mwwXaiv lus
Tsev / Kev paub / Ntsiab lus

Kev paub

Chrysogenamide A Los Ntawm Cov Kab Mob Endophytic Associated Nrog Cistanche Deserticola Thiab Nws Cov Kev Tiv Thaiv Neuroprotective Ntawm SH-SY5Y Cells

Mar 03, 2022

Hu rau: Audrey Hu Whatsapp / hp: 0086 13880143964 Email:audrey.hu@wecistanche.com

Taw qhia

Cistanche deserticola(YC Ma) yog cov kab mob cab ib txwm nyob rau sab hnub poob ntawm Tuam Tshoj. Lub qia ntawm cov nroj tsuag no yog ib qho tseem ceeb ntawm cov tshuaj suav tshuaj thiab yog siv rau kev kho mob raum tsis muaj zog thiab neurasthenia ("Chinese Medicine Dictionary", 1977). Phenylthanoid glycosides los ntawmCistanchedeserticolatau tshaj tawm tias muaj cov haujlwm hauv kev tiv thaiv thiab kho cov kab mob cranial paj hlwb thiab tshem tawm cov dawb radicals [1, 2]. Raws li qhov tseeb tias cov kab mob endophytic tuaj yeem tsim cov tshuaj tshiab thiab cov tib / zoo ib yam li cov los ntawm cov nroj tsuag tswv, tshawb nrhiav cov tshuaj nquag tshiab los ntawm cov kab mob endophytic ntawm cov nroj tsuag tshuaj tseem ceeb qhia tau hais tias tus nqi rau kev txhim kho cov khoom siv tshuaj tshiab. Nyob rau hauv lub chav kawm ntawm peb nrhiav rau tshiab neuroprotective tebchaw los ntawm endophytic fungi los ntawmCistanchedeserticolasau los ntawm Inner Mongolia nyob rau sab qaum teb sab hnub poob Tuam Tshoj, peb hom kab mob nquag tau tshuaj xyuas siv SH-SY5Y hlwb. Ntawm lawv, kab lis kev cai broth ntawm fungus No. 005, authenticated li Penicillium chrysogenum, pom ib tug tseem ceeb neurocyte tiv thaiv nyhuv tiv thaiv oxidative kev nyuaj siab-induced cell tuag nyob rau hauv SH-SY5Y hlwb. Cov kev tshawb fawb ntawm cov khoom muaj zog ntawm cov kab mob no tau coj mus rau kev sib cais ntawm chrysogenamide A (1) (Fig. 1) los ntawm cov txheej txheem kev cais tawm bioassay. Tsis tas li ntawd, plaub lub tebchaw paub tau raug cais thiab txheeb xyuas tias circumdat hauv G (2) [3], 2-[({12}}hydroxypropionyl) amino] benzamide (3) [4], 2- , 3-dihydrosorbicillin (4) [5] thiab (9Z,12Z)-2, 3-dihydroxypropyl octadeca-9, 12-dienoate (5) [6] , los ntawm kev sib piv ntawm lawv cov ntaub ntawv spectroscopic nrog cov ntaub ntawv cov ntaub ntawv. Ntawm no, peb tshaj tawm txog kev cais tawm, kev txheeb xyuas, thiab cov txiaj ntsig neuroprotective ntawm chrysogenamide A.

Cistanche deserticola

Cistanche deserticola

Cov ntaub ntawv thiab cov txheej txheem

Fungal Material Ib qho piv txwv ntawm Penicillium chrysogenum No. 005 raug cais tawm ntawm cov hauv paus hniav ntawm C. deserticola sau los ntawm Inner Mongolia nyob rau sab qaum teb sab hnub poob ntawm Tuam Tshoj. Ntawm cov qos yaj ywm dextrose agar qhov macroscopic zoo li nthuav dav, du, velvety, xiav-ntsuab colonies qee zaum overgrown nrog lub teeb hyphae; qhov chaw ntawm lub colonies feem ntau pom ntau lub teeb daj; rov qab daj. Kev tshawb nrhiav GenBank nrog 18S ribosomal DNA gene sequence ntawm No. 005 (1676 nucleotides; Gen-Bank accession tooj EU203859) tau ua tiav. Cov txiaj ntsig tau qhia ib hom Penicillium chrysogenum ua qhov sib tw ze tshaj plaws. Raws li nws cov macroscopic tsos thiab 18S rDNA gene sequence, No.005 yog ib hom Penicillium chrysogenum.

image

Fermentation thiab Extraction

Cov fungus tau loj hlob nyob rau hauv cov xwm txheej zoo li qub ntawm 24 degree rau 3{{10}}} hnub hauv 35 1000-ml conical flalflasks uas muaj cov kua nruab nrab (30{{20 }}} ml / flflask) muaj cov piam thaj (10 g / liter), maltose (20 g / liter), mannitol (20 g / liter), monosodium glutamate (10 g / liter), KH2PO4 (0.5 g / liter), MgSO4 · 7H2O (0.3 g / liter), pob kws steep cawv (1.0 g / liter) thiab poov xab extract (3.0 g / liter) thiab dej hiav txwv tom qab kho nws cov pH rau 7.0. Cov fermented tag nrho cov kua zaub (10.5 litres) tau muab rho tawm peb zaug nrog EtOAc muab ib qho EtOAc soln, uas yog concentrated nyob rau hauv txo siab kom muab ib tug crude extract (9.5 g).

Kev huv huv

Cov kua txiv hmab txiv ntoo (9.5 g) tau muab cais ua 15 feem ntawm silica gel kem siv cov kauj ruam gradient elution ntawm roj av ether / Me2CO. Cov feem 2, eluted nrog 8 : 2 roj av ether/Me2CO, tau recrystallized los ntawm MeOH, yielding 3 raws li tsis muaj xim koob (8.{{10}} mg). Qhov feem 3 (19.{{30}} mg), eluted nrog 7 : 3 roj av ether/Me2CO, tau sib cais ntxiv los ntawm cov kab rov qab theem (RP18, 40 6{{38 } } mm, Merck; MeOH - H2O 3:2 → 4: 1 → MeOH) to afford fr. 3 7 (8. } ml/minute) muab 4 (2.{{8{88}}}} mg). Qhov feem 4 (26.0 mg), eluted nrog 6 : 4 roj av ether / Me2CO, tau sib cais ntxiv los ntawm cov kab rov qab-theem (RP18, 40 60 mm, Merck; MeOH - H2O 3: 2 → 4: 1 → MeOH) kom them taus fr kev. 4-3 (5.4 mg) thiab fr. 4-9 (7.6 mg). Tom qab ntawd, fr. 4-3 tau muab cais los ntawm ntau PHPLC [YMC-pob ODS (A), 10 250 mm, 5 mm, 4.0 ml/minute] (60 feem pua ​​​​MeOH, 4.0 ml / feeb) kom tawm los 2 (1.0 mg), thiab cov fr. 4-9 tau muab cais los ntawm PHPLC uas nws kim heev (80 feem pua ​​​​MeOH, 4.0 ml / feeb) kom tawm los 1 (4.0 mg) thiab 5 (2.6 mg). 1: tau raws li daj ntseg daj khoom; [a]D 25 24.5 degree (c 0.155, MeOH); UV (MeOH) l max 208, 251 nm; CD (MeOH) (saib daim duab 4); IR (KBr) n max 3433, 3200, 3076, 2928, 2862, 1677, 1440, 1370, 1324, 1188, 1029 cm 1 ; 1 H- thiab 13C-NMR (saib Table 1); HRESI-MS m/z 448.2951 [MH] (calcd rau C28H38N3O2, 448.2964)

DPPH Radical Scavenging Effect

Ib MeOH soln (160 ml) ntawm cov qauv sib txawv (1.0 mg/ml 0.0001 mg/ml) tau ntxiv rau 40 ml DPPH (1,1- diphenyl{{8 }}picrylhydrazyl; Sigma) MeOH soln (1.5 10 4 M). Tom qab sib tov maj mam thiab tawm rau 30 feeb ntawm chav tsev kub, qhov muag pom qhov muag tau ntsuas ntawm 520 nm siv lub spectrophotometer. Cov tshuaj tiv thaiv antioxidant ntawm txhua tus qauv tau qhia nyob rau hauv cov nqe lus ntawm IC50 (mg / ml los yog mM yuav tsum tau inhibit DPPH radical tsim los ntawm 50 feem pua) thiab xam los ntawm lub log-dose inhibition nkhaus.

neuroprotective of cistanche deserticola

neuroprotective ntawm cistanche deserticola

Cell Culture thiab Tshuaj Kho Mob

Tib neeg neuroblastoma SH-SY5Y hlwb tau coj mus rau hauv ib qho nruab nrab DMEM thiab khaws cia ntawm 37 degree nyob rau hauv ib qho chaw humidified nrog 5.0 feem pua ​​CO2. Cov cell suspensions (18{13}} ml) ntawm qhov ceev ntawm 5 * 104 cell ml-1 tau plated nyob rau hauv 96- zoo microtiter daim hlau thiab incubated rau 24 teev ntawm saum toj no mob. Chrysogenamide A tov (2.0 ml hauv DMSO) ntawm qhov sib txawv ntawm qhov sib txawv tau ntxiv rau txhua qhov dej tshwj tsis yog kev tswj hwm thiab cov qauv pawg thiab txuas ntxiv incubated rau 1 teev nyob rau tib lub sijhawm. H2O2 (Sigma Chemical Co., MO, USA) tau ntxiv rau induce apoptosis hauv SH-SY5Y hlwb ntawm qhov kawg ntawm 200 mM rau 24 teev. Cell viability tau txiav txim siab siv MTT kev xeem. MTT yaj nyob rau hauv phosphate-buffered saline tau ntxiv thaum kawg ntawm incubation mus rau qhov kawg concentration ntawm 5.0 mg / ml (PBS), thiab ces incubated ntawm 37 degree rau 4 teev. Tshem tawm cov supernatant, cov khoom tsim tawm formazan tau yaj.

Cov txiaj ntsig thiab kev sib tham

1 tau txais raws li daj ntseg daj. Cov mis mos molecular raug txiav txim raws li C28H37N3O2 los ntawm HRESI-MS (saib [MH] ntawm m/z 448.2951, hu ua [MH] C28H38N3O2, 448.2964). IR spectrum qhia tias muaj NH (3433 thiab 3200 cm 1) thiab carbonyl pawg (s) (1677 cm{18}} ). 1 H-NMR (Table 1) spectrum kaw nyob rau hauv DMSO-d6 qhia peb methyl pawg (d H 0.62, 0.87, 0.98), thiab ob exchangeable-proton signals (d H 10.36 thiab 8.29). Ntxiv mus, peb lub orthos ua ke nrog cov cim muaj ntxhiab (d H 6.90 dd, J 7.3, 7.3 Hz, 6.94 d, J 7.3 Hz, thiab 7.18 J 7.3 Hz) qhia tias 1,2, 3-trisubstituted benzene nplhaib. Cov methylene protons (d H 3.23) ua ke nrog ib qho olefinic proton (d H 5.27), nrog rau ob lub vinylic methyls (d H 1.67 thiab 1.70), qhia tias muaj ib pawg 3-methyl-2-butenyl pawg. hauv 1. Ib qho kev sib txuas ntawm cov protons thiab lwm 14 methine thiab los yog methylene protons tau tsim los ntawm kev sim HMQC. Lub 13C-NMR thiab DEPT (Table 1) spectra, uas tau tshaj tawm 28 lub cim, kuj tau lees paub qhov muaj ntawm ob lub nplhaib [trisubstituted benzene nplhaib (dC 123.6 CH, 120.8 CH, 127.7 CH, 122.1 QC, thiab QC14) {79}}methyl-2-butenyl (dC 28 CH2, 121.9 CH, 132.3 QC, 25.5 CH3, thiab 17.7 CH3)]; Tsis tas li ntawd, ob lub carbonyls (dC 183.1 thiab 172.3), plaub sp3 quaternary carbons (dC 46.5, 58.7, 60.4, thiab 62.3), ob sp3 methines (dC 46.1 thiab 58.7), thiab rau sp3 methylene (dC 30.3, 7, 30. 35.2, 39.9 thiab 64.9) kuj tau pom. Txij li thaum 6 tawm ntawm 12 unsaturations tau suav rau, 1 tau suav tias muaj rau lub nplhaib. Kev soj ntsuam ntxiv ntawm cov ntaub ntawv spectral no, nrog rau 1 H-1 H COZY thiab HMBC cov txiaj ntsig, tau qhia tias 1 muaj feem cuam tshuam nrog cov pab pawg marcfortine ntawm fungal metabolites [7]. Kev txhais ntawm HMBC kev sib raug zoo (Daim duab 2) qhia tias muaj ib feem ntawm cov qauv A (HMBC kev sib raug zoo 1-NH rau C-8 thiab C-9; H-6 rau C{{ 136}}; H-5 rau C-7 thiab C-9; H-26 rau C-28 thiab C-8 thiab H{143 }} rau C-29 thiab C-30) thiab B (HMBC kev sib raug zoo H-10 rau C-3, C-22, C-21, C{150}, C-12; H-20 to C-13, C-18, C-22, C-11 thiab { {157}}NH rau C-13, C-10), thiab C, muaj rau-tus tswv cuab G nplhaib [8] nrog cov methylated carbon ntawm C-17 (HMBC kev sib raug zoo H{{ 163}} rau C-17, C{165}}). Kev sib txuas ntawm kev sib txuas ntawm A mus rau B txog C-3 tau txais kev txhawb nqa los ntawm HMBC kev sib raug zoo ntawm H-4 thiab 1-NH rau C-3; H-10 rau C-2 thiab C{172}}. Kev sib txuas ntawm cov qauv B thiab C nrog nitrogen atom raug txiav tawm los ntawm HMBC kev sib raug zoo ntawm H-12 rau C-17 thiab C-13 thiab muab piv rau lawv cov tshuaj hloov pauv ntawm C{{176. }} thiab C-17 (dC 64.9 thiab 58.7). Cov kev soj ntsuam saum toj no tau qhia tias 1 muaj cov qauv zoo sib xws rau marcfortine A tshwj tsis yog qhov sib txawv ntawm cov saw hlau sab ntawm lub nplhaib benzene thiab methyl ntawm C-17 ntawm rau lub nplhaib G. Yog li cov qauv tag nrho ntawm 1 tau muab raws li qhia hauv daim duab 1

Cov txheeb ze stereochemistry ntawm 1 tau piav qhia raws li cov ntaub ntawv NOESY (Fig. 3). Cov kev tshawb fawb yav dhau los tau qhia tias 2-oxindole alkaloid hom tebchaw tau txais kev sib haum xeeb uas lub hauv paus tsib lub nplhaib yog orthogonal rau lub dav hlau ntawm oxindole subunit [9].

image

NOESY kev sib raug zoo ntawm H{{0}} thiab H-10a, H-25, thiab nruab nrab ntawm 19-NH thiab H-10a qhia tias lawv yog ob qho tib si ntawm lub ntsej muag ntawm lub nplhaib cyclopentanone uas taw qhia lawv mus rau H-4, kho cov txheeb ze stereochemistry ntawm C-3 raws li qhia. NOESY kev sib cuam tshuam ntawm H-21, H-12a, H-10b, H-23, thiab H-24 tau muab cov khoom sib txuas ua ke rau ntawm lub ntsej muag ntawm lub nplhaib cyclopentanone. Tus txheeb ze stereochemistry tau npaj rau 1 yog pom zoo nrog cov yam ntxwv cuam tshuam ntawm tus txheeb ze stereochemistry ntawm marcfortine A [7]. Cov nyhuv paj rwb ntawm 200-250 nm tshwm sim los ntawm kev hloov pauv ntawm np* ntawm diketopiperazine amide daim ntawv cog lus, uas yog kuaj xyuas rau bicyclo-[2.2.2] diazaoctane diketopiperazine core [10, 11]. Lub CD spectrum ntawm 1 (Fig. 4) correlated rau cov cheeb tsam uas muaj feem ntawm -brevianamide A [11]. Yog li qhov tseeb stereochemistry ntawm 1 yuav tsum yog 3S, 11S, 13S, 17S, 21R thiab tau muab lub npe ntawm chrysogenamide A. Kev ntsuam xyuas ua ntej ntawm kev tiv thaiv ntawm chrysogenamide A ntawm neurocytes tau soj ntsuam siv oxidative stress-induced cell tuag 5 SY-SY. Cell los ntawm MTT kev xeem. Cov dawb radical scavenging kev ua ntawm chrysogenamide A yog thawj zaug tshuaj xyuas siv DPPH ua tus pub dawb radical. Nyob rau hauv sib piv rau vitamin C (IC50: 29.0 mM), chrysogenamide A tsis tau qhia ib tug muaj peev xwm (IC50 Ntau tshaj los yog sib npaug rau 100 mM) mus scavene DPPH dawb-radical ntawm ib tug concentration txog li 100 mM. Lub caij no, peb tau sim seb puas muaj chrysogenamide A tiv thaiv hlwb tiv thaiv oxidative kev nyuaj siab vim cell tuag hauv SH-SY5Y tib neeg neuroblastoma

hlwb. Kev ntxhov siab oxidative los ntawm hydrogen peroxide ua rau txo qis hauv cell viability los ntawm 43 feem pua ​​​​piv rau pawg tswj hwm. Chrysogenamide A inhibited cell tuag tshwm sim los ntawm hydrogen peroxide los ntawm kev txhim kho cov hlwb los ntawm 59.6 feem pua ​​​​ntawm qhov concentration ntawm 1 * 10-4 mM. Cov ntaub ntawv no tau qhia tias chrysogen amide A pom tias muaj kev tiv thaiv neurocyte tiv thaiv oxidative kev ntxhov siab vim kev tuag ntawm tes, tsis yog los ntawm nws txoj haujlwm antioxidant. Indole alkaloids uas muaj qhov txawv txav bicyclo [2.2.2] diazaoctane nplhaib system tau raug cais tawm ntawm ntau hom kab mob xws li Aspergillus [12, 9, 13], Penicillium [14 16], thiab Malbranchea [17]. 1 yog ib tug tswv cuab tshiab ntawm pawg neeg sib txuas no, nws muaj lub cev pob txha yuav tsum yog ib qho nruab nrab hauv biosynthesis ntawm citrin admins A thiab B tau tshaj tawm raws li cov chav kawm tshiab ntawm pentacyclic spiroin dolinone alkaloids hauv 2005 [18]. Los ntawm cov qauv kev pom, nws yog ib qho tseem ceeb uas yuav tau taw qhia tias 1 yog ib qho qauv tshwj xeeb nrog methylation ntawm txoj hauj lwm C-17 thiab ib qho 2- oxindole moiety muaj ib chav isoprene ntawm C-7. Qee yam ntawm cov indol alkaloids cais tawm rau hnub no pom muaj cov tshuaj tiv thaiv kab mob muaj zog [19], inhibition ntawm tib neeg qog hlwb [13], thiab cytotoxicity [10]. Rau qhov zoo tshaj plaws ntawm peb txoj kev paub, nws yog thawj daim ntawv tshaj tawm ntawm neuroprotection los ntawm hom alkaloid no.

Kev lees paubTxoj haujlwm no tau txais kev txhawb nqa nyiaj txiag los ntawm Tuam Tshoj National Natural Science Fund (No. 30472136).

Prevent Alzheimer's disease

neuroprotective ntawm cistanche deserticola: anti-Alzheimer's kab mob

Cistanche deserticola muaj ntau yam teebmeem, nyem qhov no kom paub ntau ntxiv

Cov ntaub ntawv

  1. Li LL, Wang XW, Wang XF. Antilipid peroxidation thiab antiradiation ua ntawm glycosides hauvHerba Cistanches. Tuam Tshoj J Chin Mater Med 22: 364–367 (1997)

  2. Xie JH, Wu CF. Cov nyhuv ntawm ethanolic extract ntawmCistanche deserticolantawm cov ntsiab lus ntawm monoamine neurotransmitters hauv nas hlwb. Chin Trad Tshuaj Ntsuab 24: 417–419 (1993)

  3. Dai JR, Carte BK, Sidebottom PJ, Yew ALS, Ng SB, Huang Y, Butler MS. Circumdatin G, alkaloid tshiab los ntawm fungus Aspergillus ochraceus. J Nat Prod 64: 125–126 84 Fig. 2 Key HMBC and 1 H-1 H COZY correlations of 1. Fig. 3 NOESYs of 1. Fig. 4 CD spectrum of 1.(2001)

  4. Kettering M, Sterner O, Anke T. Tshuaj tua kab mob hauv kev sib txuas lus tshuaj ntawm fungi. Zeitschrift fuer Naturforschung, C: Phau ntawv Journal of Biosciences 59: 816–823 (2004)

  5. Trifonov LS, Bieri JH, Prewo R, Dreiding AS, Hoesch L, Rast DM. Kev rho tawm thiab cov qauv elucidation ntawm peb cov metabolites los ntawm Verticillium intertextum: sorbicillin, dihydrosorbicillin thiab bisvertinoquinol. Tetrahedron 39: 4243–4256 (1983)

  6. Zhang GL, Xing QY, Zhang MZ. Glycolipids los ntawm Mirabilis Himalaya. Phytochemistry 45: 1213–1215 (1997)

  7. Polonsky J, Merrien MA, Prange T, Pascard C, Moreau S. Kev rho tawm thiab cov qauv (X-ray tsom xam) ntawm marcfortine A, alkaloid tshiab los ntawm Penicillium roqueforti. JCS Chem Comm 13: 601–602 (1980)

  8. Lee BH, Kornis GI, Cialdella JI, Clothier MF, Marshall VP, Martin DG, McNally PL, Mizsak SA, Whaley HA, Wiley VH. Microbiological hydroxylation ntawm 6 tus neeg carbon atoms ntawm marcfortine A. J Nat Prod 60: 1139–1142 (1997)

  9. Whyte AC, Gloer JB, Wicklow DT, Dowd PF. Sclerotiamide: Ib tug tswv cuab tshiab ntawm chav kawm paraherquamide nrog cov tshuaj tua kab mob muaj zog los ntawm sclerotia ntawm Aspergillus sclerotiorum. J Nat Prod 59: 1093–1095 (1996)

  10. Kato H, Yoshida T, Tokue T, Nojiri Y, Hirota H, Ohta T, Williams RM, Tsukamoto S. Notoamides AD: prenylated indole alkaloids cais los ntawm marine-derived fungus, Aspergillus sp. Angew Chem Int Ed 46: 2254–2256 (2007)

  11. Williams RM, Kwast E, Coffman H, Glinka T. Remarkable, enantio-divergent biogenesis ntawm brevianamide A thiab B. J Am Chem Soc 111: 3064–3065 (1989)

  12. Banks RM, Blanchflflower SE, Everett JR, Manger BR, Nyeem C. Novel anthelmintic metabolites los ntawm Aspergillus hom: aspergillimides. J Antibiot 50: 840–846 (1997)

  13. Qian-Cutrone J, Haung S, Shu YZ, Vyas D, Fairchild C, Menendez A, Krampitz K, Dalterio R, Klohr SE, Gao Q. J Am Chem Soc 124: 14556–14557 (2002)

  14. Wilson BJ, Yang DTC, Harris TM. Kev tsim khoom, kev cais tawm, thiab kev tshawb fawb txog kev lom neeg ua ntej ntawm brevianamide A los ntawm kab lis kev cai ntawm Penicillium Viridicatum. Appl Microbiol 26: 633–635 (1973)

  15. Birch AJ, Russell RA. Kev tshawb fawb txog biosynthesis XLIV. Cov qauv elucidations ntawm brevianamides B, C, D thiab F. Tetrahedron 28: 2999–3008 (1972)

  16. Liesch JM, Wichmann CF. Novel antinematodal thiab tshuaj tiv thaiv kab mob los ntawm Penicillium Charles. II. Tus qauv txiav txim siab ntawm paraherquamides B, C, D, E, F, thiab G. J Antibiot 43: 1380–1386 (1990) 17. Martinez-Luis S, Rodriguez R, Acevedo L, Gonzalez MC, Lira-Rocha A, Mata R Malbrancheamide, tus tshiab calmodulin inhibitor los ntawm fungus Malbranchea aurantiaca. Tetrahedron 62: 1817–1822 (2006)

  17. Mishima T, Tsuda M, Kasa Y, Ishiyama H, Fukushi E, Kawabata J, Watanabe M, Akao K, Kobayashi J. Tsis muaj tshuaj lom neeg ntawm citrinadins A thiab B los ntawm cov kab mob marine-derived. J Org Chem 70: 9430–9435 (2005)

  18. Lopez-Greta MP, Gonzalez MC, Ciavatta L, Ayala I, Moya P, Primo J. Insecticidal act of paraherquamides, paraherquamides, including paraherquamide H thiab paraherquamide I, Ob New Alkaloids cais los ntawm Penicillium cluniae. J Agric Food Chem 54: 2921–2925 (2006)

neuroprotective of cistanche deserticola: anti-Alzheimer's disease

neuroprotective ntawm cistanche deserticola: anti-Alzheimer's kab mob & Parkinson tus kab mob


Tsis muaj
Koj Tseem Yuav Zoo Li