Work

Dual Functionality of Papaya Leaf Extracts: Anti-Coronavirus Activity and Anti-Inflammation Mechanism

Year: 2024

Type: article

Abstract: Background: Papaya leaves have been used as food and traditional herbs to treat cancer, diabetes, asthma, and virus infection, but the active principle has not been understood. We hypothesized that the anti-inflammatory activity could be the predominant underlying principle.Purpose: Our study aimed to investigate the anti-inflammatory activity of papaya leaves, as well as figure out the responsible underlying mechanisms. Also, extensive study was conducted to discover its anti-coronavirus activity.Methods: We extracted papaya leaf juice with different organic solvents, the anti-inflammatory activity of papaya leaves extract was evaluated by the concentration of nitric oxide (NO), expression of pro-inflammatory protein and mRNA expression of pro-inflammatory cytokines The action of mechanism was elucidated by transcriptome analysis and validated by western blot. The neutralization of papaya leaves against HCoV-229E, SARS-CoV-2 and HCoV-OC43 were determined by microneutralization test (MNT) and plaque reduction neutralization test (PRNT). Also, HPLC-QTOF-MS was applied for the identification of predominant phytochemicals in papaya leaves.Results: The ethyl acetate (EA) fraction showed the most outstanding anti-inflammatory activity by suppressing the lipopolysaccharide (LPS)-induced production of NO (IC50 = 24.94 ± 2.4 μg/mL) and expression of pro-inflammatory protein, such as cyclooxygenase (COX-2) and inducible nitric oxide synthase (iNOS) and cytokines including interleukins (IL-1β and IL-6), and tumor necrosis factor (TNF-α) in RAW 264.7 cells. Transcriptomic analysis and western blot results revealed its anti-inflammatory mechanisms were through the MAPK signaling pathway by blocking the phosphorylation of ERK1/2, JNKs and p38, and the prevention of cell surface expression of TLR4. Furthermore, we discovered that the EA fraction could inhibit the replication of alpha-coronavirus (HCoV-229E) and beta-coronavirus (SARS-CoV-2 and HCoV-OC43) and might be able to prevent cytokine storms caused by coronavirus infection. From HPLC-QTOF-MS data, we found the predominant phytochemicals existed in EA fraction were quercetin and kaempferol glycosides, and carpaine. Counter-intuitively, further fractionation resulted in loss of activity suggesting that the synergistic effect of different components in EA fraction contribute to the overall potent activity.Conclusion: In summary, our findings provide preliminary evidence for the function of papaya leaves as a potential anti-inflammatory agent via modulation of MAPK pathways and as an anti-coronavirus agent by hindering the viral replication process, which warrants further investigation for its application in promoting human health.

Source: Foods

DOI: 10.3390/foods13203274