Ukuthuthukiswa kwe-Ginsenoside ekuphenduleni kokucindezeleka kwe-oxidative ku-organ fibrosis
Izifundo zemitholampilo nezokuhlola ezihlobene ne-organ fibrosis zibonisa ukuthi ukucindezelwa kwe-oxidative kungenye yezinto zokulamula zenqubekelaphambili ye-fibrosis, futhi ama-molecule ahlobene nokucindezeleka okwenziwe nge-oxidative angase abe abaxhumanisi bezenzakalo zamangqamuzana namaselula ezihlobene ne-fibrosis. Ukucindezeleka okwenziwe nge-oxidative kubhubhisa i-lipids, amaprotheni kanye ne-DNA, kubangela i-cell necrosis kanye ne-apoptosis, futhi kuthuthukise ukusabela kokuvuvukala. Izinhlobo zomoya-mpilo osebenzayo zingalamula i-TGF- Ukukhiqizwa kwezinhlobo zomoya-mpilo osebenzayo kudlala indima ebalulekile ekulimaleni kwesitho kanye ne-organ fibrosis.
Esibindini, izinhlobo ze-oksijini ezisebenzayo nazo zivuselela amangqamuzana e-Kupffer kanye namangqamuzana okuvuvukala ajikelezayo ukuze akhiqize abaxhumanisi be-fibrogenic, okwenza ngokuqondile amangqamuzana e-hepatic stellate futhi aholele ku-hepatic fibrosis. Ocwaningweni lwe-liver fibrosis, u-Wei et al wathola ukuthi i-ginsenoside Rg1 inganciphisa izinga lezinhlobo ze-oxygen esebenzayo kumodeli ye-liver fibrosis eyenziwa yi-carbon tetrachloride (CCl4) futhi ivikele i-fibrosis yesibindi.
Ukusabalala ngokweqile kwe-fibroblasts phakathi ne-pulmonary fibrosis kuholela ekwakhiweni kwezicubu zamaphaphu okungavamile, i-hypoxia nokulimala kwamangqamuzana. I-Hypoxia-i-inducible factor-1 (hypoxia-inducible factor-1 , HIF-1) Njenge-hypoxia factor factor, idlala indima ebalulekile ekuveleni nasekuthuthukeni kwezifo eziningi. Fu et al. Kutholwe ukuthi i-bleomycin yenza i-HIF-1 yasebenza ngemva kokwenza i-hypoxia / TGF- 1 indlela yokusayina, futhi iqhubeke ikhuthaze ukufuduka nokwanda kwama-fibroblasts nge-EMT, futhi ivimbele i-HIF-1 Ukuze yehlise ijubane inqubo ye-pulmonary fibrosis. Lokhu kutholakala kuphakamisa ukuthi ukuqondiswa kwe-hypoxia kusenesikhathi kunenzuzo engaba khona ekwelapheni i-pulmonary fibrosis. Ukucindezeleka kwe-oxidative kudlala indima ebalulekile ekwakhekeni kwe-pulmonary fibrosis, engabangela i-epithelial cell apoptosis, okungase kube isici esibalulekile ekuveleni kokuqala nasekuthuthukisweni kwe-pulmonary fibrosis. Esimeni sokuphila, isistimu ikubhalansi enamandla; Lapho umzimba uthinteka yizici ezibhubhisayo, uhlelo lwe-oxidation antioxidant luzobe lungenakulinganiswa, oluzokhiqiza inani elikhulu lama-radicals mahhala kanye nemikhiqizo yokuwohloka, ekugcineni kuholele emonakalweni we-plasma membrane futhi kukhuthaze ukwanda kwe-fibroblast kanye ne-collagen synthesis. Yang Lu et al. Kusetshenziswe i-SC monocrotaline ukuheha imodeli ye-rat pulmonary fibrosis ukuze iqhubeke nokubona umphumela wengqikithi ye-ginsenosides ku-pulmonary interstitial fibrosis. Kutholwe ukuthi i-ginsenosides ephelele inganciphisa imisebenzi ye-myeloperoxidase, i-nitric oxide synthase kanye ne-hydroxyl free radical ku-serum yamagundane we-pulmonary fibrosis, futhi andise umsebenzi we-superoxide dismutase kanye nomthamo ophelele we-antioxidant. Umshini ungase uhilele ukuvinjelwa kokulimala kwe-oxidative, okuhlobene nokuthuthukiswa kwamandla e-antioxidant.
Ukucindezeleka okwenziwe nge-oxidative kuma-myocyte enhliziyo kudlala indima ebalulekile ezifweni zenhliziyo, njenge-coronary artery disease, umfutho wegazi ophezulu kanye ne-diabetesic cardiomyopathy, kanye nokuhluleka kwenhliziyo. Ukwenyuka kwezinga lezinhlobo zomoya-mpilo osebenzayo kwenza kusebenze i-mast signal kinase nezici zokuloba, ezidala i-apoptosis ngokubhubhisa i-DNA ne-mitochondria. Ukufa kwamangqamuzana enhliziyo kukhuthaza izinguquko zokubunjwa kwe-ECM ezicutshini zenhliziyo, okuholela ekwandeni kwe-fibrosis yenhliziyo nokuvuvukala, futhi ekugcineni kuholela ekungasebenzi kahle kwenhliziyo. Hong et al. Kutholwe ukuthi i-ginsenoside MC1 ingakhuphuka ilawule amazinga e-catalase ne-superoxide dismutase, yehlise ingxenye enkulu ye-Bax: B{5}}i-cell lymphoma ne-caspase{9}}3 umsebenzi esicutshini senhliziyo yamagundane akhuluphele, okuholela ekuncipheni kokumiswa kwe-collagen. Kuyaqinisekiswa ukuthi i-ginsenoside MC1 yehlisa ingcindezi ye-oxidative futhi ithuthukisa ukusebenza kweseli kusicubu senhliziyo yamagundane akhuluphele ngendlela encike ku-AMPK, Kuphakanyiswa ukuthi inamandla njenge-ejenti entsha yokwelapha yengcindezi ye-oxidative{17}}izifo zenhliziyo ezihlobene. UZhang et al. Kutholwe ukuthi i-ginsenoside Rd ithuthukise kakhulu ukungasebenzi kahle kwe-systolic, i-fibrosis, i-myocardial hypertrophy, ukuvuvukala kanye nengcindezi ye-oxidative ebangelwa ukugcwala kwengcindezi kumagundane. Uma kuqhathaniswa neqembu lokulawula, enhliziyweni ephathwa nge-ginsenoside Rd, Akt, calcineurin a, isignali ye-extracellular regulated kinases 1 / 2 (ERK1 / 2) kanye ne-TGF- Izinga lamaphrotheni lika-1 lehle kakhulu. Le miphumela iphakamisa ukuthi i-ginsenoside Rd ithuthukisa ukungasebenzi kahle kwenhliziyo kanye nokulungiswa kabusha okubangelwa ukugcwala kwengcindezi, okuhlobene nokuvinjelwa kwezindlela eziningi zokubonisa.
Ezinso, i-TGF- Ukwenyuka kokuvezwa kokungu-1 kuzothuthukisa ukuwohloka kwe-ECM futhi kuthuthukise ukuhlanganiswa kwe-ECM, okuholela ku-glomerular ne-tubular fibrosis. U-Du kanye nolunye ucwaningo lwathola ukuthi inhlanganisela ye-ginsenoside Rg1 ne-astragaloside inganciphisa kakhulu izinga le-urea nitrogen ne-creatinine kumagundane e-diabetesic nephropathy{4}izinga le-microglobulin; Yehlisa kakhulu i-TGF- 1 kanye ne-connective tissue growth factor (CTGF), kodwa yandisa inkulumo ye-Smad 7 kuzicubu zezinso; Kuqinisekisiwe ukuthi ukusetshenziswa okuhlanganisiwe kwe-Ginsenoside Rg1 kanye ne-astragaloside IV kungase kunciphise ingcindezi ye-oxidative futhi kuvimbele i-TGF- 1 / i-Smads signal cascade ukuze kuvikelwe izinso. UZhang et al. Kutholwe ukuthi ukwelashwa kwe-notoginseng saponin R1 (NgR1) kukhuphule i-lipid yegazi kanye ne-2- i-microglobulin, i-serum creatinine namazinga e-urea nitrogen egazi kunciphisa ukungahambi kahle kwe-renal histological, okungaboniswa ngokunciphisa umthamo we-glomerular kanye ne-fibrosis ezinso ezinesifo sikashukela. Kwaphinde kwatholakala ukuthi ukwelashwa kwe-NgR1 kunganciphisa umonakalo we-mitochondrial obangelwa imikhiqizo yokuphela kwe-glycation ethuthukisiwe (iminyaka), ukunciphisa ukwanda kwezinhlobo ze-oxygen esebenzayo, ukunciphisa i-apoptosis yamaseli we-HK-2, ukukhuthaza ukubonakaliswa kwe-nuclear Nrf2 kanye ne-heme oxidase-1, futhi kuqede i-apoptosis eyenziwe kanye ne-TGF- Izinhlobo ze-oksijeni ezisebenzayo zingase zibe indlela eyinhloko yokudluliselwa kwesignali ye-oksijeni. Ucwaningo luye lwabonisa ukuthi i-NGR1 idlala indima yokuvikela ku-nephropathy yesifo sikashukela ngokuvimbela i-apoptosis kanye ne-renal fibrosis ebangelwa ingcindezi ye-oxidative. I-NGR1 ingaba i-ejenti yokwelapha engaba khona yesifo sikashukela.
Umphumela we-inhibitory we-Ginsenoside ekukhiqizeni i-collagen ku-organ fibrosis
Inqubo ye-pathological ye-organ fibrosis ukwanda kokuqukethwe kwe-collagen kanye nokufakwa ngokweqile kwezitho. Ukuwohloka kwesakhiwo somzimba okubangelwa ukufakwa kwe-collagen kuyisisekelo se-etiological sochungechunge lwezimpawu zomtholampilo.
Njengoba i-ohnchi nabanye bathola ukuthi kwakukhona inani elikhulu le-proline hydroxylase ku-hepatocytes, i-metabolism ye-hepatocytes ne-collagen idonsele ukunaka kwezazi eziningi. Ngokwezibalo, uma kuqhathaniswa nesibindi esijwayelekile, okuqukethwe kwe-collagen ku-fibrosis yesibindi kukhula okungenani izikhathi ezi-5 ~ 10. Uhlobo ⅰ kanye no-ⅲ lwe-collagen lubalelwa ku-90% wesamba se-collagen. Ngakho-ke, ukwanda kohlobo ⅰ kanye ne-ⅲ ye-collagen kungabonisa ukwanda kwe-collagen ephelele, futhi ukwanda kwe-collagen ephelele kuhlotshaniswa kahle nezinga le-iver fibrosis kanye nokuqhubeka okusebenzayo kwe-cirrhosis yesibindi. I-Ginsenoside Rg1 ingavimbela ukukhiqizwa kwe-collagen enqubweni ye-liver fibrosis kuwo womabili amazinga okuhlola amaselula nawezilwane. Ucwaningo lwangaphambilini lweqembu lethu locwaningo luthole ukuthi i-ginsenoside AD-2 inganciphisa ukuvezwa kohlobo I-collagen, i-tissue inhibitor ye-metalloproteinase 1 (TIMP-1) ne-MMP13, ivimbele ukufakwa kwe-ECM futhi ibe nomthelela we-anti liver fibrosis. Ngaphezu kwalokho, umphumela ovimbelayo we-Ginsenoside ku-collagen nawo uqinisekisiwe ezifundweni zomtholampilo. Tang et al. Kutholwe ukuthi i-Ginsenoside Rg3 ingadlula ku-TGF-/Smad kanye ne-extracellularsignal regulated kinase (ERK) izindlela zesignali zivimbela ukwanda, i-vascularization kanye nokufakwa kwe-ECM kwe-hypertrophic scar fibroblasts. Kunomehluko omkhulu phakathi kweqembu lokulawula kanye neqembu lokwelapha le-Ginsenoside Rg3. Lolu cwaningo luhlinzeka ngobufakazi obanele bokuhlola be-Ginsenoside Rg3 njengomuthi othembisayo wokwelapha isibazi se-hypertrophic ku-vivo.
U-Sun Xiaofang nabanye bakholelwa ukuthi i-Panax notoginseng saponins ingadlala indima ye-anti pulmonary fibrosis ngokwandisa i-pulmonary cathepsin K, inciphisa okuqukethwe kohlobo iii-c, uhlobo IV-C collagen, laminin ne-hyaluronic acid ku-serum ye-pulmonary fibrosis yamagundane ku-lungroxyprosis fibrosis amagundane e-lungroxyprosis amagundane kanye nokunciphisa ukukhula kwe-collagen esicutshini samaphaphu.
Esinye sezizathu eziyinhloko zezici ze-pathological ze-myocardial fibrosis kanye ne-hypertrophy ukuqoqwa kwe-collagen ku-ECM. Li et al. Kutholwe ukuthi i-ginsenoside Rg2 ingavimbela ngokuphawulekayo uhlobo lwe-collagen I (COL-1), COL-3 kanye ne-collagen edalwe i-acute myocardial infarction ngokuvula i-Akt pathway - Expression of SMA. Khuthaza ukululama kokusebenza kwenhliziyo kumagundane ngemuva kwe-myocardial infarction, vimbela ukufakwa kwe-collagen nokuvuvukala okubangelwa i-myocardial infarction, uthuthukise ukusebenza kwezinhlobo zomoya-mpilo osebenzayo futhi unciphise ukuvela kwe-myocardial fibrosis. Wang et al. Kutholwe ukuthi ukwelashwa kwe-ginsenoside Re kunciphisa kakhulu ukuqoqwa kwe-collagen nokwakheka kwe-fibrosis enhliziyweni. Ukuncipha kokuqukethwe kwe-hydroxyproline okubangelwa i-ginsenoside Re kufakazela futhi ukuthi i-ginsenoside Re ingavimbela ukunqwabelana kwe-collagen eyenziwe yi-isoproterenol.
Ukuvinjwa kwe-Unilateral ureteral kubangela ukulimala kwe-tubulointerstitial kanye nokunqwabelana kwe-collagen matrix, okuholela ku-renal interstitial fibrosis. Xie et al. Kutholwe ukuthi i-ginsenoside Rg1 ne-RB1 zehlise kakhulu ukulimala kwe-tubulointerstitial kanye nokufakwa kwe-collagen okubangelwa unilateral ureteral obstruction (UUO), kanye nokuncipha kwe-TGF- 1, edlala indima ekuvimbeleni i-renal interstitial fibrosis.
