Ntu 2: Cov Teeb Meem Ntawm Isorhamnetin Ntawm Ntshav Qab Zib Thiab Nws Cov Teeb Meem Sib Txuas: Kev Ntsuam Xyuas Ntawm Hauv Vitro Thiab Hauv Vivo Kev Tshawb Fawb Thiab Ib Daim Ntawv Tshaj Lij Tshaj Lij Tshaj Lij Tshaj Lij Tshaj Tawm Ntawm Txoj Kev Molecular

Yog xav paub ntxiv. tiv taujtina.xiang@wecistanche.com

3. Kev Tshaj Tawm Txog Kev Ua Txhaum Cai ntawm Isorhamnetin

Oxidative stress yog ib qho txheej txheem endogenous thiab exogenous uas plays lub luag haujlwm hauv kev laus. Oxidative stress tshwm sim vim dysregulation nyob rau hauv lubantioxidantKev tiv thaiv los ntawm qhov tsis txaus ntseeg ntawm ROS thiab nitrogen hom [59]. Ntau tus kws tshawb fawb tau pom tias qhov ntev mus ntev rau cov dawb radicals pab txhawb kev loj hlob ntawm cov kab mob ntev, xws li mob qog noj ntshav [60],ntshav qab zib[61], teeb meem plawv [62], thiab kab mob neurodegenerative [63]. Yog li, txoj kev tshawb fawb txog kev ua haujlwm lom neeg ntawm isorhamnetin tuaj yeem pib los ntawm kev tshawb xyuas qhov kev koom tes ntawm cov molecule hauv cov tshuaj tiv thaiv antioxidant. Isorhamnetin belongs rau cov chav kawm flavonol paub txog nws cov peev xwm antioxidant [64,65]. Ntxiv mus, ntau qhov kev tshawb fawb tau pom tias qhov noflavonolmuaj cov haujlwm antioxidant zoo kawg li, tshem tawm DPPH radical thiab ABTS radical, thiab tuaj yeem tiv thaiv lipid peroxidation [66-68]. Wu et al. qhia tias isorhamnetin thiab isorhamnetin-3-glucuronide tuaj yeem cuam tshuam tib neeg lub mis mob cancer MCF-7 cell proliferation [69]. Wei et al. ua pov thawj tias isorhamnetin inhibits kev loj hlob ntawm lub ncauj tsev menyuam kab mob qog noj ntshav HeLa [70]. Cov txheej txheem ntawm kev tiv thaiv proliferative nyhuv ntawm isorhamnetin tau meej meej ntsig txog lub voj voog ntawm tes ntawm G2 / M theem los ntawm kev ua kom lub ATM-Chk2 txoj hauv kev. Li thiab cov npoj yaig tau qhia tias isorhamnetin tuaj yeem cuam tshuam kev loj hlob ntawm gefitinib resistant PC9 hlwb (PC9-IR) los ntawm kev txo qis BCL{11}} gene qhia thiab PCNA protein qhia, inhibiting DNA synthesis thiab upregulating P53, BAX, thiab CASP3 noob qhia [22]. Nrog rau qhov no, Aonuma et al. [71] pom tau hais tias isorhamnetin tuaj yeem txo qis hypertrophy thiab fibrosis tshwm sim los ntawm angiotensin IⅡ hauv cov ntaub so ntswg los ntawm kev tswj hwm txoj kev loj hlob ntawm txoj kev loj hlob (TGF-). Tsis tas li ntawd, nws yuav muaj txiaj ntsig zoo rau cov txiaj ntsig kev kho mob ntawm cov kab mob plawv los ntawm kev tswj hwm renin-angiotensin. Isorhamnetin tau siv cov tshuaj tiv thaiv neuroprotective tiv thaiv ischemic raug mob hauv cov nas los ntawm kev txo qis infarct ntim thiab Casp3 kev ua (ib qho biomarker ntawm apoptosis) thiab txhim kho kev ua haujlwm ntawm lub paj hlwb. Ib yam li ntawd, cov nas uas tau kho nrog cov flavonol no tau pom tias tsis muaj cerebral edema, txhim kho cov ntshav-hlwb barrier muaj nuj nqi, thiab upregulated gene qhia ntawm nruj junction proteins, xws li Ocln, Zo-1, thiab Clin-5 [72]. Ishola et al. qhia tias isorhamnetin ameliorates scopolamine-induced spatial thiab non-spatial kev kawm thiab nco tsis taus hauv vivo [73]. Ib yam li ntawd, nws tuaj yeem txo cov malondialdehyde (MDA) thiab nitrite ntau lawm los ntawm kev nce qib glutathione (GSH), SOD, thiab CAT cov dej num hauv prefrontal cortex thiab hippocampus. Covanti-inflammatoryCov nyhuv ntawm isorhamnetin thiab cov txheej txheem muaj feem xyuam tau kawm dav [21]. Yang et al. [32] pom tau tias isorhamnetin tuaj yeem txo qis LPS-vim mob ntsws raug mob los ntawm inhibiting Cox-2 qhia hauv txiv neej BALB/c nas [74]. Ib yam li ntawd, txoj kev kawm hauv vivo ntawm Dou et al.[75] qhia tau tias nws tuaj yeem txo cov kab mob hauv plab los ntawm kev ua kom PXR thiab txhawb kev txhawb nqa ntawm PXR-mediated metabolism ntawm probiotics thiab downregulation ntawm nuclear factor-kappa B (NF-kB) teeb liab transduction [75].

Tsis tas li ntawd, isorhamnetin tau tshaj tawm los tiv thaiv kev mob ntsws ntsws [76]. Tsis tas li ntawd, nws tuaj yeem ua rau mob raum raug mob los ntawm inhibiting NF-kB signaling pathway activation [31]. Tsis tas li ntawd, isorhamnetin nthuav tawm anti-thrombus [77], antihypertensive [78], anti-inflammatory [26], anti-osteoporosis [79], antiplatelet kev ua haujlwm [80], hepatoprotective [81], thiab anti-hypoxia [82] teebmeem. Nws kuj tau pom tias isorhamnetin tuaj yeem txhawb kev tiv thaiv hauv lub cev [83]. Txawm li cas los xij, peb tsis tau pom ntau qhov kev tshaj tawm uas lees paub cov tshuaj tiv thaiv kab mob thiab tshuaj tiv thaiv kab mob ntawm isorhamnetin. Tseem, qee qhov kev tshawb fawb tau tshaj tawm cov kab mob bactericidal ntawm cov nroj tsuag rho tawm uas muaj isorhamnetin lossis nws cov derivatives [84-86]. Antiviral cov dej num ntawm isorhamnetin tau soj ntsuam tiv thaiv kab mob khaub thuas [87l, SARS-CoV-2 spike [24], thiab herpes simplex[88](saib cov ntsiab lus hauv daim duab 3). Hauv cov ntsiab lus, qhov nthuav molecule no yog ib qho chaw loj ntawm cov dej num lom neeg. Ntau tshaj li qhov peb tau hais, nws tau txais txiaj ntsig nrog cov haujlwm tseem ceeb los tiv thaiv kev mob ntshav qab zib uas peb kawm hauv ntu tom ntej ntawm qhov kev tshuaj xyuas no.

Nyem qhov no kom paub ntau yam khoom

4. Anti-Diabetic nyhuv ntawm Isorhamnetin

Isorhamnetin tau tshaj tawm los txo cov teeb meem metabolic hauv hom 1 mob ntshav qab zib mellitus (T1DM) thiab hom 2 mob ntshav qab zib mellitus (T2DM), tab sis txog rau tam sim no, nws tau zoo dua nrog T2DM. Piv txwv li, Matboli et al.qhia tias isorhamnetin siv ntawm peb koob tshuaj sib txawv (10, 20, 40 mg / kg rau 3 lub lis piam) muaj kev tiv thaiv kab mob ntshav qab zib los ntawm kev tswj cov insulin txoj hauv kev ntawm microscopic, molecular, thiab protein ntau hauv streptozotocin. /high fat diet-induced T2DM nas model [89]. Cov kws sau ntawv hauv txoj kev tshawb fawb no tau xaus lus tias isorhamnetin tuaj yeem siv los ua lwm txoj hauv kev thiab / lossis muaj peev xwm kho ntxiv hauv T2DM los ntawm kev hloov pauv ntawm insulin tsis kam qhia txog txoj hauv kev ntsig txog noob caj noob ces. Txawm li cas los xij, hais txog T1DM, cov nyhuv ntawm isorhamnetin tseem tsis tau kawm zoo nrog hauv vitro thiab hauv vivo qauv.

4.1.Kev Saib Xyuas Kev Mob Ntshav Qab Zib thiab Nws Txuas Nrog Metabolic Syndrome

Metabolic Syndrome yog ib lub hnub qub ntawm cardiometabolic uas muaj feem cuam tshuam thawj zaug tau piav qhia 90 xyoo dhau los [90]. Xyoo 1988, qhov kev xav ntawm syndrome X tshwm sim [91]. Nws suav nrog kev rog plab, insulin tsis kam, piam thaj intolerance (los yog hyperglycemia), kub siab, thiab dyslipidemia. Kev sib xyaw ua ke ntawm cov kev pheej hmoo no yog txuas nrog kev pheej hmoo ntawm kev tsim T2DM thiab kab mob plawv. Mob ntshav qab zib mellitus (DM) yog ib hom kab mob metabolic uas tshwm sim los ntawm cov ntshav qabzib nce siab. Nws raug faib ua hom 1 (T1DM) thiab hom 2 (T2DM). Thawj qeb ntawm ntshav qab zib (T1DM) feem ntau cuam tshuam nrog kev ua tsis tiav hauv insulin tsim tawm los ntawm kev puas tsuaj ntawm pancreatic cells los ntawm T-cell-mediated autoimmunity. Txawm li cas los xij, T2DM yog qhov tshwj xeeb rau insulin tsis kam thiab ua haujlwm [92]. Cov ua rau metabolic syndrome feem ntau tsis to taub tab sis koom nrog cov caj ces txuas nrog ib puag ncig. Ntawm cov yam ntxwv ntawm caj ces, ib tus tuaj yeem hais txog cov kev txiav txim siab corpulence, kev faib tawm ntawm cov rog rog, hyperinsulinemia, thiab ntau yam metabolism (lipoproteins) 93. Cov ntsiab lus tseem ceeb ntawm cov xwm txheej no zoo li muab los ntawm ntau qhov laj thawj. Cov xwm txheej ib puag ncig, kev ua neej nyob tsis tu ncua, haus luam yeeb, calorie ntau ntau muab rau hauv daim ntawv ntawm lipids, thiab ntxiv cov suab thaj, tshwj xeeb, paub zoo dua. Ntau lwm yam tseem ceeb tau pom tsis ntev los no, xws li muaj cov kab mob inflammatory hauv cov ntaub so ntswg adipose thiab kev hloov pauv hauv kev tso tawm ntawm adipokines [93]. Yog li ntawd, nws yog ib qho tsim nyog yuav tsum nrhiav kev kho mob kom txaus thiab muaj kev nyab xeeb los ntawm qhov tshwm sim loj ntawm tus kab mob no rau kev noj qab haus huv, suav nrog ntshav qab zib nephropathy, retinopathy, neuropathy, kab mob plawv, thiab mob ntshav qab zib ko taw [92].

4.2. Qhov cuam tshuam ntawm Isorhamnetin ntawm Associated Metabolic Pathways

Ntau qhov kev tshawb fawb hauv vitro thiab hauv vivo tau pom tias isorhamnetin tuaj yeem hloov kho cov metabolism hauv carbohydrate thiab nthuav tawm cov haujlwm tiv thaiv ntshav qab zib los ntawm kev koom nrog cov txheej txheem sib txawv. Cov kws tshawb fawb tau pom tias isorhamnetin txhawb nqa cov metabolism hauv carbohydrate los ntawm cov theem ntawm kev zom zaub mov thiab plab hnyuv nqus [94], txhim kho cov piam thaj los ntawm lub siab thiab cov leeg [19,95], tiv thaiv pancreatic-cells, thiab txo qis insulin secretion impairment [96]. Ntxiv rau, isorhamnetin tswj cov ntaub so ntswg adipose sib txawv, kev loj hlob, thiab kev loj hlob [29]. Rau kev tiv thaiv kab mob ntshav qab zib muaj peev xwm, cov kws tshawb fawb tau tshawb xyuas isorhamnetin cais tawm ntawm cov nroj tsuag tshuaj sib txawv. Hauv Table 1, peb tau teev cov chaw cog qoob loo thiab cov txheej txheem rho tawm ntawm isorhamnetin uas tswj cov ntshav qab zib cuam tshuam nrog kev sib txawv ntawm lub cev hauv lub cev. Hauv seem ntawm qhov kev tshuaj xyuas no, peb yuav sim piav qhia txog qhov cuam tshuam ntawm cov molecule no thiab nws cov metabolic precursor (quercetin) [97] ntawm cov txheej txheem mob ntshav qab zib.

4.2.1. Cov nyhuv ntawm Isorhamnetin rau Glucose Transporters

Glucose transporters (GLUT) yog ib pab pawg loj ntawm cov kab mob membrane uas thauj cov piam thaj los ntawm cov hlwb epithelial mus rau cov ntshav thiab los ntawm cov ntshav mus rau cov hlwb hla lub plab hnyuv hauv txoj kev gradient los ntawm kev thauj mus los. Qee tus ntawm lawv yog cov tshuaj insulin-dependant, tshwj xeeb tshaj yog GLUT4. Nws yog lub luag haujlwm tseem ceeb hauv kev tswj hwm cov piam thaj hauv insulin thiab tswj kev ua haujlwm ntawm insulin hauv adipose. Qhov tseeb, nws yog qhov tsim nyog tias cov tshuaj insulin, uas txhim kho cov piam thaj hauv cov ntshav, kuj tseem txhawb nqa cov neeg ua haujlwm ntawm GLUT4 mus rau cov cell membrane ntawm cov ntaub so ntswg-sensitive insulin. Nyob rau hauv ib txoj kev tshawb nrhiav hauv qab cov khoom tiv thaiv ntshav qab zibquercetinthiab isorhamnetin, cov kws sau ntawv tau ua pov thawj tias lub cev muaj zog ntawm isorhamnetin txhawb nqa GLUT4 hloov mus rau plasma membrane hauv L6 myotubes los ntawm cov txheej txheem sib txawv yam tsis hloov GLUT4 qhia [95]. Qhov tseeb, isorhamnetin tuaj yeem qhib JAK-STAT teeb liab txoj hauv kev ntawm 1 nM thiab 10nM, tso cai rau cov piam thaj hloov pauv mus rau induction. JAK-STAT yog lub teeb liab hloov pauv uas tsim los ntawm cov khoom siv transmembrane, txuas rau Janus Kinase (JAK) enzyme thiab STAT-type protein. Thaum ib lub ligand khi rau lub receptor, nws hloov nws cov conformation, activating lub enzyme JAK, uas phosphorylates STAT protein, inducing ib tug transduction cascade thiab activating transcription ntawm tej noob [100]. Hauv kev tshawb fawb silico, Selvaraj [101] tau pom tias qee yam flavonoids, suav nrog isorhamnetin, tuaj yeem cuam tshuam nrog lub chaw nquag ntawm GLUT4 protein los ntawm H-bond kev sib cuam tshuam. Qhov kev tshawb pom no tso cai rau peb nrhiav kev cuam tshuam ntawm cov molecule no ntawm cov piam thaj thauj khoom, tshwj xeeb tshaj yog GLUT 4. Los ntawm kev sib piv, quercetin txhawb nqa cov insulin thiab AMPK-nyob rau hauv tib lub L6 hlwb. Qhov tseeb, Eid et al. tau pom tias 18 h kev kho mob ntawm cov kab mob kab mob L6 skeletal leeg hlwb nrog ib koob tshuaj ntawm 50 uM quercetin tuaj yeem txhawb nqa AMPK thiab nce GULT4 translocation [102]. Ib yam li ntawd, quercetin tau pom qhov txawv txav ntawm cov tshuaj insulin-mediated GLUT4 translocation nyob rau hauv adipocytes nyob rau hauv basal thiab insulin-resistant tej yam kev mob cuam tshuam rau nws txoj cai ntawm AMPKactivity [103]. Tsis tas li ntawd, Eid et al. tau lees paub tias quercetin aglycone, muab rho tawm los ntawm Vaccinium Viti's berries, tuaj yeem txhim kho cov leeg nqaij ntawm tes qabzib [98]. Kev taw qhia feem ntawm cov txiv hmab txiv ntoo extract raws li kev noj qab haus huv hauv cov leeg nqaij pom tau tias quercetin -3-O-glycosides yog lub ntsiab lus tseem ceeb. Ntawm 50 μM, cov ntsiab lus no txhim kho cov piam thaj hauv qab nce mus txog 59 feem pua ​​​​tom qab kev kho 18h, qhov cuam tshuam loj dua li ntawm 100nM insulin.

4.2.2. Cov nyhuv ntawm Isorhamnetin ntawm Peroxisome Proliferator-Activated Receptors (PPARs)

PPARs muaj nyob rau hauv cov kev hloov pauv ntawm cov khoom siv hluav taws xob hauv chav kawm II tsev neeg nrog kev ua haujlwm tseem ceeb hauv kev tswj hwm cov piam thaj thiab lipid metabolism [104]. Lawv tau nthuav tawm nyob rau hauv ntau hom cell: pancreatic hlwb, lub siab hlwb, thiab adipose hlwb, yog li tswj tau ntau yam ntawm cov txheej txheem lom neeg los ntawm kev hloov pauv ntawm cov noob caj noob ces [105]. Hauv cov tsiaj nyeg, peb lub isoforms muaj tam sim no∶ PPAR , PPAR / δ thiab PPARy, uas tswj cov noob cuam tshuam hauv cov piam thaj thiab lipid thauj, synthesis, thiab fatty acid oxidation [106,107]. Ntau qhov kev tshawb fawb soj ntsuam tau tsom rau PPARs rau cov kab mob metabolic thiab kev kho mob ntshav qab zib. Thiazolidinediones (TZDs: pioglitazone thiab rosiglitazone) yog ib chav kawm ntawm cov tshuaj tiv thaiv kab mob hauv qhov ncauj uas txo cov ntshav qab zib ntau ntau thiab txhim kho lipid profile ntawm cov neeg mob T2DM. Ib tug loj tus naj npawb ntawm hypotheses qhia hais tias cov anti-diabetic nyhuv ntawm TZDs yog exerted ntawm PPARy. Fibrates uas lub hom phiaj PPARo kuj tau siv los kho hyperlipidemia thiab ntshav qab zib. Isorhamnetin tau raug tshaj tawm tias muaj kev cuam tshuam zoo ib yam li cov tshuaj tau hais, feem ntau yog PPARs antagonists lossis agonists [28], uas ua rau cov teeb meem metabolic tshwm sim los ntawm kev noj zaub mov muaj roj ntau lossis tsis muaj leptin [33]. Pre-adipocyte cell kab qauv 3T3-L1 hlwb tau siv dav hauv kev tshawb fawb kev rog thiab ntshav qab zib [108,109]. Kev rog rog vim ntshav qab zib yog tus cwj pwm los ntawm hypertrophy thiab hyperplasia ntawm adipocytes. Pretreatment ntawm 3T3-L1 hlwb nrog ntau koob tshuaj ntawm isorhamnetin tuaj yeem cuam tshuam adipocytes sib txawv los ntawm kev txo qis triglyceride (TG) thiab glycerol{20}}phosphate dehydrogenase (GPDH) kev ua haujlwm[29]. Ntawm qib molecular, isorhamnetin kuj tseem tuaj yeem tswj hwm mRNA kev qhia ntawm cov cim adipocytes loj, feem ntau yog cov ntaub ntawv hloov pauv PPARy thiab CCAAT / txhim kho-binding protein- (C / EBPa), tus tswv koom ua haujlwm tswj hwm ntawm adipogenesis thiab cell sib txawv [29 , 30] ib. Cov kev tshawb pom no kuj tau pom zoo nrog cov kev tshawb fawb qhia tias Nitraria retusa isorhamnetin-nplua nuj extract tuaj yeem txo cov rog hauv 3T3-L1 adipocytes nyob rau hauv ib koob tshuaj [18]. Ib leeg-molecule isorhamnetin kuj tseem tuaj yeem cuam tshuam qhov sib txawv ntawm 3T3-L1 hlwb, ua rau txo cov lipid droplet cov ntsiab lus los ntawm kev txo cov cell loj thiab tus lej. Tsis tas li ntawd, kev tswj hwm qhov ncauj ntawm Nitraria retusa extract tuaj yeem tswj hwm PPAR thiab lipogenic enzymes tsom cov noob LPL thiab FAS [17]. Qhov tseem ceeb, ib txoj kev tshawb fawb tsis ntev los no tau qhia tias isorhamnetin tuaj yeem txo cov roj ntau hauv cov tsiaj lub cev los ntawm txoj kev PPAR-dependent [27].

4.2.3. Cov txiaj ntsig ntawm Isorhamnetin rau Hepatic Enzymes

Lub siab yog ib yam kabmob uas ua lub luag haujlwm tseem ceeb hauv carbohydrate homeostasis [110]. Tshaj li cov teeb meem micro thiab macrovascular ntawm ntshav qab zib mellitus, tus neeg mob T2DM nthuav qhia ntau yam kab mob siab nrog, thawj qhov chaw, hepatic steatosis. Hauv T2DM, qhov kev pheej hmoo ntawm kev loj hlob mus rau fibrosis thiab mob siab yog ntau dua [111], nthuav tawm qee tus neeg mob ntshav qab zib rau qhov tshwm sim tseem ceeb, tshwj xeeb nrog hepatocarcinoma [112]. Nyob rau tib lub sijhawm, kab mob siab hauv cov neeg mob ntshav qab zib tau cuam tshuam nrog kev pheej hmoo siab ntawm cov hlab plawv, uas yuav muaj txiaj ntsig zoo rau kev ua kom zoo ntawm kev tiv thaiv kab mob plawv [113]. Peb tsom mus rau qhov tseem ceeb tshaj plaws ntawm daim siab mob ntsig txog ntshav qab zib: cov kab mob siab rog, kab mob siab fibrosis, thiab kab mob qog nqaij hlav hepatocellular (HCC).

Tsis-Alcoholic Steatohepatitis

Cov kab mob fatty siab los yog tsis-alcoholic steatohepatitis (NASH) sawv cev rau cov teeb meem mob siab. Nws yog tus cwj pwm raws li qhov txawv txav ntawm TGs hauv daim siab hlwb. Hauv hom 2 mob ntshav qab zib mellitus, insulin tsis kam ua rau muaj cov tshuaj lom fatty acids. Thaum qhov kev sib txuam no tshwm sim hauv daim siab hlwb nws ua rau cov kab mob uas tsis yog-alcoholic fatty siab (NAFLD) thiab hauv cov ntaub ntawv hnyav steatosis lossis NASH [111,114]. Ganbold et al. tau qhia tias isorhamnetin ameliorated hepatic steatosis thiab fibrosis nyob rau hauv NASH nas qauv qhia zoo ib yam li tib neeg NASH [19]. Qhov tseeb, piv rau pawg tswj nas, daim siab kuaj los ntawm NASH-induced pab pawg pom tau tias mob rog ntau dhau 37 feem pua ​​​​ntawm cov roj liab O zoo. Txawm li cas los xij, kev kho mob isorhamnetin hauv NASH pawg tuaj yeem txo cov roj liab Ostained cheeb tsam rau 22 feem pua. Tsis tas li ntawd, kev kho isorhamnetin txo qis NASH-vim cov noob qhia hloov pauv. Cov kws sau ntawv tau pom tias isorhamnetin zoo txhim kho cov txheej txheem lipid metabolic hauv NASH thiab inhibited de novo lipogenesis.

Hepatic Fibrosis

Hepatic fibrosis yog cov caws pliav ntau dhau los ntawm kev tsim cov ntaub so ntswg hauv daim siab. Nws yog tshwm sim los ntawm ntau lawm thiab / los yog tsis txaus degradation ntawm extracellular matrix. Muaj ntau yam ua rau daim siab fibrosis. Ntawm lawv yog NASHorigin. Thaum muaj kev tiv thaiv rau insulin, fatty acids tsim nyob rau hauv daim siab, ua rau toxicity thiab o. Qhov no yog nrog los ntawm kev tsim cov cytokines thiab reactive oxygen hom. Hauv fibrosis, cytokines yog lub luag haujlwm rau kev ua kom lub siab lub hlwb (HSCs) thiab yuav ua kom muaj ntau ntau ntawm collagen fibers [115,116]. Qhov tshwm sim yog kev ua phem rau lub sijhawm ntev, tshwj xeeb tshaj yog nyob rau hauv cov xwm txheej ntawm cov kab mob inflammatory [115]. TGF- yog tus neeg nruab nrab tseem ceeb ntawm HSC kev ua kom muaj zog thiab kev sib txuas ntawm cov cellular matrix, ua rau fibrosis [117]. Yog li, thaiv txoj hauv kev no tuaj yeem yog lub tswv yim zoo rau daim siab fibrosis [118]. Hauv cov ntsiab lus no, Yang et al. qhia tau tias isorhamnetin inhibited HSC ua kom thiab tiv thaiv TGF- -induced qhia ntawm fibrogenic noob, xws li -SMA, PAI-1, thiab COL1A1 [74]. Qhov tseeb, cov kws sau ntawv tau qhia tias qhov inhibitory nyhuv ntawm cov flavonol no yog los ntawm canonical TGF- / Smad signaling pathway inhibition. Tsis tas li ntawd, isorhamnetin qhib Nrf2-TSIS teeb liab thiab txwv tsis pub TGF- - mediated ROS ntau lawm, uas kuj ua rau inhibition ntawm fibrogenic noob qhia. Tsis tas li ntawd, isorhamnetin txo qis cov pa roj carbon tetrachloride (CCl4)-induced fibrosis hauv cov nas. Liu et al. kuj tau pom tias isorhamnetin tuaj yeem txo qis CCl4 thiab cov kab mob hauv lub cev ligation (BDL) ua rau lub siab fibrosis los ntawm inhibiting TGF- 1 ntau lawm thiab HSC ua kom [119]. Ib yam li ntawd, Lee et al. Qhia tau tias isorhamnetin, muab rho tawm los ntawm Oenanthe javanica, tuaj yeem txo cov fibrosis hauv nas HSCs los ntawm kev thaiv cov xov tooj ntawm tes ntxiv- tswj kinase (ERK) qhia txoj hauv kev thiab inhibiting kev loj hlob thiab collagen synthesis ntawm HSC-T6 hlwb [99]. Qhov tseeb, pretreatment ntawm HSC-T6 hlwb nrog cov flavonol repressed serum-induced ERK phosphorylation, tib yam li ib tug MEK inhibitor (PD98059).

Hepatocellular Carcinoma

Hepatocellular carcinoma feem ntau pom tau lig ntawm theem metastasis (hauv 64 feem pua ​​​​ntawm cov neeg mob); Qhov chaw thib ob feem ntau yog lub ntsws, cov qog nqaij hlav, lub raum, thiab cov qog adrenal [120]. Raws li tau hais los saum toj no, nrog rau kev sib sau ua ke ntawm fatty acid nyob rau hauv daim siab hlwb, physiological cuam tshuam tshwm sim nyob rau lub sij hawm xws li NASH, ces o (nrog rau zus tau tej cov cytokines thiab ROS), ces nyob rau hauv ntau heev mob cirrhosis thiab nyob rau hauv cov ntaub ntawv loj carcinoma [121,122] . Lub luag haujlwm ntawm isorhamnetin raug txiav tawm los ntawm nws cov haujlwm tiv thaiv qog nqaij hlav. Isorhamnetin, muab rho tawm los ntawm Hippophae rhamnoides L., pom muaj zog tiv thaiv qog ua haujlwm hauv hepatocellular carcinoma BEL-7402 hlwb, ua kom muaj zog cytotoxicity nrog IC50 ntawm qhov concentration ntawm 74.4 ± 1.13 ug / mL thiab 72 h incubation. Cytotoxicity ntawm no flavonol ntawm cov qog nqaij hlav cancer nyob ntawm isorhamnetin cellular tsub zuj zuj. Hloov chaw, pibenzimol hydrochloride staining ntawm isorhamnetin-kho hlwb pom cov condensed thiab fragmented nuclei thiab apoptotic lub cev. Tsis tas li ntawd, kev soj ntsuam cytometry ntws siv los ntsuas kev hloov pauv ntawm lub voj voog ntawm tes thiab sib txawv ntawm apoptosis thiab necrosis, qhia tias 13.77 feem pua ​​​​ntawm isorhamnetin-kho BEL{18}} hlwb (nrog 50ug / mL rau 48 h) tshwm sim nyob rau hauv lub siab hypodiploid. Cov hauj lwm zoo sib xws los ntawm Wei et al. tshaj tawm tias isorhamnetin inhibited lub voj voog ntawm tes ntawm lub ncauj tsev menyuam kab mob qog noj ntshav HeLa, los ntawm kev ntes G2 / M theem ntawm kev ua kom lub ataxia-telangiectasia mutated Chk2 txoj kev [75]. Hauv lwm txoj haujlwm thiab los ntawm kev sib piv, isorhamnetin-3-O-glucoside, quercetin 3-O-rhamnoside-7-O-glucoside, thiab kaempferol-3-O-glucoside{{33 }}O-rhamnoside, muab rho tawm los ntawm Cleome droserifolia, txo HepG2, lub siab hepatocellular carcinoma cell, cell viability thiab anchorage-independent cell loj hlob nyob rau hauv ib koob tshuaj thiab lub sij hawm-dependent yam tab sis nrog ib tug high-est nyhuv nrog lubquercetinderivative. Tsis tas li ntawd, lawv tau nthuav tawm qhov txo qis kev tsiv teb tsaws ntawm HepG2 hlwb [124].

4.2.4 ib. Kev cuam tshuam ntawm Isorhamnetin ntawm Pancreatic-Cell Dysfunction

Insulin yog ib yam tshuaj uas tsim los ntawm lub cev uas pab peb cov hlwb, tshwj xeeb tshaj yog cov nqaij hlwb, lub siab hlwb, hlwb adipose, thiab hlwb hlwb, nqus cov piam thaj los ntawm cov zaub mov kom hloov mus rau hauv lub zog rau tag nrho cov txheej txheem lom thiab ua haujlwm [125,126]. Hauv cov xwm txheej zoo li no, insulin yog zais los ntawm pancreatic cell, tom qab ntawd tso rau hauv cov hlab ntsha. -cell dysfunction yog tus yam ntxwv los ntawm impaired insulin secretion, qhov tseem ceeb feature ntawm T2DM, ob qho tib si nyob rau hauv nws pib thiab kev loj hlob [127]. Metabolic stress-induced -cell dysfunction hauv T2DM kuj tseem tuaj yeem cuam tshuam nrog cov roj saturated ntau hauv kev rog, ua rau muaj kev kub ntxhov thiab oxidative kev nyuaj siab nyob rau hauv-cells. Yog li ntawd, kev puas tsuaj ntawm insulin secretion yog qhov hnyav dua li insulin tsis kam [128]. Ua ke, cov tswv yim tshiab los tiv thaiv kab mob ntshav qab zib yog xav tau los tiv thaiv lossis rov ua haujlwm ntawm pancreatic-cell dysfunction. Hauv cov ntsiab lus no, Wang et al. qhia tias isorhamnetin, muab los ntawm Vernonia anthelmintic tshuaj ntsuab, tuaj yeem cuam tshuam kev loj hlob ntawm pancreatic cancer hlwb (colourectal adenocarcinoma cell line) ntawm kev ntes lub voj voog ntawm tes nyob rau theem S, uas tej zaum yuav yog lwm txoj hauv kev los tiv thaiv kab mob pancreatic carcinoma thiab nws cov teeb meem metabolic. [129]. Tsis tas li ntawd, lwm daim ntawv tshaj tawm tau qhia tias isorhamnetin thiab glycosylated daim ntawv ntawm isorhamnetin (tso tawm los ntawm Salicornia herbacea cog) tuaj yeem txhawb cov piam thaj-stimulated insulin secretion hauv insulin-secreting nas insulinoma (INS-1) pancreatic -cells yam tsis muaj kev cuam tshuam ntawm tes [ 96] ib. Tsis tas li ntawd, nws tuaj yeem tsim cov tshuaj insulin secretion los ntawm phosphorylation ntawm tag nrho ERK, insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3-kinase (PI3K), Akt, thiab ua kom muaj pancreatic thiab duodenal homeobox{ {24}} (PDX-1)[96]. Kev txhim kho ntawm cov cim no tuaj yeem txo qis kev ua haujlwm ntawm pancreatic cell dysfunction ua rau ntshav qab zib.

Tsis tas li ntawd, Grdovic et al.reported tias isorhamnetin originating los ntawm Castanea sciatica cog hom muaj kev tiv thaiv ntawm streptozotocin-induced oxidative kev puas tsuaj thiab -cell apoptotic tuag [130]. Cov txiaj ntsig zoo no tau sib raug zoo rau cov txiaj ntsig antioxidant ntawm cov molecule no los ntawm kev txo cov cellular biomarkers ntawm oxidative kev nyuaj siab, piv txwv li, MDA thiab intracellular GSHlevels, thiab txhim kho cov dej num ntawm antioxidant enzymes SOD thiab CAT. Cov nyhuv kuj tau lees paub ntawm qib molecular los ntawm qhov txo qis NF-kB kev hloov pauv tau txhawb nqa los ntawm cov cell oxidative kev nyuaj siab, thiab yog li qhia txog kev tiv thaiv hauv cov cell. Raws li qhov tshwm sim, quercetin, uas yog metabolized hauv isorhamnetin, tuaj yeem txo cov piam thaj los ntawm kev ua kom cov tshuaj insulin tso tawm hauv streptozotocin-induced type 1 diabetes model hauv nas [131]. Hauv tib tus qauv tsiaj, quercetin tau pom muaj kev tiv thaiv ntawm -cell kev ncaj ncees los ntawm kev txo cov cim oxidative kev nyuaj siab [132]. Nws kuj tseem tuaj yeem tsim cov islets hauv pancreatic hlwb [133].

4.2.5. Cov nyhuv ntawm Isorhamnetin ntawm NF-kB

NF-kB yog ib qho protein ntau ntawm cov tsev neeg ntawm kev hloov pauv cov ntsiab lus cuam tshuam nrog kev tiv thaiv kab mob thiab cov xov tooj ntawm tes kev ntxhov siab thiab suav tias yog tus neeg nruab nrab tseem ceeb ntawm kev tso tawm cov cim inflammatory xws li cytokines, chemokines, thiab cov enzymes sib txawv [130,134,135]. Lub luag haujlwm ntawm NF-k hauv pathophysiology ntawm ntshav qab zib thiab nws cov teeb meem vascular txuas tau raug tshawb xyuas [136]. Hyperglycemia activates qhov nu-clear factor uas nyob rau hauv lem induces lub secretion thiab over-expression ntawm pro-inflammatory cytokines, feem ntau TNF-, interleukins, TGF-, thiab Bcl2, ua rau vascular teeb meem xws li neuropathy, nephropathy, retinopathy, thiab cardiomyopathy [137] ]. Ntau qhov kev tshawb nrhiav txog kev tiv thaiv cov txiaj ntsig ntawm flavonols ntawm cov ntshav qab zib ua rau cov hlab ntsha tsis ua haujlwm tau pom tias isorhamnetin tuaj yeem cuam tshuam qhov ua kom NF-k los ntawm kev ua kom muaj kev ua haujlwm ntawm pancreatic antioxidant enzymes [138]. Lwm txoj kev tshawb fawb tau tshaj tawm cov nyhuv inhibitory ntawm isorhamnetin ntawm iNOS qhia thiab TSIS MUAJ ntau lawm hauv cov tshuab ua haujlwm macrophages, ua rau kev thaiv ntawm NF-k [139]. Tsis tas li ntawd, Qiu et al. tau kawm txog cov nyhuv renoprotective ntawm flavonol isorhamnetin hauv T2DM nas qauv los ntawm kev hloov kho ntawm NF-k signaling pathway [31]. Cov kws sau ntawv tau pom tias cov molecule no inhibited NF-kB signaling kev ua ub no los ntawm kev nce zus tau tej cov NF-kB p65, phospho-NF-kB p65, thiab phospho-IkB thiab inflammatory mediators TNF-, IL-1 , IL{{ 30}}, ICAM-1, thiab TGF- 1, nrog rau txo qis NF-kB p65 DNA-binding kev ua haujlwm. Tsis tas li ntawd, nws tuaj yeem txo cov kev ntxhov siab oxidative cell los ntawm kev tswj hwm MDA thiab SODlevels, ua rau rov qab ua rau lub raum puas hauv cov nas mob ntshav qab zib.