Paper Title
COX-2 Inhibition in the Treatment of COVID-19 of Aromatic Plants: Chromolaena odorata, Praxelis clematidea, Ageratum conyzoides and Ageratinaadenophora Leaf Extracts and their Bioactive Compounds

Abstract
Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 virus rapidly became a pandemic in 2019. SARS-CoV-2 infection induces cyclooxygenase-2 (COX-2) expression which may regulate the severe lung inflammation and injury seen in COVID-19 patients. However, there is substantial evidence to show that treatment with some COX inhibitors or non-steroidal anti-inflammatory drugs (NSAIDs) increases the severity of COVID-19 infection. Therefore, it is fascinating to find alternative agents, including natural products for COX-2 and other inflammatory cytokine inhibitors which has great potential in treating Covid-19 without causing serious side-effects. Chromolaena odorata, Praxelis clematidea, Ageratum conyzoides and Ageratina adenophora are Asteraceae weeds that are widespread in Thailand and many tropical and subtropical countries. The authors’ previous studies presented evidence that 70% ethanolic leaf extracts of C. odorata and its active component, scutellarin tetramethyl ether, down-regulated COX-2 and inducible nitric oxide synthase (iNOS) via the NF-ҡB pathway. In this study, the reduction of two inflammatory genes by three other plant extracts and their active components were studied using RAW264.7 macrophage cell line. The bioactive compound was identified by thin-layer chromatography (TLC) and liquid chromatography with tandem mass spectrometry (LC-MS/MS). The effect on the expression of COX-2 and iNOS genes was determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The results presented that eugenol was the main active component of all the extracts. All four plant extracts and eugenol could dramatically reduce the expression of COX-2 and iNOS genes in a dose-dependent manner. Among them, P. clematidea exhibited the highest COX-2 and iNOS inhibitory effect. This study supported the potential of these four plant extracts and bioactive compounds in the treatment of COVID-19. Keywords - COVID-19, COX-2 inhibition, Bioactive compound, Natural product, NSAIDs