I-Sinomenine, inhlanganisela eyaqala ukuhlukaniswa ne-Caulis Sinomenii ngu-Ishiwari ngeminyaka yawo-1920. Igama lekhemikhali lithi (9 ,13 ,14 ){22}}7,8-didehydro-4-hydroxy-3,7-dimethoxy-17-methylmorphinan-6-one, okuyingxenye ye-morphinan alkaloids, Yakhiwe nge-phenanthrene nucleus ne-ethylamine bridge. Isakhiwo siboniswa ku-Figure 1. I-Sinomenine iyi-crystalline powder emhlophe noma ephuzi ekhanyayo enefomula ye-molecular ye-C19H23NO4, i-molecular mass ye-329.38, ne-melting point ye-161 degree. Iyancibilika ku-ethanol, i-acetone, i-chloroform kanye ne-alkali encibilikayo, futhi inyibilika kancane emanzini, i-ether ne-benzene. I-Sinomenine futhi iyisidakamizwa se-osmotic esiphezulu, esimuncwa kahle kuzo zonke izingxenye zamathumbu amagundane. I-coefficient yayo ye-oil-water partition coefficient ingu-1.98. I-Sinomenine ingahlukaniswa njengenhlanganisela yekilasi II ohlelweni lokuhlukaniswa kwe-biopharmaceutical. I-Sinomenine iqedwa ngokushesha emzimbeni, futhi i-bioavailability yayo yomlomo iphansi, cishe ngama-30%, okukhawulela ukusetshenziswa kwayo emtholampilo ngezinga elithile. Ngakho-ke, ucwaningo lwezinhlobo ezintsha zemithamo ye-sinomenine lunokubaluleka okubalulekile kwesayensi.
Inhlanganisela ye-sinomenine ne-methotrexate, i-diclofenac sodium, i-leflunomide, i-celecoxib, i-hydroxychloroquine sulfate, i-sulfasalazine nezinye izidakamizwa zinomphumela we-synergistic futhi kunomthelela omkhulu ekwelapheni i-RA. Ngemuva kokwelashwa, inkomba yokuvuvukala okuhlangene kwesiguli, inkomba yethenda ehlangene, inkomba yokusebenza okuhlangene, nesikhathi sokuqina sasekuseni sancishiswa kakhulu, futhi zonke izinkomba zithuthukisiwe.
Impendulo yokuvuvukala kwe-RA ihlobene eduze nama-cytokines avuthayo. Izinga -lokuvuvukala kwama-cytokines (AIC) ku-RA liyehla, okuholela ekwenyukeni kwezinga-lokuvuvukala kwama-cytokines (PIC), futhi impendulo yokuvuvukala iyanda, okungase kube ukuqhubekela phambili kwe-RA Esinye sezizathu ezibalulekile ukuthi i-AIC inganqanda ukuvuvukala, futhi i-PIC ingakhuthaza ukwanda kwamaseli e-osteovial osteovial. Ucwaningo luye lwabonisa ukuthi i-sinomenine ingavimbela ngokuphawulekayo izilonda zesibili ze-adjuvant arthritis (AA) kumagundane, futhi yehlise amazinga e-IL-1 kanye ne-TNF- pro{10}ukuvuvukala{10}ku-serum nokumnika ngokuhlanganyela amagundane e-AA. Amazinga we-IL-4 kanye ne-IL-10 ephikisana nokuvuvukala ayanda, ukuze kuzuzwe inhloso yokunciphisa ukuvuvukala.
I-RA yisifo esingamahlalakhona sokuzivikela komzimba. Kunezinhlobonhlobo zamangqamuzana omzimba omzimba, okuhlanganisa i-T, B lymphocyte namaseli e-dendritic, abamba iqhaza futhi axazulule i-pathogenesis ye-RA. Kokubili ku-vivo kanye nokuphathwa kwe-in vitro ye-sinomenine kungabangela ukwanda kwama-lymphocyte we-spleen yegundane, kuvimbele i-leukocyte differentiation antigen (CD) 4+ amaseli, futhi phansi{3}}kulawule isilinganiso se-CD{4}}/CD{5}}, okuphakamisa ukuthi i-sinomenine inomphumela ovimbelayo we-T cell ku-T. Ukwengeza, olunye ucwaningo lubonise ukuthi i-sinomenine ingaphinda inciphise ngokuphawulekayo ukubonakaliswa kwama-cytokines TNF- kanye ne-TNF- kumaseli e-T ngendlela-encikile. Ama-Help cell 17 (Th17) kanye nama-T cell alawulayo (-amaseli{13}}okulawula, i-Treg) ama-T cell womabili, kodwa imisebenzi yalawa amabili emzimbeni womuntu iyaphikisana. Ukungalingani phakathi kwe-Th17 ne-Treg kungenye yezimbangela ezibalulekile ze-RA. Ngakho-ke, ngokuvimbela ukuhlukaniswa kwamaseli e-Th17, ukuthuthukisa umsebenzi we-Treg, nokufeza ibhalansi ye-Th17/Treg emzimbeni, inhloso yokwelapha i-RA ingafinyelelwa.
Esinye sezibonakaliso eziyinhloko ze-RA ukwanda ngokweqile kwamangqamuzana e-synovial, okuholela ekuqineni kolwelwesi lwe-synovial, ukwakheka kwe-pannus, ukulimala kwamathambo namalunga, ngisho nokulahlekelwa umsebenzi. Ngakho-ke, ukuvimbela ukwanda kwamaseli e-synovial kanye nokwenza i-synovial cell apoptosis ingenye yezindlela ezibalulekile zokwelapha i-RA.
Ukubhujiswa kwamathambo kuthatha isikhundla esibalulekile ekuveleni nasekuthuthukisweni kwe-RA, futhi kungenye yezimbangela eziyinhloko zokukhubazeka kwamalunga, ukuqina kanye nokungasebenzi kahle kweziguli ze-RA. Ucwaningo luye lwabonisa ukuthi i-receptor activator ye-nuclear factor-κB (RANK)/receptoractivator of nuclear factor-κB (RANKL)/osteoprotegerin (RANKL) OPG), njengeqembu le-osteoclast differentiation elawula izici zesignali, idlala indima ebalulekile ohlelweni lokubhujiswa kwamathambo e-RA. I-Sinomenine ingakhuphula ukugcinwa kwe-OPG ngokuvuselela i-osteoclast (OC), ukunciphisa ukugcinwa kwe-RANKL, ikhuthaze ukuhlukaniswa nokuvuthwa kwama-osteoblasts, futhi ivimbele ukubhujiswa kwamathambo.
Ngokusekelwe ekusebenzeni komtholampilo kwamanje kwamalungiselelo e-sinomenine ekwelapheni i-RA, kodwa uhhafu-ukuphila kwayo mfushane, i-bioavailability iphansi, kanye nesilinganiso somtholampilo sikhulu kakhulu, futhi ukwethulwa kobuchwepheshe obusha nezindlela kulindeleke ukuthi kuxazululwe le maphutha angenhla. Eminyakeni yamuva nje, abacwaningi benze ucwaningo ngezinhlobo ezintsha zemithamo ye-sinomenine liposomes, imizimba yokudlulisa, i-ethosomes, i-ethosomes yokudlulisela, ama-microemulsions, nama-microspheres ukuze bahlole ukusetshenziswa kokwakheka okusha kwe-sinomenine ekwelapheni i-RA .
