RESUMEN
The infection of coronavirus disease (COVID-19) seriously threatens human life. It is urgent to generate effective and safe specific antibodies (Abs) against the pathogenic elements of COVID-19. Mice were immunized with SARS-CoV-2 spike protein antigens: S ectodomain-1 (CoV, in short) mixed in Alum adjuvant for 2 times and boosted with CoV weekly for 6 times. A portion of mice were treated with Maotai liquor (MTL, in short) or/and heat stress (HS) together with CoV boosting. We observed that the anti-CoV Ab was successfully induced in mice that received the CoV/Alum immunization for 2 times. However, upon boosting with CoV, the CoV Ab production diminished progressively; spleen CoV Ab-producing plasma cell counts reduced, in which substantial CoV-specific Ab-producing plasma cells (sPC) were apoptotic. Apparent oxidative stress signs were observed in sPCs; the results were reproduced by exposing sPCs to CoV in the culture. The presence of MTL or/and HS prevented the CoV-induced oxidative stress in sPCs and promoted and stabilized the CoV Ab production in mice in re-exposure to CoV. In summary, CoV/Alum immunization can successfully induce CoV Ab production in mice that declines upon reexposure to CoV. Concurrent administration of MTL/HS stabilizes and promotes the CoV Ab production in mice.
Asunto(s)
Anticuerpos Neutralizantes/biosíntesis , Anticuerpos Antivirales/biosíntesis , Apoptosis , COVID-19/inmunología , Células Plasmáticas/inmunología , SARS-CoV-2/fisiología , Superóxido Dismutasa-1/fisiología , Adyuvantes Inmunológicos , Bebidas Alcohólicas , Compuestos de Alumbre , Enzima Convertidora de Angiotensina 2/fisiología , Animales , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , COVID-19/enzimología , Vacunas contra la COVID-19/inmunología , Respuesta al Choque Térmico , Inmunización Secundaria , Inmunogenicidad Vacunal , Janus Quinasa 2/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Estrés Oxidativo , Células Plasmáticas/efectos de los fármacos , Células Plasmáticas/patología , Especies Reactivas de Oxígeno/metabolismo , Factor de Transcripción STAT1/fisiología , Transducción de Señal , Organismos Libres de Patógenos Específicos , Glicoproteína de la Espiga del Coronavirus/inmunología , VacunaciónRESUMEN
Three new leucothane-type (1-3), two new micrathane-type (4, 5), eight new grayanane-type diterpenoids (6-13), and four known compounds were obtained from the ethanol extract of the leaves and twigs of Rhododendron decorum. The structures were determined based on NMR spectra, quantum chemical calculations, and X-ray crystallography. The antinociceptive activities of compounds 1, 3, 4, 6, 8, 10-13, and 15-17 were evaluated via the acetic acid-induced writhing test. Compounds 1, 8, 11-13, and 15 exhibited significant antinociceptive activities. In particular, 12 and 15 were found to be effective at doses of 0.8 and 0.08 mg/kg, respectively.