I-Epimedium(Horny Goat Weed) Extract- I-Icariin Iba Ithemba Elisha Ekulweni Nomdlavuza We-Urothelial

I-Urothelial carcinoma ingenye yezinhlobo ezivame kakhulu zomdlavuza womchamo, ukuphindaphinda kwesimila kanye ne-metastasis kuba yizici ezinkulu zokubikezela. Ngo-2023, izigameko ezilinganiselwa ku-168,560 zomdlavuza womchamo zizotholakala e-United States, cishe nokufa kwabantu abayi-32,590; cishe ama-50% alezi zimo i-urothelial carcinoma. Naphezu kokutholakala kwezinketho ezintsha zokwelapha, ezifana ne-chemotherapy-based chemotherapy kanye ne-PD1 antibody-based immunotherapy, ngaphezu kwesigamu seziguli ze-urothelial carcinoma namanje aziphenduli kulokhu kwelashwa. Ngakho-ke, kunesidingo esiphuthumayo sokuphenya ama-ejenti amasha okwelapha ukuze kuthuthukiswe ukubikezelwa kweziguli ze-urothelial carcinoma.

I-Icariin(I-ICA), isithako esiyinhloko esisebenzayo ku-Epimedium, iwumuthi wendabuko waseShayina othambisayo, ovusa amadlingozi, kanye nomuthi wamaShayina oqeda rheumatic. Uma isingenile, i-ICA ​​igaywa ku-icartin (ICT), ebese ikhipha imiphumela yayo. I-ICA inemisebenzi eminingi yebhayoloji, okuhlanganisa ukulawula ukuzivikela komzimba okuguquguqukayo, ukuba nezakhiwo ze-antioxidant, nokuvimbela ukuqhubeka kwesimila. Ngo-2022, amaphilisi e-Icaritin ane-ICT njengesithako esiyinhloko agunyazwa yi-China National Medical Products Administration (NMPA) ukuze alaphe umugqa wokuqala we-hepatocellular carcinoma esezingeni eliphezulu. Ngaphezu kwalokho, ibonise ukusebenza kahle okuphawulekayo ekwandiseni ukusinda okuphelele kweziguli ezine-hepatocellular carcinoma ethuthukisiwe. I-ICT ayibulali kuphela ngokuqondile izimila ngokufaka i-apoptosis kanye ne-autophagy, kodwa futhi ilawula i-tumor immune microenvironment futhi ikhuthaze ukuphendula kwamasosha omzimba okulwa ne-tumor. Nokho, indlela ethile i-ICT elawula ngayo i-TME, ikakhulukazi ku-urothelial carcinoma, ayiqondwa ngokugcwele.

Muva nje, abacwaningi abavela eMnyangweni We-Urology, Isibhedlela sase-Huashan, i-Fudan University bashicilele isihloko esithi "Icaritin ivimbela ukuqhubeka komdlavuza we-urothelial ngokucindezela ukungena kwe-PADI2-mediated neutrophil kanye nokwakheka kwe-neutrophil extracellular trap" kumagazini i-Acta Pharm Sin B. Ucwaningo lwembula u-Sin B. lokhoicariinkunciphise kakhulu ukusakazeka nokuqhubeka kwesimila kuyilapho kuvimbela ukungena kwe-neutrophil kanye nokuhlanganiswa kwe-NET, okubonisa ukuthi i-ICT ingase ibe i-NETs inhibitor entsha kanye nokwelashwa okusha kwe-urothelial carcinoma.

Ukuphindaphinda kwe-tumor kanye ne-metastasis yizimbangela eziyinhloko zokufa ku-urothelial carcinoma. Ku-tumor microenvironment, ama-molecule alawulayo angalungile kanye nama-immune immune cell subtypes acindezela ukungatheleleki kwe-antitumor. I-microenvironment evuthayo, ehlotshaniswa nama-neutrophils kanye nezicupho ze-neutrophil extracellular (NETs), ikhuthaza i-tumor metastasis. Nokho, okwamanje azikho izidakamizwa ezivimbela ngokuqondile ama-neutrophils nama-NET.

Kulolu cwaningo, abacwaningi bakhombise okokuqala lokhoicariin, umugqa wokuqala wokwelapha we-hepatocellular carcinoma ethuthukisiwe futhi engelapheki, inganciphisa ama-NET abangelwa i-NETosis yokuzibulala futhi ivimbele ukungena kwe-neutrophil ku-tumor microenvironment. Ngokwemishini, i-ICT ibophezela futhi ivimbele ukuvezwa kwe-PADI2 kuma-neutrophils, ngaleyo ndlela ivimbele i-PADI2-mediated histone citrullination. Ngaphezu kwalokho, i-ICT ivimbela isizukulwane se-ROS, ivimbela indlela yokusayina ye-MAPK, futhi icindezela i-NET-induced tumor metastasis.

Ngesikhathi esifanayo, i-ICT ivimbela i-tumor PADI2-mediated histone citrullination, ngaleyo ndlela ivimbele ukulotshwa kwezakhi zofuzo zokuqashwa kwe-neutrophil njenge-GM-CSF ne-IL-6. Ngokulandelayo, ukulawulwa phansi kwesisho se-IL-6 sakha iluphu yempendulo elawulayo nge-axis ye-JAK2/STAT3/IL-6. Ngocwaningo olwenziwa kabusha lwamasampula omtholampilo, abacwaningi bathola ukuhlobana phakathi kwama-neutrophils, ama-NET, i-UCa prognosis kanye nokuphunyuka komzimba. I-ICT ehlanganiswe ne-immune checkpoint inhibitors ingase ibe nomphumela we-synergistic.

Kafushane, lolu cwaningo luthole ukuthiicariinkunciphise kakhulu ukusabalala kwesimila kanye nokuqhubekela phambili ngenkathi kuvimbela ukungena kwe-neutrophil kanye nokuhlanganiswa kwe-NET, futhi ama-neutrophils nama-NET adlala indima evimbelayo ku-tumor immune microenvironment yeziguli ezine-urothelial carcinoma. Ngaphezu kwalokho, i-ICT ehlanganiswe ne-anti-PD1 immunotherapy inomphumela we-synergistic, ophakamisa isu lokwelapha elingase libe khona ezigulini ezine-urothelial carcinoma.