Epimedium(Horny Goat Weed) Extract- Icariin Amakhala Chiyembekezo Chatsopano Polimbana ndi Khansa ya Urothelial

Urothelial carcinoma ndi imodzi mwa khansa yofala kwambiri ya mkodzo, pomwe chotupa chimayambanso komanso kufalikira kwamphamvu kumakhala zinthu zazikuluzikulu zodziwira. Mu 2023, anthu pafupifupi 168,560 a khansa ya mkodzo adzapezeka ku United States, ndipo pafupifupi 32,590 amafa; pafupifupi 50% ya milandu imeneyi ndi urothelial carcinoma. Ngakhale kulipo kwa njira zatsopano zochizira, monga platinum-based chemotherapy ndi PD1 antibody-based immunotherapy, odwala opitilira theka la urothelial carcinoma samayankhabe mankhwalawa. Chifukwa chake, pakufunika kufufuzidwa kwamankhwala atsopano kuti athandizire odwala omwe ali ndi urothelial carcinoma.

Icariin(ICA), chinthu chachikulu chomwe chimagwira ntchito mu Epimedium, ndi mankhwala achi China, aphrodisiac, komanso anti-rheumatic. Ikangolowetsedwa, ICA imasinthidwa kukhala icartin (ICT), yomwe imakhala ndi zotsatira zake. ICA ili ndi zochitika zambiri zachilengedwe, kuphatikiza kuwongolera chitetezo chokwanira, kukhala ndi antioxidant katundu, ndikuletsa kukula kwa chotupa. Mu 2022, makapisozi a Icaritin okhala ndi ICT monga gawo lalikulu adavomerezedwa ndi China National Medical Products Administration (NMPA) kuti azitha kulandira chithandizo choyambirira cha khansa ya hepatocellular carcinoma. Kuphatikiza apo, idawonetsa kuthandizira kwakukulu pakutalikitsa moyo wonse wa odwala omwe ali ndi hepatocellular carcinoma. ICT sikuti imapha mwachindunji zotupa poyambitsa apoptosis ndi autophagy, komanso imayang'anira chotupa cha chitetezo chamthupi komanso kulimbikitsa chitetezo chamthupi chotsutsana ndi chotupa. Komabe, njira yeniyeni yomwe ICT imayendetsa TME, makamaka mu urothelial carcinoma, sichimveka bwino.

Posachedwapa, ofufuza a Dipatimenti ya Urology, Huashan Hospital, Fudan University adasindikiza nkhani yakuti "Icaritin imalepheretsa kupitirira kwa khansa ya urothelial popondereza kulowetsedwa kwa PADI2-mediated neutrophil ndi mapangidwe a neutrophil extracellular trap" mu magazini Acta Pharm Sin B. kutiicariinkuchepetsa kwambiri kufalikira kwa chotupa ndi kupita patsogolo kwinaku akuletsa kulowa kwa neutrophil ndi kaphatikizidwe ka NET, kusonyeza kuti ICT ikhoza kukhala NETs inhibitor yatsopano komanso chithandizo chatsopano cha urothelial carcinoma.

Kubwereranso kwa chotupa ndi metastasis ndizomwe zimayambitsa kufa mu urothelial carcinoma. Mu chotupa microenvironment, zoipa malamulo mamolekyu ndi angapo chitetezo chitetezo subtypes kupondereza antitumor chitetezo chokwanira. Kutupa kwachilengedwe, komwe kumalumikizidwa ndi neutrophils ndi misampha ya neutrophil extracellular (NETs), kumalimbikitsa metastasis ya chotupa. Komabe, pakadali pano palibe mankhwala omwe amaletsa makamaka ma neutrophils ndi NETs.

Mu kafukufukuyu, ofufuza adawonetsa koyamba iziicariin, chithandizo choyamba chapamwamba komanso chosachiritsika cha hepatocellular carcinoma, chikhoza kuchepetsa NETs chifukwa cha kudzipha NETosis ndi kuteteza neutrophil kulowa mu chotupa microenvironment. Mwamakina, ICT imamangiriza ndikuletsa kufotokoza kwa PADI2 mu neutrophils, motero kulepheretsa PADI2-mediated histone citrullination. Kuphatikiza apo, ICT imaletsa m'badwo wa ROS, imaletsa njira yolumikizira ya MAPK, ndikupondereza metastasis yopangidwa ndi NET.

Panthawi imodzimodziyo, ICT imalepheretsa chotupa cha PADI2-mediated histone citrullination, motero imalepheretsa kulembedwa kwa chibadwa cha neutrophil recruitment monga GM-CSF ndi IL-6. Komanso, kutsika kwa mawu a IL-6 kumapanga njira yoyankhira kudzera mu JAK2/STAT3/IL-6 axis. Kupyolera mu kafukufuku wobwereza wa zitsanzo zachipatala, ofufuzawo adapeza mgwirizano pakati pa neutrophils, NETs, ​​UCa prognosis ndi kuthawa kwa chitetezo cha mthupi. ICT yophatikizidwa ndi ma immune checkpoint inhibitors imatha kukhala ndi synergistic effect.

Mwachidule, kafukufukuyu anapeza kutiicariinkwambiri yafupika chotupa kufalikira ndi kupita patsogolo pamene inhibiting neutrophil kulolera ndi NET kaphatikizidwe, ndi neutrophils ndi NETs ankasewera cholepheretsa chotupa chitetezo microenvironment odwala ndi urothelial carcinoma. Kuphatikiza apo, ICT yophatikizidwa ndi anti-PD1 immunotherapy imakhala ndi mphamvu yolumikizana, ikuwonetsa njira yothandizira odwala omwe ali ndi urothelial carcinoma.