Background

Ezetimibe ine simba uye novel inhibitor yekunyudza cholesterol [1].

Cholesterol is lipid molecule uye inodiwa kuvaka uye kuchengetedza membranes hunhu kutendeseka uye fluidity. Zvakare, inoshanda seyakatangira vhitamini D, bile acids uye steroid mahomoni.

Mumasero eCaco-2 akasiyana-siyana akaiswa ne carotenoid (1 μM), ezetimibe (10 mg / L) inhibited carotenoid kutakura ne 50% inhibition ye ɑ-carotene uye β-carotene. Zvakare, yairambidza kutakurwa kweβ-cryptoxanthin, lycopene uye lutein:zeaxanthin (1: 1). Panguva imwecheteyo, ezetimibe inhibited cholesterol kutakura ne31%. Ezetimibe yakaderedza kutaura kweiyo yepamusoro receptors SR-BI, ATP inosunga kaseti inotakura, subfamily A (ABCA1), Niemann-Pick rudzi C1 Se 1 protein (NPC1L1) uye retinoid acid receptor (RAR) γ, sterol-regulatory chinhu chinosunga mapuroteni SREBP. -1 uye SREBP-2, uye chiropa X receptor (LXR) β [3].

Mu apolipoprotein E kugogodza (apoE-/-) mbeva, ezetimibe (3 mg/kg) yakadzivisa kutorwa kwecholesterol ne90%. Ezetimibe yakaderedza plasma cholesterol, yakawedzera HDL mazinga, uye inodzivisa kufambira mberi kweatherosclerosis [1]. Muchikamu chechitatu chekuedzwa kwevanhu, Ezetimibe (10 mg) yakaderedza zvakanyanya mazinga eLDL cholesterol, cholesterol yakazara uye triglycerides uye yakawedzera huwandu hweHDL cholesterol [2].

References:
[1]. Davis HR Jr, Compton DS, Hoos L, et al. Ezetimibe, ine simba cholesterol absorption inhibitor, inhibitor kukura kweatherosclerosis muApoE knockout mice. Arterioscler Thromb Vasc Biol, 2001, 21(12): 2032-2038.
[2]. Clader JW. Kuwanikwa kwezetimibe: maonero kubva kunze kwekugamuchira. J Med Chem, 2004, 47(1): 1-9.
[3]. Panguva A, Dawson HD, Harrison EH. Kutakura kweCarotenoid kwakadzikira uye kutaura kweiyo lipid transporters SR-BI, NPC1L1, uye ABCA1 inoderedzwa muCaco-2 masero anobatwa nezetimibe. J Nutr, 2005, 135(10): 2305-2312.

Tsanangudzo

Ezetimibe (SCH 58235) ine simba cholesterol absorption inhibitor. Ezetimibe is an Niemann-Pick C1-like1 (NPC1L1) inhibitor, uye ine simba Nrf2 activator.

In Vitro

Ezetimibe (Eze) inoshanda senge ine simba Nrf2 activator pasina kukonzera cytotoxicity. Ezetimibe inowedzera transactivation yeNrf2, sezvakaratidzwa ne luciferase reporter assay. Ezetimibe inokwidzawo Nrf2 chinangwa chemajini, kusanganisira GSTA1, heme oxygenase-1 (HO-1) uye Nqo-1 muHepa1c1c7 uye MEF masero. Ezetimibe inokwidza Nrf2 chinangwa chemajini muNrf2 +/+ MEF maseru, nepo induction iyi yakavharwa zvachose muNrf2-/- MEF maseru. Kutorwa pamwechete, Ezetimibe inoita senge inoveli Nrf2 inducer nenzira yakazvimiririra yeROS[1]. Munhu huh7 hepatocytes akaiswa kare neEzetimibe (10μM, 1 h) uye yakasanganiswa nepalmitic acid (PA, 0.5 mM, 24 h) kuti iite hepatic steatosis. Kurapa kweEzetimibe kunoderedza zvakanyanya PA-yakawedzera triglycerides (TG) mazinga, izvo zvinoenderana nekudzidza kwedu mhuka. Kurapa kwePA kwakakonzera kudzikira kwe20% muRNA kutaura kweATG5, ATG6, uye ATG7, iyo yakanga yawedzerwa neEzetimibe kurapwa. Mukuwedzera, kurapwa kweEzetimibe kwakawedzera zvakanyanya kuderedzwa kwePA muLC3 protein yakawanda[2].

MCE haina kuzvimiririra kusimbisa chokwadi chenzira idzi. Ndezvekureva chete.

Kutonga kweEzetimibe (Eze) kunoderedza huremu hwechiropa hwembeva dzakadyiswa methionine- uye choline-deficient (MCD) kudya. Izvi zvinoenderana nerubatsiro rweEzetimibe pane hepatic steatosis. Chiropa histology inoratidza yakadanwa akawanda macrovesicular mafuta madonhwe mumakonzo paMCD chikafu, asi kurapwa kweEzetimibe kunoderedza huwandu uye saizi yemadonhwe iwayo. Uyezve, hepatic fibrosis mumakonzo akadyisa kudya kweMCD inodzikiswa zvakanyanya neEzetimibe[1]. Ropa uye chiropa lipid mazinga anosanganisira TG, emahara fatty acids (FFA), uye yakazara cholesterol (TC) akadzikira zvakanyanya mumakonzo eEzetimibe anorapwa OLETF. Uyezve, makonzo eOLETF anoratidza akakwira serum mazinga eglucose, insulin, HOMA-IR, TG, FFA, uye TC pane LETF mhuka, iyo yakaderedzwa zvakanyanya neEzetimibe. Pamusoro pezvo, ongororo yenhoroondo yakaratidza kuti OLETF yekudzora makonzo yakaratidza madonhwe makuru elipid muhepatocytes kupfuura zera-rinofananidzwa LETO kudzora, izvo zvinodzikiswa nekutungamirwa kweEzetimibe[2].

Storage

Chimiro chemakemikari