Hesperetin from Root Extract of Clerodendrum petasites S. Moore Inhibits SARS-CoV-2 Spike Protein S1 Subunit-Induced NLRP3 Inflammasome in A549 Lung Cells via Modulation of the Akt/MAPK/AP-1 Pathway.
Punnida ArjsriKamonwan SrisawadSariya MapoungWarathit SemmarathPilaiporn ThippraphanSonthaya UmsumarngSupachai YodkeereePornngarm Limtrakul DejkriengkraikulPublished in: International journal of molecular sciences (2022)
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-1β, 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-1β , 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.
Keyphrases
- nlrp inflammasome
- anti inflammatory
- sars cov
- induced apoptosis
- oxidative stress
- signaling pathway
- cell cycle arrest
- coronavirus disease
- diabetic rats
- cell proliferation
- pi k akt
- transcription factor
- high glucose
- respiratory syndrome coronavirus
- gene expression
- ms ms
- small molecule
- endothelial cells
- high resolution
- protein kinase
- simultaneous determination
- newly diagnosed
- liquid chromatography
- solar cells