Carica papaya leaf water extract promotes innate immune response via MAPK signaling pathways

Abstract

The emergence and rapid spread of the potentially fatal coronavirus disease 2019, caused due to infection by severe acute respiratory syndrome coronavirus-2, has led to worldwide interest in developing functional bioactive ingredients that act as immunomodulatory agents. In this study, we aimed to characterize Carica papaya extract and explore its potential as an immunomodulator by performing in vitro cell screening. Papaya leaf water extract (PLW) was found to significantly increase the levels of nitric oxide (NO) and prostaglandin E 2 (PGE 2 ) by upregulating inducible nitric oxide synthase and cyclo-oxygenase-2 activity, respectively. Additionally, PLW increased the production of tumor necrosis factor-α and interleukin 1β in RAW 264.7 cells. Furthermore, PLW activated the expression of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) but not that of p38 mitogen-activated protein kinase. These results indicate that PLW increased the production of NO, PGE 2 , and pro-inflammatory cytokines by activating the JNK and ERK pathways in macrophages, thus demonstrating immunomodulatory properties. Finally, high-performance liquid chromatography fingerprint analysis indicated the presence of rutin, narirutin, and ρ-coumaric acid in PLW (6.30, 119.76, and 47.25 ppm, respectively). Treating cells with these compounds at non-toxic concentrations had no effect on NO production. Taken together, these results suggest that PLW may have potential as an immunity-enhancing supplement.

Antioxidant and Immune Stimulating Effects of Allium hookeri Extracts in the RAW 264.7 Cells and Immune-Depressed C57BL/6 Mice

“…NO was produced at 2.28~4.80 μM in AHL and 2.85~5.80 μM in AHR. Previous studies have reported that plant extracts including AH extracts stimulated the production of NO in RAW 264.7 or macrophages [ 13 , 38 , 39 , 40 ]. NO is a well-known inflammatory mediator and is released from activated macrophages during an infection or inflammation [ 41 ].…”

Immunomodulatory effects of Abelmoschus esculentus water extract through MAPK and NF-κB signaling in RAW 264.7 cells

“… 18 The immune system recognizes, removes, and metabolizes substances or organisms from the external environment through innate and acquired immune responses. 19 However, the immune system can be considered as a double-edged sword, in that its primary defense against foreign pathogens needs to be balanced with the limits that can lead to hyperactivity and hyper-inflammatory conditions. 20 …”

Rutin extraction from female Carica papaya Linn. using ultrasound and microwave-assisted extractive methods: Optimization and extraction efficiencies

“…A comparison of the rutin yield was also conducted among the four extraction methods utilized in the present paper with other studies from the literature. The comparison has determined that the obtained optimized yields of rutin from papaya leaf, obtained in the present work, were generally higher than those extracted using maceration (3.33 mg/g) [ 38 ] and extracted using hot water under 65 °C for 4 h (0.063 mg/g of papaya leaf water) [ 39 ]. This suggested the extraction methods selected in this study to be more promising.…”