Ka hope

ʻO Ezetimibe kahi mea hoʻopaneʻe ikaika a me ka mea hou no ka absorption cholesterol [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.

Ma nā pūnaewele Caco-2 i hoʻokaʻawaleʻia i hoʻokomoʻia me kahi carotenoid (1 μM), ezetimibe (10 mg / L) i kāohi i ka halihali carotenoid me ka 50% inhibition no ɑ-carotene a me β-carotene.Eia kekahi, ua kāohi 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 i 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 ʻana i ka cholesterol absorption 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 pae III o na hoao kanaka, Ezetimibe (10 mg) i hoemi nui i ka nui o ka LDL cholesterol, ka huina cholesterol a me ka triglycerides a hoonui i ka pae 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 hoʻomohala 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 hoʻoemi 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 Nrf2 activator 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 pūnaewele 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 lāʻau ʻo Ezetimibe e hoʻemi nui i nā pae triglycerides (TG) hoʻonui i ka PA, 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 i ka 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 ʻai 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 holoʻokoʻa (TC) i hoʻemi nui ʻia i nā ʻiole OLETF i mālama ʻia e Ezetimibe.Eia kekahi, hōʻike nā ʻiole OLETF i nā kiʻekiʻe serum o ka 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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