Nghien cu'u - Ky thuat
lieu 334.8 mg vd 1004.4 mg cao khb d u v c liOu/kg/
ngay frfin chuOt cong ti^ng da lam giam thdi gian fri vd lam tang so lan tron thoat thanh cbng d mb hinh nfi trdnh chu dOng, tdc dung giu'a 2 mirc l i i u la tuong duong nhau vd tuong duang vdi donepezil lieu 2.4 mg/kg. Cereneed-caps l i i u 669,6 mg va 2008,8 mg cao khb d u v c lieu/kg/ngay frfin chuOt nhat fring da lam tang ttidi gian chudt d lai fren fryc quay d md hinh thanh quay Rotarod, tdc dyng giira 2 lieu Id tuvng duong nhau vd tijong d u o n g vdi donepezil lieu 1,2 mgfl^g.
Ket luan
Cereneed-caps lieu tirong duong lieu lam sdng vd g i p 3 lan l i i u lam sang cd tdc dyng cai thign ti-f nhd trfin dpng vdt tiiyc nghigm bj gay suy gidm frl nhd bdng scopolamin frfin 2 mb hinh ne trdnh ehu dOng vd mb hinh tnjc quay Rotarod, tac dyng giua 2 lieu Id tuong duong nhau.
Tai lieu tham khao 1. Phgm Thing (2010), Bpnh Alzheimer vd cac thi sa sut tri tu$ khdc, Nhd xuit bdn Y hpc, Hd NOi.
2. Cheng L L.. Chen X. N-, Wang Y vd cgng sy (2011), "Z-ligustilide isolated from Radix Angelicae sinensis ameliorates the memory impairment induced by scopolamine in mice", Fitoterapia. 82(7). 1128-1132, 3. Wang Y. Xu Y. Pan Y et al. (2013). 'Radix Achyranthis Bidentatae improves leaming and memory
capabilities in ovariectomized rats'. Neural. Regen Res., 8(18), 1644-1654.
4. Gauthier S. and Schlaefke S. (2014). "Efficacy and tolerability of Ginkgo bildia extract EGb 761(R}
in dementia: a systematic review and meta-analysis of randomized placebo-controlled trials", Clin. Intern Aging., 9, 2065-2077.
5. Bunadri P., Neeratl V. and Memgu S. (2013),
"Neuroprotective effect of resveratrol again^
scopolamine-induced cognitive impainnent and oxidative sfrBss in rats". Arch. Bid. Sd., 65(4), 1381-1386,
6. Falsafi S. K.. Deli A.. Hoger H. et al. (2012),
"Scopolamine adminisb^tion modulates muscarinic, nicotinic and NMDA receptor systems', PLoS One. 7(2}, 75-82.
7. R. Bajo S. P., ME LPpez. L. Ganuet, E. Pereda, D. Osipova, F. Maestu & E. Pekkonen (2015).
"Scopolamine effects on functional brain connectivity;
a phannacological model of Alzheimer's disease", Scientitic Reporis, 5, 9748, doi: 10.1038/srep09748,
8. Katzung B. G. (2012), Basic Clinical Pharmacdogy 12^ Edition, McGravi^-Hill Publishing Company, New York, 97-111, 115-125.
9. H. G, Vogel (2008), Dmg effects on leaming and memory. Drug Discovery and Evaluation.
Pharmacological Assays. Springer, Beriin Heidelberg, 877-942.
10. Nguyen Nhupe Kim (2009). BSi thuie ly huySl- Huyit phu tiT,ic LP thang. Phucmg t§ hpc. Nhd xuat b^n Y hpc, Hd NOI. 136-146.
(Ngdy nhpn bai: 31/08/2016 - Ngay phan bifn: 18/09/2016 - Ngay duypt ddng: 01/11/2016)
Danh gia tac dung ha lipid mau
cua vien nang cung TabaUx tren dong vat thu'c nghiem
Nguyen Hoflng Ngan, Biii Thi Bicll Van, Nguyen V3n Bacll Pliam Birc Tliinli, Hoang Vift Dung'
Hpcvi^n Qudny 'E-mail: [email protected]Summary
Capsules of Tabatix prepared from powdered dry extracts of Docynia indica, Fallopia muitifkxa and Reynoutri japonica were experimentally evaluated in tem of anii-hyperiipidemic activity in Wistar rats. Bodf weight and lipid profile including TG, total cholesterol, HDL-ChotestemI, U}L-Cholesleml, VLDL-Cholesteml and atherogenic indexes were detennined at W and 29" day after administration of the product or contml dmg (atonrastadnj. At doses of 0.48 gAg and 0.96 g/kg, the Tabalix pmduct reduced the indexes of bkiod ^ - reducing cholesterol and TG indexes, LDL-Cholesterol, VLDL-Cholesterol and alhemgent index, increasing HDL-Choiesterol index.
Keyvmrds: Tabalix. and-hypertipidemic, indexes of blood lipid
T^PCHi DircrC HQC - II/2OI6 (S6 48? NAM 54)
legmen CIFU - fvy inuai
D a t v a n d e
Roi logn lipid mdu dang ngdy cdng t r d nfin ph6 bien frong xa hdi hien dai. tOidng nhung the, dO tuOi cua ngudi mdc bfinh ngdy cang fre hon.
HiOn nay, cd khd nhieu nhdm thuoc tan dirpc d u p c s u dyng d ^ di^u trj roi loan lipid mau vdi hiOu qua kha tot. Tuy nhifin, ngudi benh thudng g$p phai mOt so tac dyng phu khi s u dyng nhung logi thuOc ndy n h u : nhipc dau, chdng mat, buon ndn, dau byng, tifiu chay, logn dudng co, roi loan chiPC nang gan...'''. VI t h ^ , nhu cau cua xa hpi ve nhung san pham thuOc cd nguon goc t u nhien vdi tdc dyng chua bfinh tot nhung ft tac dung khbng mong muon Id can thiet. Nhdm dap ung nhu cau thj trudng, nhdm tde gid Hpe vign Qudn y da nghifin c u u bdo ch6 eh6 p h i m vifin nang eCrng Tabalix chi>a ba loai bOt cao khd tao meo, hd thu b db vd c6t khi cu. Di khdng djnh chat lupng cua ehe pham bdo che dupe, chung tbi tien hdnh danh gid tdc dyng hg lipid mdu cua c h ^ pli^m trfin dOng vdt thyc nghiOm.
N g u y e n l i f u v a p h u v n g p h a p Nguyen liOu
Vien nang eung Tabalix dupe bdo ehe vdo thang 03/2016 tgi Tmng tdm Ddo tgo - Nghien cuu Dupc. Hpc viOn Quan y. Bpt vien nang ciPng Tabalix gom thanh phcin chinh Id 3 logi bOt eao khb d u p c phoi hp'p theo ty 10 bOt tdo mfio/bOt hd thu b db/bOt cot khi cu = 2,2/1,0/1,0 vd mpt lupng vua du mOt s6 td d u v c khdc. 3 logi bpt cao khb tao mdo, hd thu d dd vd c6t khi cu dupc di^u che t u 3 dupc liOu tuong Crng bdng chi^t xuat hoi luu vdi dung mdi con 70% sau do djch chi^t du-pc cfi den cao Ibng thich hpp (khodng 1:1 den 1:2) rOi tgo bfit cao khd bdng phuong phap phun Sciy. 3 logi bOt cao khb di^u chi dupe deu dgt tieu chuan co s d da xdy dyng.
Opng vgt t h i nghigm
ChuOt c6ng trdng chung V\^star. ca hai giong, khbe mgnh, cdn ndng tgi thdi diem bdt dau thf nghiOm tiF 160,0-180.0 g.
ChuOt c6ng trdng dipp'c cung cap bdi Ban Chan nudi - Hpc vifin Qudn y, nubi dudng trong phbng nuOi dOng vgt thi nghlOm it nhcit mOt tu^n trudc khi tiOn hdnh thi nghigm. DOng vgt an thuc an theo tifiu chuan thdc dn cho dpng vdt nghifin cuu, nudc sgch dun sdi di ngupi u6ng t y do.
Hda chat, dung mdi
- Hda ch^t: cholesterol (Merck), add cholic (Merck), propylthiouracil (PTU), thuOc tham ehieu atorvastatin vifin 10 mg (Cadila Pharmaceuticals).
Dung mdi pha thuoc: dung dich cartxjxymethyl cellulose 0,5%.
Thiet bj
- Mdy xet nghifim sinh hod t y dbng Chemix 180 (Hang Sysmex).
- Can phdn tich Sartorius CP224S, dp chinh xdc 0,1 m g ( D u c )
- BO dyng cy mo dOng vgt c d nhd va cac dyng cy thi nghigm khdc.
PhiFo^g phap nghien cuoi
Hifin nay, cd khd nhifiu md hinh ddnh gid tdc dyng tren roi loan lipid m a u ^ ^ l Nghien cuu ndy lua chpn mb hinh gdy roi logn lipid mdu ngoai sinh cua Nguyfin Trcing Thbng vd CS. (2013) P', day Id md hinh d u o c car tien tO mb hinh eua Nassiri vd CS. (2009) 1^. Theo mb hinh nay, chupt cong trang dup'c gay roi logn lipid bang cdch cho uong hdn hp'p d^u cholesterol, lieu 10 ml/kg/24 gid.
Thdnh phan hon hp'p dau cholestenDl bao gom:
cholesterol 0,1 g/ml; acid cholic 0,01 g/ml; PTU 0.005 g/mt; dau lgc vua du 1 ml.
Chupt eong trdng (chung Wistar) du tieu ehuan thi nghigm. d u p c phan ngau nhifin vdo 05 lb, mdi lb l O c o n .
- Ld 1 (chdng sinh ly): hdng ngdy u6ng nudc cat 10 ml/kg, sau 2 gid u6ng dung mbi pha thuOc CMC 0,5% 10 ml/kg.
- Ld 2 {chCrng bfinh ly): hdng ngdy uong hbn hpp d^u cholesterol 10 ml/kg, sau 2 gid u6ng dung mbi pha thuoc CMC 0.5% 10 ml/kg.
- Ld 3 (Tabalix lieu 1): hdng ngdy uong hon hpp d^u cholestenal 10 ml/kg. sau 2 gid uong dung djch bOt trong vien nang Tabalix hda tan trong CMC 0,5% lieu 0,48 g/10 ml/kg.
- Lb 4 (Tabalix lieu 2): hang ngdy uong hbn hpp dau cholestenDl 10 ml/kg. sau 2 gid uong dung djch bOt trong vien nang Tabalix hoa tan trong CMC 0,5% lieu 0,96 g/10 ml/kg.
- Lb 5 (tham chieu): hdng ngay u6ng hon hpp dau cholesterol 10 ml/kg, sau 2 gid uong thu6c tham chieu atorvastatin hba tan trong CMC 0,5%
lieu 10 mg/10 ml/kg.
Cho chupt u6ng thuoc trong thdi gian 28 ngay.
Tien hdnh ddnh gia cac chi tieu tgi cdc thdi diem 0, 14 vd 28 ngdy. Cdc chi tieu ddnh gid gom cd: Trpng luong co t h ^ ; cde chi s6 lipid mau:
trigtycerid toan phan, cholesterol toan phan. VLDL- cholestenDl. LDL-cholesterol, HDL-cholesterol. chi so vua x o m a c h (Al).
TAPCHi DUOC HQC - 11/2016 (S6 487 NAM 56)
• Nghien cifu - tvy tnuai
Ket qua va ban luan
S y thay doi trpng l u v n g cua cac Id chu<>t
Ket qua dupe trinh bdy d bang 1.
nghien ci>u
Bang 1 : Su tiiay da tipng lupng cua cac Id chupt nghien cuu (g) (n =10. x ± SD) ThoidiemXN. Tnidc tiiinghi§m (a) Sau 14 ngdy (b) Sau 28 ngdy (c)
Chimg sinh ly (1) Chijng benh ly (2) Tabalix lieu 1 (3) Tabal«lieu2 (4) TTiam chieu (5)
P
169,50±4.53 169,40 ±5,02
183,60 ±3,78 183,50 ±3,98
>0,05
201,40 ±7,90 201.60±4,25
Pp.<0,C N
- .> •
Nhan xet:
So sdnh giua cac thdi diem sau so vdi topoc cho thay trpng lupng chupt eua eac Id nghien cuu deu tang, s y thay doi cd y nghta thdng ke vdi p < 0,01. So vdi giipa cde lb trong o i n g mOt thdi diem do, s y khde bigt khdng cd y nghTa thong ke (p > 0.05).
N h u vdy cdn ngng d cdc Id chuOt deu tdng sau 14 ngdy vd 28 ngdy, nhung khdng cb s y khdc bi$t cd y nghTa thOng ke giua cac Id.
S y thay doi nong dp cholesterol todn phin va TG trong mau cua cac Id chupt nghifin CLPU
Ket qua d u p c trinh bay d bang 2.
Bang 2: S u tiiay doi ndng dp cholesterol todn phin vd TG mdu (n = 10, X ± SD) '~—-—-^^ThdiOiimXN
LoNC ~~ —___ Tnroc till nghidm (al Sau 14 ngiy fbj Sau 28 ngay (c) p Wong dp Cholesterol toin phan trong mau fmmoMj
Cti<>ng smh ty (1) Chimg b^nh ty (2}
Tabatix lieu 1 (3) Tabatix tieu 2 (4) Tham diieu (5)
P
3,38 ±0,26 3,40*0,26 3,39 ±0,37 3,37 ±0,28 3,40 ±0,36
>0,05
3,44 ±0,42 4,72 ±0,57 4,35 ±0,71 4,02 ±0,48"
4,09 ±0,50' p,,<0,0); •p,<0,05:
3,49 ±0.34 5.64 ± 0.67 4,64±1,05' 4,59 ± 0 , 4 1 "
4,37 ±0,62"
" p , < 0 , 0 )
p>0,05
P. •
Wong cJp tii^yceiil Irong miu (mmol/1) Chung sinh ly (1)
ChLfngb?nllt/(2) TabaiUlieu! (3) Tabatix ti4u 2 (4) Tliam chieu (5)
P
0,73*0,13 0,77 ±0,11 0,73 ±0,08 0,75 ±015 0,79*0,12
>0,05
0,75 ±0,12 0,98 ± 0 2 4 "
0,82 ±0,23 0,81 ±0,13 0,77 ±0,08'
:0,05;' 0,05,- •
'P.,'
"Pi 0.71 ±0.06 1,03 ±0,02"' 0,84 ± 0 , 0 8 " "
0,83 ± 0 1 2 ' "
0,8610.11'- :0,(»;
<0,0)
p>0,05
*p^<0fi5 'p^<0,01 •'
Nhpn xdt:
- So vdi Id Chung sinh ly, nong dp cholesterol v d J G d Cdc Id tir lb 2 den lb 5 deu tang cd y nghTa thong kfi tgi thdi di4m sau 28 ngdy, cdn tgi thdi diem sau 14 ngdy nOng dp cholesterol d cac Id t u lb 2 den lb 5 vd nong dp TG d lb 2 (chung bOnh ly) tdng cd y nghTa thong kfi. So sdnh trong ciing mdt I d nOng dp cholesterol mau d cdc Id chupt ti> Id 2 den lb 5 vd nong dp TG d lb 2 (chung bgnh ly) tai cdc thdi diem sau 14 ngdy va sau 28 ngay tdng cd y nghTa thong kfi so vdi tnjdc thi nghifim. Nhu vay.
ChuOt uong hbn hpp dau cholesterol da lam tdng rd rOt nong dp cholesterol vd TG tnang mau.
- Tgi thdi diem sau 14 ngdy. Id uong Tabalix lifeu 2 cd nong dp cholesterol gidm eb y nghTa thfing kfi so vdi lb ChCrng bOnh ly (p < 0,01). Ld dung thuie tham chi^u cb nOng dp cholesterol vd TG gidm c6 y nghTa thong kfi so vdi c^ung bOnh ly (p < 0,05).
- Tgi thdi di^m sau 28 ngdy, edc Id uOng TabaTix va thu6c tham chieu deu cd n6ng dd cholesterol vd TG gidm cd ^ nghTa th6ng kfi so vdi lb chirng bgnh ly (p < 0,05 vd p < 0.01). So sdnh giCra cdc lb dCing Tabalix vd Id dung atorvastatin chua tfiSy cd s y khdc biOt cd y nghTa thOng kfi. Nhu vOy, Tabalix vd atorvastatin deu the hign rd tdc dyng h?
cholesterol va TG mdu.
TAP CHI DLTgfC HQC - 11/2016 ( S 6 487 NAM 5«)
Nghien cifu - Ky thuat
S y thay doi n o n g dp HDL-chotesterol m d u cua cdc Id c h u p t nghifin cinr
K^t qua diryc trinh bdy d tidng 3.
Bang 3: SuOiaydii nong dd PpL-dK^^erdmau (mmol/l)(n = 1Q,X ±SD)
^^~^-J5« (Bern XW Trudc thi Sau 14 ngay Sau 28 ngay Ltm ^ ^ - ^ nghipm (a) (b) (c)
Chmigsinhly (1) 1,06±0,17 1.08±0,06 1.09±Q.09 Chi>n9benhly(2) 1.(MtQ.34 1.2Q±0.05 1.22±Q.Q7 Tabalixlieul (3) 1.Q8±Q.45 1.29±0.13' ^^tO.tS' Tabalixli^2 (4) 1,02±0,33 1,29±0.11' 1,31tQ,17- T^am ch4u (5) 1.03 ± 0,21 1.29 ± 0.1 (T 1,30 ±0.0r
'psov<!rildchungb$f}hly<0.(^
Nh$n xet: So sanh tai cung mpt thdi diem sau 14 ngdy vd 28 ngdy, nOng dO HDL-Cholesterol d cdc Id uong thuoc deu eao hon eb y nghTa thong ke so vdi lb chung tignh ly (p < 0,05). Nhu vgy, Tabalix d muc lieu 1. lieu 2 vd aton/astatin deu the hifin ro tdc dyng Idm tang HDL-Cholestercil trfin chupt gay roi logn lipid mdu. So sanh giua 2 lb u6ng Tabalix vd lb uong Aton/astaBn chua thSy cb s y khdc bifit cd y nghTa thong ke.
S y thay d6i n6ng dp LDL-cholesterol mdu, VLDL-cholesterol cua cdc Id chupt nghien c u u
K^t qua dupe trinh bdy d bdng 4.
Bang 4: Si/thay dii nong dp LDL-cholesterd mau.
VLDL-chdestenil cua c^ Id diupt nghien cuu (n = 10.X ±SD)
^ \ ^ ^ Thoi dial
^•-^^ Xh LiNC ^ ^ ^
, Tnr&c Uli nghi^ (a)
Sau 14 ngay lb)
Sau 28 ngiy lc) Ndng dd tJ)L<:holesteml mau (mmol/l}
Chijnqsinhtv (1) Chimg b$nh ly (2) Tabat»liiu1 (3) Tabalix t ^ 2 (4) Tliam chilu (5)
1.99 ±0.32 2,01 ±0,11 1,98 ±0,46 2,01 ±0,22 2,04 ±0,32
2,01 ±0,41 3,07 ±0,58 2,69 ±0,65 2,36 ±0,48"
2,45 ±059*
2,12 ±0,41 3,96 ±0.64 2.97 i 1,00- 2,90 ±0,33"
2,68 ±0.63"
Ning S^ VIDL-Chalesteml miu (mmol/1) Chi/nqsinhly (1)
Chi>nqbOnhlv(2) TabatDctiiul (3) Tabatix lik 2 (4) Thamchi^ (5)
0,33 ±0.06 0.35 ±0,05 0.33*0,03 0.34 ±0,07 0.35 ±0,06
0,34 ±0,06 0,45 ±0,11 0,37±0,10 037 ±0,06 0,35 ±0,04-
0,32 ±0,03 0,47 ±0,01 0,38 ±0,03"
0,38 ± 0,06- 0,39 ±0,05- CblsdAI
ChCmqsinht/ (1) ChLmgb^hly(2) Tabat»l^1 (3) Tabatix 1^2 (4) TTiam chi^ (5)
2,28 ±065 2,55 ±0.99 2,53±1.15 2.56 ±0.90 2.54 ±0,46
2,18 ±0,40 2,95 ±0,54 2,36 ±0,39- 2,13 ±0,37"
2,21 ±0,58"
2,23 ±0,46 3,63 ±0,48"
2.58 ±076"
2.53*0,37"
2,39 ±0,55"
'p SO vdl 16 Chirng bdnh ly<0.(^:
"pso VOI Id chimg b4nhty< 0.01 (Ngdy nh$n bai: 13/09/2016 - Ngdy phan
Nhan xet: So vdi lb chung bfinh ly, nong dp LDL-cholesterol Id uong Tabalix li^u 2 vd Id tiiam chieu thap hon cd y nghTa thong ke tai cd 2 thdi diem sau 14 vd 28 ngay. Nong dp VLDL- cholesterol d 2 Id uong Tabatix vd lb tham chieu thap hon co y nghta thong kfi tgi thdi diem sau 28 ngdy. Chi so Al d cdc Id uong Tabatix va lb tham chifiu deu giam cd y nghTa thong ke tgi ca thdi diem sau 14 ngay va 28 ngdy. So sanh ket qua giija 2 Id uong Tabalix va lb dung atorvastatin chua thdy cb s y khdc biet cd y nghTa thong ke.
N h u vdy, Tabalix vd atorvastatin deu the hifin rd tdc dung tam giam LDL-cholesterol, VLDL- cholesterol vd giam chi so A l trfin chudt gay rdi loan lipid mau t h y c nghigm.
Ket luan
Vifin nang cung Tabalbt d muc lieu 0,48 vd 0,96 g/kg ed tdc dung tot trong dieu tri roi logn lipid mdu tren md hinh gdy roi iogn lipid mdu t h y c nghifim d chupt cong trdng, ldm gidm cholesterol vd TG trong mdu, tdng HDL-cholesterol, giam LDL-cholesterol, VLDL-cholesterol vd chi s6 Al.
Ghi chd: Kit qua cua nghidn cuv nay Id mpt phin ndi dung cda di tai ma so KHCN-TB 04C/13-18 du-pc tai trp bdi Chuong trinh 'Khoa hpc vd Cdng nghd phpc vp phdt tnin bin vimg vung Tdy Bdc' ma s6 KHCN- TB/13-18 do Dai hQC Quic gia Ha Npi la coquan chu tri.
Tai lieu ^ a m khao
1. BO m6n Dugrc fy, Trudng Ogi hpc Y H^ Npi (2001), Dupc ly hpc. NXB Y hoc, tr. 453-460
2. Dodn Th| Nhu (2006). Phuong phdp nghidn cOv tdc dung duf?c ly cua thudc tir thdo dugc. Hhd xu^t bSn Khoa hpc vd Ky thu0t. tr 131-138.
3. Nguyin Trpng Thong, Vu Thj Ngpc Thanh, Nguyen Phuong Thanh. Ddm Dinh Tranh (2014). "X§y dyng m6 hinh gay r6i logn lipid mau bing h5n hpp dSu cholesterd chua lupng thdp add cholic tf§n chuOt c6ng tring". Tpp chi NghiSn cuu Dupc & Thdng tin thuie. so 5. tr. 179-182.
4. Dadhania Sagar S., Jani Dilip K.. Nirzanni N, Shah (2012), "Pharmacological screening of Ayun/edic anti-hyperlipidemic fomiulation: an Ayurvedic approach", Joumal of Phannaceutical and Scientific Innovation, Vol. 1 (2). pp. 9-12.
5. Nassiri-AsI M..Zamansoltani R, Abbasi E„ Daneshi M. M., Zangivand A. A. (2009), "Effects of tJriica dioica extract on lipid profile in hypercholesteralemic rats", Joumal of Chinese Integrative Medicine. Vol. 7. Issue 5. pp. 428-433
bipn: 02/10/2016 - Ngay duypt ddng: 01/11/2016)
I \ P C H i DLI'OC H p c - 11/2016 (S6 487 N A M 56)
