Silibinin hmoovyog flavonoid lignan compound cais los ntawm cov noob ntawm Asteraceae cog Silybin purpurea. Nws cov khoom xyaw tseem ceeb suav nrog plaub isomers: silybin, isosilybin, silybin, thiab silybin. Nws tuaj yeem tiv thaiv kev puas tsuaj rau daim siab uas tshwm sim los ntawm cov tshuaj lom neeg lom neeg, cov khoom noj co toxins, thiab tshuaj, txhawb lub siab cell regeneration thiab kho, thiab hu ua "natural siab tiv thaiv tshuaj". Nyob rau hauv chav tsev kub, nws yog dawb crystalline hmoov, tsw tsw, me ntsis iab hauv saj, nrog hygroscopicity. Nws yooj yim soluble hauv acetone, ethyl acetate, methanol, ethanol, me ntsis soluble hauv chloroform, thiab yuav luag insoluble hauv dej.
Nws muaj ntau yam kev tiv thaiv thiab kho cov teebmeem ntawm ntau hom kev puas siab puas ntsws los ntawm daim siab co toxins xws li carbon tetrachloride, thioacetamide, muscarine, ghouline, thiab npua excrement alkaloid, thiab muaj qee yam inhibitory cuam tshuam rau qhov nce ntawm alanine aminotransferase los ntawm carbon tetrachloride. Haum rau kev kho mob ntawm cov kab mob siab tsis tu ncua, mob siab ua haujlwm siab, mob cirrhosis ntxov, mob siab rau lub siab, thiab lwm yam kab mob. Tsis tas li ntawd, cov khoom no kuj muaj cov khoom muaj zog antioxidant, uas tuaj yeem tshem tawm cov dawb radicals hauv tib neeg lub cev thiab ncua kev laus. Nws tau siv dav hauv kev lag luam xws li tshuaj, khoom noj qab haus huv, zaub mov, thiab tshuaj pleev ib ce.
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Tshuaj Formula |
C25H22O10 |
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Exact Mass |
482 |
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Molecular Luj |
482 |
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m/z |
482 (100.0%), 483 (27.0%), 484 (2.7%), 484 (2.1%) |
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Elemental Analysis |
C, 62.24; H, 4.60; O, 33.16 |
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Silibinin hmoov, lub ntuj flavonoid lignan muab rho tawm los ntawm Asteraceae cog Silymarin, tau dhau los ua ib qho ntawm cov tshuaj tseem ceeb hauv ntiaj teb kev kho kab mob siab vim nws ntau yam - lub hom phiaj hepatoprotective cuam tshuam thiab cov yam ntxwv tsis muaj tshuaj lom. Nws cov txheej txheem ntawm kev ua haujlwm npog tsib qhov ntev: antioxidant, tiv thaiv - mob, tiv thaiv fibrosis, detoxification, thiab kev tiv thaiv kab mob. Nws ua lub luag haujlwm tseem ceeb hauv kev kho mob ntawm daim siab xws li mob siab thiab mob siab, mob siab, mob siab, tshuaj- ua rau lub siab raug mob, kab mob siab cawv, thiab cirrhosis.
Core pharmacological mechanism: Tsib seem hepatoprotective network
1. Kev tsim kho ntawm kev tiv thaiv antioxidant
Silymarin tsim cov tshuaj tiv thaiv kab mob antioxidant dual los ntawm kev tshem tawm cov dawb radicals thiab inhibiting lipid peroxidation. Cov phenolic hydroxyl pawg hauv nws cov qauv tuaj yeem cuam tshuam ncaj qha nrog cov pa oxygen reactive (ROS) xws li superoxide anions (O ₂⁻) thiab hydroxyl radicals (· OH), thaum txhawb kev ua haujlwm ntawm glutathione (GSH) synthase, ua rau 40% -60% nce hauv GSH qib hauv daim siab. Cov kev tshawb fawb soj ntsuam tau pom tias nyob rau hauv cov neeg mob uas tsis yog-alcoholic steatohepatitis (NASH), kev kho mob nrog silibinin rau 12 lub lis piam ua rau 32% txo qis hauv cov ntshav malondialdehyde (MDA) qib thiab nce 25% hauv GSH / GSSG piv, txhim kho oxidative kev ntxhov siab.
2. Kev cai ntawm kev tiv thaiv - inflammatory signaling pathway
Silymarin thaiv cov kab mob inflammatory los ntawm inhibiting NF - κ B thiab MAPK txoj hauv kev. Hauv CCl ₄ - induced daim siab fibrosis qauv, silibinin tuaj yeem txo qhov kev qhia ntawm pro- mob xws li TNF - thiab IL-6 los ntawm 60% -70%, thaum txhawb kev tso tawm ntawm cov tshuaj tiv thaiv kab mob xws li IL-10. Rau cov neeg mob uas muaj kab mob siab cawv, tom qab 8 lub lis piam ntawm kev kho mob nrog silymarin ua ke nrog metoprolol, ALT qib tau txo qis los ntawm 55%, AST qib qis dua 48%, thiab cov qhab nia inflammatory (HAI) tau txhim kho los ntawm 72%.
3. Anti fibrotic kho cov hom phiaj
Silymarin blocks kev loj hlob ntawm daim siab fibrosis los ntawm ib tug dual mechanism:
Inhibition of hepatic stellate cell activation: Downregulation of fibrosis markers xws li - SMA and Collagen I expression. Nyob rau hauv tus qauv nas ntawm daim siab fibrosis tshwm sim los ntawm cov kua tsib kab ligation, silibinin tuaj yeem txo thaj tsam fibrosis los ntawm 58%.
Txhawb nqa matrix metalloproteinase (MMP) kev qhia: Upregulate MMP-2 thiab MMP-9 kev ua, ua kom lub cev muaj zog (ECM) degradation.
Kev tshawb fawb soj ntsuam pom tau hais tias nyob rau hauv cov neeg mob uas muaj kab mob siab B tom qab cirrhosis, tom qab 24 lub lis piam ntawm kev kho silibinin, lub siab hardness tus nqi (LSM) txo los ntawm 22%, thiab tus me nyuam Pugh qhab nia tau nce los ntawm 65%.
4. Txhim kho detoxification muaj nuj nqi
Silymarin txhim khu lub siab lub peev xwm metabolic rau tshuaj, cawv, thiab ib puag ncig co toxins los ntawm inducing qhia theem II detoxifying enzymes xws li GST thiab UGT.
Hauv cov neeg mob lub siab raug mob los ntawm cov tshuaj tiv thaiv tuberculosis xws li isoniazid thiab rifampicin, silibinin tuaj yeem txo cov ntshav tag nrho bilirubin (TBIL) qib los ntawm 40%, txo lub sijhawm prothrombin (PT) los ntawm 2.5 vib nas this, thiab txo qhov tshwm sim ntawm cov tshuaj - ua rau lub siab raug mob.
5. Kev ua kom zoo ntawm kev tiv thaiv kab mob sib txuas
Silymarin txhim kho kev tiv thaiv kab mob ntawm cov neeg mob uas muaj kab mob siab autoimmune (AIH) los ntawm kev tswj hwm Th1 / Th2 tshuav nyiaj li cas thiab inhibiting T cell activation. Hauv AIH qauv nas, silibinin tuaj yeem txo cov ntshav ntshav IgG los ntawm 35%, nce qhov feem ntawm CD4 ⁺ CD25 ⁺ tswj T hlwb hauv tus po los ntawm 28%, thiab txo qis kev mob siab rau lub siab.
Clinical indication: Kho kab mob siab thoob plaws tag nrho cov spectrum
1. Adjuvant therapy rau tus kab mob siab viral
Kab mob siab B / kab mob siab C:Silibinin hmoovua ke nrog nucleoside (acid) analogs (xws li entecavir) lossis cov tshuaj tiv thaiv kab mob ncaj qha (DAAs) tuaj yeem ua kom lub cev tsis zoo ntawm HBV DNA lossis HCV RNA, thiab txhim kho daim siab mob thiab fibrosis. Txoj kev tshawb no tau pom tias ntawm cov neeg mob HBeAg zoo mob siab B, qhov tsis zoo ntawm HBV DNA hauv silibinin ua ke pab pawg kho mob ntawm 6 lub hlis yog 18% siab dua li hauv ib pawg tshuaj, thiab kev txhim kho tus nqi ntawm daim siab ua haujlwm siab (Ishak) yog 75%.
Mob kab mob siab kab mob siab: Silymarin tuaj yeem txo lub sijhawm rau kev daws teeb meem jaundice (nruab nrab 3.2 hnub) thiab ua kom cov ALT / AST rov zoo li qub (nruab nrab 5.7 hnub ua ntej).
2. Kev tswj hwm ntawm tsis yog - haus dej cawv fatty siab kab mob (NAFLD)
Tej yam yooj yim fatty daim siab: Silymarin txo lub siab rog cov ntsiab lus los ntawm kev tswj cov kev qhia ntawm lipid metabolim ntsig txog cov noob xws li PPAR - thiab SREBP-1c. Hauv cov neeg mob NAFLD, tom qab 24 lub lis piam ntawm kev kho mob nrog silibinin, tus qhab nia ntawm hepatic steatosis (CAP tus nqi) txo qis los ntawm 42% thiab cov tshuaj insulin tsis kam (HOMA-IR) txo los ntawm 30%.
NASH kev loj hlob blockade: Silymarin tuaj yeem cuam tshuam hepatocyte ballooning thiab Mallory lub cev tsim hauv NASH cov neeg mob, ua rau txo qis dua lossis sib npaug rau 2 cov ntsiab lus hauv NASH cov qhab nia (NAS) hauv 68% ntawm cov neeg mob.
3. Kev cuam tshuam rau kab mob siab cawv (ALD)
Alcoholic fatty siab: Silymarin accelerates cawv metabolim los ntawm upregulating cov dej cawv dehydrogenase (ADH) thiab aldehyde dehydrogenase (ALDH). Ntawm cov neeg haus dej haus ntev ntev, silibinin tuaj yeem txo cov ntshav gamma GT los ntawm 50% thiab txo cov rog rog hauv lub siab los ntawm 45%.
Alcoholic kab mob siab: Silymarin ua ke nrog kev kho mob glucocorticoid tuaj yeem txo qhov kev tuag ntawm 28 hnub ntawm cov neeg mob uas muaj kab mob siab dej cawv loj (los ntawm 40% mus rau 25%), thaum txhim kho Maddrey cov qhab nia sib cais.
4. Kev tiv thaiv thiab kho cov tshuaj -induced siab raug mob (DILI)
Kev kho mob ntsig txog lub siab raug mob: Hauv cov neeg mob uas mob qog noj ntshav uas tau txais kev kho mob, silibinin tuaj yeem txo qhov tshwm sim ntawm ALT nce siab tom qab siv tshuaj khomob los ntawm 32% mus rau 15%, thiab qhov tshwm sim ntawm mob siab heev (siab dua lossis sib npaug rau qib 3) los ntawm 12% mus rau 4%.
Tshuaj tiv thaiv tuberculosis ua rau lub siab raug mob: Prophylactic kev tswj hwm ntawm silibinin tuaj yeem txo qhov tshwm sim ntawm daim siab raug mob thaum kho kab mob los ntawm 28% mus rau 9%, txhim kho kev ua raws li kev kho mob.
5. Kev tswj cov teeb meem hauv daim siab cirrhosis
Portal hypertension: Silymarin txo qhov kev pheej hmoo ntawm esophageal variceal los ntshav hauv cov neeg mob cirrhosis los ntawm 30% los ntawm kev txo lub siab tawv thiab txhim kho sinusoidal endothelial cell muaj nuj nqi.
Hepatic encephalopathy: Silymarin tuaj yeem tswj cov plab hnyuv microbiota, txo cov ammonia ntau lawm, thiab txhim kho cov qhab nia kuaj ntshav siab ntawm cov neeg mob uas mob siab mob siab txog li 60%.
Syntheticsilibinin hmoov: siab -purity silybin cov ntsiab lus yog 97% ~ 101%. Txoj kev npaj yog siv silymarin plhaub ua raw khoom thiab ntxiv ethyl acetate rau dej Dissolve lub silybin plhaub, rho tag nrho cov flavonoids, sau ketones nyob rau hauv lub nqus tsev vacuum, thiab ces yaj, extract, lim thiab qhuav tag nrho flavonoids kom tau lub siab - purity silybin.
Txoj Kev 1: Oxidation ntawm Silybin kom tau Silibinin
Cov khoom pib: Silybin
Cov tshuaj tiv thaiv oxidation:
Silybin reacts nrog cov oxidizing muaj zog xws li hydrogen peroxide los yog ammonium persulfate nyob rau hauv alkaline tej yam kev mob.
Chemical Equation:
Silybin + muaj zog oxidant + alkaline tej yam kev mob → C25H22O10
Extraction thiab purification:
Cais cov ntshiab silibinin los ntawm cov tshuaj tiv thaiv sib tov los ntawm kev rho tawm thiab ua kom huv si.
Txoj Kev 2: Extract Silibinin los ntawm Mis Thistle Txiv Hmab Txiv Ntoo
Extraction:
Sib tov mis thistle txiv hmab txiv ntoo hmoov nrog cov kuab tshuaj uas tsim nyog (xws li ethanol lossis dimethyl sulfoxide) thiab ua cov txheej txheem tsim nyog kom tau txais cov kua txiv hmab txiv ntoo.
Sib cais thiab purification:
Silibinin raug rho tawm los ntawm mis thistle txiv hmab txiv ntoo extract los ntawm kab chromatography, hnyav extraction, los yog lwm yam kev sib cais.
Crystallization:
Crystallize Silibinin nyob rau hauv cov kuab tshuaj tsim nyog kom tau cov ntshiab silibinin crystals.
Absorption yam ntxwv
Silibinin yog lipophilic flavonolignan monomer heev. Cov pasilibinin hmoovmuaj cov dej solubility tsis zoo, uas yog qhov tseem ceeb txwv rau txoj hnyuv nqus. Tom qab kev tswj hwm qhov ncauj, tsuas yog ib feem me me dhau los ua qhov kev sib kis thoob plaws hauv plab hnyuv epithelial hauv cov hnyuv me. Lub bioavailability ntawm unmodified raw khoom yog li ntawm 0.4% mus rau 2%. Cov active ingredient nkag tau yooj yim khi rau bile acids thiab noj cov proteins nyob rau hauv txoj hnyuv lumen, ntxiv ncua kev nqus.
Lub sij hawm mus txog qhov siab tshaj plaws plasma concentration (Tmax) yog kwv yees li 2-3 teev nyob rau hauv kev yoo mov; Thaum noj tshuaj tom qab prandially, qhov siab tshaj plaws plasma concentration (Cmax) poob los ntawm kwv yees li 30%. Cov kab mob hauv plab tuaj yeem ua rau me me metabolize nws mus rau hauv qis- cov tshuaj muaj zog metabolites, uas ua rau txo cov tshuaj muaj txiaj ntsig zoo nkag mus rau hauv lub cev.
Rau nws hloov kho los ntawm phospholipid complexation, cyclodextrin inclusion los yog nanonization, dissolution kev ua tau zoo dua, thiab qhov ncauj bioavailability yuav nce 5-10 quav.
Hauv Vivo Distribution
Tom qab nkag mus rau hauv cov hlab ntsha, ib ncig ntawm 70% ntawm silibinin khi reversibly rau plasma albumin. Unbound silibinin sai sai accumulates nyob rau hauv cov ntaub so ntswg los ntawm cov kab mob ntawm lub cev, ua rau lub siab ntau dua cov tshuaj nyob rau hauv lub siab ntau dua piv rau cov kab mob xws li lub plawv, hlwb thiab ob lub raum, conferring inherent hepatotropic targeting zoo.Cov compound NW nyuam qhuav nkag mus rau hauv lub cev tsis muaj ntshav- hlwb barrier (BBB), ua rau tsawg kawg nkaus cerebral tis. Cov feem me me faib rau ntawm daim tawv nqaij thiab plab hnyuv mucosa, muab kev txhawb nqa theoretical rau nws daim ntawv thov kev tu tawv nqaij thiab plab hnyuv los tiv thaiv - inflammatory teebmeem.
Tsis pom tseeb cov ntaub so ntswg tshwm sim; Cov tshuaj hauv nruab nrog cev cov tshuaj yeeb tshuaj poob qis tsis tu ncua raws sijhawm tom qab ib koob tshuaj, tsis muaj kev pheej hmoo ntawm cov khoom siv hauv nruab nrog cev raws li qhov ntev - noj qhov ncauj.
Biotransformation ntawm metabolic
Metabolism feem ntau tshwm sim hauv daim siab thiab plab hnyuv. Hauv hepatocytes, silibinin dhau mus rau theem II biotransformation mediated los ntawm UGT-catalyzed glucuronidation thiab SULT-catalyzed sulfation, tsim ob loj conjugated metabolites nrog bioactivity piv rau niam txiv silibinin.
Unabsorbed zoo silibinin mus txog rau hauv txoj hnyuv loj thiab degraded los ntawm anaerobic plab microbiota mus rau theem nrab metabolites xws li dihydrosilibinin, uas nws biological ua hauj lwm yog heev attenuated. Cov metabolites muaj cov polarity nce siab thiab poob lipophilicity, tshem tawm lawv cov kev ua haujlwm hepatoprotective tseem ceeb- qhov no yog qhov tseem ceeb txwv tsis pub muaj kev ua tau zoo ntawm cov pa hauv qhov ncauj silibinin. Tib neeg cytochrome P450 enzymes ua rau muaj kev cuam tshuam tsis zoo rau nws cov metabolism, ua rau muaj kev pheej hmoo tsawg ntawm cov tshuaj - yeeb tshuaj metabolic cuam tshuam.
Kev tshem tawm thiab tshem tawm
Tshaj li 70% ntawm silibinin thiab nws cov metabolites conjugated yog zais los ntawm hepatocytes rau hauv cov kua tsib thiab thaum kawg tshem tawm ntawm cov quav; qhov seem 20% -30% tau txais glomerular pom thiab raug tso tawm hauv cov zis.
Kev tshem tawm ib nrab- lub neej yog kwv yees li 6-8 teev, yog li kev noj tshuaj txhua hnub tsis tshua ua rau cov tshuaj sib xyaw ua ke.
Ib feem me me ntawm biliary metabolites rov- nkag mus rau hauv enterohepatic ncig, nruab nrab ncua ntev hauv vivo lub sijhawm ua haujlwm, tab sis tag nrho cov tshuaj recirculating load tseem txwv. Kev hloov tshuaj noj tsis tsim nyog rau cov neeg mob uas lub raum tsis zoo. Hauv cov neeg mob uas muaj cov kab mob biliary loj heev, cov kua tsib tso tawm tsis zoo tuaj yeem ua rau cov metabolites khaws cia, yuav tsum tau ceev faj.
FAQ
Dab tsi yog silibinin siv rau?
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Rau nws cov yam ntxwv zoo tshaj plaws los tiv thaiv- kab mob siab, silibinin tau siv los ua cov tshuaj ib txwm siv rau ntau tshaj 2000 xyoo hauv European thiab Asia lub teb chaws los kho ntau yam kab mob siab xws li kab mob siab thiab mob cirrhosis, thiab los tiv thaiv daim siab tiv thaiv sab nraud.
Dab tsi yog qhov txawv ntawm silymarin thiab silibinin?
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Silymarin (SIL) yog lub ntuj extract nrog hepatoprotective zog uas muaj feem ntau ntawm flavonolignans, nrog silibinin (SB) yog nws cov ntsiab lus tseem ceeb. SB tau xav tias yog lub luag haujlwm tseem ceeb rau SIL hepatoprotective zog, txawm hais tias qhov no tsis tau txheeb xyuas qhov systematically.
Cov kev phiv ntawm silibinin yog dab tsi?
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Qhov no tuaj yeem tshwm sim raws li qhov mob plab me me mus rau nruab nrab, nrog rau cov tsos mob xws li xeev siab, tsam plab, roj, thiab raws plab. Cov teebmeem no feem ntau yog ib ntus thiab yuav ploj zuj zus thaum lub cev hloov mus rau qhov ntxiv. Txhawm rau txo qhov tsis xis nyob hauv plab, feem ntau pom zoo kom noj silibinin nrog zaub mov.
Cim npe nrov: silibinin hmoov CAS 22888-70-6, lwm tus neeg, manufacturers, hoobkas, lag luam wholesale, yuav, nqe, tej, kev muag khoom