I-Epimedium(Ukhula lwebhokhwe eneempondo) Isicatshulwa- i-Icariin iba lithemba elitsha ekulweni umhlaza we-Urothelial

I-Urothelial carcinoma yenye yezona zinto zixhaphakileyo zomhlaza womchamo, kunye nokuphindaphinda kwethumba kunye ne-metastasis njengezona zinto ziphambili zokuxela kwangaphambili. Ngo-2023, kuqikelelwa ukuba iimeko ze-168,560 zomhlaza womchamo ziya kufunyaniswa e-United States, malunga nokufa kwe-32,590; malunga ne-50% yezi meko yi-urothelial carcinoma. Ngaphandle kokufumaneka kokhetho olutsha lonyango, olufana neplatinam-based chemotherapy kunye ne-PD1 antibody-based immunotherapy, ngaphezu kwesiqingatha sezigulane ze-urothelial carcinoma azikaphenduli kolu nyango. Ngoko ke, kukho imfuneko engxamisekileyo yokuphanda ii-agent ezintsha zonyango ukuze kuphuculwe i-prognosis yezigulane ze-urothelial carcinoma.

Icariin(ICA), eyona nto isebenzayo kwi-Epimedium, i-tonic, i-aphrodisiac, kunye neyeza elichasayo lemveli yaseTshayina. Nje ukuba idliwe, i-ICA ​​i-metabolized to icartin (ICT), ethi ke isebenzise iziphumo zayo. I-ICA inemisebenzi emininzi yebhayoloji, kubandakanywa nokulawula i-immunity eguquguqukayo, eneempawu ze-antioxidant, kunye nokuthintela ukuqhubeka kwethumba. Kwi-2022, ii-capsules ze-Icaritin kunye ne-ICT njengeyona nto iphambili yavunywa yi-China National Medical Products Administration (NMPA) yonyango lokuqala lwe-hepatocellular carcinoma engasebenziyo. Ukongeza, ibonise ukusebenza okubonakalayo ekwandiseni ukusinda ngokubanzi kwezigulana ezine-hepatocellular carcinoma ephezulu. I-ICT ayibulali kuphela ngokuthe ngqo amathumba ngokubangela i-apoptosis kunye ne-autophagy, kodwa ilawula i-tumor immune microenvironment kwaye ikhuthaza impendulo ye-anti-tumor immune immune. Nangona kunjalo, indlela ethile i-ICT elawula ngayo i-TME, ngakumbi kwi-urothelial carcinoma, ayiqondwa ngokupheleleyo.

Kutshanje, abaphandi abavela kwiSebe le-Urology, iSibhedlele saseHuashan, iYunivesithi yaseFudan yapapasha inqaku elinesihloko esithi "Icaritin inqanda ukuqhubela phambili komhlaza we-urothelial ngokucinezela ukungena kwe-PADI2-mediated neutrophil kunye neutrophil extracellular trap formation" kwiphephancwadi i-Acta Pharm Sin B. Uphononongo lutyhile i-Sin B. ukubaicariinukunciphisa kakhulu ukusasazeka kwe-tumor kunye nokuqhubela phambili ngelixa kuvimbela ukungena kwe-neutrophil kunye ne-NET synthesis, ebonisa ukuba i-ICT ingaba yi-NETs inhibitor entsha kunye nonyango olutsha lwe-urothelial carcinoma.

Ukuphindaphinda kwe-tumor kunye ne-metastasis zezona zizathu zokufa kwi-urothelial carcinoma. Kwi-tumor microenvironment, iimolekyuli zokulawula ezingalunganga kunye ne-immune cell subtypes zicinezela i-antitumor immunity. I-microenvironment evuthayo, ehambelana ne-neutrophils kunye ne-neutrophil extracellular traps (NETs), ikhuthaza i-tumor metastasis. Nangona kunjalo, okwangoku akukho machiza athintela ngokukodwa i-neutrophils kunye ne-NETs.

Kolu phononongo, abaphandi babonisa okokuqala ukubaicariin, unyango lokuqala lwe-hepatocellular carcinoma oluphambili kunye olunganyangekiyo, lunokunciphisa ii-NET ezibangelwa yi-NETosis yokuzibulala kunye nokuthintela ukungena kwe-neutrophil kwi-tumor microenvironment. Ngomatshini, i-ICT ibophelela kwaye inqanda ukubonakaliswa kwe-PADI2 kwi-neutrophils, ngaloo ndlela inqanda i-PADI2-mediated histone citrullination. Ukongeza, i-ICT inqanda ukuveliswa kwe-ROS, inqanda indlela yokubonisa i-MAPK, kwaye icinezela i-NET-induced tumor metastasis.

Ngelo xesha, i-ICT inqanda i-tumor PADI2-mediated histone citrullination, ngaloo ndlela inqanda ukubhalwa kweejene ze-neutrophil zokugaya ezifana ne-GM-CSF kunye ne-IL-6. Ngaloo ndlela, ukuthotywa kwe-IL-6 ibonakaliso yenza i-loop yengxelo elawulayo nge-JAK2 / STAT3 / IL-6 axis. Ngophononongo lokubuyela emva kweesampulu zeklinikhi, abaphandi bafumene unxibelelwano phakathi kwe-neutrophils, i-NETs, ​​i-UCa prognosis kunye nokuphunyuka komzimba. I-ICT edibeneyo kunye ne-immune checkpoint inhibitors ingaba nefuthe le-synergistic.

Isishwankathelo, olu phononongo lufumanise ukubaicariinyanciphisa kakhulu ukusasazeka kwethumba kunye nokuqhubela phambili ngelixa inhibiting ukungena kwe-neutrophil kunye ne-NET synthesis, kunye ne-neutrophils kunye ne-NETs idlale indima yokuthintela kwi-tumor immune microenvironment yezigulane ezine-urothelial carcinoma. Ukongeza, i-ICT idityaniswe ne-anti-PD1 immunotherapy inefuthe le-synergistic, iphakamisa isicwangciso sonyango esinokubakho kwizigulane ezine-urothelial carcinoma.