2. Academic Validation
  3. 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

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

  • Int J Mol Sci. 2022 Sep 7;23(18):10346. doi: 10.3390/ijms231810346.
Punnida Arjsri 1 2,  Kamonwan Srisawad 1 3,  Sariya Mapoung 1 2,  Warathit Semmarath 1 2 4,  Pilaiporn Thippraphan 1,  Sonthaya Umsumarng 2 5,  Supachai Yodkeeree 1 2 3,  Pornngarm Dejkriengkraikul 1 2 3
Affiliations

Affiliations

  • 1 Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
  • 2 Center for Research and Development of Natural Products for Health, Chiang Mai University, Chiang Mai 50200, Thailand.
  • 3 Anticarcinogenesis and Apoptosis Research Cluster, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
  • 4 Akkraratchkumari Veterinary College, Walailak University, Nakhon Si Thammarat 80160, Thailand.
  • 5 Division of Veterinary Preclinical Sciences, Department of Veterinary Biosciences and Veterinary Public Health, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai 50100, Thailand.
PMID: 36142258 DOI: 10.3390/ijms231810346
Abstract

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.

Keywords

COVID-19; Clerodendrum petasites; NLRP3 inflammasome; anti-inflammation; chronic inflammation; hesperetin; spike glycoprotein S1.

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