, CD3OD) 74 13 Hỡnh 4.11 Ph C-NMR ca cht PK3 (125 MHz, CD3OD) 75 Hỡnh 4.12 Ph ESI-MS (positive ion) ca cht PK4 77 Hỡnh 4.13 Ph 1H-NMR ca cht PK4(500 MHz, CD3OD) 77 Hỡnh 4.14 Ph 13C-NMR ca cht PK4 (125 MHz, CD3OD) 78 Hỡnh 4.15 Ph FT-IR ca cht PK5 80 Hỡnh 4.16 Ph 1H-NMR ca cht PK5 (500 MHz, CD3OD) 81 Hỡnh 4.17 Ph 1H-NMR (gión) ca cht PK5 (500 MHz, CD3OD) 81 Hỡnh 4.18 Ph 13C-NMR v DEPT ca cht PK5 (125 MHz, CD3OD) 82 Hỡnh 4.19 Ph 1H-NMR ca cht PK6 (500MHz, CD3OD) 84 Hỡnh 4.20 Ph 1H-NMR (gión) ca cht PK6 (500MHz, CD3OD) 84 Hỡnh 4.21 Ph 13C-NMR v DEPT ca cht PK6 (125MHz, CD3OD) 85 Hỡnh 4.22 Mt s tng tỏc chớnh ph HMBC ca cht PK7 86 Hỡnh 4.23 Mt s tng tỏc chớnh ph NOESY ca cht PK7 87 Hỡnh 4.24 Cht burselignan (PK7a) 87 www.DaiHocThuDauMot.edu.vn Hỡnh 4.25 Ph HR-ESI-MS (positive ion) ca cht PK7 88 Hỡnh 4.26 Ph 1H NMR ca cht PK7 (500 MHz, CD3OD) 89 Hỡnh 4.27 Ph 13C v DEPT ca cht PK7 (125 MHz, CD3OD) 89 Hỡnh 4.28 Ph HSQC ca cht PK7 90 Hỡnh 4.29 Ph HMBC ca cht PK7 90 Hỡnh 4.30 Ph NOESY ca cht PK7 91 Hỡnh 4.31 Ph ESI-MS (positive ion) ca cht AT1 94 Hỡnh 4.32 Ph 1H-NMR ca cht AT1 (500 MHz, CDCl3) 94 Hỡnh 4.33 Ph 13C-NMR v DEPT ca cht AT1 (125MHz, CDCl3) 95 Hỡnh 4.34 Ph ESI-MS (positive ion) ca cht AT2 97 Hỡnh 4.35 Ph H-NMR ca cht AT2 (500 MHz, CDCl3) 97 Hỡnh 4.36 Ph 13C-NMR v DEPT ca cht AT2 (125MHz, CDCl3) 98 Hỡnh 4.37 Cỏc tng tỏc chớnh trờn ph COSY, HMBC ca cht AT3 100 Hỡnh 4.38 Ph FT- IR ca cht AT3 101 Hỡnh 4.39 Ph HR-ESI-MS (positive ion) ca cht AT3 101 Hỡnh 4.40 Ph 1H-NMR ca cht AT3 (500 MHz, CD3OD) 102 Hỡnh 4.41 Ph 1H-NMR (gión) ca cht AT3 (500 MHz, CD3OD) 102 13 Hỡnh 4.42 Ph C-NMR v DEPT ca cht AT3 (125 MHz, CD3OD) 103 Hỡnh 4.43 Ph HSQC ca cht AT3 103 Hỡnh 4.44 Ph HMBC ca cht AT3 104 Hỡnh 4.45 Ph COSY ca cht AT3 104 10 www.DaiHocThuDauMot.edu.vn 10 Osman Ustun, Fatma Sezer Senol, Mine Kurkcuoglu, Ilkay Erdogan Orhan, Murat Kartal, Kemal Husnu Can Baser, Investigation on chemical composition, anticholinesterase and antioxidant activities of extracts and essential oils of Turkish Pinus species and pycnogenol, Industrial Crops and Products, 2012, 38, 115-123 11 Ipek Sỹntar, Ibrahim Tumen, Osman Ustỹn, Hikmet Kele, Esra Kỹpeli Akkol, Appraisal on the wound healing and anti-inflammatory activities of the essential oils obtained from the cones and needles of Pinus species by in vivo and in vitro experimental models, Journal of Ethnopharmacology, 2012, 139(2), 533-540 12 Nadia Fekih, Hocine Allali, Salima Merghache, Faùza Chaùb, Djamila Merghache, Mohamed El Amine, Nassim Djabou, Alain Muselli, Boufeldja Tabti, Jean Costa, Chemical composition and antibacterial activity of Pinus halepensis Miller growing in West Northern of Algeria, Asian Pacific Journal of Tropical Disease, 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158 www.DaiHocThuDauMot.edu.vn 98 D.M.Kasote, Flaxseed phenolics as natural antioxidants, International Food Research Journal, 2013, 20(1), 27-34 99 M.J.Nunez, C.P.Reyes, I.A.Jimenez, L.Moujir, I.L.Bazzocchi, Lupane triterpenoids from Maytenus Species, Journal of Natural Products, 2005, 68, 10181021 100 T.G.Fourie, E.Matthee, F.O.Snyckers, A pentacyclic triterpene acid with anti ulcer properties from cussonia natalensis, Phytochemistry, 1989, 28(10), 28512852 159 www.DaiHocThuDauMot.edu.vn NHNG ểNG GểP MI CA LUN N Tờn lun ỏn: Nghiờn cu húa hc v thm dũ hot tớnh sinh hc ca loi Thụng lỏ dt (Pinus krempfii Lecomte) v Ng gia bỡ hng (Acanthopanax trifoliatus L.Merr.) Chuyờn ngnh: Húa hu c Mó s: 62.44.27.01 H v tờn NCS: Lờ Th Hng Nhung Khúa o to: 2010 2014 Ngi hng dn: PGS.TS Trnh Th Thy TS Nguyn Thanh Tõm Tờn c s o to: Vin Húa hc Vin Hn lõm Khoa hc v Cụng ngh Vit Nam Nhng úng gúp mi ca lun ỏn: - Ln u tiờn thnh phn húa hc v hot tớnh sinh hc ca loi Thụng lỏ dt (Pinus krempfii Lecomte) Vit Nam c cụng b - T r ca loi Thụng lỏ dt ó phõn lp v xỏc nh cu trỳc ca hp cht bng cỏc phng phỏp ph (IR, MS, NMR), ú l: Tectochrysin (PK1), Pinostrobin (PK2), Pinobanksin (PK3), Galangin (PK4), Strobopinin (PK5), Cryptostrobin (PK6), Isolariciresinol (PK7) Trong ú, cht Galangin v Isolariciresinol ln u c phỏt hin t loi ny - Kt qu hot tớnh gõy c t bo ung th ngi gm KB, HepG2, Lu, MCF7 v hot tớnh chng oxi húa ca cỏc cht phõn lp c cho thy, cht PK4 v PK7 cú kh nng chng oxi húa, c bit l PK7 cú giỏ tr EC50 l 27,12 àg/ml; cht: PK3, PK4, PK6 v PK7 cú kh nng c ch s phỏt trin ca dũng t bo ung th th nghim - Triterpene khung lupane 11,23-dihydroxy-3-oxo-lup-20(29)-ene-28-oic acid (AT3) l cht mi ó c phõn lp v xỏc nh cu trỳc t loi Ng gia bỡ hng (Acanthopanax trifoliatus L.Merr.) Hai cht 24-nor-11-hydroxy-3-oxo-lup-20(29)-ene-28-oic acid (AT1) v 24-nor3,11-dihydroxy-lup-20(29)-ene-28-oic acid (AT2) c phõn lp vi hm lng khỏ cao (tng ng 0,26% v 0,25 % so vi mu khụ) - ó tng hp c 23 dn xut mi t cht AT1 v AT2 gm: dn xut ester (AT4-AT7), dn xut oxo (AT8), dn xut amide (AT9-AT17) ca AT1 v dn xut ester (AT18), dn xut amide (AT19-AT26), dn xut nitrile (AT27) ca AT2 - õy l ln u tiờn kt qu nghiờn cu v hot tớnh khỏng chng Bacillus subtilis v gõy c t bo trờn dũng t bo ung th KB, HepG2, LU, MCF7 ca mt s dn xut tng hp c cụng b Kt qu cho thy cht AT11, AT16, AT18 th hin hot tớnh khỏng chng Bacillus subtilis mc trung bỡnh; cht AT11, AT12, AT13, AT22 u cho hot tớnh cao hn so vi cht u AT1 v AT2 c bit, dn xut AT22 cú kh nng c ch mnh, tng gp 6-15 ln so vi cht u AT2 trờn c dũng t bo th nghim vi cỏc giỏ tr IC50 l 3,65 ữ 4,42àg/ml www.DaiHocThuDauMot.edu.vn H Ni, ngy 30 thỏng nm 2014 TP TH HNG DN PGS.TS.Trnh Th Thy TS Nguyn Thanh Tõm C S O TO NGHIấN CU SINH Lờ Th Hng Nhung www.DaiHocThuDauMot.edu.vn THE NEW CONTRIBUTIONS OF THE THESIS Thesis title: Study of chemistry and biological activities of Pinus krempfii Lecomte and Acanthopanax trifoliatus L.Merr Major: Organic Chemistry Code: 62.44.27.01 PhD : LeThi Hong Nhung Supervisor: Assoc Prof Trinh Thi Thuy Dr Nguyen Thanh Tam Education Insitutions: Institute of Chemistry Vietnam Academy of Science and Technology The new contributions of the thesis: - This the first time species Pinus krempfii Lecomte has been studied on the chemical constituents and biological in Vietnam - Seven compounds named Tectochrysin (PK1), Pinostrobin (PK2), Pinobanksin (PK3), Galangin (PK4), Strobopinin (PK5), Cryptostrobin (PK6), Isolariciresinol (PK7) were isolated and elucidated from the root of Pinus krempfii Lecomte Among these, two compounds PK4 and PK7 were isolated from this species for the first time - The isolated compounds has been studied on biological activities The results showed that two compounds PK4 and PK7 have fairly good antioxidant activity (PK7: EC50 = 27,12 àg/ml); four compounds: PK3, PK4, PK6 and PK7 exhibited cytotoxic activity on human cancer cell lines including KB, HepG2, Lu MCF7 - A new lupane-triterpene carboxylic acid named 11,23-dihydroxy-3-oxo-lup-20(29)ene-28-oic acid (AT3), together with two known 24-nor-11-hydroxy-3-oxo-lup-20(29)ene-28-oic acid (AT1), 24-nor-3,11-dihydroxy-lup-20(29)-ene-28-oic acid (AT2) with high content (0.26 and 0.25% of dried plant material, respectively) were isolated from the aerial part of Acanthopanax trifoliatus L.Merr - Starting from AT1 and AT2, 23 new derivatives, including: ester (AT4-AT7), oxo (AT8), amide (AT9-AT17) derivatives of AT1 and ester (AT18), amide (AT19AT26), nitrile (AT27) derivatives of AT2 have been synthesized - Some of the synthesized compounds have been selected for the cytotoxicity test on human cancer cell lines including KB, HepG2, MCF7 and Lu and antimicrobial assay to Bacillus subtilis for the first time Among these, compounds AT11, AT12, AT13, AT22 www.DaiHocThuDauMot.edu.vn showed stronger cytotoxicity than the parent compounds, especially compound AT22 are six to fifteen times more active than its lead compound on all four tested cell lines with IC50 values are 3,65 ữ 4,42àg/ml Three compounds AT11, AT16 and AT18 exhibited inhibitory activity against Bacillus subtilis with average level Hanoi, 30th September 2014 SUPERVISOR Assoc.Prof Trinh Thi Thuy Dr Nguyen Thanh Tam EDUCCATION INSTITUTION PhD STUDENT Le Thi Hong Nhung ... nghiên cứu loài Thông dẹt 1.1.1.3 Tình hình nghiên cứu hóa học hoạt tính sinh học chi Pinus 1.1.2 Loài Ngũ gia bì hương (Acanthopanax trifoliatus L. Merr. ) 1.1.2.1 Đặc điểm thực vật loài Ngũ. .. học nghiên cứu tổng hợp dẫn xuất triterpene từ công bố Trên tảng đó, l a chọn đề tài: Nghiên cứu hóa học thăm dò hoạt tính sinh học loài Thông dẹt (Pinus krempfii Lecomte) Ngũ gia bì hương (Acanthopanax. .. www.DaiHocThuDauMot.edu.vn Việc nghiên cứu thành phần hóa học hoạt tính sinh học loài Thông dẹt ý nghĩa khoa học có ý nghĩa l n mặt xã hội Loài Ngũ gia bì hương (Acanthopanax trifoliatus (L. ) Merr. ) thuộc chi Acanthopanax,