RESUMO
Inhibition of inflammatory responses from the spike glycoprotein of SARS-CoV-2 (Spike) by targeting NLRP3 inflammasome has recently been developed as an alternative form of supportive therapy besides the traditional anti-viral approaches. Clerodendrum petasites S. Moore (C. petasites) is a Thai traditional medicinal plant possessing antipyretic and anti-inflammatory activities. In this study, C. petasites ethanolic root extract (CpEE) underwent solvent-partitioned extraction to obtain the ethyl acetate fraction of C. petasites (CpEA). Subsequently, C. petasites extracts were determined for the flavonoid contents and anti-inflammatory properties against spike induction in the A549 lung cells. According to the HPLC results, CpEA significantly contained higher amounts of hesperidin and hesperetin flavonoids than CpEE (p < 0.05). A549 cells were then pre-treated with either C. petasites extracts or its active flavonoids and were primed with 100 ng/mL of spike S1 subunit (Spike S1) and determined for the anti-inflammatory properties. The results indicate that CpEA (compared with CpEE) and hesperetin (compared with hesperidin) exhibited greater anti-inflammatory properties upon Spike S1 induction through a significant reduction in IL-6, IL-1ß, and IL-18 cytokine releases in A549 cells culture supernatant (p < 0.05). Additionally, CpEA and hesperetin significantly inhibited the Spike S1-induced inflammatory gene expressions (NLRP3, IL-1ß, and IL-18, p < 0.05). Mechanistically, CpEA and hesperetin attenuated inflammasome machinery protein expressions (NLRP3, ASC, and Caspase-1), as well as inactivated the Akt/MAPK/AP-1 pathway. Overall, our findings could provide scientific-based evidence to support the use of C. petasites and hesperetin in the development of supportive therapies for the prevention of COVID-19-related chronic inflammation.
Assuntos
Antipiréticos , Tratamento Farmacológico da COVID-19 , Clerodendrum , Hesperidina , Petasites , Células A549 , Anti-Inflamatórios/farmacologia , Caspase 1/metabolismo , Clerodendrum/metabolismo , Citocinas/metabolismo , Flavonoides/farmacologia , Hesperidina/farmacologia , Humanos , Inflamassomos/metabolismo , Interleucina-18 , Interleucina-6 , Pulmão/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-akt , SARS-CoV-2 , Solventes , Glicoproteína da Espícula de Coronavírus , Fator de Transcrição AP-1RESUMO
A novel approach was employed for the synthesis of un-doped tinoxide and Cobalt-doped tinoxide (Co-doped SnO2) nanoparticles (NAPs) by using aqueous extract of Clerodendrum inerme with the help of eco-friendly superficial solution combustion method. Synthesized NAPs were characterized by different spectroscopic techniques and results from XRD, TEM, SEM, EDX and UV-Vis examines confirmed the successful synthesis, crystalline nature and spherical structure of un-doped SnO2 and Co-doped SnO2 NAPs with the average grain size of 30 and 40â¯nm; and band gap energy of 3.68 and 2.76â¯eV respectively. Antimicrobial propensity of the synthesized NAPs was determined by agar well assay, SEM, TEM and confocal laser scanning microscopic analysis against various bacterial and fungal strains. Synthesized Co-doped SnO2 NAPs were unveiled the extraordinary antibacterial and antifungal activities against E. coli, B. subtilis, A. niger, A. flavus, and C. albicans with the zone of inhibitions of 30⯱â¯0.08â¯mm and 26⯱â¯0.06â¯mm, 17⯱â¯0.04â¯mm, 23⯱â¯0.08â¯mm and 26⯱â¯0.06 respectively which were also evidenced from SEM, TEM and confocal laser scanning microscopy. In addition, green synthesized Co-doped SnO2 NAPs were demonstrated the substantial antioxidant activity by scavenging DPPH, significant in vitro anticancer and in vivo antitumor activity on breast carcinoma cells (MCF-7) and Ehrlich ascites tumor cell lines respectively than standard. The hemolytic activity disclosed low cytotoxicity of fabricated NAPs (0.89⯱â¯0.05%) at 5â¯mg/mL, which was indicated their biocompatibility potential. Hence, the multi-purpose properties of synthesized NAPs presented in the current study can be further deliberated for pharmaceutical and nanomedicine applications.