Hesperetin from Root Extract of <i>Clerodendrum petasites</i> 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
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. <i>Clerodendrum petasites</i> S. Moore (<i>...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-09-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/18/10346 |
| _version_ | 1797487448580685824 |
|---|---|
| author | Punnida Arjsri Kamonwan Srisawad Sariya Mapoung Warathit Semmarath Pilaiporn Thippraphan Sonthaya Umsumarng Supachai Yodkeeree Pornngarm Dejkriengkraikul |
| author_facet | Punnida Arjsri Kamonwan Srisawad Sariya Mapoung Warathit Semmarath Pilaiporn Thippraphan Sonthaya Umsumarng Supachai Yodkeeree Pornngarm Dejkriengkraikul |
| author_sort | Punnida Arjsri |
| collection | DOAJ |
| description | 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. <i>Clerodendrum petasites</i> S. Moore (<i>C. petasites</i>) is a Thai traditional medicinal plant possessing antipyretic and anti-inflammatory activities. In this study, <i>C. petasites</i> ethanolic root extract (CpEE) underwent solvent-partitioned extraction to obtain the ethyl acetate fraction of <i>C. petasites</i> (CpEA). Subsequently, <i>C. petasites</i> 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 (<i>p</i> < 0.05). A549 cells were then pre-treated with either <i>C. petasites</i> 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 (<i>p</i> < 0.05). Additionally, CpEA and hesperetin significantly inhibited the Spike S1-induced inflammatory gene expressions (<i>NLRP3</i>, <i>IL-1β</i>, and <i>IL-18</i>, <i>p</i> < 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 <i>C. petasites</i> and hesperetin in the development of supportive therapies for the prevention of COVID-19-related chronic inflammation. |
| first_indexed | 2024-03-09T23:47:48Z |
| format | Article |
| id | doaj.art-7f56133faa784383b53fc94e5a5efaf0 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:47:48Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-7f56133faa784383b53fc94e5a5efaf02023-11-23T16:40:02ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123181034610.3390/ijms231810346Hesperetin from Root Extract of <i>Clerodendrum petasites</i> 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 PathwayPunnida Arjsri0Kamonwan Srisawad1Sariya Mapoung2Warathit Semmarath3Pilaiporn Thippraphan4Sonthaya Umsumarng5Supachai Yodkeeree6Pornngarm Dejkriengkraikul7Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, ThailandCenter for Research and Development of Natural Products for Health, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, ThailandInhibition 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. <i>Clerodendrum petasites</i> S. Moore (<i>C. petasites</i>) is a Thai traditional medicinal plant possessing antipyretic and anti-inflammatory activities. In this study, <i>C. petasites</i> ethanolic root extract (CpEE) underwent solvent-partitioned extraction to obtain the ethyl acetate fraction of <i>C. petasites</i> (CpEA). Subsequently, <i>C. petasites</i> 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 (<i>p</i> < 0.05). A549 cells were then pre-treated with either <i>C. petasites</i> 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 (<i>p</i> < 0.05). Additionally, CpEA and hesperetin significantly inhibited the Spike S1-induced inflammatory gene expressions (<i>NLRP3</i>, <i>IL-1β</i>, and <i>IL-18</i>, <i>p</i> < 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 <i>C. petasites</i> and hesperetin in the development of supportive therapies for the prevention of COVID-19-related chronic inflammation.https://www.mdpi.com/1422-0067/23/18/10346NLRP3 inflammasomechronic inflammation<i>Clerodendrum petasites</i>hesperetinanti-inflammationspike glycoprotein S1 |
| spellingShingle | Punnida Arjsri Kamonwan Srisawad Sariya Mapoung Warathit Semmarath Pilaiporn Thippraphan Sonthaya Umsumarng Supachai Yodkeeree Pornngarm Dejkriengkraikul Hesperetin from Root Extract of <i>Clerodendrum petasites</i> 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 International Journal of Molecular Sciences NLRP3 inflammasome chronic inflammation <i>Clerodendrum petasites</i> hesperetin anti-inflammation spike glycoprotein S1 |
| title | Hesperetin from Root Extract of <i>Clerodendrum petasites</i> 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 |
| title_full | Hesperetin from Root Extract of <i>Clerodendrum petasites</i> 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 |
| title_fullStr | Hesperetin from Root Extract of <i>Clerodendrum petasites</i> 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 |
| title_full_unstemmed | Hesperetin from Root Extract of <i>Clerodendrum petasites</i> 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 |
| title_short | Hesperetin from Root Extract of <i>Clerodendrum petasites</i> 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 |
| title_sort | hesperetin from root extract of i clerodendrum petasites i 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 |
| topic | NLRP3 inflammasome chronic inflammation <i>Clerodendrum petasites</i> hesperetin anti-inflammation spike glycoprotein S1 |
| url | https://www.mdpi.com/1422-0067/23/18/10346 |
| work_keys_str_mv | AT punnidaarjsri hesperetinfromrootextractoficlerodendrumpetasitesismooreinhibitssarscov2spikeproteins1subunitinducednlrp3inflammasomeina549lungcellsviamodulationoftheaktmapkap1pathway AT kamonwansrisawad hesperetinfromrootextractoficlerodendrumpetasitesismooreinhibitssarscov2spikeproteins1subunitinducednlrp3inflammasomeina549lungcellsviamodulationoftheaktmapkap1pathway AT sariyamapoung hesperetinfromrootextractoficlerodendrumpetasitesismooreinhibitssarscov2spikeproteins1subunitinducednlrp3inflammasomeina549lungcellsviamodulationoftheaktmapkap1pathway AT warathitsemmarath hesperetinfromrootextractoficlerodendrumpetasitesismooreinhibitssarscov2spikeproteins1subunitinducednlrp3inflammasomeina549lungcellsviamodulationoftheaktmapkap1pathway AT pilaipornthippraphan hesperetinfromrootextractoficlerodendrumpetasitesismooreinhibitssarscov2spikeproteins1subunitinducednlrp3inflammasomeina549lungcellsviamodulationoftheaktmapkap1pathway AT sonthayaumsumarng hesperetinfromrootextractoficlerodendrumpetasitesismooreinhibitssarscov2spikeproteins1subunitinducednlrp3inflammasomeina549lungcellsviamodulationoftheaktmapkap1pathway AT supachaiyodkeeree hesperetinfromrootextractoficlerodendrumpetasitesismooreinhibitssarscov2spikeproteins1subunitinducednlrp3inflammasomeina549lungcellsviamodulationoftheaktmapkap1pathway AT pornngarmdejkriengkraikul hesperetinfromrootextractoficlerodendrumpetasitesismooreinhibitssarscov2spikeproteins1subunitinducednlrp3inflammasomeina549lungcellsviamodulationoftheaktmapkap1pathway |