Kāpae

ʻO Ezetimibe kahi mea paʻa a me ka mea hoʻopaneʻe o ka cholesterol absorption [1].

ʻO Cholesterol kahi mole lipid a koi ʻia e kūkulu a mālama i ka pono o ke ʻano a me ka wai. Eia kekahi, lawelawe ia ma ke ʻano he precursor o ka vitamin D, bile acids a me nā hormones steroid.

I loko o nā pūnaewele Caco-2 i hoʻokaʻawaleʻia me kahi carotenoid (1 μM), ezetimibe (10 mg / L) i kāohi i ka laweʻana i ka carotenoid me ka 50% inhibition no ka ɑ-carotene a me ka β-carotene. Eia kekahi, ua pale ia i ka lawe ʻana o β-cryptoxanthin, lycopene a me lutein: zeaxanthin (1:1). I ka manawa like, ua kāohi ʻo ezetimibe i ka lawe ʻana i ka cholesterol e 31%. Ua hoʻemi ʻo Ezetimibe i ka hōʻike ʻana o nā mea loaʻa o ka ʻili SR-BI, ATP binding cassette transporter, subfamily A (ABCA1), Niemann-Pick type C1 Like 1 protein (NPC1L1) a me retinoid acid receptor (RAR)γ, sterol-regulatory element binding proteins SREBP -1 a me SREBP-2, a me ka ate X receptor (LXR)β [3].

I nā ʻiole apolipoprotein E knockout (apoE-/-), ezetimibe (3 mg/kg) kaohi i ka lawe ʻana o ka cholesterol e 90%. Hoʻemi ʻo Ezetimibe i ka cholesterol plasma, hoʻonui i ka pae HDL, a ke kāohi i ka holomua o ka atherosclerosis [1]. I ka hoʻāʻo ʻana o ke kanaka III, ʻo Ezetimibe (10 mg) i hōʻemi nui i nā pae o ka LDL cholesterol, ka nui o ka cholesterol a me nā triglycerides a hoʻonui i ke kiʻekiʻe o ka HDL cholesterol [2].

Kuhikuhi:
[1]. Davis HR Jr, Compton DS, Hoos L, et al. ʻO Ezetimibe, kahi mea hoʻopaneʻe hoʻoheheʻe cholesterol ikaika, ke kāohi i ka ulu ʻana o ka atherosclerosis ma ApoE knockout mice. Arterioscler Thromb Vasc Biol, 2001, 21 (12): 2032-2038.
[2]. Clader JW. ʻO ka loaʻa ʻana o ezetimibe: kahi ʻike mai waho o ka mea loaʻa. J Med Chem, 2004, 47(1): 1-9.
[3]. I ka wā o A, Dawson HD, Harrison EH. Hoʻemi ʻia ka lawe ʻana o Carotenoid a hoʻohaʻahaʻa ʻia ka hōʻike ʻana o nā transporters lipid SR-BI, NPC1L1, a me ABCA1 i loko o nā pūnae Caco-2 i mālama ʻia me ka ezetimibe. J Nutr, 2005, 135 (10): 2305-2312.

wehewehe

ʻO Ezetimibe (SCH 58235) kahi mea hoʻopaneʻe hoʻoheheʻe cholesterol ikaika. ʻO Ezetimibe kahi mea hoʻopiʻi Niemann-Pick C1-like1 (NPC1L1), a he mea hoʻoikaika ikaika Nrf2.

In Vitro

Hana ʻo Ezetimibe (Eze) ma ke ʻano he mea hoʻoulu Nrf2 ikaika me ka ʻole o ka cytotoxicity. Hoʻonui ʻo Ezetimibe i ka transactivation o Nrf2, e like me ka mea i hōʻike ʻia e kahi luciferase reporter assay. Hoʻopili pū ʻo Ezetimibe i nā genes target Nrf2, me GSTA1, heme oxygenase-1 (HO-1) a me Nqo-1 i nā cell Hepa1c1c7 a me MEF. Hoʻopiʻi ʻo Ezetimibe i nā genes target Nrf2 ma nā pūnaewele Nrf2 +/+ MEF, ʻoiai ua paʻa loa kēia induction i nā cell Nrf2-/- MEF. Hoʻohui pū ʻia, hana ʻo Ezetimibe ma ke ʻano he Nrf2 inducer ma kahi ʻano kūʻokoʻa ROS [1]. Hoʻoponopono mua ʻia nā hepatocytes huh7 kanaka me Ezetimibe (10μM, 1 h) a incubated me ka palmitic acid (PA, 0.5 mM, 24 h) e hoʻoulu i ka steatosis hepatic. ʻO ka mālama ʻana iā Ezetimibe e hoʻemi nui i nā pae triglycerides (TG) i hoʻonui ʻia, i kūlike me kā mākou noiʻi holoholona. ʻO ka hoʻomaʻamaʻa PA ka hopena ma kahi o 20% ka emi ʻana o ka hōʻike mRNA o ATG5, ATG6, a me ATG7, i hoʻonui ʻia e ka mālama ʻana iā Ezetimibe. Eia kekahi, ua hoʻonui nui ka mālama ʻana iā Ezetimibe i ka hoʻemi ʻana o PA i ka nui o ka protein LC3 [2].

ʻAʻole ʻo MCE i hōʻoia kūʻokoʻa i ka pololei o kēia mau ʻano. No ka kuhikuhi wale no.

ʻO ka hoʻohana ʻana iā Ezetimibe (Eze) e hōʻemi i ke kaumaha o ke akepaʻa o nā ʻiole i hānai ʻia i ka ʻai methionine a me ka choline-deficient (MCD). Kūlike kēia me nā hopena maikaʻi o Ezetimibe ma ka hepatic steatosis. Hōʻike ka moʻolelo moʻolelo i ka nui o nā kulu momona macrovesicular i nā ʻiole ma ka ʻai MCD, akā hoʻemi nui ka mālama ʻana iā Ezetimibe i ka helu a me ka nui o kēlā mau droplets. Eia kekahi, ʻo ka fibrosis hepatic i nā ʻiole i hānai ʻia i ka meaʻai MCD ua hoʻemi nui ʻia e Ezetimibe [1]. ʻO ka pae koko a me ka ate me ka TG, nā ʻakika momona manuahi (FFA), a me ka cholesterol piha (TC) i hoʻemi nui ʻia i nā ʻiole OLETF i mālama ʻia e Ezetimibe. Eia kekahi, hōʻike nā ʻiole OLETF i ke kiʻekiʻe o ka serum glucose, insulin, HOMA-IR, TG, FFA, a me TC ma mua o nā holoholona LETF, i hoʻemi nui ʻia e Ezetimibe. Eia kekahi, ua hōʻike ʻia ka loiloi histological e hōʻike ana nā ʻiole mana OLETF i ka nui o ka lipid droplets i nā hepatocytes ma mua o nā mana LETO i hoʻohālikelike ʻia i nā makahiki, i hoʻopaʻa ʻia e ka lawelawe ʻana iā Ezetimibe [2].

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