Ngo-Agasti 26, 2015 / iYunivesithi yaseKyushu / iiNgxelo zeNzululwazi

Umbhalo/Wu Tingyao

Iqela lophando likaKuniyoshi Shimizu, unjingalwazi onxulumene neZiko leSayensi yezoLimo kwiYunivesithi yaseKyushu eJapan, uqinisekisile ukuba i-31 triterpenoids eyodwa kumzimba ovelisa iziqhamo weGanoderma inqanda i-neuraminidase yeentsholongwane ezihlanu ze-influenza A ukuya kumaqondo ahlukeneyo, phakathi kwawo kukho ezimbini. i-triterpenoids ide ilungele uphuhliso njengamachiza okulwa umkhuhlane.Iziphumo zophando zipapashwe "kwiNgxelo zeNzululwazi" phantsi kweqela lokushicilela "Indalo" ekupheleni kuka-Agasti 2015.

I-Neuraminidase yenye yeeproteni ezimbini eziphuma kumphezulu wentsholongwane yomkhuhlane A.Intsholongwane yomkhuhlane nganye imalunga nekhulu lezi proteases.Xa intsholongwane ihlasela iseli kwaye isebenzisa izinto ezikwiseli ukuphinda-phinda amasuntswana entsholongwane amatsha, i-neuraminidase iyafuneka ukuze amasuntswana entsholongwane amatsha ahlukane neseli kwaye osuleleke ngakumbi ezinye iiseli.Ngoko ke, xa i-neuraminidase ilahlekelwa ngumsebenzi wayo, intsholongwane entsha iya kuvalelwa kwiseli kwaye ayikwazi ukubaleka, isongelo kumninimzi siya kuncitshiswa, kwaye isifo sinokulawulwa.I-oseltamivir (i-Tamiflu) esetyenziswa ngokuqhelekileyo kwikliniki kukusebenzisa lo mgaqo ukuthintela ukwanda kunye nokusasazeka kwentsholongwane.

Ngokophando olwenziwe nguKuniyoshi Shimizu, kugxininiso lwe-200 μM, ezi Ganoderma triterpenoids zithintele umsebenzi we-H1N1, H5N1, H7N9 kunye neentlobo ezimbini ezixhathisayo ze-mutant NA (H1N1, N295S) kunye ne-NA (H3N2, E119V) ukuya kwiidigri ezahlukeneyo.Ngokubanzi, i-inhibitory effect kwi-neuraminidase yohlobo lwe-N1 (ingakumbi i-H5N1) iyona nto ibhetele, kwaye i-inhibitory effect kwi-neuraminidase ye-H7N9 iyona nto imbi.Phakathi kwezi triterpenoids, i-ganoderic acid TQ kunye ne-ganoderic acid TR ibonise amanqanaba aphezulu okuthintela, kunye nemiphumo yala ma-compounds amabini ukusuka kwi-55.4% ukuya kwi-96.5% inhibition kwii-subtypes ze-NA ezahlukeneyo.

Uhlalutyo olongezelelweyo lwe-structure-activity relationship yezi triterpenoids lubonise ukuba i-triterpenoids, enempembelelo engcono yokuthintela kwi-N1 neuraminidase, inesakhiwo esingundoqo "se-tetracyclic triterpenoids ene-double bonds, isebe njengeqela le-carboxylic, kunye ne-oxygen- equlathe iqela kwisiza se-R5” (Umqolo A kumzobo ongezantsi).Ukuba isakhiwo esiphambili sesinye ezimbini (Umqolo B kunye no-C kumzobo ongezantsi), umphumo uya kuba mbi.

(Umthombo / i-Sci Rep. 2015 Aug 26; 5: 13194.)

Kwi-silico docking isetyenziselwa ukulinganisa ukusebenzisana kwe-ganoderic acids (TQ kunye ne-TR) kunye ne-neuraminidases (H1N1 kunye ne-H5N1).Ngenxa yoko, kwafunyaniswa ukuba zombini i-ganoderic acids kunye ne-Tamiflu zikwazi ukubopha ngokuthe ngqo kwindawo esebenzayo ye-neuraminidase.Le ndawo esebenzayo yenziwe ziintsalela ezininzi ze-amino acid.I-Ganoderma acids i-TQ kunye ne-TR iya kubophelela kwii-amino acid eziseleyo ze-Arg292 kunye ne-Glu119.I-Tamiflu inenye inketho kodwa inokwenza ukuba i-neuraminidase ingasebenzi.

Xa kuthelekiswa nokuthintela ezinye iiproteni kwintsholongwane yomkhuhlane (ezifana neprotein ye-M2, evula iqokobhe lentsholongwane ngeli xesha intsholongwane ibophelela kwiseli yomkhosi kwaye ithumela iijene zentsholongwane kwiseli), i-neuraminidase inhibitors okwangoku ibonwa njengesebenzayo kwaye incinci. amayeza okunyanga umkhuhlane.Ngoko ke, abaphandi bakholelwa ukuba i-ganoderic acids i-TQ kunye ne-TR, efana kodwa ingafaniyo kwindlela ye-Tamiflu, inethuba lokusetyenziswa njengesizukulwana esitsha samachiza okulwa nomkhuhlane okanye izikhombisi zoyilo.

Nangona kunjalo, kukho imfuneko yokuba ichiza lisetyenziswe njengechiza lokulwa nomkhuhlane, oko kukuthi, ichiza kufuneka lithintele ngokufanelekileyo ukuveliswa kwentsholongwane ngaphandle kokonakalisa iiseli ezosulelwe yintsholongwane.Nangona kunjalo, kuvavanyo lweeseli ezosulelwe ziintsholongwane eziphilayo kunye nemigca yeeseli zomhlaza wamabele (MCF-7), kwafunyaniswa ukuba xa abaphandi besebenzisa ezi ntlobo zimbini ze-ganoderic acids zodwa, babethandabuza malunga ne-cytotoxicity ephezulu, kodwa bafumana olunye uhlobo. ye-Ganoderma triterpenoid, i-ganoderol B, ine-inhibitory effect kwi-H5N1 (kodwa i-inhibitory effect impofu), kodwa ayikho i-cytotoxic.Ngoko ke, abaphandi bakholelwa ukuba indlela yokuphucula ukhuseleko lwe-ganoderic acids TQ kunye ne-TR ngokuguqulwa kwesakhiwo sekhemikhali ngelixa begcina inhibition yabo yomsebenzi we-neuraminidase kufuneka ithathelwe ingqalelo ngononophelo.

[Umthombo] Zhu Q, et al.Ukuvinjelwa kwe-neuraminidase yi-Ganoderma triterpenoids kunye nefuthe loyilo lwe-neuraminidase inhibitor.Sci Rep. 2015 Aug 26;5:13194.doi: 10.1038/srep13194.

ISIPHELO

Malunga nombhali/ Nksz. Wu Tingyao
UWu Tingyao unike ingxelo ngolwazi lweGanoderma lokuqala ukusukela ngo-1999. Ungumbhali wencwadiUkunyanga ngeGanoderma(ipapashwe kwiNdlu yePeople's Medical Publishing House ngo-Epreli 2017).
 
★ Eli nqaku lipapashwe phantsi kogunyaziso olulodwa lombhali.★ Le misebenzi ingasentla ayinakuphinda iveliswe, icatshulwe okanye isetyenziswe ngezinye iindlela ngaphandle kokugunyaziswa ngumbhali.★ Ukwaphulwa kwengxelo engentla, umbhali uya kulandela uxanduva olusemthethweni olufanelekileyo.★ Umbhalo wokuqala weli nqaku ubhalwe ngesiTshayina nguWu Tingyao waza waguqulelwa kwisiNgesi nguAlfred Liu.Ukuba kukho nakuphi na ukungangqinelani phakathi kwenguqulelo (isiNgesi) kunye neyoqobo (isiTshayina), isiTshayina sokuqala siya koyisa.Ukuba abafundi banayo nayiphi na imibuzo, nceda uqhagamshelane nombhali wokuqala, uNks. Wu Tingyao.